RSS 1.0Radiology Publications
ABOUT THIS COLLECTION
The mission of the Department of Radiology at UMass Chan Medical School is to bring scientific advances in medical imaging to clinical application. This collection showcases journal articles and other publications written by faculty and researchers of the Department of Radiology.
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Recently Published
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International Inter-observer Variability of Breast Density AssessmentObjective: To determine variability in visually assessed mammographic breast density categorization among radiologists practicing in Indonesia, the Netherlands, South Africa, and the United States. Methods: Two-hundred consecutive 2D full field digital screening mammograms performed from September-December 2017 were selected and retrospectively reviewed from four global locations for a total of 800 mammograms. Three breast radiologists in each location (team) provided consensus density assessments of all 800 mammograms using BI-RADS® density categorization. Inter-reader agreement was compared using Gwet's AC2 with quadratic weighting across all four density categories and Gwet's AC1 for binary comparison of combined not dense versus dense categories. Variability of distribution between teams was calculated using the Stuart-Maxwell test of marginal homogeneity across all four categories and using McNemar's test for not dense versus dense categories. To compare readers from a particular country on their own 200 mammograms versus the other three teams, density distribution was calculated using conditional logistic regression. Results: For all 800 mammograms, inter-reader weighted agreement for distribution among four density categories is 0.86 (Gwet's AC2 with quadratic weighting 95%, CI 0.85-0.88) and for not dense vs dense categories it is 0.66 (Gwet's AC1 95%, CI 0.63-0.70). Density distribution across four density categories was significantly different when teams were compared to each other and one team versus the other three teams combined (p<0.001). Overall, all readers placed the largest number of mammograms in the scattered and heterogeneous categories. Conclusion: While reader teams from four different global locations had almost perfect inter-reader agreement in BI-RADS® density categorization, variability in density distribution across four categories remains statistically significant.
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A pilot study of robotic surgery case videos for first-year medical student anatomyThere has been a recent shift in medical student anatomy education with greater incorporation of virtual resources. Multiple approaches to virtual anatomy resources have been described, but few involve video or images from surgical procedures. In this pilot study, a series of surgical case videos was created using robotic surgery video footage for a first-year medical student anatomy course. Five operations were included that covered thoracic, abdominal, and pelvic anatomy. Students were surveyed at the end of the course regarding their experience with the videos and their perceptions towards a surgical career. Overall, participants agreed that the videos were an effective learning tool, were useful regardless of career interest, and that in the future it would be useful to incorporate additional surgical case videos. Respondents highlighted the importance of audio narration with future videos and provided suggestions for future operations that they would like to see included. In summary, this pilot study describes the creation and implementation of a surgical video anatomy curriculum and student survey results suggest this may be an effective approach to video-based anatomy education for further curricular development.
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Cryo-EM structure of the human cardiac myosin filament [preprint]Pumping of the heart is powered by filaments of the motor protein myosin, which pull on actin filaments to generate cardiac contraction. In addition to myosin, the filaments contain cardiac myosin-binding protein C (cMyBP-C), which modulates contractility in response to physiological stimuli, and titin, which functions as a scaffold for filament assembly 1 . Myosin, cMyBP-C and titin are all subject to mutation, which can lead to heart failure. Despite the central importance of cardiac myosin filaments to life, their molecular structure has remained a mystery for 60 years 2 . Here, we have solved the structure of the main (cMyBP-C-containing) region of the human cardiac filament to 6 Å resolution by cryo-EM. The reconstruction reveals the architecture of titin and cMyBP-C for the first time, and shows how myosin's motor domains (heads) form 3 different types of motif (providing functional flexibility), which interact with each other and with specific domains of titin and cMyBP-C to dictate filament architecture and regulate function. A novel packing of myosin tails in the filament backbone is also resolved. The structure suggests how cMyBP-C helps generate the cardiac super-relaxed state 3 , how titin and cMyBP-C may contribute to length-dependent activation 4 , and how mutations in myosin and cMyBP-C might disrupt interactions, causing disease 5, 6 . A similar structure is likely in vertebrate skeletal myosin filaments. The reconstruction resolves past uncertainties, and integrates previous data on cardiac muscle structure and function. It provides a new paradigm for interpreting structural, physiological and clinical observations, and for the design of potential therapeutic drugs.
