August 2018
Clinical Phenomapping and Outcomes After Heart Transplantation.BACKGROUND: Survival after heart transplantation (HTx) is limited by complications related to alloreactivity, immune suppression, and adverse effects of pharmacologic therapies. We hypothesize that time-dependent phenomapping of clinical and molecular data sets is a valuable approach to clinical assessments and guiding medical management to improve outcomes. METHODS: We analyzed clinical, therapeutic, biomarker, and outcome data from 94 adult HTx patients and 1,557 clinical encounters performed between January 2010 and April 2013. Multivariate analyses were used to evaluate the association between immunosuppression therapy, biomarkers, and the combined clinical end point of death, allograft loss, retransplantation, and rejection. Data were analyzed by K-means clustering (K = 2) to identify patterns of similar combined immunosuppression management, and percentile slopes were computed to examine the changes in dosages over time. Findings were correlated with clinical parameters, human leucocyte antigen antibody titers, and peripheral blood mononuclear cell gene expression of the AlloMap (CareDx, Inc., Brisbane, CA) test genes. An intragraft, heart tissue gene coexpression network analysis was performed.
August 2018
Differences in the Radius of Curvature Between Femoral Condyles: Implications for Osteochondral Allograft Matching.BACKGROUND: The radius of curvature (ROC) is an important variable related to potential cartilage incongruities in the transplantation of a large femoral osteochondral allograft. The anterior-posterior length (APL) of a condyle is used as a criterion for donor-graft acceptance. We hypothesized that there would be a linear correlation between the ROC and APL of a condyle, that the ROC and APL would differ significantly between the medial femoral condyle (MFC) and the lateral femoral condyle (LFC), and that a donor graft from the LFC would be suitable for an MFC defect. METHODS: Knee magnetic resonance imaging scans of 147 patients with no cartilage defects were analyzed. Best-fit circles in the sagittal plane were determined at standardized locations on each condyle. Assuming the use of a 20-mm graft that was flush to the edges of the native cartilage, the central graft prominence was calculated for potential donor-host differences in the ROC.
August 2018
Ablation Treatment of Primary and Secondary Liver Tumors Under Contrast-enhanced Ultrasound Guidance in Field Practice of Interventional Ultrasound Centers. A Multicenter Study.The present retrospective study was aimed at characterizing the clinical impact of contrast-enhanced ultrasound (CEUS) as a guidance technique for ablation of primary and secondary liver tumors at six interventional ultrasound centers. 148 patients (103M/45F, median age 74 yrs.) with 151 liver target lesions (median size 15 mm, 86.7% Hepatocellular Carcinomas) in whom CEUS guidance was used for Percutaneous Ethanol Injection (35.2%), Radiofrequency (46.3%) and Microwave (18.5%) were selected during the period 2008-2016. CEUS-guided ablations represented 7.3% (range 2.5%-13.8%) of 2015 ablative sessions performed at the participating centers. Indications to CEUS-guided ablation were: improvement of conspicuity of the target (28.5%), a target lesion undetectable on B-mode ultrasound (29.8%), detection of viable areas in nodules with either incomplete ablation or local tumor progression (41.7%). Overall, complete radiological ablation was obtained in 113/151 tumors (74.8%), with heat-based techniques (RF and MW) achieving higher rate of successful ablation (86.7%) than PEI (51%). Neither deaths nor major complications occurred after ablations. CEUS guidance demonstrates improved visibility and effectiveness in aiding ablation procedures that are otherwise technically difficult using only B-Mode US guidance.
August 2018
Do Multiple Mini-Interview and Traditional Interview Scores Differ in Their Associations With Acceptance Offers Within and Across Five California Medical Schools?PURPOSE: In single-school studies, multiple mini-interview (MMI) and traditional interview (TI) scores are associated with acceptance offers. Unexamined is whether scores at one school are associated with acceptance at other schools; such analyses would mitigate single-school design biases and better estimate how well interviews capture desired applicant attributes. Using data from the 5 California Longitudinal Evaluation of Admissions Practices (CA-LEAP) medical schools, the authors examined associations of MMI and TI scores with acceptance offers within and across schools. METHOD: The analyses included applicants who interviewed at ≥1 CA-LEAP school during the 2011-2013 admissions cycles. Three CA-LEAP schools employed TIs and 2 employed MMIs. Interview scores were standardized (z scores: mean = 0, SD = 1), and associations with acceptance offers were examined within and across schools in analyses stratified by school, adjusting for applicant sociodemographics, academic metrics, year, and total number of interviews.
August 2018
Nature's Wastebasket: The Role of the External Carotid Artery in Acute Stroke.We describe a novel technical approach to acute stroke illustrated by the case of a 41 year old male who presented with tandem right common carotid artery (CCA) and M1 occlusions. His NIHSS was 17 and Alberta stroke programe early CT score (ASPECTs) was 8. Thrombectomy initially proved challenging due to large volume CCA thrombus that repeatedly occluded the aspiration catheters. However, by inflating a balloon distally and pulling clot into the adjacent ECA, we were able to quickly restore distal contrast flow to the intracranial circulation and achieve Thrombolysis In Cerebral Infarction/Arterial Occlusive Lesion (TICI2C/AOL3) revascularization.
August 2018
4-Hydroxy-7-oxo-5-heptenoic Acid Lactone Is a Potent Inducer of the Complement Pathway in Human Retinal Pigmented Epithelial Cells.We previously discovered that oxidative cleavage of docosahexaenoate (DHA), which is especially abundant in the retinal photoreceptor rod outer segments and retinal pigmented endothelial (RPE) cells, generates 4-hydroxy-7-oxo-5-heptenoate (HOHA) lactone, and that HOHA lactone can enter RPE cells that metabolize it through conjugation with glutathione (GSH). The consequent depletion of GSH results in oxidative stress. We now find that HOHA lactone induces upregulation of the antioxidant transcription factor Nrf2 in ARPE-19 cells. This leads to expression of GCLM, HO1, and NQO1, three known Nrf2-responsive antioxidant genes. Besides this protective response, HOHA lactone also triggers a countervailing inflammatory activation of innate immunity. Evidence for a contribution of the complement pathway to age-related macular degeneration (AMD) pathology includes the presence of complement proteins in drusen and Bruch's membrane from AMD donor eyes, and the identification of genetic susceptibility loci for AMD in the complement pathway. In eye tissues from a mouse model of AMD, accumulation of complement protein in Bruch's membrane below the RPE suggested that the complement pathway targets this interface, where lesions occur in the RPE and photoreceptor rod outer segments. In animal models of AMD, intravenous injection of NaIO3 to induce oxidative injury selectively destroys the RPE and causes secretion of factor C3 from the RPE into areas directly adjacent to sites of RPE damage. However, a molecular-level link between oxidative injury and complement activation remained elusive. We now find that sub-micromolar concentrations of HOHA lactone foster expression of C3, CFB, and C5 in ARPE-19 cells and induce a countervailing upregulation of CD55, an inhibitor of C3 convertase production and complement cascade amplification. Ultimately, HOHA lactone causes membrane attack complex formation on the plasma membrane. Thus, HOHA lactone provides a molecular-level connection between free-radical-induced oxidative cleavage of DHA and activation of the complement pathway in AMD pathology.
August 2018
IRF2BPL Is Associated with Neurological Phenotypes.Interferon regulatory factor 2 binding protein-like (IRF2BPL) encodes a member of the IRF2BP family of transcriptional regulators. Currently the biological function of this gene is obscure, and the gene has not been associated with a Mendelian disease. Here we describe seven individuals who carry damaging heterozygous variants in IRF2BPL and are affected with neurological symptoms. Five individuals who carry IRF2BPL nonsense variants resulting in a premature stop codon display severe neurodevelopmental regression, hypotonia, progressive ataxia, seizures, and a lack of coordination. Two additional individuals, both with missense variants, display global developmental delay and seizures and a relatively milder phenotype than those with nonsense alleles. The IRF2BPL bioinformatics signature based on population genomics is consistent with a gene that is intolerant to variation. We show that the fruit-fly IRF2BPL ortholog, called pits (protein interacting with Ttk69 and Sin3A), is broadly detected, including in the nervous system. Complete loss of pits is lethal early in development, whereas partial knockdown with RNA interference in neurons leads to neurodegeneration, revealing a requirement for this gene in proper neuronal function and maintenance. The identified IRF2BPL nonsense variants behave as severe loss-of-function alleles in this model organism, and ectopic expression of the missense variants leads to a range of phenotypes. Taken together, our results show that IRF2BPL and pits are required in the nervous system in humans and flies, and their loss leads to a range of neurological phenotypes in both species.
August 2018
Managing Incidental Findings on Thoracic CT: Mediastinal and Cardiovascular Findings. A White Paper of the ACR Incidental Findings Committee.The ACR Incidental Findings Committee presents recommendations for managing incidentally detected mediastinal and cardiovascular findings found on CT. The Chest Subcommittee was composed of thoracic radiologists who developed the provided guidance. These recommendations represent a combination of current published evidence and expert opinion and were finalized by informal iterative consensus. The recommendations address the most commonly encountered mediastinal and cardiovascular incidental findings and are not intended to be a comprehensive review of all incidental findings associated with these compartments. Our goal is to improve the quality of care by providing guidance on how to manage incidentally detected thoracic findings.
