A modified method of 3D-SSP analysis for amyloid PET imaging using [¹¹C]BF-227

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 ¹⁸F-fluorodeoxyglucose (FDG) template. We developed a new method of 3D-SSP analysis for amyloid PET imaging, and used it to analyze ¹¹C-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.