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Radiofrequency Ablation Provides Rapid and Durable Pain Relief for the Palliative Treatment of Lytic Bone Metastases Independent of Radiation Therapy: Final Results from the OsteoCool Tumor Ablation Post-Market StudyPurpose: The OsteoCool Tumor Ablation Post-Market Study (OPuS One) was a prospective, multi-national, single-arm study to investigate safety and effectiveness of radiofrequency ablation (RFA) for palliation of painful lytic bone metastases with 12 months of follow-up. RFA has demonstrated effective palliation of osseous metastases in small clinical studies with short-term follow-up; however, a long-term assessment with robust subject numbers is lacking. Materials and methods: Prospective assessments were conducted at Baseline, 3 days, 1 week, and 1, 3, 6, and 12-months. Pain and quality of life were measured prior to RFA and postoperatively using the Brief Pain Inventory, European Quality of Life-5 Dimension, and European Organization for Research and Treatment of Cancer Care Quality of Life Questionnaire for palliative care. Radiation, chemotherapy and opioid usage, and related adverse events were collected. Results: 206 subjects were treated with RFA at 15 institutions in OPuS One. Worst pain, average pain, pain interference and quality of life significantly improved at all visits starting 3 days post-RFA and sustained to 12 months (P < 0.0001). Post hoc analysis found neither systemic chemotherapy nor local radiation therapy at the index site of RFA influenced worst pain, average pain, or pain interference. Six subjects had device/procedure-related adverse events. Conclusion: RFA for lytic metastases provides rapid (within 3 days) and statistically significant pain and quality of life improvements with sustained long-term relief through 12 months and a high degree of safety, independent of radiation. Level of evidence: 2B, PROSPECTIVE, NON-RANDOMIZED, POST-MARKET STUDY: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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World Federation for Interventional Stroke Treatment (WIST) multispecialty training guidelines for endovascular stroke interventionIntroduction: Today, endovascular treatment (EVT) is the therapy of choice for strokes due to acute large vessel occlusion, irrespective of prior thrombolysis. This necessitates fast, coordinated multi-specialty collaboration. Currently, in most countries, the number of physicians and centres with expertise in EVT is limited. Thus, only a small proportion of eligible patients receive this potentially life-saving therapy, often after significant delays. Hence, there is an unmet need to train a sufficient number of physicians and centres in acute stroke intervention in order to allow widespread and timely access to EVT. Aim: To provide multi-specialty training guidelines for competency, accreditation and certification of centres and physicians in EVT for acute large vessel occlusion strokes. Material and methods: The World Federation for Interventional Stroke Treatment (WIST) consists of experts in the field of endovascular stroke treatment. This interdisciplinary working group developed competency - rather than time-based - guidelines for operator training, taking into consideration trainees' previous skillsets and experience. Existing training concepts from mostly single specialty organizations were analysed and incorporated. Results: The WIST establishes an individualized approach to acquiring clinical knowledge and procedural skills to meet the competency requirements for certification of interventionalists of various disciplines and stroke centres in EVT. WIST guidelines encourage acquisition of skills using innovative training methods such as structured supervised high-fidelity simulation and procedural performance on human perfused cadaveric models. Conclusions: WIST multispecialty guidelines outline competency and quality standards for physicians and centres to perform safe and effective EVT. The role of quality control and quality assurance is highlighted. Summary: The World Federation for Interventional Stroke Treatment (WIST) establishes an individualized approach to acquiring clinical knowledge and procedural skills to meet the competency requirements for certification of interventionalists of various disciplines and stroke centres in endovascular treatment (EVT). WIST guidelines encourage acquisition of skills using innovative training methods such as structured supervised high-fidelity simulation and procedural performance on human perfused cadaveric models. WIST multispecialty guidelines outline competency and quality standards for physicians and centers to perform safe and effective EVT. The role of quality control and quality assurance is highlighted. Simultaneous publication: The WIST 2023 Guidelines are published simultaneously in Europe (Adv Interv Cardiol 2023, PMID 37090217).
