bf-227 and Cognitive-Dysfunction

Three-dimensional stereotactic surface projection (3D-SSP) analyses have been widely used in dementia imaging studies. However, 3D-SSP sometimes shows paradoxical results on amyloid positron emission tomography (PET) analyses. This is thought to be caused by errors in anatomical standardization (AS) based on an (18)F-fluorodeoxyglucose (FDG) template. We developed a new method of 3D-SSP analysis for amyloid PET imaging, and used it to analyze (11)C-labeled 2-(2-[2-dimethylaminothiazol-5-yl]ethenyl)-6-(2-[fluoro]ethoxy)benzoxazole (BF-227) PET images of subjects with mild cognitive impairment (MCI) and Alzheimer's disease (AD).. The subjects were 20 with MCI, 19 patients with AD, and 17 healthy controls. Twelve subjects with MCI were followed up for 3 years or more, and conversion to AD was seen in 6 cases. All subjects underwent PET with both FDG and BF-227. For AS and 3D-SSP analyses of PET data, Neurostat (University of Washington, WA, USA) was used. Method 1 involves AS for BF-227 images using an FDG template. In this study, we developed a new method (Method 2) for AS: First, an FDG image was subjected to AS using an FDG template. Then, the BF-227 image of the same patient was registered to the FDG image, and AS was performed using the transformation parameters calculated for AS of the corresponding FDG images. Regional values were normalized by the average value obtained at the cerebellum and values were calculated for the frontal, parietal, temporal, and occipital lobes. For statistical comparison of the 3 groups, we applied one-way analysis of variance followed by the Bonferroni post hoc test. For statistical comparison between converters and non-converters, the t test was applied. Statistical significance was defined as p < 0.05.. Among the 56 cases we studied, Method 1 demonstrated slight distortions after AS of the image in 16 cases and heavy distortions in 4 cases in which the distortions were not observed with Method 2. Both methods demonstrated that the values in AD and MCI patients were significantly higher than those in the controls, in the parietal, temporal, and occipital lobes. However, only Method 2 showed significant differences in the frontal lobes. In addition, Method 2 could demonstrate a significantly higher value in MCI-to-AD converters in the parietal and frontal lobes.. Method 2 corrects AS errors that often occur when using Method 1, and has made appropriate 3D-SSP analysis of amyloid PET imaging possible. This new method of 3D-SSP analysis for BF-227 PET could prove useful for detecting differences between normal groups and AD and MCI groups, and between converters and non-converters.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Benzoxazoles; Carbon Radioisotopes; Case-Control Studies; Cognitive Dysfunction; Female; Humans; Imaging, Three-Dimensional; Male; Plaque, Amyloid; Positron-Emission Tomography; Reference Standards; Thiazoles

To examine the usefulness of the early phase [(11)C]BF-227 positron emission tomography (PET) for (1) conferring additional diagnostic value by providing perfusion-like information and (2) obtaining the appropriate anatomical standardization (AS) using three-dimensional stereotactic surface projection (3D-SSP) method.. This study included 20 mild cognitive impairment (MCI), 19 Alzheimer's disease (AD), and 17 normal cognitive (NC) subjects. Early- and late-phase BF-227 PET images were obtained 0-10 and 40-60 min after the injection, respectively. AS for late-phase BF-227 images were performed by 2 methods: (1) method A, for AS of late-phase BF-227 images using (8)F-fluorodeoxyglucose (FDG) images of the same subject and (2) method B, for AS of late-phase BF-227 images using early phase BF-227 images.. Method B was successfully used for AS in all cases. The Z score maps of 3D-SSP analyses of FDG PET and early phase BF-227 PET for AD and MCI groups showed a typical AD-like pattern. Regional analyses revealed that the early phase BF-227 PET showed significant differences between AD and NC, and MCI and NC.. The early phase BF-227 PET images showed significant abnormal findings for the AD and MCI groups. AS of late-phase BF-227 images using early phase BF-227 images were successful, and enabled appropriate 3D-SSP analyses.

Topics: Aged; Alzheimer Disease; Benzoxazoles; Brain; Carbon Radioisotopes; Cognitive Dysfunction; Female; Fluorodeoxyglucose F18; Humans; Imaging, Three-Dimensional; Male; Positron-Emission Tomography; Radiopharmaceuticals; Reproducibility of Results; Thiazoles

Two methods are commonly used in brain image voxel-based analyses widely used for dementia work-ups: 3-dimensional stereotactic surface projections (3D-SSP) and statistical parametric mapping (SPM). The methods calculate the Z-scores of the cortical voxels that represent the significance of differences compared to a database of brain images with normal findings, and visualize them as surface brain maps. The methods are considered useful in amyloid positron emission tomography (PET) analyses to detect small amounts of amyloid-β deposits in early-stage Alzheimer's disease (AD), but are not fully validated. We analyzed the (11)C-labeled 2-(2-[2-dimethylaminothiazol-5-yl]ethenyl)-6-(2-[fluoro]ethoxy)benzoxazole (BF-227) amyloid PET imaging of 56 subjects (20 individuals with mild cognitive impairment [MCI], 19 AD patients, and 17 non-demented [ND] volunteers) with 3D-SSP and the easy Z-score imaging system (eZIS) that is an SPM-based method. To clarify these methods' limitations, we visually compared Z-score maps output from the two methods and investigated the causes of discrepancies between them. Discrepancies were found in 27 subjects (9 MCI, 13 AD, and 5 ND). Relatively high white matter uptake was considered to cause higher Z-scores on 3D-SSP in 4 subjects (1 MCI and 3 ND). Meanwhile, in 17 subjects (6 MCI, 9 AD, and 2 ND), Z-score overestimation on eZIS corresponded with high skull uptake and disappeared after removing the skull uptake ("scalping"). Our results suggest that non-specific uptakes in the white matter and skull account for errors in voxel-based amyloid PET analyses. Thus, diagnoses based on 3D-SSP data require checking white matter uptake, and "scalping" is recommended before eZIS analysis.

Topics: Aged; Alzheimer Disease; Amyloid; Artifacts; Benzoxazoles; Cognitive Dysfunction; Dementia; Demography; Female; Humans; Male; Positron-Emission Tomography; Skull; Thiazoles; White Matter