Abstract:Accurate patient positioning is critical for precise radiotherapy dose delivery, as positioning errors can significantly affect treatment outcomes. This study introduces a novel method for tracking loco-regional tissue deformation through Cherenkov image analysis during fractionated breast cancer radiotherapy. The primary goal was to develop and test an algorithm for Cherenkov-based regional position accuracy quantification, specifically for loco-regional deformations, which lack ideal quantification methods in radiotherapy. Blood vessel detection and segmentation were developed in Cherenkov images using a tissue phantom with incremental movements, and later applied to images from fractionated whole breast radiotherapy in human patients (n=10). A combined rigid and non-rigid registration technique was used to detect inter- and intra-fractional positioning variations. This approach quantified positioning variations in two parts: a global shift from rigid registration and a two-dimensional variation map of loco-regional deformation from non-rigid registration. The methodology was validated using an anthropomorphic chest phantom experiment, where known treatment couch translations and respiratory motion were simulated to assess inter- and intra-fractional uncertainties, yielding an average accuracy of 0.83 mm for couch translations up to 20 mm. Analysis of clinical Cherenkov data from ten breast cancer patients showed an inter-fraction setup variation of 3.7 plus minus 2.4 mm relative to the first fraction and loco-regional deformations (95th percentile) of up to 3.3 plus minus 1.9 mm. This study presents a Cherenkov-based approach to quantify global and local positioning variations, demonstrating feasibility in addressing loco-regional deformations that conventional imaging techniques fail to capture.