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Sarcoid-Like Reaction Involving Bone Marrow in Patient on Immune Checkpoint Inhibitor TherapyClinically useful high-quality radiologic depiction relevant to radiologists' practice. Treatment-induced sarcoid-like reactions, due to T-cell mediated non-caseating granuloma formation, are increasingly encountered in the precision oncology era [1, 2]. Most commonly involved sites are the lungs and lymph nodes. Sarcoid-like reaction in bone marrow is rare, with fewer than 100 reported cases. On imaging, sarcoid-like reaction of bone marrow may mimic skeletal metastasis. Thus, it is important that radiologists be aware of this entity. Although imaging may suggest sarcoid-like reaction of bone marrow, definitive diagnosis requires biopsy.
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Atypical and Typical Distant Sarcoid-like Reactions during Treatment of Metastatic MelanomaImages in cancer: Sarcoid-like reactions are reported in 4%–14% of patients with cancer and are likely driven by T-cell–mediated hypersensitivity reactions forming granulomas (1). They can occur with infection, treatment, or the presence of foreign bodies (2) and have been increasingly reported in the era of precision targeted and immune checkpoint inhibitor therapy (3,4), including the use of BRAF and MEK inhibitors (Figure) (5). The classic pattern mimics sarcoidosis and involves mediastinal and hilar lymph nodes, which may be enlarged and demonstrate increased fluorodeoxyglucose (FDG) uptake at FDG PET/CT; pulmonary nodules and infiltrates may or may not be present (1,2). The incidence of extrathoracic sarcoid-like reactions is unknown but rare (6), with case reports documenting reactions including the liver, spleen, skin, central nervous system, pancreas, bone, and eyes (6,7). Absence of findings at baseline and emergence after treatment initiation can be helpful to identify a sarcoid-like reaction, although it may be indistinguishable from disease and may require tissue sampling. Radiologists should recognize these patterns to avoid confusion with disease progression. If necessary, steroids are the mainstay of treatment; immunotherapy discontinuation may be required in severe cases.
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Tectonic infarct analysis: A computational tool for automated whole-brain infarct analysis from TTC-stained tissueBackground: Infarct volume measured from 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain slices is critical to in vivo stroke models. In this study, we developed an interactive, tunable, software that automatically computes whole-brain infarct metrics from serial TTC-stained brain sections. Methods: Three rat ischemic stroke cohorts were used in this study (Total n = 91 rats; Cohort 1 n = 21, Cohort 2 n = 40, Cohort 3 n = 30). For each, brains were serially-sliced, stained with TTC and scanned on both anterior and posterior sides. Ground truth annotation and infarct morphometric analysis (e.g., brain-Vbrain, infarct-Vinfarct, and non-infarct-Vnon-infarct volumes) were completed by domain experts. We used Cohort 1 for brain and infarct segmentation model development (n = 3 training cases with 36 slices [18 anterior and posterior faces], n = 18 testing cases with 218 slices [109 anterior and posterior faces]), as well as infarct morphometrics automation. The infarct quantification pipeline and pre-trained model were packaged as a standalone software and applied to Cohort 2, an internal validation dataset. Finally, software and model trainability were tested as a use-case with Cohort 3, a dataset from a separate institute. Results: Both high segmentation and statistically significant quantification performance (correlation between manual and software) were observed across all datasets. Segmentation performance: Cohort 1 brain accuracy = 0.95/f1-score = 0.90, infarct accuracy = 0.96/f1-score = 0.89; Cohort 2 brain accuracy = 0.97/f1-score = 0.90, infarct accuracy = 0.97/f1-score = 0.80; Cohort 3 brain accuracy = 0.96/f1-score = 0.92, infarct accuracy = 0.95/f1-score = 0.82. Infarct quantification (cohort average): Vbrain (ρ = 0.87, p < 0.001), Vinfarct (0.92, p < 0.001), Vnon-infarct (0.80, p < 0.001), %infarct (0.87, p = 0.001), and infarct:non-infact ratio (ρ = 0.92, p < 0.001). Conclusion: Tectonic Infarct Analysis software offers a robust and adaptable approach for rapid TTC-based stroke assessment.
