Abstract
BACKGROUND AND PURPOSE: Radiotherapy (RT) response in gynecologic cancers varies widely and is influenced by several factors. We evaluated whether fibrosis detected with inversion-recovery ultrashort-echo-time (IR-UTE) MRI (magnetic-resonance-imaging) signal-intensity (SI) could serve as noninvasive biomarkers of treatment response in patients imaged serially during external-beam RT (EBRT) and brachytherapy (BT). MATERIALS AND METHODS: Patients: Fifteen patients with gynecologic cancer were included. Five participants underwent seven MRIs: pre-RT, weeks 1 (RT(wk1)), 2 (RT(wk2)), and 3 (RT(wk3)) of EBRT, post-EBRT, 1-week post-BT, and 12 weeks post-BT. Ten participants did not receive MRI in RT(wk1), RT(wk2), or 1-week post-BT. Imaging: T2-weighted, diffusion-weighted images, and dynamic-contrast-enhanced MR images were acquired to segment the remnant-tumor-volume. Diffuse-fibrosis (F(Diffuse)) was imaged with non-contrast dual-echo IR research application, only retaining the ultrashort-(50 µs)-echo SI. Dense-fibrosis (F(Dense)) imaging utilized Late-Gadolinium-Enhanced IR-UTE, acquired ∼ 15 min post-Gadavist. Analysis: R2* (apparent transverse relaxation rate) maps, indicative of hypoxia, were generated using R2* MRI. The mean F(Diffuse) SI, F(Dense) SI, and R2* within the remnant-tumor-volume were determined and compared over the course of RT. RESULTS: Changes in F(Diffuse) SI and F(Dense) SI were observed after 14 Gy. Across all patients, F(Diffuse) SI peaked during RT(wk2) and F(Dense) SI peaked during RT(wk3). F(Dense) SI was higher during RT(wk3) than pre-RT (p < 0.05). Minor changes in F(Dense) SI were observed post-BT week-12 (p > 0.05). Remnant-tumor R2* correlated with F(Dense) SI (p = 0.03). CONCLUSIONS: The largest increase in F(Dense) occurred early during EBRT. Elevated F(Dense) correlated with elevated R2* in the remnant-tumor, suggesting that fibrosis is an early indicator of radiation-resistant hypoxic regions.