Abstract: FR-PO933
Computationally Derived Characterization of Tubular Changes in Relation to the Development of Interstitial Fibrosis
Session Information
- Glomerular Diseases: Potpourri
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Fan, Fan, Emory University, Atlanta, Georgia, United States
- Liu, Qian, The Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania, United States
- Zee, Jarcy, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
- Ozeki, Takaya, University of Michigan Department of Internal Medicine, Ann Arbor, Michigan, United States
- Demeke, Dawit S., University of Michigan Department of Pathology, Ann Arbor, Michigan, United States
- Wang, Bangchen, Duke University Department of Pathology, Durham, North Carolina, United States
- Jacobs, Jackson, Emory University School of Medicine, Atlanta, Georgia, United States
- Shah, Manav P., Emory University School of Medicine, Atlanta, Georgia, United States
- Farris, Alton Brad, Emory University Department of Pathology and Laboratory Medicine, Atlanta, Georgia, United States
- Mariani, Laura H., University of Michigan Department of Internal Medicine, Ann Arbor, Michigan, United States
- Lafata, Kyle Jon, Duke University Department of Radiation Oncology, Durham, North Carolina, United States
- Chen, Yijiang, Stanford University Department of Radiation Oncology, Stanford, California, United States
- Holzman, Lawrence B., University of Pennsylvania Department of Medicine, Philadelphia, Pennsylvania, United States
- Hodgin, Jeffrey B., University of Michigan Department of Pathology, Ann Arbor, Michigan, United States
- Madabhushi, Anant, Emory University School of Medicine, Atlanta, Georgia, United States
- Barisoni, Laura, Duke University Department of Pathology, Durham, North Carolina, United States
- Janowczyk, Andrew, Emory University School of Medicine, Atlanta, United States
Background
The development of interstitial fibrosis & tubular atrophy (IFTA) is a progressive process. Visually it is challenging to quantify the spectrum of tubular changes from normal to atrophy and their spatial relationship with degree of interstitial fibrosis. This study utilizes computational image analysis to uncover tubular pathomic signatures that reflect the spectrum of tubular changes and their relationship with the microenvironment.
Methods
Cortex, pre-, mature-, and non-IFTA sub-regions were manually segmented in n=254 NEPTUNE/CureGN PAS-stained whole slide images (WSIs, n=135 FSGS,119 MCD/MCD-like). We developed and applied segmentation algorithms for tubular epithelium, lumen, nuclei, and basement membranes (288,172 tubules and 323,6081 nuclei) on 13 nephrectomies (reference tissue) and the NEPTUNE/CureGN dataset. 9 out of the 99 extracted, hand-crafted tubule-level features were previously shown to be associated with clinical outcomes and mapped to WSIs to identify the spectrum of tubular pathomic signatures across non-, pre-, and mature- IFTA regions.
Results
A progressive simplification of the tubular epithelium, thickening/area of the tubular basement membranes, and decreased nuclear distance to lumen from normal to full tubular atrophy was witnessed as one transitions between less to more diseased regions (Figure 1.1). The trajectory of tubular changes corresponds to the development of interstitial scarring (Figure 1.2).
Conclusion
Clinically relevant computationally derived tubular characteristics quantify the tubular changes across the spectrum of IFTA development, providing insights into tubule-level heterogeneity and atrophy pathway. This level of detail and quantification is not possible with human assessment alone and opens new opportunities for disease trajectory and biomarker studies.
Funding
- NIDDK Support