A non-invasive ultrasound imaging method to measure acute radiation-induced bladder wall thickening in rats

Abstract

Background. Methods for the non-invasive quantification of changes in bladder wall thickness (BWT) as potential predictors of radiation cystitis (RC) in pre-clinical research would be desirable. The use of ultrasound (US) for this aim seems promising, but is still relatively unexplored. A method using US for BWT quantification in rats was developed and applied to measure early radiation-induced BWT changes. Methods. Two groups (n=9 each) of female Fischer rats were treated with a single radiation dose of 25-30 and 35-40Gy respectively, using an image-guided micro-irradiator; six untreated rats were monitored as a control group. Empty, half-filled and fully-filled bladder volumes were determined for four non-irradiated rats by measuring axes from US 3D-images and applying the ellipsoid formula. Mean BWT was estimated for both ventral and dorsal bladder sides through the measurement of the bladder wall area along a segment of 4mm in the central sagittal scan, in order to minimize operator-dependence on the measurement position. US acquisitions of all fully-filled rat bladders were also acquired immediately before, and 4 and 28 days after irradiation. Mean BWTs normalized to the baseline value and corrected for filling were then used to evaluate acute bladder wall thickening and to quantify the dose-effect. Results. The relationship between mean BWT and bladder volume in unirradiated rats showed that for a bladder volume >1.5mL the BWT is almost constant and equal to 0.30mm with variations within ±15%. The average ratios between BWT-post and BWT-pre irradiation showed a dose-effect relationship. Bladder wall thickening was observed for the 25-30 Gy and 35-40 Gy groups in 2/9 (22%) and 5/9 (56%) cases at day 4 and in 4/9 (44%) and 8/9 (89%) cases at day 28, respectively. The two groups showed significantly different BWTs both relative to the control group (p<0.0001) and between them (p=0.022). The BWT increment was on average 1.32±0.41, and was 1.30±0.21 after 25-30Gy and 1.47±0.29 and 1.90±0.83 after 35-40Gy at days 4 and 28 respectively. Conclusions. The feasibility of using US on a preclinical rat model to detect BWT changes after bladder irradiation was demonstrated, and a clear dose-effect relationship was quantified. Although preliminary, these results are promising in addressing the potential role of this non-invasive approach in quantifying RC.