Abstract

PURPOSE: Widely-used CBCT-guided irradiators in pre-clinical radiation research are limited to localize soft tissue target due to low imaging contrast. Knowledge of target volume is a fundamental need for radiotherapy (RT). Without such information to guide radiation, normal tissue can be over-irradiated, introducing experimental uncertainties. It led us to develop high contrast quantitative bioluminescence tomography (QBLT) for guidance. The use of 3D bioluminescence signal, related to cell viability, for pre-clinical radiation research is one step toward biology-guided RT.METHODS: Our QBLT system enables multi-projection and multi-spectral bioluminescence imaging (BLI) to maximize input data for the tomographic reconstruction. Accurate quantification of spectrum and dynamic change of in vivo signal were also accounted for the QBLT. A spectral-derivative method was implemented to eliminate the modeling of the light propagation from animal surface to detector. We demonstrated the QBLT capability of guiding conformal RT using a bioluminescent glioblastoma (GBM) model in vivo. A threshold was determined to delineate QBLT reconstructed gross target volume (GTVQBLT), which provides the best overlap between the GTVQBLT and CBCT contrast labelled GBM (GTV), used as the ground truth for GBM volume. To account for the uncertainty of GTVQBLT in target positioning and volume delineation, a margin was determined and added to the GTVQBLT to form a QBLT planning target volume (PTVQBLT) for guidance.RESULTS: The QBLT can reconstruct in vivo GBM with localization accuracy within 1 mm. A 0.5 mm margin was determined and added to GTVQBLT to form PTVQBLT, largely improving tumor coverage from 75.0% (0 mm margin) to 97.9% in average, while minimizing normal tissue toxicity. With the goal of prescribed dose 5 Gy covering 95% of PTVQBLT, QBLT-guided 7-field conformal RT can effectively irradiate 99.4 ± 1.0% of GTV.CONCLUSION: The QBLT provides a unique opportunity for investigators to use biological information for target delineation, guiding conformal irradiation, and reducing normal tissue involvement, expected to increase reproducibility of scientific discovery.

View details for DOI 10.1016/j.ijrobp.2021.08.010

View details for PubMedID 34411639