October 2020
Gut-on-a-chip: Current Progress and Future Opportunities.Organ-on-a-chip technology tries to mimic the complexity of native tissues in vitro. Important progress has recently been made in using this technology to study the gut with and without microbiota. These in vitro models can serve as an alternative to animal models for studying physiology, pathology, and pharmacology. While these models have greater physiological relevance than two-dimensional (2D) cell systems in vitro, endocrine and immunological functions in gut-on-a-chip models are still poorly represented. Furthermore, the construction of complex models, in which different cell types and structures interact, remains a challenge. Generally, gut-on-a-chip models have the potential to advance our understanding of the basic interactions found within the gut and lay the foundation for future applications in understanding pathophysiology, developing drugs, and personalizing medical treatments.
October 2020
Case 286.History A 70-year-old man had a posterior left thigh lesion confirmed to be biopsy-proven melanoma. The patient underwent wide excision and sentinel node biopsy, which showed absence of residual melanoma. Two years later, the patient noticed a subcentimeter subcutaneous lump in his thigh. Repeat excisional biopsy showed involvement of the surrounding soft tissue, consistent with a satellite lesion. Follow-up combined PET/CT revealed satellite nodules around the primary lesion, enabling confirmation of subcutaneous metastatic disease. The patient was subsequently started on nivolumab, an anti-programmed cell death 1 (PD-1) immune checkpoint inhibitor that blocks PD-1 and is approved as a first-line treatment in patients with advanced metastatic melanoma. On the baseline scan prior to starting nivolumab, there were no CT findings that suggested metastatic disease, nor were there enlarged mediastinal or hilar lymph nodes. Five months after initiation of nivolumab treatment, the first follow-up chest CT scan was performed and showed new findings in the mediastinum (Fig 1) and bilateral lungs (Figs 2, 3). The patient remained asymptomatic during the treatment period. Furthermore, the subcutaneous metastatic disease remained stable during the treatment period, and no other site of metastatic disease was noted on follow-up CT scans obtained during the first 5 months of treatment. The patient had no prior history of infectious or occupational exposures. During the nivolumab treatment cycle, his pertinent laboratory values and physical examination findings were unremarkable.
October 2020
Association of Tumor Grade, Enhancement on Multiphasic CT and Microvessel Density in Patients with clear cell renal cell Carcinoma.PURPOSE: Clear cell renal cell carcinoma (ccRCC) comprises nearly 90% of all diagnosed RCC subtypes and has the worst prognosis and highest metastatic potential. The strongest prognostic factors for patients with ccRCC include histological subtype and Fuhrman grade, which are incorporated into prognostic models. Since ccRCC is a highly vascularized tumor, there may be differences in enhancement patterns on multidetector CT (MDCT) due to the hemodynamics and microvessel density (MVD) of the lesions. This may provide a noninvasive method to characterize incidentally detected low- and high-grade ccRCCs on MDCT. The purpose of our study was to determine the correlation between MDCT enhancement parameters, ccRCC MVD, and Fuhrman grade to determine its utility and value in assessing tumor vascularity and grade in vivo. METHODS: In this retrospective, 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. A 3D volume of interest (VOI) was obtained for every tumor and absolute enhancement and the wash-in/wash-out of enhancement for each phase was assessed. Immunohistochemistry on resected specimens was used to quantify MVD. Linear regression and Pearson correlation were used to investigate the strength of the association between 3D VOI enhancement and MVD. Stepwise logistic regression analysis determined independent predictors of HG ccRCC. Cut-off values and odds Ratio (OR) with 95% CIs were reported. The clinical, radiomic, and pathologic features with the highest performance in the stepwise logistic regression analysis were evaluated using receiver operator characteristics (ROC) and area under the curve (AUC).
October 2020
Radiology's Information Architecture Could Migrate to One Emulating That of Smartphones.Diagnostic radiology (DxR), having had successful serial co-evolutions with imaging equipment and PACS, is faced with another. With a backdrop termed "globotics transition," it should create an IT and informatics infrastructure capable of integrating artificial intelligence (AI) into current critical communication functions of PACS and incorporating functions currently residing in balkanized products. DxR will face the challenge of adopting sustaining and disruptive AI innovations simultaneously. In this co-evolution, a major selection force for AI will be increasing the flow of information and patients; "increasing" means faster flow over larger areas defined by geography and content. Larger content includes a broader spectrum of imaging and nonimaging information streams that facilitate medical decision making. Evolution to faster flow will gravitate toward a hierarchical IT architecture consisting of many small channels feeding into fewer larger channels, something potentially difficult for current PACS. Smartphone-like architecture optimized for communication and integration could provide a large-channel backbone and many smaller feeding channels for basic functions, as well as those needing to innovate rapidly. New, more flexible architectures stimulate market competition in which DxR could act as an artificial selection force to influence development of faster increased flow in current PACS companies, in disruptors such as consolidated AI companies, or in entirely new entrants like Apple or Google. In this co-evolution, DxR should be able to stimulate design of a modern communication medium that increases the flow of information and decreases the time and energy necessary to absorb it, thereby creating even more indispensable clinical value for itself.
October 2020
Efficacy of 3T Multiparametric MR Imaging followed by 3T in-Bore MR-Guided Biopsy for Detection of Clinically Significant Prostate Cancer Based on PIRADSv2.1 Score.PURPOSE: To evaluate the diagnostic yield of 3T in-Bore magnetic resonance-guided biopsy (3T IB-MRGB) for detection of clinically significant prostate cancer (csPCa), based on assessment using the Prostate Imaging Reporting and Data System version 2.1 (PIRADSv2.1). MATERIALS & METHODS: This single-center study examined individuals who underwent 3T multiparametric prostate magnetic resonance (MR) imaging and subsequent 3T IB-MRGB. The final study cohort included 379 men (with 475 targets) divided into 3 subcohorts: biopsy-naïve men (n = 123), individuals with a history of negative trans-rectal-ultrasonography (TRUS) biopsy results (n = 106), and men with low-grade PCa under active surveillance (n = 150). csPCa was defined as having a Gleason score (GS) ≥3+4.
October 2020
Tocilizumab in Systemic Sclerosis: a Randomised, Double-blind, Placebo-controlled, Phase 3 Trial.BACKGROUND: A phase 2 trial of tocilizumab showed preliminary evidence of efficacy in systemic sclerosis. We assessed skin fibrosis and systemic sclerosis-associated interstitial lung disease (SSc-ILD) in a phase 3 trial to investigate the safety and efficacy of tocilizumab, an anti-interleukin-6 receptor antibody, in the treatment of systemic sclerosis. METHODS: In this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial, participants were recruited from 75 sites in 20 countries across Europe, North America, Latin America, and Japan. Adults with diffuse cutaneous systemic sclerosis for 60 months or less and a modified Rodnan skin score (mRSS) of 10-35 at screening were randomly assigned (1:1) with a voice-web-response system to receive subcutaneous tocilizumab 162 mg or placebo weekly for 48 weeks, stratified by IL-6 levels; participants and investigators were masked to treatment group. The primary endpoint was the difference in change from baseline to week 48 in mRSS. Percentage of predicted forced vital capacity (FVC% predicted) at week 48, time to treatment failure, and patient-reported and physician-reported outcomes were secondary endpoints. This trial is registered with ClinicalTrials.gov (number NCT02453256) and is closed to accrual.
October 2020
Inline Balloon-assisted Vascular Sheath Fragment Removal.BACKGROUND: Unretrievable foreign bodies are associated with high morbidity and mortality. While the majority of reported cases involve the venous circulation, intra-arterial foreign body displacement have the potential to migrate more distally with a higher risk for dissection and hemorrhagic complications during retrieval. As the number of intravascular procedures continues to increase, there is also likely to be a concomittant increase in the number of retrieval procedures, particular for fractured catheters and sheaths. Although snaring is frequently the traditional, 'go-to' method for retrieval, there are inherent risks of further dislodgement or fracture. CASE REPORT: We describe a case that involves retrieval of a fractured sheath that originated in the common femoral artery but migrated into the popliteal artery. Different retrieval approaches were employed, however ultimately balloon assisted, over-the-wire retrieval was the successful approach.
October 2020
Automatic Needle Tracking Using Mask R-CNN for MRI-guided Percutaneous Interventions.PURPOSE: Accurate needle tracking provides essential information for MRI-guided percutaneous interventions. Passive needle tracking using MR images is challenged by variations of the needle-induced signal void feature in different situations. This work aimed to develop an automatic needle tracking algorithm for MRI-guided interventions based on the Mask Region Proposal-Based Convolutional Neural Network (R-CNN). METHODS: Mask R-CNN was adapted and trained to segment the needle feature using 250 intra-procedural images from 85 MRI-guided prostate biopsy cases and 180 real-time images from MRI-guided needle insertion in ex vivo tissue. The segmentation masks were passed into the needle feature localization algorithm to extract the needle feature tip location and axis orientation. The proposed algorithm was tested using 208 intra-procedural images from 40 MRI-guided prostate biopsy cases, and 3 real-time MRI datasets in ex vivo tissue. The algorithm results were compared with human-annotated references.
October 2020
Characterization of Uterine Motion in Early Gestation Using MRI-Based Motion Tracking.Magnetic resonance imaging (MRI) is a promising non-invasive imaging technique that can be safely used to study placental development and function. However, studies of the human placenta performed by MRI are limited by uterine motion and motion in the uterus during MRI remains one of the major limiting factors. Here, we aimed to investigate the characterization of uterine activity during MRI in the second trimester of pregnancy using MRI-based motion tracking. In total, 46 pregnant women were scanned twice (first scan between 14 and 18 weeks and second scan between 19 and 24 weeks), and 20 pregnant subjects underwent a single MRI between 14 and 18 weeks GA, resulting in 112 MRI scans. An MRI-based algorithm was used to track uterine motion in the superior-inferior and left-right directions. Uterine contraction and maternal motion cases were separated by the experts, and unpaired Wilcoxon tests were performed within the groups of gestational age (GA), fetal sex, and placental location in terms of the overall intensity measures of the uterine activity. In total, 22.3% of cases had uterine contraction during MRI, which increased from 18.6% at 14-18 weeks to 26.4% at 19-24 weeks GA. The dominant direction of the uterine contraction and maternal motion was the superior to the inferior direction during early gestation.
October 2020
Diffusion Magnetic Resonance Imaging Phenotypes Predict Overall Survival Benefit From Bevacizumab or Surgery in Recurrent Glioblastoma With Large Tumor Burden.Background: Diffusion magnetic resonance (MR) characteristics are a predictive imaging biomarker for survival benefit in recurrent glioblastoma treated with anti-vascular endothelial growth factor (VEGF) therapy; however, its use in large volume recurrence has not been evaluated. OBJECTIVE: To determine if diffusion MR characteristics can predict survival outcomes in patients with large volume recurrent glioblastoma treated with bevacizumab or repeat resection. METHODS: A total of 32 patients with large volume (>20 cc or > 3.4 cm diameter) recurrent glioblastoma treated with bevacizumab and 35 patients treated with repeat surgery were included. Pretreatment tumor volume and apparent diffusion coefficient (ADC) histogram analysis were used to phenotype patients as having high (>1.24 µm2/ms) or low (<1.24 µm2/ms) ADCL, the mean value of the lower peak in a double Gaussian model of the ADC histogram within the contrast enhancing tumor.
October 2020
Spontaneous Resolution of Dural and Pial Arteriovenous Fistulae Arising After Superficial Temporal Artery to Middle Cerebral Artery Bypass for Moyamoya Disease.BACKGROUND: Superficial temporal artery (STA)-to-middle cerebral artery bypass is frequently performed for moyamoya disease. We discuss an unusual case in a moyamoya patient complicated by the development of dural and pial arteriovenous fistulae (AVF). Both AVF then spontaneously resolved 2 years after surgery. CASE DESCRIPTION: A patient in the fifth decade of life presented after multiple strokes resulting in right-sided weakness and numbness. Magnetic resonance imaging revealed remote strokes, and angiography revealed Suzuki grade 3 moyamoya angiopathy bilaterally. With a diminutive left STA, we initially performed left-sided dual-vessel pial synangioses. After radiographic evidence of robust revascularization and improved hemispheric perfusion, a combined right STA-middle cerebral artery bypass was done. However, routine 8-month postoperative angiography identified dural and pial AVF within the prior operative field. On the 2-year surveillance cerebral angiogram, both AVF were no longer present.
October 2020
Noninvasive Assessment of Abdominal Adipose Tissues and Quantification of Hepatic and Pancreatic Fat Fractions in Type 2 Diabetes Mellitus.The purpose of this study was to evaluate adipose tissue distributions and hepatic and pancreatic fat contents using a 6-point Dixon MRI technique in type 2 diabetes mellitus (T2DM), and to assess associations between fat distributions and biochemical markers of insulin resistance. Intra-abdominal MRI was investigated in 14 T2DM patients, 13 age- and sex-matched healthy controls (HC) and 11 young HC using a 3 T Prisma MRI scanner. All T2DM subjects completed a fasting comprehensive metabolic panel, and demographic measurements were taken according to standardized methodologies. We observed excellent correlation (R2 = 0.94) between hepatic fat fraction quantified using 6-point Dixon MRI and gold standard MRS, establishing the accuracy and reliability of the Dixon technique. Significantly increased visceral adipose tissue (VAT) volumes were found in T2DM patients compared to age-matched HC (1569.81 ± 670.62 cm3 vs. 1106.60 ± 566.85 cm3, p = .04). We also observed a trend of increasing subcutaneous adipose tissues (SAT), and total abdominal fat (TAT) volumes in T2DM compared to age-matched HC. Hepatic fat fraction percentage (HFF%) was 44.6% higher in T2DM compared to age-matched HC and 64.4% higher compared to young HC. Pancreatic fat fractions in the head and body/tail were higher in T2DM patients compared to both healthy cohorts. We also observed correlations between fat contents of the liver and pancreas in T2DM patients, and association between biochemical markers of T2DM with HFF, indicating a risk for non-alcoholic fatty liver disease among T2DM. In summary, this study provides evidence of T2DM patients having increased liver and pancreatic fat, as well as increased adipose tissues.
