Integrating Laser Plasma Accelerated Proton Beams and Thermoacoustic Imaging into an Image-Guided Small Animal Therapy Platform

Proton beam therapy has shown great promise for cancer treatment due to its high precision in irradiating tumor volumes. However, due to the massive size and expense of the cyclotrons/synchrotrons needed to accelerate the protons, the widespread use of proton therapy is limited. Laser plasma accelerated (LPA) proton beams may be a potential alternative to conventional proton beams: by shooting an ultraintense, ultrashort pulsed laser at a thin target, a plasma sheath electric field may be formed with the capability of accelerating protons to potentially therapeutic energies in very short distances. In addition to accessibility, there is significant uncertainty in proton range in heterogeneous tissues. Thermoacoustic computed tomographic (TACT) imaging has the potential to provide in vivo dose imaging and range verification to address these uncertainties. TACT measures thermoacoustic waves generated from the absorbed dose and implements a 3D filtered backprojection to reconstruct volumetric images of the dose. The purpose of this thesis is to determine the feasibility of integrating LPA proton beams with thermoacoustic imaging into a novel image-guided small animal therapy platform as an early step towards clinical  translation to address the issues of accessibility and dosimetric spatial uncertainty. A Monte Carlo (MC) method is used to simulate an LPA proton beam with characteristics based on literature, thermoacoustic waves are simulated on a voxel-wise basis of the MC dose, and 3D filtered backprojection is used to reconstruct a volumetric image of the dose. In Specific Aim 1, the dependence of image accuracy on transducer array angular coverage is investigated; in Specific Aim 2, an iterative reconstruction algorithm is implemented to improve image accuracy through increased sampling of projection space when transducer array angular coverage is insufficient; and in Specific Aim 3, the detector sensitivity to dose is determined for several therapeutic endpoints. The work presented in this thesis not only demonstrates the feasibility of integrating LPA and thermoacoustic technologies but necessary design changes to realize a functional small animal platform.