Feasibility study of TSPO quantification with [18F]FEPPA using population-based input function

Abstract

PurposeThe input function (IF) is a core element in the quantification of Translocator protein 18 kDa with positron emission tomography (PET), as no suitable reference region with negligible binding has been identified. Arterial blood sampling is indeed needed to create the IF (ASIF). In the present manuscript we study individualization of a population based input function (PBIF) with a single arterial manual sample to estimate total distribution volume (VT) for [18F]FEPPA and to replicate previously published clinical studies in which the ASIF was used.MethodsThe data of 3 previous [18F]FEPPA studies (39 of healthy controls (HC), 16 patients with Parkinson’s disease (PD) and 18 with Alzheimer’s disease (AD)) was reanalyzed with the new approach. PBIF was used with the Logan graphical analysis (GA) neglecting the vascular contribution to estimate VT. Time of linearization of the GA was determined with the maximum error criteria. The optimal calibration of the PBIF was determined based on the area under the curve (AUC) of the IF and the agreement range of VT between methods. The shape of the IF between groups was studied while taking into account genotyping of the polymorphism (rs6971).ResultsPBIF scaled with a single value of activity due to unmetabolized radioligand in arterial plasma, calculated as the average of a sample taken at 60 min and a sample taken at 90 min post-injection, yielded a good interval of agreement between methods and optimized the area under the curve of IF. In HC, gray matter VTs estimated by PBIF highly correlated with those using the standard method (r2 = 0.82, p = 0.0001). Bland-Altman plots revealed PBIF slightly underestimates (~1 mL/cm3) VT calculated by ASIF (including a vascular contribution). It was verified that the AUC of the ASIF were independent of genotype and disease (HC, PD, and AD). Previous clinical results were replicated using PBIF but with lower statistical power.ConclusionA single arterial blood sample taken 75 minute post-injection contains enough information to individualize the IF in the groups of subjects studied; however, the higher variability produced requires an increase in sample size to reach the same effect size.

Reliable quantification of 18F-GE-180 PET neuroinflammation studies using an individually scaled population-based input function or late tissue-to-blood ratio

“…This is explained by the fact that the population-based input function does not well describe the early phase of the true individual input function due to remaining inter-subject variability of the position, the height, and the width of the input function peak despite the use of a standardized injection protocol. This effect can be reduced by shifting the population-based input function such that its peak matches the peak of a whole-blood curve in the brain derived from the PET data [46]. However, the impact on the time integral of the input function at late time points (included in the linear fit of the invasive Logan plot) is negligible.…”

“…This is analogous to PET with [ 18 F]fluorodeoxyglucose (FDG), where the (scan-time corrected) late lesion-to-blood uptake ratio shows excellent correlation with the FDG metabolic rate constant estimated by graphical analysis, better than the widely used standard uptake value (SUV) [36,37]. The performance of population-based input functions might be improved by using two or more blood samples for individual scaling of the input function template [31,33,34,46]. However, regional V T estimates obtained with the population-based method PB1 using a single blood sample at 27.5 min were strongly correlated with the regional reference V T in this study (mean Pearson coefficient over all ROIs = 0.989 ± 0.006, range 0.971-0.992; all p < 10 −10 ).…”

Activated Microglia in the Brain: Mitochondrial and Cell Membrane-Associated Targets for Positron Emission Tomography

“…The authors classified [ [88] whereas in the reports by Suridjan [89] [90] and Mabrouk [88] were included also people with severe cognitive impairment.…”

Brief Computer‐Based Information Processing Measures are Linked to White Matter Integrity in Pediatric‐Onset Multiple Sclerosis

“…Diffusion tensor imaging (DTI) can quantify the anisotropy of water diffusion, which can indicate the degree of myelination, integrity, and other microstructural properties of white and gray matter in the brain . In POMS, diffuse reductions in fractional anisotropy (FA) in NAWM have been identified, representing potential microstructural or demyelination processes occurring in occult tissue.…”

“…Diffusion tensor imaging (DTI) can quantify the anisotropy of water diffusion, which can indicate the degree of myelination, integrity, and other microstructural properties of white and gray matter in the brain. 9,10 In POMS, diffuse reductions in fractional anisotropy (FA) in NAWM have been identified, 11,12 representing potential microstructural or demyelination processes occurring in occult tissue. Additionally, the thalamus has been identified as a vulnerable target to both adult and pediatric MS. 13 Critical gaps in this literature exist, however, regarding whether these disruptions in white and deep gray matter integrity relate to cognitive changes in POMS.…”