Date of Award
8-1-2024
Degree Name
Doctor of Philosophy (PhD)
Degree Type
Dissertation
Abstract
Radiopharmaceutical therapies (RPTs) using α- or β-particle-emitting isotopes are becoming increasingly important in cancer treatment. Reliable (accurate and precise) quantification of absorbed doses in lesions and vital organs is important for the safety and effectiveness of these therapies. Quantitative single-photon emission computed tomography (SPECT) provides a mechanism for such dose quantifications by quantifying the regional activity uptake. This dissertation aims to develop methodologies for reliable SPECT-based regional uptake quantification for patients treated with α-particle-emitting RPTs (α-RPTs). A significant challenge with conventional reconstruction-based quantitative (RBQ) SPECT methods is the ill-posed nature of image reconstruction, which is further complicated by the limited photon counts typical in α-RPT. To address these, we developed a projection-domain low-count quantitative SPECT (LC-QSPECT) method that estimates regional uptake directly from projection data while accounting for multiple image degrading effects in α-RPT. Clinically realistic simulation studies, including an in silico clinical trial (ISIT-QA) with 268 virtual patients treated with 223Ra-based α-RPTs, demonstrated that LC-QSPECT could provide reliable regional uptake estimates with good reproducibility across SPECT scanner-collimator configurations, significantly outperforming conventional RBQ methods. These promising results motivate clinical evaluations, but the limited SPECT data for α-RPT patients necessitate a prospective clinical trial. As a preliminary step, we investigated the feasibility of applying LC-QSPECT to actual patients with low-count SPECT using existing patient data from 177Lu-DOTATATE (Lu-tate)-based RPT, where we replicated the low-count challenges using Poisson resampling. Results showed that LC-QSPECT was successfully applied. The method yielded liver and kidney uptake estimates very close to those obtained with the conventional RBQ method at normal counts and yielded reliable estimates for synthetic lesions simulated on these patient data. Next, we extended the method to the emerging 227Th-based α-RPTs. A more complex task of quantifying regional uptake of both 227Th and 223Ra in patients is required for dose quantification in these therapies, which is challenged by the high crosstalk contamination of these isotopes. To address this, we extend the LC-QSPECT to jointly estimate the regional uptake of both isotopes using projections from multiple energy windows. Realistic simulation studies demonstrated that this method yielded reliable regional uptake estimates of both isotopes and outperformed state-of-the-art RBQ methods. Finally, to achieve more reliable regional uptake quantification for α-RPTs, optimizing SPECT system and protocol designs to capture measurements with the highest information content for the quantification task is another important direction. These optimizations require an optimal estimator for regional uptake quantification. To this end, we developed a Wiener-estimator-based projection-domain LC-QSPECT (WIN-PDQ) method. The method accounts for potential uptake heterogeneity within VOIs while estimating the regional uptake. Realistic simulation studies demonstrated that this method provided reliable quantifications, consistently outperforming conventional RBQ and previously proposed projection-domain methods. These results highlight the reliability of the WIN-PDQ method, supporting its potential in optimizing SPECT systems and protocols for improved imaging quality.
Language
English (en)
Chair
Abhinav Jha