Cerebellar Amyloid-β Plaques: How Frequent Are They, and Do They Influence ¹⁸F-Florbetaben SUV Ratios?

Abstract

SUV ratios (SUVRs) are used for relative quantification of 18 Fflorbetaben scans. The cerebellar cortex can be used as a reference region for quantification. However, cerebellar amyloid-β (Aβ) plaques may be present in Alzheimer disease (AD). The aim of this study was to assess the influence of Aβ pathology, including neuritic plaques, diffuse plaques, and vascular deposits, in 18 F-florbetaben SUVR when cerebellum is used as the reference. Methods: Using immunohistochemistry to demonstrate Aβ plaques and vascular deposits, and using the Bielschowsky method to demonstrate neuritic plaques, we performed a neuropathologic assessment of the frontal, occipital, anterior cingulate, and posterior cingulate cerebral cortices and the cerebellar cortex of 87 end-of-life patients (64 with AD, 14 with other types of dementia, and 9 nondemented aged volunteers; mean age ± SD, 80.4 ± 10.2 y) who had undergone 18 F-florbetaben PET before death. The lesions were rated as absent (none or sparse) or present (moderate or frequent). Mean cortical SUVRs were compared among cases with different cerebellar Aβ loads. Results: None of the 83 evaluable cerebellar samples showed frequent diffuse Aβ or neuritic plaques; 8 samples showed frequent vascular Aβ deposits. Diffuse Aβ plaques were rated as absent in 78 samples (94%) and present in 5 samples (6%). Vascular Aβ was rated as absent in 62 samples (74.7%) and present in 21 samples (25.3%). No significant differences in cerebellar SUVs were found among cases with different amounts or types of Aβ deposits in the cerebral cortex. Both diffuse and neuritic plaques were found in the cerebral cortex of 26-44 cases. No significant SUVR differences were found between these brains with different cerebellar Aβ loads. Conclusion: The effect of cerebellar plaques on cortical 18 F-florbetaben SUVRs appears to be negligible even in advanced stages of AD with a higher cerebellar Aβ load.

Optimized classification of 18F-Florbetaben PET scans as positive and negative using an SUVR quantitative approach and comparison to visual assessment

“…However, the cerebellar gray matter is likely to be devoid of Aβ in the clinical intended population for brain Aβ imaging. Additionally, the effect of cerebellar plaques in cortical FBB SUVRs appears to be negligible even in advanced stages of AD with high cortical Aβ load (Catafau et al, 2016). For this reason, GCER is commonly used as RR for relative FBB uptake quantification.…”

Optimal Reference Region to Measure Longitudinal Amyloid-β Change with 18F-Florbetaben PET

“…CGM can, however, be affected by amyloid accumulation in late disease stages, but this effect is unlikely to happen in patients with MCI, such as those enrolled in the present study, or the clinically intended population for brain Ab imaging. Indeed, the effect of cerebellar plaques in cortical 18 F-florbetaben SUVRs appears to be negligible, even in advanced stages of AD with high cortical Ab load (9). Another potential limitation of CGM, which is shared by the pons, is that it seems to be vulnerable to scatter and truncation as a result of its position close to the edge of the scanner field of view.…”

“…In the intended clinical population for brain Ab imaging, however, CGM is likely to be devoid of Ab. Furthermore, the effect of cerebellar plaques in cortical 18 F-florbetaben SUVRs appears to be negligible, even in advanced stages of AD with high cortical Ab load (9). Limitations of this RR, however, include the small size of the region and its proximity to the edge of the scanner field of view, where truncation or scatter influence can decrease the signal-to-noise ratio (6,10).…”

18F‐Florbetaben PET/CT to Assess Alzheimer's Disease: A new Analysis Method for Regional Amyloid Quantification

“…For each patient, the normalized amyloid PET images were used for SUVR computation within each volumetric ROI. For the SUVR computation, we selected all the AAL brain regions as target regions and excluded those that were not related to dementia, then used cerebellum as reference region which corresponds to “Cerebellum_4_5” of AAL atlas as the brain region which is not significantly affected by pathological amyloid burden . We did not apply any mask for GM because MRI was not part of the normalization process.…”