Photon Absorption Remote Sensing Virtual Histopathology: A Preliminary Exploration of Diagnostic Equivalence to Gold-Standard H&E Staining in Skin Cancer Excisional Biopsies

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Main Authors: Ecclestone, Benjamin R., Tweel, James E. D., Daoud, Marie Abi, Gaouda, Hager, Dinakaran, Deepak, Wallace, Michael P., Somani, Ally Khan, Bigras, Gilbert, Mackey, John R., Reza, Parsin Haji
Format: Preprint
Published: 2025
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author Ecclestone, Benjamin R.
Tweel, James E. D.
Daoud, Marie Abi
Gaouda, Hager
Dinakaran, Deepak
Wallace, Michael P.
Somani, Ally Khan
Bigras, Gilbert
Mackey, John R.
Reza, Parsin Haji
author_facet Ecclestone, Benjamin R.
Tweel, James E. D.
Daoud, Marie Abi
Gaouda, Hager
Dinakaran, Deepak
Wallace, Michael P.
Somani, Ally Khan
Bigras, Gilbert
Mackey, John R.
Reza, Parsin Haji
contents Photon Absorption Remote Sensing (PARS) enables label-free imaging of subcellular morphology by observing biomolecule specific absorption interactions. Coupled with deep-learning, PARS produces label-free virtual Hematoxylin and Eosin (H&E) stained images in unprocessed tissues. This study evaluates the diagnostic performance of PARS virtual H&E images in excisional skin biopsies, including Squamous (SCC), Basal (BCC) Cell Carcinoma, and normal skin. Sixteen unstained formalin-fixed paraffin-embedded skin excisions were PARS imaged, virtually H&E stained, then chemically stained and imaged at 40x. Seven fellowship trained dermatopathologists assessed all images. Example PARS and chemical H&E whole-slide images from this study are available at the BioImage Archive (https://doi.org/10.6019/S-BIAD2324). Concordance analysis indicates 95.5% agreement between primary diagnoses from PARS versus H&E images (Cohen's k=0.93). Inter-rater reliability was near-perfect for both image types (Fleiss' k=0.89 for PARS, k=0.80 for H&E). For subtype classification, agreement was near-perfect 91% (k=0.73) for SCC and was perfect for BCC. For malignancy confinement (e.g., cancer margins), agreement was 92% between PARS and H&E (k=0.718). During assessment dermatopathologists could not reliably distinguish image origin (PARS vs. H&E), and diagnostic confidence was equivalent. Inter-rater reliability for PARS virtual H&E was consistent with reported histologic evaluation benchmarks. These results indicate that PARS virtual histology may be diagnostically equivalent to chemical H&E staining in dermatopathology diagnostics, while enabling assessment directly from unlabeled slides. In turn, the label-free PARS virtual H&E imaging workflow may preserve tissue for downstream analysis while producing data well-suited for AI integration potentially accelerating and enhancing skin cancer diagnostics.
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id arxiv_https___arxiv_org_abs_2504_18737
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Photon Absorption Remote Sensing Virtual Histopathology: A Preliminary Exploration of Diagnostic Equivalence to Gold-Standard H&E Staining in Skin Cancer Excisional Biopsies
Ecclestone, Benjamin R.
Tweel, James E. D.
Daoud, Marie Abi
Gaouda, Hager
Dinakaran, Deepak
Wallace, Michael P.
Somani, Ally Khan
Bigras, Gilbert
Mackey, John R.
Reza, Parsin Haji
Quantitative Methods
Image and Video Processing
Photon Absorption Remote Sensing (PARS) enables label-free imaging of subcellular morphology by observing biomolecule specific absorption interactions. Coupled with deep-learning, PARS produces label-free virtual Hematoxylin and Eosin (H&E) stained images in unprocessed tissues. This study evaluates the diagnostic performance of PARS virtual H&E images in excisional skin biopsies, including Squamous (SCC), Basal (BCC) Cell Carcinoma, and normal skin. Sixteen unstained formalin-fixed paraffin-embedded skin excisions were PARS imaged, virtually H&E stained, then chemically stained and imaged at 40x. Seven fellowship trained dermatopathologists assessed all images. Example PARS and chemical H&E whole-slide images from this study are available at the BioImage Archive (https://doi.org/10.6019/S-BIAD2324). Concordance analysis indicates 95.5% agreement between primary diagnoses from PARS versus H&E images (Cohen's k=0.93). Inter-rater reliability was near-perfect for both image types (Fleiss' k=0.89 for PARS, k=0.80 for H&E). For subtype classification, agreement was near-perfect 91% (k=0.73) for SCC and was perfect for BCC. For malignancy confinement (e.g., cancer margins), agreement was 92% between PARS and H&E (k=0.718). During assessment dermatopathologists could not reliably distinguish image origin (PARS vs. H&E), and diagnostic confidence was equivalent. Inter-rater reliability for PARS virtual H&E was consistent with reported histologic evaluation benchmarks. These results indicate that PARS virtual histology may be diagnostically equivalent to chemical H&E staining in dermatopathology diagnostics, while enabling assessment directly from unlabeled slides. In turn, the label-free PARS virtual H&E imaging workflow may preserve tissue for downstream analysis while producing data well-suited for AI integration potentially accelerating and enhancing skin cancer diagnostics.
title Photon Absorption Remote Sensing Virtual Histopathology: A Preliminary Exploration of Diagnostic Equivalence to Gold-Standard H&E Staining in Skin Cancer Excisional Biopsies
topic Quantitative Methods
Image and Video Processing
url https://arxiv.org/abs/2504.18737