October 2020
Radiographic and Histopathologic Features in Sarcoidosis: A Pictorial Display.Sarcoidosis is a multisystemic granulomatous disorder that can affect virtually any organ. However, pulmonary and thoracic lymph node involvement predominates; abnormalities on chest radiographs are present in 80 to 90% of patients with sarcoidosis. High-resolution computed tomographic (HRCT) scans are superior to chest X-rays in assessing extent of disease, and some CT features may discriminate an active inflammatory component (which may be amenable to therapy) from fibrosis (for which therapy is not indicated). Typical findings on HRCT include micronodules, perilymphatic and bronchocentric distribution, perihilar opacities, and varying degrees of fibrosis. Less common findings on CT include mass-like or alveolar opacities, miliary opacities, mosaic attenuation, honeycomb cysts, and cavitation. With progressive disease, fibrosis, architectural distortion, upper lobe volume loss with hilar retraction, coarse linear bands, cysts, and bullae may be observed. We discuss the salient CT findings in patients with sarcoidosis (with a major focus on pulmonary features) and present classical radiographic and histopathological images of a few extrapulmonary sites.
October 2020
The MUC5B Promoter Variant does not Predict Progression of Interstitial Lung Disease in Systemic Sclerosis.OBJECTIVE: To investigate the prevalence of the MUC5B promoter variant rs35705950 in patients with systemic sclerosis-interstitial lung disease (SSc-ILD) and whether its presence predicts response to immunosuppression with cyclophosphamide (CYC) and mycophenolate (MMF). METHODS: SSc-ILD patients who participated in Scleroderma Lung Study (SLS) II (MMF versus CYC) were included in this study (N = 142). TaqMan Genotyping Assays were used to determine the MUC5B rs35705950 single nucleotide polymorphism. Joint models were created to examine how the presence of this variant affected the course of the forced vital capacity (FVC) over 2 years. Linear regression models were used to investigate the relationship between the presence of this variant and the change in quantitative radiographic fibrosis.
October 2020
p38 Mitogen-activated Protein Kinase Regulates Chamber-specific Perinatal Growth in Heart.In the mammalian heart, the left ventricle (LV) rapidly becomes more dominant in size and function over the right ventricle (RV) after birth. The molecular regulators responsible for this chamber-specific differential growth are largely unknown. We found that cardiomyocytes in the neonatal mouse RV had lower proliferation, more apoptosis, and a smaller average size compared with the LV. This chamber-specific growth pattern was associated with a selective activation of p38 mitogen-activated protein kinase (MAPK) activity in the RV and simultaneous inactivation in the LV. Cardiomyocyte-specific deletion of both the Mapk14 and Mapk11 genes in mice resulted in loss of p38 MAPK expression and activity in the neonatal heart. Inactivation of p38 activity led to a marked increase in cardiomyocyte proliferation and hypertrophy but diminished cardiomyocyte apoptosis, specifically in the RV. Consequently, the p38-inactivated hearts showed RV-specific enlargement postnatally, progressing to pulmonary hypertension and right heart failure at the adult stage. Chamber-specific p38 activity was associated with differential expression of dual-specific phosphatases (DUSPs) in neonatal hearts, including DUSP26. Unbiased transcriptome analysis revealed that IRE1α/XBP1-mediated gene regulation contributed to p38 MAPK-dependent regulation of neonatal cardiomyocyte proliferation and binucleation. These findings establish an obligatory role of DUSP/p38/IRE1α signaling in cardiomyocytes for chamber-specific growth in the postnatal heart.
September 2020
Fat-water Separation by Fast Metabolite Cycling Magnetic Resonance Spectroscopic Imaging at 3 T: A Method to Generate Separate Quantitative Distribution Maps of Musculoskeletal Lipid Components.PURPOSE: To provide a rapid, noninvasive fat-water separation technique that allows producing quantitative maps of particular lipid components. METHODS: The calf muscles in 5 healthy adolescents (age 12-16 years; body mass index = 20 ± 3 kg/m2 ) were scanned by two different fat fraction measurement methods. A density-weighted concentric-ring trajectory metabolite-cycling MRSI technique was implemented to collect data with a nominal resolution of 0.25 mL within 3 minutes and 16 seconds. For comparative purposes, the standard Dixon technique was performed. The two techniques were compared using structural similarity analysis. Additionally, the difference in the distribution of each lipid over the adolescent calf muscles was assessed based on the MRSI data.
September 2020
Human Islets Contain a Subpopulation of Glucagon-like Peptide-1 Secreting α Cells that is Increased in Type 2 Diabetes.OBJECTIVES: Our study shows that glucagon-like peptide-1 (GLP-1) is secreted within human islets and may play an unexpectedly important paracrine role in islet physiology and pathophysiology. It is known that α cells within rodent and human pancreatic islets are capable of secreting GLP-1, but little is known about the functional role that islet-derived GLP-1 plays in human islets. METHODS: We used flow cytometry, immunohistochemistry, perifusions, and calcium imaging techniques to analyse GLP-1 expression and function in islets isolated from cadaveric human donors with or without type 2 diabetes. We also used immunohistochemistry to analyse GLP-1 expression within islets from pancreatic biopsies obtained from living donors.
September 2020
Magnetic Resonance Imaging of High-intensity Focused Ultrasound-stimulated Drug Release from a Self-reporting Core@shell Nanoparticle Platform.We developed a theranostic approach exemplifying a concept called an "exchange method" that controls and "images" drug release from nanoparticles using magnetic resonance imaging-guided high-intensity focused ultrasound. The controllable amount of released drug and therapeutic efficacy can be self-reported by associated MRI contrast changes in solution and in cells.
September 2020
Contemporary Renal Imaging.This issue of Radiologic Clinics of North America provides a timely and practical state-of-the-art update on imaging the kidneys for the practicing radiologist. Changes in this area have occurred at a rapid pace in imaging diagnosis and treatment as well as in technologic developments and clinical management paradigms. Ongoing advances in imaging have introduced new challenges, including the optimization and standardization of protocols, interpretation, and reporting across radiologic practices. In this issue, authors provide a broad and in-depth summary of the current state-of-the-art in renal imaging with a focus on renal mass imaging and intervention by some of the leading authorities in the field today. The articles are designed as a practical and fairly comprehensive review of traditional topics covering computed tomography (CT), MR imaging, and US imaging as well as contrast reactions and imaging pitfalls. There is also an article on protocol optimization for comprehensive renal evaluation by indication and an article on renal mass reporting. Another article provides an update on solid renal mass characterization on CT and MR imaging, and one article covers renal mass biopsy and ablation. For a look into the future, additional articles focus on advances in radiomics and artificial intelligence for renal mass characterization, and a practical update on hereditary renal cell carcinoma and imaging implications. Finally, additional articles are included addressing the role of imaging in surveillance of low-risk renal masses, new thoughts on cystic renal masses, postoperative and postprocedural imaging, and imaging the kidneys in the setting of trauma.
September 2020
3-T Multiparametric MRI Followed by In-Bore MR-Guided Biopsy for Detecting Clinically Significant Prostate Cancer After Prior Negative Transrectal Ultrasound-Guided Biopsy.OBJECTIVE. The purpose of this study was to evaluate the rate of detection of clinically significant prostate cancer (csPCa), as assessed on the basis of Prostate Imaging Reporting and Data System version 2.1 (PI-RADSv2.1) guidelines, using 3-T in-bore MR-guided biopsy (MRGB) for a cohort of patients suspected of having csPCa despite having a history of recent negative transrectal ultrasound-guided biopsy results. MATERIALS AND METHODS. The cohort in this retrospective, single-center study was derived from a database of 330 patients who underwent multiparametric MRI (mpMRI) followed by in-bore transrectal 3-T MRGB. Seventy-nine patients (mean [± SD] age, 64.1 ± 8.6 years) with prior negative transrectal ultrasound-guided biopsy results and positive pre-MRGB mpMRI results (PI-RADS score ≥ 3) composed the final cohort. The rate of detection of PCa and csPCa (the latter of which was defined by a Gleason score of 3 + 4 or higher) was stratified according to updated PI-RADSv2.1 assessment.
September 2020
In Vitro Modeling of Human Brain Arteriovenous Malformation for Endovascular Simulation and Flow Analysis.BACKGROUND: Current in vitro models for human brain arteriovenous malformation (AVM) analyzing the efficacy of embolic materials or flow conditions are limited by a lack of realistic anatomic features of complex AVM nidus. The purpose of this study was to evaluate a newly developed in vitro AVM model for embolic material testing, preclinical training, and flow analysis. METHODS: Three-dimensional (3D) images of the AVM nidus were extracted from 3D rotational angiography from a patient. Inner vascular mold was printed using a 3D printer, coated with polydimethylsiloxanes, and then was removed by acetone, leaving a hollow AVM model. Injections of liquid embolic material and 4-dimensional (4D) flow magnetic resonance imaging (MRI) were performed using the AVM models. Additionally, computational fluid dynamics analysis was performed to examine the flow volume rate as compared with 4D flow MRI.
September 2020
Retrograde Transvenous Obliteration (RTO): A New Treatment Option for Hepatic Encephalopathy.Hepatic Encephalopathy (HE) is a complication of liver disease, consisting of brain dysfunction often due to portosystemic shunting of blood flow in the liver. HE can range from minimal HE, presenting with normal neurological function, to overt HE, with neurological and neuropsychiatric abnormalities. Various clinical grading systems are used to differentiate HE to provide the appropriate treatments. Traditional treatment of HE aims to identify and resolve precipitating factors through targeting hyperammonemia and administering antibiotics or probiotics. While retrograde transvenous obliteration (RTO), including balloon-occluded retrograde transvenous obliteration, coil-assisted retrograde transvenous obliteration or plug-assisted retrograde tranvenous obliteration, is an established procedure to manage gastric varices, little is known about its potential to treat HE. RTO is a procedure to occlude a spontaneous portosystemic shunt, minimizing shunting of portal blood to systemic circulation. Though there is not a large study with HE patients who have undergone RTO; the results appear promising in reducing HE. Side effects, however, should be considered in the treatment of HE such as the transient worsening of portal hypertension and the formation of additional shunts. While additional studies are needed to assess the long-term success, RTO appears to be an effective alternative method to alleviate clinical symptoms of HE when pharmacological therapies and other conservative medical managements have failed.
September 2020
Early-Stage Radiology Volume Effects and Considerations with the Coronavirus Disease 2019 (COVID-19) Pandemic: Adaptations, Risks, and Lessons Learned.OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic resulted in significant loss of radiologic volume as a result of shelter-at-home mandates and delay of non-time-sensitive imaging studies to preserve capacity for the pandemic. We analyze the volume-related impact of the COVID-19 pandemic on six academic medical systems (AMSs), three in high COVID-19 surge (high-surge) and three in low COVID-19 surge (low-surge) regions, and a large national private practice coalition. We sought to assess adaptations, risks of actions, and lessons learned. METHODS: Percent change of 2020 volume per week was compared with the corresponding 2019 volume calculated for each of the 14 imaging modalities and overall total, outpatient, emergency, and inpatient studies in high-surge AMSs and low-surge AMSs and the practice coalition.
September 2020
Percutaneous Thermal Ablation for Treatment of T1a Renal Cell Carcinomas.Based on Surveillance, Epidemiology, and End Results studies, most renal cancers are low grade and slow growing. Long-term, single-center studies show excellent outcomes for T1a renal cell carcinoma (RCC), comparable to partial nephrectomy without affecting renal function and with much lower rates of complications. However, there are no multicenter randomized controlled trials of multiple ablative modalities or comparison with partial nephrectomy, and most studies are single-arm observational studies with short-term and intermediate follow-up. For treatment of stage T1a RCC, percutaneous TA is an effective alternative to surgery with preservation of renal function, low risk, and comparable overall and disease-specific survival.
September 2020
Multiparametric MR-PET Measurements in Hypermetabolic Regions Reflect Differences in Molecular Status and Tumor Grade in Treatment-naïve Diffuse Gliomas.PURPOSE: To assess whether hypermetabolically-defined regions of interest (ROIs) on 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (FDOPA) positron emission tomography (PET) could be used to evaluate physiological features and whether there are measurable differences between molecular subtypes and tumor grades.METHODS: Sixty-eight treatment-naïve glioma patients who underwent FDOPA PET and magnetic resonance imaging (MRI) were retrospectively included. Fluid-attenuated inversion recovery hyperintense regions (FLAIRROI) were segmented. FDOPA hypermetabolic regions (FDOPAROI, tumor-to-striatum ratios > 1) within FLAIRROI were extracted. Normalized maximum standardized uptake value (nSUVmax), volume of each ROI, and median relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) within FLAIRROI or FDOPAROI were calculated. Imaging metrics were compared using Students t or Mann-Whitney U tests. Area under the curve (AUC) of receiver-operating characteristic curves were used to determine whether imaging metrics within FLAIRROI or FDOPAROI can discriminate different molecular statuses or grades.
September 2020
Engineered Hydrogels for Brain Tumor Culture and Therapy.Brain tumors' severity ranges from benign to highly aggressive and invasive. Bioengineering tools can assist in understanding the pathophysiology of these tumors from outside the body and facilitate development of suitable antitumoral treatments. Here, we first describe the physiology and cellular composition of brain tumors. Then, we discuss the development of three-dimensional tissue models utilizing brain tumor cells. In particular, we highlight the role of hydrogels in providing a biomimetic support for the cells to grow into defined structures. Microscale technologies, such as electrospinning and bioprinting, and advanced cellular models aim to mimic the extracellular matrix and natural cellular localization in engineered tumor tissues. Lastly, we review current applications and prospects of hydrogels for therapeutic purposes, such as drug delivery and co-administration with other therapies. Through further development, hydrogels can serve as a reliable option for in vitro modeling and treatment of brain tumors for translational medicine.
