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Background and Purpose: To evaluate the radiomics-based model performance for differentiation between glioblastoma (GB) and brain metastases (BM) using magnetization prepared rapid gradient echo (MPRAGE) and volumetric interpolated breath-hold examination (VIBE) T1-contrast enhanced sequences., Materials and Methods: T1-CE MPRAGE and VIBE sequences acquired in 108 patients (31 GBs and 77 BM) during the same MRI session were retrospectively evaluated. Post standardized image pre-processing and segmentation, radiomics features were extracted from necrotic and enhancing tumor components. Pearson correlation analysis of radiomics features from tumor subcomponents was also performed. A total of 90 machine learning (ML) pipelines were evaluated using a five-fold cross validation. Performance was measured by mean AUC-ROC, Log-loss and Brier scores., Results: A feature-wise comparison showed that the radiomic features between sequences were strongly correlated, with the highest correlation for shape-based features. The mean AUC across the top-ten pipelines ranged between 0.851-0.890 with T1-CE MPRAGE and between 0.869-0.907 with T1-CE VIBE sequence. Top performing models for the MPRAGE sequence commonly used support vector machines, while those for VIBE sequence used either support vector machines or random forest. Common feature reduction methods for top-performing models included linear combination filter and least absolute shrinkage and selection operator (LASSO) for both sequences. For the same ML-feature reduction pipeline, model performances were comparable (AUC-ROC difference range: [-0.078, 0.046])., Conclusions: Radiomic features derived from T1-CE MPRAGE and VIBE sequences are strongly correlated and may have similar overall classification performance for differentiating GB from BM., Abbreviations: BM: Brain metastases, GB: glioblastoma, T1-CE: T1 contrast enhanced sequence, MPRAGE: magnetization prepared rapid gradient echo, ML: machine learning, RF: random forest, VIBE: volumetric interpolated breath-hold examination., Competing Interests: Disclosure of potential conflicts of interest: None., (© 2024 by American Journal of Neuroradiology.)

Accurate segmentation of retinal layers in optical coherence tomography (OCT) images is critical for assessing diseases that affect the optic nerve, but existing automated algorithms often fail when pathology causes irregular layer topology, such as extreme thinning of the ganglion cell-inner plexiform layer (GCIPL). Deep LOGISMOS, a hybrid approach that combines the strengths of deep learning and 3D graph search to overcome their limitations, was developed to improve the accuracy, robustness and generalizability of retinal layer segmentation. The method was trained on 124 OCT volumes from both eyes of 31 non-arteritic anterior ischemic optic neuropathy (NAION) patients and tested on three cross-sectional datasets with available reference tracings: Test-NAION (40 volumes from both eyes of 20 NAION subjects), Test-G (29 volumes from 29 glaucoma subjects/eyes), and Test-JHU (35 volumes from 21 multiple sclerosis and 14 control subjects/eyes) and one longitudinal dataset without reference tracings: Test-G-L (155 volumes from 15 glaucoma patients/eyes). In the three test datasets with reference tracings (Test-NAION, Test-G, and Test-JHU), Deep LOGISMOS achieved very high Dice similarity coefficients (%) on GCIPL: 89.97±3.59, 90.63±2.56, and 94.06±1.76, respectively. In the same context, Deep LOGISMOS outperformed the Iowa reference algorithms by improving the Dice score by 17.5, 5.4, and 7.5, and also surpassed the deep learning framework nnU-Net with improvements of 4.4, 3.7, and 1.0. For the 15 severe glaucoma eyes with marked GCIPL thinning (Test-G-L), it demonstrated reliable regional GCIPL thickness measurement over five years. The proposed Deep LOGISMOS approach has potential to enhance precise quantification of retinal structures, aiding diagnosis and treatment management of optic nerve diseases., Competing Interests: Z. Chen, None; H. Zhang, None; E.F. Linton, None; B.A. Johnson, None; Y.J. Choi, None; M.J. Kupersmith, None; M. Sonka, University of Iowa (Patents), Medical Imaging Applications, LLC (Co-Founder), VIDA Diagnostics, Inc. (Co-Founder); M.K. Garvin, University of Iowa (Patent); R.H. Kardon, FaceX, LLC (Co-Founder), J-K Wang, None., (© 2024 Optica Publishing Group.)

