Novel Clinical-Grade Prostate Cancer Detection and Grading Model: Development and Prospective Validation Using Real World Data, with Performance Assessment on IHC Requested Cases

Artificial intelligence may assist healthcare systems in meeting increasing demand for pathology services while maintaining diagnostic quality and reducing turnaround time and costs. We aimed to investigate the performance of an institutionally developed system for prostate cancer detection, grading, and workflow optimization and to contrast this with commercial alternatives. From August 2021 to March 2023, we scanned 21,396 slides from 1,147 patients with positive biopsies. We developed models for cancer detection, grading, and screening of equivocal cases for IHC ordering. We compared a task-specific model trained using the PANDA dataset of prostate cancer biopsies with one built using features extracted by the general-purpose histology foundation model, UNI and compare their performance in an unfiltered prospectively collected dataset that reflects our patient population (1737 slides,95 patients). We evaluated the contributions of a bespoke model designed to improve sensitivity in detecting small cancer foci and scoring of broader patterns observed at lower resolution. We found high concordance between the developed systems and pathologist reference in detection (AUC 98.5, sensitivity 95.0, and specificity 97.8), ISUP grading (quadratic Cohen's kappa 0.869), grade group 3 or higher (AUC 97.5, sensitivity 94.9, specificity 96.6) and comparable to published data from commercial systems. Screening could reduce IHC ordering for equivocal cases by 44.5% with an overall error rate of 1.8% (1.4% false positive, 0.4% false negative rates). Institutions like academic medical centers that have high scanning volumes and report abstraction capabilities can develop accurate computational pathology models for internal use. These models have the potential to aid in quality control role and to improve workflow in the pathology lab to help meet future challenges in prostate cancer diagnosis.

Sequential Multi-Dimensional Self-Supervised Learning for Clinical Time Series

Self-supervised learning (SSL) for clinical time series data has received significant attention in recent literature, since these data are highly rich and provide important information about a patient's physiological state. However, most existing SSL methods for clinical time series are limited in that they are designed for unimodal time series, such as a sequence of structured features (e.g., lab values and vitals signs) or an individual high-dimensional physiological signal (e.g., an electrocardiogram). These existing methods cannot be readily extended to model time series that exhibit multimodality, with structured features and high-dimensional data being recorded at each timestep in the sequence. In this work, we address this gap and propose a new SSL method -- Sequential Multi-Dimensional SSL -- where a SSL loss is applied both at the level of the entire sequence and at the level of the individual high-dimensional data points in the sequence in order to better capture information at both scales. Our strategy is agnostic to the specific form of loss function used at each level -- it can be contrastive, as in SimCLR, or non-contrastive, as in VICReg. We evaluate our method on two real-world clinical datasets, where the time series contains sequences of (1) high-frequency electrocardiograms and (2) structured data from lab values and vitals signs. Our experimental results indicate that pre-training with our method and then fine-tuning on downstream tasks improves performance over baselines on both datasets, and in several settings, can lead to improvements across different self-supervised loss functions.

Wearable Respiration Monitoring: Interpretable Inference with Context and Sensor Biomarkers

Breathing rate (BR), minute ventilation (VE), and other respiratory parameters are essential for real-time patient monitoring in many acute health conditions, such as asthma. The clinical standard for measuring respiration, namely Spirometry, is hardly suitable for continuous use. Wearables can track many physiological signals, like ECG and motion, yet not respiration. Deriving respiration from other modalities has become an area of active research. In this work, we infer respiratory parameters from wearable ECG and wrist motion signals. We propose a modular and generalizable classification-regression pipeline to utilize available context information, such as physical activity, in learning context-conditioned inference models. Morphological and power domain novel features from the wearable ECG are extracted to use with these models. Exploratory feature selection methods are incorporated in this pipeline to discover application-specific interpretable biomarkers. Using data from 15 subjects, we evaluate two implementations of the proposed pipeline: for inferring BR and VE. Each implementation compares generalized linear model, random forest, support vector machine, Gaussian process regression, and neighborhood component analysis as contextual regression models. Permutation, regularization, and relevance determination methods are used to rank the ECG features to identify robust ECG biomarkers across models and activities. This work demonstrates the potential of wearable sensors not only in continuous monitoring, but also in designing biomarker-driven preventive measures.