September 2020
Diagnostic Value of Molecular Testing in Sonographically Suspicious Thyroid Nodules.OBJECTIVE: Molecular testing can refine the diagnosis for the 20% of thyroid fine-needle aspiration biopsies that have indeterminate cytology. We assessed the diagnostic accuracy of molecular testing based on ultrasound risk classification. METHODS: This retrospective cohort study analyzed all thyroid nodules with indeterminate cytology at an academic US medical center (2012-2016). All indeterminate nodules underwent reflexive molecular testing with the Afirma Gene Expression Classifier (GEC). Radiologists performed blinded reviews to categorize each nodule according to the American Thyroid Association (ATA) ultrasound classification and the American College of Radiology Thyroid Imaging, Reporting and Data System. GEC results and diagnostic performance were compared across ultrasound risk categories.
August 2020
Abdominal Wall and Pelvic Hernias: Classic and Unusual Hernias and Their Mimics.Abdominal and pelvic wall hernias are classically defined as a weakness or opening of the muscular wall through which abdominal or pelvic tissues protrude. The aim of this manuscript is to review the imaging findings of abdominal and pelvic wall hernias and their mimics and to discuss pearls and pitfalls for accurately diagnosing and classifying these entities.
August 2020
Cost Effectiveness of External Beam Radiation Therapy versus Percutaneous Image-Guided Cryoablation for Palliation of Uncomplicated Bone Metastases.PURPOSE: To evaluate the cost effectiveness of incorporating cryoablation in the treatment regimens for uncomplicated bone metastases using radiation therapy (RT) in single-fraction RT (SFRT) or multiple-fraction RT (MFRT) regimens. MATERIALS & METHODS: A Markov model was constructed using 1-month cycles over a lifetime horizon to compare the cost effectiveness of multiple strategies, including RT followed by RT (RT-RT) for recurrent pain, RT followed by cryoablation (RT-ablation), and cryoablation followed by RT (ablation-RT). RT-RT consisted of 8 Gy in 1 fraction/8 Gy in 1 fraction (SFRT-SFRT) and 30 Gy in 10 fractions/20 Gy in 5 fractions (MFRT-MFRT). Probabilities and utilities were extracted from a search of the medical literature. Costs were calculated from a payer perspective using 2017 Medicare reimbursement in an outpatient setting. Incremental cost effectiveness ratios (ICERs) were calculated using strategies evaluated for willingness-to-pay threshold of $100,000 per quality-adjusted life-year (QALY). To account for model uncertainty, one-way and probabilistic sensitivity analyses were performed.
August 2020
Inferior Vena Cava Rupture Caused by Perforation Route through a Collateral Vein during Endovascular Treatment of Budd-Chiari Syndrome: Case Report.Budd-Chiari syndrome (BCS) is an uncommon disorder defined as an obstruction of the hepatic venous outflow. Percutaneous transluminal balloon angioplasty is a less invasive treatment option for BCS patients. However, there are no reports regarding inferior vena cava (IVC) rupture caused by perforation route through a collateral vein during treatment of BCS. Here, we report a male patient with BCS who had a long segmental obstruction of the IVC and its collateral vessels. Here, IVC rupture occurred at the distal end of the obstructed IVC during a percutaneous angioplasty; the rupture was repaired successfully with an endovascular stent graft.
August 2020
Notable Papers and Trends from 2019 in Sensors, Signals, and Imaging Informatics.OBJECTIVE: To highlight noteworthy papers that are representative of 2019 developments in the fields of sensors, signals, and imaging informatics. METHOD: A broad literature search was conducted in January 2020 using PubMed. Separate predefined queries were created for sensors/signals and imaging informatics using a combination of Medical Subject Heading (MeSH) terms and keywords. Section editors reviewed the titles and abstracts of both sets of results. Papers were assessed on a three-point Likert scale by two co-editors, rated from 3 (do not include) to 1 (should be included). Papers with an average score of 2 or less were then read by all three section editors, and the group nominated top papers based on consensus. These candidate best papers were then rated by at least six external reviewers.
August 2020
Leptomeningeal Carcinomatosis of Prostate Cancer: A Case Report and Review of the Literature.Leptomeningeal carcinomatosis is a rare complication of prostate cancer. It is likely underdiagnosed as suggested by autopsy studies and is expected to become more prevalent with increasing survival of prostate cancer patients. Prostate cancer leptomeningeal carcinomatosis is associated with rapid functional decline and a median survival of approximately 1 month. Diagnosis is challenging because the clinical manifestations are varied, and no gold-standard diagnostic approach exists. Treatment of prostate cancer leptomeningeal carcinomatosis is not standardized and multiple approaches have been reported, mostly as case studies. Herein we report a case of a 73-year-old patient with metastatic castration-resistant prostate cancer who presented to our clinic with subacute cognitive decline, ataxia, and urinary incontinence, and was found to have leptomeningeal carcinomatosis.
August 2020
Interventional Radiology Image-Guided Suprapubic Cystostomy Using Trocar versus Seldinger Technique: A Comparative Analysis of Outcomes and Complications.OBJECTIVE: To compare two techniques-trocar and Seldinger-for performing percutaneous suprapubic cystostomy. MATERIALS & METHODS: 125 patients, mean age 71.8 ± 16.5 years (range, 15-102 years), underwent primary suprapubic cystostomy from January 2013 to December 2018. Trocar access (N = 60) was performed as a single step using a puncture cannula without guidewire access. Seldinger access (N = 65) involved needle puncture, guidewire placement, and serial dilation. A retrospective review of patient records was conducted.
August 2020
Predictors and Functional Outcomes of Fast, Intermediate, and Slow Progression Among Patients With Acute Ischemic Stroke.BACKGROUND & PURPOSE: We aimed to delineate the determinants of the initial speed of infarct progression and the association of speed of infarct progression (SIP) with procedural and functional outcomes. METHODS: From a prospectively maintained stroke center registry, consecutive anterior circulation ischemic stroke patients with large artery occlusion, National Institutes of Health Stroke Scale score ≥4, and multimodal vessel, ischemic core, and tissue-at-risk imaging within 24 hours of onset were included. Initial SIP was calculated as ischemic core volume at first imaging divided by the time from stroke onset to imaging.
August 2020
Artificial Intelligence in Head and Neck Imaging: A Glimpse into the Future.Artificial intelligence, specifically machine learning and deep learning, is a rapidly developing field in imaging sciences with the potential to improve the efficiency and effectiveness of radiologists. This review covers common technical terms and basic concepts in imaging artificial intelligence and briefly reviews the application of these techniques to general imaging as well as head and neck imaging. Artificial intelligence has the potential to contribute improvements to all areas of patient care, including image acquisition, processing, segmentation, automated detection of findings, integration of clinical information, quality improvement, and research. Numerous challenges remain, however, before widespread imaging clinical adoption and integration occur.
August 2020
Type V Collagen in Scar Tissue Regulates the Size of Scar after Heart Injury.Scar tissue size following myocardial infarction is an independent predictor of cardiovascular outcomes, yet little is known about factors regulating scar size. We demonstrate that collagen V, a minor constituent of heart scars, regulates the size of heart scars after ischemic injury. Depletion of collagen V led to a paradoxical increase in post-infarction scar size with worsening of heart function. A systems genetics approach across 100 in-bred strains of mice demonstrated that collagen V is a critical driver of postinjury heart function. We show that collagen V deficiency alters the mechanical properties of scar tissue, and altered reciprocal feedback between matrix and cells induces expression of mechanosensitive integrins that drive fibroblast activation and increase scar size. Cilengitide, an inhibitor of specific integrins, rescues the phenotype of increased post-injury scarring in collagen-V-deficient mice. These observations demonstrate that collagen V regulates scar size in an integrin-dependent manner.
August 2020
Prostate Microstructure in Prostate Cancer Using 3-T MRI with Diffusion-Relaxation Correlation Spectrum Imaging: Validation with Whole-Mount Digital Histopathology.BACKGROUND: Microstructural MRI has the potential to improve diagnosis and characterization of prostate cancer (PCa), but validation with histopathology is lacking. Purpose To validate ex vivo diffusion-relaxation correlation spectrum imaging (DR-CSI) in the characterization of microstructural tissue compartments in prostate specimens from men with PCa by using registered whole-mount digital histopathology (WMHP) as the reference standard. MATERIALS & METHODS: Men with PCa who underwent 3-T MRI and robotic-assisted radical prostatectomy between June 2018 and January 2019 were prospectively studied. After prostatectomy, the fresh whole prostate specimens were imaged in patient-specific three-dimensionally printed molds by using 3-T MRI with DR-CSI and were then sliced to create coregistered WMHP slides. The DR-CSI spectral signal component fractions (fA, fB, fC) were compared with epithelial, stromal, and luminal area fractions (fepithelium, fstroma, flumen) quantified in PCa and benign tissue regions. A linear mixed-effects model assessed the correlations between (fA, fB, fC) and (fepithelium, fstroma, flumen), and the strength of correlations was evaluated by using Spearman correlation coefficients. Differences between PCa and benign tissues in terms of DR-CSI signal components and microscopic tissue compartments were assessed using two-sided t tests.
August 2020
Minimally Invasive Repair of Ascending Aortic Pseudoaneurysms: An Alternative to Open Surgical Repair in High-Risk Patients.Development of a pseudoaneurysm of the ascending aorta is an uncommon complication of aortic surgery. Several nonsurgical techniques are available for treatment of ascending aortic pseudoaneurysms (AAPs). This report outlines a single-center retrospective experience with 14 nonsurgical procedures for treatment of AAPs in 10 patients. Modified stent grafts, septal defect occlusion devices, coil embolics, and liquid embolics were deployed by transthoracic and endovascular approaches. Complete stasis of the AAP was achieved in 7 of 10 patients (70%). Mean postprocedural recoveries occurred within 3.5 days. Nonsurgical techniques for repair of AAPs offer a comparatively safe and effective alternative to open surgical repair.
July 2020
Dynamic Contrast-enhanced (DCE) MR Imaging: the Role of Qualitative and Quantitative Parameters for Evaluating Prostate Tumors Stratified by Gleason Score and PI-RADS v2.Purpose: To investigate the role of qualitative and quantitative DCE-MRI parameters in prostate cancer (PCa) stratified by whole-mount histopathology (WMHP) Gleason score (GS) and PI-RADSv2. Methods: This retrospective study included 323 PCa tumors in 254 men, who underwent 3T MRI prior to prostatectomy, 7/2009-12/2016. Qualitative DCE curve types included type 1 (progressive), type 2 (plateau) and type 3 (washout). Quantitative DCE-MRI pharmacokinetic (PK) parameters included Ktrans (influx volume transfer coefficient), Kep (efflux reflux rate constant) and iAUC (initial area under the curve). DCE-MRI features of true positive lesions were evaluated for overall, index, transition zone (TZ) and peripheral zone (PZ), based on GS grade (low = 6, high > 6) and PI-RADSv2 score using SPSSv24.
July 2020
Increased Rate of Successful First Passage Recanalization During Mechanical Thrombectomy for M2 Occlusion.BACKGROUND: Mechanical thrombectomy (MT) is the standard of care for the treatment of acute ischemic stroke (AIS) caused by anterior circulation large-vessel occlusion. However, the true safety and efficacy of MT in medium-size vessel occlusions such as the M2 segment of the middle cerebral artery have yet to be completely defined. In this study, we analyze the safety and efficacy of MT in M2 occlusions compared with M1 occlusions. METHODS: A retrospective analysis was performed of patients with AIS secondary to M1 and M2 occlusions between 2011 and 2018. The inclusion criteria were 1) AIS secondary to M1 or M2 occlusion, 2) MT performed by stentrieval technique alone, aspiration technique, or combined stentrieval-aspiration techniques. Basic patient characteristics, number of passages, first passage recanalization success (≥TICI [Thrombolysis in Cerebral Ischemia] grade 2b), total recanalization success, hemorrhagic complications (including intracerebral hemorrhage [ICH] and subarachnoid hemorrhage), and clinical outcomes were compared between both groups.
July 2020
Recent Innovations in Renal Vascular Imaging.Noninvasive imaging of the vascular renal system is a common request in diagnostic radiology. Typical indications include suspected renovascular hypertension, vasculitis, neoplasm, vascular malformation, and structural diseases of the kidney. Profound knowledge of the renal anatomy, including vascular supply and variants, is mandatory for radiologists and allows for optimized protocolling and interpretation of imaging studies. Besides renal ultrasound, computed tomography and MR imaging are commonly requested cross-sectional studies for renal and renal vascular imaging. This article discusses basic renal vascular anatomy, common imaging findings, and current and potential future imaging protocols for various renovascular pathologic conditions.
July 2020
Intravascular Carcinomatosis of the Brain: a Report of Two Cases.Although central nervous system (CNS) metastases are common in advanced cancer, CNS involvement solely by intravascular tumor cells, known as intravascular carcinomatosis, is extremely rare. We report two cases of brain metastasis in which tumor cells were restricted to the vascular lumina without parenchymal involvement, resulting in ischemic lesions. The first patient is a previously healthy young woman who presented with symptoms of community-acquired pneumonia and progressed to respiratory failure. Computed tomography of the brain showed infarcts of differing ages. At autopsy, she was found to have widely metastatic cervical squamous cell carcinoma and cerebral tumor emboli with multifocal infarcts, mainly microinfarcts. The second patient is an elderly man with cognitive impairment and mild Parkinsonism who presented with symptoms of a urinary tract infection. Magnetic resonance imaging of the brain showed atrophy and changes suggestive of chronic microvascular ischemic disease. Postmortem examination demonstrated prostatic adenocarcinoma and cerebral tumor emboli with multifocal infarcts. These cases illustrate that this pattern of intracranial metastasis may rarely be a cause of cerebral ischemic lesions and emphasize the importance of thorough pathologic examination of the brain.