Purpose: To determine if machine learning (ML) or deep learning (DL) pipelines perform better in AI-based three-class classification of glioblastoma (GBM), intracranial metastatic disease (IMD) and primary CNS lymphoma (PCNSL)., Methodology: Retrospective analysis included 502 cases for training (208 GBM, 67 PCNSL and 227 IMD), with external validation on 86 cases (27:27:32). Multiparametric MRI images (T1W, T2W, FLAIR, DWI and T1-CE) were co-registered, resampled, denoised and intensity normalized, followed by semiautomatic 3D segmentation of the enhancing tumor (ET) and peritumoral region (PTR). Model performance was assessed using several ML pipelines and 3D-convolutional neural networks (3D-CNN) using sequence specific masks, as well as combination of masks. All pipelines were trained and evaluated with 5-fold nested cross-validation on internal data followed by external validation using multi-class AUC., Results: Two ML models achieved similar performance on test set, one using T2-ET and T2-PTR masks (AUC: 0.885, 95% CI: [0.816, 0.935] and another using T1-CE-ET and FLAIR-PTR mask (AUC: 0.878, CI: [0.804, 0.930]). The best performing DL models achieved an AUC of 0.854, (CI [0.774, 0.914]) on external data using T1-CE-ET and T2-PTR masks, followed by model derived from T1-CE-ET, ADC-ET and FLAIR-PTR masks (AUC: 0.851, CI [0.772, 0.909])., Conclusion: Both ML and DL derived pipelines achieved similar performance. T1-CE mask was used in three of the top four overall models. Additionally, all four models had some mask derived from PTR, either T2WI or FLAIR., Competing Interests: Declaration of Competing Interest GB: Research grant from Foundation of Sarcoidosis Research, that is unrelated to the submitted work. SM: Grant funding from NIH/ NCI, NovoCure Inc and Galelio CDS, unrelated to current work. SR: Full time employee of Avid Radiopharmaceuticals. MS: Inventor on patents and patent applications in computer vision and medical image analysis; Co-founder of Medical Imaging Applications, LLC, Coralville, Iowa, USA and VIDA Diagnostics, Inc., Coralville, Iowa, USA. Rest of the authors report no relationships that could be construed as a conflict of interest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Rationale and Objectives: Imaging-based differentiation between glioblastoma (GB) and brain metastases (BM) remains challenging. Our aim was to evaluate the performance of 3D-convolutional neural networks (CNN) to address this binary classification problem., Materials and Methods: T1-CE, T2WI, and FLAIR 3D-segmented masks of 307 patients (157 GB and 150 BM) were generated post resampling, co-registration normalization and semi-automated 3D-segmentation and used for internal model development. Subsequent external validation was performed on 59 cases (27 GB and 32 BM) from another institution. Four different mask-sequence combinations were evaluated using area under the curve (AUC), precision, recall and F1-scores. Diagnostic performance of a neuroradiologist and a general radiologist, both without and with the model output available, was also assessed., Results: 3D-model using the T1-CE tumor mask (TM) showed the highest performance [AUC 0.93 (95% CI 0.858-0.995)] on the external test set, followed closely by the model using T1-CE TM and FLAIR mask of peri-tumoral region (PTR) [AUC of 0.91 (95% CI 0.834-0.986)]. Models using T2WI masks showed robust performance on the internal dataset but lower performance on the external set. Both neuroradiologist and general radiologist showed improved performance with model output provided [AUC increased from 0.89 to 0.968 (p = 0.06) and from 0.78 to 0.965 (p = 0.007) respectively], the latter being statistically significant., Conclusion: 3D-CNNs showed robust performance for differentiating GB from BMs, with T1-CE TM, either alone or combined with FLAIR-PTR masks. Availability of model output significantly improved the accuracy of the general radiologist., Competing Interests: Declaration of Competing Interest GB: Research grant from Foundation of Sarcoidosis Research, that is unrelated to the submitted work. SM: Grant funding from NIH/ NCI, NovoCure Inc and Galelio CDS, unrelated to current work. SR: Full time employee of Avid Radiopharmaceuticals. MS: Inventor on patents and patent applications in computer vision and medical image analysis; Co-founder of Medical Imaging Applications, LLC, Coralville, Iowa, USA and VIDA Diagnostics, Inc., Coralville, Iowa, USA. Rest of the authors report no relationships that could be construed as a conflict of interest., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Lipid-rich plaque covered by a thin fibrous cap (FC) has been identified as a frequent morphological substrate for the development of acute coronary syndrome. Optical coherence tomography (OCT) permits the identification and measurement of the FC. Near-infrared spectroscopy (NIRS) has been approved for detection of coronary lipids., Aims: We aimed to assess the ability of detailed OCT analysis to identify coronary lipids, using NIRS as the reference method., Methods: In total, 40 patients with acute coronary syndrome underwent imaging of a non-culprit lesion by both NIRS and OCT. For each segment, the NIRS-derived 4 mm segment with maximal lipid core burden index (maxLCBI 4mm ) was assessed. OCT analysis was performed using a semi-automated method including measurement of the fibrous cap thickness (FCT) of all detected fibroatheromas. Subsequent quantitative volumetric evaluation furnished FCT, FC surface area (FC SA), lipid arc, and FC (fibrous cap) volume data. OCT features of lipid plaques were compared with maxLCBI 4mm . Predictors of maxLCBI 4mm >400 was assessed by using univariable and multivariable analysis., Results: OCT features (mean FCT, total FC SA, FC volume, maximal, mean, and total lipid arcs) strongly correlated with the maxLCBI 4mm ( p  = 0.012 for the mean FCT, respectively p  < 0.001 for all other aforementioned features). The strongest predictors of maxLCBI 4mm >400 were the maximal ( p  = 0.002) and mean ( p  = 0.002) lipid arc, and total FC SA ( p  = 0.012)., Conclusions: We found a strong correlation between the OCT-derived features and NIRS findings. Detailed OCT analysis may be reliably used for detection of the presence of coronary lipids.

