Image Derived Estimates of Fibrosis Using Ultrashort Echo Time MRI in Gynecologic Cancer

Abstract

Fibrosis forms during and after radiation therapy (RT) due to wound-healing and cell death. In gynecologic cancer patients treated with EBRT and HDR, we evaluated image derived (ID) acute fibrosis (IDFA) and chronic fibrosis (IDFC) estimates using non-contrast and late gadolinium contrast enhanced (LGE) inversion recovery ultrashort echo time (IR UTE) MRI, respectively. We hypothesized that that ID markers can quantify FA and FC within tumor as a result of response to RT and that fibrosis changes over the course of RT are associated with tumor regression. Subjects: Three subjects with cervical squamous cell carcinoma (SCC), 1 subject with cervical adenocarcinoma, and 2 subjects with vaginal SCC undergoing RT were included. Image Acquisition & Analysis: 1.5T MR imaging at four time-points (TPs): pre-RT, on-RT, post-RT, and post 3mo RT. IDFA imaging: Stack of spirals dual echo (TE = 50, 2690µs), TI = 60ms IR UTE research application. Subtracting the two echoes yielded short TE signal intensity (SI). IDFC imaging: stack of spirals dual echo IR UTE research application, TE = 50µs, TI = 200ms, acquired 15 minutes following contrast. Remnant tumor was contoured at each TP with T2, ADC, and DCE. Relative IDFA, IDFC quantification: voxel-wise IR UTE and LGE IR UTE signal intensity (SI) normalized to gluteal muscle SI. The sum of normalized IDFA and IDFC SI within the remnant tumor at each TP was divided by the corresponding tumor volume yielding tumor intensity (TI) TIFA and TIFC fibrosis accumulation estimates. The coefficients of variation (COV) for TIFA and TIFC were calculated by varying tumor margins and re-computing TIFA and TIFC. Univariate relationships were evaluated using linear regression. The COVs for TIFA = 13% and TIFC = 7%. IDFA and IDFC were observed pre-RT on the tumor periphery, on-RT and post-RT within the tumor, with IDFA potentially transforming into IDFC. Table 1 shows that a greater decrease in tumor volume post RT was correlated with a larger pre-RT TIFA (r = -0.85, p = .03). Decrease in tumor volume was correlated with a larger TIFC post-RT (r = -0.79, p = .05). Post 3 month TIFC was associated with tumor reduction (r = 0.82, n = 4). In this pilot study, we developed reproducible methods to quantify IDFA and IDFC within remnant tumor. Our results suggest that IDFA and IDFC may be associated with tumor response based on tumor volume.