Research Publications

December 2019

Ashammakhi N, Kim HJ, Ehsanipour A, Bierman RD, Kaarela O, Xue C, Khademhosseini A, Seidlits SK.

Spinal cord injury (SCI) is a serious problem that primarily affects younger and middle-aged adults at its onset. To date, no effective regenerative treatment has been developed. Over the last decade, researchers have made significant advances in stem cell technology, biomaterials, nanotechnology, and immune engineering, which may be applied as regenerative therapies for the spinal cord. Although the results of clinical trials using specific cell-based therapies have proven safe, their efficacy has not yet been demonstrated. The pathophysiology of SCI is multifaceted, complex and yet to be fully understood. Thus, combinatorial therapies that simultaneously leverage multiple approaches will likely be required to achieve satisfactory outcomes. Although combinations of biomaterials with pharmacologic agents or cells have been explored, few studies have combined these modalities in a systematic way. For most strategies, clinical translation will be facilitated by the use of minimally invasive therapies, which are the focus of this review. In addition, this review discusses previously explored therapies designed to promote neuroregeneration and neuroprotection after SCI, while highlighting present challenges and future directions. Impact Statement To date there are no effective treatments that can regenerate the spinal cord after injury. Although there have been significant preclinical advances in bioengineering and regenerative medicine over the last decade, these have not translated into effective clinical therapies for spinal cord injury. This review focuses on minimally invasive therapies, providing extensive background as well as updates on recent technological developments and current clinical trials. This review is a comprehensive resource for researchers working towards regenerative therapies for spinal cord injury that will help guide future innovation.

December 2019

Chawla S, Blay JY, Rutkowski P, Le Cesne A, Reichardt P, Gelderblom H, Grimer RJ, Choy E, Skubitz K, Seeger L, Schuetze SM, Henshaw R, Dai T, Jandial D, Palmerini E.

BACKGROUND: Giant-cell tumour of bone (GCTB) is a rare, locally aggressive osteoclastogenic stromal tumour of the bone. This phase 2 study aimed to assess the safety and activity of denosumab in patients with surgically salvageable or unsalvageable GCTB. METHODS: In this multicentre, open-label, phase 2 study done at 30 sites in 12 countries we enrolled adults and skeletally mature adolescents (aged ≥12 years) weighing at least 45 kg with histologically confirmed and radiographically measurable GCTB, Karnofsky performance status 50% or higher (Eastern Cooperative Oncology Group status 0, 1, or 2), and measurable active disease within 1 year of study enrolment. Patients had surgically unsalvageable GCTB (cohort 1), had surgically salvageable GCTB with planned surgery expected to result in severe morbidity (cohort 2), or were enrolled from a previous study of denosumab for GCTB (cohort 3). Patients received 120 mg subcutaneous denosumab once every 4 weeks during the treatment phase, with loading doses (120 mg subcutaneously) administered on study days 8 and 15 to patients in cohorts 1 and 2 (patients in cohort 3 did not receive loading doses). The primary endpoint was safety in terms of the type, frequency, and severity of adverse events; secondary endpoints included time to disease progression from cohort 1 and the proportion of patients without surgery at month 6 for cohort 2. The safety analysis set included all enrolled patients who received at least one dose of denosumab.

December 2019

Felker ER, Raman SS, Lu DSK, Tuttle M, Margolis DJ, ElKhoury FF, Sayre J, Marks LS.

OBJECTIVE. The purpose of this study was to compare in a multireader manner the diagnostic accuracies of 3-T multiparametric MRI interpretation and serial prostate-specific antigen (PSA) measurement in predicting the presence of residual clinically significant prostate cancer after focal laser ablation. MATERIALS AND METHODS. Eighteen men had undergone focal laser ablation for low- or intermediate-risk prostate cancer as part of two National Cancer Institute-funded phase 1 clinical trials. Multiparametric MRI was performed immediately after and 6 and 12 months after focal laser ablation. Serial PSA measurements after focal laser ablation were recorded, and MRI-ultrasound fusion biopsy was performed 6 and 12 months after ablation and served as the reference standard. Multiparametric MRI was performed at 3 T with pelvic phased-array coils. T2-weighted, DW, and dynamic contrast-enhanced MR images were retrospectively assessed by two blinded radiologists using a 3-point Likert scale (0-2). Inter-reader agreement was assessed with the Cohen kappa statistic. The diagnostic accuracies of multiparametric MRI and PSA measurement were compared.

December 2019

Fetah KL, DiPardo BJ, Kongadzem EM, Tomlinson JS, Elzagheid A, Elmusrati M, Khademhosseini A, Ashammakhi N.

Cancer is one of the leading causes of death worldwide, despite the large efforts to improve the understanding of cancer biology and development of treatments. The attempts to improve cancer treatment are limited by the complexity of the local milieu in which cancer cells exist. The tumor microenvironment (TME) consists of a diverse population of tumor cells and stromal cells with immune constituents, microvasculature, extracellular matrix components, and gradients of oxygen, nutrients, and growth factors. The TME is not recapitulated in traditional models used in cancer investigation, limiting the translation of preliminary findings to clinical practice. Advances in 3D cell culture, tissue engineering, and microfluidics have led to the development of "cancer-on-a-chip" platforms that expand the ability to model the TME in vitro and allow for high-throughput analysis. The advances in the development of cancer-on-a-chip platforms, implications for drug development, challenges to leveraging this technology for improved cancer treatment, and future integration with artificial intelligence for improved predictive drug screening models are discussed.

December 2019

Fefferman NR, Jordan SG, Slanetz PJ, Morgan DE, Gordon LL, Suh RD, Mullins ME.

RATIONALE AND OBJECTIVES: The Alliance of Directors and Vice Chairs in Education group identified the need to develop an education budget template as resource for our community. Having a framework and working knowledge of budgetary considerations is crucial to those with general oversight and executive managerial responsibility for departmental educational programs. METHODS: An online survey was sent to all the Alliance of Directors and Vice Chairs in Education members. Survey questions included education funding sources, presence of vice chair of finance, expectation of revenue generation, existing education budget, funding decision-makers, education budget formulation and approval, vice chair of education's role in budget, education budget line items, and income statement review.

December 2019

Hsieh SS, Hoffman JM, Noo F.

PURPOSE: The computational burden associated with model-based iterative reconstruction (MBIR) is still a practical limitation. Iterative coordinate descent (ICD) is an optimization approach for MBIR that has sometimes been thought to be incompatible with modern computing architectures, especially graphics processing units (GPUs). The purpose of this work is to accelerate the previously released open-source FreeCT_ICD to include GPU acceleration and to demonstrate computational performance with ICD that is comparable with simultaneous update approaches. METHODS: FreeCT_ICD uses a stored system matrix (SSM), which precalculates the forward projector in the form of a sparse matrix and then reconstructs on a rotating coordinate grid to exploit helical symmetry. In our GPU ICD implementation, we shuffle the sinogram memory ordering such that data access in the sinogram coalesce into fewer transactions. We also update NS voxels in the xy-plane simultaneously to improve occupancy. Conventional ICD updates voxels sequentially (NS = 1). Using NS > 1 eliminates existing convergence guarantees. Convergence behavior in a clinical dataset was therefore studied empirically.

December 2019

Nguyen KL, Yoshida T, Kathuria-Prakash N, Zaki IH, Varallyay CG, Semple SI, Saouaf R, Rigsby CK, Stoumpos S, Whitehead KK, Griffin LM, Saloner D, Hope MD, Prince MR, Fogel MA, Schiebler ML, Roditi GH, Radjenovic A, Newby DE, Neuwelt EA, Bashir MR, Hu P, Finn JP.

BACKGROUND: Ferumoxytol is approved for use in the treatment of iron deficiency anemia, but it can serve as an alternative to gadolinium-based contrast agents. On the basis of postmarketing surveillance data, the Food and Drug Administration issued a black box warning regarding the risks of rare but serious acute hypersensitivity reactions during fast high-dose injection (510 mg iron in 17 seconds) for therapeutic use. Whereas single-center safety data for diagnostic use have been positive, multicenter data are lacking. PURPOSE: To report multicenter safety data for off-label diagnostic ferumoxytol use. MATERIALS AND METHODS: The multicenter ferumoxytol MRI registry was established as an open-label nonrandomized surveillance databank without industry involvement. Each center monitored all ferumoxytol administrations, classified adverse events (AEs) using the National Cancer Institute Common Terminology Criteria for Adverse Events (grade 1-5), and assessed the relationship of AEs to ferumoxytol administration. AEs related to or possibly related to ferumoxytol injection were considered adverse reactions. The core laboratory adjudicated the AEs and classified them with the American College of Radiology (ACR) classification. Analysis of variance was used to compare vital signs.

December 2019

Shakibajahromi B, Borhani-Haghighi A, Ghaedian M, Feiz F, Molavi Vardanjani H, Safari A, Salehi A, Mowla A.

OBJECTIVES: One of the most important prognostic factors of cerebral venous sinus thrombosis (CVST) is intracranial hemorrhage (ICH). We studied the risk factors, clinical, and radiologic characteristics of early, delayed, and expanded ICH in Iranian patients with CVST. MATERIALS AND METHODS: In a retrospective study, from August 2012 to September 2016, all adult patients with a confirmed diagnosis of CVST were recruited. Demographic, clinical, and radiologic characteristics of the patients were recorded. The predictors of early, delayed, and expanded ICH were assessed through logistic regression analysis.

December 2019

Suurmond CE, Lasli S, van den Dolder FW, Ung A, Kim HJ, Bandaru P, Lee K, Cho HJ, Ahadian S, Ashammakhi N, Dokmeci MR, Lee J, Khademhosseini A.

The liver has a complex and unique microenvironment with multiple cell-cell interactions and internal vascular networks. Although nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with multiple phases, no proper model could fully recapitulate the in vivo microenvironment to understand NAFLD progression. Here, an in vitro human liver model of NAFLD by coculturing human hepatocytes, umbilical vein endothelial cells (HUVECs), and Kupffer cells (KCs) into spheroids is presented. Analysis of indirect cross-talk using conditioned media between steatotic spheroids-composed of hepatocellular carcinoma-derived cells (HepG2) and HUVECs-and mouse KCs reveals that the latter can be activated showing increased cell area, elevated production of reactive oxygen species (ROS), and proinflammatory cytokines. Spheroids incorporating human KCs (HKCs) can also be induced into steatotic stage by supplementing fat. Steatotic spheroids with/without HKCs show different levels of steatotic stages through lipid accumulation and ROS production. Steatotic spheroids made from an immortalized hepatic progenitor cell line (HepaRG) compared to those made from HepG2 cells display similar trends of functionality, but elevated levels of proinflammatory cytokines, and improved reversibility of steatosis. The in vitro human liver system proposed makes strides in developing a model to mimic and monitor the progression of NAFLD.

December 2019

vanSonnenberg E, Mueller PR.

Hepatocellular carcinoma (HCC) is a worldwide scourge. As the third most common cause of deaths from cancer after lung and colon cancer, it is estimated that 700 000 to 800 000 new cases of HCC occur worldwide each year. The majority of cases occur geographically in Asia and Africa. The frequency of HCC is increasing markedly in the West and in the United States (approximately 33 000 new cases annually), with both men and women being at risk. Risk factors for HCC development include cirrhosis, viral hepatitis B and C, alcoholism, iron overload (eg, hemochromatosis, thalassemia), steroid abuse, and nonalcoholic fatty liver disease related to obesity.

December 2019

Volkmann ER, Tashkin DP, Kuwana M, Li N, Roth MD, Charles J, Hant FN, Bogatkevich GS, Akter T, Kim G, Goldin J, Khanna D, Clements PJ, Furst DE, Elashoff RM, Silver RM, Assassi S.

OBJECTIVE: To investigate the relationship between Krebs von den Lungen 6 (KL-6) and CCL18 levels and the severity and progression of systemic sclerosis (SSc)-related interstitial lung disease (ILD). METHODS: Patients enrolled in the Scleroderma Lung Study II (cyclophosphamide [CYC] versus mycophenolate mofetil [MMF]) were included. Baseline and 12-month plasma samples were analyzed by enzyme-linked immunosorbent assay to assess CCL18 and KL-6 levels. The forced vital capacity (FVC) and the diffusing capacity for carbon monoxide (DLco) were measured every 3 months. Joint models were created to investigate the relationship between baseline CCL18 and KL-6 levels and the course of the FVC and DLco over 1 year according to treatment arm.

December 2019

Yeung C, Chen S, King B, Lin H, King K, Akhtar F, Diaz G, Wang B, Zhu J, Sun W, Khademhosseini A, Emaminejad S.

Embedding microfluidic architectures with microneedles enables fluid management capabilities that present new degrees of freedom for transdermal drug delivery. To this end, fabrication schemes that can simultaneously create and integrate complex millimeter/centimeter-long microfluidic structures and micrometer-scale microneedle features are necessary. Accordingly, three-dimensional (3D) printing techniques are suitable candidates because they allow the rapid realization of customizable yet intricate microfluidic and microneedle features. However, previously reported 3D-printing approaches utilized costly instrumentation that lacked the desired versatility to print both features in a single step and the throughput to render components within distinct length-scales. Here, for the first time in literature, we devise a fabrication scheme to create hollow microneedles interfaced with microfluidic structures in a single step. Our method utilizes stereolithography 3D-printing and pushes its boundaries (achieving print resolutions below the full width half maximum laser spot size resolution) to create complex architectures with lower cost and higher print speed and throughput than previously reported methods. To demonstrate a potential application, a microfluidic-enabled microneedle architecture was printed to render hydrodynamic mixing and transdermal drug delivery within a single device. The presented architectures can be adopted in future biomedical devices to facilitate new modes of operations for transdermal drug delivery applications such as combinational therapy for preclinical testing of biologic treatments.

December 2019

Zhang L, Armstrong T, Li X, Wu HH.

PURPOSE: To develop and evaluate a variable-flip-angle golden-angle-ordered 3D stack-of-radial MRI technique for simultaneous proton resonance frequency shift (PRF) and T₁-based thermometry in aqueous and adipose tissues, respectively. METHODS: The proposed technique acquires multiecho radial k-space data in segments with alternating flip angles to measure 3D temperature maps dynamically on the basis of PRF and T₁ . A sliding-window k-space weighted image contrast filter is used to increase temporal resolution. PRF is measured in aqueous tissues and T₁ in adipose tissues using fat/water masks. The accuracy for T₁ quantification was evaluated in a reference T₁ /T₂ phantom. In vivo nonheating experiments were conducted in healthy subjects to evaluate the stability of PRF and T₁ in the brain, prostate, and breast. The proposed technique was used to monitor high-intensity focused ultrasound (HIFU) ablation in ex vivo porcine fat/muscle tissues and compared to temperature probe readings.

November 2019

Ellingson BM.

Identification and delineation of tumor burden on MR images is a critical, yet challenging, function for clinical care and neuro-oncology research. Changes in tumor burden on structural MRI sequences are used as surrogates for efficacy throughout the entire drug development pipeline, from initial preclinical evaluations through clinical tests in human patients. DeepNeuro, the algorithm recently published by Chang et al,1 and other automated approaches to tumor segmentation (see reviews by Gordillo et al, Işın et al, and Bauer et al), combined with standardization of image acquisition and knowledgeable interpretation of radiographic changes, hold great promise for accurate, repeatable, efficient, and inexpensive tumor segmentation.

November 2019

Expert Panel on Musculoskeletal Imaging, Walker EA, Beaman FD, Wessell DE, Cassidy RC, Czuczman GJ, Demertzis JL, Lenchik L, Motamedi K, Pierce JL, Sharma A, Ying-Kou Yung E, Kransdorf MJ.

Diabetes-related foot complications such as soft-tissue infection, osteomyelitis, and neuropathic osteoarthropathy account for up to 20% of all diabetic-related North American hospital admissions. Radiography of the foot is usually appropriate as the initial screening examination in diabetic patients with suspected osteomyelitis of the foot. For follow-up examination, MRI of the foot with or without contrast enhancement demonstrates excellent soft-tissue contrast and sensitivity to marrow abnormalities with high-resolution detail in multiple anatomic planes and is usually appropriate when osteomyelitis or early neuropathic arthropathy is suspected. This publication of diabetes-related foot complications summarizes the literature and makes recommendations for imaging based on the available data. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

November 2019

Fois CAM, Le TYL, Schindeler A, Naficy S, McClure DD, Read MN, Valtchev P, Khademhosseini A, Dehghani F.

Models of the human gastrointestinal tract (GIT) can be powerful tools for examining the biological interactions of food products and pharmaceuticals. This can be done under normal healthy conditions or using models of disease-many of which have no curative therapy. This report outlines the field of gastrointestinal modeling, with a particular focus on the intestine. Traditional in vivo animal models are compared to a range of in vitro models. In vitro systems are elaborated over time, recently culminating with microfluidic intestines-on-chips (IsOC) and 3D bioengineered models. Macroscale models are also reviewed for their important contribution in the microbiota studies. Lastly, it is discussed how in silico approaches may have utility in predicting and interpreting experimental data. The various advantages and limitations of the different systems are contrasted. It is posited that only through complementary use of these models will salient research questions be able to be addressed.

November 2019

Holly LT, Wang C, Woodworth DC, Salamon N, Ellingson BM.

Cervical degenerative disease is a major cause of neck disability, but it has been understudied in patients with cervical spondylotic (CS), largely due to the fact that the neurological impairment associated with this condition tends to be the primary treatment focus. This observational study examined the cerebral functional alterations occurring in advanced cervical spondylosis and myelopathy using resting state functional MRI. Associations between functional connectivity (FC) and neck disability using the Neck Disability Index (NDI) were assessed. Results of the study demonstrated an increase in FC with increasing in neck disability in regions associated with sensorimotor system (both postcentral gyri and precentral gyri, bilaterally, with the SMA; bilateral precentral gyri and the left postcentral gyrus, with the left superior frontal gyrus; bilateral SMA and the left putamen, with the superior frontal gyri). Accounting for the difference in neurological function (mJOA score), strong connectivity between the precentral gyri and the SMA associated with the neck disability. Consistent with studies in chronic pain conditions, these findings suggest neck disability is associated with altered cerebral FC in cervical spondylosis patients.

November 2019

Hung ML, Lee EW.

Transjugular intrahepatic portosystemic shunt (TIPS) is a well-established procedure used in the management of complications of portal hypertension. Although the most robust evidence supports the use of TIPS as salvage therapy in variceal hemorrhage, secondary prophylaxis of variceal bleeding, and treatment of refractory ascites, there is also data to suggest its efficacy in other indications such as hepatic hydrothorax, hepatorenal syndrome, and Budd-Chiari syndrome. Recent literature also suggests that TIPS may improve survival for certain subpopulations if placed early after variceal bleeding. This article provides an updated evidence-based review of the indications for TIPS. Outcomes, complications, and adequate patient selection are also discussed.

November 2019

Lee J, Manoharan V, Cheung L, Lee S, Cha BH, Newman P, Farzad R, Mehrotra S, Zhang K, Khan F, Ghaderi M, Lin YD, Aftab S, Mostafalu P, Miscuglio M, Li J, Mandal BB, Hussain MA, Wan KT, Tang XS, Khademhosseini A, Shin SR.

Myocardial microenvironment plays a decisive role in guiding the function and fate of cardiomyocytes, and engineering this extracellular niche holds great promise for cardiac tissue regeneration. Platforms utilizing hybrid hydrogels containing various types of conductive nanoparticles have been a critical tool for constructing engineered cardiac tissues with outstanding mechanical integrity and improved electrophysiological properties. However, there has been no attempt to directly compare the efficacy of these hybrid hydrogels and decipher the mechanisms behind how these platforms differentially regulate cardiomyocyte behavior. Here, we employed gelatin methacryloyl (GelMA) hydrogels containing three different types of carbon-based nanoparticles: carbon nanotubes (CNTs), graphene oxide (GO), and reduced GO (rGO), to investigate the influence of these hybrid scaffolds on the structural organization and functionality of cardiomyocytes. Using immunofluorescent staining for assessing cellular organization and proliferation, we showed that electrically conductive scaffolds (CNT- and rGO-GelMA compared to relatively nonconductive GO-GelMA) played a significant role in promoting desirable morphology of cardiomyocytes and elevated the expression of functional cardiac markers, while maintaining their viability. Electrophysiological analysis revealed that these engineered cardiac tissues showed distinct cardiomyocyte phenotypes and different levels of maturity based on the substrate (CNT-GelMA: ventricular-like, GO-GelMA: atrial-like, and rGO-GelMA: ventricular/atrial mixed phenotypes). Through analysis of gene-expression patterns, we uncovered that the engineered cardiac tissues matured on CNT-GelMA and native cardiac tissues showed comparable expression levels of maturation markers. Furthermore, we demonstrated that engineered cardiac tissues matured on CNT-GelMA have increased functionality through integrin-mediated mechanotransduction (via YAP/TAZ) in contrast to cardiomyocytes cultured on rGO-GelMA.

November 2019

Levin ES, Plotkin B, Levine BD, Motamedi K, Burton L, Seeger LL.

OBJECTIVE: To determine the clinical significance of T2 signal hyperintensity in the proximal patellar tendon seen on MRI of the knee. MATERIALS AND METHODS: MRIs of 100 patients who underwent MRI of the knee between 1 May 2018 and 15 July 2018 were retrospectively evaluated. All examinations were performed on 3-Tesla MRI scanners with a dedicated knee coil and in accordance with our institution's standard knee MRI protocol. The presence of increased T2 signal was assessed on both sagittal and axial T2-weighted fat-saturated images. The amount of increased signal in the proximal patellar tendon on T2-weighted images was characterized as: none, mild, moderate, or severe. A corresponding chart review of the referring physicians' notes was performed to determine the presence of clinical symptoms of patellar tendinopathy. Patellar tendinopathy was considered present if the clinical notes described tenderness on palpation of the inferior patellar pole, infrapatellar tenderness, or patellar tendinosis/tendinitis.