Background: There is conflicting evidence on the role of acetylsalicylic acid (ASA) use in the development of cardiac allograft vasculopathy (CAV)., Methods: A nationwide prospective two-center study investigated changes in the coronary artery vasculature by highly automated 3-D optical coherence tomography (OCT) analysis at 1 month and 12 months after heart transplant (HTx). The influence of ASA use on coronary artery microvascular changes was analyzed in the overall study cohort and after propensity score matching for selected clinical CAV risk factors., Results: In total, 175 patients (mean age 52 ± 12 years, 79% male) were recruited. During the 1-year follow-up, both intimal and media thickness progressed, with ASA having no effect on its progression. However, detailed OCT analysis revealed that ASA use was associated with a lower increase in lipid plaque (LP) burden (p = .013), while it did not affect the other observed pathologies. Propensity score matching of 120 patients (60 patient pairs) showed similar results, with ASA use associated with lower progression of LPs (p = .002), while having no impact on layered fibrotic plaque (p = .224), calcification (p = .231), macrophage infiltration (p = .197), or the absolute coronary artery risk score (p = .277). According to Kaplan-Meier analysis, ASA use was not associated with a significant difference in survival (p = .699) CONCLUSION: This study showed a benefit of early ASA use after HTx on LP progression. However, ASA use did not have any impact on the progression of other OCT-observed pathologies or long-term survival., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: General deep-learning (DL)-based semantic segmentation methods with expert level accuracy may fail in 3D medical image segmentation due to complex tissue structures, lack of large datasets with ground truth, etc. For expeditious diagnosis, there is a compelling need to predict segmentation quality without ground truth. In some medical imaging applications, maintaining the quality of segmentation is crucial to the localized regions where disease is prevalent rather than just globally maintaining high-average segmentation quality. We propose a DL framework to identify regions of segmentation inaccuracies by combining a 3D generative adversarial network (GAN) and a convolutional regression network., Approach: Our approach is methodologically based on the learned ability to reconstruct the original images identifying the regions of location-specific segmentation failures, in which the reconstruction does not match the underlying original image. We use conditional GAN to reconstruct input images masked by the segmentation results. The regression network is trained to predict the patch-wise Dice similarity coefficient (DSC), conditioned on the segmentation results. The method relies directly on the extracted segmentation related features and does not need to use ground truth during the inference phase to identify erroneous regions in the computed segmentation., Results: We evaluated the proposed method on two public datasets: osteoarthritis initiative 4D (3D + time) knee MRI (knee-MR) and 3D non-small cell lung cancer CT (lung-CT). For the patch-wise DSC prediction, we observed the mean absolute errors of 0.01 and 0.04 with the independent standard for the knee-MR and lung-CT data, respectively., Conclusions: This method shows promising results in localizing the erroneous segmentation regions that may aid the downstream analysis of disease diagnosis and prognosis prediction., (© 2023 Society of Photo-Optical Instrumentation Engineers (SPIE).)

Purpose: Explaining deep learning model decisions, especially those for medical image segmentation, is a critical step toward the understanding and validation that will enable these powerful tools to see more widespread adoption in healthcare. We introduce kernel-weighted contribution, a visual explanation method for three-dimensional medical image segmentation models that produces accurate and interpretable explanations. Unlike previous attribution methods, kernel-weighted contribution is explicitly designed for medical image segmentation models and assesses feature importance using the relative contribution of each considered activation map to the predicted segmentation., Approach: We evaluate our method on a synthetic dataset that provides complete knowledge over input features and a comprehensive explanation quality metric using this ground truth. Our method and three other prevalent attribution methods were applied to five different model layer combinations to explain segmentation predictions for 100 test samples and compared using this metric., Results: Kernel-weighted contribution produced superior explanations of obtained image segmentations when applied to both encoder and decoder sections of a trained model as compared to other layer combinations ( p < 0.0005 ). In between-method comparisons, kernel-weighted contribution produced superior explanations compared with other methods using the same model layers in four of five experiments ( p < 0.0005 ) and showed equivalently superior performance to GradCAM++ when only using non-transpose convolution layers of the model decoder ( p = 0.008 )., Conclusion: The reported method produced explanations of superior quality uniquely suited to fully utilize the specific architectural considerations present in image and especially medical image segmentation models. Both the synthetic dataset and implementation of our method are available to the research community., (© 2023 Society of Photo-Optical Instrumentation Engineers (SPIE).)

Despite the advancement in deep learning-based semantic segmentation methods, which have achieved accuracy levels of field experts in many computer vision applications, the same general approaches may frequently fail in 3D medical image segmentation due to complex tissue structures, noisy acquisition, disease-related pathologies, as well as the lack of sufficiently large datasets with associated annotations. For expeditious diagnosis and quantitative image analysis in large-scale clinical trials, there is a compelling need to predict segmentation quality without ground truth. In this paper, we propose a deep learning framework to locate erroneous regions on the boundary surfaces of segmented objects for quality control and assessment of segmentation. A Convolutional Neural Network (CNN) is explored to learn the boundary related image features of multi-objects that can be used to identify location-specific inaccurate segmentation. The predicted error locations can facilitate efficient user interaction for interactive image segmentation (IIS). We evaluated the proposed method on two data sets: Osteoarthritis Initiative (OAI) 3D knee MRI and 3D calf muscle MRI. The average sensitivity scores of 0.95 and 0.92, and the average positive predictive values of 0.78 and 0.91 were achieved, respectively, for erroneous surface region detection of knee cartilage segmentation and calf muscle segmentation. Our experiment demonstrated promising performance of the proposed method for segmentation quality assessment by automated detection of erroneous surface regions in medical images., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Quantitative analysis of neurite growth and morphology is essential for understanding the determinants of neural development and regeneration, however, it is complicated by the labor-intensive process of measuring diverse parameters of neurite outgrowth. Consequently, automated approaches have been developed to study neurite morphology in a high-throughput and comprehensive manner. These approaches include computer-automated algorithms known as 'convolutional neural networks' (CNNs)-powerful models capable of learning complex tasks without the biases of hand-crafted models. Nevertheless, their complexity often relegates them to functioning as 'black boxes.' Therefore, research in the field of explainable AI is imperative to comprehend the