Harnessing non-destructive 3D pathology

This Learning Wednesday paper note highlights “Harnessing non-destructive 3D pathology.” The study is relevant to digital pathology, focusing on how three-dimensional tissue context can alter what researchers see and measure.

Selected notes from the paper

"Disease diagnosis and characterization depend upon the rapid and accurate pathological analysis of biopsies and surgically excised tissues."

"Unfortunately, interobserver variance amongst pathologists is high, with kappa values ranging from 0.3 and 0.8."

"3D pathology has the potential to provide a transformative improvement in diagnostic performance for a number of reasons: vastly greater (multiple log orders) sampling of tissue specimens, volumetric imaging of cell distributions and tissue structures that are prognostic and predictive, nondestructive imaging, which allows valuable biopsy specimens to be used for downstream molecular assays, and a simplified process with cost benefits for pathology laboratories."

"The ability to render 3D datasets with color palettes that mimic conventional slide-based H&E histology and IHC will likely be important for pathologists to trust and adopt 3D pathology methods in the near future."

"As AI algorithms are increasingly validated and trusted by clinicians, they may eventually be utilized for fully automated analysis of 3D pathology datasets, with pathologist oversight if necessary."

"Early incorporation of AI analysis will likely be for triaging unequivocal cases, in order to reduce pathologist workloads, and to guide their efforts towards regions of ambiguity and/or diagnostic importance."

"Recent FDA approval of digital pathology solutions indicates that pathology is entering into a phase of modernization and change that will likely evolve over the next half-century."

"3D pathology methods do not interfere with current histopathology methods, allowing continued reliance on existing disease-classification schemes."

"Open-top light-sheet (OTLS) microscopy was specifically designed for high-throughput 3D pathology of large clinical specimens."

"A follow-up study by Reder et al., using the OTLS technology, provided additional insights into the potential value of 3D pathology, including the high variability in glandular morphology throughout an entire core-needle biopsy, which could have a dramatic influence on treatment decisions."

"AI approaches integrating multiple data types have already been used in cancers of the lung, breast, brain, and prostate, as well as for cardiovascular and neurological diseases."

"3D pathology has the potential to form a bridge between anatomic pathology and other diagnostic disciplines such as genomics and radiology."

"Studies showing clear advantages for improving clinical outcomes will cause oncologists and patients to demand these new services."

he use of computational 3D pathology for guiding the clinical management of prostate cancer."

Alpenglow Perspective

From an Alpenglow perspective, this paper is useful because it connects digital pathology to a broader need in 3D spatial biology by measuring tissue architecture across depth while preserving context for quantitative analysis.