November 2019

Mathevosian S, Plotnik AN, McWilliams JP.

Eight patients with giant prostatic enlargement > 200 mL and lower urinary tract symptoms who underwent bilateral prostatic artery embolization (PAE) were reviewed. Mean prostate volume decreased from 318.2 mL to 212.2 mL (P < .01). At 5-month mean follow-up, International Prostate Symptom Score decreased by 16.7 points (P < .05), and urinary quality of life improved by 3.0 points (P < .01). Three of 4 catheter-dependent patients no longer needed catheterization after the procedure. No major complications were encountered. Preliminary results suggest PAE is safe and effective in patients with giant prostatic enlargement > 200 mL.

November 2019

Nariai H, Hussain SA, Bernardo D, Fallah A, Murata KK, Nguyen JC, Rajaraman RR, Rao LM, Matsumoto JH, Lerner JT, Salamon N, Elashoff D, Sankar R, Wu JY.

OBJECTIVE: To investigate spatial correlation between interictal HFOs and neuroimaging abnormalities, and to determine if complete removal of prospectively identified interictal HFOs correlates with post-surgical seizure-freedom. METHODS: Interictal fast ripples (FRs: 250-500 Hz) in 19 consecutive children with pharmacoresistant focal epilepsy who underwent extra-operative electrocorticography (ECoG) recording were prospectively analyzed. The interictal FRs were sampled at 2000 Hz and were visually identified during 10 min of slow wave sleep. Interictal FRs, MRI and FDG-PET were delineated on patient-specific reconstructed three-dimensional brain MRI.

November 2019

Nasiri N, Hosseini S, Alini M, Khademhosseini A, Baghaban Eslaminejad M.

Osteoarthritis (OA) is one of the main causes of pain and disability worldwide. In recent years, numerous efforts have been made in pharmaceutical and surgical therapies for OA management. The therapeutic features of mesenchymal stem cells (MSCs), have led to numerous preclinical and clinical trials that confirmed the efficacy of cell therapy as treatment for OA. Recent works have attempted to customize cell participation in tissue regeneration using site specific targeting approaches. Targeting approaches are based on direct modifications to the surface of MSCs or indirect modifications on an engineered nanomediator. Here, we provide a comprehensive review of the advances in targeted cell delivery and define the priorities for future work in terms of OA and cartilage regeneration.

November 2019

Yu YN, Liu MW, Villablanca JP, Li ML, Xu YY, Gao S, Feng F, Liebeskind DS, Scalzo F, Xu WH.

BACKGROUND AND PURPOSE: Vessel wall imaging can identify intracranial atherosclerotic plaque and give clues about its components. We aimed to investigate whether the plaque hyperintensity in the middle cerebral artery on T2-weighted vessel wall imaging is associated with ischemic stroke. MATERIALS AND METHODS: We retrospectively reviewed our institutional vessel wall MR imaging data base. Patients with an acute ischemic stroke within 7-day onset in the MCA territory were enrolled. Patients with stroke and stenotic MCA plaque (stenosis degree, ≥50%) were included for analysis. Ipsilateral MCA plaque was defined as symptomatic, and contralateral plaque, as asymptomatic. Plaque was manually delineated on T2-weighted vessel wall imaging. The plaque signal was normalized to the ipsilateral muscle signal. The thresholds and volume of normalized plaque signal were investigated using logistic regression and receiver operating characteristic analysis to determine the association between normalized plaque signal and stroke.

October 2019

Arafati A, Hu P, Finn JP, Rickers C, Cheng AL, Jafarkhani H, Kheradvar A.

Cardiac MRI (CMR) allows non-invasive, non-ionizing assessment of cardiac function and anatomy in patients with congenital heart disease (CHD). The utility of CMR as a non-invasive imaging tool for evaluation of CHD have been growing exponentially over the past decade. The algorithms based on artificial intelligence (AI), and in particular, deep learning, have rapidly become a methodology of choice for analyzing CMR. A wide range of applications for AI have been developed to tackle challenges in various aspects of CMR, and significant advances have also been made from image acquisition to image analysis and diagnosis. We include an overview of AI definitions, different architectures, and details on well-known methods. This paper reviews the major deep learning concepts used for analyses of patients with CHD. In the end, we have summarized a list of open challenges and concerns to be considered for future studies.

October 2019

Bongers M, Gupta J, Garza-Leal JG, Brown M, Felberbaum R.

OBJECTIVE: The aim of this research was to evaluate uterine-wall integrity 12 months after transcervical fibroid ablation (TFA) of uterine fibroids with the Sonata^® system (Gynesonics Inc., Redwood City, CA). MATERIALS AND METHODS: INTEGRITY is a secondary analysis of the FAST-EU clinical trial, a prospective, longitudinal, multicenter single-armed trial involving women with heavy menstrual bleeding secondary to fibroids who were treated at 7 academic and community hospitals in the United Kingdom, the Netherlands, and Mexico with transcervical, intrauterine, ultrasound-guided radiofrequency ablation (the Sonata system). TFA was performed on up to 5 fibroids per subject ranging from 1-5 cm in diameter as determined by magnetic resonance imaging (MRI). All measurements and comparisons, including uterine-wall thicknesses were derived from baseline and 12-month MRI scans by an independent core MRI center. Scans were analyzed to assess preservation of uterine-wall integrity and reviewed for uterine-wall anomalies after TFA with the Sonata system.

October 2019

Ding PX, Han XW, Liu C, Ding JY, Lee EW.

Percutaneous transluminal balloon angioplasty (PTA) is the main treatment option for Budd-Chiari syndrome (BCS) with inferior vena cava (IVC) obstruction. However, IVC rupture caused by PTA has never been reported. MATERIALS AND METHODS: Between August 2004 and December 2016, a consecutive cohort of 617 BCS patients with obstructed IVC who underwent PTA with or without stent placement were reviewed retrospectively to identify IVC rupture. Pre- and post-procedural imaging data, clinical and procedural technical data were analyzed.

October 2019

Graham DS, Russell TA, Eckardt MA, Motamedi K, Seeger LL, Singh AS, Bernthal NM, Kalbasi A, Dry SM, Nelson SD, Elashoff D, Levine BD, Eilber FC.

OBJECTIVES: Peripheral nerve sheath tumors (PNSTs) are clinically heterogenous, comprising benign (BPNST) and malignant (MPNST) variants. BPNSTs can be managed with nerve-sparing excision or observation. MPNSTs require radical resection and multidisciplinary oncologic management (1, 15). Image-guided core-needle biopsy (IGCNBx) is the well-established standard to obtain preoperative tissue diagnosis of soft tissue tumors. However, there has been resistance to performing IGCNBx of PNSTs because of the presumed risk of nerve injury and unknown accuracy in determining malignancy. We sought to define the accuracy and safety of IGCNBx in PNSTs. MATERIALS AND METHODS: All patients that underwent both IGCNBx and surgical resection of a PNST at our institution between 2002 and 2016 were analyzed. The accuracy of IGCNBx in determining malignancy was calculated, including subgroup analyses by histologic subtype and neurofibromatosis 1 status. Complication data were collected and analyzed.

October 2019

Hassan AE, Shariff U, Saver JL, Goyal M, Liebeskind D, Jahan R, Qureshi AI.

BACKGROUND: Procedural time in patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy may affect clinical outcomes. We performed a pooled analysis of the effect of procedural time on clinical outcomes using data from three prospective endovascular treatment trials. OBJECTIVE: To examine the relationship between endovascular procedural time and clinical outcomes of patients with AIS following endovascular treatment.

October 2019

Hsu MJ, Tran DN, Srinivasa RN, Padia SA.

A 75-year-old man with isolated liver metastasis from prostate cancer refractory to systemic chemotherapy was referred for radioembolization (Fig 1). The chronically occluded celiac artery could not be traversed. Retrograde cannulation of the gastroduodenal artery was performed via the superior mesenteric artery using a 0.021-inch Direxion microcatheter (Boston Scientific, Marlborough, Massachusetts) and 0.016-inch Fathom wire (Boston Scientific) with successful catheterization of the right hepatic artery.

October 2019

Krysan K, Tran LM, Grimes BS, Fishbein GA, Seki A, Gardner BK, Walser TC, Salehi-Rad R, Yanagawa J, Lee JM, Sharma S, Aberle DR, Spira AE, Elashoff DA, Wallace WD, Fishbein MC, Dubinett SM.

Epithelial cells in the field of lung injury can give rise to distinct premalignant lesions that may bear unique genetic aberrations. A subset of these lesions may escape immune surveillance and progress to invasive cancer; however, the mutational landscape that may predict progression has not been determined. Knowledge of premalignant lesion composition and the associated microenvironment is critical for understanding tumorigenesis and the development of effective preventive and interception strategies. To identify somatic mutations and the extent of immune cell infiltration in adenomatous premalignancy and associated lung adenocarcinomas, we sequenced exomes from 41 lung cancer resection specimens, including 89 premalignant atypical adenomatous hyperplasia lesions, 15 adenocarcinomas in situ, and 55 invasive adenocarcinomas and their adjacent normal lung tissues. We defined nonsynonymous somatic mutations occurring in both premalignancy and the associated tumor as progression-associated mutations whose predicted neoantigens were highly correlated with infiltration of CD8⁺ and CD4⁺ T cells as well as upregulation of PD-L1 in premalignant lesions, suggesting the presence of an adaptive immune response to these neoantigens. Each patient had a unique repertoire of somatic mutations and associated neoantigens. Collectively, these results provide evidence for mutational heterogeneity, pathway dysregulation, and immune recognition in pulmonary premalignancy.Significance: These findings identify progression-associated somatic mutations, oncogenic pathways, and association between the mutational landscape and adaptive immune responses in adenomatous premalignancy.

October 2019

Maletkovic J, Dabbagh A, Zhang D, Zahid A, Bergsneider M, Wang MB, Linetsky M, Salamon N, Yong WH, Vinters HV, Heaney AP.

OBJECTIVE: We evaluated tumor recurrence and regrowth rates following endoscopic transnasal transsphenoidal (TNTS) surgical removal in a consecutive series of clinically nonfunctioning pituitary adenomas (CNFTs). DESIGN: Retrospective chart review of clinical, biochemical, and sellar MRI findings in all TNTS surgeries in patients with CNFT, performed by a single surgeon, between 2008 and 2015 (n = 280). PATIENTS: Ninety-three patients met eligibility criteria, with complete clinical, biochemical, and imaging follow-up for a 3-year minimum.

October 2019

Miri AK, Mostafavi E, Khorsandi D, Hu SK, Malpica M, Khademhosseini A.

Recent advances in bioprinting technologies have enabled rapid manufacturing of organ-on-chip models along with biomimetic tissue microarchitectures. Bioprinting techniques can be used to integrate microfluidic channels and flow connections in organ-on-chip models. We review bioprinters in two categories of nozzle-based and optical-based methods, and then discuss their fabrication parameters such as resolution, replication fidelity, fabrication time, and cost for micro-tissue models and microfluidic applications. The use of bioprinters has shown successful replicates of functional engineered tissue models integrated within a desired microfluidic system, which facilitates the observation of metabolism or secretion of models and sophisticated control of a dynamic environment. This may provide a wider order of tissue engineering fabrication in mimicking physiological conditions for enhancing further applications such as drug development and pathological studies.

October 2019

Omigbodun AO, Noo F, McNitt-Gray M, Hsu W, Hsieh SS.

PURPOSE: An important challenge for deep learning models is generalizing to new datasets that may be acquired with acquisition protocols different from the training set. It is not always feasible to expand training data to the range encountered in clinical practice. We introduce a new technique, physics-based data augmentation (PBDA), that can emulate new computed tomography (CT) data acquisition protocols. We demonstrate two forms of PBDA, emulating increases in slice thickness and reductions of dose, on the specific problem of false-positive reduction in the automatic detection of lung nodules. METHODS: We worked with CT images from the lung image database consortium (LIDC) collection. We employed a hybrid ensemble convolutional neural network (CNN), which consists of multiple CNN modules (VGG, DenseNet, ResNet), for a classification task of determining whether an image patch was a suspicious nodule or a false positive. To emulate a reduction in tube current, we injected noise by simulating forward projection, noise addition, and backprojection corresponding to 1.5 mAs (a "chest x-ray" dose). To simulate thick slice CT scans from thin slice CT scans, we grouped and averaged spatially contiguous CT within thin slice data. The neural network was trained with 10% of the LIDC dataset that was selected to have either the highest tube current or the thinnest slices. The network was tested on the remaining data. We compared PBDA to a baseline with standard geometric augmentations (such as shifts and rotations) and Gaussian noise addition.

October 2019

Quirk M, Srinivasa RN, McWilliams JP, Plotnik AN.

Chronic kidney disease (CKD) secondary to obstructive uropathy is a known complication of advanced benign prostatic hyperplasia (BPH) (1). Prostatic artery embolization (PAE) effectively treats lower urinary tract symptoms related to BPH and relieves urinary obstruction but requires angiography, typically with iodinated contrast material, which is relatively contraindicated in CKD. This case of obstructive uropathy was treated with PAE performed with predominantly carbon dioxide (CO2) contrast material.

October 2019

Three-Dimensional Bioprinting of Functional Skeletal Muscle Tissue Using GelatinMethacryloyl-Alginate Bioinks.

Skeletal muscle tissue engineering aims to fabricate tissue constructs to replace or restore diseased or injured skeletal muscle tissues in the body. Several biomaterials and microscale technologies have been used in muscle tissue engineering. However, it is still challenging to mimic the function and structure of the native muscle tissues. Three-dimensional (3D) bioprinting is a powerful tool to mimic the hierarchical structure of native tissues. Here, 3D bioprinting was used to fabricate tissue constructs using gelatin methacryloyl (GelMA)-alginate bioinks. Mechanical and rheological properties of GelMA-alginate hydrogels were characterized. C2C12 myoblasts at the density 8 x 10⁶ cells/mL were used as the cell model. The effects of alginate concentration (0, 6, and 8% (w/v)) and crosslinking mechanism (UV crosslinking or ionic crosslinking with UV crosslinking) on printability, cell viability, proliferation, and differentiation of bioinks were studied.

October 2019

Sung K.

BACKGROUND: An estimation of an intravascular dispersion parameter was previously proposed to improve the overall accuracy and precision of the model parameters, but the high computation complexity can limit its practical usability in prostate dynamic contrast-enhanced MRI (DCE-MRI). PURPOSE: To compare and evaluate the model fitting uncertainty and error in the model parameter estimation using different DCE-MRI analysis models and to evaluate the ability of the intravascular dispersion parameter to delineate between noncancerous and cancerous prostate tissue in the transition and peripheral zones. STUDY TYPE: Retrospective. POPULATION: Fifty-three patients who underwent radical prostatectomy. FIELD STRENGTH/SEQUENCE: 3 T/3D RF-spoiled gradient echo sequence. ASSESSMENT: The coefficient of variation was used to assess the model fitting uncertainty by adding random noise to the time-concentration curves, and the Akaike information criterion was used to assess the model fitting error. The parametric maps derived from four DCE-MRI analysis models were evaluated by evaluating the delineation between noncancerous tissue and prostate cancer or clinically significant prostate cancer. STATISTICAL TESTS: The receiver operating curve analysis was performed to compare the ability to delineate between noncancerous and prostate cancer tissue in the transition and peripheral zones.

October 2019

van Luijtelaar A, Greenwood BM, Ahmed HU, Barqawi AB, Barret E, Bomers JGR, Brausi MA, Choyke PL, Cooperberg MR, Eggener S, Feller JF, Frauscher F, George AK, Hindley RG, Jenniskens SFM, Klotz L, Kovacs G, Lindner U, Loeb S, Margolis DJ, Marks LS, May S, Mcclure TD, Montironi R, Nour SG, Oto A, Polascik TJ, Rastinehad AR, De Reyke TM, Reijnen JS, de la Rosette JJMCH, Sedelaar JPM, Sperling DS, Walser EM, Ward JF, Villers A, Ghai S, Fütterer JJ.

PURPOSE: To define the role of focal laser ablation (FLA) as clinical treatment of prostate cancer (PCa) using the Delphi consensus method. METHODS: A panel of international experts in the field of focal therapy (FT) in PCa conducted a collaborative consensus project using the Delphi method. Experts were invited to online questionnaires focusing on patient selection and treatment of PCa with FLA during four subsequent rounds. After each round, outcomes were displayed, and questionnaires were modified based on the comments provided by panelists. Results were finalized and discussed during face-to-face meetings.

October 2019

Volkmann ER, Tashkin DP, Sim M, Li N, Khanna D, Roth MD, Clements PJ, Hoffmann-Vold AM, Furst DE, Kim G, Goldin J, Elashoff RM.

OBJECTIVE: To compare safety and efficacy outcomes between the cyclophosphamide (CYC) arms of Scleroderma Lung Study (SLS) I and II. METHODS: Participants enrolled in the CYC arms of SLS I (n = 79) and II (n = 69) were included. SLS I and II randomized participants to oral CYC for 1 year and followed patients for an additional year off therapy (in SLS II, patients received placebo in Year 2). Eligibility criteria for SLS I and II were nearly identical. Outcomes included the forced vital capacity (FVC%)-predicted and DLCO%-predicted (measured every 3 mos) and quantitative radiographic extent of interstitial lung disease (measured at 1 and 2 yrs for SLS I and SLS II, respectively). Joint models were created to evaluate the treatment effect on the course of the FVC/DLCO over 2 years while controlling for baseline disease severity.

September 2019

Albertson NR, Chick JFB, Jiao A, Healey TL, Plotnik AN, Srinivasa RN.

While the tools and techniques employed by interventional radiologists on a day-to-day basis translate well to learning the skills required to perform basic endoscopic interventions, collaboration with other specialties is crucial to the success of an interventional radiology endoscopy program. As in any field in medicine, the paramount goal is to improve patient care. Adding the ability to directly visualize structures through an endoscope to certain interventional radiologic procedures may greatly augment the efficacy, safety, and success of interventional radiology procedures. Colleagues in urology, gastroenterology, and surgery should be involved in decision-making and treatment planning to ensure that a shared vision for optimal patient care is achieved.

September 2019

Bajgiran AM, Mirak SA, Sung K, Sisk AE, Reiter RE, Raman SS.

OBJECTIVE. The purpose of this study is to evaluate the performance of the apparent diffusion coefficient ratio (ADCratio; the ADC of the suspected prostate cancer [PCa] focus on MRI divided by the ADC in a noncancerous reference area) with that of conventional ADC for detection of high-grade PCa (Gleason score [GS] ≥ 3 + 4) versus low-grade PCa (GS = 3 + 3) with whole-mount (WM) histopathologic analysis used as a reference. MATERIALS AND METHODS. The cohort of this retrospective study included 218 men with 240 unilateral PCa lesions assessed by both 3-T multiparametric MRI and whole-mount histopathologic analysis. ROIs were placed on individual lesions verified by WM histopathologic analysis, to calculate the mean ADC (ADC_{tumor_mean}) and lowest ADC within each lesion (ADC_{tumor_min}), and within non-tumor-containing regions of the same tumor zone but on the contralateral side (ADC_benign), to calculate the background ADC. The ADCratio_mean (the ADC_{tumor_mean} divided by the ADC_benign) was calculated. The performance of individual ADC_tumor and ADCratio_mean values in discriminating PCa with a GS of 3 + 3 from PCa with a GS of 3 + 4 or greater was assessed using the AUC value.

September 2019

Gaonkar B, Villaroman D, Beckett J, Ahn C, Attiah M, Babayan D, Villablanca JP, Salamon N, Bui A, Macyszyn L.

BACKGROUND AND PURPOSE: Quantitative imaging biomarkers have not been established for the diagnosis of spinal canal stenosis. This work aimed to lay the groundwork to establish such biomarkers by leveraging the developments in machine learning and medical imaging informatics. MATERIALS AND METHODS: Machine learning algorithms were trained to segment lumbar spinal canal areas on axial views and intervertebral discs on sagittal views of lumbar MRIs. These were used to measure spinal canal areas at each lumbar level (L1 through L5). Machine-generated delineations were compared with 2 sets of human-generated delineations to validate the proposed techniques. Then, we use these machine learning methods to delineate and measure lumbar spinal canal areas in a normative cohort and to analyze their variation with respect to age, sex, and height using a variable-intercept mixed model.

September 2019

Johnson DC, Yang JJ, Kwan L, Barsa DE, Mirak SA, Pooli A, Sadun T, Jayadevan R, Zhou S, Priester AM, Natarajan S, Bajgiran AM, Shakeri S, Sisk A, Felker ER, Raman SS, Marks LS, Reiter RE.

BACKGROUND: Hemiablation is a less morbid treatment alternative for appropriately selected patients with unilateral prostate cancer (PCa). However, to the authors' knowledge, traditional diagnostic techniques inadequately identify appropriate candidates. In the current study, the authors quantified the accuracy for identifying hemiablation candidates using contemporary diagnostic techniques, including multiparametric magnetic resonance imaging (mpMRI) and MRI-fusion with complete systematic template biopsy. METHODS: A retrospective analysis of patients undergoing MRI and MRI-fusion prostate biopsy, including full systematic template biopsy, prior to radical prostatectomy in a single tertiary academic institution between June 2010 and February 2018 was performed. Hemiablation candidates had unilateral intermediate-risk PCa (Gleason score [GS] of 3+4 or 4+3, clinical T classification ≤T2, and prostate-specific antigen level <20 ng/dL) on MRI-fusion biopsy and 2) no contralateral highly or very highly suspicious Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) MRI lesions. Hemiablation candidates were inappropriately selected if pathologists identified contralateral GS ≥3+4 or high-risk ipsilateral PCa on prostatectomy. The authors tested a range of hemiablation inclusion criteria and performed multivariable analysis of preoperative predictors of undetected contralateral disease.

September 2019

Justinvil GN, Leidholdt EM Jr, Balter S, Graves LL, Loring BA, Brenner AC, Boyle NG, Srinivasa RN, Moran JM.