July 2018
Percutaneous Image-guided Core Biopsy of Solid Renal Masses: Analysis of safety, Efficacy, Pathologic Interpretation, and Clinical Significance.PURPOSE: To determine the efficacy, safety and clinical utility of CT and US-guided percutaneous renal mass biopsy. MATERIALS AND METHODS: A retrospective IRB-approved, HIPAA-compliant study of a cohort of 183 consecutive patients who underwent percutaneous, CT or US-guided renal mass biopsy (RMB) from March 2002 through December 2012 was performed. RMB was performed in 183 consecutive patients for suspected solid renal mass of whom 14/183 (7.7%) were excluded because biopsies were performed at an outside institution, medical records were incomplete, or lesions were poorly visualized. Ten patients had multiple biopsies for new growing masses. Using US, CT or CT/US fusion-guidance, a 17G or 19G cannula needle was placed at the margin of the mass and an 18G or 20G core biopsy gun was used to obtain several tissue cores. Renal parenchymal biopsies for medical renal diseases were excluded. Imaging variables (including size, location, and extent of disease), number of core biopsies, patient demographics (age, gender), clinical indication, final pathologic diagnosis, immunohistochemical (IHC) studies, and subsequent final pathological diagnosis on nephrectomy were evaluated.
July 2018
Free-breathing Quantification of Hepatic Fat in Healthy Children and Children with Nonalcoholic Fatty Liver Disease Using a Multi-echo 3-D Stack-of-radial MRI Technique.BACKGROUND: In adults, noninvasive chemical shift encoded Cartesian magnetic resonance imaging (MRI) and single-voxel magnetic resonance (MR) spectroscopy (SVS) accurately quantify hepatic steatosis but require breath-holding. In children, especially young and sick children, breath-holding is often limited or not feasible. Sedation can facilitate breath-holding but is highly undesirable. For these reasons, there is a need to develop free-breathing MRI technology that accurately quantifies steatosis in all children. OBJECTIVE: This study aimed to compare non-sedated free-breathing multi-echo 3-D stack-of-radial (radial) MRI versus standard breath-holding MRI and SVS techniques in a group of children for fat quantification with respect to image quality, accuracy and repeatability. MATERIALS AND METHODS: Healthy children (n=10, median age [±interquartile range]: 10.9 [±3.3] years) and overweight children with nonalcoholic fatty liver disease (NAFLD) (n=9, median age: 15.2 [±3.2] years) were imaged at 3 Tesla using free-breathing radial MRI, breath-holding Cartesian MRI and breath-holding SVS. Acquisitions were performed twice to assess repeatability (within-subject mean difference, MDwithin). Images and hepatic proton-density fat fraction (PDFF) maps were scored for image quality. Free-breathing and breath-holding PDFF were compared using linear regression (correlation coefficient, r and concordance correlation coefficient, ρc) and Bland-Altman analysis (mean difference). P<0.05 was considered significant.
July 2018
Visual and semi-automatic non-invasive detection of interictal fast ripples: A potential biomarker of epilepsy in children with tuberous sclerosis complex.OBJECTIVES: We aim to establish that interictal fast ripples (FR; 250-500 Hz) are detectable on scalp EEG, and to investigate their association to epilepsy. METHODS: Scalp EEG recordings of a subset of children with tuberous sclerosis complex (TSC)-associated epilepsy from two large multicenter observational TSC studies were analyzed and compared to control children without epilepsy or any other brain-based diagnoses. FR were identified both by human visual review and compared with semi-automated review utilizing a deep learning-based FR detector.
July 2018
Medical School Applicant Characteristics Associated With Performance in Multiple Mini-Interviews Versus Traditional Interviews: A Multi-Institutional Study.PURPOSE: To examine applicant characteristics associated with multiple mini-interview (MMI) or traditional interview (TI) performance at five California medical schools. METHOD: Of the five California Longitudinal Evaluation of Admission Practices consortium schools, three used TIs and two used MMIs. Schools provided retrospective data on 2011-2013 admissions cycle interviewees: age, gender, race/ethnicity (underrepresented in medicine [UIM] or not), disadvantaged (DA) status, undergraduate GPA, Medical College Admission Test (MCAT) score, and interview score (standardized as z score; mean = 0; SD = 1). Adjusted linear regression analyses, stratified by interview type, examined associations with interview performance.
July 2018
DTI-based Upper Limit of Voxel Free Water Fraction.BACKGROUND: Free water (FW) in neuroimaging is non-flowing extracellular water in the cranium and brain tissue, and includes both cerebral spinal fluid (CSF) and fluid in intercellular space or edema. For a region such as a voxel (spatial unit of measurement in neuroimaging), the FW fraction is defined as the volume fraction of FW within that volume. Quantifying the FW fraction allows estimating contamination by fluid of neuroimaging or magnetic resonance spectroscopy measurements within a voxel. NEW METHOD: An upper limit to the fraction of FW within a voxel, based on any diffusion tensor imaging (DTI) sequence including a standard single shell at one b-value, can be derived from the standard diffusion tensor by scaling the third eigenvalue of the diffusion tensor. Assuming a two-compartment model, the diffusivity of a voxel is a combination of tissue and FW diffusivity. FW fraction is FW volume divided by voxel volume. Assuming FW diffuses equally in all directions, the diffusivity component is representable by a single, non-tensor diffusivity value. Since the diffusivity of water is known for a given temperature, and brain temperature is relatively constant, the FW diffusivity value can be assumed constant. The third eigenvector of the voxel diffusion tensor is the direction of least diffusivity and since the FW component of diffusivity is equal in all directions, we show that FW diffusivity cannot be lower than the third eigenvalue. Assuming FW contributes proportionally to voxel diffusivity, we show that the third eigenvalue divided by water diffusivity (as a constant based on known water diffusivity at 36.7 °C) forms an upper limit on the FW-fraction (fUL).
July 2018
Microfluidics-Enabled Multimaterial Maskless Stereolithographic Bioprinting.A stereolithography-based bioprinting platform for multimaterial fabrication of heterogeneous hydrogel constructs is presented. Dynamic patterning by a digital micromirror device, synchronized by a moving stage and a microfluidic device containing four on/off pneumatic valves, is used to create 3D constructs. The novel microfluidic device is capable of fast switching between different (cell-loaded) hydrogel bioinks, to achieve layer-by-layer multimaterial bioprinting. Compared to conventional stereolithography-based bioprinters, the system provides the unique advantage of multimaterial fabrication capability at high spatial resolution. To demonstrate the multimaterial capacity of this system, a variety of hydrogel constructs are generated, including those based on poly(ethylene glycol) diacrylate (PEGDA) and gelatin methacryloyl (GelMA). The biocompatibility of this system is validated by introducing cell-laden GelMA into the microfluidic device and fabricating cellularized constructs. A pattern of a PEGDA frame and three different concentrations of GelMA, loaded with vascular endothelial growth factor, are further assessed for its neovascularization potential in a rat model. The proposed system provides a robust platform for bioprinting of high-fidelity multimaterial microstructures on demand for applications in tissue engineering, regenerative medicine, and biosensing, which are otherwise not readily achievable at high speed with conventional stereolithographic biofabrication platforms.
July 2018
A Prospective Phase 2 Study Evaluating Safety and Efficacy of Combining Stereotactic Body Radiation Therapy With Heat-based Ablation for Centrally Located Lung Tumors.PURPOSE: Stereotactic body radiation therapy (SBRT) and heat-based ablation (HBA) are both potentially safe and effective treatments for primary and metastatic lung tumors. Both are suboptimal for centrally located tumors, with SBRT having a higher risk of significant toxicity and HBA having lower efficacy. This study evaluates the safety and efficacy of combination SBRT-HBA to determine whether combined treatment can result in superior outcomes to each treatment alone. METHODS AND MATERIALS: Patients with 1 or 2 primary or metastatic lung tumors ≤ 5 cm in size were enrolled in a prospective phase 2 trial and treated with SBRT in 3 fractions followed by HBA. Tumors < 1 cm from the central bronchial tree received a total of 36 Gy, and tumors 1 to 2 cm away received 42 Gy. HBA was delivered within 10 days after SBRT. The primary endpoints were local control, toxicity, and degree of decline in lung function. The secondary endpoints were progression-free survival and overall survival.
June 2018
Smart Scaffolds in Tissue Regeneration.Recent advances in biofabrication technologies and chemical synthesis approaches have enabled the fabrication of smart scaffolds that aim to mimic the dynamic nature of the native extracellular matrix. These scaffolds have paved the way for tissue regeneration in a dynamic and controllable manner.
June 2018
Posterior Communicating Artery Aneurysms Demonstrate Faster Interval Growth Than Other Growing Aneurysms.Background Posterior communicating artery aneurysms are often associated with a high rupture risk. This study compares the differences in the rate of growth and morphological characteristics between growing posterior communicating artery aneurysms and other types of growing aneurysms. Materials and methods Thirteen patients with growing internal carotid artery aneurysms were scanned using Siemens 64 slice computed tomography scanners. Three patients had ophthalmic aneurysms, three had superior hypophyseal aneurysms and seven had posterior communicating artery aneurysms. Each aneurysm case had three distinct time points, with an average separation time of 1.3 ± 0.6 years. Annual aneurysm dimensional growth, annual volume growth, annual increase in surface area, size ratio, aspect ratio, and non-sphericity index were analysed. Results Posterior communicating artery aneurysms demonstrated significantly higher annual increases in dimensional growth, volume and surface area when compared to other internal carotid artery aneurysms. Posterior communicating artery aneurysms also demonstrated a significantly higher increase in aspect ratio, size ratio and lower non-sphericity index. Discussion Posterior communicating artery aneurysms had significantly greater growth per year when compared to other types of internal carotid artery aneurysms, and had different morphological characteristics.