relationship between CNN image analysis output and predefined morphological parameters of neurite growth in order to assess the applicability of these machine learning approaches. In this study, drawing inspiration from the field of automated feature selection, we investigate the correlation between quantified metrics of neurite morphology and the image analysis results from NeuriteNet-a CNN developed to analyze neurite growth. NeuriteNet accurately distinguishes images of neurite growth based on different treatment groups within two separate experimental systems. These systems differentiate between neurons cultured on different substrate conditions and neurons subjected to drug treatment inhibiting neurite outgrowth. By examining the model's function and patterns of activation underlying its classification decisions, we discover that NeuriteNet focuses on aspects of neuron morphology that represent quantifiable metrics distinguishing these groups. Additionally, it incorporates factors that are not encompassed by neuron morphology tracing analyses. NeuriteNet presents a novel tool ideally suited for screening morphological differences in heterogeneous neuron groups while also providing impetus for targeted follow-up studies., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: The purpose of this work was to investigate the use of a segmentation approach that could potentially improve the speed and reproducibility of contouring during magnetic resonance-guided adaptive radiation therapy., Methods and Materials: The segmentation algorithm was based on a hybrid deep neural network and graph optimization approach that also allows rapid user intervention (Deep layered optimal graph image segmentation of multiple objects and surfaces [LOGISMOS] + just enough interaction [JEI]). A total of 115 magnetic resonance-data sets were used for training and quantitative assessment. Expert segmentations were used as the independent standard for the prostate, seminal vesicles, bladder, rectum, and femoral heads for all 115 data sets. In addition, 3 independent radiation oncologists contoured the prostate, seminal vesicles, and rectum for a subset of patients such that the interobserver variability could be quantified. Consensus contours were then generated from these independent contours using a simultaneous truth and performance level estimation approach, and the deviation of Deep LOGISMOS + JEI contours to the consensus contours was evaluated and compared with the interobserver variability., Results: The absolute accuracy of Deep LOGISMOS + JEI generated contours was evaluated using median absolute surface-to-surface distance which ranged from a minimum of 0.20 mm for the bladder to a maximum of 0.93 mm for the prostate compared with the independent standard across all data sets. The median relative surface-to-surface distance was less than 0.17 mm for all organs, indicating that the Deep LOGISMOS + JEI algorithm did not exhibit a systematic under- or oversegmentation. Interobserver variability testing yielded a mean absolute surface-to-surface distance of 0.93, 1.04, and 0.81 mm for the prostate, seminal vesicles, and rectum, respectively. In comparison, the deviation of Deep LOGISMOS + JEI from consensus simultaneous truth and performance level estimation contours was 0.57, 0.64, and 0.55 mm for the same organs. On average, the Deep LOGISMOS algorithm took less than 26 seconds for contour segmentation., Conclusions: Deep LOGISMOS + JEI segmentation efficiently generated clinically acceptable prostate and normal tissue contours, potentially limiting the need for time intensive manual contouring with each fraction., Competing Interests: Daniel E. Hyer reports a relationship with Elekta that includes consulting or advisory, funding grants, and speaking and lecture fees. Joseph Caster reports a relationship with Elekta that includes funding grants. Joel St-Aubin reports a relationship with Elekta that includes funding grants and speaking and lecture fees. Jeffrey Snyder reports a relationship with Elekta that includes funding grants and speaking and lecture fees. Honghai Zhang reports financial support was provided by the National Institute of Biomedical Imaging and Bioengineering. Sean Mullan reports financial support provided by National Heart Lung and Blood Institute. John Buatti reports a relationship with American Society for Radiation Oncology that includes board membership. Milan Sonka reports financial support from the National Institute of Biomedical Imaging and Bioengineering.

Background: Automated segmentation of individual calf muscle compartments in 3D MR images is gaining importance in diagnosing muscle disease, monitoring its progression, and prediction of the disease course. Although deep convolutional neural networks have ushered in a revolution in medical image segmentation, achieving clinically acceptable results is a challenging task and the availability of sufficiently large annotated datasets still limits their applicability., Purpose: In this paper, we present a novel approach combing deep learning and graph optimization in the paradigm of assisted annotation for solving general segmentation problems in 3D, 4D, and generally n-D with limited annotation cost., Methods: Deep LOGISMOS combines deep-learning-based pre-segmentation of objects of interest provided by our convolutional neural network, FilterNet+, and our 3D multi-objects LOGISMOS framework (layered optimal graph image segmentation of multiple objects and surfaces) that uses newly designed trainable machine-learned cost functions. In the paradigm of assisted annotation, multi-object JEI for efficient editing of automated Deep LOGISMOS segmentation was employed to form a new larger training set with significant decrease of manual tracing effort., Results: We have evaluated our method on 350 lower leg (left/right) T1-weighted MR images from 93 subjects (47 healthy, 46 patients with muscular morbidity) by fourfold cross-validation. Compared with the fully manual annotation approach, the annotation cost with assisted annotation is reduced by 95%, from 8 h to 25 min in this study. The experimental results showed average Dice similarity coefficient (DSC) of 96.56 ± 0.26 % $96.56\pm 0.26 \%$ and average absolute surface positioning error of 0.63 pixels (0.44 mm) for the five 3D muscle compartments for each leg. These results significantly improve our previously reported method and outperform the state-of-the-art nnUNet method., Conclusions: Our proposed approach can not only dramatically reduce the expert's annotation efforts but also significantly improve the segmentation performance compared to the state-of-the-art nnUNet method. The notable performance improvements suggest the clinical-use potential of our new fully automated simultaneous segmentation of calf muscle compartments., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Syncope, a form of transient loss of consciousness, remains a complex medical condition for which adverse cardiovascular outcomes, including death, are of major concern but rarely occur. Current risk stratification algorithms have not completely delineated which patients benefit from hospitalization and specific interventions. Patients are often admitted unnecessarily and at high cost. Artificial intelligence (AI) and machine learning may help define the transient loss of consciousness event, diagnose the cause, assess short- and long-term risks, predict recurrence, and determine need for hospitalization and therapeutic intervention; however, several challenges remain, including medicolegal and ethical concerns. This collaborative statement, from a multidisciplinary group of clinicians, investigators, and scientists, focuses on the potential role of AI in syncope management with a goal to inspire creation of AI-derived clinical decision support tools that may improve patient outcomes, streamline diagnostics, and reduce health-care costs., Competing Interests: This research was funded by the Iowa Initiative for Artificial Intelligence (IIAI), Carver College of Medicine Office of Research, University of Iowa. Dr Olshansky is on the Data and Safety Monitoring Board of AstraZeneca. Dr Sonka is an inventor and has patents and patent applications in computer vision and medical image analysis; and is a cofounder of Medical Imaging Applications, LLC, Coralville, Iowa, USA and VIDA Diagnostics, Inc, Coralville, Iowa, USA. Dr Venkatesh Thiruganasambandamoorthy is supported through a Physicians’ Services Incorporated Foundation Mid-Career Clinical Researcher award and University of Ottawa Tier-1 Clinical Research Chair in Cardiovascular Emergencies award. Dr Thiruganasambandamoorthy has received peer-reviewed grant funds for studies from the following governmental or non-profit agencies: the 10.13039/501100000241Physicians’ Services Incorporated Foundation—Ontario, Canada, 10.13039/501100000024Canadian Institutes of Health Research, 10.13039/100004411Heart and Stroke Foundation Canada, and the Cardiac Arrhythmia Network of Canada as part of the Networks of Centres of Excellence (NCE; and is a consultant for the NIH funded Practical Approaches to Care in Emergency Syncope (PACES) study. