Deep learning for fetal inflammatory response diagnosis in the umbilical cord

Abstract

Introduction: Inflammation of the umbilical cord can be seen as a result of ascending intrauterine infection or other inflammatory stimuli. Acute fetal inflammatory response (FIR) is characterized by infiltration of the umbilical cord by fetal neutrophils, and can be associated with neonatal sepsis or fetal inflammatory response syndrome. Recent advances in deep learning in digital pathology have demonstrated favorable performance across a wide range of clinical tasks, such as diagnosis and prognosis. In this study we classified FIR from whole slide images (WSI).

Methods: We digitized 4100 histological slides of umbilical cord stained with hematoxylin and eosin (H&E) and extracted placental diagnoses from the electronic health record. We build models using attention-based whole slide learning models. We compared strategies between features extracted by a model (ConvNeXtXLarge) pretrained on non-medical images (ImageNet), and one pretrained using histopathology images (UNI). We trained multiple iterations of each model and combined them into an ensemble.

Results: The predictions from the ensemble of models trained using UNI achieved an overall balanced accuracy of 0.836 on the test dataset. In comparison, the ensembled predictions using ConvNeXtXLarge had a lower balanced accuracy of 0.7209. Heatmaps generated from top accuracy model appropriately highlighted arteritis in cases of FIR 2. In FIR 1, the highest performing model assigned high attention to areas of activated-appearing stroma in Wharton's Jelly. However, other high-performing models assigned attention to umbilical vessels.

Discussion: We developed models for diagnosis of FIR from placental histology images, helping reduce interobserver variability among pathologists. Future work may examine the utility of these models for identifying infants at risk of systemic inflammatory response or early onset neonatal sepsis.

Keywords: Acute umbilical arteritis; Acute umbilical funisitis; Attention-based machine learning models; Fetal inflammatory response; Foundation models in pathology; Machine learning pathology models.