PURPOSE: Fluoroscopically guided interventional (FGI) procedures often have lower complication rates compared with alternative surgical procedures, providing an option for patients with a high risk of perioperative mortality. Although severe radiation injuries are rare, patients receiving peak skin doses exceeding 3 Gy can suffer from radiation-induced tissue injuries, ranging from transient erythema to nonhealing wounds. As these iatrogenic injuries may manifest weeks to months postprocedure, proper diagnosis and timely medical intervention are less likely. Clinically, the lack of situational awareness for monitoring air kerma continues to be a challenge despite the recommendations of numerous organizations on ways to achieve fluoroscopy safety. For patient safety efforts, this study aimed to identify and mitigate systematic gaps associated with potentially high-radiation dose fluoroscopic procedures in US Department of Veterans Affairs (VA) and non-VA medical institutions. METHODS: In this study, a multi-institutional team utilized Healthcare Failure Mode and Effect Analysis (HFMEA) on an example implantable cardioverter defibrillator lead extraction procedure

September 2019

Khayat M, Khayat A, Chick JFB, Healey TL, Srinivasa RN.

September 2019

Kuo F, Park J, Chow K, Chen A, Walsworth MK.

Although peripheral nerve injuries secondary to angiography and endovascular interventions are uncommon and usually not permanent, they can result in significant functional impairment. Most arteries used in access for angiography and endovascular therapies lie in close proximity to a nerve. The nerve may be injured by needle puncture, or by compression from hematoma, pseudoaneurysm, hemostasis devices, or by manual compression with incidence in literature ranging from as low as 0.04% for femoral access in a large retrospective study to 9% for brachial and axillary access. Given the increasing frequency of endovascular arterial procedures and the increasing use of nontraditional access points, it is important that the interventionalist have a working knowledge of peripheral nerve anatomy and function as it relates to relevant arterial access sites to avoid injury.

September 2019

Makary MS, Farrell JJ, Khayat M, Chick JFB, Srinivasa RN.

Percutaneous endoscopy operated by interventional radiologists has the potential to become an effective tool to both help diagnose and treat benign and malignant biliary strictures. This is particularly true in cases where endoscopic retrograde cholangiopancreatography fails or is not feasible due to surgically-altered anatomy. Both preoperative clinical and technical procedural factors must be taken into consideration when pursuing percutaneous endoscopy. In this article, clinical evaluation, perioperative management, and procedural techniques for biliary endoscopy for benign and malignant strictures are reviewed.

September 2019

Mer J, Chick JFB, Healey TL, Johnson EJ, Srinivasa RN.

A sound understanding of billing and coding is essential to start a successful interventional radiology endoscopy practice. While the codes utilized are similar to gastrointestinal and genitourinary endoscopy codes, physicians and institutional coders need to be familiar with the codes used for these types of procedures in the interventional radiology setting. The following manuscript gives a brief overview of aspects relating to credentialing, billing, and coding in interventional radiology endoscopy.

September 2019

Miri AK, Mostafavi E, Khorsandi D, Hu SK, Malpica M, Khademhosseini A.

Recent advances in bioprinting technologies have enabled rapid manufacturing of organ-on-chip models along with biomimetic tissue microarchitectures. Bioprinting techniques can be used to integrate microfluidic channels and flow connections in organ-on-chip models. We review bioprinters in two categories of nozzle-based and optical-based methods, and then discuss their fabrication parameters such as resolution, replication fidelity, fabrication time, and cost for micro-tissue models and microfluidic applications. The use of bioprinters has shown successful replicates of functional engineered tissue models integrated within a desired microfluidic system, which facilitates the observation of metabolism or secretion of models and sophisticated control of a dynamic environment. This may provide a wider order of tissue engineering fabrication in mimicking physiological conditions for enhancing further applications such as drug development and pathological studies.

September 2019

Munden RF, Chiles C, Boiselle PM, Sicks JD, Aberle DR, Gatsonis CA.

In the National Lung Screening Trial (NLST) all cases with a 4-mm nodule (micronodule) and no other findings were classified as a negative study. The prevalence and malignant potential of micronodules in the NLST is evaluated to understand if this classification was appropriate. METHODS AND MATERIALS: In the NLST a total of 53,452 participants were enrolled with 26,722 undergoing low-dose computed tomography (CT) screening. To determine whether a micronodule developed into a lung cancer, a list from the NLST database of those participants who developed lung cancer and had a micronodule recorded was selected. The CT images of this subset were reviewed by experienced, fellowship-trained thoracic radiologists (R.F.M., C.C., P.M.B., and D.R.A.), all of whom participated as readers in the NLST.

September 2019

Oliai C, Douek ML, Rhoane C, Bhutada A, Ge PS, Runyon BA, Wang X, Hurvitz SA.

PURPOSE: Pseudocirrhosis has been demonstrated to mimic cirrhosis radiographically, but studies evaluating the pathophysiology and clinical features are lacking. To better understand the incidence, risk factors, clinical course, and etiology of pseudocirrhosis, we performed a retrospective analysis of consecutively treated patients with metastatic breast cancer (MBC). METHODS: Of 374 patients treated for MBC from 2006 to 2012, 199 had imaging available for review. One radiologist evaluated computed tomography scans for evidence of pseudocirrhosis. Features of groups with and without pseudocirrhosis were compared by Kaplan-Meier product-limit survival estimates and log-rank tests. Wilcoxon Rank-Sum testing evaluated if patients more heavily treated were more likely to develop pseudocirrhosis. Univariate and multivariate Cox proportional hazard models investigated factors associated with mortality.

September 2019

Raymond CJ, Khayat M, Chick JFB, Srinivasa RN.

Endoscopy is an underutilized technique in the practice of interventional radiology. The objectives of this article are to discuss potential uses of interventional radiology-operated endoscopy and to outline basic endoscopy setup and equipment uses. Endoscopy represents a new frontier to the fluoroscopically-guided procedures in biliary, gastrointestinal, and genitourinary disease that interventional radiologists commonly perform. It shows promise to improve interventional radiology procedure success rates and reduce procedure-associated risk for patients. Endoscopy has been traditionally performed by gastroenterologists and urologists and is relatively new in the practice of interventional radiology. The hand-eye coordination and manual dexterity required to perform standard image-guided procedures places interventional radiologists in a unique position to introduce endoscopy into standard practice. A focused and collaborative effort is needed by interventional radiologists to learn the techniques required to successfully integrate endoscopy into practice.

September 2019

Schabath MB, Aberle DR.

In a landmark analysis, investigators of the Multicentric Italian Lung Detection (MILD) trial have confirmed 10-year mortality reductions with lung cancer screening using low-dose helical CT (LDCT). These data complement the reduced lung cancer-specific mortality reported in the National Lung Screening Trial and reinforce the rationale for broad implementation of LDCT screening in high-risk populations.

September 2019

Sheth SA, Lee S, Warach SJ, Gralla J, Jahan R, Goyal M, Nogueira RG, Zaidat OO, Pereira VM, Siddiqui A, Lutsep H, Liebeskind DS, McCullough LD, Saver JL.

Background and Purpose- We determined the effect of sex on outcome after endovascular stroke thrombectomy in acute ischemic stroke, including lifelong disability outcomes. Methods- We analyzed patients treated with the Solitaire stent retriever in the combined SWIFT (Solitaire FR With the Intention for Thrombectomy), STAR (Solitaire FR Thrombectomy for Acute Revascularization), and SWIFT PRIME (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment) cohorts. Ordinal and logistic regression were used to examine known factors influencing outcome after endovascular stroke thrombectomy and study the effect of sex on the association between these factors and outcomes, including age and time to reperfusion. Years of optimal life after thrombectomy were defined as disability-adjusted life years and calculated by projecting disability through adjusted poststroke life expectancy by sex.

September 2019

Shi Y, Wong WK, Goldin JG, Brown MS, Kim GHJ.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by an unpredictable progressive decline in lung function. Natural history of IPF is unknown and the prediction of disease progression at the time of diagnosis is notoriously difficult. High resolution computed tomography (HRCT) has been used for the diagnosis of IPF, but not generally for monitoring purpose. The objective of this work is to develop a novel predictive model for the radiological progression pattern at voxel-wise level using only baseline HRCT scans. Mainly, there are two challenges: (a) obtaining a data set of features for region of interest (ROI) on baseline HRCT scans and their follow-up status; and (b) simultaneously selecting important features from high-dimensional space, and optimizing the prediction performance. We resolved the first challenge by implementing a study design and having an expert radiologist contour ROIs at baseline scans, depending on its progression status in follow-up visits. For the second challenge, we integrated the feature selection with prediction by developing an algorithm using a wrapper method that combines quantum particle swarm optimization to select a small number of features with random forest to classify early patterns of progression. We applied our proposed algorithm to analyze anonymized HRCT images from 50 IPF subjects from a multi-center clinical trial. We showed that it yields a parsimonious model with 81.8% sensitivity, 82.2% specificity and an overall accuracy rate of 82.1% at the ROI level. These results are superior to other popular feature selections and classification methods, in that our method produces higher accuracy in prediction of progression and more balanced sensitivity and specificity with a smaller number of selected features. Our work is the first approach to show that it is possible to use only baseline HRCT scans to predict progressive ROIs at 6 months to 1year follow-ups using artificial intelligence.

September 2019

Shi Y, Wong WK, Goldin JG, Brown MS, Kim GHJ.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by an unpredictable progressive decline in lung function. Natural history of IPF is unknown and the prediction of disease progression at the time of diagnosis is notoriously difficult. High resolution computed tomography (HRCT) has been used for the diagnosis of IPF, but not generally for monitoring purpose. The objective of this work is to develop a novel predictive model for the radiological progression pattern at voxel-wise level using only baseline HRCT scans. Mainly, there are two challenges: (a) obtaining a data set of features for region of interest (ROI) on baseline HRCT scans and their follow-up status; and (b) simultaneously selecting important features from high-dimensional space, and optimizing the prediction performance. We resolved the first challenge by implementing a study design and having an expert radiologist contour ROIs at baseline scans, depending on its progression status in follow-up visits. For the second challenge, we integrated the feature selection with prediction by developing an algorithm using a wrapper method that combines quantum particle swarm optimization to select a small number of features with random forest to classify early patterns of progression. We applied our proposed algorithm to analyze anonymized HRCT images from 50 IPF subjects from a multi-center clinical trial. We showed that it yields a parsimonious model with 81.8% sensitivity, 82.2% specificity and an overall accuracy rate of 82.1% at the ROI level. These results are superior to other popular feature selections and classification methods, in that our method produces higher accuracy in prediction of progression and more balanced sensitivity and specificity with a smaller number of selected features. Our work is the first approach to show that it is possible to use only baseline HRCT scans to predict progressive ROIs at 6 months to 1year follow-ups using artificial intelligence.

September 2019

Srinivasa RN, Chick JFB.

Interventional Radiology is a specialty rooted in innovation. From the development of the Seldinger technique by Dr Sven-Ivar Seldinger in 1953 to the targeted locoregional oncologic interventions performed routinely today, Interventional Radiology provides therapy to patients in near-hopeless clinical scenarios by using revolutionary techniques when mainstay therapies have failed. Among these techniques is endoscopy as an adjunct to image-guided interventions.

September 2019

Zhao T, McNitt-Gray M, Ruan D.

PURPOSE: Reducing dose level to achieve ALARA is an important task in diagnostic and therapeutic applications of computed tomography (CT) imaging. Effective image quality enhancement strategies are crucial to compensate for the degradation caused by dose reduction. In the past few years, deep learning approaches have demonstrated promising denoising performance on natural/synthetic images. This study tailors a neural network model for (ultra-)low-dose CT denoising, and assesses its performance in enhancing CT image quality and emphysema quantification. METHODS: The noise statistics in low-dose CT images has its unique characteristics and differs from that used in general denoising models. In this study, we first simulate the paired ultra-low-dose and targeted high-quality image of reference, with a well-validated pipeline. These paired images are used to train a denoising convolutional neural network (DnCNN) with residual mapping. The performance of the DnCNN tailored to CT denoising (DnCNN-CT) is assessed over various dose reduction levels, with respect to both image quality and emphysema scoring quantification. The possible over-smoothing behavior of DnCNN and its impact on different subcohort of patients are also investigated.

August 2019

Deng T, Zhang L, Wu HH, Zink JI.

Periodic high-intensity focused ultrasound modulation of a nanoparticle generates reversible MRI T1 relaxivity changes at the 1.5 mm3 focal point causing periodic T1-weighted signal changes. Fourier analysis extracts signal changes at the modulation frequency, and a modulation enhancement map spotlights the precise region of interest by increasing contrast almost 100-fold.

August 2019

Ding PX, Han XW, Liu C, Zhang Y, Cheng AL, Wu Y, Liang XX, Gao XM, Lee EW.

AIM: To evaluate individualized treatment strategy (ITS) and long-term outcomes of endovascular treatment of Budd-Chiari syndrome (BCS) with obstructed inferior vena cava (IVC) based on different degrees of hepatic vein (HV) involvement. METHODS: From January 2006 to June 2017, 456 consecutive patients with BCS with obstructed IVC underwent endovascular treatment with ITS. All patients received IVC recanalization. Then, 426 patients with at least one patent HV received no additional treatment. Twenty-fivepatients with membranous or segmental occlusion of HVs underwent HV recanalization and for the remaining five patients with diffuse HVs occlusion, a transjugular intrahepatic portosystemic shunt (TIPS) was performed.

August 2019

Ellingson BM, Woodworth DC, Leu K, Salamon N, Holly LT.

OBJECTIVES: Although a number of studies have implicated ischemia and hypoxia in the pathogenesis of cervical spondylosis, quantification remains difficult and the role of ischemia and hypoxia on disease progression and disease severity in human cervical spondylosis remains largely unknown. Therefore, the objective of this study was to assess spinal cord perfusion and oxygenation in human cervical spondylosis and examine the relationship between perfusion, degree of spinal cord compression, and neurological status. METHODS: Twenty-two patients with cervical spondylosis with or without myelopathy received a dynamic susceptibility contrast perfusion MRI exam consisting of a novel spin-and-gradient echo echoplanar acquisition before, during, and following gadolinium-based contrast injection. Estimation of relative spinal cord blood volume (rSCBV), the reversible relaxation rate (R₂á), and relative oxygen extraction fraction (rOEF = R₂á/rSCBV) was performed at the site of compression and compared with anterior-posterior spinal cord diameter and modified Japanese Orthopedic Association (mJOA) score, a measure of neurological impairment.

August 2019

Felker ER, Raman SS, Shakeri S, Mirak SA, Bajgiran AM, Kwan L, Khoshnoodi P, ElKhoury FF, Margolis DJA, Karow D, Lu DSK, White N, Marks LS.

OBJECTIVE. The purpose of this article is to evaluate restriction spectrum imaging (RSI) in men undergoing MRI-ultrasound fusion biopsy for suspected prostate cancer (PCa) and to compare the performance of RSI with that of conventional DWI. MATERIALS AND METHODS. One hundred ninety-eight biopsy-naïve men enrolled in a concurrent prospective clinical trial evaluating MRI-targeted prostate biopsy underwent multiparametric MRI with RSI. Clinical and imaging features were compared between men with and without clinically significant (CS) PCa (MRI-ultrasound fusion biopsy Gleason score ≥ 3 + 4). RSI z score and apparent diffusion coefficient (ADC) were correlated, and their diagnostic performances were compared.

August 2019

Hu J, Albadawi H, Chong BW, Deipolyi AR, Sheth RA, Khademhosseini A, Oklu R.

Minimally invasive transcatheter embolization is a common nonsurgical procedure in interventional radiology used for the deliberate occlusion of blood vessels for the treatment of diseased or injured vasculature. A wide variety of embolic agents including metallic coils, calibrated microspheres, and liquids are available for clinical practice. Additionally, advances in biomaterials, such as shape-memory foams, biodegradable polymers, and in situ gelling solutions have led to the development of novel preclinical embolic agents. The aim here is to provide a comprehensive overview of current and emerging technologies in endovascular embolization with respect to devices, materials, mechanisms, and design guidelines. Limitations and challenges in embolic materials are also discussed to promote advancement in the field.

August 2019

Kaur T, Johanis M, Miao T, Romiyo P, Duong C, Sun MZ, Ferraro R, Salamon N, McArthur D, Yang I, Gopen Q.

Superior semicircular canal dehiscence (SSCD) is a rare inner ear disorder with variable amounts of auditory and vestibular dysfunction. In addition to the absence of bone overlying the superior semicircular canal, thinning of bone in this area can also initiate the vestibulocochlear symptoms of SSCD. We evaluated normal bone thickness overlying the course of the semicircular canal using computed tomography (CT) scans and assessed correlations between bone thickness and age, gender, and location of the thinnest bone. A single-institution retrospective chart review was conducted on 133 high-resolution CT scans from 76 healthy, asymptomatic patients between ages 9 and 96 years. These CT scans of the temporal bone were obtained between January 2012 and August 2017. The superior semicircular canal dome thickness at the apex was reported with a mean of 1.25 mm for all 76 patients; the 10th percentile was 0.60 mm, and the 90th percentile was 2.08 mm. The thinnest area of bone at any location yielded a mean of 0.86 mm. The normal bone thickness overlying the superior semicircular canal does not depend on gender or age. The thinnest location was evenly distributed across the superior semicircular canal. A bone thickness of 0.40 mm or greater was present in 90% of normal patients based on CT scan measurements at the thinnest location.

August 2019

Moriarty JM, Shah R, Hage AN, Srinivasa RN, Aboulhosn JA.

Ascending aortic pseudoaneurysms pose a difficult therapeutic dilemma. Surgical repair carries high morbidity and mortality risk and may be challenging in patients with unfavorable anatomy or prior aortic surgery. Endovascular repair is difficult due to short landing zones, need for precise delivery, and the lack of adequately sized commercially available devices. This report describes a case of back-table modification of a thoracic aortic stent graft successfully deployed using an "innominate bounce" technique.

August 2019

Motealleh A, Çelebi-Saltik B, Ermis N, Nowak S, Khademhosseini A, Kehr NS.

In this study, we report the step-gradient nanocomposite (NC) hydrogel generated easily by spatial connection of different nanocomposite hydrogel pastes varying in the concentrations of nanomaterials with the aid of a 3D printing technique. The prepared 3D printed gradient NC hydrogel has self-adhesive properties and is used to direct the migration of fibroblast cells towards the higher concentration of biopolymer-coated silica-based nanomaterials (NMs) within the 3D network of the hydrogel. Furthermore, we demonstrate the potential application of our gradient NC hydrogel in migration and subsequent enhanced osteogenic differentiation of human bone marrow derived mesenchymal stem cells (hBM MSC). The osteogenic differentiation of hBM MSC is achieved in the absence of osteogenic differentiation medium due to the silica-based NMs. The increase in the NM content in the gradient construct promotes hBM MSC migration and results in higher Ca²⁺ deposition.

August 2019

Nguyen KL, Shao J, Ghodrati VK, Ajijola OA, Dharmakumar R, Finn JP, Hu P.

Researchers recently proposed using native myocar-dial T₁ mapping with vasodilator stress testing forevaluation of ischemic heart disease (IHD)(1).Achange of 1.5% in native T₁ between rest and peakstress was able to detect significant epicardial coro-nary stenosis(1). Although this approach is prom-ising, the modest amplitude and narrow dynamicrange for native T₁ reactivity (percentage of change in T₁ at peak vasodilation relative to baseline) may posechallenges in daily clinical practice. We propose toincrease the amplitude and dynamic range of T₁ reactivity through the off-label use of ferumoxytol(Feraheme, AMAG Pharmaceuticals, Waltham, Mas-sachusetts). Ferumoxytol is used for intravenoustreatment of iron deficiency anemia, but it hassuperparamagnetic properties with high r₁ relaxivityand a long intravascular half-life. We posited thatferumoxytol would sensitize the myocardial T₁ to thevasodilator-induced dynamic differences betweenrest and peak stress and significantly boost the T₁ reactivity. Because ferumoxytol shortens the T₁,weexpected the myocardial T₁ to decrease during vaso-dilator stress because of the increased distributionspace of ferumoxytol.

August 2019

Petousis P, Han SX, Hsu W, Bui AAT.

Cancer screening can benefit from individualized decision-making tools that decrease overdiagnosis. The heterogeneity of cancer screening participants advocates the need for more personalized methods. Partially observable Markov decision processes (POMDPs), when defined with an appropriate reward function, can be used to suggest optimal, individualized screening policies. However, determining an appropriate reward function can be challenging. Here, we propose the use of inverse reinforcement learning (IRL) to form rewards functions for lung and breast cancer screening POMDPs. Using experts (physicians) retrospective screening decisions for lung and breast cancer screening, we developed two POMDP models with corresponding reward functions. Specifically, the maximum entropy (MaxEnt) IRL algorithm with an adaptive step size was employed to learn rewards more efficiently; and combined with a multiplicative model to learn state-action pair rewards for a POMDP. The POMDP screening models were evaluated based on their ability to recommend appropriate screening decisions before the diagnosis of cancer. The reward functions learned with the MaxEnt IRL algorithm, when combined with POMDP models in lung and breast cancer screening, demonstrate performance comparable to experts. The Cohen's Kappa score of agreement between the POMDPs and physicians' predictions was high in breast cancer and had a decreasing trend in lung cancer.

August 2019

Ross MK, Okelo SO, Bui AAT.

AS ONE OF the most common chronic diagnoses of childhood, asthma is estimated to affect over six million children in the United States. The condition is heterogeneous, with a myriad of underlying inflammatory and socioenvironmental factors contributing to its prevalence, severity, control, and outcomes. This heterogeneity poses a challenge in implementing a universal treatment approach. While there are an increasing number of biologic medications targeted to specific inflammation pathways, they are expensive and not all children meet criteria for administration. Progress has been made toward understanding the genetics and epigenetics of asthma, but no treatments in this domain are available yet.

August 2019

Shen S, Han SX, Aberle DR, Bui AA, Hsu W.

