Clinical and Pathological Validation of CT-Based Regional Harmonization Methods of Amyloid PET

Abstract

Purpose The CT-based regional direct comparison Centiloid (dcCL) method was developed to harmonize and quantify regional β-amyloid (Aβ) burden. In the present study, we aimed to investigate correlations between the CT-based regional dcCL scales and Aβ pathological burdens and to validate the clinical utility using thresholds derived from pathological assessment. Patients and Methods We included a pathological cohort of 63 cases and a clinical cohort of 4062 participants, and obtained modified Consortium to Establish a Registry for Alzheimer’s Disease criteria (mCERAD) scores by assessment of neuritic plaque burdens in multiple areas of each cortical region. PET and CT images were processed using the CT-based regional dcCL method to calculate scales in 6 distinct regions. Results The CT-based regional dcCL scales were correlated with neuritic plaque burdens represented by mCERAD scores, globally and regionally (r = 0.56~0.76). In addition, striatum dcCL scales reflected Aβ involvement in the striatum (P < 0.001). The regional dcCL scales could predict significant Aβ deposition in specific brain regions with high accuracy: area under the receiver operating characteristic curve of 0.81–0.97 with an mCERAD cutoff of 1.5 and area under the receiver operating characteristic curve of 0.88–0.93 with an mCERAD cutoff of 0.5. When applying the dcCL thresholds of 1.5 mCERAD scores, the G(−)R(+) group showed lower performances in memory and global cognitive functions and had less hippocampal volume compared with the G(−)R(−) group (P < 0.001). However, when applying the dcCL thresholds of 0.5 mCERAD scores, there were no differences in the global cognitive functions between the 2 groups. Conclusions The thresholds of regional dcCL scales derived from pathological assessments might provide clinicians with a better understanding of biomarker-guided diagnosis and distinguishable clinical phenotypes, which are particularly useful when harmonizing different PET ligands with only PET/CT.