Promise of Fully Integrated PET/MRI: Noninvasive Clinical Quantification of Cerebral Glucose Metabolism

Abstract

We describe a fully automated processing pipeline to support the noninvasive absolute quantification of the cerebral metabolic rate for glucose (CMRGlc) in a clinical setting. This pipeline takes advantage of "anatometabolic" information associated with fully integrated PET/MRI. Methods: Ten healthy volunteers (5 men and /5 women; 27 ± 7 y old; 70 ± 10 kg) underwent a test-retest 18 F-FDG PET/MRI examination of the brain. The imaging protocol consisted of a 60-min PET list-mode acquisition with parallel MRI acquisitions, including 3-dimensional time-of-flight MR angiography, MRI navigators, and a T1-weighted MRI scan. State-of-the-art MRI-based attenuation correction was derived from T1-weighted MRI (pseudo-CT [pCT]). For validation purposes, a low-dose CT scan was also performed. Arterial blood samples were collected as the reference standard (arterial input function [AIF]). The developed pipeline allows the derivation of an image-derived input function (IDIF), which is subsequently used to create CMRGlc maps by means of a Patlak analysis. The pipeline also includes motion correction using the MRI navigator sequence as well as a novel partial-volume correction that accounts for background heterogeneity. Finally, CMRGlc maps are used to generate a normative database to facilitate the detection of metabolic abnormalities in future patient scans. To assess the performance of the developed pipeline, IDIFs extracted by both CT-based attenuation correction (CT-IDIF) and MRI-based attenuation correction (pCT-IDIF) were compared with the reference standard (AIF) using the absolute percentage difference between the areas under the curves as well as the absolute percentage difference in regional CMRGlc values. Results: The absolute percentage differences between the areas under the curves for CT-IDIF and pCT-IDIF were determined to be 1.4% ± 1.0% and 3.4% ± 2.6%, respectively. The absolute percentage difference in regional CMRGlc values based on CT-IDIF and pCT-IDIF differed by less than 6% from the reference values obtained from the AIF. Conclusion: By taking advantage of the capabilities of fully integrated PET/MRI, we developed a fully automated computational pipeline that allows the noninvasive determination of regional CMRGlc values in a clinical setting. This methodology might facilitate the proliferation of fully quantitative imaging into the clinical arena and, as a result, might contribute to improved diagnostic efficacy.

Minimally invasive quantification of cerebral P2X7R occupancy using dynamic [18F]JNJ-64413739 PET and MRA-driven image derived input function

“…Therefore a Logan graphical analysis is assumed to be less dependent on the accurate determination of the rapidly changing peak of the input function which could be poorly estimated 23 . This is confirmed by several previous studies 25 , 38 , 39 . However, since metabolization of [ 18 F]JNJ-739 is rather fast (only 30% ± 5% of parent tracer at 20 min post-injection), the contribution of later time points of the metabolite-corrected arterial plasma input function is limited such that cumulated activity concentrations at later time points, which are used for the Logan graphical analysis estimation, are more dependent on the accurate estimation of peak activity concentrations, shortly after tracer injection.…”

Magnetic Resonance-Based Attenuation Correction and Scatter Correction in Neurological Positron Emission Tomography/Magnetic Resonance Imaging—Current Status With Emerging Applications

“…Using TOF MR angiography can improve the delineation of the arterial volume in PET [184,[189][190][191]. The IDIF could be implemented in an automated pipeline to provide absolute values of cerebral glucose metabolism in a clinically feasible manner [192]. The IDIF measured from either MRI and PET could also be used interchangeably [193].…”

Binding of the synaptic vesicle radiotracer [11C]UCB-J is unchanged during functional brain activation using a visual stimulation task

“…60 , 61 Studies have reported intrasubject variability of up to 25% in test–retest comparisons even in healthy people scanned at close points in time under well-controlled research conditions. 62 As a result, [ 18 F]FDG PET requires careful control of scanning conditions (for example, patient fasting) and its sensitivity is limited to detect only relatively large changes or group differences, approximately 25% or greater. 62 In contrast, our present results and previous test–retest data with [ 11 C]UCB-J PET suggest that changes in synaptic density as small as 10% can be identified, which could allow for the detection of earlier or subtler disease effects.…”

“…62 As a result, [ 18 F]FDG PET requires careful control of scanning conditions (for example, patient fasting) and its sensitivity is limited to detect only relatively large changes or group differences, approximately 25% or greater. 62 In contrast, our present results and previous test–retest data with [ 11 C]UCB-J PET suggest that changes in synaptic density as small as 10% can be identified, which could allow for the detection of earlier or subtler disease effects. The data presented here support the assertion that in vivo [ 11 C]UCB-J binding can be interpreted as a static measure of SV2A protein density with negligible influence of variability in brain function.…”