July 2020
Using Chaotic Advection for Facile High-Throughput Fabrication of Ordered Multilayer Micro- and Nanostructures: Continuous Chaotic Printing.This paper introduces the concept of continuous chaotic printing, i.e. the use of chaotic flows for deterministic and continuous extrusion of fibers with internal multilayered micro- or nanostructures. Two free-flowing materials are coextruded through a printhead containing a miniaturized Kenics static mixer (KSM) composed of multiple helicoidal elements. This produces a fiber with a well-defined internal multilayer microarchitecture at high-throughput (>1.0 m min-1). The number of mixing elements and the printhead diameter determine the number and thickness of the internal lamellae, which are generated according to successive bifurcations that yield a vast amount of inter-material surface area (∽102 cm2 cm-3) at high resolution (∽10 µm). This creates structures with extremely high surface area to volume ratio (SAV). Comparison of experimental and computational results demonstrates that continuous chaotic 3D printing is a robust process with predictable output. In an exciting new development, we demonstrate a method for scaling down these microstructures by 3 orders of magnitude, to the nanoscale level (∽150 nm), by feeding the output of a continuous chaotic 3D printhead into an electrospinner. The simplicity and high resolution of continuous chaotic printing strongly supports its potential use in novel applications, including-but not limited to-bioprinting of multi-scale layered biological structures such as bacterial communities, living tissues composed of organized multiple mammalian cell types, and fabrication of smart multi-material and multilayered constructs for biomedical applications.
July 2020
PK Papyrus Coronary Stent for the Treatment of Diminutive and Tortuous Visceral Artery Pseudoaneurysms.Postsurgical pseudoaneurysms of visceral arteries can be challenging to treat, and treatment success is constrained, in part, by the capabilities of the available devices. A 62-year-old patient status post-Whipple surgery for duodenal adenocarcinoma with an unremarkable postoperative course presented to our institution 4 months after surgery for abdominal pain and was found to have a complex pseudoaneurysm of the hepatic artery/gastroduodenal stump according to an outside institution hospital CT scan. Diagnostic angiography revealed two adjacent pseudoaneurysms, a large, broad-based pseudoaneurysm adjacent to a smaller narrow-necked pseudoaneurysm within 2-3 mm of one another (Fig. 1A).
July 2020
Left Atrial Appendage Mechanical Exclusion: Procedural Planning Using Cardiovascular Computed Tomographic Angiography.Left atrial appendage (LAA) mechanical exclusion is being investigated for nonpharmacologic stroke risk reduction in selected patients with atrial fibrillation. There are multiple potential approaches in various stages of development and clinical application, each of which depends on specific cardiothoracic anatomic characteristics for optimal performance. Multiple imaging modalities can be utilized for application of this technology, with transesophageal echocardiography used for intraprocedural guidance. Cardiovascular computed tomographic angiography can act as a virtual patient avatar, allowing for the assessment of cardiac structures in the context of surrounding cardiac, coronary vascular, thoracic vascular, and visceral and skeletal anatomy, aiding preprocedural decision-making, planning, and follow-up. Although transesophageal echocardiography is used for intraprocedural guidance, computed tomographic angiography may be a useful adjunct for preprocedure assessment of LAA sizing and anatomic obstacles or contraindications to deployment, aiding in the assessment of optimal approaches. Potential approaches to LAA exclusion include endovascular occlusion, epicardial ligation, primary minimally invasive intercostal thoracotomy with thoracoscopic LAA ligation or appendectomy, and minimally invasive or open closure as part of cardiothoracic surgery for other indications. The goals of these procedures are complete isolation or exclusion of the entire appendage without leaving a residual appendage stump or residual flow with avoidance of acute or chronic damage to surrounding cardiovascular structures. The cardiovascular imager plays an important role in the preprocedural and postprocedural assessment of the patient undergoing LAA exclusion.
July 2020
The Role of Chest Imaging in Patient Management During the COVID-19 Pandemic: A Multinational Consensus Statement From the Fleischner Society.With more than 900,000 confirmed cases worldwide and nearly 50,000 deaths during the first 3 months of 2020, the coronavirus disease 2019 (COVID-19) pandemic has emerged as an unprecedented health care crisis. The spread of COVID-19 has been heterogeneous, resulting in some regions having sporadic transmission and relatively few hospitalized patients with COVID-19 and others having community transmission that has led to overwhelming numbers of severe cases. For these regions, health care delivery has been disrupted and compromised by critical resource constraints in diagnostic testing, hospital beds, ventilators, and health care workers who have fallen ill to the virus exacerbated by shortages of personal protective equipment. Although mild cases mimic common upper respiratory viral infections, respiratory dysfunction becomes the principal source of morbidity and mortality as the disease advances. Thoracic imaging with chest radiography and CT are key tools for pulmonary disease diagnosis and management, but their role in the management of COVID-19 has not been considered within the multivariable context of the severity of respiratory disease, pretest probability, risk factors for disease progression, and critical resource constraints. To address this deficit, a multidisciplinary panel comprised principally of radiologists and pulmonologists from 10 countries with experience managing patients with COVID-19 across a spectrum of health care environments evaluated the utility of imaging within three scenarios representing varying risk factors, community conditions, and resource constraints. Fourteen key questions, corresponding to 11 decision points within the three scenarios and three additional clinical situations, were rated by the panel based on the anticipated value of the information that thoracic imaging would be expected to provide. The results were aggregated, resulting in five main and three additional recommendations intended to guide medical practitioners in the use of chest radiography and CT in the management of COVID-19.
July 2020
Free-Floating Right Atrial Thrombus Removed by Aspiration Thrombectomy under Transesophageal Guidance.A 74-year-old man presented to our hospital with shortness of breath, hypoxia, and hypotension transiently requiring vasoactive support. He was diagnosed with bilateral pulmonary embolism, deep vein thrombosis, and a mobile right atrial mass.
July 2020
Fatal Intracranial Hemorrhage from Brain AVM in a 7-week-old Infant: Case Report and Recent Literature Review.Brain arteriovenous malformations (AVMs) are vascular abnormalities that typically present with spontaneous hemorrhage, seizure, or as a mass lesion. Pediatric brain AVMs are rarely diagnosed but carry a higher rate of rupture. We report a 7-week-old infant with rapid fatal intracranial hemorrhage from an undiagnosed brain. AVM confirmed at autopsy. Literature review on pediatric patients who had acute death caused by previously undiagnosed brain AVM from 1992 to 2018 revealed that cerebellum is the most frequent location of such AVMs, followed by thalamus. All the children had extensive intracranial hemorrhage that led to their deterioration despite surgical intervention.
June 2020
Mechanical Cues Regulating Proangiogenic Potential of Human Mesenchymal Stem Cells through YAP-Mediated Mechanosensing.Stem cells secrete trophic factors that induce angiogenesis. These soluble factors are promising candidates for stem cell-based therapies, especially for cardiovascular diseases. Mechanical stimuli and biophysical factors presented in the stem cell microenvironment play important roles in guiding their behaviors. However, the complex interplay and precise role of these cues in directing pro-angiogenic signaling remain unclear. Here, a platform is designed using gelatin methacryloyl hydrogels with tunable rigidity and a dynamic mechanical compression bioreactor to evaluate the influence of matrix rigidity and mechanical stimuli on the secretion of pro-angiogenic factors from human mesenchymal stem cells (hMSCs). Cells cultured in matrices mimicking mechanical elasticity of bone tissues in vivo show elevated secretion of vascular endothelial growth factor (VEGF), one of representative signaling proteins promoting angiogenesis, as well as increased vascularization of human umbilical vein endothelial cells (HUVECs) with a supplement of conditioned media from hMSCs cultured across different conditions. When hMSCs are cultured in matrices stimulated with a range of cyclic compressions, increased VEGF secretion is observed with increasing mechanical strains, which is also in line with the enhanced tubulogenesis of HUVECs. Moreover, it is demonstrated that matrix stiffness and cyclic compression modulate secretion of pro-angiogenic molecules from hMSCs through yes-associated protein activity.
June 2020
Interpretation of Pediatric Chest Radiographs by Non-radiologist Clinicians in Botswana.A manuscript by Fawole et al. [1] in this issue of Pediatric Radiology is important because the authors examine a frequent problem seen in low- to medium-income countries: the scarcity of trained radiologists to provide adequate care. As a consequence, most of the chest radiographs and other imaging studies in these pediatric populations are interpreted by clinicians. As mentioned by the authors, pneumonia is the leading cause of death in children younger than 5 years, and the great majority of deaths occur in low- to medium-income countries; chest radiographs are the primary modality used in identifying pneumonia [2]. The authors listed the limitations encountered in these countries and how, although clinicians can reliably diagnose the disease on chest radiographs, agreement is highest among radiologists. Therefore, educational approaches to improve clinicians' competence in interpreting imaging studies are welcome while we await an increase in the number of trained specialists.
June 2020
Stanford DRO Toolkit: Digital Reference Objects for Standardization of Radiomic Features.Several institutions have developed image feature extraction software to compute quantitative descriptors of medical images for radiomics analyses. With radiomics increasingly proposed for use in research and clinical contexts, new techniques are necessary for standardizing and replicating radiomics findings across software implementations. We have developed a software toolkit for the creation of 3D digital reference objects with customizable size, shape, intensity, texture, and margin sharpness values. Using user-supplied input parameters, these objects are defined mathematically as continuous functions, discretized, and then saved as DICOM objects. Here, we present the definition of these objects, parameterized derivations of a subset of their radiomics values, computer code for object generation, example use cases, and a user-downloadable sample collection used for the examples cited in this paper.
June 2020
Consensus Recommendations for a Standardized Brain Tumor Imaging Protocol for Clinical Trials in Brain Metastases.A recent meeting was held on March 22, 2019, among the FDA, clinical scientists, pharmaceutical and biotech companies, clinical trials cooperative groups, and patient advocacy groups to discuss challenges and potential solutions for increasing development of therapeutics for central nervous system metastases. A key issue identified at this meeting was the need for consistent tumor measurement for reliable tumor response assessment, including the first step of standardized image acquisition with an MRI protocol that could be implemented in multicenter studies aimed at testing new therapeutics. This document builds upon previous consensus recommendations for a standardized brain tumor imaging protocol (BTIP) in high-grade gliomas and defines a protocol for brain metastases (BTIP-BM) that addresses unique challenges associated with assessment of CNS metastases. The "minimum standard" recommended pulse sequences include: (i) parameter matched pre- and post-contrast inversion recovery (IR)-prepared, isotropic 3D T1-weighted gradient echo (IR-GRE); (ii) axial 2D T2-weighted turbo spin echo acquired after injection of gadolinium-based contrast agent and before post-contrast 3D T1-weighted images; (iii) axial 2D or 3D T2-weighted fluid attenuated inversion recovery; (iv) axial 2D, 3-directional diffusion-weighted images; and (v) post-contrast 2D T1-weighted spin echo images for increased lesion conspicuity. Recommended sequence parameters are provided for both 1.5T and 3T MR systems. An "ideal" protocol is also provided, which replaces IR-GRE with 3D TSE T1-weighted imaging pre- and post-gadolinium, and is best performed at 3T, for which dynamic susceptibility contrast perfusion is included. Recommended perfusion parameters are given.
June 2020
Approach to Pulmonary Arteriovenous Malformations: A Comprehensive Update.Pulmonary arteriovenous malformations (PAVMs) are abnormal direct vascular communications between pulmonary arteries and veins which create high-flow right-to-left shunts. They are most frequently congenital, usually in the setting of hereditary hemorrhagic telangiectasia (HHT). PAVMs may be asymptomatic or present with a wide variety of clinical manifestations such as dyspnea, hypoxemia, or chest pain. Even when asymptomatic, presence of PAVMs increases patients' risk of serious, potentially preventable complications including stroke or brain abscess. Transcatheter embolotherapy is considered the gold standard for treatment of PAVMs. Though previous guidelines have been published regarding the management of PAVMs, several aspects of PAVM screening and management remain debated among the experts, suggesting the need for thorough reexamination of the current literature. The authors of this review present an updated approach to the diagnostic workup and management of PAVMs, with an emphasis on areas of controversy, based on the latest literature and our institutional experience.
June 2020
Standardization in Quantitative Imaging: A Multicenter Comparison of Radiomic Features from Different Software Packages on Digital Reference Objects and Patient Data Sets.Radiomic features are being increasingly studied for clinical applications. We aimed to assess the agreement among radiomic features when computed by several groups by using different software packages under very tightly controlled conditions, which included standardized feature definitions and common image data sets. Ten sites (9 from the NCI's Quantitative Imaging Network] positron emission tomography-computed tomography working group plus one site from outside that group) participated in this project. Nine common quantitative imaging features were selected for comparison including features that describe morphology, intensity, shape, and texture. The common image data sets were: three 3D digital reference objects (DROs) and 10 patient image scans from the Lung Image Database Consortium data set using a specific lesion in each scan. Each object (DRO or lesion) was accompanied by an already-defined volume of interest, from which the features were calculated. Feature values for each object (DRO or lesion) were reported. The coefficient of variation (CV), expressed as a percentage, was calculated across software packages for each feature on each object. Thirteen sets of results were obtained for the DROs and patient data sets. Five of the 9 features showed excellent agreement with CV < 1%; 1 feature had moderate agreement (CV < 10%), and 3 features had larger variations (CV ≥ 10%) even after attempts at harmonization of feature calculations. This work highlights the value of feature definition standardization as well as the need to further clarify definitions for some features.
June 2020
Alternatives to Surgery for Early-Stage Non-Small Cell Lung Cancer: Thermal Ablation.Thermal ablation involves the application of heat or cold energy to the lung under image guidance to eradicate tumors. It is indicated for treatment of early-stage non-small cell lung cancer in nonsurgical patients. Ablation technologies have advanced, such that nearly all small tumors can now be treated safely and effectively. Ablation does not cause a lasting decline in pulmonary function tests and may therefore be used to treat multiple synchronous and metachronous lung tumors, a chief advantage over other treatments. Large series with intermediate- and long-term data have been reported showing favorable overall survival, similar to radiation therapy.