June 2018
Patient-Specific Bioinks for 3D Bioprinting of Tissue Engineering Scaffolds.Bioprinting has emerged as a promising tool in tissue engineering and regenerative medicine. Various 3D printing strategies have been developed to enable bioprinting of various biopolymers and hydrogels. However, the incorporation of biological factors has not been well explored. As the importance of personalized medicine is becoming more clear, the need for the development of bioinks containing autologous/patient-specific biological factors for tissue engineering applications becomes more evident. Platelet-rich plasma (PRP) is used as a patient-specific source of autologous growth factors that can be easily incorporated to hydrogels and printed into 3D constructs. PRP contains a cocktail of growth factors enhancing angiogenesis, stem cell recruitment, and tissue regeneration. Here, the development of an alginate-based bioink that can be printed and crosslinked upon implantation through exposure to native calcium ions is reported. This platform can be used for the controlled release of PRP-associated growth factors which may ultimately enhance vascularization and stem cell migration.
June 2018
Respiratory Motion-resolved, Self-gated 4D-MRI Using Rotating Cartesian K-space (ROCK): Initial Clinical Experience on an MRI-guided Radiotherapy System.PURPOSE: To optimize and evaluate the respiratory motion-resolved, self-gated 4D-MRI using Rotating Cartesian K-space (ROCK-4D-MRI) method in a 0.35 T MRI-guided radiotherapy (MRgRT) system. METHODS AND MATERIALS: The study included seven patients with abdominal tumors treated on the MRgRT system. ROCK-4D-MRI and 2D-CINE, was performed immediately after one of the treatment fractions. Motion quantification based on 4D-MRI was compared with those based on 2D-CINE. The image quality of 4D-MRI was evaluated against 4D-CT. The gross tumor volumes (GTV) were defined based on individual respiratory phases of both 4D-MRI and 4D-CT and compared for their variability over the respiratory cycle.
June 2018
Caval Thrombus Management: The Data, Where We Are, and How It Is Done.Thromboses of the superior and inferior vena cava, either isolated or associated with distal deep venous thrombosis, are uncommon, but confer potentially serious morbidity and mortality. Incidence is increasing, especially with the prominence of intravascular devices. The range of treatment options is also expanding to include medical management, surgery, and endovascular techniques which are now frequently considered first line therapy due to lower reintervention rates and decreased periprocedural morbidity. Currently, there are no official guidelines for screening or treatment. This article reviews the etiology, diagnosis, and management of caval thromboses, including equipment, procedural steps, outcomes, and complications, particularly with regard to endovascular techniques, such as catheter-directed thrombolysis, pharmacomechanical catheter-directed thrombolysis, angioplasty, and stenting.
June 2018
Percutaneous Radiofrequency Ablation of Small (1-2 cm) Hepatocellular Carcinomas Inconspicuous on B-Mode Ultrasonographic Imaging: Usefulness of Combined Fusion Imaging with MRI and Contrast-Enhanced Ultrasonography.PURPOSE: To assess usefulness of adding contrast-enhanced ultrasonography (CEUS) to fusion imaging (FI) for percutaneous radiofrequency ablation (RFA) of hepatocellular carcinomas (HCCs) inconspicuous on FI alone. Therapeutic outcomes of RFA under CEUS-added FI guidance for HCCs inconspicuous on FI alone were also evaluated. METHODS: This prospective study was approved by the institutional review board and informed consent was obtained from all patients. Planning US was performed with FI for 126 patients with a single HCC (1-2 cm) to evaluate the feasibility of RFA by grading lesion conspicuity score using a four-point scale. RFA was performed under CEUS-added FI guidance for HCCs inconspicuous on FI alone. We evaluated how many HCCs initially inconspicuous on FI became conspicuous after adding CEUS. After CEUS-added FI-guided RFA, therapeutic outcomes including rates of technical success, primary technique efficacy, major complications, and local tumor progression were assessed.
June 2018
Underutilization of Supplemental Magnetic Resonance Imaging Screening Among Patients at High Breast Cancer Risk.Breast cancer is the most common noncutaneous malignancy among women in the United States. Based on population-based randomized control trials, mammography is the gold standard for screening due to demonstration of reduced mortality rate. However, the sensitivity of mammography is reduced in specific populations, such as in women with dense breasts despite high risk, defined as an estimated lifetime risk of >20%. The combination of mammography and contrast-enhanced breast magnetic resonance imaging (MRI) has been shown to increase the cancer detection rate in high-risk women compared with mammography alone. Multiple national societies, including the American Cancer Society, National Comprehensive Cancer Network, and American College of Radiology/Society of Breast Imaging, recommend supplemental breast MRI for screening in high-risk women. Nevertheless, screening breast MRI is underutilized.
June 2018
In-room Assessment of Intravascular Velocity from Time-resolved Rotational Angiography in Patients with Arteriovenous Malformation: a Pilot Study.BACKGROUND: Time-resolved rotational angiography (t-RA) enables interventionists to better comprehend complex arteriovenous malformations (AVMs), thereby facilitating endovascular treatment. However, its use in evaluating hemodynamic changes has rarely been explored. OBJECTIVE: This study uses t-RA to estimate intravascular flow in patients with AVM to compare this with flow in the normal population. METHODS: Patients with available t-RA scans were prospectively categorized into one of three groups: hemorrhagic AVM, non-hemorrhagic AVM and control. Pulsatile time-density curves (TDCs) for C1, C6 and VOIMCA were used for amplitude and velocity estimation. C1 was at the cervical internal carotid artery (ICA), 2-3 cm below the carotid canal, C6 was at the paraclinoid segment of the ICA, and VOIMCA was at the junction of the first and second segment of the middle cerebral artery (MCA). A waveform amplitude ratio was defined as (peak - trough)/trough contrast intensity. VICA was defined as the distance between C6 and C1 divided by the time required for the wave to pass, and correspondingly, the average velocity of MCA (VMCA) was defined as the distance between C6 and VOIMCA divided by the duration for the same peak to travel from C6 and VOIMCA, AVM volume was estimated by MR angiography.
June 2018
Gene Expression Classifier vs Targeted Next-Generation Sequencing in the Management of Indeterminate Thyroid Nodules.CONTEXT: Molecular testing has reduced the need for diagnostic hemithyroidectomy for indeterminate thyroid nodules. No studies have directly compared molecular testing techniques. OBJECTIVE: Compare the diagnostic performance of Afirma Gene Expression Classifier (GEC) with that of ThyroSeq v2 next-generation sequencing assay. DESIGN: Parallel randomized trial, monthly block randomization of patients with Bethesda III/IV cytology to GEC or ThyroSeq v2. SETTING: University of California, Los Angeles. PARTICIPANTS: Patients who underwent thyroid biopsy (April 2016 to June 2017). INTERVENTION: Testing with GEC or ThyroSeq v2.
June 2018
How Should the FDA Review Diagnostic Radiopharmaceuticals?The purpose of this article is to reconsider the manner in which the U.S. Food and Drug Administration (FDA) reviews diagnostic radiopharmaceuticals. Mass characteristics of several common nonradioactive drugs and several diagnostic radiopharmaceuticals are considered. A history of the regulation of radiopharmaceuticals is presented. The Society of Nuclear Medicine and Molecular Imaging and the American College of Nuclear Medicine should choose the membership of a radiopharmaceutical advisory committee, and the FDA should contract with them to do so. Members of the radiopharmaceutical advisory committee should decide on the data to be presented by the manufacturer or the compounder and review those data, and the FDA should honor their decision. In this way, requirements would be radiopharmaceutical-specific, and much information of questionable usefulness would be foregone.
June 2018
Intervention in Massive Pulmonary Embolus: Catheter Thrombectomy/Thromboaspiration versus Systemic Lysis versus Surgical Thrombectomy.Massive pulmonary embolus (PE), defined as hemodynamic shock from acute PE, is a life-threatening condition. Deaths from massive PE, especially when unsuspected, occur within minutes to hours of onset and as such prompt intervention can be lifesaving. Acute massive PE patients have traditionally been candidates for treatment with intravenous systemic thrombolysis to improve pulmonary artery pressure, arteriovenous oxygenation, and pulmonary perfusion in an effort to reduce mortality. However, patients with contraindications to systemic thrombolysis or those who have failed thrombolysis may benefit from other techniques including endovascular and surgical embolectomy. This article will review the current medical management as well as catheter-directed therapies and surgical embolectomy in the treatment of patients with massive PE.
June 2018
Imaging and Management of Intrathoracic Renal Cell Carcinoma Metastases.BJECTIVE: Renal cell carcinoma (RCC) has a propensity to metastasize to the chest, with the lungs being the most common distant metastatic site. The histologic subtype of RCC has implications for prognosis. CONCLUSION: Significant advances have been made in the management of metastatic RCC, both in systemic and locoregional therapies. The aim of this article is to review appearances of intrathoracic metastases from RCC and to discuss treatment considerations.
