Relationship of Hypoxia and Fibrosis during Gynecologic Cancer Radiotherapy Using Quantitative R2* and Late Gadolinium Enhanced Ultrashort Echo Time MRI
Abstract
Purpose
To determine whether dense-fibrosis (FDense) measured with Late-Gadolinium-Enhanced-Inversion-Recovery ultrashort-echo-time (LGE-IR-UTE) MRI spatially correlates with R2* maps (a marker associated with hypoxia) in gynecologic-cancer patients during external-beam-radiotherapy (EBRT) followed by HDR brachytherapy (HDR-BT).
Methods
Patients (n=15) underwent whole-pelvis EBRT followed by HDR-BT, receiving 71-79.8Gy total dose. MR images were acquired on a 1.5T scanner pre-RT, during EBRT weeks 1,2,3,6, and 1-week post-BT. LGE-IR-UTE MRI quantified FDense, as previously detailed (Sheikh, Radiation Oncology (2024)). At each time-point, the remnant tumor gross tumor volume (GTV) was contoured on mpMRI by a radiologist. R2* maps were generated. Mean FDense signal-intensity (SI) and mean R2* were computed within the pre-RT GTV0 and at each time-point GTVn. Global associations between FDense SI and R2* were evaluated using Pearson correlation. For regional analysis, FDense and R2* maps were masked to encompass only the tumor, resampled to a common reference grid, and partitioned into 1×1×1 cm³ regions-of-interest (ROIs); mean FDense SI and mean R2* were computed per ROI and Pearson correlation calculated across ROIs at EBRT week 3, when substantial tumor shrinkage was observed; with tumors <1 cm³ at week 3 excluded. To evaluate intra-tumoral spatial heterogeneity, FDense SI was compared between a 3 mm peripheral ring surrounding the GTV and the tumor core (GTV contracted by 3 mm).
Results
Across all patients, global (r=0.56, p=0.03) and regional (r=0.49, p<0.01) FDense SI correlated with R2* at EBRT week 3. FDense SI was higher in the peripheral ring than in the tumor core (p = 0.01), indicating greater dense-fibrosis at the tumor margin.
Conclusion
During RT, spatial R2* increases coincided with FDense SI increases within remnant tumor regions. These findings suggest that early fibrosis and hypoxia-associated changes evolve concurrently and exhibit spatial heterogeneity, with increased fibrosis at the tumor periphery potentially contributing to subsequent hypoxia.