Voxel-Based Analysis of Amyloid Positron Emission Tomography Probe [¹¹C]BF-227 Uptake in Mild Cognitive Impairment and Alzheimer’s Disease

Abstract

Aim: To determine early brain changes in the distribution of an amyloid positron emission tomography (PET) probe, ¹¹C-labeled BF-227 or [¹¹C]BF-227, in order to accurately predict the progression of mild cognitive impairment (MCI) to Alzheimer’s disease (AD). Patients and Methods: Amyloid plaque burden was evaluated using [¹¹C]BF-227 PET in AD, MCI and aged normal controls. A voxel-based analysis of [¹¹C]BF-227 PET images was performed to characterize the culprit brain lesion in patients with MCI who were destined to progress to AD, referred to as MCI converters (MCI-C). In addition, binding characteristics of BF-227 to amyloid deposits were examined using postmortem AD brain samples. Results: Voxel-based statistical analyses of the BF-227 PET images clearly demonstrated an abnormal distribution of BF-227 mainly in the posterior association area in MCI-C and patients with AD. BF-227 uptake in the lateral temporal cortex was consistently observed in almost all MCI-C and patients with AD, and it distinguished MCI-C from MCI nonconverters. BF-227 binding strongly correlated with dense amyloid-β protein plaque density, but not with diffuse plaque density in the frontal cortex. Conclusion: BF-227 uptake in the lateral temporal cortex is a reliable indicator that can be used for predicting prognosis in patients with MCI.

Pitfalls of Voxel-Based Amyloid PET Analyses for Diagnosis of Alzheimer’s Disease: Artifacts due to Non-Specific Uptake in the White Matter and the Skull

“…A previous study by our colleagues showed that 3D-SSP was useful for detecting differences among groups (Kaneta et al 2011), but the presence of overestimated data in the ND group may have reduced the differences from the AD and MCI groups. In another study, most AD patients and MCIto-AD converters showed high Z-scores in the temporal cortices in the eZIS results (Shao et al 2010). Some of these results might have been influenced by artifacts resulted from high skull uptake.…”

“…Diffuse, high uptake in the white matter and local high uptake in part of the skull (arrows) are demonstrated on the original PET image. (Aalto et al 2009;Shao et al 2010;Shin et al 2010;Kaneta et al 2011), but did not focus on differences in the individual results between the two methods. To the best of our knowledge, this report is the first to perform a head-to-head comparison between the results of these two methods for amyloid PET analyses, and to demonstrate the differences in the results described here.…”

“…The different characteristics and pitfalls of each method have been revealed. Voxel-based amyloid PET analyses have also been reported using these methods (Aalto et al 2009;Shao et al 2010;Shin et al 2010;Kaneta et al 2011). Previously, AS errors in 3D-SSP amyloid PET analysis were reported (Kaneta et al 2011); however, the limitations of voxel-based-methods specific to amyloid PET have not been thoroughly investigated.…”

Evaluation of MoCA Scale Ratings with Cognitive Level Correlation in Mild Cognitive Disorders

“…In voxel-based positron emission tomography (PET) that was performed using the BF 227 ligand, patients with AD and MCI were reported to have an abnormal distribution pattern in the field of posterior association (15). It has been reported that changes in latency and amplitudes of movement-related cortical potentials (MRCP) can indicate the presence of frontal dysfunction electrophysiologically in cases with MCI (16). These are difficult and expensive examinations to access and implement.…”

P1‐149: Structural MRI and amyloid PET imaging for prediction of conversion to Alzheimer's disease in patients with mild cognitive impairment: A meta‐analysis

“…Eight studies satisfied all inclusion and exclusion criteria (Table 2). 29,32,[34][35][36][37][38][39] Weighted Hedges' s g from the random effects models was 1.316 (95% CI 0.920-1.712) ( Figure 2B). Tests for heterogeneity were not significant (Q=9.554, p=0.215, I-squared=26.735).…”