Kristopher Standish

Basudha Pal, Sharif Amit Kamran, Brendon Lutnick et al.

Psoriasis (PsO) severity scoring is important for clinical trials but is hindered by inter-rater variability and the burden of in person clinical evaluation. Remote imaging using patient captured mobile photos offers scalability but introduces challenges, such as variation in lighting, background, and device quality that are often imperceptible to humans but can impact model performance. These factors, along with inconsistencies in dermatologist annotations, reduce the reliability of automated severity scoring. We propose a framework to automatically flag problematic training images that introduce spurious correlations which degrade model generalization, using a gradient based interpretability approach. By tracing the gradients of misclassified validation images, we detect training samples where model errors align with inconsistently rated examples or are affected by subtle, nonclinical artifacts. We apply this method to a ConvNeXT based weakly supervised model designed to classify PsO severity from phone images. Removing 8.2% of flagged images improves model AUC-ROC by 5% (85% to 90%) on a held out test set. Commonly, multiple annotators and an adjudication process ensure annotation accuracy, which is expensive and time consuming. Our method detects training images with annotation inconsistencies, potentially removing the need for manual review. When applied to a subset of training data rated by two dermatologists, the method identifies over 90% of cases with inter-rater disagreement by reviewing only the top 30% of samples. This improves automated scoring for remote assessments, ensuring robustness despite data collection variability.

Sharif A. Kamran, Molly V. Lucas, Brendon Lutnick et al.

Psoriasis is a chronic skin condition that requires long-term treatment and monitoring. Although, the Psoriasis Area and Severity Index (PASI) is utilized as a standard measurement to assess psoriasis severity in clinical trials, it has many drawbacks such as (1) patient burden for in-person clinic visits for assessment of psoriasis, (2) time required for investigator scoring and (3) variability of inter- and intra-rater scoring. To address these drawbacks, we propose a novel and interpretable deep learning architecture called PSO-Net, which maps digital images from different anatomical regions to derive attention-based scores. Regional scores are further combined to estimate an absolute PASI score. Moreover, we devise a novel regression activation map for interpretability through ranking attention scores. Using this approach, we achieved inter-class correlation scores of 82.2% [95% CI: 77- 87%] and 87.8% [95% CI: 84-91%] with two different clinician raters, respectively.

Shikha Dubey, Patricia Raciti, Kristopher Standish et al.

High-fidelity registration of histopathological whole slide images (WSIs), such as hematoxylin & eosin (H&E) and immunohistochemistry (IHC), is vital for integrated molecular analysis but challenging to evaluate without ground-truth (GT) annotations. Existing WSI-level assessments -- using annotated landmarks or intensity-based similarity metrics -- are often time-consuming, unreliable, and computationally intensive, limiting large-scale applicability. This study proposes a fast, unsupervised framework that jointly employs down-sampled tissue masks- and deformations-based metrics for registration quality assessment (RQA) of registered H&E and IHC WSI pairs. The masks-based metrics measure global structural correspondence, while the deformations-based metrics evaluate local smoothness, continuity, and transformation realism. Validation across multiple IHC markers and multi-expert assessments demonstrate a strong correlation between automated metrics and human evaluations. In the absence of GT, this framework offers reliable, real-time RQA with high fidelity and minimal computational resources, making it suitable for large-scale quality control in digital pathology.

Damola Agbelese, Krishna Chaitanya, Pushpak Pati et al.

Reliable uncertainty quantification (UQ) is essential in medical AI. Evidential Deep Learning (EDL) offers a computationally efficient way to quantify model uncertainty alongside predictions, unlike traditional methods such as Monte Carlo (MC) Dropout and Deep Ensembles (DE). However, all these methods often rely on a single expert's annotations as ground truth for model training, overlooking the inter-rater variability in healthcare. To address this issue, we propose MEGAN, a Multi-Expert Gating Network that aggregates uncertainty estimates and predictions from multiple AI experts via EDL models trained with diverse ground truths and modeling strategies. MEGAN's gating network optimally combines predictions and uncertainties from each EDL model, enhancing overall prediction confidence and calibration. We extensively benchmark MEGAN on endoscopy videos for Ulcerative colitis (UC) disease severity estimation, assessed by visual labeling of Mayo Endoscopic Subscore (MES), where inter-rater variability is prevalent. In large-scale prospective UC clinical trial, MEGAN achieved a 3.5% improvement in F1-score and a 30.5% reduction in Expected Calibration Error (ECE) compared to existing methods. Furthermore, MEGAN facilitated uncertainty-guided sample stratification, reducing the annotation burden and potentially increasing efficiency and consistency in UC trials.

Evan Schwab, Gabriela Oana Cula, Kristopher Standish et al.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by relapsing inflammation of the large intestine. The severity of UC is often represented by the Mayo Endoscopic Subscore (MES) which quantifies mucosal disease activity from endoscopy videos. In clinical trials, an endoscopy video is assigned an MES based upon the most severe disease activity observed in the video. For this reason, severe inflammation spread throughout the colon will receive the same MES as an otherwise healthy colon with severe inflammation restricted to a small, localized segment. Therefore, the extent of disease activity throughout the large intestine, and overall response to treatment, may not be completely captured by the MES. In this work, we aim to automatically estimate UC severity for each frame in an endoscopy video to provide a higher resolution assessment of disease activity throughout the colon. Because annotating severity at the frame-level is expensive, labor-intensive, and highly subjective, we propose a novel weakly supervised, ordinal classification method to estimate frame severity from video MES labels alone. Using clinical trial data, we first achieved 0.92 and 0.90 AUC for predicting mucosal healing and remission of UC, respectively. Then, for severity estimation, we demonstrate that our models achieve substantial Cohen's Kappa agreement with ground truth MES labels, comparable to the inter-rater agreement of expert clinicians. These findings indicate that our framework could serve as a foundation for novel clinical endpoints, based on a more localized scoring system, to better evaluate UC drug efficacy in clinical trials.

AJ Venkatakrishnan, Arjun Puranik, Akash Anand et al.

The COVID-19 pandemic demands assimilation of all available biomedical knowledge to decode its mechanisms of pathogenicity and transmission. Despite the recent renaissance in unsupervised neural networks for decoding unstructured natural languages, a platform for the real-time synthesis of the exponentially growing biomedical literature and its comprehensive triangulation with deep omic insights is not available. Here, we present the nferX platform for dynamic inference from over 45 quadrillion possible conceptual associations extracted from unstructured biomedical text, and their triangulation with Single Cell RNA-sequencing based insights from over 25 tissues. Using this platform, we identify intersections between the pathologic manifestations of COVID-19 and the comprehensive expression profile of the SARS-CoV-2 receptor ACE2. We find that tongue keratinocytes and olfactory epithelial cells are likely under-appreciated targets of SARS-CoV-2 infection, correlating with reported loss of sense of taste and smell as early indicators of COVID-19 infection, including in otherwise asymptomatic patients. Airway club cells, ciliated cells and type II pneumocytes in the lung, and enterocytes of the gut also express ACE2. This study demonstrates how a holistic data science platform can leverage unprecedented quantities of structured and unstructured publicly available data to accelerate the generation of impactful biological insights and hypotheses.