Patlak plot

Abstract: 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.

Abstract: The blood-to-brain transfer rate constant (Ki) of Gd-DTPA was determined in MRI studies of a rat model of transient cerebral ischemia. The longitudinal relaxation rate, R1, was estimated using repeated Look-Locker measurements. A model-independent analysis of ΔR1, the Patlak plot, produced maps of Ki for Gd-DTPA and the distribution volume of the mobile protons (Vp) with intravascular-Gd changed R1's. The Ki's of Gd-DTPA were estimated in regions of interest with blood–brain barrier (BBB) opening (regions of interest, ROIs) and compared to those of 14C-sucrose determined shortly thereafter by quantitative autoradiography. The Ki's for both Gd-DTPA and sucrose were much higher than normal within the ROIs (n = 7); linear regression of Ki for Gd-DTPA vs. Ki for sucrose yielded a slope of 0.43 ± 0.11 and r2 = 0.72 (P = 0.01). Thus, Ki for Gd-DTPA varied in parallel with, but was less than, Ki for sucrose. In the ROIs, mean Vp was 0.071 ml g−1 and much higher than mean vascular volume estimated by dynamic-contrast-enhancement (0.013 ml g−1) or mean Vp in contralateral brain (0.015 ml g−1). This elevated Vp may reflect increased capillary permeability to water. In conclusion, Ki can be reliably calculated from Gd-DTPA-MRI data by Patlak plots. Magn Reson Med 50:283–292, 2003. © 2003 Wiley-Liss, Inc.

Abstract: Purpose To determine the accuracy of single-kidney glomerular filtration rate (GFR) determination using contrast-enhanced dynamic magnetic resonance imaging (MRI) and the Rutland-Patlak plot technique. Materials and Methods Twenty-eight adult patients were included. As reference method, the GFR was measured by plasma clearance using a small bolus injection of iopromide. A three-dimensional gradient-echo (GRE) sequence with a flip angle of 50° was used for MRI; this showed a good linear relationship between gadolinium (Gd)-DTPA concentration and signal change when measured up to a Gd-DTPA concentration of 10 mmol/liter. A slab containing both kidneys and the abdominal aorta was measured 30 times in approximately 3.5 minutes. During this measurement, 15 mL of Gd-DTPA, 0.5 mol/liter diluted to a volume of 60 mL, was injected over 60 seconds. A Rutland-Patlak plot was calculated from the signal changes in the aorta and the renal parenchyma. Single-kidney GFR was calculated for different time windows from the Rutland-Patlak plot slope. Results The best correlation compared to the reference method was found with the GFR calculated from the slope of the Rutland-Patlak plot 40–110 seconds postaortic rise. Pearson's correlation coefficient was r = 0.86, SD was 14.8 mL/minute. In many of the patients, a decrease of the renal signal was observed in the excretory phase, which was probably caused by very high Gd-DTPA concentrations in the collecting tubules. Conclusion Single-kidney GFR can be calculated from dynamic contrast-enhanced MRI. We found a promising correlation of global GFR calculated by MRI compared to the reference method. In any future study, the amount of Gd-DTPA should by reduced to avoid artificial signal drop in the excretory phase induced by the T2* effect. J. Magn. Reson. Imaging 2003;18:714–725. © 2003 Wiley-Liss, Inc.

Abstract: 1158 Objectives: To demonstrate that dynamic whole-body (DWB) PET is a clinical imaging tool with significant potential. DWB PET can be performed within reasonable clinical imaging times and enables generation of multiple types of PET images with complementary information in a single imaging session (<30min). Methods: Current clinical PET protocols mirror the pattern established for traditional radiology in that they are optimized for qualitative as opposed to quantitative assessment, with documented limitations [1]. Radiotracer distribution is a dynamic process that varies substantially between organs (particularly tumors) and between patients. The uptake periods used in clinical protocols are somewhat arbitrary and are not expected to be optimal for all clinical cases. We argue that a new paradigm of DWB-PET is both feasible and has significant potential. It is made possible by ongoing technical developments; significant advancements in PET hardware, combined with statistical image reconstruction have made it possible to acquire multi-pass eyes-to-thighs imaging in clinically feasible times, achieving adequate statistical quality in less than 5 min/pass. Patlak analysis [2] is particularly suited for generation of parametric images from DWB PET because it is applicable to FDG and it does not require PET scans to sample the early tracer kinetics. Thus, DWB imaging can be used to produce parametric images of (i) Patlak slope (influx rate Ki) and (ii) intercept (distribution volume V), while also providing (iii) conventional SUV images by summation of dynamic frames. There are also means to reduce noise in the parametric Patlak slope and intercept images, by use of constrained statistical regression [3, 4], and direct 4D reconstruction of parametric images from sinogram data [5]. Results: Parametric images of both Patlak slope Ki and intercept V can be generated, in addition to conventional SUV images by summation of the dynamic frames (Figure 1a). Thus, three distinct images can be obtained from the same imaging session. The Ki image generally shows reduced normal organ uptake, particularly in the liver. Furthermore, direct 4D parametric image reconstruction can significantly improve quality and quantitative accuracy of DWB images (Figure 1b). We also have results demonstrating application of DWB imaging to beyond FDG PET/CT, for instance to PET/MR imaging, as well as Ga-68 DOTATOC PET/CT. Conclusions: DWB-PET has a number of advantages. It can minimize time dependence of SUV activity: SUV uptake changes in time in direct proportion to changes in image uptake. Given variable scan times inherent in a busy clinical practice, this is an issue, and the proposed measures are expected to be less subject to such alterations. Furthermore, it can remove background uptake, allow small and less FDG avid tumors to be identified, and produce more quantitative estimates of tumor uptake. Overall, a new paradigm of DWB PET imaging (applicable to both PET/CT and PET/MRI) generates quantitative measures that may contribute significantly added clinical value to conventional SUV images.