While deep learning methods have demonstrated performance comparable to human readers in tasks such as computer-aided diagnosis, these models are difficult to interpret, do not incorporate prior domain knowledge, and are often considered as a "black-box." The lack of model interpretability hinders them from being fully understood by end users such as radiologists. In this paper, we present a novel interpretable deep hierarchical semantic convolutional neural network (HSCNN) to predict whether a given pulmonary nodule observed on a computed tomography (CT) scan is malignant. Our network provides two levels of output: 1) low-level semantic features; and 2) a high-level prediction of nodule malignancy. The low-level outputs reflect diagnostic features often reported by radiologists and serve to explain how the model interprets the images in an expert-interpretable manner. The information from these low-level outputs, along with the representations learned by the convolutional layers, are then combined and used to infer the high-level output. This unified architecture is trained by optimizing a global loss function including both low- and high-level tasks, thereby learning all the parameters within a joint framework. Our experimental results using the Lung Image Database Consortium (LIDC) show that the proposed method not only produces interpretable lung cancer predictions but also achieves significantly better results compared to using a 3D CNN alone.

August 2019

Silverman SG, Pedrosa I, Ellis JH, Hindman NM, Schieda N, Smith AD, Remer EM, Shinagare AB, Curci NE, Raman SS, Wells SA, Kaffenberger SD, Wang ZJ, Chandarana H, Davenport MS.

Cystic renal cell carcinoma (RCC) is almost certainly overdiagnosed and overtreated. Efforts to diagnose and treat RCC at a curable stage result in many benign neoplasms and indolent cancers being resected without clear benefit. This is especially true for cystic masses, which compared with solid masses are more likely to be benign and, when malignant, less aggressive. For more than 30 years, the Bosniak classification has been used to stratify the risk of malignancy in cystic renal masses. Although it is widely used and still effective, the classification does not formally incorporate masses identified at MRI or US or masses that are incompletely characterized but are highly likely to be benign, and it is affected by interreader variability and variable reported malignancy rates. The Bosniak classification system cannot fully differentiate aggressive from indolent cancers and results in many benign masses being resected. This proposed update to the Bosniak classification addresses some of these shortcomings. The primary modifications incorporate MRI, establish definitions for previously vague imaging terms, and enable a greater proportion of masses to enter lower-risk classes. Although the update will require validation, it aims to expand the number of cystic masses to which the Bosniak classification can be applied while improving its precision and accuracy for the likelihood of cancer in each class.

August 2019

Simopoulos DN, Sisk AE Jr, Priester A, Felker ER, Kwan L, Delfin MK, Reiter RE, Marks LS.

OBJECTIVE: To study the relationship of maximum cancer core length (MCCL), on targeted biopsy (TB) of magnetic resonance imaging (MRI)-visible index lesions, to volume of that tumour found at radical prostatectomy (RP). PATIENTS AND METHODS: In all, 205 men undergoing fusion biopsy and RP were divided into two groups: 136 in whom the MCCL came from an index MRI-visible lesion (TB) and 69 in whom MCCL came from a non-targeted lesion (non-targeted biopsy [NTB]). MRI was 3-T multi-parametric and biopsy was via MRI-ultrasonography fusion.

August 2019

Tafti BA, Genshaft S, Suh R, Abtin F.

Lung ablation is ever more recognized since its initial report and use almost two decades ago. With technological advancements in thermal modalities, particularly microwave ablation and cryoablation, better identification of the cohort of patients who best benefit from ablation, and understanding the role of imaging after ablation, image-guided thermal ablation for primary and secondary pulmonary malignancies is increasingly recognized and accepted as a cogent form of local therapy.

July 2019

Abtin F, De Baere T, Dupuy DE, Genshaft S, Healey T, Khan S, Suh R.

Interventional oncology and management of thoracic malignancies with ablative techniques are becoming ever more recognized therapeutic options. With increased understanding, development, and utility of the ablative techniques, the indications are expanding and efficacy improving. Lung cancer was among the first indications for lung ablation and remains most challenging with multiple therapeutic options. For inoperable patients, the current literature demonstrates equivalent survivals between ablation, sublobar resection, and stereotactic body radiation. Oligometastatic disease remains the most common indication for lung ablation and is gaining acceptance among the oncology community, as lung ablation provides limited patient downtime, repeatability, and minimal to no loss of respiratory function. Other indications for ablation are being explored, including recurrent mesothelioma, drop metastasis from thymoma, and limited pleural metastasis, with excellent local control of tumor and limited complications. Follow-up after ablation is essential to detect early complications, observe the natural evolution of the ablation zone, and detect recurrence. Standardized imaging follow-up allows for these goals to be achieved and provides a framework for oncology practice. In this article, the role of ablation in the management of thoracic neoplasms and postablation imaging features are reviewed. The radiologists, in particular, thoracic radiologists should be able to identify candidates who can benefit from ablation familiarize themselves with postablation imaging features, and recognize the evolution of the postablation zone and hence detect early recurrence.

July 2019

Coy HJ, Douek ML, Ruchalski K, Kim HJ, Gutierrez A, Patel M, Sai V, Margolis DJA, Kaplan A, Brown M, Goldin J, Raman SS.

BACKGROUND: Progression-free survival (PFS) determined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) is the reference standard to assess efficacy of treatments in patients with clear cell renal cell carcinoma. Purpose To assess the most common components of radiologic progressive disease as defined by RECIST 1.1 in patients with clear cell renal cell carcinoma and how the progression events impact PFS. MATERIALS & METHODS: This secondary analysis of the phase III METEOR trial conducted between 2013 and 2014 included patients with metastatic clear cell renal cell carcinoma, with at least one target lesion at baseline and one follow-up time point, who were determined according to RECIST 1.1 to have progressive disease. A chest, abdominal, and pelvic scan were acquired at each time point. Kruskal-Wallis analysis was used to test differences in median PFS among the RECIST 1.1 progression events. The Holm-Bonferroni method was used to compare the median PFS of the progression events for the family-wise error rate of 5% to adjust P values for multiple comparisons.

July 2019

Ge X, Zhao H, Zhou Z, Li X, Sun B, Wu H, Wan J, Xu J, Villablanca JP, Liu X.

BACKGROUND AND PURPOSE: Fractional flow measured on 3D-TOF-MRA was proposed to quantify cerebral hemodynamic changes in patients with artery stenosis. We investigated the association between fractional flow and cerebral perfusion changes in patients with symptomatic MCA stenosis. MATERIALS AND METHODS: This prospective study was approved by the institutional review board, and all participants provided written informed consent. From June 2015 to May 2018, four hundred twenty-nine patients with symptomatic intracranial arterial stenosis were consecutively recruited and underwent conventional brain MR imaging, 3D-TOF-MRA, and brain CTP. A total of 91 patients with unilateral M1 segment stenosis of the MCA and a stenosis degree of 50%∼99% were included in the analysis. Fractional flow was measured by comparing distal and proximal signal intensity changes across the stenosis on 3D-TOF-MRA. The cutoff value for fractional flow for discriminating between normal perfusion and hypoperfusion was obtained from the receiver operating characteristic curve. Associations between fractional flow and hypoperfusion were assessed using univariate and multivariate analyses.

July 2019

Houlahan KE, Salmasi A, Sadun TY, Pooli A, Felker ER, Livingstone J, Huang V, Raman SS, Ahuja P, Sisk AE Jr, Boutros PC, Reiter RE.

Multiparametric magnetic resonance imaging (mpMRI) has transformed the management of localized prostate cancer by improving identification of clinically significant disease at diagnosis. Approximately 20% of primary prostate tumors are invisible to mpMRI, and we hypothesize that this invisibility reflects fundamental molecular properties of the tumor. We therefore profiled the genomes and transcriptomes of 40 International Society of Urological Pathology grade 2 tumors: 20 mpMRI-invisible (Prostate Imaging-Reporting and Data System [PI-RADS] v2 <3) and 20 mpMRI-visible (PI-RADS v2 5) tumors. mpMRI-visible tumors were enriched in hallmarks of nimbosus, an aggressive pathological, molecular, and microenvironmental phenomenon in prostate cancer. These hallmarks included genomes with increased mutation density, a higher prevalence of intraductal carcinoma/cribriform architecture pathology, and altered abundance of 102 transcripts, including overexpression of noncoding RNAs such as SCHLAP1. Multiple small nucleolar RNAs (snoRNAs) were identified, and a snoRNA signature synergized with nimbosus hallmarks to discriminate visible from invisible tumors. These data suggest a confluence of aggressive molecular and microenvironmental phenomena underlie mpMRI visibility of localized prostate cancer. PATIENT SUMMARY: We examined the correlation between tumor biology and magnetic resonance imaging (MRI) visibility in a group of patients with low- intermediate-risk prostate cancer. We observed that MRI findings are associated with biological features of aggressive prostate cancer.

July 2019

Jahan R, Saver JL, Schwamm LH, Fonarow GC, Liang L, Matsouaka RA, Xian Y, Holmes DN, Peterson ED, Yavagal D, Smith EE.

IMPORTANCE: Randomized clinical trials suggest benefit of endovascular-reperfusion therapy for large vessel occlusion in acute ischemic stroke (AIS) is time dependent, but the extent to which it influences outcome and generalizability to routine clinical practice remains uncertain. OBJECTIVE: To characterize the association of speed of treatment with outcome among patients with AIS undergoing endovascular-reperfusion therapy. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study using data prospectively collected from January 2015 to December 2016 in the Get With The Guidelines-Stroke nationwide US quality registry, with final follow-up through April 15, 2017. Participants were 6756 patients with anterior circulation large vessel occlusion AIS treated with endovascular-reperfusion therapy with onset-to-puncture time of 8 hours or less. EXPOSURES: Onset (last-known well time) to arterial puncture, and hospital arrival to arterial puncture (door-to-puncture time). MAIN OUTCOMES AND MEASURES: Substantial reperfusion (modified Thrombolysis in Cerebral Infarction score 2b-3), ambulatory status, global disability (modified Rankin Scale [mRS]) and destination at discharge, symptomatic intracranial hemorrhage (sICH), and in-hospital mortality/hospice discharge.

July 2019

Pomykala KL, Farolfi A, Hadaschik B, Fendler WP, Herrmann K.

According to SEER Cancer Statistics Review there are around 165,000 new prostate cancer cases estimated in 2018 accounting for 9.5% of all newly diagnosed cancers. Accurate staging of primary prostate cancer is important for therapy selection (local vs systemic). Recent developments in molecular imaging may significantly impact staging procedures and management. Accordingly, this article addresses the current clinical standard, discusses the areas of unmet clinical need for imaging and then summarizes the most commonlyused molecular imaging probes. Finally, the authors dare an outlook to the short-term future role of molecular imaging in primary staging of prostate cancer.

July 2019

Pan PJ, Ullman HE, Mathern GW, Salamon N.

BACKGROUND: Hemispherotomy can be an effective treatment for refractory childhood epilepsy. However, the extent of postoperative brain development after hemispherotomy remains incompletely understood. This study aims to provide an anatomic foundation in assessing development of the contralateral hemisphere, by measuring volumetric growth after hemispherotomy. METHODS: Eleven patients with hemimegalencephaly, Rasmussen's encephalitis, and cerebral infarction who underwent hemispherotomy before age 12 years, an immediate preoperative magnetic resonance imaging, and at least three years of follow-up magnetic resonance imagings were retrospectively analyzed. The volume of the contralateral hemisphere was measured before and after surgery. Growth curves were compared with those of healthy individuals from an open database. The growth rate relative to the healthy individuals ("catch-up rate") was calculated.

July 2019

Ramesh S, Duckwiler G, Goldberg RA, Rootman DB.

PURPOSE: To review a representative case series and share a stepwise approach to the diagnosis and treatment of periorbital venolymphatic malformations. METHODS: A case series of 9 patients with representative periorbital venolymphatic malformations. All patients managed at the University of California, Los Angeles Orbital Center for a vascular malformation over the last 5 years were reviewed. Cases representative of the varied pathologic findings and techniques were selected. The clinical, radiologic, and intraoperative findings are presented and a survey of techniques composed.

July 2019

Sheikhi A, de Rutte J, Haghniaz R, Akouissi O, Sohrabi A, Di Carlo D, Khademhosseini A.

Despite the significant advances in designing injectable bulk hydrogels, the inability to control the pore interconnectivity and decoupling it from the matrix stiffness has tremendously limited the applicability of stiff, flowable hydrogels for 3D cellular engineering, e.g., in hard tissue engineering. To overcome this persistent challenge, here, we introduce a universal method to convert thermosensitive macromolecules with chemically-crosslinkable moieties into annealable building blocks, forming 3D microporous beaded scaffolds in a bottom-up approach. In particular, we show gelatin methacryloyl (GelMA), a widely used biomaterial in tissue engineering, may be converted into physically-crosslinked microbeads using a facile microfluidic approach, followed by flow of the microbead suspension and chemical crosslinking in situ to fabricate microporous beaded GelMA (B-GelMA) scaffolds with interconnected pores, promoting cell functionality and rapid (within minutes) 3D seeding in stiff scaffolds, which are otherwise impossible in the bulk gel counterparts. This novel approach may set the stage for the next generation modular hydrogels with orthogonal porosity and stiffness made up of a broad range of natural and synthetic biomaterials. • This method combines well-known flow focusing microfluidic devices with facile post-processing steps to fabricate microporous scaffolds. • Temperature-driven physical crosslinking of the microbeads enables the facile purification of gel building blocks without further chemical reactions. • This method provides a simple approach to fabricate microporous scaffolds, which overcomes some of the challenges of newly emerging beaded scaffolds, including oxygen-mediated impaired crosslinking.

July 2019

Wang J, Yu J, Zhang Y, Zhang X, Kahkoska AR, Chen G, Wang Z, Sun W, Cai L, Chen Z, Qian C, Shen Q, Khademhosseini A, Buse JB, Gu Z.

Glucose-responsive insulin delivery systems with robust responsiveness that has been validated in animal models, especially in large animal models, remain elusive. Here, we exploit a new strategy to form a micro-sized complex between a charge-switchable polymer with a glucose-sensing moiety and insulin driven by electrostatic interaction. Both high insulin loading efficiency (95%) and loading capacity (49%) can be achieved. In the presence of a hyperglycemic state, the glucose-responsive phenylboronic acid (PBA) binds glucose instantly and converts the charge of the polymeric moiety from positive to negative, thereby enabling the release of insulin from the complex. Adjusting the ratio of the positively charged group to PBA achieves inhibited insulin release from the complex under normoglycemic conditions and promoted release under hyperglycemic conditions. Through chemically induced type 1 diabetic mouse and swine models, in vivo hyperglycemia-triggered insulin release with fast response is demonstrated after the complex is administrated by either subcutaneous injection or transdermal microneedle array patch.

July 2019

Wieduwild R, Xu Y, Ostrovidov S, Khademhosseini A, Zhang Y, Orive G.

In recent years, many mechanical, physical, chemical, and biochemical features of biomatrices have emerged as important properties to dictate the fates of cells. To construct chemically defined biomaterials to recapitulate various biological niches for both cell biology research and therapeutic utilities, it has become increasingly clear that a simple hydrated polymer network would not be able to provide the complex cues and signaling required for many types of cells. The researchers are facing a growing list of mechanophysical and biochemical properties, while each of them could be an important cellular trigger. To include all these design parameters in screening and synthesis is practically difficult, if not impossible. Developing novel high throughput screening technology by combining assay miniaturization, computer simulations, and modeling can help researchers to tackle the challenge to identify the most relevant parameters to tailor materials for specific applications.

June 2019

Armstrong T, Ly KV, Ghahremani S, Calkins KL, Wu HH.

BACKGROUND: Body composition and hepatic fat correlate with future risk for metabolic syndrome. In children, many conventional techniques for quantifying body composition and hepatic fat have limitations. MRI is a noninvasive research tool to study body composition and hepatic fat in infants; however, conventional Cartesian MRI is sensitive to motion, particularly in the abdomen because of respiration. Therefore we developed a free-breathing MRI technique to quantify body composition and hepatic fat in infants. OBJECTIVE: In infants, we aimed to (1) compare the image quality between free-breathing 3-D stack-of-radial MRI (free-breathing radial) and 3-D Cartesian MRI in the liver and (2) determine the feasibility of using free-breathing radial MRI to quantify body composition and hepatic proton-density fat fraction (PDFF). MATERIALS AND METHODS: Ten infants ages 2-7 months were scanned with free-breathing radial (two abdominal; one head and chest) and Cartesian (one abdominal) MRI sequences. The median preparation and scan times were reported. To assess feasibility for hepatic PDFF quantification, a radiologist masked to the MRI technique scored abdominal scans for motion artifacts in the liver using a 3-point scale (1, or non-diagnostic, to 3, or no artifacts). Median visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and brown adipose tissue (BAT) volume and PDFF, and hepatic PDFF were measured using free-breathing radial MRI. We assessed repeatability of free-breathing radial hepatic PDFF (coefficient of repeatability) between back-to-back scans. We determined differences in the distribution of image-quality scores using McNemar-Bowker tests. P<0.05 was considered significant.

June 2019

Ashammakhi N, Ahadian S, Pountos I, Hu SK, Tellisi N, Bandaru P, Ostrovidov S, Dokmeci MR, Khademhosseini A.

Three-dimensional (3D) bioprinting is an emerging biofabrication technology, driving many innovations and opening new avenues in regenerative therapeutics. The aim of 3D bioprinting is to fabricate grafts in vitro, which can then be implanted in vivo. However, the tissue culture ex vivo carries safety risks and thereby complicated manufacturing equipment and practice are required for tissues to be implanted in the humans. The implantation of printed tissues also adds complexities due to the difficulty in maintaining the structural integrity of fabricated constructs. To tackle this challenge, the concept of in situ 3D bioprinting has been suggested in which tissues are directly printed at the site of injury or defect. Such approach could be combined with cells freshly isolated from patients to produce custom-made grafts that resemble target tissue and fit precisely to target defects. Moreover, the natural cellular microenvironment in the body can be harnessed for tissue maturation resulting in the tissue regeneration and repair. Here, we discuss literature reports on in situ 3D printing and we describe future directions and challenges for in situ 3D bioprinting. We expect that this novel technology would find great attention in different biomedical fields in near future.

June 2019

Coy H, Hsieh K, Wu W, Nagarajan MB, Young JR, Douek ML, Brown MS, Scalzo F, Raman SS.

PURPOSE: Currently, all solid enhancing renal masses without microscopic fat are considered malignant until proven otherwise and there is substantial overlap in the imaging findings of benign and malignant renal masses, particularly between clear cell RCC (ccRCC) and benign oncocytoma (ONC). Radiomics has attracted increased attention for its utility in pre-operative work-up on routine clinical images. Radiomics based approaches have converted medical images into mineable data and identified prognostic imaging signatures that machine learning algorithms can use to construct predictive models by learning the decision boundaries of the underlying data distribution. The TensorFlow™ framework from Google is a state-of-the-art open-source software library that can be used for training deep learning neural networks for performing machine learning tasks. The purpose of this study was to investigate the diagnostic value and feasibility of a deep learning-based renal lesion classifier using open-source Google TensorFlow™ Inception in differentiating ccRCC from ONC on routine four-phase MDCT in patients with pathologically confirmed renal masses. METHODS: With institutional review board approval for this 1996 Health Insurance Portability and Accountability Act compliant retrospective study and a waiver of informed consent, we queried our institution's pathology, clinical, and radiology databases for histologically proven cases of ccRCC and ONC obtained between January 2000 and January 2016 scanned with a an intravenous contrast-enhanced four-phase renal mass protocol (unenhanced (UN), corticomedullary (CM), nephrographic (NP), and excretory (EX) phases). To extract features to be used for the machine learning model, the entire renal mass was contoured in the axial plane in each of the four phases, resulting in a 3D volume of interest (VOI) representative of the entire renal mass. We investigated thirteen different approaches to convert the acquired VOI data into a set of images that adequately represented each tumor which was used to train the final layer of the neural network model. Training was performed over 4000 iterations. In each iteration, 90% of the data were designated as training data and the remaining 10% served as validation data and a leave-one-out cross-validation scheme was implemented. Accuracy, sensitivity, specificity, positive (PPV) and negative predictive (NPV) values, and CIs were calculated for the classification of the thirteen processing modes.

June 2019

Ghazanfari S, Alberti KA, Xu Q, Khademhosseini A.

Due to the limited success rate of currently available vascular replacements, tissue engineering has received tremendous attention in recent years. A main challenge in the field of regenerative medicine is creating a mechanically functional tissue with a well-organized extracellular matrix, particularly of collagen and elastin. In this study, the native collagen scaffold derived from decellularized tendon sections, as a scaffold having the potential to be used for vascular tissue engineering applications, was studied. We showed that the elasticity of the scaffolds was improved when crosslinked with the bovine elastin. The effect of different concentrations of elastin on mechanical properties of the collagen scaffolds was evaluated of which 15% elastin concentration was selected for further analysis based on the results. Addition of 15% elastin to collagen scaffolds significantly decreased Young's modulus and the tensile stress at the maximum load and increased the tensile strain at the maximum load of the constructs as compared to those of the collagen scaffolds or control samples. Moreover, tubular elastin modified collagen scaffolds showed significantly higher burst pressure compared to the control samples. Smooth muscle cells and endothelial cells cultured on the elastin modified collagen scaffolds showed high viability (>80%) after 1, 3, and 7 days. Furthermore, the cells showed a high tendency to align with the collagen fibers within the scaffold and produced their own extracellular matrix over time. In conclusion, the results show that the decellularized tendon sections have a great potential to be used as scaffolds for vascular tissue engineering applications.

June 2019

Hardy AJ, Angel E, Bostani M, Cagnon C, McNitt-Gray M.