June 2018
Measuring Human Placental Blood Flow with Multidelay 3D GRASE Pseudocontinuous Arterial Spin Labeling at 3T.BACKGROUND: Placenta influences the health of both a woman and her fetus during pregnancy. Maternal blood supply to placenta can be measured noninvasively using arterial spin labeling (ASL). PURPOSE: To present a multidelay pseudocontinuous arterial spin labeling (pCASL) combined with a fast 3D inner-volume gradient- and spin-echo (GRASE) imaging technique to simultaneously measure placental blood flow (PBF) and arterial transit time (ATT), and to study PBF and ATT evolution with gestational age during the second trimester. The PBF values were compared with uterine arterial Doppler ultrasound to assess its potential clinical utility. STUDY TYPE: This was a prospective study. SUBJECTS: Thirty-four pregnant women. FIELD STRENGTH/SEQUENCE: Multidelay 3D inner-volume GRASE pCASL sequence on 3T MR scanners. ASSESSMENT: Subjects underwent two longitudinal MRI scans within the second trimester, conducted between 14-16 and 19-22 weeks of gestational age, respectively. Placental perfusion was measured using the free-breathing pCASL sequence at three postlabeling delays (PLDs), followed by offline motion correction and model fitting for estimation of PBF and ATT. STATISTICAL TESTS: A paired t-test was conducted to evaluate the significance of PBF/ATT variations with placental development. A two-sample t-test was conducted to evaluate the significance of PBF difference in subjects with and without early diastolic notch.
June 2018
Polyphenol Uses in Biomaterials Engineering.Polyphenols are micronutrients obtained from diet that have been suggested to play an important role in health. The health benefits of polyphenols and their protective effects in food systems as antioxidant compounds are well known and have been extensively investigated. However, their functional roles as a "processing cofactor" in tissue engineering applications are less widely known. This review focuses on the functionality of polyphenols and their application in biomaterials. Polyphenols have been used to stabilize collagen and to improve its resistance to degradation in biological systems. Therefore, they have been proposed to improve the performance of biomedical devices used in cardiovascular systems by improving the mechanical properties of grafted heart valves, enhancing microcirculation through the relaxation of the arterial walls and improving the capillary blood flow and pressure resistance. Polyphenols have been found to stimulate bone formation, mineralization, as well as the proliferation, differentiation, and the survival of osteoblasts. These effects are brought about by the stimulatory effect of polyphenols on osteoblast cells and their protective effect against oxidative stress and inflammatory cytokines. In addition, polyphenols inhibit the differentiation of the osteoclast cells. Collectively, these actions lead to promote bone formation and to reduce bone resorption, respectively. Moreover, polyphenols can increase the cross-linking of dentine and hence its mechanical stability. Overall, polyphenols provide interesting properties that will stimulate further research in the bioengineering field.
May 2018
Injectable Shear-thinning Hydrogels for Delivering Osteogenic and Angiogenic Cells and Growth Factors.Bone nonunion may occur when the fracture is unstable, or blood supply is impeded. To provide an effective treatment for the healing of nonunion defects, we introduce an injectable osteogenic hydrogel that can deliver cells and vasculogenic growth factors. We used a silicate-based shear-thinning hydrogel (STH) to engineer an injectable scaffold and incorporated polycaprolactone (PCL) nanoparticles that entrap and release vasculogenic growth factors in a controlled manner. By adjusting the solid composition of gelatin and silicate nanoplatelets in the STH, we defined optimal conditions that enable injection of STHs, which can deliver cells and growth factors. Different types of STHs could be simultaneously injected into 3D constructs through a single extrusion head composed of multiple syringes and needles, while maintaining their engineered structure in a continuous manner. The injected STHs were also capable of filling any irregularly shaped defects in bone. Osteogenic cells and endothelial cells were encapsulated in STHs with and without vasculogenic growth factors, respectively, and when co-cultured, their growth and differentiation were significantly enhanced compared to cells grown in monoculture. This study introduces an initial step of developing a new platform of shape-tunable materials with controlled release of angiogenic growth factors by utilizing PCL nanoparticles.
May 2018
Apparent Diffusion Coefficient Signal Intensity Ratio Predicts the Effect of Revascularization on Ischemic Cerebral Edema.BACKGROUND: Apparent diffusion coefficient (ADC) imaging is a biomarker of cytotoxic injury that predicts edema formation and outcome after ischemic stroke. It therefore has the potential to serve as a "tissue clock" to describe the extent of ischemic injury and potentially predict response to therapy. The goal of this study was to determine the relationship between baseline ADC signal intensity, revascularization, and edema formation. METHODS: We examined the ADC signal intensity ratio (ADCr) of the stroke lesion (defined as the baseline DWI hyperintense region) compared to the contralateral normal hemisphere in 65 subjects from the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy trial. The associations between ADCr, neurologic outcome, and cerebral edema were examined. Finally, we explored the interaction between baseline ADCr and vessel recanalization at day 7 on post-stroke edema.
May 2018
The Multifaceted Uses and Therapeutic Advantages of Nanoparticles for Atherosclerosis Research.Nanoparticles are uniquely suited for the study and development of potential therapies against atherosclerosis by virtue of their size, fine-tunable properties, and ability to incorporate therapies and/or imaging modalities. Furthermore, nanoparticles can be specifically targeted to the atherosclerotic plaque, evading off-target effects and/or associated cytotoxicity. There has been a wealth of knowledge available concerning the use of nanotechnologies in cardiovascular disease and atherosclerosis, in particular in animal models, but with a major focus on imaging agents. In fact, roughly 60% of articles from an initial search for this review included examples of imaging applications of nanoparticles. Thus, this review focuses on experimental therapy interventions applied to and observed in animal models. Particular emphasis is placed on how nanoparticle materials and properties allow researchers to learn a great deal about atherosclerosis. The objective of this review was to provide an update for nanoparticle use in imaging and drug delivery studies and to illustrate how nanoparticles can be used for sensing and modelling, for studying fundamental biological mechanisms, and for the delivery of biotherapeutics such as proteins, peptides, nucleic acids, and even cells all with the goal of attenuating atherosclerosis. Furthermore, the various atherosclerosis processes targeted mainly for imaging studies have been summarized in the hopes of inspiring new and exciting targeted therapeutic and/or imaging strategies.
May 2018
Reproducibility, Temporal Stability, and Functional Correlation of Diffusion MR Measurements within the Spinal Cord in Patients with Asymptomatic Cervical Stenosis or Cervical Myelopathy.OBJECTIVE The purpose of this study was to quantify the reproducibility, temporal stability, and functional correlation of diffusion MR characteristics in the spinal cord in patients with cervical stenosis with or without myelopathy. The association between longitudinal diffusion tensor imaging (DTI) measurements and serial neurological function assessment was explored at both the group and individual level. METHODS Sixty-six nonoperatively treated patients with cervical stenosis were prospectively followed (3 months to > 5 years) using synchronous serial MRI and functional outcome assessment. A total of 183 separate MRI examinations were performed, separated by at least 3 months, and each patient had a minimum of 2 MRI scans (range 2-5 scans). Anatomical and DTI measurements were performed within the spinal cord at the C1-2 region as well as at the area of highest compression. Coefficients of variance (COVs) were compared across measurements in both reference tissue and areas of compression for anatomical measurements, fractional anisotropy (FA), and mean diffusivity (MD). The correlation between diffusion MR measures at the site of compression and evaluations of neurological function assessed using the modified Japanese Orthopaedic Association (mJOA) scale at multiple time points was evaluated.
May 2018
ACR Appropriateness Criteria® Shoulder Pain-Traumatic.Traumatic shoulder pain is pain directly attributed to a traumatic event, either acute or chronic. This pain may be the result of either fracture (the clavicle, scapula, or proximal humerus) or soft-tissue injury (most commonly of the rotator cuff, acromioclavicular ligaments, or labroligamentous complex). Imaging assessment of traumatic shoulder pain begins with conventional radiography and, depending on physical examination findings, will require MRI or MR arthrography for assessment of soft-tissue injuries and CT for delineation of fracture planes. Ultrasound excels in assessment of rotator cuff injuries but has limited usefulness for assessment of the deep soft-tissues. CT angiography and conventional arteriography are helpful for assessment of vascular injury, and bone scintigraphy can be used in assessment of complex regional pain syndrome after traumatic shoulder injury. 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 2018
ACR Appropriateness Criteria® Soft-Tissue Masses.Imaging is an integral component of the evaluation of patients with a suspected soft-tissue mass. Imaging can not only confirm the presence of a mass but can provide essential information necessary for diagnosis, local staging, and biopsy planning. Although the objectives of the evaluation have not changed, the choices available for imaging of musculoskeletal masses have evolved dramatically in recent years. The purpose of this document is to identify the most common clinical scenarios and the most appropriate imaging for their assessment on the basis of the current literature and to provide general guidance for those scenarios that are not specifically addressed. 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 2018
Bioinks for 3D Bioprinting: an Overview.Bioprinting is an emerging technology with various applications in making functional tissue constructs to replace injured or diseased tissues. It is a relatively new approach that provides high reproducibility and precise control over the fabricated constructs in an automated manner, potentially enabling high-throughput production. During the bioprinting process, a solution of a biomaterial or a mixture of several biomaterials in the hydrogel form, usually encapsulating the desired cell types, termed the bioink, is used for creating tissue constructs. This bioink can be cross-linked or stabilized during or immediately after bioprinting to generate the final shape, structure, and architecture of the designed construct. Bioinks may be made from natural or synthetic biomaterials alone, or a combination of the two as hybrid materials. In certain cases, cell aggregates without any additional biomaterials can also be adopted for use as a bioink for bioprinting processes. An ideal bioink should possess proper mechanical, rheological, and biological properties of the target tissues, which are essential to ensure correct functionality of the bioprinted tissues and organs. In this review, we provide an in-depth discussion of the different bioinks currently employed for bioprinting, and outline some future perspectives in their further development.
