Amyloid PET Z-score Quantification and correlation with visual semiquantitative grading

Abstract

Background and purpose: Amyloid PET imaging plays a crucial role in the diagnosis of Alzheimer's disease (AD) and determines eligibility for anti-amyloid therapies. While visual interpretation using Regional Cortical Tracer Uptake (RCTU) and Brain Amyloid Plaque Load (BAPL) scores remains standard in clinical practice, it is subject to inter-reader variability and may not fully depict the amyloid distribution pattern. RCTU scoring evaluates cortical tracer uptake quantified as 1: no uptake, 2: focal and 3: diffuse uptake, while BAPL provides an overall summary score of amyloid plaque load depending on highest RCTU score. Quantitative techniques such as Centiloid scale or Z-scores may assist in diagnosis, grading and treatment monitoring. This study evaluates the feasibility of a Z-score quantification generated from normative database comparison and its correlation with visual RCTU grading.

Materials and methods: We retrospectively analyzed 100 patients who underwent [F18]-Florbetaben PET imaging between August and October 2024 for cognitive impairment. Visual interpretation was performed using RCTU scoring and overall BAPL score. Quantitative Z-scores were calculated for four cortical regions (frontal, parietal, posterior cingulate/precuneus, and lateral temporal) using a normative database. Correlation between visual and quantitative scores was assessed using Spearman's correlation. Z-score differences among RCTU categories were evaluated with Kruskal Wallis and Mann Whitney tests.

Results: Among 100 patients (median age 78), 31 were amyloid negative (BAPL1), and 69 were amyloid positive (11 BAPL2, and 58 BAPL3). A total of 400 cortical regions were evaluated (143 RCTU1, 46 RCTU2, 211 RCTU3). Strong positive correlations were observed between RCTU and Z-scores in all regions (ρ = 0.78-0.88, p < 0.0001). The regional Z-scores showed significant differences between RCTU1 and RCTU2, RCTU1 and RCTU3, as well as between RCTU2 and RCTU3 across all four regions (p<0.05 for all comparisons. Pooled regional analysis also showed statistically significant differences in Z-scores between all RCTU groups (p < 0.0001).

Conclusions: Quantitative regional Z-scores derived from amyloid PET imaging demonstrate a strong correlation with visual assessment (RCTU score), validating their feasibility in clinical interpretation. These findings support the integration of quantitative tools into routine practice to enhance diagnostic confidence, reduce reader variability, and monitoring for amyloid-targeted therapies.

Abbreviations: AD = Alzheimer's Disease; RCTU = Regional Cortical Tracer Uptake; BAPL = Brain Amyloid Plaque Load; PiB = Pittsburgh Compound B; SUVR = Standardized Uptake Value Ratio; SPM = Statistical Parametric Mapping; SSP = Stereotactic Surface Projections.