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Non-Invasive Intracranial Pressure Monitoring(1) Background: Intracranial pressure (ICP) monitoring plays a key role in the treatment of patients in intensive care units, as well as during long-term surgeries and interventions. The gold standard is invasive measurement and monitoring via ventricular drainage or a parenchymal probe. In recent decades, numerous methods for non-invasive measurement have been evaluated but none have become established in routine clinical practice. The aim of this study was to reflect on the current state of research and shed light on relevant techniques for future clinical application. (2) Methods: We performed a PubMed search for "non-invasive AND ICP AND (measurement OR monitoring)" and identified 306 results. On the basis of these search results, we conducted an in-depth source analysis to identify additional methods. Studies were analyzed for design, patient type (e.g., infants, adults, and shunt patients), statistical evaluation (correlation, accuracy, and reliability), number of included measurements, and statistical assessment of accuracy and reliability. (3) Results: MRI-ICP and two-depth Doppler showed the most potential (and were the most complex methods). Tympanic membrane temperature, diffuse correlation spectroscopy, natural resonance frequency, and retinal vein approaches were also promising. (4) Conclusions: To date, no convincing evidence supports the use of a particular method for non-invasive intracranial pressure measurement. However, many new approaches are under development.
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De novo lipogenesis fuels adipocyte autophagosome and lysosome membrane dynamicsAdipocytes robustly synthesize fatty acids (FA) from carbohydrate through the de novo lipogenesis (DNL) pathway, yet surprisingly DNL contributes little to their abundant triglyceride stored in lipid droplets. This conundrum raises the hypothesis that adipocyte DNL instead enables membrane expansions to occur in processes like autophagy, which requires an abundant supply of phospholipids. We report here that adipocyte Fasn deficiency in vitro and in vivo markedly impairs autophagy, evident by autophagosome accumulation and severely compromised degradation of the autophagic substrate p62. Our data indicate the impairment occurs at the level of autophagosome-lysosome fusion, and indeed, loss of Fasn decreases certain membrane phosphoinositides necessary for autophagosome and lysosome maturation and fusion. Autophagy dependence on FA produced by Fasn is not fully alleviated by exogenous FA in cultured adipocytes, and interestingly, imaging studies reveal that Fasn colocalizes with nascent autophagosomes. Together, our studies identify DNL as a critical source of FAs to fuel autophagosome and lysosome maturation and fusion in adipocytes.
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Development of a clot-adhesive coating to improve the performance of thrombectomy devicesBackground: The first-pass complete recanalization by mechanical thrombectomy (MT) for the treatment of stroke remains limited due to the poor integration of the clot within current devices. Aspiration can help retrieval of the main clot but fails to prevent secondary embolism in the distal arterial territory. The dense meshes of extracellular DNA, recently described in stroke-related clots, might serve as an anchoring platform for MT devices. We aimed to evaluate the potential of a DNA-reacting surface to aid the retention of both the main clot and small fragments within the thrombectomy device to improve the potential of MT procedures. Methods: Device-suitable alloy samples were coated with 15 different compounds and put in contact with extracellular DNA or with human peripheral whole blood, to compare their binding to DNA versus blood elements in vitro. Clinical-grade MT devices were coated with two selected compounds and evaluated in functional bench tests to study clot retrieval efficacy and quantify distal emboli using an M1 occlusion model. Results: Binding properties of samples coated with all compounds were increased for DNA (≈3-fold) and decreased (≈5-fold) for blood elements, as compared with the bare alloy samples in vitro. Functional testing showed that surface modification with DNA-binding compounds improved clot retrieval and significantly reduced distal emboli during experimental MT of large vessel occlusion in a three-dimensional model. Conclusion: Our results suggest that clot retrieval devices coated with DNA-binding compounds can considerably improve the outcome of the MT procedures in stroke patients.
