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Updated: Oct 20, 2025

Hybrid PET/MRI Imaging of Alzheimer's Disease Based on 18F-AV-1451
Published on: April 18, 2025
Heuristic scoring method utilizing FDG-PET statistical parametric mapping in the evaluation of suspected Alzheimer
Jeremy N Ford1, Elizabeth M Sweeney2, Myrto Skafida3
1Department of Radiology, Massachusetts General Hospital Boston, MA, United States.
Abstract:
Distinguishing frontotemporal lobar degeneration (FTLD) and Alzheimer Disease (AD) on FDG-PET based on qualitative review alone can pose a diagnostic challenge. SPM has been shown to improve diagnostic performance in research settings, but translation to clinical practice has been lacking. Our purpose was to create a heuristic scoring method based on statistical parametric mapping z-scores. We aimed to compare the performance of the scoring method to the initial qualitative read and a machine learning (ML)-based method as benchmarks. FDG-PET/CT or PET/MRI of 65 patients with suspected dementia were processed using SPM software, yielding z-scores from either whole brain (W) or cerebellar (C) normalization relative to a healthy cohort. A non-ML, heuristic scoring system was applied using region counts below a preset z-score cutoff. W z-scores, C z-scores, or WC z-scores (z-scores from both W and C normalization) served as features to build random forest models. The neurological diagnosis was used as the gold standard. The sensitivity of the non-ML scoring system and the random forest models to detect AD was higher than the initial qualitative read of the standard FDG-PET [0.89-1.00 vs. 0.22 (95% CI, 0-0.33)]. A categorical random forest model to distinguish AD, FTLD, and normal cases had similar accuracy than the non-ML scoring model (0.63 vs. 0.61). Our non-ML-based scoring system of SPM z-scores approximated the diagnostic performance of a ML-based method and demonstrated higher sensitivity in the detection of AD compared to qualitative reads. This approach may improve the diagnostic performance.
Insights
A new heuristic scoring method using statistical parametric mapping (SPM) z-scores improves the detection of Alzheimer Disease (AD) and frontotemporal lobar degeneration (FTLD) on FDG-PET scans. This approach offers higher sensitivity than qualitative reads and matches machine learning performance.
Area of Science:
- Neuroimaging
- Nuclear Medicine
- Neurology
Background:
- Distinguishing frontotemporal lobar degeneration (FTLD) from Alzheimer Disease (AD) on FDG-PET can be challenging with qualitative review alone.
- Statistical Parametric Mapping (SPM) shows promise in research but lacks clinical translation for dementia diagnosis.
Purpose of the Study:
- To develop a heuristic scoring method using SPM z-scores for dementia diagnosis.
- To compare this non-ML scoring method against initial qualitative reads and machine learning (ML) benchmarks.
Main Methods:
- 65 patients with suspected dementia underwent FDG-PET/CT or PET/MRI.
- SPM software generated z-scores using whole brain (W) or cerebellar (C) normalization.
- A non-ML heuristic scoring system was applied using region counts below a z-score cutoff; random forest models were built using W, C, or WC z-scores.
Main Results:
- The non-ML scoring system and random forest models showed significantly higher sensitivity for detecting AD compared to initial qualitative reads (0.89-1.00 vs. 0.22).
- A categorical random forest model distinguishing AD, FTLD, and normal cases had accuracy comparable to the non-ML scoring model (0.63 vs. 0.61).
Conclusions:
- The non-ML heuristic scoring system using SPM z-scores approximates ML-based diagnostic performance.
- This novel approach demonstrates improved sensitivity for AD detection over qualitative reads and may enhance clinical diagnostic performance.
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