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Caldendrin is a Ca 2+ binding protein that interacts with multiple effectors, such as the Ca v 1 L-type Ca 2+ channel, which play a prominent role in regulating the outgrowth of dendrites and axons (i.e., neurites) during development and in response to injury. Here, we investigated the role of caldendrin in Ca v 1-dependent pathways that impinge upon neurite growth in dorsal root ganglion neurons (DRGNs). By immunofluorescence, caldendrin was localized in medium- and large- diameter DRGNs. Compared to DRGNs cultured from WT mice, DRGNs of caldendrin knockout (KO) mice exhibited enhanced neurite regeneration and outgrowth. Strong depolarization, which normally represses neurite growth through activation of Ca v 1 channels, had no effect on neurite growth in DRGN cultures from female caldendrin KO mice. Remarkably, DRGNs from caldendrin KO males were no different from those of WT males in terms of depolarization-dependent neurite growth repression. We conclude that caldendrin opposes neurite regeneration and growth, and this involves coupling of Ca v 1 channels to growth-inhibitory pathways in DRGNs of females but not males., (© 2023. The Author(s).)

Optical Coherence Tomography (OCT) is an intravascular imaging modality enabling detailed evaluation of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). However, its clinical application remains hampered by time-consuming manual quantitative analysis. We aimed to validate a semi-automated quantitative OCT analysis software (Iowa Coronary Wall Analyzer, ICWA-OCT) to improve OCT-analysis in HTx patients. 23 patients underwent OCT evaluation of all three major coronary arteries at 3 months (3M) and 12 months (12M) after HTx. We analyzed OCT recordings using the semiautomatic software and compared results with measurements from a validated manual software. For semi-automated analysis, 31,228 frames from 114 vessels were available. The validation was based on a subset of 4287 matched frames. We applied mixed model statistics to accommodate the multilevel data structure with method as a fixed effect. Lumen (minimum, mean, maximum) and media (mean, maximum) metrics showed no significant differences. Mean and maximum intima area were underestimated by the semi-automated method (β-method mean  = - 0.289 mm 2 , p < 0.01; β-method max  = - 0.695 mm 2 , p < 0.01). Bland-Altman analyses showed increasing semi-automatic underestimation of intima measurements with increasing intimal extent. Comparing 3M to 12M progression between methods, mean intimal area showed minor underestimation (β-method mean  = - 1.03 mm 2 , p = 0.04). Lumen and media metrics showed excellent agreement between the manual and semi-automated method. Intima metrics and progressions from 3M to 12M were slightly underestimated by the semi-automated OCT software with unknown clinical relevance. The semi-automated software has the future potential to provide robust and time-saving evaluation of CAV progression., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Medieval bindings fragments have become increasingly interesting to Humanities researchers as sources for the textual and material history of medieval Europeans. Later book binders used these discarded and repurposed pieces of earlier medieval manuscripts to reinforce the structures of other manuscripts and printed books. That many of these fragments are contained within and obscured by decorative bindings that cannot be dismantled ethically has limited their discovery and description. Although previous attempts to recover these texts using IRT and MA-XRF scanning have been successful, the extensive time required to scan a single book, and the need to modify or create specialized IRT or MA-XRF equipment for this method are drawbacks. Our research proposes and tests the capabilities of medical CT scanning technologies (commonly available at research university medical schools) for making visible and legible these fragments hidden under leather bindings. Our research team identified three sixteenth-century printed codices in our university libraries that were evidently bound in tawed leather by one workshop. The damaged cover of one of these three had revealed medieval manuscript fragments on the book spine; this codex served as a control for testing the other two volumes to see if they, too, contain fragments. The use of a medical CT scanner proved successful in visualizing interior book-spine structures and some letterforms, but not all of the text was made visible. The partial success of CT-scanning points to the value of further experimentation, given the relatively wide availability of medical imaging technologies, with their potential for short, non-destructive, 3D imaging times., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2023.)

Background: The association between genetic polymorphisms and early cardiac allograft vasculopathy (CAV) development is relatively unexplored. Identification of genes involved in the CAV process may offer new insights into pathophysiology and lead to a wider range of therapeutic options., Methods: This prospective study of 109 patients investigated 44 single nucleotide polymorphisms (SNPs) within the susceptibility loci potentially related to coronary artery disease, carotid artery intima-media thickness (cIMT), and in nitric oxide synthase gene. Genotyping was done by the Fluidigm SNP Type assays and Fluidigm 48.48 Dynamic Array IFC. The intima thickness progression (IT) was evaluated by coronary optical coherence tomography performed 1 month and 12 months after heart transplantation (HTx)., Results: During the first post-HTx year, the mean intima thickness (IT) increased by 24.0 ± 34.2 µm (p < 0.001) and lumen area decreased by ‒0.9 ± 1.8 mm2 (p < 0.001). The rs1570360 (A/G) SNP of the vascular endothelial growth factor A (VEGFA) gene showed the strongest association with intima thickness progression, even in the presence of the traditional CAV risk factors. SNPs previously related to carotid artery intima-media thickness rs11785239 (PRAG1), rs6584389 (PAX2), rs13225723 (LINC02577) and rs17477177 (CCDC71L), were among the five most significantly associated with IT progression but lost their significance once traditional CAV risk factors had been added., Conclusion: Results of this study suggest that genetic variability may play an important role in CAV development. The vascular endothelial growth factor A gene SNP rs1570360 showed the strongest association with intima thickness (IT) progression measured by OCT, even in the presence of the traditional CAV risk factors (Tab. 3, Fig. 3, Ref. 36). Text in PDF www.elis.sk Keywords: cardiac allograft vasculopathy, optical coherence tomography, vascular endothelial growth factor A, intimal thickening, genetic polymorphism.

