Simplified parametric methods for [11C]PIB studies.
ABSTRACT The purpose of the present study was to evaluate the performance of various parametric reference tissue models for quantification of [11C]PIB studies. Several models with and without fixing the reference tissue efflux rate constant (k'(2)) were investigated using both simulations and clinical data. The following parametric methods were evaluated: receptor parametric mapping (basis function implementation of the simplified reference tissue model with and without fixed k'(2)), reference Logan, and several multi-linear reference tissue methods (again with and without fixed k'(2)). In addition, standardised uptake value ratios with cerebellum (SUV(r)) were evaluated. Simulations were used to assess the effects of variation in flow (R(1)), fractional blood volume (V(b)) and binding potential (BP(ND)) itself on precision and accuracy of parametric BP(ND). For clinical studies, most parametric methods showed comparable performance, with poorest results for SUV(r). Best performance was obtained for receptor parametric mapping (RPM2) and one of the multi-linear reference tissue models (MRTM2), both with fixed k'(2): BP(ND) outcome was less affected by noise and the images showed better contrast than other tested methods. RPM2 and MRTM2 also provided best accuracy and precision in the simulation studies and are therefore the methods of choice for parametric analysis of clinical [11C]PIB studies.
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Article: Amyloid imaging in clinical trials.[Show abstract] [Hide abstract]
ABSTRACT: The possibility to map amyloid-beta, the Alzheimer's disease hallmark protein, in vivo opens the application for amyloid imaging in clinical trials with disease-modifying agents. Monitoring change in amyloid burden, particularly when potential amyloid-lowering drugs are at play, requires accurate analytical methods. Studies to date have used suboptimal methods that do not account for heterogeneous changes in flow associated with disease progression and potentially with anti-amyloid drugs. In this commentary, we discuss practical and methodological issues regarding longitudinal amyloid imaging and propose several quantitative, yet feasible, alternatives for reliable assessment of changes over time in amyloid burden.Alzheimer's Research and Therapy 08/2013; 5(4):36. · 4.39 Impact Factor
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ABSTRACT: Abstract Objective: Traumatic brain injury (TBI) is an epigenetic risk factor for Alzheimer's disease (AD) and amyloid β (Aβ) deposition is observed histopathologically in the traumatized brain. This study was conducted to detect cerebral Aβ deposition using amyloid positron emission tomography (PET) in patients with neuropsychological impairment after TBI. Methods: Twelve patients with post-traumatic neuropsychological impairment (11 men and one woman, age range = 21-78 years) were examined using Pittsburgh Compound B ((11)C-PIB) PET at the chronic stage after TBI (range = 5-129 months). Results: (11)C-PIB was positive in three patients and negative in the other nine patients. There was no correlation between (11)C-PIB deposition and the severity of injury; initial CT findings; elapsed time from the injury; and neuropsychological test scores. Conclusions: The absence of Aβ deposition in many patients with chronic neuropsychological impairment after TBI does not support the premise that Aβ pathology progresses over time in the traumatized brain. Early and sequential (11)C-PIB PET examination may clarify the time course of Aβ deposition in the traumatized brain and the relationship between traumatic brain insult and subsequent neuropsychological impairment.Brain Injury 05/2013; · 1.51 Impact Factor
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ABSTRACT: The present multimodal neuroimaging study examined whether amyloid pathology and glucose metabolism are related to cortical volume loss over time in Alzheimer's disease (AD) patients and healthy elderly controls. Structural MRI scans of eleven AD patients and ten controls were available at baseline and follow-up (mean interval 2.5 years). Change in brain structure over time was defined as percent change of cortical volume within seven a-priori defined regions that typically show the strongest structural loss in AD. In addition, two PET scans were performed at baseline: [(11)C]PIB to assess amyloid-β plaque load and [(18)F]FDG to assess glucose metabolism. [(11)C]PIB binding and [(18)F]FDG uptake were measured in the precuneus, a region in which both amyloid deposition and glucose hypometabolism occur early in the course of AD. While amyloid-β plaque load at baseline was not related to cortical volume loss over time in either group, glucose metabolism within the group of AD patients was significantly related to volume loss over time (rho = 0.56, p < 0.05). The present study shows that in a group of AD patients amyloid-β plaque load as measured by [(11)C]PIB behaves as a trait marker (i.e., all AD patients showed elevated levels of amyloid, not related to subsequent disease course), whilst hypometabolism as measured by [(18)F]FDG changed over time indicating that it could serve as a state marker that is predictive of neurodegeneration.European Journal of Nuclear Medicine 03/2014; · 4.53 Impact Factor