May 2018
Disease-Related Microstructural Differences in the Brain in Women With Provoked Vestibulodynia.Provoked vestibulodynia (PVD) is a chronic pelvic pain disorder affecting 16% of the female population. Neuroimaging studies have highlighted central abnormalities in PVD, similar to other chronic pelvic pain disorders, including brain regions involved in sensory processing and modulation of pain. The aim of the study was to determine alterations in the subvoxel, microstructural organization within tissues in PVD compared with healthy control participants (HCs) and a disease control group (irritable bowel syndrome [IBS]). Diffusion tensor imaging magnetic resonance imaging was conducted in 87 age-matched premenopausal women (29 PVD, 29 HCs, 29 IBS). Statistical parameter mapping of fractional anisotropy (FA) and mean diffusivity (MD) maps were used to identify microstructural difference in the brain specific to PVD or shared with IBS. PVD alterations in microstructural organization of the brain were predominantly observed in fibers associated with sensorimotor integration and pain processing that relay information between the thalamus, basal ganglia, sensorimotor, and insular cortex. PVD, compared with HCs, showed extensive increases in the FA of somatosensory and basal ganglia regions. In contrast, PVD and IBS subjects did not show any FA-related group differences. PVD subjects showed greater MD in the basal ganglia compared with HCs (higher MD in the internal capsule and pallidum) and IBS (higher MD in the putamen and pallidum). Increases in MD were associated with increased vaginal muscle tenderness and vulvar pain. The current findings highlight possible shared mechanisms between 2 different pelvic pain disorders, but also highlight the widespread alterations observed specifically in PVD compared with HCs. PERSPECTIVE: Alterations in microstructure in PVD were observed in fibers associated with sensorimotor integration and pain processing, which were also associated with increased vaginal muscle tenderness and vulvar pain. These alterations may be contributing to increased pain sensitivity and tenderness, highlighting the need for new therapies targeting the central nervous system.
May 2018
Percutaneous Transthoracic Treatment of Ascending Aortic and Root Pseudoaneurysms: Procedural Aspects and Guidance with the Use of Multimodality Imaging.Open repair of ascending aortic pseudoaneurysms (AAPs) is currently the standard of care, but it is associated with high morbidity and mortality. A single-center retrospective experience of 4 patients after cardiac surgery undergoing 5 percutaneous transthoracic embolization procedures is presented. In 3 of the 4 patients, the primary outcome of complete thrombosis was achieved after the first procedure, with a mean follow-up time of 11.5 months. In all 5 procedures, the patients tolerated the procedure well without associated acute complications. Percutaneous transthoracic embolization of AAPs offers an alternate minimally invasive treatment pathway for prohibitive-risk candidates.
May 2018
Superior Hypogastric Nerve Block in Uterine Fibroid Embolization Patients with Radial Artery Access: Vascular Considerations, Anesthetic Choices, and Rescue Options.Adequately treating pain and nausea following uterine artery embolization (UAE) is a continuing challenge. Superior hypogastric nerve block (SHNB) is a successful adjunct technique for decreasing pain after embolization. This letter discusses safety measures for administration of SHNB during UAE using radial artery access, including avoiding inadvertent intravascular injection, choosing the optimal anesthetic, and treating local anesthetic systemic toxicity.
May 2018
Comparison of Double-Freeze versus Modified Triple-Freeze Pulmonary Cryoablation and Hemorrhage Volume Using Different Probe Sizes in an In Vivo Porcine Lung.PURPOSE: To determine size of ablation zone and pulmonary hemorrhage in double-freeze (DF) vs modified triple-freeze (mTF) cryoablation protocols with different probe sizes in porcine lung. MATERIALS AND METHODS: In 10 healthy adult pigs, 20 pulmonary cryoablations were performed using either a 2.4-mm or a 1.7-mm probe. Either conventional DF or mTF protocol was used. Serial noncontrast CT scans were performed during ablations. Ablation iceball and hemorrhage volumes were measured and compared between protocols and probe sizes.
May 2018
Early Blood-Brain Barrier Disruption after Mechanical Thrombectomy in Acute Ischemic Stroke.BACKGROUND AND PURPOSE: The impact of blood-brain barrier (BBB) disruption can be detected by intraparenchymal hyperdense lesion on the computed tomography (CT) scan after endovascular stroke therapy. The purpose of this study was to determine whether early BBB disruption predicts intracranial hemorrhage and poor outcome in patients with acute ischemic stroke treated with mechanical thrombectomy. METHODS: We analyzed patients with anterior circulation stroke treated with mechanical thrombectomy and identified BBB disruption on the noncontrast CT images immediately after endovascular treatment. Follow-up CT or magnetic resonance imaging scan was performed at 24 hours to assess intracranial hemorrhage. We dichotomized patients into those with moderate BBB disruption versus those with minor BBB disruption and no BBB disruption. We evaluated the association of moderate BBB disruption after mechanical thrombectomy with intracranial hemorrhage and clinical outcomes.
May 2018
Abnormal Trajectory of Intracortical Myelination in Schizophrenia Implicates White Matter in Disease Pathophysiology and the Therapeutic Mechanism of Action of Antipsychotics.BACKGROUND: Postmortem and imaging studies provide converging evidence that the frontal lobe myelination trajectory is dysregulated in schizophrenia (SZ) and suggest that early in treatment, antipsychotic medications increase intracortical myelin (ICM). We used magnetic resonance imaging to examine whether the ICM trajectory in SZ is dysregulated and altered by antipsychotic treatment. METHODS: We examined 93 subjects with SZ (64 men and 29 women) taking second-generation oral antipsychotics with medication exposures of 0-333 months in conjunction with 80 healthy control subjects (52 men and 28 women). Frontal lobe ICM volume was estimated using a novel dual contrast magnetic resonance imaging method that combines two images that track different tissue components.
April 2018
Assessing the Effect of Lifetime Contralateral Breast Cancer Risk on the Selection of Contralateral Prophylactic Mastectomy for Unilateral Breast Cancer.INTRODUCTION: Contralateral prophylactic mastectomy (CPM) rates are rising, with fear implicated as a contributing factor. This study used a contralateral breast cancer (CBC) risk stratification tool to assess whether the selection of CPM is reflective of future CBC risk. PATIENTS AND METHODS: This retrospective study evaluated 404 women with unilateral breast cancer treated with breast conservation, unilateral mastectomy, or bilateral mastectomy within a single multidisciplinary clinic. Women were evaluated by the Manchester risk tool to calculate lifetime CBC risk. Logistic regression analysis was used to evaluate whether CBC risk was associated with CPM, and the clinical rationale for prophylactic mastectomy justification was recorded.
April 2018
Spectral Resolution and High-flux Capability Tradeoffs in CdTe Detectors for Clinical CT.PURPOSE: Photon-counting detectors using CdTe or CZT substrates are promising candidates for future CT systems but suffer from a number of nonidealities, including charge sharing and pulse pileup. By increasing the pixel size of the detector, the system can improve charge sharing characteristics at the expense of increasing pileup. The purpose of this work is to describe these considerations in the optimization of the detector pixel pitch. METHODS: The transport of x rays through the CdTe substrate was simulated in a Monte Carlo fashion using GEANT4. Deposited energy was converted into charges distributed as a Gaussian function with size dependent on interaction depth to capture spreading from diffusion and Coulomb repulsion. The charges were then collected in a pixelated fashion. Pulse pileup was incorporated separately with Monte Carlo simulation. The Cramér-Rao lower bound (CRLB) of the measurement variance was numerically estimated for the basis material projections. Noise in these estimates was propagated into CT images. We simulated pixel pitches of 250, 350, and 450 microns and compared the results to a photon counting detector with pileup but otherwise ideal energy response and an ideal dual-energy system (80/140 kVp with tin filtration). The modeled CdTe thickness was 2 mm, the incident spectrum was 140 kVp and 500 mA, and the effective dead time was 67 ns. Charge summing circuitry was not modeled. We restricted our simulations to objects of uniform thickness and did not consider the potential advantage of smaller pixels at high spatial frequencies.
April 2018
Understanding Brain Penetrance of Anticancer Drugs.This paper explicates the impact of tumor capillary permeability for glioma World Health Organization (WHO) grades II to IV on brain-penetrant drug entry and distribution within the tumor and the brain adjacent to tumor (leading edge). In addition, we consider the distribution of non-brain penetrant drugs and how, in some cases, large-molecular-weight drugs might achieve good distribution into tumor and brain adjacent to tumor.