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Development of an in-vitro model based on patient vessel geometry for simulated use testing in neurointerventional surgeryBackground: Neurointerventionalists use in-vitro vascular models to train for worst-case scenarios and test new devices in a simulated use environment to predict clinical performance. According to the Food and Drug Administration (FDA), any neurovascular navigation device should be able to successfully navigate two 360-degree turns and two 180-degree turns at the distal portion of the anatomical model. Here, we present a device benchmarking vascular model that complies with FDA recommendations. Methods: Our vascular model was assembled from quantitative characterization of 49 patients who underwent CT angiography either for acute ischemic stroke caused by large vessel occlusion or for aneurysm treatment. Following complete characterization of these data, the vascular segments were 3D reconstructed from CT angiograms of 6 selected patients that presented with challenging anatomy. The curvature and total rotational angle were calculated for each segment and the anatomical parts that complied with FDA recommendations were fused together into a single in-vitro model. Results: The model was constructed containing two common carotid branches arising from a type two aortic arch and the dimensions of the overall model exceeded the recommendations of the FDA. Two experienced neurointerventionalists tested the model for navigation difficulty using several devices on an in-vitro perfusion system and concluded that the model provided a realistic, challenging scenario. Conclusions: This model provides a first prototype designed according to FDA recommendations of cumulative angle while also integrating an aggregation of actual patient-specific anatomy. The availability of this clinically relevant benchmark model presents a potential standardized approach for neurovascular device testing.
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Prospective study on embolization of intracranial aneurysms with the pipeline device (PREMIER study): 3-year results with the application of a flow diverter specific occlusion classificationBACKGROUND: The pipeline embolization device (PED; Medtronic) has presented as a safe and efficacious treatment for small- and medium-sized intracranial aneurysms. Independently adjudicated long-term results of the device in treating these lesions are still indeterminate. We present 3-year results, with additional application of a flow diverter specific occlusion scale. METHODS: PREMIER (prospective study on embolization of intracranial aneurysms with pipeline embolization device) is a prospective, single-arm trial. Inclusion criteria were patients with unruptured wide-necked intracranial aneurysms < /=12 mm. Primary effectiveness (complete aneurysm occlusion) and safety (major neurologic event) endpoints were independently monitored and adjudicated. RESULTS: As per the protocol, of 141 patients treated with a PED, 25 (17.7%) required angiographic follow-up after the first year due to incomplete aneurysm occlusion. According to the Core Radiology Laboratory review, three (12%) of these patients progressed to complete occlusion, with an overall rate of complete aneurysm occlusion at 3 years of 83.3% (115/138). Further angiographic evaluation using the modified Cekirge-Saatci classification demonstrated that complete occlusion, neck residual, or aneurysm size reduction occurred in 97.1%. The overall combined safety endpoint at 3 years was 2.8% (4/141), with only one non-debilitating major event occurring after the first year. There was one case of aneurysm recurrence but no cases of delayed rupture in this series. CONCLUSIONS: The PED device presents as a safe and effective modality in treating small- and medium-sized intracranial aneurysms. The application of a flow diverter specific occlusion classification attested the long-term durability with higher rate of successful aneurysm occlusion and no documented aneurysm rupture. TRIAL REGISTRATION: NCT02186561.
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Chronic Wound Image Augmentation and Assessment Using Semi-Supervised Progressive Multi-Granularity EfficientNetGoal: Augment a small, imbalanced, wound dataset by using semi-supervised learning with a secondary dataset. Then utilize the augmented wound dataset for deep learning-based wound assessment. Methods: The clinically-validated Photographic Wound Assessment Tool (PWAT) scores eight wound attributes: Size, Depth, Necrotic Tissue Type, Necrotic Tissue Amount, Granulation Tissue type, Granulation Tissue Amount, Edges, Periulcer Skin Viability to comprehensively assess chronic wound images. A small corpus of 1639 wound images labeled with ground truth PWAT scores was used as reference. A Semi-Supervised learning and Progressive Multi-Granularity training mechanism were used to leverage a secondary corpus of 9870 unlabeled wound images. Wound scoring utilized the EfficientNet Convolutional Neural Network on the augmented wound corpus. Results: Our proposed Semi-Supervised PMG EfficientNet (SS-PMG-EfficientNet) approach estimated all 8 PWAT sub-scores with classification accuracies and F1 scores of about 90% on average, and outperformed a comprehensive list of baseline models and had a 7% improvement over the prior state-of-the-art (without data augmentation). We also demonstrate that synthetic wound image generation using Generative Adversarial Networks (GANs) did not improve wound assessment. Conclusions: Semi-supervised learning on unlabeled wound images in a secondary dataset achieved impressive performance for deep learning-based wound grading.
