Although cone-beam CT (CBCT) has been used to guide irradiation for pre-clinical radiotherapy(RT) research, it is limited to localize soft tissue target especially in a low imaging contrast environment. Knowledge of target shape is a fundamental need for RT. Without such information to guide radiation, normal tissue can be irradiated unnecessarily, leading to experimental uncertainties. Recognition of this need led us to develop quantitative bioluminescence tomography (QBLT), which provides strong imaging contrast to localize optical targets. We demonstrated its capability of guiding conformal RT using an orthotopic bioluminescent glioblastoma (GBM) model. With multi-projection and multi-spectral bioluminescence imaging and a novel spectral derivative method, our QBLT system is able to reconstruct GBM with localization accuracy <1mm. An optimal threshold was determined to delineate QBLT reconstructed gross target volume (GTV_{QBLT}), which provides the best overlap between the GTV_{QBLT} and CBCT contrast labeled GBM (GTV), used as the ground truth for the GBM volume. To account for the uncertainty of QBLT in target localization and volume delineation, we also innovated a margin design; a 0.5mm margin was determined and added to GTV_{QBLT} to form a planning target volume (PTV_{QBLT}), which largely improved tumor coverage from 75% (0mm margin) to 98% and the corresponding variation (n=10) of the tumor coverage was significantly reduced. Moreover, with prescribed dose 5Gy covering 95% of PTV_{QBLT}, QBLT-guided 7-field conformal RT can irradiate 99.4 pm 1.0% of GTV vs. 65.5 pm 18.5% with conventional single field irradiation (n=10). Our QBLT-guided system provides a unique opportunity for researchers to guide irradiation for soft tissue targets and increase rigorous and reproducibility of scientific discovery.
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