June 2020
Discovering and Interpreting Transcriptomic Drivers of Imaging Traits Using Neural Networks.Motivation: Cancer heterogeneity is observed at multiple biological levels. To improve our understanding of these differences and their relevance in medicine, approaches to link organ- and tissue-level information from diagnostic images and cellular-level information from genomics are needed. However, these 'radiogenomic' studies often use linear or shallow models, depend on feature selection, or consider one gene at a time to map images to genes. Moreover, no study has systematically attempted to understand the molecular basis of imaging traits based on the interpretation of what the neural network has learned. These studies are thus limited in their ability to understand the transcriptomic drivers of imaging traits, which could provide additional context for determining clinical outcomes.
June 2020
Treatment with Mycophenolate and Cyclophosphamide Leads to Clinically Meaningful Improvements in Patient-Reported Outcomes in Scleroderma Lung Disease: Results of Scleroderma Lung Study II.OBJECTIVE: Our objective was to determine if treatment with cyclophosphamide (CYC) and mycophenolate mofetil (MMF) improves patient-reported outcomes (PROs) among patients with systemic sclerosis-related interstitial lung disease (SSc-ILD). METHODS: This study examined PROs in patients with SSc-ILD (N = 142) who participated in the Scleroderma Lung Study II, a randomized controlled trial comparing MMF for 2 years with oral CYC for 1 year followed by 1 year of a placebo. Joint models were created to evaluate the course of PROs over 2 years. The difference in PRO scores from baseline to 24 months was measured, and the percentage of patients meeting the minimum clinically important difference (MCID) was calculated. Correlations between PROs and SSc-ILD disease severity measures were also examined.
June 2020
Biodegradable β-Cyclodextrin Conjugated Gelatin Methacryloyl Microneedle for Delivery of Water-Insoluble Drug.Transdermal delivery of water-insoluble drugs via hydrogel-based microneedle (MN) arrays is crucial for improving their therapeutic efficacies. However, direct loading of water-insoluble drug into hydrophilic matrices remains challenging. Here, a biodegradable MN array patch that is fabricated from naturally derived polymer conjugates of gelatin methacryloyl and β-cyclodextrin (GelMA-β-CD) is reported. When curcumin, an unstable and water-insoluble anticancer drug, is loaded as a model drug, its stability and solubility are improved due to the formation of an inclusion complex. The polymer-drug complex GelMA-β-CD/CUR can be formulated into MN arrays with sufficient mechanical strength for skin penetration and tunable drug release profile. Anticancer efficacy of released curcumin is observed in three-dimensional B16F10 melanoma models. The GelMA-β-CD/CUR MN exhibits relatively higher therapeutic efficacy through more localized and deeper penetrated manner compared with a control nontransdermal patch. In vivo studies also verify biocompatibility and degradability of the GelMA-β-CD MN arrays patch.
May 2020
Safety and Efficacy of VB-111, an Anticancer Gene Therapy, in Patients with Recurrent Glioblastoma: Results of a Phase I/II Study.BACKGROUND: VB-111 is a non-replicating adenovirus carrying a Fas-chimera transgene, leading to targeted apoptosis of tumor vascular endothelium and induction of a tumor-specific immune response. This phase I/II study evaluated the safety, tolerability, and efficacy of VB-111 with and without bevacizumab in recurrent glioblastoma (rGBM). METHODS: Patients with rGBM (n = 72) received VB-111 in 4 treatment groups: subtherapeutic (VB-111 dose escalation), limited exposure (LE; VB-111 monotherapy until progression), primed combination (VB-111 monotherapy continued upon progression with combination of bevacizumab), and unprimed combination (upfront combination of VB-111 and bevacizumab). The primary endpoint was median overall survival (OS). Secondary endpoints were safety, overall response rate, and progression-free survival (PFS).
May 2020
Integration of Chest CT CAD into the Clinical Workflow and Impact on Radiologist Efficiency.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 2020
Diffusion MRI Changes in the Anterior Subventricular Zone Following Chemoradiation in Glioblastoma with Posterior Ventricular Involvement.INTRODUCTION: There is growing evidence that the subventricular zone (SVZ) plays a key role in glioblastoma (GBM) tumorigenesis. However, little is known regarding how the SVZ, which is a harbor for adult neural stem cells, may be influenced by chemoradiation. The current diffusion-weighted imaging (DWI) study explored ipsilateral and contralateral alterations in the anterior SVZ in GBM patients with posterior enhancing lesions following chemoradiation. METHODS: Forty GBM patients with tumor involvement in the posterior SVZ (mean age = 57 ± 10; left-hemisphere N = 25; right-hemisphere N = 15) were evaluated using DWI before and after chemoradiation. Regions-of-interest were drawn on the ipsilesional and contralesional anterior SVZ on apparent diffusion coefficient (ADC) maps for both timepoints. ADC histogram analysis was performed by modeling a bimodal, double Gaussian distribution to obtain ADCL, defined as the mean of the lower Gaussian distribution.
May 2020
A Randomized Controlled Phase III Study of VB-111 Combined with Bevacizumab vs Bevacizumab Monotherapy in Patients with Recurrent Glioblastoma (GLOBE).BACKGROUND: Ofranergene obadenovec (VB-111) is an anticancer viral therapy that demonstrated in a phase II study a survival benefit for patients with recurrent glioblastoma (rGBM) who were primed with VB-111 monotherapy that was continued after progression with concomitant bevacizumab. METHODS: This pivotal phase III randomized, controlled trial compared the efficacy and safety of upfront combination of VB-111 and bevacizumab versus bevacizumab monotherapy. Patients were randomized 1:1 to receive VB-111 1013 viral particles every 8 weeks in combination with bevacizumab 10 mg/kg every 2 weeks (combination arm) or bevacizumab monotherapy (control arm). The primary endpoint was overall survival (OS), and secondary endpoints were objective response rate (ORR) by Response Assessment in Neuro-Oncology (RANO) criteria and progression-free survival (PFS).
May 2020
ACR Appropriateness Criteria® Primary Bone Tumors.Although primary bone tumors are relatively uncommon, appropriate imaging evaluation is essential when they are suspected or incidentally detected. In almost all cases, radiographs are the most appropriate initial imaging study for screening and characterization of primary bone tumors. Radiographs often provide sufficient information for diagnosis and to guide the treating clinician. However, when conventional radiographs alone are inadequate, they still often guide the selection of the most appropriate next step for advanced imaging. MRI and CT are typically the most appropriate next step. MRI provides excellent soft-tissue contrast allowing for evaluation of the tissue composition (such as fat, hemorrhage, fluid levels) and anatomic extent of bone tumors. CT provides complementary information, with its ability to detect subtle matrix mineralization or periosteal reaction that may not be seen on radiographs or MRI. This publication focuses on six common variants to guide diagnosis and management of primary bone tumors. In addition to conventional radiographs, appropriate use of MRI, CT, PET/CT, 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 2020
Microneedle Drug Eluting Balloon for Enhanced Drug Delivery to Vascular Tissue.High rates of restenosis and neointimal formation have driven increasing interest in the application of drug eluting balloons (DEB) as counteractive measures for intraluminal drug delivery. The use of DEBs eliminates the need for stents so that serious side effects including in-stent restenosis and stent thrombosis can be avoided and long-term medication of anti-platelet agent is not needed. Despite their benefits, DEBs have poor drug delivery efficiency due to short balloon inflation times (30-60 s) that limit the passive drug diffusion from the balloon surface to the luminal lesion. To increase drug delivery efficiency, a microneedle DEB (MNDEB) was developed by a conformal transfer molding process using a thin polydimethylsiloxane mold bearing a negative array of MNs of 200 μm in height. A MN array composed of UV curable resin was formed onto the surface of DEB, and drugs were coated onto the structure. The mechanical properties of the MN array were investigated and MN penetration into luminal vasculature was confirmed in vivo. An increase in drug delivery efficiency compared to a standard DEB was demonstrated in an in vivo test in a rabbit aorta. Finally, the superior therapeutic efficacy of MNDEBs was evaluated using an atherosclerosis rabbit model.
May 2020
Ferrous Sulfate-directed Dual-cross-linked Hyaluronic Acid Hydrogels with Long-term Delivery of Donepezil.Ferrous sulfate (FeSO4)-directed dual-cross-linked hydrogels were designed for application in single-syringe injections. The use of FeSO4, rather than other iron salts, can modulate the gelation time and make it available for subcutaneous injection with a single syringe. These hydrogels are based on hyaluronic acid-dopamine (HA-dp) that contain donepezil (DPZ)-entrapping poly(lactic-co-glycolic acid) (PLGA) microsphere (MS). Although DPZ has been administered orally, its sustained release formulation via subcutaneous injection may reduce the dosing frequency for patients with Alzheimer's disease. The HA-dp conjugate was synthesized via an amide bond reaction for coordination of dp with a metal ion (Fe2+ or Fe3+) and self-polymerization of dp. The HA-dp/DPZ-loaded PLGA MS (PD MS)/FeSO4 gel system was considerably hardened via both the coordination of the metal ion with HA-dp and covalent bonding of dp. In addition, a quick restoration of the collapsed gel structure and sustained DPZ release from the HA-dp/PD MS/FeSO4 structure were achieved. The pharmacokinetic parameters after its subcutaneous injection in a rat indicate the sustained release and absorption of DPZ from the HA-dp/PD MS/FeSO4 system. The proposed system can be prepared by a simple method and can be efficiently and safely used for the long-term delivery of DPZ after the subcutaneous injection.
May 2020
State of the Art: Toward Improving Outcomes of Lung and Liver Tumor Biopsies in Clinical Trials-A Multidisciplinary Approach.PURPOSE: National Cancer Institute (NCI)-sponsored clinical trial network studies frequently require biopsy specimens for pharmacodynamic and molecular biomarker analyses, including paired pre- and post-treatment samples. The purpose of this meeting of NCI-sponsored investigators was to identify local institutional standard procedures found to ensure quantitative and qualitative specimen adequacy. METHODS: NCI convened a conference on best biopsy practices, focusing on the clinical research community. Topics discussed were (1) criteria for specimen adequacy in the personalized medicine era, (2) team-based approaches to ensure specimen adequacy and quality control, and (3) risk considerations relevant to academic and community practitioners and their patients.
May 2020
24/7/365 Neuroradiologist Coverage Improves Resident Perception of Educational Experience, Referring Physician Satisfaction, and Turnaround Time.PURPOSE: To quantitatively and qualitatively assess the impact of attending neuroradiology coverage on radiology resident perceptions of the on-call experience, referring physician satisfaction, and final report turnaround times. MATERIALS AND METHODS: 24/7/365 attending neuroradiologist coverage began in October 2016 at our institution. In March 2017, an online survey of referring physicians, (emergency medicine, neurosurgery, and stroke neurology) and radiology residents was administered at a large academic medical center. Referring physicians were queried regarding their perceptions of patient care, report accuracy, timeliness, and availability of attending radiologists before and after the implementation of overnight neuroradiology coverage. Radiology residents were asked about their level of independence, workload, and education while on-call. Turnaround time (TAT) was measured over a 5-month period before and after the implementation of overnight neuroradiology coverage.
May 2020
Engineering Tough, Injectable, Naturally Derived, Bioadhesive Composite Hydrogels.Engineering mechanically robust bioadhesive hydrogels that can withstand large strains may open new opportunities for the sutureless sealing of highly stretchable tissues. While typical chemical modifications of hydrogels, such as increasing the functional group density of crosslinkable moieties and blending them with other polymers or nanomaterials have resulted in improved mechanical stiffness, the modified hydrogels have often exhibited increased brittleness resulting in deteriorated sealing capabilities under large strains. Furthermore, highly elastic hydrogels, such as tropoelastin derivatives are highly expensive. Here, gelatin methacryloyl (GelMA) is hybridized with methacrylate-modified alginate (AlgMA) to enable ion-induced reversible crosslinking that can dissipate energy under strain. The hybrid hydrogels provide a photocrosslinkable, injectable, and bioadhesive platform with an excellent toughness that can be tailored using divalent cations, such as calcium. This class of hybrid biopolymers with more than 600% improved toughness compared to GelMA may set the stage for durable, mechanically resilient, and cost-effective tissue sealants. This strategy to increase the toughness of hydrogels may be extended to other crosslinkable polymers with similarly reactive moieties.
May 2020
Influence of the Location and Zone of Tumor in Prostate Cancer Detection and Localization on 3-T Multiparametric MRI Based on PI-RADS Version 2.OBJECTIVE. The objective of our study was to determine the performance of 3-T multiparametric MRI (mpMRI) for prostate cancer (PCa) detection and localization, stratified by anatomic zone and level, using Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) and whole-mount histopathology (WMHP) as reference. MATERIALS AND METHODS. Multiparametric MRI examinations of 415 consecutive men were compared with thin-section WMHP results. A genitourinary radiologist and pathologist collectively determined concordance. Two radiologists assigned PI-RADSv2 scores and sector location to all detected foci by consensus. Tumor detection rates were calculated for clinical and pathologic (tumor location and zone) variables. Both rigid and adjusted sector-matching models were used to account for fixation-related issues.
May 2020
Intermodality Feature Fusion Combining Unenhanced Computed Tomography and Ferumoxytol-enhanced Magnetic Resonance Angiography for Patient-specific Vascular Mapping in Renal Impairment.OBJECTIVE: The purpose of this study was to establish the feasibility of fusing complementary, high-contrast features from unenhanced computed tomography (CT) and ferumoxytol-enhanced magnetic resonance angiography (FE-MRA) for preprocedural vascular mapping in patients with renal impairment. METHODSS: In this Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant study, 15 consecutive patients underwent both FE-MRA and unenhanced CT scanning, and the complementary high-contrast features from both modalities were fused to form an integrated, multifeature image. Source images from CT and MRA were segmented and registered. To validate the accuracy, precision, and concordance of fused images to source images, unambiguous landmarks, such as wires from implantable medical devices or indwelling catheters, were marked on three-dimensional (3D) models of the respective modalities, followed by rigid co-registration, interactive fusion, and fine adjustment. We then compared the positional offsets using pacing wires or catheters in the source FE-MRA (defined as points of interest [POIs]) and fused images (n = 5 patients, n = 247 points). Points within 3D image space were referenced to the respective modalities: x (right-left), y (anterior-posterior), and z (cranial-caudal). The respective 3D orthogonal reference axes from both image sets were aligned, such that with perfect registration, a given point would have the same (x, y, z) component values in both sets. The 3D offsets (Δx mm, Δy mm, Δz mm) for each of the corresponding POIs represent nonconcordance between the source FE-MRA and fused images. The offsets were compared using concordance correlation coefficients. Interobserver agreement was assessed using intraclass correlation coefficients and Bland-Altman analyses.
