Tailoring Brachytherapy by Identification of Fibrosis vs. Tumor: Evaluating Acute and Chronic Fibrosis via UTE MRI in Gynecological Cancer

Abstract

<h3>Purpose/Objective(s)</h3> Radiation injury triggers inflammation, fibroblast migration, and deposition of collagen (acute fibrosis) that later remodels into denser matrices forming scar (chronic fibrosis) at the previous location of tumor. Non-contrast enhanced Short-Inversion-Time (STIR) ultra-short echo time (UTE) MRI has been used to quantify collagen fractions in collagen/aqueous-solution mixtures and to evaluate acute fibrosis. Late-gadolinium enhanced (LGE) IR UTE MRI is a technique that has been used to evaluate chronic scar in the heart. The role of these UTE MR techniques to monitor evolving fibrosis over the course of radiation in cancer has not been studied. We hypothesize that the percentage of fibrosis relative to initial tumor volume increases over the course of external beam radiation prior to brachytherapy in gynecological cancer. <h3>Materials/Methods</h3> <i>Subjects:</i> Cervical and vaginal cancer patients undergoing concurrent chemoradiation were included. MR images were acquired pre- and 1 day post 45 Gy EBRT. <i>Image Acquisition</i>: Imaging was performed on 1.5T MRI using a prototype stack of spirals dual echo (TE_1,2=50, 2690µs) STIR UTE sequence with TI=60, or 80ms. To evaluate acute (diffuse) fibrosis, which has a short-TE, TE₂ images were subtracted from TE₁ images. Chronic fibrosis (necrotic scar) was evaluated using TE₁ of LGE IR UTE, TI=200ms, acquired ≥10 min after contrast injection. <i>Image Analysis:</i> All images were rigidly registered to the treatment planning CT. EBRT CTV contours were propagated onto the MR images. STIR-UTE images were segmented using region-growing. Acute fibrosis (F_A) and chronic fibrosis (F_C) contours were segmented on the non-contrast STIR UTE and on the LGE UTE, respectively. Fibrosis signals were normalized between successive scans based on the femoral heads' cartilage signal. Percentages of the F_A and F_C within the CTV were determined and compared pre- and post-EBRT using a paired t-test. <h3>Results</h3> In five cervical cancer and two vaginal cancer patients, F_A was observed in the irradiated tumor and lymph nodes. The extent of baseline F_A vs. F_C was not significantly different (p=.2) (Table 1). Baseline F_A was significantly lower than post-treatment F_A within the CTV (pre-treatment/post-treatment: 11±11%/34±15%, p=.01). F_C was significantly higher (pre-treatment/post-treatment: 5±2%/18±10%, p=.01). Post-EBRT, there was a significant difference between F_A and F_C within the CTV (p=.01) suggesting a faster increase in acute fibrosis as compared to scar, which requires more time to mature. <h3>Conclusion</h3> We observed an increase in F_A and F_C post-EBRT within the CTV. F_A can serve as an early indicator of F_C. Identifying regions of fibrosis has the potential to guide brachytherapy treatment planning. Future work will focus on precisely prescribing high-doses of brachytherapy to remnant tumor.