April 2018
Engineering a Clinically Translatable Bioartificial Pancreas to Treat Type I Diabetes.Encapsulating, or immunoisolating, insulin-secreting cells within implantable, semipermeable membranes is an emerging treatment for type 1 diabetes. This approach can eliminate the need for immunosuppressive drug treatments to prevent transplant rejection and overcome the shortage of donor tissues by utilizing cells derived from allogeneic or xenogeneic sources. Encapsulation device designs are being optimized alongside the development of clinically viable, replenishable, insulin-producing stem cells, for the first time creating the possibility of widespread therapeutic use of this technology. Here, we highlight the status of the most advanced and widely explored implementations of cell encapsulation with an eye toward translating the potential of this technological approach to medical reality.
April 2018
The Synergy of Scaffold-Based and Scaffold-Free Tissue Engineering Strategies.Tissue engineering (TE) is a highly interdisciplinary research field driven by the goal to restore, replace, or regenerate defective tissues. Throughout more than two decades of intense research, different technological approaches, which can be principally categorized into scaffold-based and scaffold-free strategies, have been developed. In this opinion article, we discuss the emergence of a third strategy in TE. This synergetic strategy integrates the advantages of both of these traditional approaches, while being clearly distinct from them. Its characteristic attributes, numerous practical benefits, and recent literature reports supporting our opinion, are discussed in detail.
April 2018
Increased Affinity of Endothelial Cells to NiTi Using Ultraviolet Irradiation: An in Vitro Study.Nickel-titanium alloy (NiTi) is one of the most popular materials used endovascularly because of its shape memory and superelasticity. The NiTi device needs to be covered by endothelial cells after being placed in the blood vessel to reduce ischemic complications. The objective of this study was to examine the impact of ultraviolet (UV) irradiation on the biocompatibility of NiTi surfaces with endothelial cells. NiTi sheets were treated with UV irradiation for 48 h and human aorta derived endothelial cells were used in this study. UV irradiation converted the NiTi surface to hydrophilic state and increased albumin adsorption. The number of endothelial cell migration, attachment, proliferation as well as their metabolic activity were significantly increased on UV treated NiTi. This study provides the first evidence of the photoactivation of NiTi surfaces by UV irradiation and demonstrates improved biocompatibility of UV-treated NiTi surfaces with vascular endothelial cells. These results suggest that UV irradiation may promote endothelialization of NiTi devices in blood vessels.
April 2018
An Expert Consensus for the Management of Chronic Hepatitis B in Asian Americans.BACKGROUND: Hepatitis B virus (HBV) infection is common with major clinical consequences. In Asian Americans, the HBsAg carrier rate ranges from 2% to 16% which approximates the rates from their countries of origin. Similarly, HBV is the most important cause of cirrhosis, hepatocellular carcinoma (HCC) and liver related deaths in HBsAg positive Asians worldwide. AIM: To generate recommendations for the management of Asian Americans infected with HBV. METHODS: These guidelines are based on relevant data derived from medical reports on HBV from Asian countries as well as from studies in the HBsAg positive Asian Americans. The guidelines herein differ from other recommendations in the treatment of both HBeAg positive and negative chronic hepatitis B (CHB), in the approach to HCC surveillance, and in the management of HBV in pregnant women.
April 2018
Feasibility and Safety of Intrathoracic Biopsy and Repeat Biopsy for Evaluation of Programmed Cell Death Ligand-1 Expression for Immunotherapy in Non-Small Cell Lung Cancer.Purpose To determine feasibility and safety of biopsy and repeat biopsy for assessment of programmed cell death ligand-1 (PD-L1) status. Materials and Methods This retrospective analysis reviewed 101 patients who underwent transthoracic core needle biopsy for the KEYNOTE-001 (MK-3475) clinical trial of pembrolizumab, an antiprogrammed cell death-1 therapy for non-small cell lung cancer, from May 2012 to September 2014. Sixty-one male patients (mean age, 66.1 years; range 36-83 years) and 40 female patients (mean age, 66.8 years; age range, 36-90 years) were included. Data collected included population characteristics, treatment history, target location, size, and depth from pleura. Adequacy of the tissue sample for diagnostic testing and rates of biopsy-related complications were assessed. Statistical analysis was performed by using univariate and multivariate generalized linear models to determine significant risk factors for biopsy complications. Results A total of 110 intrathoracic biopsies were performed, and 101 (91.8%) were performed as repeat biopsies subsequent to a previous percutaneous or bronchoscopic biopsy or previous surgical biopsy or resection. More than 84.5% (93 of 110) of biopsies were performed in patients who had undergone previous local or systemic therapy. Specimens were adequate for evaluation of PD-L1 expression in 96.4% of biopsies. Procedure-related complications occurred in 28 biopsies (25.4%); pneumothorax was most common (22.7%). Overall mean number of core needle biopsy samples obtained was 7.9 samples. Conclusion Image-guided transthoracic core needle biopsy is an effective method for obtaining tissue for PD-L1 expression analysis.
March 2018
Semi-automated Pulmonary Nodule Interval Segmentation Using the NLST Data.PURPOSE: To study the variability in volume change estimates of pulmonary nodules due to segmentation approaches used across several algorithms and to evaluate these effects on the ability to predict nodule malignancy. METHODS: We obtained 100 patient image datasets from the National Lung Screening Trial (NLST) that had a nodule detected on each of two consecutive low dose computed tomography (LDCT) scans, with an equal proportion of malignant and benign cases (50 malignant, 50 benign). Information about the nodule location for the cases was provided by a screen capture with a bounding box and its axial location was indicated. Five participating quantitative imaging network (QIN) institutions performed nodule segmentation using their preferred semi-automated algorithms with no manual correction; teams were allowed to provide additional manually corrected segmentations (analyzed separately). The teams were asked to provide segmentation masks for each nodule at both time points. From these masks, the volume was estimated for the nodule at each time point; the change in volume (absolute and percent change) across time points was estimated as well. We used the concordance correlation coefficient (CCC) to compare the similarity of computed nodule volumes (absolute and percent change) across algorithms. We used Logistic regression model on the change in volume (absolute change and percent change) of the nodules to predict the malignancy status, the area under the receiver operating characteristic curve (AUROC) and confidence intervals were reported. Because the size of nodules was expected to have a substantial effect on segmentation variability, analysis of change in volumes was stratified by lesion size, where lesions were grouped into those with a longest diameter of <8 mm and those with longest diameter ≥ 8 mm.
March 2018
Synergistic Interplay Between the Two Major Bone Minerals, Hydroxyapatite and Whitlockite Nanoparticles, for Osteogenic Differentiation of Mesenchymal Stem Cells.The inorganic part of human bone is mainly composed of hydroxyapatite (HAP: Ca10(PO4)6(OH)2) and whitlockite (WH: Ca18Mg2(HPO4)2(PO4)12) minerals, where the WH phase occupies up to 20-35% of total weight. These two bone minerals have different crystal structures and physicochemical properties, implying their distinguished role in bone physiology. However, until now, the biological significance of the presence of a certain ratio between HAP and WH in bone is unclear. To address this fundamental question, bone mimetic scaffolds are designed to encapsulate human mesenchymal stem cells (MSCs) for assessing their osteogenic activity depending on different ratios of HAP and WH. Interestingly, cellular growth and osteogenic differentiation are significantly promoted when MSCs are grown with a 3-1 ratio of HAP and WH nanoparticles, which is similar to bone. One of the reasons for this synergism between HAP and WH in hydrogel scaffolds is that, while WH nanoparticles can enhance osteogenic differentiation of MSCs compared to HAP, WH counterintuitively decreases the mechanical stiffness of nanocomposite hydrogels and hinders the osteogenic activity of cells. Taken together, these findings identify the optimal ratio between two major minerals in bone mimetic scaffolds to maximize the osteogenic differentiation of MSCs.
March 2018
Evidence and Context of Use for Contrast Enhancement as a Surrogate of Disease Burden and Treatment Response in Malignant Glioma.The use of contrast enhancement within the brain on CT or MRI has been the gold standard for diagnosis and therapeutic response assessment in malignant gliomas for decades. The use of contrast enhancing tumor size, however, remains controversial as a tool for accurately diagnosing and assessing treatment efficacy in malignant gliomas, particularly in the current, quickly evolving therapeutic landscape. The current article consolidates overwhelming evidence from hundreds of studies in the field of neuro-oncology, providing the necessary evidence base and specific contexts of use for consideration of contrast enhancing tumor size as an appropriate surrogate biomarker for disease burden and as a tool for measuring treatment response in malignant glioma, including glioblastoma.
March 2018
Radiologic Progression of Glioblastoma Under Therapy-an Exploratory Analysis of AVAglio.BACKGROUND: In this exploratory analysis of AVAglio, a randomized phase III clinical study that investigated the addition of bevacizumab (Bev) to radiotherapy/temozolomide in newly diagnosed glioblastoma, we aim to radiologically characterize glioblastoma on therapy until progression and investigate whether the type of radiologic progression differs between treatment arms and is related to survival and molecular data. METHODS: Five progression types (PTs) were categorized using an adapted algorithm according to MRI contrast enhancement behavior in T1- and T2-weighted images in 621 patients (Bev, n = 299; placebo, n = 322). Frequencies of PTs (designated as classic T1, cT1 relapse, T2 diffuse, T2 circumscribed, and primary nonresponder), time to progression (PFS), and overall survival (OS) were assessed within each treatment arm and compared with molecular subtypes and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status.