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Mesh modeling of system geometry and anatomy phantoms for realistic GATE simulations and their inclusion in SPECT reconstructionObjective: Monte-Carlo simulation studies have been essential for advancing various developments in SPECT imaging, such as system design and accurate image reconstruction. Among the simulation software available, GATE is one of the most used simulation toolkits in nuclear medicine, which allows building systems and attenuation phantom geometries based on the combination of idealized volumes. However, these idealized volumes are inadequate for modeling free-form shape components of such geometries. Recent GATE versions alleviate these major limitations by allowing users to import triangulated surface meshes. Approach: In this study, we describe our mesh-based simulations of a next-generation multi-pinhole SPECT system dedicated to clinical brain imaging, called AdaptiSPECT-C. To simulate realistic imaging data, we incorporated in our simulation the XCAT phantom, which provides an advanced anatomical description of the human body. An additional challenge with the AdaptiSPECT-C geometry is that the default voxelized XCAT attenuation phantom was not usable in our simulation due to intersection of objects of dissimilar materials caused by overlap of the air containing regions of the XCAT beyond the surface of the phantom and the components of the imaging system. Main results: We validated our mesh-based modeling against the one constructed by idealized volumes for a simplified single vertex configuration of AdaptiSPECT-C through simulated projection data of 123I-activity distributions. We resolved the overlap conflict by creating and incorporating a mesh-based attenuation phantom following a volume hierarchy. We then evaluated our reconstructions with attenuation and scatter correction for projections obtained from simulation consisting of mesh-based modeling of the system and the attenuation phantom for brain imaging. Our approach demonstrated similar performance as the reference scheme simulated in air for uniform and clinical-like 123I-IMP brain perfusion source distributions. Significance: This work enables the simulation of complex SPECT acquisitions and reconstructions for emulating realistic imaging data close to those of actual patients.
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Changes in Stage at Presentation among Lung and Breast Cancer Patients During the COVID-19 PandemicBackground: The COVID-19 pandemic altered access to healthcare by decreasing number of patients able to receive preventative care and cancer screening. We hypothesized that given these changes in access to care, radiologic screening for breast and lung cancer would be decreased, and patients with these cancers would consequently present at later stages of their disease. Design: Retrospective cross-sectional study of 2017-September 2021 UMass Memorial Tumor Registry for adult breast and lung cancer patients. Changes in stage at presentation of breast and lung cancer during the COVID-19 pandemic were measured, defined as prior to and during COVID-19. Results: There were no statistically significant changes in the overall stage of presentation before or during the COVID-19 pandemic for either breast or lung cancer patients. Analysis of case presentation and stage during periods of COVID-19 surges that occurred over the time of this study compared to pre-pandemic data demonstrated a statistically significant decrease in overall presentation of breast cancer patients in the first surge, with no other statistically significant changes in breast cancer presentation. A non-statistically significant decrease in lung cancer presentations was seen during the initial surge of COVID-19. There was also a statistically significant increase in early-stage presentation of lung cancer during the second and third COVID-19 surges. Conclusions: In the two years after the COVID-19 pandemic we were not able to demonstrate stage migration at presentation of breast and lung cancer patients to later stages despite decreases in overall presentation during the initial two years of the COVID pandemic. An increase in early-stage lung cancer during the second and third surges is interesting and could be related to increased chest imaging for COVID pneumonia.
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Multiple expressions of "expert" abnormality gist in novices following perceptual learningWith a brief half-second presentation, a medical expert can determine at above chance levels whether a medical scan she sees is abnormal based on a first impression arising from an initial global image process, termed "gist." The nature of gist processing is debated but this debate stems from results in medical experts who have years of perceptual experience. The aim of the present study was to determine if gist processing for medical images occurs in naïve (non-medically trained) participants who received a brief perceptual training and to tease apart the nature of that gist signal. We trained 20 naïve participants on a brief perceptual-adaptive training of histology images. After training, naïve observers were able to obtain abnormality detection and abnormality categorization above chance, from a brief 500 ms masked presentation of a histology image, hence showing "gist." The global signal demonstrated in perceptually trained naïve participants demonstrated multiple dissociable components, with some of these components relating to how rapidly naïve participants learned a normal template during perceptual learning. We suggest that multiple gist signals are present when experts view medical images derived from the tens of thousands of images that they are exposed to throughout their training and careers. We also suggest that a directed learning of a normal template may produce better abnormality detection and identification in radiologists and pathologists.