Background: Syncope, a common problem encountered in the emergency department (ED), has a multitude of causes ranging from benign to life-threatening. Hospitalization may be required, but the management can vary substantially depending on specific clinical characteristics. Models predicting admission and hospitalization length of stay (LoS) are lacking. The purpose of this study was to design an effective, exploratory model using machine learning (ML) technology to predict LoS for patients presenting with syncope. Methods: This was a retrospective analysis using over 4 million patients from the National Emergency Department Sample (NEDS) database presenting to the ED with syncope between 2016−2019. A multilayer perceptron neural network with one hidden layer was trained and validated on this data set. Results: Receiver Operator Characteristics (ROC) were determined for each of the five ANN models with varying cutoffs for LoS. A fair area under the curve (AUC of 0.78) to good (AUC of 0.88) prediction performance was achieved based on sequential analysis at different cutoff points, starting from the same day discharge and ending at the longest analyzed cutoff LoS ≤7 days versus >7 days, accordingly. The ML algorithm showed significant sensitivity and specificity in predicting short (≤48 h) versus long (>48 h) LoS, with an AUC of 0.81. Conclusions: Using variables available to triaging ED clinicians, ML shows promise in predicting hospital LoS with fair to good performance for patients presenting with syncope.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis. Surgical resection remains the only potential curative treatment option for early-stage resectable PDAC. Patients with locally advanced or micrometastatic disease should ideally undergo neoadjuvant therapy prior to surgical resection for an optimal treatment outcome. Computerized tomography (CT) scan is the most common imaging modality obtained prior to surgery. However, the ability of CT scans to assess the nodal status and resectability remains suboptimal and depends heavily on physician experience. Improved preoperative radiographic tumor staging with the prediction of postoperative margin and the lymph node status could have important implications in treatment sequencing. This paper proposes a novel machine learning predictive model, utilizing a three-dimensional convoluted neural network (3D-CNN), to reliably predict the presence of lymph node metastasis and the postoperative positive margin status based on preoperative CT scans., Methods: A total of 881 CT scans were obtained from 110 patients with PDAC. Patients and images were separated into training and validation groups for both lymph node and margin prediction studies. Per-scan analysis and per-patient analysis (utilizing majority voting method) were performed., Results: For a lymph node prediction 3D-CNN model, accuracy was 90% for per-patient analysis and 75% for per-scan analysis. For a postoperative margin prediction 3D-CNN model, accuracy was 81% for per-patient analysis and 76% for per-scan analysis., Discussion: This paper provides a proof of concept that utilizing radiomics and the 3D-CNN deep learning framework may be used preoperatively to improve the prediction of positive resection margins as well as the presence of lymph node metastatic disease. Further investigations should be performed with larger cohorts to increase the generalizability of this model; however, there is a great promise in the use of convoluted neural networks to assist clinicians with treatment selection for patients with PDAC., Competing Interests: CC received research support from Checkmate Pharmaceuticals, Angiodynamics, and Optimum Therapeutics for clinical trials and research projects unrelated to this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chang, Liu, Saey, Chang, Shrader, Steckly, Rajput, Sonka and Chan.)

Knee cartilage and bone segmentation is critical for physicians to analyze and diagnose articular damage and knee osteoarthritis (OA). Deep learning (DL) methods for medical image segmentation have largely outperformed traditional methods, but they often need large amounts of annotated data for model training, which is very costly and time-consuming for medical experts, especially on 3D images. In this paper, we report a new knee cartilage and bone segmentation framework, KCB-Net, for 3D MR images based on sparse annotation. KCB-Net selects a small subset of slices from 3D images for annotation, and seeks to bridge the performance gap between sparse annotation and full annotation. Specifically, it first identifies a subset of the most effective and representative slices with an unsupervised scheme; it then trains an ensemble model using the annotated slices; next, it self-trains the model using 3D images containing pseudo-labels generated by the ensemble method and improved by a bi-directional hierarchical earth mover's distance (bi-HEMD) algorithm; finally, it fine-tunes the segmentation results using the primal-dual Internal Point Method (IPM). Experiments on four 3D MR knee joint datasets (the SKI10 dataset, OAI ZIB dataset, Iowa dataset, and iMorphics dataset) show that our new framework outperforms state-of-the-art methods on full annotation, and yields high quality results for small annotation ratios even as low as 10%., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Imaging-based characteristics associated with the progression of stable coronary atherosclerotic lesions are poorly defined. Utilizing a combination of optical coherence tomography (OCT) and intravascular ultrasound (IVUS) imaging, we aimed to characterize the lesions prone to progression through clinical validation of a semiautomated OCT computational program., Methods: Patients with stable coronary artery disease underwent nonculprit vessel imaging with IVUS and OCT at baseline and IVUS at the 12-month follow-up. After coregistration of baseline and follow-up IVUS images, paired 5-mm segments from each patient were identified, demonstrating the greatest plaque progression and regression as measured by the change in plaque burden. Experienced readers identified plaque features on corresponding baseline OCT segments, and predictors of plaque progression were assessed by multivariable analysis. Each segment then underwent volumetric assessment of the fibrous cap (FC) using proprietary software., Results: Among 23 patients (70% men; median age, 67 years), experienced-reader analysis demonstrated that for every 100 μm increase in mean FC thickness, plaques were 87% less likely to progress ( P = .01), which persisted on multivariable analysis controlling for baseline plaque burden ( P = .05). Automated FC analysis ( n = 17 paired segments) confirmed this finding ( P = .01) and found thinner minimal FC thickness ( P = .01) and larger FC surface area of <65 μm ( P = .02) and <100 μm ( P = .04) in progressing segments than in regressing segments. No additional imaging features predicted plaque progression., Conclusions: A semiautomated FC analysis tool confirmed the significant association between thinner FC and stable coronary plaque progression along entire vessel segments, illustrating the diffuse nature of FC thinning and suggesting a future clinical role in predicting the progression of stable coronary artery disease., Competing Interests: Declaration of competing interest Dr Lopez is a consultant for Abbott-St Jude, runs educational training programs related to optical coherence tomography, and is an investigator in clinical trials with optical coherence tomography. Drs Kassis, Kovarnik, Chen, Weber, Martin, Darki, Woo, Wahle, and Sonka reported no financial interests.