March 2018
Electrically Driven Microengineered Bioinspired Soft Robots.To create life-like movements, living muscle actuator technologies have borrowed inspiration from biomimetic concepts in developing bioinspired robots. Here, the development of a bioinspired soft robotics system, with integrated self-actuating cardiac muscles on a hierarchically structured scaffold with flexible gold microelectrodes is reported. Inspired by the movement of living organisms, a batoid-fish-shaped substrate is designed and reported, which is composed of two micropatterned hydrogel layers. The first layer is a poly(ethylene glycol) hydrogel substrate, which provides a mechanically stable structure for the robot, followed by a layer of gelatin methacryloyl embedded with carbon nanotubes, which serves as a cell culture substrate, to create the actuation component for the soft body robot. In addition, flexible Au microelectrodes are embedded into the biomimetic scaffold, which not only enhance the mechanical integrity of the device, but also increase its electrical conductivity. After culturing and maturation of cardiomyocytes on the biomimetic scaffold, they show excellent myofiber organization and provide self-actuating motions aligned with the direction of the contractile force of the cells. The Au microelectrodes placed below the cell layer further provide localized electrical stimulation and control of the beating behavior of the bioinspired soft robot.
March 2018
Gadolinium Deposition in the Paediatric Brain: T1-weighted Hyperintensity within the Dentate Nucleus Following Repeated Gadolinium-based Contrast Agent Administration.AIM: To determine whether repeated gadolinium-based contrast agent administration (GBCA) in children is associated with the development of increased T1-weighted signal intensity within the cerebellar dentate nucleus. MATERIALS AND METHODS: With institutional review board approval for this The Health Insurance Portability and Accountability Act-compliant retrospective study, a cohort of 41 patients under the age of 18 years who underwent at least four contrast-enhanced magnetic resonance imaging (MR) examinations of the brain from 2005 to 2015 were identified. For each examination, both dentate nuclei were manually contoured, and the mean dentate nucleus-to-pons signal intensity (DN-P SI) ratio was calculated. The DN-P SI ratios from the last to first MRI examination were compared, and the correlation between DN-P SI ratio and cumulative gadolinium dose was calculated using a linear mixed effect model to control for potentially confounding variables.
March 2018
ASPECTS-based Reperfusion Status on Arterial Spin Labeling is Associated with Clinical Outcome in Acute Ischemic Stroke Patients.The purpose of this study was to develop and evaluate a scoring system for assessing reperfusion status based on arterial spin labeled (ASL) perfusion MRI in acute ischemic stroke (AIS) patients receiving thrombolysis and/or endovascular treatment. Pseudo-continuous ASL with background suppressed 3D GRASE was acquired along with DWI in 90 patients within 24 h post-treatment. An automatic reperfusion scoring system (auto-RPS) was devised based on the Alberta Stroke Program Early CT Score (ASPECTS) template, and compared with manual RPS and DWI-ASPECTS. TICI (thrombolysis in cerebral infarction) scores were graded in 48 patients who received endovascular treatment. Favorable outcomes were defined by a modified Rankin Scale score of 0-2 at three months. Auto-RPS was positively correlated with DWI-ASPECTS (ρ = 0.6, P < 0.001) and was on average 1 point lower than DWI-ASPECTS ( P < 0.001). The area under the receiver operating characteristic curve for discriminating poor functional outcome (n = 90) was 0.75 (95% CI, 0.64-0.86) for manual RPS, 0.85 (95% CI, 0.76-0.94) for auto-RPS, and 0.81 (95% CI, 0.71-0.90) for DWI-ASPECTS. Multiple logistic regression analysis in the TICI-graded patients (n = 48) showed that auto-RPS is highly associated with functional outcome (OR = 25.2, 95% CI 4.02-496, P < 0.01). Post treatment auto-RPS within 24 h provides a useful tool to predict functional outcome in AIS patients.
February 2018
Cardiac Magnetic Resonance Imaging Using Wideband Sequences in Patients with Nonconditional Cardiac Implanted Electronic Devices.BACKGROUND: Magnetic resonance imaging (MRI) has been performed safely in patients without MRI-conditional cardiac implantable electronic devices (CIEDs), but experience specifically with cardiac magnetic resonance imaging (CMR) is limited in this patient population. OBJECTIVE: Evaluate the safety of CMR in non-MRI-conditional CIEDs and the interpretability of images using wideband sequences. METHODS: We performed 114 consecutive CMR studies in 111 patients (mean age 59 ± 14 years, with 12 pacemakers, 73 implantable cardioverter defibrillators, 29 biventricular defibrillators) using a wideband pulse sequence for late gadolinium enhancement (LGE) imaging. A standardized protocol for device management and patient monitoring was followed. Patients were evaluated for major clinical adverse events and device parameter changes immediately after CMR and at clinical follow-up.
February 2018
Diagnostic Criteria for Idiopathic Pulmonary Fibrosis: a Fleischner Society White Paper.This Review provides an updated approach to the diagnosis of idiopathic pulmonary fibrosis (IPF), based on a systematic search of the medical literature and the expert opinion of members of the Fleischner Society. A checklist is provided for the clinical evaluation of patients with suspected usual interstitial pneumonia (UIP). The role of CT is expanded to permit diagnosis of IPF without surgical lung biopsy in select cases when CT shows a probable UIP pattern. Additional investigations, including surgical lung biopsy, should be considered in patients with either clinical or CT findings that are indeterminate for IPF. A multidisciplinary approach is particularly important when deciding to perform additional diagnostic assessments, integrating biopsy results with clinical and CT features, and establishing a working diagnosis of IPF if lung tissue is not available. A working diagnosis of IPF should be reviewed at regular intervals since the diagnosis might change. Criteria are presented to establish confident and working diagnoses of IPF.
February 2018
A Structured Global Health Training Program for Radiology Residents.The World Health Organization (WHO) increasingly recognizes the need and utility for quality diagnostic tests. Historically, imaging has played a key role for diagnosis and treatment plans for global health infectious diseases, like tuberculosis and human immunovirus (HIV) and acquired immunodeficiency syndrome. However, according to the WHO, there is a global rise in noncommunicable diseases, such as cancer and cardiovascular diseases, for which imaging has been an integral part of care in areas of high access to health care for decades [1]. In analysis of WHO member states, a wide gap is shown between nations that have imaging and related treatment services and those that have minimal to no access [2]. This background supports the increasing trend for radiology to be part of global health initiatives and underscores the dire need for medical imaging services in areas that currently lack access and human capacity [3]...
February 2018
Investigating the Minimum Scan Parameters Required to Generate Free-breathing Motion Artefact-free Fast-helical CT.OBJECTIVE: A recently proposed "5DCT" protocol uses deformable registration of free-breathing fast-helical CT scans to generate a breathing motion model. In order to allow accurate registration, free-breathing images are required to be free of doubling-artefacts, which arise when tissue motion is greater than scan speed. METHODS: Using a unique set of digital phantoms based on patient data and verified with a motion phantom, this work identifies the minimum scanner parameters required to successfully generate free-breathing artefact-free fast-helical scans. A motion phantom and 5 patients were imaged 25 times under free-breathing conditions in alternating directions with a 64-slice CT scanner employing a low-dose fast-helical protocol. A series of high temporal resolution (0.1 s) 5DCT scan data sets was generated in each case. A simulated CT scanner was used to "image" each free-breathing data set. Various CT scanner detector widths and rotation times were simulated, and verified using the motion phantom results. Motion-induced artefacts were quantified in patient images using structural similarity maps to determine the similarity between axial slices.
January 2018
Quantitative Bone Scan Lesion Area as an Early Surrogate Outcome Measure Indicative of Overall Survival in Metastatic Prostate Cancer.A clinical validation of the bone scan lesion area (BSLA) as a quantitative imaging biomarker was performed in metastatic castration-resistant prostate cancer (mCRPC). BSLA was computed from whole-body bone scintigraphy at baseline and week 12 posttreatment in a cohort of 198 mCRPC subjects (127 treated and 71 placebo) from a clinical trial involving a different drug from the initial biomarker development. BSLA computation involved automated image normalization, lesion segmentation, and summation of the total area of segmented lesions on bone scan AP and PA views as a measure of tumor burden. As a predictive biomarker, treated subjects with baseline BSLA [Formula: see text] had longer survival than those with higher BSLA ([Formula: see text] and [Formula: see text]). As a surrogate outcome biomarker, subjects were categorized as progressive disease (PD) if the BSLA increased by a prespecified 30% or more from baseline to week 12 and non-PD otherwise. Overall survival rates between PD and non-PD groups were statistically different ([Formula: see text] and [Formula: see text]). Subjects without PD at week 12 had longer survival than subjects with PD: median 398 days versus 280 days. BSLA has now been demonstrated to be an early surrogate outcome for overall survival in different prostate cancer drug treatments.
