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Using medical images to evaluate disease severity and change over time is a routine and important task in clinical decision making. Grading systems are often used, but are unreliable as domain experts disagree on disease severity category thresholds. These discrete categories also do not reflect the underlying continuous spectrum of disease severity. To address these issues, we developed a convolutional Siamese neural network approach to evaluate disease severity at single time points and change between longitudinal patient visits on a continuous spectrum. We demonstrate this in two medical imaging domains: retinopathy of prematurity (ROP) in retinal photographs and osteoarthritis in knee radiographs. Our patient cohorts consist of 4861 images from 870 patients in the Imaging and Informatics in Retinopathy of Prematurity (i-ROP) cohort study and 10,012 images from 3021 patients in the Multicenter Osteoarthritis Study (MOST), both of which feature longitudinal imaging data. Multiple expert clinician raters ranked 100 retinal images and 100 knee radiographs from excluded test sets for severity of ROP and osteoarthritis, respectively. The Siamese neural network output for each image in comparison to a pool of normal reference images correlates with disease severity rank ( ρ  = 0.87 for ROP and ρ  = 0.89 for osteoarthritis), both within and between the clinical grading categories. Thus, this output can represent the continuous spectrum of disease severity at any single time point. The difference in these outputs can be used to show change over time. Alternatively, paired images from the same patient at two time points can be directly compared using the Siamese neural network, resulting in an additional continuous measure of change between images. Importantly, our approach does not require manual localization of the pathology of interest and requires only a binary label for training (same versus different). The location of disease and site of change detected by the algorithm can be visualized using an occlusion sensitivity map-based approach. For a longitudinal binary change detection task, our Siamese neural networks achieve test set receiving operator characteristic area under the curves (AUCs) of up to 0.90 in evaluating ROP or knee osteoarthritis change, depending on the change detection strategy. The overall performance on this binary task is similar compared to a conventional convolutional deep-neural network trained for multi-class classification. Our results demonstrate that convolutional Siamese neural networks can be a powerful tool for evaluating the continuous spectrum of disease severity and change in medical imaging.

The HPV-automated visual evaluation (PAVE) Study is an extensive, multinational initiative designed to advance cervical cancer prevention in resource-constrained regions. Cervical cancer disproportionally affects regions with limited access to preventive measures. PAVE aims to assess a novel screening-triage-treatment strategy integrating self-sampled HPV testing, deep-learning-based automated visual evaluation (AVE), and targeted therapies. Phase 1 efficacy involves screening up to 100,000 women aged 25-49 across nine countries, using self-collected vaginal samples for hierarchical HPV evaluation: HPV16, else HPV18/45, else HPV31/33/35/52/58, else HPV39/51/56/59/68 else negative. HPV-positive individuals undergo further evaluation, including pelvic exams, cervical imaging, and biopsies. AVE algorithms analyze images, assigning risk scores for precancer, validated against histologic high-grade precancer. Phase 1, however, does not integrate AVE results into patient management, contrasting them with local standard care.Phase 2 effectiveness focuses on deploying AVE software and HPV genotype data in real-time clinical decision-making, evaluating feasibility, acceptability, cost-effectiveness, and health communication of the PAVE strategy in practice. Currently, sites have commenced fieldwork, and conclusive results are pending. The study aspires to validate a screen-triage-treat protocol utilizing innovative biomarkers to deliver an accurate, feasible, and cost-effective strategy for cervical cancer prevention in resource-limited areas. Should the study validate PAVE, its broader implementation could be recommended, potentially expanding cervical cancer prevention worldwide. The consortial sites are responsible for their own study costs. Research equipment and supplies, and the NCI-affiliated staff are funded by the National Cancer Institute Intramural Research Program including supplemental funding from the Cancer Cures Moonshot Initiative. No commercial support was obtained. Brian Befano was supported by NCI/ NIH under Grant T32CA09168.

Recent progress in deep learning (DL) is producing a new generation of tools across numerous clinical applications. Within the analysis of brain tumors in magnetic resonance imaging, DL finds applications in tumor segmentation, quantification, and classification. It facilitates objective and reproducible measurements crucial for diagnosis, treatment planning, and disease monitoring. Furthermore, it holds the potential to pave the way for personalized medicine through the prediction of tumor type, grade, genetic mutations, and patient survival outcomes. In this review, we explore the transformative potential of DL for brain tumor care and discuss existing applications, limitations, and future directions and opportunities.