Accurate 3D segmentation of calf muscle compartments in volumetric MR images is essential to diagnose as well as assess progression of muscular diseases. Recently, good segmentation performance was achieved using state-of-the-art deep learning approaches, which, however, require large amounts of annotated data for training. Considering that obtaining sufficiently large medical image annotation datasets is often difficult, time-consuming, and requires expert knowledge, minimizing the necessary sizes of expert-annotated training datasets is of great importance. This paper reports CMC-Net, a new deep learning framework for calf muscle compartment segmentation in 3D MR images that selects an effective small subset of 2D slices from the 3D images to be labelled, while also utilizing unannotated slices to facilitate proper generalization of the subsequent training steps. Our model consists of three parts: (1) an unsupervised method to select the most representative 2D slices on which expert annotation is performed; (2) ensemble model training employing these annotated as well as additional unannotated 2D slices; (3) a model-tuning method using pseudo-labels generated by the ensemble model that results in a trained deep network capable of accurate 3D segmentations. Experiments on segmentation of calf muscle compartments in 3D MR images show that our new approach achieves good performance with very small annotation ratios, and when utilizing full annotation, it outperforms state-of-the-art full annotation segmentation methods. Additional experiments on a 3D MR thigh dataset further verify the ability of our method in segmenting leg muscle groups with sparse annotation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Purpose: We explored the feasibility of automated, arterial input function independent, vendor neutral prediction of core infarct, and penumbral tissue using complete and partial computed tomographic perfusion data sets through neural networks., Methods: Using retrospective computed tomographic perfusion data from 57 patients, split as training/validation (60%/40%), we developed and validated separate 2-dimensional U-net models for cerebral blood flow (CBF) and time to maximum (Tmax) maps calculation to predict core infarct and tissue at risk, respectively. Once trained, the full sets of 28 input images were sequentially reduced to equitemporal 14, 10, and 7 time points. The averaged structural similarity index measure between the model-derived images and ground truth perfusion maps was compared. Volumes for core infarct and Tmax were compared using the Pearson correlation coefficient., Results: Both CBF and Tmax maps derived using 28 and 14 time points had similar structural similarity index measure (0.80-0.81; P >0.05) when compared with ground truth images. The Pearson correlation for the CBF and Tmax volumes derived from the model using 28-tp with ground truth volumes derived from the RAPID software was 0.69 for CBF and 0.74 for Tmax. The predicted maps were fully concordant in terms of laterality to the commercial perfusion maps. The mean Dice scores were 0.54 for the core infarct and 0.63 for the hypoperfusion maps., Conclusions: Artificial intelligence model-derived volumes show good correlation with RAPID-derived volumes for CBF and Tmax. Within the constraints of a small sample size, the perfusion map quality is similar when using 14-tp instead of 28-tp. Our findings provide proof of concept that vendor neutral artificial intelligence models for computed tomographic perfusion processing using complete or partial image data sets appear feasible. The model accuracy could be further optimized using larger data sets.

Background: During development or regeneration, neurons extend processes (i.e., neurites) via mechanisms that can be readily analyzed in culture. However, defining the impact of a drug or genetic manipulation on such mechanisms can be challenging due to the complex arborization and heterogeneous patterns of neurite growth in vitro. New Method: NeuriteNet is a Convolutional Neural Network (CNN) sorting model that uses a novel adaptation of the XRAI saliency map overlay, which is a region-based attribution method. NeuriteNet compares neuronal populations based on differences in neurite growth patterns, sorts them into respective groups, and overlays a saliency map indicating which areas differentiated the image for the sorting procedure., Results: In this study, we demonstrate that NeuriteNet effectively sorts images corresponding to dissociated neurons into control and treatment groups according to known morphological differences. Furthermore, the saliency map overlay highlights the distinguishing features of the neuron when sorting the images into treatment groups. NeuriteNet also identifies novel morphological differences in neurons cultured from control and genetically modified mouse strains. Comparison with Existing Methods: Unlike other neurite analysis platforms, NeuriteNet does not require manual manipulations, such as segmentation of neurites prior to analysis, and is more accurate than experienced researchers for categorizing neurons according to their pattern of neurite growth., Conclusions: NeuriteNet can be used to effectively screen for morphological differences in a heterogeneous group of neurons and to provide feedback on the key features distinguishing those groups via the saliency map overlay., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: Despite the robust diagnostic performance of MRI-based radiomic features for differentiating between glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL) reported on prior studies, the best sequence or a combination of sequences and model performance across various machine learning pipelines remain undefined. Herein, we compare the diagnostic performance of multiple radiomics-based models to differentiate GBM from PCNSL., Methods: Our retrospective study included 94 patients (34 with PCNSL and 60 with GBM). Model performance was assessed using various MRI sequences across 45 possible model and feature selection combinations for nine different sequence permutations. Predictive performance was assessed using fivefold repeated cross-validation with five repeats. The best and worst performing models were compared to assess differences in performance., Results: The predictive performance, both using individual and a combination of sequences, was fairly robust across multiple top performing models (AUC: 0.961-0.977) but did show considerable variation between the best and worst performing models. The top performing individual sequences had comparable performance to multiparametric models. The best prediction model in our study used a combination of ADC, FLAIR, and T1-CE achieving the highest AUC of 0.977, while the second ranked model used T1-CE and ADC, achieving a cross-validated AUC of 0.975., Conclusion: Radiomics-based predictive accuracy can vary considerably, based on the model and feature selection methods as well as the combination of sequences used. Also, models derived from limited sequences show performance comparable to those derived from all five sequences., Key Points: • Radiomics-based diagnostic performance of various machine learning models for differentiating glioblastoma and PCNSL varies considerably. • ML models using limited or multiple MRI sequences can provide comparable performance, based on the chosen model. • Embedded feature selection models perform better than models using a priori feature reduction., (© 2021. European Society of Radiology.)

