Dataset Information

Partial volume correction analysis for ¹¹C-UCB-J PET studies of Alzheimer's disease.

ABSTRACT:

Purpose

¹¹C-UCB-J PET imaging, targeting synaptic vesicle glycoprotein 2A (SV2A), has been shown to be a useful indicator of synaptic density in Alzheimer's disease (AD). For SV2A imaging, a decrease in apparent tracer uptake is often due to the combination of gray-matter (GM) atrophy and SV2A decrease in the remaining tissue. Our aim is to reveal the true SV2A change by performing partial volume correction (PVC).

Methods

We performed two PVC algorithms, Müller-Gärtner (MG) and 'iterative Yang' (IY), on 17 AD participants and 11 cognitive normal (CN) participants using the brain-dedicated HRRT scanner. Distribution volume V_T, the rate constant K₁, binding potential BP_ND (centrum semiovale as reference region), and tissue volume were compared.

Results

In most regions, both PVC algorithms reduced the between-group differences. Alternatively, in hippocampus, IY increased the significance of between-group differences while MG reduced it (V_T, BP_ND and K₁ group differences: uncorrected: 20%, 27%, 17%; MG: 18%, 22%, 14%; IY: 22%, 28%, 17%). The group difference in hippocampal volume (10%) was substantially smaller than any PET measures. MG increased GM binding values to a greater extent than IY due to differences in algorithm assumptions.

Conclusion

¹¹C-UCB-J binding is significantly reduced in AD hippocampus, but PVC is important to adjust for significant volume reduction. After correction, PET measures are substantially more sensitive to group differences than volumetric MRI measures. Assumptions of each PVC algorithm are important and should be carefully examined and validated. For ¹¹C-UCB-J, the less stringent assumptions of IY support its use as a PVC algorithm over MG.

SUBMITTER: Lu Y

PROVIDER: S-EPMC8454285 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAttempts to associate amyloid-β (Aβ) pathogenesis with synaptic loss in Alzheimer's disease (AD) have thus far been limited to small numbers of postmortem studies. Aβ plaque burden is not well-correlated with indices of clinical severity or neurodegeneration-at least in the dementia stage-as deposition of Aβ reaches a ceiling. In this study, we examined in vivo the association between fibrillar Aβ deposition and synaptic density in early AD using positron emission tomography (PET). We hypothesized that global Aβ deposition would be more strongly inversely associated with hippocampal synaptic density in participants with amnestic mild cognitive impairment (aMCI; a stage of continued Aβ accumulation) compared to those with dementia (a stage of relative Aβ plateau).MethodsWe measured SV2A binding ([11C]UCB-J) and Aβ deposition ([11C]PiB) in 14 participants with aMCI due to AD and 24 participants with mild AD dementia. Distribution volume ratios (DVR) with a cerebellar reference region were calculated for both tracers to investigate the association between global Aβ deposition and SV2A binding in hippocampus. Exploratory analyses examined correlations between both global and regional Aβ deposition and SV2A binding across a broad range of brain regions using both ROI- and surface-based approaches.ResultsWe observed a significant inverse association between global Aβ deposition and hippocampal SV2A binding in participants with aMCI (r = - 0.55, P = 0.04), but not mild dementia (r = 0.05, P = 0.82; difference statistically significant by Fisher z = - 1.80, P = 0.04). Exploratory analyses across other ROIs and whole brain analyses demonstrated no broad or consistent associations between global Aβ deposition and regional SV2A binding in either diagnostic group. ROI-based analyses of the association between regional Aβ deposition and SV2A binding also revealed no consistent pattern but suggested a "paradoxical" positive association between local Aβ deposition and SV2A binding in the hippocampus.ConclusionsOur findings lend support to a model in which fibrillar Aβ is still accumulating in the early stages of clinical disease but approaching a relative plateau, a point at which Aβ may uncouple from neurodegenerative processes including synaptic loss. Future research should investigate the relationship between Aβ deposition and synaptic loss in larger cohorts beginning preclinically and followed longitudinally in conjunction with other biomarkers.

Project description:BackgroundAccurate quantification of PET studies depends on the spatial resolution of the PET data. The commonly limited PET resolution results in partial volume effects (PVE). Iterative deconvolution methods (IDM) have been proposed as a means to correct for PVE. IDM improves spatial resolution of PET studies without the need for structural information (e.g. MR scans). On the other hand, deconvolution also increases noise, which results in lower signal-to-noise ratios (SNR). The aim of this study was to implement IDM in combination with HighlY constrained back-PRojection (HYPR) denoising to mitigate poor SNR properties of conventional IDM.MethodsAn anthropomorphic Hoffman brain phantom was filled with an [18F]FDG solution of ~25 kBq mL-1 and scanned for 30 min on a Philips Ingenuity TF PET/CT scanner (Philips, Cleveland, USA) using a dynamic brain protocol with various frame durations ranging from 10 to 300 s. Van Cittert IDM was used for PVC of the scans. In addition, HYPR was used to improve SNR of the dynamic PET images, applying it both before and/or after IDM. The Hoffman phantom dataset was used to optimise IDM parameters (number of iterations, type of algorithm, with/without HYPR) and the order of HYPR implementation based on the best average agreement of measured and actual activity concentrations in the regions. Next, dynamic [11C]flumazenil (five healthy subjects) and [11C]PIB (four healthy subjects and four patients with Alzheimer's disease) scans were used to assess the impact of IDM with and without HYPR on plasma input-derived distribution volumes (V T) across various regions of the brain.ResultsIn the case of [11C]flumazenil scans, Hypr-IDM-Hypr showed an increase of 5 to 20% in the regional V T whereas a 0 to 10% increase or decrease was seen in the case of [11C]PIB depending on the volume of interest or type of subject (healthy or patient). References for these comparisons were the V Ts from the PVE-uncorrected scans.ConclusionsIDM improved quantitative accuracy of measured activity concentrations. Moreover, the use of IDM in combination with HYPR (Hypr-IDM-Hypr) was able to correct for PVE without increasing noise.

Dataset Information

Partial volume correction analysis for ¹¹C-UCB-J PET studies of Alzheimer's disease.

Purpose

Methods

Results

Conclusion

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Partial volume correction analysis for 11C-UCB-J PET studies of Alzheimer's disease.

Purpose

Methods

Results

Conclusion

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Partial volume correction analysis for ¹¹C-UCB-J PET studies of Alzheimer's disease.