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 D0, 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 D0 (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.