PURPOSE: The purpose of this work was to estimate scanner-independent CTDIvol -to-fetal-dose coefficients for tube current-modulated (TCM) and fixed tube current (FTC) computed tomography (CT) examinations of pregnant patients of various gestational ages undergoing abdominal/pelvic CT examinations. METHODS: For 24 pregnant patients of gestational age from <5 to 36 weeks who underwent clinically indicated CT examinations, voxelized models of maternal and fetal (or embryo) anatomy were created from abdominal/pelvic image data. Absolute fetal dose (D_fetus) was estimated using Monte Carlo (MC) simulations of helical scans covering the abdomen and pelvis for TCM and FTC scans. Estimated TCM schemes were generated for each patient model using a validated method that accounts for patient attenuation and scanner output limits for one scanner model and were incorporated into MC simulations. FTC scans were also simulated for each patient model with multidetector row CT scanners from four manufacturers. Normalized fetal dose estimates, nD_fetus , was obtained by dividing D_fetus from the MC simulations by CTDI_vol. Patient size was described using water equivalent diameter (D_w) measured at the three-dimensional geometric centroid of the fetus. Fetal depth (DE_f ) was measured from the anterior skin surface to the anterior part of the fetus. nD_fetus and D_w were correlated using an exponential model to develop equations for fetal dose conversion coefficients for TCM and FTC abdominal/pelvic CT examinations. Additionally, bivariate linear regression was performed to analyze the correlation of nD_fetus with D_w and fetal depth (DE_f ). For one scanner model, nD_fetus from TCM was compared to FTC and the size-specific dose estimate (SSDE) conversion coefficients (f-factors) from American Association of Physicists in Medicine (AAPM) Report 204. nD_fetus from FTC simulations was averaged across all scanners for each patient...

June 2019

Khademhosseini A, Nel AE, Bunje H, DeSantis CJ, Andrews AM, Blaik RA, Gu Z, Meng H, Ozcan A, Tolbert SH, Xia T, Zink JI, Weiss PS.

This year, the University of California, Los Angeles (UCLA) celebrates its centennial. We join in this celebration with a virtual issue of ACS Nano featuring research and ideas from UCLA faculty and our collaborators around the world.(1) UCLA hosts one of the world's major nano centers, the California NanoSystems Institute (CNSI),(2) which is a partnership between UCLA, UC Santa Barbara, and the University of California (UC) system.

Key to the success of interdisciplinary research, including nanoscience and nanotechnology, at UCLA is its compactness–while UCLA is the largest of the UC campuses by any measure of population, it is also the smallest by area. Around one courtyard, the Court of Science, are all of engineering, all of science, medicine, CNSI, and the Institute of the Environment. Within one block are the School of Public Health, all of neuroscience, and the top hospital in the region. Faculty, students, and staff from science, engineering, medicine, and beyond see each other frequently, share problems and approaches, and we work together.

June 2019

Liu LY, Ji MS, Nguyen NT, Chow FE, Molaie DM, Pianka ST, Green RM, Liau LM, Ellingson BM, Nghiemphu PL, Cloughesy TF, Lai A.

Aim: Long-term survivors (LTS) after glioma recurrence while on bevacizumab (Bev) therapy are rarely reported in the current literature. The purpose of this case series is to confirm the existence of and describe a large cohort of recurrent glioma LTS treated with Bev (Bev-LTS). Patients & methods: We identified Bev-LTS as patients with post-Bev initiation survival times of ≥3 years among 1397 Bev treated recurrent glioma patients. Results: Among 962 grade-IV, 221 grade III, and 214 grade II Bev-treated glioma patients, we identified 28 (2.9%), 14 (6.3%) and 8 (3.7%) Bev-LTS patients, respectively. 45 Bev-LTS patients recurred on Bev, with 36 of those patients continuing therapy.

June 2019

Ly KV, Armstrong T, Yeh J, Ghahremani S, Kim GH, Wu HH, Calkins KL.

OBJECTIVE: Conventional, breath-holding magnetic resonance imaging (MRI) assesses body composition by measuring fat volumes and proton density fat fraction (PDFF). However, breath-holding MRI is not always feasible in children. This study's objective was to use free-breathing MRI to quantify visceral and subcutaneous fat volumes and PDFFs and correlate these measurements with hepatic PDFF. METHODS: This was an observational, hypothesis-forming study that enrolled 2 groups of children (ages 6-17 years), healthy children and overweight children with presumed nonalcoholic fatty liver disease. Free-breathing MRI was used to measure visceral and subcutaneous fat volumes and PDFFs, and hepatic PDFF. Imaging biomarkers were compared between groups, and correlations coefficients (r) and coefficients of determination (R) were calculated.

June 2019

Miri AK, Mirzaee I, Hassan S, Mesbah Oskui S, Nieto D, Khademhosseini A, Zhang YS.

Recent advancements in bioprinting techniques have enabled convenient fabrication of micro-tissues in organ-on-a-chip platforms. In a sense, the success of bioprinted micro-tissues depends on how close their architectures are to the anatomical features of their native counterparts. The bioprinting resolution largely relates to the technical specifications of the bioprinter platforms and the physicochemical properties of the bioinks. In this article, we compare inkjet, extrusion, and light-assisted bioprinting technologies for fabrication of micro-tissues towards construction of biomimetic organ-on-a-chip platforms. Our theoretical analyses reveal that for a given printhead diameter, surface contact angle dominates inkjet bioprinting resolution, while nozzle moving speed and the nonlinearity of viscosity for bioinks regulate extrusion bioprinting resolution. The resolution of light-assisted bioprinting is strongly affected by the photocrosslinking behavior and light characteristics. Our tutorial guideline for optimizing bioprinting resolution would potentially help model the complex microenvironment of biological tissues in organ-on-a-chip platforms.

June 2019

Ostrovidov S, Salehi S, Costantini M, Suthiwanich K, Ebrahimi M, Sadeghian RB, Fujie T, Shi X, Cannata S, Gargioli C, Tamayol A, Dokmeci MR, Orive G, Swieszkowski W, Khademhosseini A.

Skeletal muscle tissue engineering (SMTE) aims at repairing defective skeletal muscles. Until now, numerous developments are made in SMTE; however, it is still challenging to recapitulate the complexity of muscles with current methods of fabrication. Here, after a brief description of the anatomy of skeletal muscle and a short state-of-the-art on developments made in SMTE with "conventional methods," the use of 3D bioprinting as a new tool for SMTE is in focus. The current bioprinting methods are discussed, and an overview of the bioink formulations and properties used in 3D bioprinting is provided. Finally, different advances made in SMTE by 3D bioprinting are highlighted, and future needs and a short perspective are provided.

June 2019

Padia SA.

While the most compelling levels of evidence for the use of Yttrium-90 (90Y) radioembolization are in patients with hepatocellular carcinoma and hepatic metastases from colorectal cancer, a growing body of literature supports its use in other primary and secondary hepatic malignancies. This includes intrahepatic cholangiocarcinoma, as well as hepatic metastases from neuroendocrine cancer, ocular melanoma, and breast cancer. While is it not feasible to conduct prospective, randomized trials for radioembolization in the setting of these malignancies due to the low overall prevalence of liver-only disease, numerous single-arm studies in the last several years make a compelling argument for its use in select situations. This clinical update summarizes those findings.

June 2019

Roberts DG, Plotnik AN, Chick JF, Srinivasa RN.

Interventional radiology-operated percutaneous endoscopy has seen a recent resurgence with potential to return to the scope of Interventional Radiology practice. Endoscopy adds a new dimension to the Interventional Radiology armamentarium by offering a unique opportunity to diagnose and treat conditions under direct visualization with improved maneuverability. Cholecystoscopy (gallbladder endoscopy), as a method for percutaneous removal of gallstones, is an effective treatment option in patients with symptomatic cholelithiasis who are poor candidates for surgical cholecystectomy. This article presents a case of Interventional Radiology-operated cholecystoscopy using ultrasonic lithotripsy and stone basket retrieval with an emphasis on the equipment, technique, and peri-procedural management essential to the procedure, as well as a review of the literature.

June 2019

Shakeri S, Afshari Mirak S, Mohammadian Bajgiran A, Pantuck A, Sisk A, Ahuja P, Lu DS, Raman SS.

PURPOSE: To evaluate the effect of size and central location of the tumor on safety and efficacy of percutaneous CEUS- and CT-guided MWA in biopsy-proven renal cell carcinomas (RCCs). MATERIALS AND METHODS: In this IRB-approved retrospective study, 69 biopsy-proven renal tumors in 56 patients, who underwent MWA in our institution from January 2013 to March 2017, were evaluated. Data collection included demographics, tumor characteristics, procedural protocols, and follow-up visits within 6 months post procedure. Primary outcomes were assessed by technical success (TS), local tumor progression (LTP), and complications. The Kaplan-Meier analysis was used for survival rate.

June 2019

Shenoy KD, Stanzione N, Caron JE, Fishbein GA, Abtin F, Lluri G, Hirschowitz SL.

Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare and aggressive subset of poorly differentiated squamous cell carcinoma that is defined by t(15,19) and typically presents in the midline structures of the head, neck, and mediastinum. We report two cases of NMC that presented uniquely with malignant pleural and pericardial effusions including one with cardiac tamponade at presentation. The first case is of a 25-year-old male patient who presented with progressive dyspnea associated with palpitations and dizziness on standing, found to have large bilateral pleural effusions. The second case is of a previously healthy 29-year-old male patient who presented with progressive dyspnea, cough with expectoration, and a large right lower neck mass of 3 months onset, and a large left pleural effusion and left lung infiltrate on imaging studies. Both cases showed malignant cells on cytology suggestive of poorly differentiated carcinoma. Subsequent histopathological and immunochemistry studies were consistent with the diagnosis of NMC. Both patients had a rapid decline in status and suffered comorbidities secondary to their carcinoma, inevitably leading to their death. It is important to consider NUT midline carcinomas can present in a variety of clinical scenarios, and it is important to consider in the differential diagnoses when evaluating malignant effusion cytology. Utilization of ancillary testing with a broad immunostain profile including NUT studies, as well as fluorescent in-situ hydridization (FISH) studies are helpful and necessary in making the appropriate diagnosis.

June 2019

Wang YL, Yao J, Chakhoyan A, Raymond C, Salamon N, Liau LM, Nghiemphu PL, Lai A, Pope WB, Nguyen N, Ji M, Cloughesy TF, Ellingson BM.

BACKGROUND AND PURPOSE: Acidification of the tumor microenvironment from abnormal metabolism along with angiogenesis to meet metabolic demands are both hallmarks of malignant brain tumors; however, the interdependency of tumor acidity and vascularity has not been explored. Therefore, our aim was to investigate the association between pH-sensitive amine chemical exchange saturation transfer echoplanar imaging (CEST-EPI) and relative cerebral blood volume (CBV) measurements obtained from dynamic susceptibility contrast (DSC) perfusion MRI in patients with gliomas. MATERIALS AND METHODS: In this retrospective study, 90 patients with histologically confirmed gliomas were scanned between 2015 and 2018 (median age, 50.3 years; male/female ratio = 59:31). pH-weighting was obtained using chemical exchange saturation transfer echo-planar imaging estimation of the magnetization transfer ratio asymmetry at 3 ppm, and CBV was estimated using DSC-MR imaging. The voxelwise correlation and patient-wise median value correlation between the magnetization transfer ratio asymmetry at 3 ppm and CBV within T2-hyperintense lesions and contrast-enhancing lesions were evaluated using the Pearson correlation analysis.

May 2019

Winter A, Aberle DR, Hsu W.

INTRODUCTION: We performed an external validation of the Brock model using the National Lung Screening Trial (NLST) data set, following strict guidelines set forth by the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis statement. We report how external validation results can be interpreted and highlight the role of recalibration and model updating. MATERIALS AND METHODS: We assessed model discrimination and calibration using the NLST data set. Adhering to the inclusion/exclusion criteria reported by McWilliams et al, we identified 7879 non-calcified nodules discovered at the baseline low-dose CT screen with 2 years of follow-up. We characterised differences between Pan-Canadian Early Detection of Lung Cancer Study and NLST cohorts. We calculated the slope on the prognostic index and the intercept coefficient by fitting the original Brock model to NLST. We also assessed the impact of model recalibration and the addition of new covariates such as body mass index, smoking status, pack-years and asbestos.

June 2019

Yokota H, Vijayasarathi A, Cekic M, Hirata Y, Linetsky M, Ho M, Kim W, Salamon N.

PURPOSE: To investigate the pathological change of the glymphatic system in idiopathic normal pressure hydrocephalus (iNPH) using diffusion tensor imaging (DTI) analysis. MATERIALS AND METHODS: 24 right-handed patients were referred to our hydrocephalus clinic for assessment of ventriculomegaly and gait impairment. 12 of 24 were diagnosed as pseudo-iNPH (piNPH) based on assessment by a neurologist. Diffusivity maps in the direction of the x-axis (right-to-left) (Dx), y-axis (anterior-to-posterior) (Dy), and z-axis (inferior-to-superior) (Dz) were computed. The diffusion map was coregistered to International Consortium for Brain Mapping (ICBM) DTI-81 atlas. The analysis along the perivascular space (ALPS) index was defined as mean (Dxpro, Dypro)/mean (Dypro, Dzasc), where Dxpro and Dxasc are Dx values in the projection and association fiber areas, respectively. Evans index and callosal angle were also assessed on each case.

June 2019

Zhao S, Caruso F, Dähne L, Decher G, De Geest BG, Fan J, Feliu N, Gogotsi Y, Hammond PT, Hersam MC, Khademhosseini A, Kotov N, Leporatti S, Li Y, Lisdat F, Liz-Marzán LM, Moya S, Mulvaney P, Rogach AL, Roy S, Shchukin DG, Skirtach AG, Stevens MM, Sukhorukov GB, Weiss PS, Yue Z, Zhu D, Parak WJ.

Layer-by-layer (LbL) assembly is a widely used tool for engineering materials and coatings. In this Perspective, dedicated to the memory of ACS Nano associate editor Prof. Dr. Helmuth Möhwald, we discuss the developments and applications that are to come in LbL assembly, focusing on coatings, bulk materials, membranes, nanocomposites, and delivery vehicles.

June 2019

Zheng T, Pour Shahid Saeed Abadi P, Seo J, Cha BH, Miccoli B, Li YC, Park K, Park S, Choi SJ, Bayaniahangar R, Zhang D, Lee SH, Lee CK, Khademhosseini A, Shin SR.

Biocompatible, electrically conductive microfibers with superior mechanical properties have received a great attention due to their potential applications in various biomedical applications such as implantable medical devices, biosensors, artificial muscles, and microactuators. Here, we developed an electrically conductive and mechanically stable carbon nanotube-based microactuator with a low degradability that makes it usable for an implantable device in the body or biological environments. The microfiber was composed of hyaluronic acid (HA) hydrogel and single-wall carbon nanotubes (SWCNTs) (HA/SWCNT). HA hydrogel acts as biosurfactant and ion-conducting binder to improve the dispersion of SWCNTs resulting in enhanced electrical and mechanical properties of the hybrid microfiber. In addition, HA was crosslinked to prevent the leaking of the nanotubes from the composite. Crosslinking of HA hydrogel significantly enhances Young's modulus, the failure strain, the toughness, the stability of the electrical conductivity, and the resistance to biodegradation and creep of hybrid microfibers. The obtained crosslinked HA/SWCNT hybrid microfibers show an excellent capacitance and actuation behavior under mechanical loading with a low potential of ±1 V in a biological environment. Furthermore, the HA/SWCNT microfibers exhibit an excellent in vitro viability. Finally, the biocompatibility is shown through the resolution of an early inflammatory response in less than 3 weeks after the implantation of the microfibers in the subcutaneous tissue of mice.

June 2019

Zhong X, Cao R, Shakeri S, Scalzo F, Lee Y, Enzmann DR, Wu HH, Raman SS, Sung K.

PURPOSE: The purpose of the study was to propose a deep transfer learning (DTL)-based model to distinguish indolent from clinically significant prostate cancer (PCa) lesions and to compare the DTL-based model with a deep learning (DL) model without transfer learning and PIRADS v2 score on 3 Tesla multi-parametric MRI (3T mp-MRI) with whole-mount histopathology (WMHP) validation. METHODS: With IRB approval, 140 patients with 3T mp-MRI and WMHP comprised the study cohort. The DTL-based model was trained on 169 lesions in 110 arbitrarily selected patients and tested on the remaining 47 lesions in 30 patients. We compared the DTL-based model with the same DL model architecture trained from scratch and the classification based on PIRADS v2 score with a threshold of 4 using accuracy, sensitivity, specificity, and area under curve (AUC). Bootstrapping with 2000 resamples was performed to estimate the 95% confidence interval (CI) for AUC.

June 2019

Zhong X, Shakeri S, Liu D, Sayre J, Raman SS, Wu HH, Sung K.

Variable flip angle (VFA) imaging is widely used for the estimation of T₁ relaxation in the prostate, but may have limited repeatability and reproducibility due to its sensitivity to B₁^✛ inhomogeneity. PURPOSE: To assess the repeatability and reproducibility of prostate T₁ estimation with and without compensating for B₁^✛ variation. STUDY TYPE: Prospective. POPULATION: Twenty-one volunteers were prospectively recruited and scanned twice on two 3 T MRI scanners, resulting in 84 VFA T₁ exams. FIELD STRENGTH/SEQUENCE: 3 T/2D saturated turbo fast low angle shot (FLASH) and 3D dual-echo FLASH. ASSESSMENT: Two B₁^✛ mapping techniques, including reference region VFA (RR-VFA) and saturated turbo FLASH (satTFL), were used for B₁^✛ correction, and T₁ maps with and without B₁^✛ correction were tested for intrascanner repeatability and interscanner reproducibility. Volumetric regions of interest (ROIs) were drawn on the transition zone, peripheral zone of the prostate, and the obturator internus left and right muscles in the corresponding slices. STATISTICAL TESTS: The average T₁ within each ROI for each scan was compared for both intra- and interscanner variability using concordance correlation coefficient and a Bland-Altman plot.

May 2019

Brown M, Browning P, Wahi-Anwar MW, Murphy M, Delgado J, Greenspan H, Abtin F, Ghahremani S, Yaghmai N, da Costa I, Becker M, Goldin J.

RATIONALE AND OBJECTIVES: The purpose of this paper is to describe the integration of a commercial chest CT computer-aided detection (CAD) system into the clinical radiology reporting workflow and perform an initial investigation of its impact on radiologist efficiency. It seeks to complement research into CAD sensitivity and specificity of stand-alone systems, by focusing on report generation time when the CAD is integrated into the clinical workflow. MATERIALS AND METHODS: A commercial chest CT CAD software that provides automated detection and measurement of lung nodules, ascending and descending aorta, and pleural effusion was integrated with a commercial radiology report dictation application. The CAD system automatically prepopulated a radiology report template, thus offering the potential for increased efficiency. The integrated system was evaluated using 40 scans from a publicly available lung nodule database. Each scan was read using two methods: (1) without CAD analytics, i.e., manually populated report with measurements using electronic calipers, and (2) with CAD analytics to prepopulate the report for reader review and editing. Three radiologists participated as readers in this study.

May 2019

Ellingson BM, Hesterman C, Johnston M, Dudeck NR, Charles AC, Villablanca JP.

The use of advanced imaging in routine diagnostic practice appears to provide only limited value in patients with migraine who have not experienced recent changes in headache characteristics or symptoms. However, advanced imaging may have potential for studying the biological manifestations and pathophysiology of migraine headaches. Migraine with aura appears to have characteristic spatiotemporal changes in structural anatomy, function, hemodynamics, metabolism, and biochemistry, whereas migraine without aura produces more subtle and complex changes. Large, controlled, multicenter imaging-based observational trials are needed to confirm the anecdotal evidence in the literature and test the scientific hypotheses thought to underscore migraine pathophysiology.

May 2019

Expert Panel on Musculoskeletal Imaging:, Torabi M, Lenchik L, Beaman FD, Wessell DE, Bussell JK, Cassidy RC, Czuczman GJ, Demertzis JL, Khurana B, Klitzke A, Motamedi K, Pierce JL, Sharma A, Walker EA, Kransdorf MJ.

Hand and wrist injuries are common reasons for musculoskeletal-related emergency department visits. Imaging is essential for evaluating many of these injuries. In most cases, conventional radiographs provide sufficient information to guide the treating clinician. This review focuses on seven common variants to guide diagnosis of hand and wrist injuries. In addition to radiographs, appropriate use of CT, MRI, bone scan, and ultrasound are discussed. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

May 2019

Expert Panel on Neurological Imaging and Musculoskeletal Imaging:, Beckmann NM, West OC, Nunez D Jr, Kirsch CFE, Aulino JM, Broder JS, Cassidy RC, Czuczman GJ, Demertzis JL, Johnson MM, Motamedi K, Reitman C, Shah LM, Than K, Ying-Kou Yung E, Beaman FD, Kransdorf MJ, Bykowski J.

Injuries to the cervical and thoracolumbar spine are commonly encountered in trauma patients presenting for treatment. Cervical spine injuries occur in 3% to 4% and thoracolumbar fractures in 4% to 7% of blunt trauma patients presenting to the emergency department. Clear, validated criteria exist for screening the cervical spine in blunt trauma. Screening criteria for cervical vascular injury and thoracolumbar spine injury have less validation and widespread acceptance compared with cervical spine screening. No validated criteria exist for screening of neurologic injuries in the setting of spine trauma. CT is preferred to radiographs for initial assessment of spine trauma. CT angiography and MR angiography are both acceptable in assessment for cervical vascular injury. MRI is preferred to CT myelography for assessing neurologic injury in the setting of spine trauma. MRI is usually appropriate when there is concern for ligament injury or in screening obtunded patients for cervical spine instability. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

May 2019

Galldiks N, Langen KJ, Albert NL, Chamberlain M, Soffietti R, Kim MM, Law I, Le Rhun E, Chang S, Schwarting J, Combs SE, Preusser M, Forsyth P, Pope W, Weller M, Tonn JC.

