# Comparison of MRI-, CT- and PET-based anatomical standardization for Centiloid scale calculation in [18F]florbetapir positron emission tomography

## TL;DR

This study compares different methods for standardizing amyloid PET scans when MRI data is unavailable, finding that CT scans and PET-only methods can be used but with some limitations.

## Contribution

The study evaluates the clinical applicability of CT scan-based and PET-only anatomical standardization as alternatives to MRI-based methods for Centiloid scale calculation in amyloid PET.

## Key findings

- CT scan-based standardization systematically underestimates Centiloid values compared to MRI-based methods.
- PET-only standardization slightly underestimates Centiloid values but is more accurate than CT-based methods.
- For clearly positive or negative cases, omitting MRI does not affect diagnostic thresholds.

## Abstract

The Centiloid (CL) method is a standardized quantitative approach for amyloid positron emission tomography (PET) that involves the anatomical standardization of PET images. The Global Alzheimer’s Association Interactive Network recommends performing this anatomical standardization using contemporaneously acquired three-dimensional (3D) T1-weighted magnetic resonance imaging (MRI). However, in clinical practice, contemporaneous 3D T1WI is not always available due to outdated imaging or missing sequences. Recently, alternative methods utilizing low-dose computed tomography (CT) scan images from PET/CT scan or PET images themselves for anatomical standardization have been proposed and implemented in commercially available software. This study aimed to compare the CL obtained via MRI-based standardization with CT scan-based and PET-only standardizations. Further, the clinical applicability of these alternative methods was assessed.

We retrospectively analyzed 68 patients who underwent [18 F]florbetapir PET/CT scan imaging. The CL were calculated using two commercially available software programs—AMYclz® Neuro (PDR Pharma, Tokyo) and BRAINEER® Model A (Splink, Tokyo)—under three conditions: anatomical standardization with MRI, CT scan, and a PET-derived template. The correlations and differences among these methods were evaluated.

68 patients (age: 70.8 ± 11.2) were included in the analysis. The median CL was 33.87 (3.53–76.57). CT scan-based standardization had lower CL than MRI-based standardization (mean difference: −5.9 ± 4.8). Meanwhile, PET-only standardization had slightly lower CL than MRI-based standardization (-2.1 ± 11.0). The differences in the CL were generally within ± 15. In cases with evidently positive (CL ≥ 50) or clearly negative (CL ≤ 5) findings, the omission of MRI did not affect exceeding the threshold.

When contemporaneous 3D T1WI is not available, CT scan-based or PET-only anatomical standardization can be a practical alternative for the qualitative assessment of amyloid PET. However, users should recognize that CT scan-based methods have a systematic tendency to underestimate CL values compared with MRI-based methods. Meanwhile, PET-only methods have a tendency to slightly underestimate CL values. The omission of MRI may be acceptable for clear positive or negative cases. However, caution is required for borderline cases, particularly in situations requiring precise quantification such as treatment monitoring.

The online version contains supplementary material available at 10.1007/s12149-025-02134-4.