Developing Methods for Quantitative PET: Application to Multimodal Human and Rat Brain Imaging

Positron Emission Tomography (PET) is a functional medical imaging tool that enables the visualization of radio-labeled biologically active molecules (tracer) distributed inside a living body. PET is also combined with other modalities such as CT and MRI with either software or hardware methods to gain synergy. However numerous technical and biological issues remain to be addressed to improve the utility of PET in multimodal imaging for both clinical and preclinical applications. Patient movement during the PET/CT dynamic scan is one of the major problems in clinical study and automated MRI template-based volume of interest (VOI) analysis is one of the key issues in preclinical brain studies for PET. PET/CT is an imaging system that combines PET and CT, in which CT not only provides structure information but also aids attenuation correction for PET. This multimodal medical imaging has become prevalence in clinical diagnosis. However, head movements occurring during PET/CT dynamic scans can create large artifacts in CT-based attenuation corrected PET due to mismatches between CT and PET images. We have thus developed an automated movement correction (MC) procedure for PET/CT dynamic brain scans. MC method was first validated in a Hoffman phantom study and further evaluated with patient FDDNP (a tracer that binds beta-amyloid and tau-protein depositions in tissue) and FDG (a glucose analogue) scans. Results showed that the use of MC for PET/CT dynamic scan significantly improved image quality and allowed more accurate tracer quantitative analysis.To accurately analyze longitudinal FDG preclinical PET brain scans, especially to quantitate image values in small brain structures, an automated MRI template-based volume of interest (VOI) analysis method has been established. The method was applied to longitudinal rat brain FDG PET images to evaluate regional cerebral metabolic change that could not be done without such a template-based analysis methodology. A 6-month study in normal young adult rats showed stable FDG uptake in sensorimotor cortex and lateral prefrontal cortex, a linear decline of relative FDG uptake in striatum, hippocampus and medial prefrontal cortex, while a linear increase in the relative FDG uptake was observed in cerebellum and brain stem. This linear progressive change in regional brain metabolism is first elucidated in normal young adult rats. The method was also applied to rat brain FDG PET images to evaluate the acute and long-term effects of chemotherapy on regional cerebral metabolism