In Vivo Microstructure Imaging in Oropharyngeal Squamous Cell Carcinoma Using the Random Walk With Barriers Model

Abstract

Background Apparent diffusion coefficient is not specifically sensitive to tumor microstructure and therapy‐induced cellular changes. Purpose To investigate time‐dependent diffusion imaging with the short‐time‐limit random walk with barriers model (STL‐RWBM) for quantifying microstructure parameters and early cancer cellular response to therapy. Study Type Prospective. Population Twenty‐seven patients (median age of 58 years and 7.4% of females) with p16+/p16− oropharyngeal/oral cavity squamous cell carcinomas (OPSCC/OCSCC) underwent MRI scans before therapy, of which 16 patients had second scans at 2 weeks of the 7‐weeks chemoradiation therapy (CRT). Field Strength/Sequence 3‐T, diffusion sequence with oscillating gradient spine echo (OGSE) and pulse gradient spin echo (PGSE). Assessment Diffusion weighted images were acquired using OGSE and PGSE. Effective diffusion times were derived for the STL‐RWBM to estimate free diffusion coefficient D 0 , volume‐to‐surface area ratio of cellular membranes V / S , and cell membrane permeability κ . Mean values of these parameters were calculated in tumor volumes. Statistical Tests Tumor microstructure parameters were compared with clinical stages of p16+ I‐II OPSCC, p16+ III OPSCC, and p16− IV OCSCC by Spearman's rank correlation and with digital pathological analysis of a resected tissue sample. Tumor microstructure parameter responses during CRT in the 16 patients were assessed by paired t ‐tests. A P ‐value of <0.05 was considered statistically significant. Results The derived effective diffusion times affected estimated values of V / S and κ by 40%. The tumor V / S values were significantly correlated with clinical stages ( r = 0.47) as an increase from low to high clinical stages. The in vivo estimated cell size agreed with one from pathological analysis of a tissue sample. Early tumor cellular responses showed a significant increase in D 0 (14%, P = 0.03) and non‐significant increases in κ (56%, P = 0.6) and V / S (10%, P = 0.1). Data Conclusion Effective diffusion time estimation might impact microstructure parameter estimation. The tumor V / S was correlated with OPSCC/OCSCC clinical stages. Level of Evidence 1 Technical Efficacy Stage 1

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