Inversion-recovery ultrashort-echo-time (IR-UTE) MRI-based detection of radiation dose heterogeneity in gynecologic cancer patients treated with HDR brachytherapy.

Purpose: To evaluate the relationship between delivered radiation (RT) and post-RT inversion-recovery ultrashort-echo-time (IR-UTE) MRI signal-intensity (SI) in gynecologic cancer patients treated with high-dose-rate (HDR) brachytherapy (BT).

Methods: Seven patients underwent whole-pelvis RT (WPRT) followed by BT to the high-risk clinical target volume (HR-CTV). MR images were acquired at three time-points; pre-RT, post-WPRT/pre-BT, and 3-6 months post-BT. Diffuse-fibrosis (F_Diffuse) was imaged with a non-contrast dual-echo IR (inversion time [TI] = 60 ms) UTE research application, with image-subtraction of the later echo, only retaining the ultrashort-echo SI. Dense-fibrosis (F_Dense) imaging utilized single-echo Late-Gadolinium-Enhanced IR-UTE, acquired ∼ 15 min post-Gadavist injection. Resulting F_Diffuse and F_Dense SI were normalized to the corresponding gluteal-muscle SI. Images were deformably registered between time-points based on normal tissue anatomy. The remnant tumor at both time-points was segmented using multi-parametric MRI. Contours corresponding to the 50%, 100%, 150%, and 200% isodose lines (IDLs) of the prescription BT-dose were created. Mean F_Diffuse and F_Dense SI within (i) each IDL contour and (ii) the remnant tumor were calculated. Post-BT F_Diffuse and F_Dense SI were correlated with prescribed BT-dose. To determine the relationship between BT-dose and IR-UTE SI, the differences in the post-BT F_Dense across IDLs was determined using paired t-tests with Bonferroni correction.

Results: F_Dense was higher in regions of higher dose for 6/7 patients, with mean ± SD values of 357 ± 103% and 331 ± 97% (p = .03) in the 100% and 50% IDL, respectively. F_Dense was higher in regions of higher dose in the responsive regions with mean ± SD values of 380 ± 122% and 356 ± 135% (p = .03) in the 150% and 50% IDL, respectively. Within the segmented remnant tumor, an increase in prescribed dose correlated with an increase in F_Dense post-BT (n = 5, r = .89, p = .04). Post-BT F_Diffuse inversely correlated (n = 7, r = -.83, p = .02) with prescribed BT-dose within the 100% IDL.

Conclusions: Results suggest that F_Dense SI 3-6 months post-BT is a sensitive measure of tissue response to heterogeneous BT radiation-dose. Future studies will validate whether F_Diffuse and F_Dense are accurate biomarkers of fibrotic radiation response.