May 2020
Prostate Diffusion MRI with Minimal Echo Time Using Eddy Current Nulled Convex Optimized Diffusion Encoding.BACKGROUND: Prostate diffusion-weighted imaging (DWI) using monopolar encoding is sensitive to eddy-current-induced distortion artifacts. Twice-refocused bipolar encoding suppresses eddy current artifacts, but increases echo time (TE), leading to lower signal-to-noise ratio (SNR). Optimization of the diffusion encoding might improve prostate DWI. PURPOSE: To evaluate eddy current nulled convex optimized diffusion encoding (ENCODE) for prostate DWI with minimal TE. STUDY TYPE: Prospective cohort study. POPULATION: A diffusion phantom, an ex vivo prostate specimen, 10 healthy male subjects (27 ± 3 years old), and five prostate cancer patients (62 ± 7 years old). FIELD STRENGTH/SEQUENCE: 3T; single-shot spin-echo echoplanar DWI. ASSESSMENT: Eddy-current artifacts, TE, SNR, apparent diffusion coefficient (ADC), and image quality scores from three independent readers were compared between monopolar, bipolar, and ENCODE prostate DWI for standard-resolution (1.6 × 1.6 mm2 , partial Fourier factor [pF] = 6/8) and higher-resolution protocols (1.6 × 1.6 mm2 , pF = off; 1.0 × 1.0 mm2 , pF = 6/8). STATISTICAL TESTING: SNR and ADC differences between techniques were tested with Kruskal-Wallis and Wilcoxon signed-rank tests (P < 0.05 considered significant).
April 2020
Thinning or Dehiscence of Bone in Structures of the Middle Cranial Fossa Floor in Superior Semicircular Canal Dehiscence.BACKGROUND: Superior semicircular canal dehiscence (SSCD) is a rare inner ear disorder; currently, it is unknown whether the etiopathology underlying this structural irregularity affects neighboring structures. The goal is to investigate the prevalence of bone thinning in areas of the middle cranial fossa (MCF) floor in SSCD and non-SSCD patients. METHODS: This retrospective study analyzed 100 patients from March 2011 to June 2017 at a tertiary referral center. 100 patients undergoing 118 SSCD repair surgeries (18 bilateral) were identified. 12 SSCD ears were excluded due to lack of pre-operative computed tomography (CT) scans or history of prior SSCD repair at an outside facility. Non-SSCD ears were identified from routinely-obtained CT scans for temporal bone fracture (fractured sides excluded) for a total of 101 ears; 26 non-SSCD ears were excluded due to lack of high-resolution imaging.
April 2020
Obstructed Membranous Transformation of the Inferior Vena Cava in Patients with Hepatic Vein-type Budd-Chiari Syndrome: A Case Series.Budd-Chiari syndrome (BCS) is a rare disease characterized by the obstruction of hepatic venous outflow due to occlusion of the hepatic vein (HV) or the inferior vena cava (IVC). The pathophysiology of IVC and HV membranous transformation, which can form in isolation or simultaneously, remains unclear in patients with combined-type BCS. Here we report three cases of patients with BCS demonstrating conversion from HV-type to combined-type. Three patients with only HV-type BCS underwent percutaneous balloon angioplasty (PTA) of the obstructed HV. During follow up, membranous transformation of the IVC was observed. This condition was subsequently treated with PTA of the IVC. These cases demonstrate that HV-type BCS may convert to combined-type BCS.
April 2020
An Electronic Form for Reporting Results of Targeted Prostate Biopsy: Urology Integrated Diagnostic Report (Uro-IDR).OBJECTIVE: To detail the development of an electronic report that graphically conveys all relevant information from targeted prostate biopsy. METHODS: The Urology Integrated Diagnostic Report (Uro-IDR) is based on a published framework (RadPath) which enables the compilation of diagnostic data from urology, radiology, and pathology. Each component of the Uro-IDR is generated by the contributing clinician, is assembled in one document, and provides correlation of the 3 inputs at a glance. Upon completion, the Uro-IDR is automatically linked to the electronic medical record as an interactive file and can also be downloaded for offline sharing as a PDF.
April 2020
Existence of a Dose-Length Effect in Spinal Nerves Receiving Single-Session Stereotactic Ablative Radiation Therapy.PURPOSE: The spinal nerves have been observed to have a similar single-session dose tolerance to that of the spinal cord in pigs. Small-animal studies have shown that spinal cord dose tolerance depends on the length irradiated. This work aims to determine whether a dose-length effect exists for spinal nerves. METHODS AND MATERIALS: Twenty-seven Yucatan minipigs underwent computed tomography and magnetic resonance imaging for treatment planning, followed by single-session stereotactic ablative radiation therapy. A 0.5 cm length of the left-sided C6, C7, and C8 spinal nerves was targeted. The pigs were distributed into 6 groups with prescription doses of 16 Gy (n = 5), 18 Gy (n = 5), 20 Gy (n = 5), 22 Gy (n = 5), 24 Gy (n = 5), or 36 Gy (n = 2) and corresponding maximum doses of 16.7, 19.1, 21.3, 23.1, 25.5, and 38.6 Gy, respectively. Neurologic status was assessed with a serial electrodiagnostic examination and daily observation of gait for approximately 52 weeks. A histopathologic examination of paraffin-embedded sections with Luxol fast blue/periodic acid-Schiff's staining was also performed.
April 2020
Updated 10-year Outcomes of Percutaneous Radiofrequency Ablation as First-line Therapy for Single Hepatocellular Carcinoma < 3 cm: Emphasis on Association of Local Tumor Progression and Overall Survival.OBJECTIVES: The purpose of this study was to evaluate the 10-year overall survival and local tumor progression (LTP) of percutaneous radiofrequency ablation (RFA) for single nodular hepatocellular carcinoma (HCC) < 3 cm using a large longitudinal hospital registry and clinical factors associated with overall survival and LTP. METHODS: A total of 467 newly diagnosed patients with single nodular HCC < 3 cm who underwent RFA as first-line therapy between January 2008 to December 2016 were analyzed. Overall survival and LTP were estimated using the Kaplan-Meier method. Cox regression and competing risks Cox regression analysis were performed to identify prognostic factors for overall survival and LTP, respectively.
April 2020
Human Placenta Blood Flow During Early Gestation With Pseudocontinuous Arterial Spin Labeling MRI.BACKGROUND: Noninvasive measurement of placental blood flow is the major technical challenge for predicting ischemic placenta (IPD). Pseudocontinuous arterial spin labeling (pCASL) MRI was recently shown to be promising, but the potential value in predicting the subsequence development of IPD is not known. PURPOSE: To derive global and regional placental blood flow parameters from longitudinal measurements of pCASL MRI and to assess the associations between perfusion-related parameters and IPD. STUDY TYPE: Prospective. POPULATION: Eighty-four women completed two pCASL MRI scans (first; 14-18 weeks and second; 19-24 weeks) from prospectively recruited 118 subjects. A total of 69 subjects were included for the analysis, of which 15 subjects developed IPD. FIELD STRENGTH/SEQUENCE: 3T/T2 -weighted half-Fourier single-shot turbo spin-echo (HASTE) and pCASL. ASSESSMENT: Four perfusion-related parameters in the placenta were derived: placenta volume, placental blood flow (PBF), high PBF (hPBF), and relative hPBF. The longitudinal changes of the parameters and their association with IPD were tested after being normalizing to the 16th and 20th weeks of gestation. STATISTICAL TESTS: Comparisons between two gestational ages within subjects were performed using the paired Wilcoxon tests, and comparisons between normal and IPD groups were performed using the unpaired Wilcoxon tests.
April 2020
MRI-guided Targeted Needle Placement During Motion Using Hydrostatic Actuators.BACKGROUND: Magnetic resonance imaging (MRI) has unique advantages for guiding interventions, but the narrow space is a major challenge. This study evaluates the feasibility of a remote-controlled hydrostatic actuator system for MRI-guided targeted needle placement. METHODS: The effects of the hydrostatic actuator system on MR image quality were evaluated. Using a reference step-and-shoot method (SS) and the proposed actuator-assisted method (AA), two operators performed MRI-guided needle placement in targets (n = 12) in a motion phantom.
April 2020
Stimuli-Responsive Delivery of Growth Factors for Tissue Engineering.Growth factors (GFs) play a crucial role in directing stem cell behavior and transmitting information between different cell populations for tissue regeneration. However, their utility as therapeutics is limited by their short half-life within the physiological microenvironment and significant side effects caused by off-target effects or improper dosage. "Smart" materials that can not only sustain therapeutic delivery over a treatment period but also facilitate on-demand release upon activation are attracting significant interest in the field of GF delivery for tissue engineering. Three properties are essential in engineering these "smart" materials: 1) the cargo vehicle protects the encapsulated therapeutic; 2) release is targeted to the site of injury; 3) cargo release can be modulated by disease-specific stimuli. The aim of this review is to summarize the current research on stimuli-responsive materials as intelligent vehicles for controlled GF delivery; Five main subfields of tissue engineering are discussed: skin, bone and cartilage, muscle, blood vessel, and nerve. Challenges in achieving such "smart" materials and perspectives on future applications of stimuli-responsive GF delivery for tissue regeneration are also discussed.
April 2020
A Novel Anthropomorphic Multimodality Phantom for MRI-based Radiotherapy Quality Assurance Testing.PURPOSE: Increased utilization of magnetic resonance imaging (MRI) in radiotherapy has caused a growing need for phantoms that provide tissue-like contrast in both computed tomography (CT) and MRI images. Such phantoms can be used to compare MRI-based processes with CT-based clinical standards. Here, we develop and demonstrate the clinical utility of a three-dimensional (3D)-printed anthropomorphic pelvis phantom containing materials capable of T1, T2, and electron density matching for a clinically relevant set of soft tissues and bone. METHODS: The phantom design was based on a male pelvic anatomy template with thin boundaries separating tissue types. Slots were included to allow insertion of various dosimeters. The phantom structure was created using a 3D printer. The tissue compartments were filled with carrageenan-based materials designed to match the T1 and T2 relaxation times and electron densities of the corresponding tissues. CT and MRI images of the phantom were acquired and used to compare phantom T1 and T2 relaxation times and electron densities to literature-reported values for human tissue. To demonstrate clinical utility, the phantom was used for end-to-end testing of an MRI-only treatment simulation and planning workflow. Based on a T2 -weighted MRI image, synthetic CT (sCT) images were created using a statistical decomposition algorithm (MRIPlanner, Spectronic Research AB, Sweden) and used for dose calculation of volumetric-modulated arc therapy (VMAT) and seven-field intensity-modulated radiation therapy (IMRT) prostate plans. The plans were delivered on a Truebeam STX (Varian Medical Systems, Palo Alto, CA), with film and a 0.3 cc ion chamber used to measure the delivered dose. Doses calculated on the CT and sCTs were compared using common dose volume histogram metrics.
April 2020
First-in-Human Phase I Study to Evaluate the Brain-Penetrant PI3K/mTOR Inhibitor GDC-0084 in Patients with Progressive or Recurrent High-Grade Glioma.PURPOSE: GDC-0084 is an oral, brain-penetrant small-molecule inhibitor of PI3K and mTOR. A first-in-human, phase I study was conducted in patients with recurrent high-grade glioma. PATIENTS AND METHODS: GDC-0084 was administered orally, once daily, to evaluate safety, pharmacokinetics (PK), and activity. Fluorodeoxyglucose-PET (FDG-PET) was performed to measure metabolic responses.
April 2020
Gelatin Methacryloyl Microneedle Patches for Minimally Invasive Extraction of Skin Interstitial Fluid.The extraction of interstitial fluid (ISF) from skin using microneedles (MNs) has attracted growing interest in recent years due to its potential for minimally invasive diagnostics and biosensors. ISF collection by absorption into a hydrogel MN patch is a promising way that requires the materials to have outstanding swelling ability. Here, a gelatin methacryloyl (GelMA) patch is developed with an 11 × 11 array of MNs for minimally invasive sampling of ISF. The properties of the patch can be tuned by altering the concentration of the GelMA prepolymer and the crosslinking time; patches are created with swelling ratios between 293% and 423% and compressive moduli between 3.34 MPa and 7.23 MPa. The optimized GelMA MN patch demonstrates efficient extraction of ISF. Furthermore, it efficiently and quantitatively detects glucose and vancomycin in ISF in an in vivo study. This minimally invasive approach of extracting ISF with a GelMA MN patch has the potential to complement blood sampling for the monitoring of target molecules from patients.
