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