Brain metastases (BM) from extracranial cancer are associated with significant morbidity and mortality. Effective local treatment options are stereotactic radiotherapy, including radiosurgery or fractionated external beam radiotherapy, and surgical resection. The use of systemic treatment for intracranial disease control also is improving. BM diagnosis, treatment planning, and follow-up is most often based on contrast-enhanced magnetic resonance imaging (MRI). However, anatomic imaging modalities including standard MRI have limitations in accurately characterizing posttherapeutic reactive changes and treatment response. Molecular imaging techniques such as positron emission tomography (PET) characterize specific metabolic and cellular features of metastases, potentially providing clinically relevant information supplementing anatomic MRI. Here, the Response Assessment in Neuro-Oncology working group provides recommendations for the use of PET imaging in the clinical management of patients with BM based on evidence from studies validated by histology and/or clinical outcome.

May 2019

Hoffman J, Emaminejad N, Wahi-Anwar M, Kim GH, Brown M, Young S, McNitt-Gray M.

PURPOSE: With recent substantial improvements in modern computing, interest in quantitative imaging with CT has seen a dramatic increase. As a result, the need to both create and analyze large, high-quality datasets of clinical studies has increased as well. At present, no efficient, widely available method exists to accomplish this. The purpose of this technical note is to describe an open-source high-throughput computational pipeline framework for the reconstruction and analysis of diagnostic CT imaging data to conduct large-scale quantitative imaging studies and to accelerate and improve quantitative imaging research. METHODS: The pipeline consists of two, primary "blocks": reconstruction and analysis. Reconstruction is carried out via a graphics processing unit (GPU) queuing framework developed specifically for the pipeline that allows a dataset to be reconstructed using a variety of different parameter configurations such as slice thickness, reconstruction kernel, and simulated acquisition dose. The analysis portion then automatically analyzes the output of the reconstruction using "modules" that can be combined in various ways to conduct different experiments. Acceleration of analysis is achieved using cluster processing. Efficiency and performance of the pipeline are demonstrated using an example 142 subject lung screening cohort reconstructed 36 different ways and analyzed using quantitative emphysema scoring techniques.

May 2019

Hoffman T, Khademhosseini A, Langer R.

In this Perspective, we discuss the impact of the past 25 years of tissue engineering on the development of clinical therapies. Based on their success and other significant research accomplishments, platforms of innovation were identified. Their discoveries will enable tissue engineering inspired therapies to meet the requirements necessary for large-scale manufacturing and Food and Drug Administration (FDA) approval for a diverse range of indications.

May 2019

Johnson DC, Raman SS, Mirak SA, Kwan L, Bajgiran AM, Hsu W, Maehara CK, Ahuja P, Faiena I, Pooli A, Salmasi A, Sisk A, Felker ER, Lu DSK, Reiter RE.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) undoubtedly affects the diagnosis and treatment of localized prostate cancer (CaP). However, clinicians need a better understanding of its accuracy and limitations in detecting individual CaP foci to optimize management. OBJECTIVE: To determine the per-lesion detection rate for CaP foci by mpMRI and identify predictors of tumor detection. DESIGN, SETTING, AND PARTICIPANTS: We carried out a retrospective analysis of a prospectively managed database correlating lesion-specific results from mpMRI co-registered with whole-mount pathology (WMP) prostatectomy specimens from June 2010 to February 2018. Participants include 588 consecutive patients with biopsy-proven CaP undergoing 3-T mpMRI before radical prostatectomy at a single tertiary institution. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We measured mpMRI sensitivity in detecting individual CaP and clinically significant (any Gleason score ≥7) CaP foci and predictors of tumor detection using multivariate analysis.

May 2019

Kao SD, Edwards MP, Kee ST, Moriarty JM.

A 47-year-old male with a remote renal transplant due to pediatric glomerulonephritis on oral anticoagulation for symptomatic deep venous thrombosis and pulmonary emboli presented with sudden hip and groin pain. The patient was found to have a spinal epidural hematoma, underwent reversal of anticoagulation, and subsequently developed worsening renal function. Imaging revealed occlusive iliocaval venous thrombosis with extension to the renal allograft. Given risk of epidural hematoma expansion, the patient was deemed high risk for thrombolysis. The AngioVac system was used for single session thrombus removal. The patient's renal function improved and no focal neurologic sequelae was noted postprocedure. Six-month follow-up showed persistent vessel patency.

May 2019

Liebeskind DS, Bracard S, Guillemin F, Jahan R, Jovin TG, Majoie CB, Mitchell PJ, van der Lugt A, Menon BK, San Román L, Campbell BC, Muir KW, Hill MD, Dippel DW, Saver JL, Demchuk AM, Dávalos A, White P, Brown S, Goyal M; HERMES Collaborators.

BACKGROUND: Revascularization after endovascular therapy for acute ischemic stroke is measured by the Thrombolysis In Cerebral Infarction (TICI) scale, yet variability exists in scale definitions. We examined the degree of reperfusion with the expanded TICI (eTICI) scale and association with outcomes in the HERMES collaboration of recent endovascular trials. METHODS: The HERMES Imaging Core, blind to all other data, evaluated angiography after endovascular therapy in HERMES. A battery of TICI scores (mTICI, TICI, TICI2C) was used to define reperfusion of the initial target occlusion defined by non-invasive imaging and conventional angiography.

May 2019

McWilliams JP, Bilhim TA, Carnevale FC, Bhatia S, Isaacson AJ, Bagla S, Sapoval MR, Golzarian J, Salem R, McClure TD, Kava BR, Spies JB, Sabharwal T, McCafferty I, Tam AL.

Benign prostatic hyperplasia (BPH) describes the proliferation of the glandular and stromal tissue in the transition zone of the prostate, which may result in bladder outlet obstruction and consequent lower urinary tract symptoms (LUTS). The prevalence of BPH increases with age, affecting more than 70% of men older than 70 years (1), and one fourth of men older than 70 years have moderate to severe LUTS that impair their quality of life (QOL) 2, 3. Thus, BPH and ensuing LUTS represent a significant health issue affecting millions of men.

May 2019

Mohajeri S, Bezabeh T, Ijare OB, King SB, Thomas MA, Minuk G, Lipschitz J, Kirkpatrick I, Micflikier AB, Summers R, Smith ICP.

Primary sclerosing cholangitis (PSC) has been considered to be either an "autoimmune disease" or a "bile acid-induced injury." In vitro MRS studies on PSC patients have limitations due to the contamination of bile with contrast agent (commonly administered during endoscopic retrograde cholangiopancreatography) and/or the use of patient cohorts with other diseases as controls. The objective of this study was to quantify biliary metabolites using in vivo 1 H MRS and gain insight into the pathogenesis of PSC. Biliary metabolites in 10 PSC patients and 14 healthy controls were quantified in vivo using ¹H MRS on a 3 T MR scanner. The concentrations of total bile acids plus cholesterol, glycine-conjugated bile acids, taurine-conjugated bile acids, and choline-containing phospholipids (chol-PLs) were compared between the two groups. There were statistically significant decreases in the levels of the above mentioned biliary metabolites in the PSC patients compared with controls. The reduction in bile acid secretion in bile of PSC patients indicates accumulation of bile acids in hepatocytes. Moreover, reduction in the levels of chol-PLs in bile may increase the toxic effects of bile acids. Our findings suggest that the bile duct injury in PSC patients is most likely due to "bile acid-induced injury."

May 2019

Salamon N.

May 2019

Shreve L, Lee EW.

Portal hypertension, a consequence of end-stage liver disease and liver cirrhosis can lead to significant morbidity and mortality for patients through abnormal fluid accumulation as well as the formation of portosystemic shunts and varices. Treatment of the sequelae of portal hypertension can be achieved through endovascular management by referral to an interventional radiologist on an outpatient or emergent basis as required. Current techniques include the placement of peritoneovenous shunts and tunneled peritoneal drains, the creation of transjugular intrahepatic portosystemic shunts, or the obliteration of shunts via balloon-occluded retrograde transvenous obliteration (BRTO). In addition, newer procedural techniques utilizing vascular plugs and coils have reduced risks of the traditional BRTO procedure. Modified-BRTO procedures, known as plug-assisted and coil-assisted retrograde transvenous obliteration (PARTO and CARTO, respectively) have become the standard of care at many institutions for the treatment of gastric varices and portosystemic shunt-induced hepatic encephalopathy. This review examines the most recent literature of the management of portal hypertension by interventional radiologists, evaluating treatment options as well as the clinical and technical outcomes of TIPS, peritoneovenous shunts, tunneled peritoneal drains, BRTOs, and modified-BRTOs as well as future directions in the development of procedural techniques.

May 2019

Tafti BA, Padia SA.

Dosimetry for yttrium-90 radioembolization continues to generate interest and controversy, as multiple approaches have been used effectively. Traditionally, simple formulas primarily based on patients' body weight or perfused liver volume were used. Over the past several years, dosimetry refinements have led to marked improvements in this therapy from both a safety and efficacy standpoint. Technetium-99m macroaggregated albumin single photon emission computed tomography (SPECT) optimizes pretreatment dosimetry to ensure delivery of a therapeutic radiation dose to the tumor while minimizing nontarget radiation to healthy hepatic tissue. Post-treatment yttrium-90 PET utilizing the inherent internal pair production of yttrium-90 accurately calculates the absorbed dose to tumors and to the normal hepatic parenchyma, which correlates with patient outcomes. As dosimetric calculations become more complex, quantitative imaging with Tc-99m SPECT and Y-90 PET may set the new standard for radioembolization dosimetry.

May 2019

Yao J, Tan CHP, Schlossman J, Chakhoyan A, Raymond C, Pope WB, Salamon N, Lai A, Ji M, Nghiemphu PL, Liau LM, Cloughesy TF, Ellingson BM.

PURPOSE: The objective of the current study was to explore the efficacy of using pH-weighted amine CEST-EPI as a potential non-invasive imaging biomarker for treatment response and/or failure in recurrent GBM patients treated with bevacizumab. METHOD: A total of 11 patients with recurrent GBM treated with bevacizumab were included in this prospective study. CEST-EPI, perfusion MRI, and standardized anatomic MRI were obtained in patients before and after bevacizumab administration. CEST-EPI measures of magnetization transfer ratio asymmetry (MTR_asym) at 3 ppm were used for pH-weighted imaging contrast. Multiple measures were examined for their association with progression-free survival (PFS).

May 2019

Young JJ, Pahwa A, Patel M, Jude CM, Nguyen M, Deshmukh M, Huang L, Mohammad SF.

Gastric cancer is a leading cause of cancer-related deaths worldwide and is associated with an overall 5-year survival rate of less than 20%. The most common histologic subtype of gastric cancer is adenocarcinoma. Imaging techniques for evaluating gastric adenocarcinoma include endoscopic US, fluoroscopic upper gastrointestinal imaging, CT, PET/CT, and MRI. Hydrodynamic multiphasic contrast material-enhanced CT is the imaging modality of choice for preoperative clinical staging of regional, nodal, and metastatic involvement. Radiologic manifestations of gastric adenocarcinoma at double-contrast upper gastrointestinal imaging and CT include polyps, ulceration, indistensibility, wall thickening, and abnormal enhancement. There are multiple pathways of disease spread. These pathways include lymphatic dissemination; subperitoneal dissemination along the perigastric ligaments, mesentery, or omentum; direct invasion into adjacent organs; transperitoneal seeding; and hematogenous dissemination. The spread of disease is affected by the location of the tumor in the stomach, and the ligamentous and lymphatic anatomy. Key imaging features that affect clinical staging with use of the TNM classification system for gastric adenocarcinoma, as described in the eighth edition of the AJCC Cancer Staging Manual, are briefly discussed. Accurate radiologic assessment of gastric adenocarcinoma requires identification of perigastric ligament infiltration, regional and metastatic nodal disease, and direct and metastatic organ involvement, all of which directly affect tumor staging, treatment, and prognosis.

April 2019

Bandaru P, Chu D, Sun W, Lasli S, Zhao C, Hou S, Zhang S, Ni J, Cefaloni G, Ahadian S, Dokmeci MR, Sengupta S, Lee J, Khademhosseini A.

Cells secrete substances that are essential to the understanding of numerous immunological phenomena and are extensively used in clinical diagnoses. Countless techniques for screening of biomarker secretion in living cells have generated valuable information on cell function and physiology, but low volume and real-time analysis is a bottleneck for a range of approaches. Here, a simple, highly sensitive assay using a high-throughput micropillar and microwell array chip (MIMIC) platform is presented for monitoring of biomarkers secreted by cancer cells. The sensing element is a micropillar array that uses the enzyme-linked immunosorbent assay (ELISA) mechanism to detect captured biomolecules. When integrated with a microwell array where few cells are localized, interleukin 8 (IL-8) secretion can be monitored with nanoliter volume using multiple micropillar arrays. The trend of cell secretions measured using MIMICs matches the results from conventional ELISA well while it requires orders of magnitude less cells and volumes. Moreover, the proposed MIMIC is examined to be used as a drug screening platform by delivering drugs using micropillar arrays in combination with a microfluidic system and then detecting biomolecules from cells as exposed to drugs.

April 2019

Comotto M, Saghazadeh S, Bagherifard S, Aliakbarian B, Kazemzadeh-Narbat M, Sharifi F, Mousavi Shaegh SA, Arab-Tehrany E, Annabi N, Perego P, Khademhosseini A, Tamayol A.

Traditional wound dressings are not effective enough to regulate the moisture content and remove excessive exudate from the environment. Wet wound dressings formed from hydrogels such as alginate are widely used in clinical practice for treatment of skin disorders. Here, we functionalize alginate dressings with natural antioxidants such as curcumin and t-resveratrol to render them both anti-inflammatory and antibacterial. The hydrogel maintains excellent mechanical properties and oxygen permeability over time. The release rate of the compounds from the hydrogels is assessed and their impact on bacterial and cellular growth is evaluated. The antioxidant compounds act as bactericidal agents and improve cell viability. The optimal concentration of active compounds in the engineered alginate-based dressings is determined.

April 2019

Ghannam JS, Cooper KJ, Bundy JJ, Srinivasa RN, Patel N, Cline MR, Chick JFB.

Endovascular treatment of malignant intrahepatic inferior vena cava stenosis involves venoplasty and stenting. Intravascular migration is a complication associated with stents. This technical report describes the retrieval of migrated intracardiac Gianturco Z-stents using rigid endobronchial forceps.

April 2019

Ho KC, Scalzo F, Sarma KV, Speier W, El-Saden S, Arnold C.

Predicting infarct volume from magnetic resonance perfusion-weighted imaging can provide helpful information to clinicians in deciding how aggressively to treat acute stroke patients. Models have been developed to predict tissue fate, yet these models are mostly built using hand-crafted features (e.g., time-to-maximum) derived from perfusion images, which are sensitive to deconvolution methods. We demonstrate the application of deep convolution neural networks (CNNs) on predicting final stroke infarct volume using only the source perfusion images. We propose a deep CNN architecture that improves feature learning and achieves an area under the curve of 0.871±0.024, outperforming existing tissue fate models. We further validate the proposed deep CNN with existing 2-D and 3-D deep CNNs for images/video classification, showing the importance of the proposed architecture. Our work leverages deep learning techniques in stroke tissue outcome prediction, advancing magnetic resonance imaging perfusion analysis one step closer to an operational decision support tool for stroke treatment guidance.

April 2019

Kim H, Mentzer J, Taira R.

BACKGROUND: Physical activity data provides important information on disease onset, progression, and treatment outcomes. Although analyzing physical activity data in conjunction with other clinical and microbiological data will lead to new insights crucial for improving human health, it has been hampered partly because of the large variations in the way the data are collected and presented. OBJECTIVE: The aim of this study was to develop a Physical Activity Ontology (PACO) to support structuring and standardizing heterogeneous descriptions of physical activities. METHODS: We prepared a corpus of 1140 unique sentences collected from various physical activity questionnaires and scales as well as existing standardized terminologies and ontologies. We extracted concepts relevant to physical activity from the corpus using a natural language processing toolkit called Multipurpose Text Processing Tool. The target concepts were formalized into an ontology using Protégé (version 4). Evaluation of PACO was performed to ensure logical and structural consistency as well as adherence to the best practice principles of building an ontology. A use case application of PACO was demonstrated by structuring and standardizing 36 exercise habit statements and then automatically classifying them to a defined class of either sufficiently active or insufficiently active using FaCT++, an ontology reasoner available in Protégé.

April 2019

Levin ES, Plotkin B.

Total elbow arthroplasty is currently an established surgical treatment for several pathologies of the elbow. Although initially used primarily in the treatment of rheumatoid arthritis, indications for total elbow arthroplasty have expanded and now include trauma, primary and secondary osteoarthritis, fracture nonunion, and following neoplasm resection. Desired outcomes of elbow arthroplasty include decreasing patient pain, restoration of function and mobility, and prevention of or treatment for instability. In comparison with total elbow arthroplasty, radial head replacements are most commonly performed following trauma. An additional technique, capitellar resurfacing arthroplasty, was developed in an effort to prevent early-onset osteoarthritis secondary to altered elbow biomechanics following radial head replacement. Complications of these surgeries include loosening, fracture, instability and dissociation, bushing wear, and particle disease.

April 2019

Miri AK, Khalilpour A, Cecen B, Maharjan S, Shin SR, Khademhosseini A.

A basic prerequisite for the survival and function of three-dimensional (3D) engineered tissue constructs is the establishment of blood vessels. 3D bioprinting of vascular networks with hierarchical structures that resemble in vivo structures has allowed blood circulation within thick tissue constructs to accelerate vascularization and enhance tissue regeneration. Successful rapid vascularization of tissue constructs requires synergy between fabrication of perfusable channels and functional bioinks that induce angiogenesis and capillary formation within constructs. Combinations of 3D bioprinting techniques and four-dimensional (4D) printing concepts through patterning proangiogenic factors may offer novel solutions for implantation of thick constructs. In this review, we cover current bioprinting techniques for vascularized tissue constructs with vasculatures ranging from capillaries to large blood vessels and discuss how to implement these approaches for patterning proangiogenic factors to maintain long-term, stimuli-controlled formation of new capillaries.

April 2019

Paez-Mayorga J, Hernández-Vargas G, Ruiz-Esparza GU, Iqbal HMN, Wang X, Zhang YS, Parra-Saldivar R, Khademhosseini A.

The advances in biotechnology, biomechanics, and biomaterials can be used to develop organ models that aim to accurately emulate their natural counterparts. Heart disease, one of the leading causes of death in modern society, has attracted particular attention in the field of tissue engineering. To avoid incorrect prognosis of patients suffering from heart disease, or from adverse consequences of classical therapeutic approaches, as well as to address the shortage of heart donors, new solutions are urgently needed. Biotechnological advances in cardiac tissue engineering from a bioreactor perspective, in which recapitulation of functional, biochemical, and physiological characteristics of the cardiac tissue can be used to recreate its natural microenvironment, are reviewed. Detailed examples of functional and preclinical applications of engineered cardiac constructs and the state-of-the-art systems from a bioreactor perspective are provided. Finally, the current trends and future directions of the field for its translation to clinical settings are discussed.

April 2019

Rinoldi C, Costantini M, Kijeńska-Gawrońska E, Testa S, Fornetti E, Heljak M, Ćwiklińska M, Buda R, Baldi J, Cannata S, Guzowski J, Gargioli C, Khademhosseini A, Swieszkowski W.

Fiber-based approaches hold great promise for tendon tissue engineering enabling the possibility of manufacturing aligned hydrogel filaments that can guide collagen fiber orientation, thereby providing a biomimetic micro-environment for cell attachment, orientation, migration, and proliferation. In this study, a 3D system composed of cell-laden, highly aligned hydrogel yarns is designed and obtained via wet spinning in order to reproduce the morphology and structure of tendon fascicles. A bioink composed of alginate and gelatin methacryloyl (GelMA) is optimized for spinning and loaded with human bone morrow mesenchymal stem cells (hBM-MSCs). The produced scaffolds are subjected to mechanical stretching to recapitulate the strains occurring in native tendon tissue. Stem cell differentiation is promoted by addition of bone morphogenetic protein 12 (BMP-12) in the culture medium. The aligned orientation of the fibers combined with mechanical stimulation results in highly preferential longitudinal cell orientation and demonstrates enhanced collagen type I and III expression. Additionally, the combination of biochemical and mechanical stimulations promotes the expression of specific tenogenic markers, signatures of efficient cell differentiation towards tendon. The obtained results suggest that the proposed 3D cell-laden aligned system can be used for engineering of scaffolds for tendon regeneration.

April 2019

Zhou SR, Simopoulos DN, Jayadevan R, Felker ER, Delfin MK, Barsa DE, Kwan L, Marks LS.

OBJECTIVE: To investigate safety, efficacy, and quality of life impact of hemi-gland cryotherapy for clinically-significant prostate cancer (CaP), when patient selection and follow-up includes MRI-guided biopsy. METHODS: Twenty-nine men with unilateral CaP (all clinically significant with prostate volume <60 cc) were enrolled in a prospective observational trial of hemi-gland cryotherapy. Mean patient age was 68.7 years. Median prostate-specific antigen (PSA) was 6.6 ng/mL. MRI-guided biopsy (3T-MRI, Artemis US fusion) was used for diagnosis and repeated at 6-month follow-up in all men. Treatment was under general anesthesia using the BTG/Galil system. Validated questionnaires were used to determine effects of treatment on urinary and sexual function and quality of life.

March 2019

Canon CL, Enzmann DR, Grist TM, Meltzer CC, Norbash A, Omary RA, Rawson JV, Recht MP.

The Society of Chairs of Academic Radiology Departments (SCARD), as stated in our bylaws, advances the art and science of radiology by the development of policies and initiatives essential for the success of the clinical, research, and educational missions of radiology and imaging sciences [1]. Faculty well-being and diversity with inclusion are necessary for this success. Supported parental leave is not only about health and wellness but it is also about equity and creation of an inclusive environment.

March 2019

Chang K, Quinones-Baldrich W, Kwon M, Archie M, Finn P.