March 2020
BRCA and Beyond: Comprehensive Image-rich Review of Hereditary Breast and Gynecologic Cancer Syndromes.In addition to the well-characterized BRCA1 and BRCA2 hereditary breast and ovarian cancer syndromes, many other syndromes that are associated with genetic mutations predispose individuals to an increased risk of breast and gynecologic malignancies. Many mutated genes encode for tumor-suppressor products and are inherited in an autosomal dominant manner. Mutations markedly increase an individual's lifetime risk of cancers in different organ systems, depending on the associated syndrome. These syndromes include Lynch syndrome, the most common hereditary cause of endometrial cancer, and Peutz-Jeghers syndrome, which increases the risks of breast cancer, ovarian cancer, and cervical adenoma malignum. Li-Fraumeni syndrome and Cowden syndrome increase the risk of breast cancer, and Gorlin syndrome increases the risk of ovarian fibromas. With advances in genetic testing, clinicians' knowledge and awareness of the numerous additional genes associated with breast and ovarian cancers, such as ATM, CHEK2, and PALB2, are rapidly expanding. Radiologists have essential roles in patient management, which include developing optimal screening protocols for these patients and closely monitoring them for the development or recurrence of disease-specific malignancies. Radiologists' roles continue to increase and evolve as more mutations are identified and high-risk imaging screening recommendations expand to identify these patients. Understanding the epidemiologic, genetic, and pathophysiologic features and the cancers associated with these syndromes enables radiologists to appropriately contribute to patient management, ensure accurate and timely diagnosis, and make syndrome-specific imaging recommendations. ©RSNA, 2020.
March 2020
A Case Report of a Novel Germline GNAS Mutation in Sonic Hedgehog Activated Medulloblastoma.Medulloblastoma is the most common malignant brain tumor of childhood. Our knowledge of medulloblastoma has been advanced by the study of genetic cancer predisposition syndromes, which are associated with approximately 6% of cases. We describe a case of a novel germline GNAS mutation in medulloblastoma, in accordance with the CARE guidelines.
March 2020
Longitudinal MRI Findings in Patients with Newly Diagnosed Glioblastoma after Intraoperative Radiotherapy.BACKGROUND AND PURPOSE: Post-radiation treatment effects (pseudoprogression/radionecrosis) may bias MRI-based tumor response evaluation. To understand these changes specifically after high doses of radiotherapy, we analyzed MRIs of patients enrolled in the INTRAGO study (NCT02104882), a phase I/II dose-escalation trial of intraoperative radiotherapy (20-40 Gy) in glioblastoma. METHODS: INTRAGO patients were evaluated and compared to control patients who received standard therapy with focus on contrast enhancement patterns/volume, T2 lesion volume, and mean rCBV.
March 2020
Multi-scale Cellular Engineering: From Molecules to Organ-on-a-chip.Recent technological advances in cellular and molecular engineering have provided new insights into biology and enabled the design, manufacturing, and manipulation of complex living systems. Here, we summarize the state of advances at the molecular, cellular, and multi-cellular levels using experimental and computational tools. The areas of focus include intrinsically disordered proteins, synthetic proteins, spatiotemporally dynamic extracellular matrices, organ-on-a-chip approaches, and computational modeling, which all have tremendous potential for advancing fundamental and translational science. Perspectives on the current limitations and future directions are also described, with the goal of stimulating interest to overcome these hurdles using multi-disciplinary approaches.
March 2020
Onset to Reperfusion Time as a Determinant of Outcomes Across a Wide Range of ASPECTS in Endovascular Thrombectomy: Pooled Analysis of the SWIFT, SWIFT PRIME, and STAR Studies.BACKGROUND: The time-benefit relationship of endovascular thrombectomy (EVT) according to the size of the core infarct has been incompletely explored in prior studies. We investigated whether established infarct core size on baseline imaging modifies the relationship between onset-to-reperfusion time (OTR) and functional outcomes in patients with acute ischemic stroke treated with EVT. METHODS: We analyzed a database containing individual patient data pooled from three prospective Solitaire stent retriever studies. The inclusion criteria were treatment with a Solitaire device and achievement of substantial reperfusion (modified Thrombolysis in Cerebral Infarction 2b-3). Main analyses were performed in patients with baseline Alberta Stroke Program Early CT Scores (ASPECTSs) of 7-10.
March 2020
Tumescent Injections in Subcutaneous Pig Tissue Disperse Fluids Volumetrically and Maintain Elevated Local Concentrations of Additives for Several Hours, Suggesting a Treatment for Drug Resistant Wounds.PURPOSE: Bolus injection of fluid into subcutaneous tissue results in accumulation of fluid at the injection site. The fluid does not form a pool. Rather, the injection pressure forces the interstitial matrix to expand to accommodate the excess fluid in its volume, and the fluid becomes bound similar to that in a hydrogel. We seek to understand the properties and dynamics of externally tumesced (swollen) subcutaneous tissue as a first step in assessing whether tumescent antibiotic injections into wounds may provide a novel method of treatment. METHODS: Subcutaneous injections of saline are performed in live and dead pigs and the physical properties (volume, expansion ratio, residence time, apparent diffusion constant) of the resulting fluid deposits are observed with diffusion-weighted magnetic resonance imaging, computed tomography, and 3D scanning.
March 2020
Detection of Acute Infarction on Non-Contrast-enhanced CT: Closing the Gap with MRI via Machine Learning.Stroke is the leading cause of substantial disability and is the fifth leading cause of death in the United States, costing our health care system more than $20 billion per year. Over the past 5 years, the treatment of acute ischemic stroke has been revolutionized. The ability to offer reperfusion therapies to a broader population of patients with acute ischemic stroke is one of the greatest achievements of cerebrovascular medicine in recent years and was made possible in part by the effective use of pretreatment neuroimaging. One of the key variables to improve patient selection for reperfusion therapies is the estimation of the extent of early ischemic changes (ie, ischemic core) at pretreatment imaging.
March 2020
Tumor Size Matters-Understanding Concomitant Tumor Immunity in the Context of Hypofractionated Radiotherapy with Immunotherapy.The purpose of this study was to determine the dynamic contributions of different immune cell subsets to primary and abscopal tumor regression after hypofractionated radiation therapy (hRT) and the impact of anti-PD-1 therapy. A bilateral syngeneic FSA1 fibrosarcoma model was used in immunocompetent C3H mice, with delayed inoculation to mimic primary and microscopic disease. The effect of tumor burden on intratumoral and splenic immune cell content was delineated as a prelude to hRT on macroscopic T1 tumors with 3 fractions of 8 Gy while microscopic T2 tumors were left untreated. This was performed with and without systemic anti-PD-1.
March 2020
Rate of Change in Maximum 18F-FDOPA PET Uptake and Non-enhancing Tumor Volume Predict Malignant Transformation and Overall Survival in Low-Grade Gliomas.
PURPOSE: To examine whether the rate of change in maximum
March 2020
Electrochemical Cytosensors for Detection of Breast Cancer Cells.Breast cancer is one of lethal cancers among women with its metastasis leading to cancer-related morbidity and mortality. Circulating tumor cells (CTCs) derived from a primary tumor can be detected in the venous blood of cancer patients. Monitoring CTCs in blood samples has increased exponentially over the past decades and holds great promise in the diagnosis and treatment of metastatic breast cancer. Electrochemical cytosensors, classified as a class of electrochemical biosensors for sensitive detection and enumeration of targeted cells with minimally invasive methods, have the advantages of electrochemical biosensors, such as simplicity, low cost, and low limit of detection. Here, we review recent progress in the detection of CTCs from breast cancer with a focus on electrochemical cytosensors. This review describes platforms benefiting from these cytosensors to identify cancerous breast cells. Furthermore, strategies for signal amplification and also generation of reusable electrochemical cytosensors are introduced. In addition, breast cancer markers and biorecognition elements for cell capturing are reviewed.
March 2020
Unionizing Radiology: A Potential Response to Increasing Corporatization.Recent work has highlighted the trend of consolidation within radiology and health care at large. Traditionally, the practice of radiology has been highly fragmented, organized into local and regional practices, owned by radiologists. In the past few years, there has been an increase in local practice acquisitions by corporate-, venture capital-, or private equity-backed national entities (NEs), described collectively herein as "corporatization."
March 2020
High Throughput Image Labeling on Chest Computed Tomography by Deep Learning.When mining image data from PACs or clinical trials or processing large volumes of data without curation, the relevant scans must be identified among irrelevant or redundant data. Only images acquired with appropriate technical factors, patient positioning, and physiological conditions may be applicable to a particular image processing or machine learning task. Automatic labeling is important to make big data mining practical by replacing conventional manual review of every single-image series. Digital imaging and communications in medicine headers usually do not provide all the necessary labels and are sometimes incorrect. We propose an image-based high throughput labeling pipeline using deep learning, aimed at identifying scan direction, scan posture, lung coverage, contrast usage, and breath-hold types. They were posed as different classification problems and some of them involved further segmentation and identification of anatomic landmarks. Images of different view planes were used depending on the specific classification problem. All of our models achieved accuracy > 99% on test set across different tasks using a research database from multicenter clinical trials.
March 2020
Percutaneous Thermal Ablation of Subcapsular Hepatocellular Carcinomas: Influence of Tumor-surface Contact and Protrusion on Therapeutic Efficacy and Safety.PURPOSE: To evaluate therapeutic efficacy and complication of percutaneous thermal ablation of subcapsular hepatocellular carcinomas (HCCs), and how these may be influenced by the degree of tumor to liver surface contact and tumor protrusion from liver surface. MATERIALS AND METHODS: Our retrospective study was approved by the Institutional Review Board. Between January 2006 and December 2013, 290 patients (82 women, 208 men; mean age, 64.5 years; range, 33-89 years) with 474 subcapsular (within 1 cm to the liver surface) HCCs (mean size, 23.7 mm; range, 6-71 mm) underwent percutaneous thermal ablation. The HCCs were divided into surface contact group (n = 243) and non-surface contact group (n = 231). The former was further subdivided into exophytic and non-exophytic HCCs. Technical success, primary technique efficacy, local tumor progression (LTP), and secondary technique efficacy rates were analyzed and compared by the chi-square test or Fisher exact test. Prognostic factors for LTP and secondary technique efficacy were assessed using the Cox regression model. Major complications were also assessed.
February 2020
Assessment of Response to Neoadjuvant Therapy Using CT Texture Analysis in Patients With Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma.OBJECTIVE. The goal of this study was to assess the correlation between CT-derived texture features of pancreatic ductal adenocarcinoma (PDAC) and histologic and biochemical markers of response to neoadjuvant treatment as well as disease-free survival in patients with potentially resectable PDAC. SUBJECTS AND METHODS. Thirty-nine patients completed this prospective study protocol between November 2013 and December 2016. All patients received neoadjuvant chemotherapy, underwent surgical resection, and had histologic grading of tumor response. Similar CT protocol was used for all patients. Pancreatic (late arterial) phase of pre- and posttreatment CT scans were evaluated. Histogram analysis and spatial-band-pass filtration were used to extract textural features. Correlation between textural parameters, histologic response, biochemical response, and genetic mutations was assessed using Mann-Whitney test, chi-square analysis, and multivariate logistic regression. Association with disease-free survival was assessed using Kaplan-Meier method and Cox model.
February 2020
Renal Denervation as Adjunctive Therapy to Cardiac Sympathetic Denervation for Ablation Refractory Ventricular Tachycardia.BACKGROUND: Autonomic modulation is finding an increasing role in the treatment of ventricular arrhythmias. Renal denervation (RDN) has been described as a treatment modality for refractory ventricular tachycardia (VT) in case series. OBJECTIVE: The purpose of this study was to evaluate RDN as an adjunctive therapy to cardiac sympathetic denervation (CSD) for ablation refractory VT. METHODS: Patients who underwent RDN after radiofrequency ablation and CSD procedures at our center from 2012 to 2019 were evaluated.
February 2020
Constraints in Estimating the Proton Density Fat Fraction.The study evaluates four physically motivated constraints in the estimation of the proton density fat fraction (PDFF). Least squares approaches were developed for constraining the parameters in PDFF quantification based on the physics of magnetic resonance imaging. These were smooth fieldmap, smooth initial phase, nonnegative proton density and moderate R2✶ values. The constraints were evaluated in terms of their influence on the bias and standard deviation of the estimated parameters using numerical simulations and in vivo data acquired at 0.35 T. Results show that unconstrained least squares estimation is noisy and biased and that constraints can be effective at reducing both the standard deviation and bias.
February 2020
3D-Printed Ultra-Robust Surface-Doped Porous Silicone Sensors for Wearable Biomonitoring.Three-dimensional flexible porous conductors have significantly advanced wearable sensors and stretchable devices because of their specific high surface area. Dip coating of porous polymers with graphene is a facile, low cost, and scalable approach to integrate conductive layers with the flexible polymer substrate platforms; however, the products often suffer from nanoparticle delamination and overtime decay. Here, a fabrication scheme based on accessible methods and safe materials is introduced to surface-dope porous silicone sensors with graphene nanoplatelets. The sensors are internally shaped with ordered, interconnected, and tortuous internal geometries (i.e., triply periodic minimal surfaces) using fused deposition modeling (FDM) 3D-printed sacrificial molds. The molds were dip coated to transfer-embed graphene onto the silicone rubber (SR) surface. The presented procedure exhibited a stable coating on the porous silicone samples with long-term electrical resistance durability over ∼12 months period and high resistance against harsh conditions (exposure to organic solvents). Besides, the sensors retained conductivity upon severe compressive deformations (over 75% compressive strain) with high strain-recoverability and behaved robustly in response to cyclic deformations (over 400 cycles), temperature, and humidity. The sensors exhibited a gauge factor as high as 10 within the compressive strain range of 2-10%. Given the tunable sensitivity, the engineered biocompatible and flexible devices captured movements as rigorous as walking and running to the small deformations resulted by human pulse.
February 2020
Engineering Biomaterials with Micro/Nanotechnologies for Cell Reprogramming.Cell reprogramming is a revolutionized biotechnology that offers a powerful tool to engineer cell fate and function for regenerative medicine, disease modeling, drug discovery, and beyond. Leveraging advances in biomaterials and micro/nanotechnologies can enhance the reprogramming performance in vitro and in vivo through the development of delivery strategies and the control of biophysical and biochemical cues. In this review, we present an overview of the state-of-the-art technologies for cell reprogramming and highlight the recent breakthroughs in engineering biomaterials with micro/nanotechnologies to improve reprogramming efficiency and quality. Finally, we discuss future directions and challenges for reprogramming technologies and clinical translation.
