PET/SPECT/spectral-CT/CBCT imaging in a small-animal radiation therapy platform: A Monte Carlo study-Part I:...

In spite of the tremendous potential of game-changing biological image- and/or biologically guided radiation therapy (RT) and adaptive radiation therapy for cancer treatment, existing limited strategies for integrating molecular imaging and/or biological information with RT have impeded the translation of preclinical research findings to clinical applications. Additionally, there is an urgent need for a highly integrated small-animal radiation therapy (SART) platform that can seamlessly combine therapeutic and diagnostic capabilities to comprehensively enhance RT for cancer treatment.

We investigated a highly integrated quad-modal on-board imaging configuration combining positron emission tomography (PET), single-photon emission computed tomography (SPECT), photon-counting spectral CT, and cone-beam computed tomography (CBCT) in a SART platform using a Monte Carlo model as a proof-of-concept.

The quad-modal on-board imaging configuration of the SART platform was designed and evaluated by using the GATE Monte Carlo code. A partial-ring on-board PET imaging subsystem, utilizing advanced semiconductor thallium bromide detector technology, was designed to achieve high sensitivity and spatial resolution. On-board SPECT, photon-counting spectral-CT, and CBCT imaging were performed using a single cadmium zinc telluride flat detector panel. The absolute peak sensitivity and scatter fraction of the PET subsystem were estimated by using simulated phantoms described in the NEMA NU-4 standard. The spatial resolution of the PET image of the platform was evaluated by imaging a simulated micro-Derenzo hot-rod phantom. To evaluate the quantitative imaging capability of the system's spectral CT, the Bayesian eigentissue decomposition (ETD) method was utilized to quantitatively decompose the virtual noncontrast (VNC) electron densities and iodine contrast agent fractions in the Kidney1 inserts mixed with the iodine contrast agent within the simulated phantoms. The performance of the proposed quad-model imaging in the platform was validated by imaging a simulated phantom with multiple imaging probes, including an iodine contrast agent and radioisotopes of ¹⁸F and ^99mTc.

The PET subsystem demonstrated an absolute peak sensitivity of 18.5% at the scanner center, with an energy window of 175-560 KeV, and a scatter fraction of only 3.5% for the mouse phantom, with a default energy window of 480-540 KeV. The spatial resolution of PET on-board imaging exceeded 1.2 mm. All imaging probes were identified clearly within the phantom. The PET and SPECT images agreed well with the actual spatial distributions of the tracers within the phantom. Average relative errors on electron density and iodine contrast agent fraction in the Kidney1 inserts were less than 3%. High-quality PET images, SPECT images, spectral-CT images (including iodine contrast agent fraction images and VNC electron density images), and CBCT images of the simulated phantom demonstrated the comprehensive multimodal imaging capability of the system.

The results demonstrated the feasibility of the proposed quad-modal imaging configuration in a SART platform. The design incorporates anatomical, molecular, and functional information about tumors, thereby facilitating successful translation of preclinical studies into clinical practices.