High-resolution microscopy images of tissue specimens provide detailed information about the morphology of normal and diseased tissue. Image analysis of tissue morphology can help cancer researchers develop a better understanding of cancer biology. Segmentation of nuclei and classification of tissue images are two common tasks in tissue image analysis. Development of accurate and efficient algorithms for these tasks is a challenging problem because of the complexity of tissue morphology and tumor heterogeneity. In this paper we present two computer algorithms; one designed for segmentation of nuclei and the other for classification of whole slide tissue images. The segmentation algorithm implements a multiscale deep residual aggregation network to accurately segment nuclear material and then separate clumped nuclei into individual nuclei. The classification algorithm initially carries out patch-level classification via a deep learning method, then patch-level statistical and morphological features are used as input to a random forest regression model for whole slide image classification. The segmentation and classification algorithms were evaluated in the MICCAI 2017 Digital Pathology challenge. The segmentation algorithm achieved an accuracy score of 0.78. The classification algorithm achieved an accuracy score of 0.81. These scores were the highest in the challenge.

BackgroundPrior work has demonstrated the near-perfect accuracy of a deep learning retinal image analysis system for diagnosing plus disease in retinopathy of prematurity (ROP). Here we assess the screening potential of this scoring system by determining its ability to detect all components of ROP diagnosis.MethodsClinical examination and fundus photography were performed at seven participating centres. A deep learning system was trained to detect plus disease, generating a quantitative assessment of retinal vascular abnormality (the i-ROP plus score) on a 1–9 scale. Overall ROP disease category was established using a consensus reference standard diagnosis combining clinical and image-based diagnosis. Experts then ranked ordered a second data set of 100 posterior images according to overall ROP severity.Results4861 examinations from 870 infants were analysed. 155 examinations (3%) had a reference standard diagnosis of type 1 ROP. The i-ROP deep learning (DL) vascular severity score had an area under the receiver operating curve of 0.960 for detecting type 1 ROP. Establishing a threshold i-ROP DL score of 3 conferred 94% sensitivity, 79% specificity, 13% positive predictive value and 99.7% negative predictive value for type 1 ROP. There was strong correlation between expert rank ordering of overall ROP severity and the i-ROP DL vascular severity score (Spearman correlation coefficient=0.93; p<0.0001).ConclusionThe i-ROP DL system accurately identifies diagnostic categories and overall disease severity in an automated fashion, after being trained only on posterior pole vascular morphology. These data provide proof of concept that a deep learning screening platform could improve objectivity of ROP diagnosis and accessibility of screening.

Predicting 30-day procedure-related mortality risk and 30-day unplanned readmission in patients undergoing lower extremity endovascular interventions for peripheral artery disease (PAD) may assist in improving patient outcomes. Risk prediction of 30-day mortality can help clinicians identify treatment plans to reduce the risk of death, and prediction of 30-day unplanned readmission may improve outcomes by identifying patients who may benefit from readmission prevention strategies. The goal of this study is to develop machine learning models to stratify risk of 30-day procedure-related mortality and 30-day unplanned readmission in patients undergoing lower extremity infra-inguinal endovascular interventions. We used a cohort of 14,444 cases from the American College of Surgeons National Surgical Quality Improvement Program database. For each outcome, we developed and evaluated multiple machine learning models, including Support Vector Machines, Multilayer Perceptrons, and Gradient Boosting Machines, and selected a random forest as the best-performing model for both outcomes. Our 30-day procedure-related mortality model achieved an AUC of 0.75 (95% CI: 0.71–0.79) and our 30-day unplanned readmission model achieved an AUC of 0.68 (95% CI: 0.67–0.71). Stratification of the test set by race (white and non-white), sex (male and female), and age (≥65 years and <65 years) and subsequent evaluation of demographic parity by AUC shows that both models perform equally well across race, sex, and age groups. We interpret the model globally and locally using Gini impurity and SHapley Additive exPlanations (SHAP). Using the top five predictors for death and mortality, we demonstrate differences in survival for subgroups stratified by these predictors, which underscores the utility of our model.

Exercise‐induced hyperemia in calf muscles was recently shown to be quantifiable with high‐resolution magnetic resonance imaging (MRI). However, processing of the MRI data to obtain muscle‐perfusion maps is time‐consuming. This study proposes to substantially accelerate the mapping of muscle perfusion using a deep‐learning method called artificial neural network (NN). Forty‐eight MRI scans were acquired from 21 healthy subjects and patients with peripheral artery disease (PAD). For optimal training of NN, different training‐data sets were compared, investigating the effect of data diversity and reference perfusion accuracy. Reference perfusion was estimated by tracer kinetic model fitting initialized with multiple values (multigrid model fitting). Result: The NN method was much faster than tracer kinetic model fitting. To generate a perfusion map of matrix 128 × 128 on a same computer, multigrid model fitting took about 80 min, single‐grid or regular model fitting about 3 min, while the NN method took about 1 s. Compared to the reference values, NN trained with a diverse group gave estimates with mean absolute error (MAE) of 15.9 ml/min/100g and correlation coefficient (R) of 0.949, significantly more accurate than regular model fitting (MAE 22.3 ml/min/100g, R 0.889, p < .001). Conclusion: the NN method enables rapid perfusion mapping, and if properly trained, estimates perfusion with accuracy comparable to multigrid model fitting. A recent study reported the potential of using DCE MRI method to map muscle perfusion after stimulation of exercise. This current study proposed a deep learning method to enable rapid processing of the data so that perfusion maps can be obtained online.

