Focused kV X-rays for Preclinical Studies of Radiation-based Neuromodulation

Abstract

Clinical observations suggest that precisely targeted irradiation can alter local neuronal function without neuronal destruction. The advancement of functional brain imaging has revealed regions of hypermetabolism that correlate with psychiatric illnesses. Radiation-based neuromodulation may offer an optimal tool to downregulate the hypermetabolic foci while preserving basic nerve functions. Achieving reliable radiomodulation in the absence of ablation, however, requires a delicate balance. Because there exists very little radiobiology information about radiomodulation and many neuroanatomical targets involved in psychiatric behaviors are believed to be similar in rodents and humans, preclinical small animal studies are critical for target identification, treatment dose planning, and treatment response evaluation. However, the target sizes in laboratory rodents are frequently below the minimum radiation field size of currently available devices. We performed Monte Carlo (MC) simulation to prove the concept of using focused kV x-ray technique to precisely deliver dose to ∼1 mm target in a rodent brain. Experiments were performed to focus 45 kVp x-rays with a polycapillary x-ray lens, which consists of a large number of small hollow curved and tapered glass tubes. The lens guides x-rays through these tubes resembling fiber optics by multiple total reflections. The x-ray transport in the lens was modeled by MC-based geometric ray tracing including defect modeling. The doses were calculated using a simulation toolkit and confirmed by phantom measurements using solid water sandwiched with films. A geometric rat brain model was created for MC treatment planning and dosimetric calculation. A focal spot size of <0.2 mm perpendicular to the beam direction can be achieved and maintained over ∼5 mm in the beam direction. The EBT3 film measured focal spot sizes and depth doses along the beam axis agree with the simulations within 10%. An example simulation was performed using multi-arc scanning for conformal irradiation to the shell region of one rat nucleus accumbens with a volume of 0.5 (LR) x 1.5 (SI) x 0.5 (AP) mm3 plus a 0.25 mm margin. The region is fundamental in brain activity related to addiction. The dose conforms to the target with fast dose fall off outside. The 70% isodose line covers 1.00 x 2.00 x 1.05 mm3. The 90% to 20% dose fall-offs are 0.2 (LR), 0.2 (SI), and 1.0 (AP) mm, respectively. AP is the depth direction of the partial arcs. Its penumbra can be improved further with arcs from more non-coplanar angles. This will also reduce the skull dose; whose current max is 47% of the prescription dose. The use of focused kV x-rays allows precise irradiation to target of just ∼1 mm without irradiating a large surrounding region, which could alter the treatment response and thus the clinical translation potential. It enables the study of radio-neuromodulation and dose volume effect to a small functional region in rat brain, which is impossible with current devices.