THE DEVELOPMENT OF A CT-BASED FRAMEWORK FOR RADIATION DOSIMETRY IN YTTRIUM-90 RADIOEMBOLIZATION

Abstract

Transarterial radioembolization (TARE) is a radiation-based embolic therapy for the treatment of liver cancer. In TARE, yttrium-90 (90Y)-infused microspheres are administered via the hepatic arterial vasculature to facilitate the delivery of radiation to a target volume. Positron emission tomography (PET) imaging can provide estimates of the absorbed radiation dose following 90Y TARE. However, these estimates are often associated with substantial uncertainty due in part to the inadequate spatial resolution of PET imaging. Computed tomography (CT) has the potential to provide superior spatial resolution imaging of microsphere distributions, which could improve absorbed dose estimates and refine our understanding of the dose-response relationship. This thesis presents the development, implementation, and validation of a CT-based framework for post-treatment dosimetry in 90Y TARE.

Three manuscripts form the foundation of this thesis. The first manuscript, titled “Quantification of the Inherent Radiopacity of Glass Microspheres for Precision Dosimetry in Yttrium-90 Radioembolization,” describes the development and analysis of a calibration phantom to relate radiopaque microsphere concentration to CT voxel intensity. Based on the findings of this first study, the construction and optimization of a clinical calibration phantom was ongoing throughout the remainder of the project. Preliminary results suggest the clinical phantom is well-suited to the needs of CT-based dosimetry in 90Y TARE. The second manuscript, titled “Post-Administration Dosimetry in Yttrium-90 Radioembolization through Micro-CT Imaging of Radiopaque Microspheres in a Porcine Renal Model,” analyzes micro-CT image data of radiopaque microsphere distributions to demonstrate the increased confidence provided by CT-based dosimetry in characterizing the absorbed dose heterogeneity in 90Y TARE. The third manuscript, titled “Precision Dosimetry in Yttrium-90 Radioembolization through CT Imaging of Radiopaque Microspheres in a Rabbit Liver Model,” validates CT-based dosimetry in 90Y TARE through a comparison to conventional PET-based dosimetry, while also revealing benefits of improved dose distribution visualization, reduced partial volume effects, and the mitigation of respiratory motion effects.

Together, these works demonstrate that post-treatment CT imaging of in vivo radiopaque microsphere distributions provides the means to perform accurate and precise dosimetry in 90Y TARE. This novel approach to radiation dosimetry will permit individualized treatment planning that should translate into improved patient outcomes.