Watson, A. H. | bioRxiv Science

bioRxiv2025

Validation of deep learning enabled software MetronMind to measure vertebral heart size and vertebral left atrial size in dogs

Vertebral heart size (VHS) and vertebral left atrial size (VLAS) are objective radiographic measurements of heart and left atrial size respectively and are associated with inter and intraobserver variability when measured by humans. Artificial intelligence (AI) tools to determine VHS and VLAS have been developed which may reduce variability and save time. Two manual methods for measuring VHS and VLAS on right and left lateral canine thoracic radiographs were compared. Measurements of VHS and VLAS made by deep learning enabled program, MetronMind, were compared to a trained observer on right and left lateral radiographs from 1058 client-owned dogs including 80 breeds with a variety of heart sizes, thoracic conformations and radiographic quality. This was a retrospective, single center, method comparison study. Pearsons correlation, Bland-Altman plots and Passing-Bablok regression were used to assess agreement. Correlation between traditional and modified manual measurements for VHS and VLAS were strong (r=0.994 and r=0.974 respectively), with minimal bias (-0.10 and 0.04 vertebrae respectively) indicating that the modified methods closely approximate traditional measurements obtained from right lateral views. MetronMind measurements of VHS and VLAS from right lateral radiographs correlated well with the human observers modified measurements (r=0.947 and r=0.811 respectively), showing small mean biases (0.08 and 0.07 vertebrae respectively). Correlation between left and right lateral radiographic measurements of VHS (0.87 and 0.91) was higher than for VLAS (0.73 and 0.64) and bias was larger for VHS (0.26 and 0.31 vertebrae) than VLAS (-0.13 and -0.10 vertebrae) for humans and MetronMind respectively. MetronMind can therefore assist veterinarians with measuring VHS and VLAS in dogs and right lateral radiographs are preferred. Future studies are needed to compare artificial intelligence derived radiographic measures with echocardiographic measures of cardiac size.

physiology↗

bioRxiv2020

LRG1 destabilizes tumor vessels and restricts immunotherapeutic potency

Vascular dysfunction contributes to the pro-oncogenic tumor microenvironment and impedes the delivery of therapeutics. Normalizing of the tumor vasculature has therefore become a potential therapeutic objective. We previously reported that the secreted glycoprotein, leucine-rich -2-glycoprotein 1 (LRG1), contributes to the formation of pathogenic neovascularization. Here we show that in mouse models of cancer, Lrg1 is induced in tumor endothelial cells. We demonstrate that the expression of LRG1 impacts on tumor progression as Lrg1 deletion or treatment with a LRG1 function-blocking antibody inhibited tumor growth and improved survival. Inhibition of LRG1 increased endothelial cell pericyte coverage and improved vascular function resulting in significantly enhanced efficacy of cisplatin chemotherapy, adoptive T-cell therapy and immune checkpoint inhibition (anti-PD1) therapy. With immunotherapy, LRG1 inhibition led to a significant shift in the tumor microenvironment from being predominantly immune silent (cold) to immune active (hot). LRG1 therefore drives vascular abnormalization and its inhibition represents a novel and effective means of improving the efficacy of cancer therapeutics.

cancer biology↗