UC Davis

PET/CT systems are used to visualize and quantify molecular processes in vivo. The extended axial field of view (FOV) of total-body PET/CT systems, like the recently developed uEXPLORER, leads to increased system sensitivity and can allow for reduced scan time and dose, improvements in image quality, and most importantly for this work, the ability to fit the entire body of a subject within the FOV. The FOV includes large blood pools in addition to any organ of interest, allowing for the use of an appropriate image-derived input function (IDIF) for the purposes of quantitative total-body PET kinetic modeling. Although the first clinical scans on the uEXPLORER at UC Davis were performed in 2019, in vivo assessment of the quantitative performance of the scanner and the development of total-body PET kinetic modeling methods are necessary to extend single-organ and limited FOV studies to encompass organs throughout the entire body. Thus, this work focused on the development of total-body PET kinetic modeling methods. First, via a group of fourteen healthy volunteers who underwent 60-minute dynamic PET acquisitions on the uEXPLORER system with the commonly used radiotracer [18F]-fluorodeoxyglucose (FDG), in vivo performance metrics were established to quantitatively assess differences in the reconstructed images from a newly installed total-body PET system (e.g., due to software updates and reconstruction settings), and methods to mitigate the impact of motion (e.g., respiratory) and partial volume effects across a wide range of organs were determined. Then, with the same cohort of healthy subjects in addition to seven patients with genitourinary cancer, the computational efficiency of voxel-wise total-body PET kinetic modeling was increased by a factor of 6.7 through the development of the leading-edge method for time delay correction of the IDIF. Without delay correction there was an underestimation of blood volume, vb (69.4%), and the rate of FDG transport from blood to tissue, K1 (4.8%). Total-body PET kinetic modeling methods developed above using FDG datasets were extended to the assessment of [11C]-butanol for total-body imaging of tissue blood flow (perfusion). The application of total-body PET/CT for radiation dosimetry of tracers with rapid kinetics and short half-life was demonstrated with this tracer. Radiation doses were estimated on an early small-scale prototype of a total-body PET scanner in two young rhesus monkeys and subsequently on the uEXPLORER in humans. Average adult dosimetry estimates of total effective dose were consistent (rhesus monkeys-derived: 3.67 uSv/MBq, human-derived: 3.64 uSv/MBq). Perfusion test-retest reproducibility was established in healthy volunteers at a wide range of flow values and showed good repeatability (slope 0.9, Pearson’s r = 0.97, p < 0.001) with up to two weeks between acquisitions. Intra-human sensitivity assessments were performed in two ways: (1) a rest-stress paradigm with a cold pressor test and (2) the comparison of right and left lower limbs for an individual with peripheral artery disease. Initial studies demonstrated changes in perfusion in both cases. In this work, appropriate methods for the quantitative assessment of total-body dynamic PET images were developed; computational efficiency of total-body kinetic modeling was increased 6.7-fold; and ultimately, these methods were developed and exploited in the measurement of FDG transport, FDG metabolism and [11C]-butanol perfusion, in organs throughout the body.