Within the EXPLORER Consortium, the construction of the world's first total-body PET/CT scanner has recently been completed. The 194-cm axial field of view of the EXPLORER PET/CT scanner is sufficient to cover, for the first time, the entire human adult body in a single acquisition in more than 99% of the population and allows total-body pharmacokinetic studies with frame durations as short as 1 s. The large increase in sensitivity arising from total-body coverage as well as increased solid angle for detection at any point within the body allows whole-body ¹⁸F-FDG PET studies to be acquired with unprecedented count density, improving the signal-to-noise ratio of the resulting images. Alternatively, the sensitivity gain can be used to acquire diagnostic PET images with very small amounts of activity in the field of view (25 MBq, 0.7 mCi or less), with very short acquisition times (∼1 min or less) or at later time points after the tracer's administration. We report here on the first human imaging studies on the EXPLORER scanner using a range of different protocols that provide initial evidence in support of these claims. These case studies provide the foundation for future carefully controlled trials to quantitatively evaluate the improvements possible through total-body PET imaging.

The world's first 194-cm-long total-body PET/CT scanner (uEXPLORER) has been built by the EXPLORER Consortium to offer a transformative platform for human molecular imaging in clinical research and health care. Its total-body coverage and ultra-high sensitivity provide opportunities for more accurate tracer kinetic analysis in studies of physiology, biochemistry, and pharmacology. The objective of this study was to demonstrate the capability of total-body parametric imaging and to quantify the improvement in image quality and kinetic parameter estimation by direct and kernel reconstruction of the uEXPLORER data. Methods: We developed quantitative parametric image reconstruction methods for kinetic analysis and used them to analyze the first human dynamic total-body PET study. A healthy female subject was recruited, and a 1-h dynamic scan was acquired during and after an intravenous injection of 256 MBq of ¹⁸F-FDG. Dynamic data were reconstructed using a 3-dimensional time-of-flight list-mode ordered-subsets expectation maximization (OSEM) algorithm and a kernel-based algorithm with all quantitative corrections implemented in the forward model. The Patlak graphical model was used to analyze the ¹⁸F-FDG kinetics in the whole body. The input function was extracted from a region over the descending aorta. For comparison, indirect Patlak analysis from reconstructed frames and direct reconstruction of parametric images from the list-mode data were obtained for the last 30 min of data. Results: Images reconstructed by OSEM showed good quality with low noise, even for the 1-s frames. The image quality was further improved using the kernel method. Total-body Patlak parametric images were obtained using either indirect estimation or direct reconstruction. The direct reconstruction method improved the parametric image quality, having a better contrast-versus-noise tradeoff than the indirect method, with a 2- to 3-fold variance reduction. The kernel-based indirect Patlak method offered image quality similar to the direct Patlak method, with less computation time and faster convergence. Conclusion: This study demonstrated the capability of total-body parametric imaging using the uEXPLORER. Furthermore, the results showed the benefits of kernel-regularized reconstruction and direct parametric reconstruction. Both can achieve superior image quality for tracer kinetic studies compared with the conventional indirect OSEM for total-body imaging.