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Current and upcoming radionuclide therapies in the direction of precision oncology: A narrative reviewAs new molecular tracers are identified to target specific receptors, tissue, and tumor types, opportunities arise for the development of both diagnostic tracers and their therapeutic counterparts, termed "theranostics." While diagnostic tracers utilize positron emitters or gamma-emitting radionuclides, their theranostic counterparts are typically bound to beta and alpha emitters, which can deliver specific and localized radiation to targets with minimal collateral damage to uninvolved surrounding structures. This is an exciting time in molecular imaging and therapy and a step towards personalized and precise medicine in which patients who were either without treatment options or not candidates for other therapies now have expanded options, with tangible data showing improved outcomes. This manuscript explores the current state of theranostics, providing background, treatment specifics, and toxicities, and discusses future potential trends.
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Resident Perspective of the Virtual Diagnostic Radiology Residency Interview Process: A National Survey From the Association of Program Directors in RadiologyRationale and objectives: The purpose of this study was to assess differences in first-year radiology resident perception of the match process and early satisfaction with residency programs between those who matched in 2020 versus 2021, the first virtual application cycle after the start of the COVID-19 pandemic. Materials and methods: A 33-question survey was distributed to first-year diagnostic radiology residents at programs throughout the United States through the Association of Program Directors in Radiology. Responses were collected in June of 2022 from residents who matched in 2020 and in July of 2022 from residents who matched in 2021. Questions were designed to assess applicant demographics, outcomes and attitudes towards the interview process. Comparison was made between the two cohorts. Results: Of the 2231 matched residents in the 2020 and 2021 match years, 108 residents (4.8%) received, responded, and met inclusion criteria for the survey. Forty-three of 46 (92.5%) respondents that matched in 2020 interviewed in-person compared to one of 60 (1.7%) that matched in 2021 (p < 0.0001). There was no difference in satisfaction of match results, current training programs, work culture, satisfaction with facilities, and depiction of residency structure. Applicants from the 2021 cohort were more likely to express concerns about interview hoarding, having enough time to ask questions on interview days, and ability to accurately present themselves in interviews but were more likely to favor virtual interviews for future cycles. Conclusion: The virtual interview process is perceived neutrally or positively by most early diagnostic radiology residents and produced similar satisfactory results compared to applicants that interviewed in person. Attention should be given to concerns of those who matched virtually if the virtual interview process is to be continued.
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Tet-Regulated Expression and Optical Clearing for In Vivo Visualization of Genetically Encoded Chimeric dCas9/Fluorescent Protein ProbesThe catalytically inactive mutant of Cas9 (dCas9) endonuclease has multiple biomedical applications, with the most useful being the activation/repression of transcription. dCas9 family members are also emerging as potential experimental tools for gene mapping at the level of individual live cells and intact tissue. We performed initial testing on a set of tools for Cas9-mediated visualization of nuclear compartments. We investigated doxycycline (Dox)-inducible (Tet-On) intracellular distribution of constructs encoding dCas9 orthologs from St. thermophilus (St) and N. meningitides (Nm) fused with EGFP and mCherry fluorescent proteins (FP) in human A549 cells. We also studied time-dependent expression of these chimeric fluorescent constructs (dCas9-FP) after Tet-On induction in live cells and compared it with the time course of dCas9-FP expression in experimental dCas9-FP-expressing tumor xenografts using a combination of fluorescence imaging and in vivo contrast-assisted magnetic resonance imaging for assessing the extent of tumor perfusion. In vivo Dox-induction of mCherry-chimera expression occurred in tumor xenografts as early as 24 h post-induction and was visualized by using optical clearing (OC) of the skin. OC via topical application of gadobutrol enabled high-contrast imaging of FP expression in tumor xenografts due to a 1.1-1.2-fold increase in FI in both the red and green channels.
