Spill-in counts in the quantification of 18F-florbetapir on Aβ-negative subjects: the effect of including white matter in the reference region

Abstract

BackgroundWe aim to provide a systematic study of the impact of white matter (WM) spill-in on the calculation of standardized uptake value ratios (SUVRs) on Aβ-negative subjects, and we study the effect of including WM in the reference region as a compensation. In addition, different partial volume correction (PVC) methods are applied and evaluated.MethodsWe evaluated magnetic resonance imaging and 18F-AV-45 positron emission tomography data from 122 cognitively normal (CN) patients recruited at the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Cortex SUVRs were obtained by using the cerebellar grey matter (CGM) (SUVRCGM) and the whole cerebellum (SUVRWC) as reference regions. The correlations between the different SUVRs and the WM uptake (WM-SUVRCGM) were studied in patients, and in a well-controlled framework based on Monte Carlo (MC) simulation. Activity maps for the MC simulation were derived from ADNI patients by using a voxel-wise iterative process (BrainViset). Ten WM uptakes covering the spectrum of WM values obtained from patient data were simulated for different patients. Three different PVC methods were tested (a) the regional voxel-based (RBV), (b) the iterative Yang (iY), and (c) a simplified analytical correction derived from our MC simulation.ResultsWM-SUVRCGM followed a normal distribution with an average of 1.79 and a standard deviation of 0.243 (13.6%). SUVRCGM was linearly correlated to WM-SUVRCGM (r = 0.82, linear fit slope = 0.28). SUVRWC was linearly correlated to WM-SUVRCGM (r = 0.64, linear fit slope = 0.13). Our MC results showed that these correlations are compatible with those produced by isolated spill-in effect (slopes of 0.23 and 0.11). The impact of the spill-in was mitigated by using PVC for SUVRCGM (slopes of 0.06 and 0.07 for iY and RBV), while SUVRWC showed a negative correlation with SUVRCGM after PVC. The proposed analytical correction also reduced the observed correlations when applied to patient data (r = 0.27 for SUVRCGM, r = 0.18 for SUVRWC).ConclusionsThere is a high correlation between WM uptake and the measured SUVR due to spill-in effect, and that this effect is reduced when including WM in the reference region. We also evaluated the performance of PVC, and we proposed an analytical correction that can be applied to preprocessed data.

Error propagation analysis of seven partial volume correction algorithms for [18F]THK-5351 brain PET imaging

“…Radiopharmaceutical uptake in atrophied cortical regions of elderly subject is more difficult to quantify due to more severe PVE than normal cortical regions in young subjects. Furthermore, some radiopharmaceuticals for Aβ and tau PET imaging have high non-specific binding in white matter and these spill into targeted grey matter regions leading overestimation of accumulations [ 8 , 9 ]. The non-specific binding in white matter is not significant in studies of cerebral blood flow, glucose metabolism, and neuro-receptor imaging but in case of pathological Aβ and tau imaging is sometimes significant [ 9 ].…”

“…Furthermore, some radiopharmaceuticals for Aβ and tau PET imaging have high non-specific binding in white matter and these spill into targeted grey matter regions leading overestimation of accumulations [ 8 , 9 ]. The non-specific binding in white matter is not significant in studies of cerebral blood flow, glucose metabolism, and neuro-receptor imaging but in case of pathological Aβ and tau imaging is sometimes significant [ 9 ]. Therefore, in order to detect or diagnosis AD in the early phase, PVC is considered necessary [ 10 ].…”

“…There have been several reports which stated that application of PVC for of tau and amyloid PET imaging improved the accuracy and precision of the quantification of radiopharmaceutical-uptake [ 8 – 18 ]. Lopez-Gonzalez et al investigated the effect of white matter spill-in on SUVRs by using the regional voxel-based (RBV) [ 7 ] and iterative Yang (IY) [ 1 ] PVC algorithms [ 9 ]. However, in many cases, the applied PVC methods were limited to the classical and popular Müller-Gärtner (MG) [ 19 ] and geometric transfer matrix (GTM) methods [ 20 , 21 ] and similar algorithms.…”

Investigation of the benefit of PVC in high resolution PET as a post and within reconstruction method for FDG brain data

“…In a recent research [38] where the spill-in effect of counts was examined in amyloid negative subjects; the investigation of WM concentration was proved to be a valuable component in amyloid imaging. Using that same simulation software (Sim-SET) but for a different PET scanner, the acquisition times for the Monte-Carlo simulations was comparable to our methodology.…”

Corrección de atenuación en equipos PET-RM. Comparación de métodos mediante simulación Monte Carlo.

“…Se simuló un escáner Siemens Biograph con 32 anillos de detectores de 41.2 cm de radio basados en germanato de bismuto (BGO), usando 18 F como isótopo. 17,18 No se modelaron eventos aleatorios ni tiempo muerto en los detectores. Se usó adquisición 3D con span 1 y ventana de energía de 350 a 650 keV.…”