A 15-year-old boy presented first in 2012 with chronic abdominal pain and high-output congestive heart failure (CHF) due to a left iliac vein aneurysm secondary to high-flow pelvic arteriovenous malformation (AVM). Despite several embolization interventions with coils and Onyx (ev3, Covidien, Plymouth, Minn), the patient continued to have episodes of CHF. Magnetic resonance imaging (MRI) demonstrated a left iliac vein aneurysm with a diameter of 13 cm (A, left). To reduce flow from the AVM, an endograft from the inferior vena cava to the left external iliac vein was deployed, successfully treating his CHF.

March 2019

Cloughesy TF, Mochizuki AY, Orpilla JR, Hugo W, Lee AH, Davidson TB, Wang AC, Ellingson BM, Rytlewski JA, Sanders CM, Kawaguchi ES, Du L, Li G, Yong WH, Gaffey SC, Cohen AL, Mellinghoff IK, Lee EQ, Reardon DA, O'Brien BJ, Butowski NA, Nghiemphu PL, Clarke JL, Arrillaga-Romany IC, Colman H, Kaley TJ, de Groot JF, Liau LM, Wen PY, Prins RM.

Glioblastoma is the most common primary malignant brain tumor in adults and is associated with poor survival. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical programmed cell death protein 1 (PD-1) blockade alone. Neoadjuvant PD-1 blockade was associated with upregulation of T cell- and interferon-γ-related gene expression, but downregulation of cell-cycle-related gene expression within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 in the tumor microenvironment, enhanced clonal expansion of T cells, decreased PD-1 expression on peripheral blood T cells and a decreasing monocytic population was observed more frequently in the neoadjuvant group than in patients treated only in the adjuvant setting. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor.

March 2019

Colby GP, Baharvahdat H, Mowla A, Young R, Shwe Y, Jahan R, Tateshima S, Szeder V, Nour M, Vinuela F, Duckwiler G.

BACKGROUND: Extensive evidence supports mechanical thrombectomy using stentrievers (SR) for acute large vessel occlusion (aLVO). Aspiration is also used as a first pass or adjunct technique during clot removal. Here we report technical results from mechanical thrombectomy cases using SR alone, aspiration alone (AD), or a combination of SR and aspiration (SA) as a first pass for aLVO. METHODS: An institutional stroke database was reviewed for patients presenting to a single academic institution with anterior circulation aLVO and who were treated with mechanical thrombectomy from 2011 to 2017. Patients managed with SR alone, AD, or a combination of these 2 techniques (SA) were identified. The rate of successful recanalization after the first thrombectomy attempt was compared between the 3 groups.

March 2019

England JR, Cheng PM.

OBJECTIVE: The purpose of this article is to highlight best practices for writing and reviewing articles on artificial intelligence for medical image analysis.

March 2019

Jerant A, Henderson MC, Griffin E, Hall TR, Kelly CJ, Peterson EM, Wofsy D, Tancredi DJ, Sousa FJ, Franks P.

PURPOSE: To compare the predictive validities of medical school admissions multiple mini-interviews (MMIs) and traditional interviews (TIs). METHOD: This longitudinal observational study of 2011-2013 matriculants to five California public medical schools examined the associations of MMI scores (two schools) and TI scores (three schools) with subsequent academic performance. Regression models adjusted for sociodemographics and undergraduate academic metrics examined associations of standardized mean MMI and TI scores with United States Medical Licensing Examination Step 1 and Step 2 Clinical Knowledge (CK) scores and, for required clerkships, with mean National Board of Medical Examiners Clinical Science subject (shelf) exam score and number of honors grades.

March 2019

Ko H, Suthiwanich K, Mary H, Zanganeh S, Hu SK, Ahadian S, Yang Y, Choi G, Fetah K, Niu Y, Mao JJ, Khademhosseini A.

Physicochemical and biological gradients are desirable features for hydrogels to enhance their relevance to biological environments for three-dimensional (3D) cell culture. Therefore, simple and efficient techniques to generate chemical, physical and biological gradients within hydrogels are highly desirable. This work demonstrates a technique to generate biomolecular and mechanical gradients in photocrosslinkable hydrogels by stacking and crosslinking prehydrogel solution in a layer by layer manner. Partial crosslinking of the hydrogel allows mixing of prehydrogel solution with the previous hydrogel layer, which makes a smooth gradient profile, rather than discrete layers. This technique enables the generation of concentration gradients of bovine serum albumin in both gelatin methacryloyl (GelMA) and poly(ethylene glycol) diacrylate hydrogels, as well as mechanical gradients across a hydrogel containing varying gel concentrations. Fluorescence microscopy, mechanical testing, and scanning electron microscopy show that the gradient profiles can be controlled by changing both the volume and concentration of each layer as well as intensity of UV exposure. GelMA hydrogel gradients with different Young's moduli were successfully used to culture human fibroblasts. The fibroblasts migrated along the gradient axis and showed different morphologies. In general, the proposed technique provides a rapid and simple approach to design and fabricate 3D hydrogel gradients for in vitro biological studies and potentially for in vivo tissue engineering applications.

March 2019

Mirak SA, Shakeri S, Bajgiran AM, Felker ER, Sung KH, Asvadi NH, Khoshnoodi P, Markovic D, Ponzini D, Ahuja P, Sisk A, Reiter RE, Lu D, Raman SS.

PURPOSE: We investigated the performance of 3 Tesla multiparametric magnetic resonance imaging with and without an endorectal coil to detect prostate cancer with a whole mount histopathology reference. MATERIALS AND METHODS: This retrospective HIPAA (Health Insurance Portability and Accountability Act) compliant, institutional review board approved, case-control study included patients who underwent 3 Tesla multiparametric magnetic resonance imaging with and without an endorectal coil from July 2009 to December 2016 prior to prostatectomy. The tumor detection rate was calculated for total and index lesions. Lesion magnetic resonance imaging and histopathology features were compared between the 2 groups. Using SPSS®, version 24 p <0.05 was considered significant.

March 2019

Mohammadian Bajgiran A, Afshari Mirak S, Shakeri S, Felker ER, Ponzini D, Ahuja P, Sisk AE, Lu DS, Raman SS.

PURPOSE: To determine the characteristics of missed prostate cancer (PCa) lesions on 3T multiparametric-MRI (mpMRI) based on PI-RADSv2 with whole-mount histopathology (WMHP) correlation. MATERIALS AND METHODS: This IRB-approved, HIPAA-compliant study, included 614 consecutive men with 3T mpMRI prior to prostatectomy at a single tertiary center between 12/2009 and 4/2017. Clinical, mpMRI, and pathologic features were obtained. PI-RADSv2-based MRI detected lesions were matched with previously finalized WMHP by a genitourinary (GU) radiologist and a GU pathologist. Patients with no mpMRI detected PCa lesion, but with at least one lesion ≥ 1 cm on WMHP, were reviewed retrospectively and assigned a PI-RADSv2 score. Tumor characteristics were compared between missed and detected lesions.

March 2019

Moulin K, Aliotta E, Ennis DB.

PURPOSE: To study the impact of variable flow-encoding strength on intravoxel incoherent motion (IVIM) liver imaging of diffusion and perfusion. THEORY: Signal attenuation in DWI arises from (1) intravoxel microvascular blood flow, which depends on the flow-encoding strength α (first gradient moment) of the diffusion-encoding waveform, and (2) intravoxel spin diffusion, which depends on the b-value of the diffusion-encoding gradient waveforms α and b-value. Both are linked to the diffusion-encoding gradient waveform and conventionally are not independently controlled. METHODS: In this work a convex optimization framework was used to generate gradient waveforms with independent α and b-value. Thirty-six unique α and b-value sample points from 5 different gradient waveforms were used to reconstruct perfusion fraction (f), coefficient of diffusion (D), and blood velocity standard deviation (V_b ) maps using a recently proposed IVIM model. Faster acquisition strategies were evaluated with 1000 random subsampling strategies of 16, 8, and 4 α and b-value. Among the subsampled reconstructions, the sampling schemes that minimized the difference with the fully sampled reconstruction were reported.

March 2019

Pan P, Lee EW, Eghbalieh N, Trieu H.

Transarterial embolization of bone tumors is effective in both decreasing intraoperative hemorrhage and alleviating symptoms. Transradial access has been associated with a lower risk of access site complications when compared to transfemoral access. Three cases of transarterial embolization of bony metastases in the upper extremity and shoulder girdle were performed with an ipsilateral transradial access. In each case, significant decrease in tumor blush was noted after embolization, and no auxiliary access site was needed. Positive outcomes were observed in all three patients, including successful subsequent surgery without significant hemorrhage and notable post-procedural pain reduction.

March 2019

Sakai N, Imamura H, Adachi H, Tani S, Tokunaga S, Funatsu T, Suzuki K, Adachi H, Sasaki N, Kawabata S, Akiyama R, Horiuchi K, Ohara N, Kono T, Fujiwara S, Kaneko N, Tateshima S.

OBJECTIVE: To describe our initial experience with the Versi Retriever for mechanical thrombectomy in patients with acute ischemic stroke. METHODS: This study is a single-center, single-arm, first-in-man registry under institutional review board control to evaluate the efficacy and safety of the new stent retriever, the Versi Retriever. Patients with acute ischemic stroke were consecutively enrolled between September and November 2017. The clinical and procedural data were retrospectively analyzed. The angiographic result after the procedure was self-graded based on the Thrombolysis in Cerebral Infarction (TICI) scale by each operator.

March 2019

Shirzaei Sani E, Kheirkhah A, Rana D, Sun Z, Foulsham W, Sheikhi A, Khademhosseini A, Dana R, Annabi N.

Corneal injuries are common causes of visual impairment worldwide. Accordingly, there is an unmet need for transparent biomaterials that have high adhesion, cohesion, and regenerative properties. Herein, we engineer a highly biocompatible and transparent bioadhesive for corneal reconstruction using a visible light cross-linkable, naturally derived polymer, GelCORE (gel for corneal regeneration). The physical properties of GelCORE could be finely tuned by changing prepolymer concentration and photocrosslinking time. GelCORE revealed higher tissue adhesion compared to commercial adhesives. Furthermore, in situ photopolymerization of GelCORE facilitated easy delivery to the cornea, allowing for bioadhesive curing precisely according to the required geometry of the defect. In vivo experiments, using a rabbit stromal defect model, showed that bioadhesive could effectively seal corneal defects and induce stromal regeneration and re-epithelialization. Overall, GelCORE has many advantages including low cost and ease of production and use. This makes GelCORE a promising bioadhesive for corneal repair.

March 2019

Small AJ, Denton KL, Aboulhosn JA.

A 60-year-old woman presented with transient lower extremity weakness and dysarthria 12 years after transcatheter patent foramen ovale (PFO) closure with a Starflex device (NMT Medical, Boston, MA). Her PFO was originally discovered during an evaluation for dyspnea. After device closure, her dyspnea rexolved and she took clopidogrel for 1 year, then aspirin for several years, thereafter, but this had been discontinued for many years before the acute neurological event.

March 2019

Trujillo-de Santiago G, Sharifi R, Yue K, Sani ES, Kashaf SS, Alvarez MM, Leijten J, Khademhosseini A, Dana R, Annabi N.

Closure of ocular wounds after an accident or surgery is typically performed by suturing, which is associated with numerous potential complications, including suture breakage, inflammation, secondary neovascularization, erosion to the surface and secondary infection, and astigmatism; for example, more than half of post-corneal transplant infections are due to suture related complications. Tissue adhesives provide promising substitutes for sutures in ophthalmic surgery. Ocular adhesives are not only intended to address the shortcomings of sutures, but also designed to be easy to use, and can potentially minimize post-operative complications. Herein, recent progress in the design, synthesis, and application of ocular adhesives, along with their advantages, limitations, and potential are discussed. This review covers two main classes of ocular adhesives: (1) synthetic adhesives based on cyanoacrylates, polyethylene glycol (PEG), and other synthetic polymers, and (2) adhesives based on naturally derived polymers, such as proteins and polysaccharides. In addition, different technologies to cover and protect ocular wounds such as contact bandage lenses, contact lenses coupled with novel technologies, and decellularized corneas are discussed. Continued advances in this area can help improve both patient satisfaction and clinical outcomes.

March 2019

Tubi MA, Lutkenhoff E, Blanco MB, McArthur D, Villablanca P, Ellingson B, Diaz-Arrastia R, Van Ness P, Real C, Shrestha V, Engel J Jr, Vespa PM.

OBJECTIVE: Injury severity after traumatic brain injury (TBI) is a well-established risk factor for the development of post-traumatic epilepsy (PTE). However, whether lesion location influences the susceptibility of seizures and development of PTE longitudinally has yet to be defined. We hypothesized that lesion location, specifically in the temporal lobe, would be associated with an increased incidence of both early seizures and PTE. As secondary analysis measures, we assessed the degree of brain atrophy and functional recovery, and performed a between-group analysis, comparing patients who developed PTE with those who did not develop PTE. METHODS: We assessed early seizure incidence (n = 90) and longitudinal development of PTE (n = 46) in a prospective convenience sample of patients with moderate-severe TBI. Acutely, patients were monitored with prospective cEEG and a high-resolution Magnetic Resonance Imaging (MRI) scan for lesion location classification. Chronically, patients underwent a high-resolution MRI, clinical assessment, and were longitudinally monitored for development of epilepsy for a minimum of 2 years post-injury.

March 2019

Wang JW, Padia SA, Lee EW, Moriarty JM, McWilliams JP, Kee ST, Plotnik AN, Sayre JW, Srinivasa RN.

PURPOSE: To report technical success and clinical outcomes of transfemoral venous access for upper extremity dialysis interventions. MATERIALS AND METHODS: A total of 15 patients underwent a transfemoral venous approach for fistulography (n = 4; 27%) or thrombectomy (n = 11; 73%) over a 14-month period. Access characteristics, sheath size, thrombectomy method, angioplasty site, fluoroscopy time, radiation dose, technical and clinical success, complications, and post-intervention primary and secondary patency rates were recorded.

March 2019

Woodworth DC, Holly LT, Mayer EA, Salamon N, Ellingson BM.

BACKGROUND: Advanced cervical spondylosis (CS) can cause structural damage to the spinal cord resulting in long-term neurological impairment including neck pain and motor weakness. We hypothesized long-term structural reorganization within the brain in patients with CS. OBJECTIVE: To explore the associations between cortical thickness, subcortical volumes, neurological symptoms, and pain severity in CS patients with or without myelopathy and healthy controls (HCs). METHODS: High-resolution T1-weighted structural magnetic resonance imaging (MRI) scans from 26 CS patients and 45 HCs were acquired. Cortical thickness and subcortical volumes were computed and compared to the modified Japanese Orthopedic Association (mJOA) and the Neck Disability Index (NDI) scores.

February 2019

Bundy JJ, Hussain J, Patel N, Khayat M, Chick JFB, Gemmete JJ, Srinivasa RN.

Gastric varices are a common manifestation of portal hypertension and are associated with a high rate of mortality and rebleeding. Balloon-occluded retrograde transvenous obliteration (BRTO) is a commonly used method to sclerose gastric varices and has a high clinical success. Common complications following BRTO include portal or splenic vein thrombosis, systemic sclerosant extravasation, pulmonary emboli, and inferior vena cava thrombosis. This report describes a patient with vascular plug migration into the left pulmonary artery with subsequent endovascular retrieval.

February 2019

Dzubur E, Khalil C, Almario CV, Noah B, Minhas D, Ishimori M, Arnold C, Park Y, Kay J, Weisman MH, Spiegel BMR.

OBJECTIVE: Few studies have examined ankylosing spondylitis (AS) patients' concerns about and perceptions of biologic therapies, apart from traditional surveys. In this study, we used social media data to examine the knowledge, attitudes, and beliefs of AS patients regarding biologic therapies. METHODS: We collected posts published on 601 social media sites between January 1, 2016 and April 26, 2017. In each post, both an AS keyword and a biologic were mentioned. To explore themes within the collection of posts in an unsupervised manner, a latent Dirichlet allocation topic model was fit to the data set. Each discovered topic was represented as a discrete distribution over the words in the collection, similar to a word cloud. The topics were manually reviewed to identify themes, which were confirmed using thematic data analysis.

February 2019

Faughnan ME, Gossage JR, Chakinala MM, Oh SP, Kasthuri R, Hughes CCW, McWilliams JP, Parambil JG, Vozoris N, Donaldson J, Paul G, Berry P, Sprecher DL.

Pazopanib (Votrient) is an orally administered tyrosine kinase inhibitor that blocks VEGF receptors potentially serving as anti-angiogenic treatment for hereditary hemorrhagic telangiectasia (HHT). We report a prospective, multi-center, open-label, dose-escalating study [50 mg, 100 mg, 200 mg, and 400 mg], designed as a proof-of-concept study to demonstrate efficacy of pazopanib on HHT-related bleeding, and to measure safety. Patients, recruited at 5 HHT Centers, required ≥ 2 Curacao criteria AND [anemia OR severe epistaxis with iron deficiency]. Co-primary outcomes, hemoglobin (Hgb) and epistaxis severity, were measured during and after treatment, and compared to baseline. Safety monitoring occurred every 1.5 weeks. Seven patients were treated with 50 mg pazopanib daily. Six/seven showed at least 50% decrease in epistaxis duration relative to baseline at some point during study; 3 showed at least 50% decrease in duration during Weeks 11 and 12. Six patients showed a decrease in ESS of > 0.71 (MID) relative to baseline at some point during study; 3/6 showed a sustained improvement. Four patients showed > 2 gm improvement in Hgb relative to baseline at one or more points during study. Health-related QOL scores improved on all SF-36 domains at Week 6 and/or Week 12, except general health (unchanged). There were 19 adverse events (AE) including one severe AE (elevated LFTs, withdrawn from dosing at 43 days); with no serious AE. In conclusion, we observed an improvement in Hgb and/or epistaxis in all treated patients. This occurred at a dose much lower than typically used for oncologic indications, with no serious AE. Further studies of pazopanib efficacy are warranted.

February 2019

Hardy AJ, Bostani M, Hernandez AM, Zankl M, McCollough C, Cagnon C, Boone JM, McNitt-Gray M.

PURPOSE: Size-specific dose estimates (SSDE) conversion factors have been determined by AAPM Report 204 to adjust CTDI_vol to account for patient size but were limited to body CT examinations. The purpose of this work was to determine conversion factors that could be used for an SSDE for helical, head CT examinations for patients of different sizes. METHODS: Validated Monte Carlo (MC) simulation methods were used to estimate dose to the center of the scan volume from a routine, helical head examination for a group of patient models representing a range of ages and sizes. Ten GSF/ICRP voxelized phantom models and five pediatric voxelized patient models created from CT image data were used in this study. CT scans were simulated using a Siemens multidetector row CT equivalent source model. Scan parameters were taken from the AAPM Routine Head protocols for a fixed tube current (FTC), helical protocol, and scan lengths were adapted to the anatomy of each patient model. MC simulations were performed using mesh tallies to produce voxelized dose distributions for the entire scan volume of each model. Three tally regions were investigated: (1) a small 0.6 cc volume at the center of the scan volume, (2) 0.8-1.0 cm axial slab at the center of the scan volume, and (3) the entire scan volume. Mean dose to brain parenchyma for all three regions was calculated. Mean bone dose and a mass-weighted average dose, consisting of brain parenchyma and bone, were also calculated for the slab in the central plane and the entire scan volume. All dose measures were then normalized by CTDI_vol for the 16 cm phantom (CTDI_vol,16 ). Conversion factors were determined by calculating the relationship between normalized doses and water equivalent diameter (D_w ).

February 2019

Hsu W, Zhou X, Petruse A, Chau N, Lee-Felker S, Hoyt A, Wenger N, Elashoff D, Naeim A.

PURPOSE: To analyze women with suspicious findings (assessed as Breast Imaging Reporting and Data System [BI-RADS] 4), examining the value of clinical and imaging predictors in predicting cancer diagnosis. PATIENTS AND METHODS: A set of 2138 examinations (1978 women) given a BI-RADS 4 with matching pathology results were analyzed. Predictors such as patient demographics, clinical risk factors, and imaging-derived features such as BI-RADS assessment and qualitative breast density were considered. Independent predictors of breast cancer were determined by univariate analysis and multivariate logistic regression.

February 2019

Jahan R, Villablanca JP, Harris RJ, Duarte-Vogel S, Williams CK, Vinters HV, Rao N, Enzmann DR, Ellingson BM.

BACKGROUND: A reliable animal model of ischemic stroke is vital for pre-clinical evaluation of stroke therapies. We describe a reproducible middle cerebral artery (MCA) embolic occlusion in the French Lop rabbit characterized with multimodal MRI and histopathologic tissue analysis. NEW METHOD: Fluoroscopic-guided microcatheter placement was performed in five consecutive subjects with angiographic confirmation of MCA occlusion with autologous clot. Multimodal MRI was obtained prior to occlusion and up to six hours post after which repeat angiography confirmed sustained occlusion. The brain was harvested for histopathologic examination.

February 2019

Kong M, Lee J, Yazdi IK, Miri AK, Lin YD, Seo J, Zhang YS, Khademhosseini A, Shin SR.

Cardiac tissue is characterized by being dynamic and contractile, imparting the important role of biomechanical cues in the regulation of normal physiological activity or pathological remodeling. However, the dynamic mechanical tension ability also varies due to extracellular matrix remodeling in fibrosis, accompanied with the phenotypic transition from cardiac fibroblasts (CFs) to myofibroblasts. It is hypothesized that the dynamic mechanical tension ability regulates cardiac phenotypic transition within fibrosis in a strain-mediated manner. In this study, a microdevice that is able to simultaneously and accurately mimic the biomechanical properties of the cardiac physiological and pathological microenvironment is developed. The microdevice can apply cyclic compressions with gradient magnitudes (5-20%) and tunable frequency onto gelatin methacryloyl (GelMA) hydrogels laden with CFs, and also enables the integration of cytokines. The strain-response correlations between mechanical compression and CFs spreading, and proliferation and fibrotic phenotype remolding, are investigated. Results reveal that mechanical compression plays a crucial role in the CFs phenotypic transition, depending on the strain of mechanical load and myofibroblast maturity of CFs encapsulated in GelMA hydrogels. The results provide evidence regarding the strain-response correlation of mechanical stimulation in CFs phenotypic remodeling, which can be used to develop new preventive or therapeutic strategies for cardiac fibrosis.