January 2018
Improved Spatiotemporal Resolution of Dynamic Susceptibility Contrast Perfusion MRI in Brain Tumors Using Simultaneous Multi-Slice Echo-Planar Imaging.DSC perfusion MR imaging in brain tumors requires a trade-off between spatial and temporal resolution, resulting in less spatial coverage to meet the temporal resolution requirements for accurate relative CBV estimation. DSC-MR imaging could potentially benefit from the advantages associated with simultaneous multi-slice imaging, including increased spatiotemporal resolution. In the current article, we demonstrate how simultaneous multi-slice EPI can be used to improve DSC-MR imaging spatiotemporal resolution in patients with glioblastoma.
January 2018
Evaluating Casama: Contextualized Semantic Maps for Summarization of Lung Cancer Studies.OBJECTIVE: It is crucial for clinicians to stay up to date on current literature in order to apply recent evidence to clinical decision making. Automatic summarization systems can help clinicians quickly view an aggregated summary of literature on a topic. Casama, a representation and summarization system based on "contextualized semantic maps," captures the findings of biomedical studies as well as the contexts associated with patient population and study design. This paper presents a user-oriented evaluation of Casama in comparison to a context-free representation, SemRep. MATERIALS AND METHODS: The effectiveness of the representation was evaluated by presenting users with manually annotated Casama and SemRep summaries of ten articles on driver mutations in cancer. Automatic annotations were evaluated on a collection of articles on EGFR mutation in lung cancer. Seven users completed a questionnaire rating the summarization quality for various topics and applications.
January 2018
Nature's Wastebasket: The Role of the External Carotid Artery in Acute Stroke.We describe a novel technical approach to acute stroke illustrated by the case of a 41 year old male who presented with tandem right common carotid artery (CCA) and M1 occlusions. His NIHSS was 17 and Alberta stroke programe early CT score (ASPECTs) was 8. Thrombectomy initially proved challenging due to large volume CCA thrombus that repeatedly occluded the aspiration catheters. However, by inflating a balloon distally and pulling clot into the adjacent ECA, we were able to quickly restore distal contrast flow to the intracranial circulation and achieve Thrombolysis In Cerebral Infarction/Arterial Occlusive Lesion (TICI2C/AOL3) revascularization.
January 2018
Low-dose CT Perfusion with Projection View Sharing.PURPOSE: CT Perfusion (CTP) is a widely used clinical imaging modality. However, CTP typically involves the use of substantial radiation dose (CTDIvol ≥~200 mGy). The purpose of this study is to present a low-dose CTP technique using a projection view-sharing reconstruction algorithm originally developed for dynamic MRI - "K-space Weighted Image Contrast" (KWIC). METHODS: The KWIC reconstruction is based on an angle-bisection scheme. In KWIC, a Fourier transform was performed along each projection to form a "k-space"-like CT data space, based on the central-slice theorem. As a projection view-sharing technique, KWIC preserves the spatiotemporal resolution of undersampled CTP data by progressively increasing the number of projection views shared for more distant regions of "k-space". KWIC reconstruction was evaluated on a digital FORBILD head phantom with numerically simulated time-varying objects. The numerically simulated scans were undersampled using the angle-bisection scheme to achieve 50%, 25%, and 12.5% of the original dose (288, 144, and 72 projections, respectively). The area-under-the-curve (AUC), time-to-peak (TTP), and full width half maximum (FWHM) were measured in KWIC recons and compared to fully sampled filtered back projection (FBP) reconstructions. KWIC reconstruction and dose reduction was also implemented for three clinical CTP cases (45 s, 1156 projections per turn, 1 s/turn, CTDIvol 217 mGy). Quantitative perfusion metrics were computed and compared between KWIC reconstructed CTP data and those of standard FBP reconstruction.
January 2018
High Resolution Three-Dimensional Delayed Contrast MRI Detects Endolymphatic Hydrops in Patients With Vertigo and Vestibular Schwannoma.OBJECTIVE: Advances in high resolution magnetic resonance imaging (MRI) have enabled the detection of endolymphatic hydrops (EH), a pathological ballooning of the endolymphatic fluid system, known to be associated with Menière's disease. When a patient has a known diagnosis of vestibular schwannoma and develops recurrent episodic vertigo spells, many surgeons recommend surgical intervention, attributing the vestibular symptoms to the vestibular schwannoma. The aim of this study is to evaluate the clinical outcome in patients with vestibular schwannoma and EH, treated medically, for recurrent spells of vertigo. PATIENTS: Two patients with EH and vestibular schwannoma who presented with recurrent spells of vertigo are included. Both had characteristic low frequency hearing loss ipsilateral to the schwannoma. INTERVENTION: MRI sequences with 3T scanner (Skyra, Siemens Healthcare, Erlangen, Germany) using high resolution three-dimensional delayed postcontrast protocol included "cisternographic" T2 and delayed intravenous-enhanced three-dimensional fluid-attenuation inversion recovery (DIVE-3D-FLAIR) sequences, performed with 2350ms (bright perilymph) and 2050ms (bright endolymph) inversion times and with subtracted images.
January 2018
Ferumoxytol-enhanced MR Angiography for Vascular Access Mapping before Transcatheter Aortic Valve Replacement in Patients with Renal Impairment: A Step Toward Patient-specific Care.PURPOSE: To assess the technical feasibility of the use of ferumoxytol-enhanced (FE) magnetic resonance (MR) angiography for vascular mapping before transcatheter aortic valve replacement in patients with renal impairment. MATERIALS AND METHODS: This was an institutional review board-approved and HIPAA-compliant study. FE MR angiography was performed at 3.0 T or 1.5 T. Unenhanced computed tomographic (CT) images were used to overlay vascular calcification on FE MR angiographic images as composite fused three-dimensional data. Image quality of the subclavian and aortoiliofemoral arterial tree and confidence in the assessment of calcification were evaluated by using a four-point scale (4 = excellent vascular definition or strong confidence). Signal intensity nonuniformity as reflected by the heterogeneity index (ratio between the mean standard deviation of luminal signal intensity and the mean luminal signal intensity), signal-to-noise ratio, and consistency of luminal diameter measurements were quantified. Findings at FE MR angiography were compared with pelvic angiograms.
January 2018
Brain Metastases: Neuroimaging.Magnetic resonance imaging (MRI) is the cornerstone for evaluating patients with brain masses such as primary and metastatic tumors. Important challenges in effectively detecting and diagnosing brain metastases and in accurately characterizing their subsequent response to treatment remain. These difficulties include discriminating metastases from potential mimics such as primary brain tumors and infection, detecting small metastases, and differentiating treatment response from tumor recurrence and progression. Optimal patient management could be benefited by improved and well-validated prognostic and predictive imaging markers, as well as early response markers to identify successful treatment prior to changes in tumor size. To address these fundamental needs, newer MRI techniques including diffusion and perfusion imaging, MR spectroscopy, and positron emission tomography (PET) tracers beyond traditionally used 18-fluorodeoxyglucose are the subject of extensive ongoing investigations, with several promising avenues of added value already identified. These newer techniques provide a wealth of physiologic and metabolic information that may supplement standard MR evaluation, by providing the ability to monitor and characterize cellularity, angiogenesis, perfusion, pH, hypoxia, metabolite concentrations, and other critical features of malignancy. This chapter reviews standard and advanced imaging of brain metastases provided by computed tomography, MRI, and amino acid PET, focusing on potential biomarkers that can serve as problem-solving tools in the clinical management of patients with brain metastases.
January 2018
Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma.BACKGROUND: Despite current therapies, diffuse cutaneous systemic sclerosis (scleroderma) often has a devastating outcome. We compared myeloablative CD34+ selected autologous hematopoietic stem-cell transplantation with immunosuppression by means of 12 monthly infusions of cyclophosphamide in patients with scleroderma. METHODS: We randomly assigned adults (18 to 69 years of age) with severe scleroderma to undergo myeloablative autologous stem-cell transplantation (36 participants) or to receive cyclophosphamide (39 participants). The primary end point was a global rank composite score comparing participants with each other on the basis of a hierarchy of disease features assessed at 54 months: death, event-free survival (survival without respiratory, renal, or cardiac failure), forced vital capacity, the score on the Disability Index of the Health Assessment Questionnaire, and the modified Rodnan skin score.
January 2018
Visual Aids for Patient, Family, and Physician Decision Making About Endovascular Thrombectomy for Acute Ischemic Stroke.BACKGROUND AND PURPOSE: Rapid decision making optimizes outcomes from endovascular thrombectomy for acute cerebral ischemia. Visual displays facilitate swift review of potential outcomes and can accelerate decision processes. METHODS: From patient-level, pooled randomized trial data, 100 person-icon arrays (Kuiper-Marshall personographs) were generated showing beneficial and adverse effects of endovascular thrombectomy for patients with acute cerebral ischemia and large vessel occlusion using (1) automated (algorithmic) and (2) expert-guided joint outcome table specification.
January 2018
Lung Cancer Radiogenomics: The Increasing Value of Imaging in Personalized Management of Lung Cancer Patients.Radiogenomics provide a large-scale data analytical framework that aims to understand the broad multiscale relationships between the complex information encoded in medical images (including computational, quantitative, and semantic image features) and their underlying clinical, therapeutic, and biological associations. As such it is a powerful and increasingly important tool for both clinicians and researchers involved in the imaging, evaluation, understanding, and management of lung cancers. Herein we provide an overview of the growing field of lung cancer radiogenomics and its applications.