Background: Changes in choroidal thickness are associated with various ocular diseases, and the choroid can be imaged using spectral-domain optical coherence tomography (SD-OCT) and enhanced depth imaging OCT (EDI-OCT)., New Method: Eighty macular SD-OCT volumes from 80 patients were obtained using the Zeiss Cirrus machine. Eleven additional control subjects had two Cirrus scans done in one visit along with enhanced depth imaging (EDI-OCT) using the Heidelberg Spectralis machine. To automatically segment choroidal layers from the OCT volumes, our graph-theoretic approach was utilized. The segmentation results were compared with reference standards from two independent graders, and the accuracy of automated segmentation was calculated using unsigned/signed border positioning/thickness errors and Dice similarity coefficient (DSC). The repeatability and reproducibility of our choroidal thicknesses were determined by intraclass correlation coefficient (ICC), coefficient of variation (CV), and repeatability coefficient (RC)., Results: The mean unsigned/signed border positioning errors for the choroidal inner and outer surfaces are 3.39 ± 1.26 µm (mean ± standard deviation)/- 1.52 ± 1.63 µm and 16.09 ± 6.21 µm/4.73 ± 9.53 µm, respectively. The mean unsigned/signed choroidal thickness errors are 16.54 ± 6.47 µm/6.25 ± 9.91 µm, and the mean DSC is 0.949 ± 0.025. The ICC (95% confidence interval), CV, RC values are 0.991 (0.977-0.997), 2.48%, 14.25 µm for the repeatability and 0.991 (0.977-0.997), 2.49%, 14.30 µm for the reproducibility studies, respectively., Comparison With Existing Method(s): The proposed method outperformed our previous method using choroidal vessel segmentation and inter-grader variability., Conclusions: This automated segmentation method can reliably measure choroidal thickness using different OCT platforms., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Prior radiomics studies have focused on two-class brain tumor classification, which limits generalizability. The performance of radiomics in differentiating the three most common malignant brain tumors (glioblastoma (GBM), primary central nervous system lymphoma (PCNSL), and metastatic disease) is assessed; factors affecting the model performance and usefulness of a single sequence versus multiparametric MRI (MP-MRI) remain largely unaddressed. This retrospective study included 253 patients (120 metastatic (lung and brain), 40 PCNSL, and 93 GBM). Radiomic features were extracted for whole a tumor mask (enhancing plus necrotic) and an edema mask (first pipeline), as well as for separate enhancing and necrotic and edema masks (second pipeline). Model performance was evaluated using MP-MRI, individual sequences, and the T1 contrast enhanced (T1-CE) sequence without the edema mask across 45 model/feature selection combinations. The second pipeline showed significantly high performance across all combinations (Brier score: 0.311-0.325). GBRM fit using the full feature set from the T1-CE sequence was the best model. The majority of the top models were built using a full feature set and inbuilt feature selection. No significant difference was seen between the top-performing models for MP-MRI (AUC 0.910) and T1-CE sequence with (AUC 0.908) and without edema masks (AUC 0.894). T1-CE is the single best sequence with comparable performance to that of multiparametric MRI (MP-MRI). Model performance varies based on tumor subregion and the combination of model/feature selection methods.

Few studies have addressed radiomics based differentiation of Glioblastoma (GBM) and intracranial metastatic disease (IMD). However, the effect of different tumor masks, comparison of single versus multiparametric MRI (mp-MRI) or select combination of sequences remains undefined. We cross-compared multiple radiomics based machine learning (ML) models using mp-MRI to determine optimized configurations. Our retrospective study included 60 GBM and 60 IMD patients. Forty-five combinations of ML models and feature reduction strategies were assessed for features extracted from whole tumor and edema masks using mp-MRI [T1W, T2W, T1-contrast enhanced (T1-CE), ADC, FLAIR], individual MRI sequences and combined T1-CE and FLAIR sequences. Model performance was assessed using receiver operating characteristic curve. For mp-MRI, the best model was LASSO model fit using full feature set (AUC 0.953). FLAIR was the best individual sequence (LASSO-full feature set, AUC 0.951). For combined T1-CE/FLAIR sequence, adaBoost-full feature set was the best performer (AUC 0.951). No significant difference was seen between top models across all scenarios, including models using FLAIR only, mp-MRI and combined T1-CE/FLAIR sequence. Top features were extracted from both the whole tumor and edema masks. Shape sphericity is an important discriminating feature.