Main Session
Sep
28
PQA 03 - Digital Health Innovation and Informatics, Patient Safety & Quality, and Radiation and Cancer Biology
Presenter(s)
Aleksandra Ilina, PhD - Dartmouth College, Hanover, NH
A. Ilina1, V. Demidov1,2, J. Gunn1, A. F. Pétusseau1, X. Cao1, C. Narita1, D. J. Gladstone3, and B. W. Pogue1; 1Thayer School of Engineering at Dartmouth College, Hanover, NH, 2Dartmouth Cancer Center, Lebanon, NH, 3Geisel School of Medicine at Dartmouth & Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, NH
Purpose/Objective(s):
FLASH radiotherapy (UHDR-RT) has been shown to reduce normal tissue toxicity compared with conventional dose-rate radiotherapy (CDR-RT) at equivalent doses, while maintaining tumor control. However, the biological mechanisms underlying this “FLASH effect” remain incompletely understood. Early alterations in tissue—occurring before overt toxicity—may hold key insights into dose-rate–dependent responses, particularly related to tissue oxygenation and cellular metabolism. This study aims to identify early microscopic biomarkers of radiation injury and characterize how these markers differ between CDR and UHDR irradiation prior to the onset of visible skin reactions.Materials/Methods:
Hind-leg skin of female C57BL/6 mice was irradiated with single doses of 20, 24, or 27 Gy using either CDR (0.1 Gy/s) or UHDR (100 Gy/s) dose rates delivered by a 9 MeV Mobetron linac. Longitudinal imaging was performed daily for 14 days post-irradiation using optical coherence tomography (OCT) to quantify epidermal and dermal thickness, and an intensified CMOS camera to capture native tissue autofluorescence. Skin reactions were blindly and independently scored. Histological validation with hematoxylin and eosin (H&E) staining was conducted on a subset of animals at Day 10.Results:
Early, quantifiable changes in both epidermal and dermal thickness were detected before the appearance of clinically visible skin damage. These pre-toxicity morphological changes—characterized by dermal and epidermal thickening—were dose-dependent and demonstrated clear divergence between UHDR and CDR cohorts. Notably, a pronounced autofluorescence signal emerged early following UHDR-RT but was absent in the CDR group. H&E analysis revealed dose-rate–dependent differences in the severity and progression of hyperkeratosis and vacuolar degeneration, further supporting early microscopic divergence between treatment modalities.Conclusion:
OCT-derived thickness metrics, tissue autofluorescence, and histological markers together form a sensitive multimodal panel for detecting early radiation-induced skin changes and distinguishing dose-rate–dependent biological responses. These early divergences between UHDR and CDR irradiation provide valuable insight into the mechanisms that may contribute to the FLASH effect and support the development of early biomarkers for normal-tissue sparing.