February 2019

Luo Z, Sun W, Fang J, Lee K, Li S, Gu Z, Dokmeci MR, Khademhosseini A.

Biocompatible and bioresponsive microneedles (MNs) are emerging technology platforms for sustained drug release with a potential to be a key player in transdermal delivery of therapeutics. In this paper, an innovative biodegradable MNs patch for the sustained delivery of drugs using a polymer patch, which can adjust delivery rates based on its crosslinking degree, is reported. Gelatin methacryloyl (GelMA) is used as the base for engineering biodegradable MNs. The anticancer drug doxorubicin (DOX) is loaded into GelMA MNs using the one molding step. The GelMA MNs can efficiently penetrate the stratum corneum layer of a mouse cadaver skin. Mechanical properties and drug release behavior of the GelMA MNs can be adjusted by tuning the degree of crosslinking. The efficacy of the DOX released from the GelMA MNs is tested and the anticancer efficacy of the released drugs against melanoma cell line A375 is demonstrated. Since GelMA is a versatile material in engineering tissue scaffolds, it is expected that the GelMA MNs can be used as a platform for the delivery of various therapeutics.

February 2019

Moriarty JM, Gonzalez Quesada CJ, Wang AC, Yang EH.

A 49-year-old female with pleuritic chest discomfort and dyspnea on exertion was found to have an unexpected intracardiac foreign object. A ventriculoperitoneal shunt (VPS) had been placed 5 years earlier. Chest radiography immediately after placement was unremarkable. Once migrated into the venous system and pulmonary artery, it had formed a tight knot with adherent thrombus, as noted after retrieval (Fig 3). Transfemoral endovascular removal was performed using a snare advanced through a 70-cm-long 14-Fr sheath. After its withdrawal, the pleuritic pain continued. A new VPS was inserted. VPSs have been known to kink and migrate into the pulmonary arteries. The most likely mechanism for entry into the venous system is unrecognized traversal of a neck vein during VPS placement. The soft catheter can be later "sucked" into the venous system with respiration.

February 2019

Plotnik AN, Roberts DG, Srinivasa RN, McWilliams JP.

Urinary obstruction secondary to benign prostatic hyperplasia is a late manifestation of the disease, and a poor prognostic sign for responding to conservative therapies. Prostatic artery embolization - when performed successfully - can be an effective treatment for reducing obstructive urinary symptoms. Outlined in this report is the successful recanalization of a prostatic artery chronic total occlusion prior to embolization in an 89-year-old man with benign prostatic hyperplasia, who initially presented with urinary obstruction. Prostatic artery recanalization was possible using a specialized crossing technique from peripheral arterial disease interventions, and allowed for more distal embolization of the prostate gland. This technique may be useful when advanced atherosclerotic disease limits the feasibility and clinical success of prostatic artery embolization.

February 2019

Quirk MT, Lu DS.

The detection of portal vein tumor thrombus (PVTT) in patients with hepatocellular carcinoma (HCC) has important implications for prognosis and treatment. Liver transplantation (LT) is contraindicated due to high rates of recurrence, and the presence of PVTT also informs the choice of locoregional therapy. PVTT and other forms of macrovascular invasion figure into most of the major staging systems for HCC.

February 2019

Schwab K, Hoffman RM, Phiri L, Kahn D, Longwe L, Banda BA, Gama K, Chimombo M, Shih R, Schooley A, Pool KL.

The diagnosis of tuberculosis (TB) in patients infected with human immunodeficiency virus (HIV) can be challenging in resource-limited settings. Extrapulmonary TB is particularly underdiagnosed, with data suggesting that half of patients with disseminated TB are not diagnosed until autopsy.

February 2019

Sharifi F, Htwe SS, Righi M, Liu H, Pietralunga A, Yesil-Celiktas O, Maharjan S, Cha BH, Shin SR, Dokmeci MR, Vrana NE, Ghaemmaghami AM, Khademhosseini A, Zhang YS.

Understanding the foreign body response (FBR) and desiging strategies to modulate such a response represent a grand challenge for implant devices and biomaterials. Here, the development of a microfluidic platform is reported, i.e., the FBR-on-a-chip (FBROC) for modeling the cascade of events during immune cell response to implants. The platform models the native implant microenvironment where the implants are interfaced directly with surrounding tissues, as well as vasculature with circulating immune cells. The study demonstrates that the release of cytokines such as monocyte chemoattractant protein 1 (MCP-1) from the extracellular matrix (ECM)-like hydrogels in the bottom tissue chamber induces trans-endothelial migration of circulating monocytes in the vascular channel toward the hydrogels, thus mimicking implant-induced inflammation. Data using patient-derived peripheral blood mononuclear cells further reveal inter-patient differences in FBR, highlighting the potential of this platform for monitoring FBR in a personalized manner. The prototype FBROC platform provides an enabling strategy to interrogate FBR on various implants, including biomaterials and engineered tissue constructs, in a physiologically relevant and individual-specific manner.

February 2019

Sheikhi A, de Rutte J, Haghniaz R, Akouissi O, Sohrabi A, Di Carlo D, Khademhosseini A.

Naturally-derived proteins, such as collagen, elastin, fibroin, and gelatin (denatured collagen) hold a remarkable promise for tissue engineering and regenerative medicine. Gelatin methacryloyl (GelMA), synthesized from the methacryloyl modification of gelatin, mimicking the structure of extracellular matrix, has widely been used as a universal multi-responsive scaffold for a broad spectrum of applications, spanning from cell therapy to bioprinting and organoid development. Despite the widespread applications of GelMA, coupled stiffness and porosity has inhibited its applications in 3D cellular engineering wherein a stiff scaffold with large pores is demanded (e.g., at concentrations >10 wt%). Taking advantage of the orthogonal thermo-chemical responsivity of GelMA, we have developed microfluidic-assisted annealable GelMA beads, that are first stabilized by temperature-mediated physical crosslinking, flowed to form a scaffold structure, and then chemically annealed using light to fabricate novel bead-based 3D GelMA scaffolds with high mechanical resilience. We show how beaded GelMA (B-GelMA) provides a self-standing microporous environment with an orthogonal void fraction and stiffness, promoting cell adhesion, proliferation, and rapid 3D seeding at a high polymer concentration (~20 wt%) that would otherwise be impossible for bulk GelMA. B-GelMA, decorated with methacryloyl and arginylglycylaspartic acid (RGD) peptide motifs, does not require additional functionalization for annealing and cell adhesion, providing a versatile biorthogonal platform with orthogonal stiffness and porosity for a myriad of biomedical applications. This technology provides a universal method to convert polymeric materials with orthogonal physico-chemical responsivity to modular platforms, opening a new horizon for converting bulk hydrogels to beaded hydrogels (B-hydrogels) with decoupled porosity and stiffness.

January 2019

Armstrong T, Liu D, Martin T, Masamed R, Janzen C, Wong C, Chanlaw T, Devaskar SU, Sung K, Wu HH.

BACKGROUND: Multiecho gradient-echo Cartesian MRI characterizes placental oxygenation by quantifying R^✱₂. Previous research was performed at 1.5T using breath-held 2D imaging during later gestational age (GA). PURPOSE: To evaluate the accuracy and repeatability of a free-breathing (FB) 3D multiecho gradient-echo stack-of-radial technique (radial) for placental R^✱₂ mapping at 3T and report placental R^✱₂ during early GA. STUDY TYPE: Prospective. POPULATION: Thirty subjects with normal pregnancies and three subjects with ischemic placental disease (IPD) were scanned twice: between 14-18 and 19-23 weeks GA. FIELD STRENGTH: 3T. SEQUENCE: FB radial. ASSESSMENT: Linear correlation (concordance coefficient, ρ_c ) and Bland-Altman analyses (mean difference, MD) were performed to evaluate radial R^✱₂ mapping accuracy compared to Cartesian in a phantom. Radial R^✱₂ mapping repeatability was characterized using the coefficient of repeatability (CR) between back-to-back scans. The mean and spatial coefficient of variation (CV) of R^✱₂ was determined for all subjects, and separately for anterior and posterior placentas, at each GA range. STATISTICAL TESTS: ρc was tested for significance. Differences in mean R^✱₂ and CV were tested using Wilcoxon Signed-Rank and Rank-Sum tests. P < 0.05 was considered significant. Z-scores for the IPD subjects were determined.

January 2019

Ashammakhi N, Ahadian S, Darabi MA, El Tahchi M, Lee J, Suthiwanich K, Sheikhi A, Dokmeci MR, Oklu R, Khademhosseini A.

Advances in biomaterial synthesis and fabrication, stem cell biology, bioimaging, microsurgery procedures, and microscale technologies have made minimally invasive therapeutics a viable tool in regenerative medicine. Therapeutics, herein defined as cells, biomaterials, biomolecules, and their combinations, can be delivered in a minimally invasive way to regenerate different tissues in the body, such as bone, cartilage, pancreas, cardiac, skeletal muscle, liver, skin, and neural tissues. Sophisticated methods of tracking, sensing, and stimulation of therapeutics in vivo using nano-biomaterials and soft bioelectronic devices provide great opportunities to further develop minimally invasive and regenerative therapeutics (MIRET). In general, minimally invasive delivery methods offer high yield with low risk of complications and reduced costs compared to conventional delivery methods. Here, minimally invasive approaches for delivering regenerative therapeutics into the body are reviewed. The use of MIRET to treat different tissues and organs is described. Although some clinical trials have been performed using MIRET, it is hoped that such therapeutics find wider applications to treat patients. Finally, some future perspective and challenges for this emerging field are highlighted.

January 2019

Biglari S, Le TYL, Tan RP, Wise SG, Zambon A, Codolo G, De Bernard M, Warkiani M, Schindeler A, Naficy S, Valtchev P, Khademhosseini A, Dehghani F.

January 2019

Coy H, Young JR, Douek ML, Pantuck A, Brown MS, Sayre J, Raman SS.

PURPOSE: The purpose of the study was to determine if enhancement features and qualitative imaging features on multiphasic multidetector computed tomography (MDCT) were associated with tumor grade in patients with clear cell renal cell carcinoma (ccRCC). METHODS: In this retrospective, IRB approved, HIPAA-compliant, institutional review board-approved study with waiver of informed consent, 127 consecutive patients with 89 low grade (LG) and 43 high grade (HG) ccRCCs underwent preoperative four-phase MDCT in unenhanced (UN), corticomedullary (CM), nephrographic (NP), and excretory (EX) phases. Previously published quantitative (absolute peak lesion enhancement, absolute peak lesion enhancement relative to normal enhancing renal cortex, 3D whole lesion enhancement and the wash-in/wash-out of enhancement within the 3D whole lesion ROI) and qualitative (enhancement pattern; presence of necrosis; pattern of; tumor margin; tumor-parenchymal interface, tumor-parenchymal interaction; intratumoral vascularity; collecting system infiltration; renal vein invasion; and calcification) assessments were obtained for each lesion independently by two fellowship-trained genitourinary radiologists. Comparisons between variables included X², ANOVA, and student t test. p values less than 0.05 were considered to be significant. Inter-reader agreement was obtained with the Gwet agreement coefficient (AC1) and standard error (SE) was reported.

January 2019

Ghannam JS, Cline MR, Hage AN, Chick JFB, Srinivasa RN, Dasika NL, Srinivasa RN, Gemmete JJ.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) placement has been extensively studied in adults. The experience with TIPS placement in pediatric patients, however, is limited. OBJECTIVE: The purpose of this study was to report technical success and clinical outcomes in pediatric patients undergoing TIPS placement. MATERIALS AND METHODS: Twenty-one children - 12 (57%) boys and 9 (43%) girls, mean age 12.1 years (range, 2-17 years) - underwent TIPS placement from January 1997 to January 2017. Etiologies of hepatic dysfunction included biliary atresia (n=5; 24%), cryptogenic cirrhosis (n=4; 19%), portal or hepatic vein thrombosis (n=4, 14%), autosomal-recessive polycystic kidney disease (n=3; 14%), primary sclerosing cholangitis (n=2; 10%) and others (n=3, 14%). Indications for TIPS placement included variceal hemorrhage (n=20; 95%) and refractory ascites (n=1; 5%). Technical success, manometry findings, stent type, hemodynamic success, complications, liver enzymes, and clinical outcomes were recorded.

January 2019

Hung ML, Lee EW, McWilliams JP, Padia SA, Ding P, Kee ST.

OBJECTIVES: The purpose of this study was to describe a single institution's experience with transradial access (TRA) for angiographic interventions, and to compare technical success, complication rate and radiation dose of procedures performed with TRA to those performed with transfemoral access (TFA). METHODS: A retrospective cohort study of patients undergoing peripheral interventions via TRA or TFA from 2015 to 2017 was performed. The cohort comprised 33 patients undergoing 44 procedures via TRA and 37 patients undergoing 44 procedures via TFA. Outcome measures were technical success, access-related complications, fluoroscopy time and radiation exposure. Differences at p < 0.05 were considered to be statistically significant.

January 2019

Orive G, Santos-Vizcaino E, Pedraz JL, Hernandez RM, Vela Ramirez JE, Dolatshahi-Pirouz A, Khademhosseini A, Peppas NA, Emerich DF.

January 2019

Scarboro SB, Cody D, Stingo FC, Alvarez P, Followill D, Court L, Zhang D, McNitt-Gray M, Kry SF.

Aluminum oxide based optically stimulated luminescent dosimeters (OSLD) have been recognized as a useful dosimeter for measuring CT dose, particularly for patient dose measurements. Despite the increasing use of this dosimeter, appropriate dosimeter calibration techniques have not been established in the literature; while the manufacturer offers a calibration procedure, it is known to have relatively large uncertainties. The purpose of this work was to evaluate two clinical approaches for calibrating these dosimeters for CT applications, and to determine the uncertainty associated with measurements using these techniques. Three unique calibration procedures were used to calculate dose for a range of CT conditions using a commercially available OSLD and reader. The three calibration procedures included calibration (a) using the vendor-provided method, (b) relative to a 120 kVp CT spectrum in air, and (c) relative to a megavoltage beam (implemented with ⁶⁰ Co). The dose measured using each of these approaches was compared to dose measured using a calibrated farmer-type ion chamber. Finally, the uncertainty in the dose measured using each approach was determined. For the CT and megavoltage calibration methods, the dose measured using the OSLD nanoDot was within 5% of the dose measured using an ion chamber for a wide range of different CT scan parameters (80-140 kVp, and with measurements at a range of positions). When calibrated using the vendor-recommended protocol, the OSLD measured doses were on average 15.5% lower than ion chamber doses. Two clinical calibration techniques have been evaluated and are presented in this work as alternatives to the vendor-provided calibration approach. These techniques provide high precision for OSLD-based measurements in a CT environment.

January 2019

Sheikhi A, Hayashi J, Eichenbaum J, Gutin M, Kuntjoro N, Khorsandi D, Khademhosseini A.

The recent decade has witnessed a growing demand to substitute synthetic materials with naturally-derived platforms for minimizing their undesirable footprints in biomedicine, environment, and ecosystems. Among the natural materials, cellulose, the most abundant biopolymer in the world with key properties, such as biocompatibility, biorenewability, and sustainability has drawn significant attention. The hierarchical structure of cellulose fibers, one of the main constituents of plant cell walls, has been nanoengineered and broken down to nanoscale building blocks, providing an infrastructure for nanomedicine. Microorganisms, such as certain types of bacteria, are another source of nanocelluloses known as bacterial nanocellulose (BNC), which benefit from high purity and crystallinity. Chemical and mechanical treatments of cellulose fibrils made up of alternating crystalline and amorphous regions have yielded cellulose nanocrystals (CNC), hairy CNC (HCNC), and cellulose nanofibrils (CNF) with dimensions spanning from a few nanometers up to several microns. Cellulose nanocrystals and nanofibrils may readily bind drugs, proteins, and nanoparticles through physical interactions or be chemically modified to covalently accommodate cargos. Engineering surface properties, such as chemical functionality, charge, area, crystallinity, and hydrophilicity, plays a pivotal role in controlling the cargo loading/releasing capacity and rate, stability, toxicity, immunogenicity, and biodegradation of nanocellulose-based delivery platforms. This review provides insights into the recent advances in nanoengineering cellulose crystals and fibrils to develop vehicles, encompassing colloidal nanoparticles, hydrogels, aerogels, films, coatings, capsules, and membranes, for the delivery of a broad range of bioactive cargos, such as chemotherapeutic drugs, anti-inflammatory agents, antibacterial compounds, and probiotics. SYNOPSIS: Engineering certain types of microorganisms as well as the hierarchical structure of cellulose fibers, one of the main building blocks of plant cell walls, has yielded unique families of cellulose-based nanomaterials, which have leveraged the effective delivery of bioactive molecules.

January 2019

Sun W, Lee J, Zhang S, Benyshek C, Dokmeci MR, Khademhosseini A.

Advances in genomic sequencing and bioinformatics have led to the prospect of precision medicine where therapeutics can be advised by the genetic background of individuals. For example, mapping cancer genomics has revealed numerous genes that affect the therapeutic outcome of a drug. Through materials and cell engineering, many opportunities exist for engineers to contribute to precision medicine, such as engineering biosensors for diagnosis and health status monitoring, developing smart formulations for the controlled release of drugs, programming immune cells for targeted cancer therapy, differentiating pluripotent stem cells into desired lineages, fabricating bioscaffolds that support cell growth, or constructing "organs-on-chips" that can screen the effects of drugs. Collective engineering efforts will help transform precision medicine into a more personalized and effective healthcare approach. As continuous progress is made in engineering techniques, more tools will be available to fully realize precision medicine's potential.

January 2019

Wu HH, Priester A, Khoshnoodi P, Zhang Z, Shakeri S, Afshari Mirak S, Asvadi NH, Ahuja P, Sung K, Natarajan S, Sisk A, Reiter R, Raman S, Enzmann D.

BACKGROUND: Patient-specific 3D-printed molds and ex vivo MRI of the resected prostate have been two important strategies to align MRI with whole-mount histopathology (WMHP) for prostate cancer (PCa) research, but the combination of these two strategies has not been systematically evaluated. PURPOSE: To develop and evaluate a system that combines patient-specific 3D-printed molds with ex vivo MRI (ExV) to spatially align in vivo MRI (InV), ExV, and WMHP in PCa patients. STUDY TYPE: Prospective cohort study. POPULATION: Seventeen PCa patients who underwent 3T MRI and robotic-assisted laparoscopic radical prostatectomy (RALP). FIELD STRENGTH/SEQUENCES: T2 -weighted turbo spin-echo sequences at 3T. ASSESSMENT: Immediately after RALP, the fresh whole prostate specimens were imaged in patient-specific 3D-printed molds by 3T MRI and then sectioned to create WMHP slides. The time required for ExV was measured to assess impact on workflow. InV, ExV, and WMHP images were registered. Spatial alignment was evaluated using: slide offset (mm) between ExV slice locations and WMHP slides; overlap of the 3D prostate contour on InV versus ExV using Dice's coefficient (0 to 1); and 2D target registration error (TRE, mm) between corresponding landmarks on InV, ExV, and WMHP. Data are reported as mean ± standard deviation (SD). STATISTICAL TESTING: Differences in 2D TRE before versus after registration were compared using the Wilcoxon signed-rank test (P < 0.05 considered significant).

January 2019

Wu X, Kim GH, Salisbury ML, Barber D, Bartholmai BJ, Brown KK, Conoscenti CS, De Backer J, Flaherty KR, Gruden JF, Hoffman EA, Humphries SM, Jacob J, Maher TM, Raghu G, Richeldi L, Ross BD, Schlenker-Herceg R, Sverzellati N, Wells AU, Martinez FJ, Lynch DA, Goldin J, Walsh SLF.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with great variability in disease severity and rate of progression. The need for a reliable, sensitive, and objective biomarker to track disease progression and response to therapy remains a great challenge in IPF clinical trials. Over the past decade, quantitative computed tomography (QCT) has emerged as an area of intensive research to address this need. We have gathered a group of pulmonologists, radiologists and scientists with expertise in this area to define the current status and future promise of this imaging technique in the evaluation and management of IPF. In this Pulmonary Perspective, we review the development and validation of six computer-based QCT methods and offer insight into the optimal use of an imaging-based biomarker as a tool for prognostication, prediction of response to therapy, and potential surrogate endpoint in future therapeutic trials.

January 2019

Zhao T, Hoffman J, McNitt-Gray M, Ruan D.

PURPOSE: It is important to enhance image quality for low-dose CT acquisitions to push the ALARA boundary. Current state-of-the-art block-matching three-dimensional (BM3D) denoising scheme assumes white Gaussian noise (WGN) model. This study proposes a novel filtering module to be incorporated into the BM3D framework for ultra-low-dose CT denoising, by accounting for its specific power spectral properties. METHODS: In the current BM3D algorithm, the Wiener filtering is applied in the transform domain to a post-thresholding signal for enhanced denoising. However, unlike most natural/synthetic images, low-dose CTs do not obey the ideal Gaussian noise model. Based on the specific noise properties of ultra-low-dose CT, we derive the optimal transform-domain coefficients of Wiener filter based on the minimum mean-square-error (MMSE) criterion, taking the noise spectrum and the signal/noise cross spectrum into consideration. In the absence of ground-truth signal, the hard-thresholding denoising module in the previous stage is used as a plug-in estimator. We evaluate the denoising performance on thoracic CT image datasets containing paired full-dose and ultra-low-dose images simulated by a well-validated clinical engine (or pipeline). We also assess its clinical implication by applying the denoising methods to the emphysema quantification task. Our modified BM3D method is compared with the current one, using peak signal-to-noise ratio (PSNR) and emphysema scoring results as evaluation metrics.