February 2020
Using Transitional Changes on High-Resolution Computed Tomography to Monitor the Impact of Cyclophosphamide or Mycophenolate Mofetil on Systemic Sclerosis-Related Interstitial Lung Disease.OBJECTIVE: To examine changes in the extent of specific patterns of interstitial lung disease (ILD) as they transition from one pattern to another in response to immunosuppressive therapy in systemic sclerosis-related ILD (SSc-ILD). METHODS: We evaluated changes in the quantitative extent of specific lung patterns of ILD using volumetric high-resolution computed tomography (HRCT) scans obtained at baseline and after 2 years of therapy in patients treated with either cyclophosphamide (CYC) for 1 year or mycophenolate mofetil (MMF) for 2 years in Scleroderma Lung Study II. ILD patterns included lung fibrosis, ground glass, honeycombing, and normal lung. Net change was calculated as the difference in the probability of change from one ILD pattern to another. Wilcoxon's signed rank test was used to compare the changes.
February 2020
Prediction of Idiopathic Pulmonary Fibrosis Progression Using Early Quantitative Changes on CT Imaging for a Short Term of Clinical 18-24-month Follow-ups.OBJECTIVE: High-resolution computed tomography (HRCT) plays an indispensable role in the diagnosis of idiopathic pulmonary fibrosis (IPF). Due to unpredictability in progression and the short median survival of 2-5 years, it is critical to delineate the patients with rapid progression. The aim is to evaluate the predictability of IPF progression using the early quantitative changes. METHODS: Automated texture-based quantitative lung fibrosis (QLF) was calculated from the anonymized HRCT. Two datasets were collected retrospectively: (1) a pilot study of 35 subjects with three sequential scans (baseline and 6 and 12 months) to obtain a threshold, where visual assessments were stable at 6 months but worsened at 12 months; (2) 157 independent subjects to test the threshold. Landmark Cox regressions were used to compare the progression-free survival (PFS) defined by pulmonary function using the threshold from the early changes in QLF. C-indexes were reported as estimations of the concordance of prediction.
February 2020
Key Components of Engineering Vascularized 3-dimensional Bioprinted Bone Constructs.Vascularization has a pivotal role in engineering successful tissue constructs. However, it remains a major hurdle of bone tissue engineering, especially in clinical applications for the treatment of large bone defects. Development of vascularized and clinically-relevant engineered bone substitutes with sufficient blood supply capable of maintaining implant viability and supporting subsequent host tissue integration remains a major challenge. Since only cells that are 100-200 µm from blood vessels can receive oxygen through diffusion, engineered constructs that are thicker than 400 µm face a challenging oxygenation problem. Following implantation in vivo, spontaneous ingrowth of capillaries in thick engineered constructs is too slow. Thus, it is critical to provide optimal conditions to support vascularization in engineered bone constructs. To achieve this, an in-depth understanding of the mechanisms of angiogenesis and bone development is required. In addition, it is also important to mimic the physiological milieu of native bone to fabricate more successful vascularized bone constructs. Numerous applications of engineered vascularization with cell-and/or microfabrication-based approaches seek to meet these aims. Three-dimensional (3D) printing promises to create patient-specific bone constructs in the future. In this review, we discuss the major components of fabricating vascularized 3D bioprinted bone constructs, analyze their related challenges, and highlight promising future trends.
February 2020
Safety of Intravenous Thrombolysis Among Patients Taking Direct Oral Anticoagulants: A Systematic Review and Meta-Analysis.BACKGROUND AND PURPOSE: There are scarce data regarding the safety of intravenous thrombolysis (IVT) in acute ischemic stroke among patients on direct oral anticoagulants (DOACs). METHODS: We performed a systematic review and meta-analysis of the current literature. Data regarding all adult patients pretreated with DOAC who received IVT for acute ischemic stroke were recorded. Meta-analysis was performed by comparing the rate of symptomatic intracerebral hemorrhage in these patients with (1) stroke patients without prior anticoagulation therapy and (2) patients on warfarin with international normalized ratio <1.7. Meta-analyses were further conducted in subgroups as follows: (1) administration of DOAC within 48 hours versus an unknown interval before IVT, (2) consideration of symptomatic intracerebral hemorrhage outcome according to the National Institute of Neurological Disorders (NINDS) versus the European Cooperative Acute Stroke Study II (ECASS-II) criteria.
February 2020
Reduced Left Amygdala Volume in Patients with Dissociative Seizures (Psychogenic Nonepileptic Seizures).PURPOSE: This study specifically investigated differences of amygdalar and hippocampal volumes between patients with dissociative seizures (DS), mesial temporal lobe sclerosis (MTS), and normal controls (NC). METHODS: Between 2003 and 2018, 127 patients diagnosed with DS and 278 with MTS were recruited. An additional 52 NC subjects were recruited between 2015 and 2018. We retrospectively selected 29 patients with DS (male:female, 6:23) with absence of structural confounding factors and obtained sex- and age-matched MTS and NC. We used Neuroreader to assess the volume of the amygdala and hippocampus as a percentage of total intracranial volume based on thin-slice (0.9-1.2 mm) T1-weighted images. Statistical analyses controlled for psychiatric comorbidity and logistic regression were used to evaluate efficacy of these values for individual-level diagnosis.
February 2020
Deep Learning Detection of Penumbral Tissue on Arterial Spin Labeling in Stroke.BACKGROUND and PURPOSE: Selection of patients with acute ischemic stroke for endovascular treatment generally relies on dynamic susceptibility contrast magnetic resonance imaging or computed tomography perfusion. Dynamic susceptibility contrast magnetic resonance imaging requires injection of contrast, whereas computed tomography perfusion requires high doses of ionizing radiation. The purpose of this work was to develop and evaluate a deep learning (DL)-based algorithm for assisting the selection of suitable patients with acute ischemic stroke for endovascular treatment based on 3-dimensional pseudo-continuous arterial spin labeling (pCASL). METHODS: A total of 167 image sets of 3-dimensional pCASL data from 137 patients with acute ischemic stroke scanned on 1.5T and 3.0T Siemens MR systems were included for neural network training. The concurrently acquired dynamic susceptibility contrast magnetic resonance imaging was used to produce labels of hypoperfused brain regions, analyzed using commercial software. The DL and 6 machine learning (ML) algorithms were trained with 10-fold cross-validation. The eligibility for endovascular treatment was determined retrospectively based on the criteria of perfusion/diffusion mismatch in the DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke). The trained DL algorithm was further applied on twelve 3-dimensional pCASL data sets acquired on 1.5T and 3T General Electric MR systems, without fine-tuning of parameters.
January 2020
Advances in Controlled Oxygen Generating Biomaterials for Tissue Engineering and Regenerative Therapy.Oxygen (O2) generating biomaterials are emerging as important compositions to improve our capabilities in supporting tissue engineering and regenerative therapeutics. Several in vitro studies demonstrated the usefulness of O2 releasing biomaterials in enhancing cell survival and differentiation. However, more efforts are needed to develop materials that can provide sustained O2 release for the long-term. In this paper, we present different O2 generating sources, including hydrogen peroxide, sodium percarbonate, calcium peroxide and magnesium peroxide, and also cover types of carriers and relevant methods of fabricating O2 generating systems. Then, the applications of O2 generating materials in supporting engineered constructs, supplying high O2 demanding cell transplants, and supporting ischemic tissues are discussed. Moreover, the challenges and future perspectives are highlighted.
January 2020
Treatment of Recurrent Pulmonary Arteriovenous Malformations: Comparison of Proximal Versus Distal Embolization Technique.PURPOSE: To examine the characteristics of recurrent pulmonary arteriovenous malformations (PAVMs) and compare the success of proximal versus distal embolization technique for treatment of recanalized PAVMs. MATERIALS: Between July 2007 and October 2018, 26 consecutive patients underwent embolization of 64 previously treated recurrent PAVMs at a single center with imaging follow-up. PAVM angioarchitecture was classified as either simple (1 feeding artery) or complex (≥ 2 feeding arteries). The mechanism of recurrence was characterized as recanalization (flow through previously placed embolic material) or reperfusion (flow through accessory arteries). For recanalized PAVMs, we compared embolizing proximal to or within the existing embolic (proximal embolization technique) versus embolizing distal to the existing embolic (distal embolization technique). Follow-up imaging was reviewed to determine treatment success, defined as decrease of the draining vein or sac size by at least 70%.
January 2020
Factors Associated with Symptomology of Celiac Artery Compression and Outcomes following Median Arcuate Ligament Release.BACKGROUND: This study aims to identify potential risk factors for becoming symptomatic in patients with radiographic celiac artery compression (CAC) as well as prognostic factors for patients with median arcuate ligament syndrome (MALS) who underwent surgical ligament release. METHODS: This is a retrospective cohort study of patients with findings of CAC on computed tomography or magnetic resonance angiography (CT/MRA) who were asymptomatic and who were diagnosed with MALS at a single university hospital between January 2001 and 2018.
January 2020
Cirrhotic Nodule Transformation to Hepatocellular Carcinoma: Natural History and Predictive Biomarkers on Contrast-Enhanced Ultrasound.OBJECTIVE. The objective of our study was to identify sonographic biomarkers predicting or indicating eventual malignant transformation of pathologically confirmed cirrhotic nodules. MATERIALS AND METHODS. Thirty-nine consecutive patients with 44 pathologically confirmed cirrhotic nodules (mean size, 17.5 ± 8.5 [SD] mm) who initially underwent contrast-enhanced ultrasound examination at detection and then underwent follow-up conventional ultrasound every 3-4 months thereafter were retrospectively included. Malignant transformation was identified on the basis of noninvasive diagnostic criteria for hepatocellular carcinoma or rebiopsy. Malignant transformation biomarkers were identified from clinical and sonographic variables and the performance thereof was evaluated using ROC curves.
January 2020
Long-Term Survival after Percutaneous Radiofrequency Ablation of Pathologically Proven Renal Cell Carcinoma in 100 Patients.PURPOSE: To determine the long-term survival of patients treated with percutaneous radiofrequency (RF) ablation for pathologically proven renal cell carcinoma (RCC). MATERIALS AND METHODS: In this single-center retrospective study, 100 patients with 125 RCCs (100 clear-cell, 19 papillary, and 6 chromophobe) 0.8-8 cm in size treated with RF ablation were evaluated at a single large tertiary-care center between 2004 and 2015. Technical success, primary and secondary technique efficacy, and pre- and postprocedural estimated glomerular filtration rate (eGFR) at 3-6 months and 2-3 years were recorded. Overall survival, cancer-specific survival, and local tumor progression-free survival were calculated by Kaplan-Meier survival curves. Complications were classified per the Clavien-Dindo system. Statistical testing was done via χ2 tests for proportions and paired t test for changes in eGFR. Statistical significance was set at α = 0.05.
January 2020
Pamrevlumab, an Anti-connective Tissue Growth Factor Therapy, for Idiopathic Pulmonary Fibrosis (PRAISE): a Phase 2, Randomised, Double-blind, Placebo-controlled Trial.BACKGROUND: Connective tissue growth factor (CTGF) is a secreted glycoprotein that has a central role in the process of fibrosis. This study was designed to assess the safety, tolerability, and efficacy of pamrevlumab (FG-3019), a fully recombinant human monoclonal antibody against CTGF, in idiopathic pulmonary fibrosis. The aim was to establish whether pamrevlumab could slow, stop, or reverse progression of idiopathic pulmonary fibrosis. METHODS: The phase 2, randomised, double-blind, placebo-controlled PRAISE trial was done at 39 medical centres in seven countries (Australia, Bulgaria, Canada, India, New Zealand, South Africa, and the USA). Patients with idiopathic pulmonary fibrosis and percentage of predicted forced vital capacity (FVC) of 55% or greater were enrolled and randomly assigned (1:1) by use of interactive responsive technology to intravenous infusion of pamrevlumab 30 mg/kg or placebo every 3 weeks over 48 weeks (16 infusions). The primary efficacy outcome was change from baseline in percentage of predicted FVC at week 48. Disease progression (defined as a decline from baseline in percentage of predicted FVC of ≥10%, or death) at week 48 was a key secondary efficacy outcome. All patients in the pamrevlumab group received at least one dose of the study drug and were analysed for safety. Two patients in the placebo group were excluded from the intention-to-treat population for the efficacy analyses because of enrolment error. This trial is registered with ClinicalTrials.gov, NCT01890265.
January 2020
Patient Safety Analysis in Radiation Burden of Head Computed Tomography Imaging in 1185 Neurosurgical Inpatients.OBJECTIVE: We performed a retrospective analysis in a cohort of 1185 patients at our institution who were identified as undergoing ≥1 head computed tomography (CT) examinations during their inpatient stay on the neurosurgery service, to quantify the number, type, and associated radiation burden of head CT procedures performed by the neurosurgery service. METHODS: CT procedure records and radiology reports were obtained via database search and directly validated against records retrieved from manual chart review. Next, dosimetry data from the head CT procedures were extracted via automated text mining of electronic radiology reports.
January 2020
Room-Temperature-Formed PEDOT:PSS Hydrogels Enable Injectable, Soft, and Healable Organic Bioelectronics.There is an increasing need to develop conducting hydrogels for bioelectronic applications. In particular, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) hydrogels have become a research hotspot due to their excellent biocompatibility and stability. However, injectable PEDOT:PSS hydrogels have been rarely reported. Such syringe-injectable hydrogels are highly desirable for minimally invasive biomedical therapeutics. Here, an approach is demonstrated to develop injectable PEDOT:PSS hydrogels by taking advantage of the room-temperature gelation property of PEDOT:PSS. These PEDOT:PSS hydrogels form spontaneously after syringe injection of the PEDOT:PSS suspension into the desired location, without the need of any additional treatments. A facile strategy is also presented for large-scale production of injectable PEDOT:PSS hydrogel fibers at room temperature. Finally, it is demonstrated that these room-temperature-formed PEDOT:PSS hydrogels (RT-PEDOT:PSS hydrogel) and hydrogel fibers can be used for the development of soft and self-healable hydrogel bioelectronic devices.
