The Feasibility of Biologically Guided Radiation Therapy Implemented in a Small-Animal Radiation Therapy Platform Integrated with Quad-Modal On-Board Imaging

Abstract

<h3>Purpose/Objective(s)</h3> Unparallel evolution between clinical radiation therapy (RT) paradigms and preclinical RT techniques, especially in biologically guided RT, has posed a challenge to completely validate the benefits and pitfalls of novel RT techniques prior to their translation to bedside practices. In this study, we firstly investigated the feasibility of biologically guided RT implemented within a small animal radiation therapy (SART) platform, with quad-modal on-board positron emission tomography (PET), single-photon emission computed tomography (SPECT), spectral CT, and cone-beam computed tomography (CBCT) imaging integrated, in a Monte Carlo model as a proof-of-concept. <h3>Materials/Methods</h3> The SART platform with quad-modal imaging guidance was modeled by using a planning tool. A preclinical biologically guided RT workflow with quad-modal imaging guidance was designed, in which image-guided RT and emission-guided radiation therapy (EGRT) can be implemented. To demonstrate the potential of contrast-enhanced spectral CT used in biologically guided RT for simultaneously guiding dose prescription based on tracer uptakes and dose calculation based on underlying tissue electron densities in the platform, iodine uptake fractions and virtual non-contrast electron densities in the Kidney1 inserts within a simulated phantom, mixed with an iodine contrast agent at electron fractions of 0.02 and 0.03, were decomposed quantitatively by using the Bayesian eigen tissue decomposition method and the maximum a posterior (MAP) estimation. To demonstrate EGRT implemented in the platform, the preliminary algorithm of EGRT was illustrated by introducing a 2-mm setup error to a target in the simulated phantom. The dose calculation was implemented after the set of binary micro-multileaf collimator (bmMLC) configurations was determined. The dose distributions delivered by EGRT were compared to that delivered by the conventional RT method with three treatment beams with and without setup error. <h3>Results</h3> For the Kidney1 insert with an iodine contrast agent fraction of 0.02, the average relative errors in the iodine contrast agent fraction and the underlying electron density estimated were 0.64% and 0.95%, respectively. In EGRT, the simulations resulted in 4339 and 5197 beamlet responses in an exemplary dose slice delivery with and without the 2-mm setup error, respectively. Compared to the conventional RT method, EGRT scheme introduced into the SART platform was validated to be more robust to setup errors while providing improved tumor targeting and a lesser dose burden on normal tissues during the treatment beam delivery in preclinical RT setting. <h3>Conclusion</h3> The results demonstrated the successful implementation of biologically guided RT within the SART platform with quad-model imaging guidance. With the comprehensive image- and emission-guided RT schemes integrated, this novel SART platform affords one-stop preclinical RT studies.