Objectives Intra-tumor heterogeneity has been previously shown to be an independent predictor of patient survival. The goal of this study is to assess the role of quantitative MRI-based measures of intra-tumor heterogeneity as predictors of survival in patients with metastatic colorectal cancer. Methods In this IRB-approved retrospective study, we identified 55 patients with stage 4 colon cancer with known hepatic metastasis on MRI. Ninety-four metastatic hepatic lesions were identified on post-contrast images and manually volumetrically segmented. A heterogeneity phenotype vector was extracted from each lesion. Univariate regression analysis was used to assess the contribution of 110 extracted features to survival prediction. A random forest–based machine learning technique was applied to the feature vector and to the standard prognostic clinical and pathologic variables. The dataset was divided into a training and test set at a ratio of 4:1. ROC analysis and confusion matrix analysis were used to assess classification performance. Results Mean survival time was 39 ± 3.9 months for the study population. A total of 22 texture features were associated with patient survival ( p < 0.05). The trained random forest machine learning model that included standard clinical and pathological prognostic variables resulted in an area under the ROC curve of 0.83. A model that adds imaging-based heterogeneity features to the clinical and pathological variables resulted in improved model performance for survival prediction with an AUC of 0.94. Conclusions MRI-based texture features are associated with patient outcomes and improve the performance of standard clinical and pathological variables for predicting patient survival in metastatic colorectal cancer. Key Points • MRI-based tumor heterogeneity texture features are associated with patient survival outcomes. • MRI-based tumor texture features complement standard clinical and pathological variables for prognosis prediction in metastatic colorectal cancer. • Agglomerative hierarchical clustering shows that patient survival outcomes are associated with different MRI tumor profiles.

The integration of artificial intelligence into clinical workflows requires reliable and robust models. Repeatability is a key attribute of model robustness. Ideal repeatable models output predictions without variation during independent tests carried out under similar conditions. However, slight variations, though not ideal, may be unavoidable and acceptable in practice. During model development and evaluation, much attention is given to classification performance while model repeatability is rarely assessed, leading to the development of models that are unusable in clinical practice. In this work, we evaluate the repeatability of four model types (binary classification, multi-class classification, ordinal classification, and regression) on images that were acquired from the same patient during the same visit. We study the each model’s performance on four medical image classification tasks from public and private datasets: knee osteoarthritis, cervical cancer screening, breast density estimation, and retinopathy of prematurity. Repeatability is measured and compared on ResNet and DenseNet architectures. Moreover, we assess the impact of sampling Monte Carlo dropout predictions at test time on classification performance and repeatability. Leveraging Monte Carlo predictions significantly increases repeatability, in particular at the class boundaries, for all tasks on the binary, multi-class, and ordinal models leading to an average reduction of the 95% limits of agreement by 16% points and of the class disagreement rate by 7% points. The classification accuracy improves in most settings along with the repeatability. Our results suggest that beyond about 20 Monte Carlo iterations, there is no further gain in repeatability. In addition to the higher test-retest agreement, Monte Carlo predictions are better calibrated which leads to output probabilities reflecting more accurately the true likelihood of being correctly classified.

Predicting 30-day procedure-related mortality risk and 30-day unplanned readmission in patients undergoing lower extremity endovascular interventions for peripheral artery disease (PAD) may assist in improving patient outcomes. Risk prediction of 30-day mortality can help clinicians identify treatment plans to reduce the risk of death, and prediction of 30-day unplanned readmission may improve outcomes by identifying patients who may benefit from readmission prevention strategies. The goal of this study is to develop machine learning models to stratify risk of 30-day procedure-related mortality and 30-day unplanned readmission in patients undergoing lower extremity infra-inguinal endovascular interventions. We used a cohort of 14,444 cases from the American College of Surgeons National Surgical Quality Improvement Program database. For each outcome, we developed and evaluated multiple machine learning models, including Support Vector Machines, Multilayer Perceptrons, and Gradient Boosting Machines, and selected a random forest as the best-performing model for both outcomes. Our 30-day procedure-related mortality model achieved an AUC of 0.75 (95% CI: 0.71–0.79) and our 30-day unplanned readmission model achieved an AUC of 0.68 (95% CI: 0.67–0.71). Stratification of the test set by race (white and non-white), sex (male and female), and age (≥65 years and <65 years) and subsequent evaluation of demographic parity by AUC shows that both models perform equally well across race, sex, and age groups. We interpret the model globally and locally using Gini impurity and SHapley Additive exPlanations (SHAP). Using the top five predictors for death and mortality, we demonstrate differences in survival for subgroups stratified by these predictors, which underscores the utility of our model.