Subregional Biomarkers in FDG PET for Alzheimer’s Diagnosis and Staging: An Interpretable and Explainable model
Bibliographic record
Abstract
Abstract Objective To investigate the radiomics features of the hippocampus and the amygdala subregions in FDG-PET images that can best differentiate Mild Cognitive Impairment (MCI), Alzheimer’s Disease (AD), and healthy patients. Methods Baseline FDG-PET data from 555 participants in the ADNI dataset were analyzed, comprising 189 cognitively normal (CN) individuals, 201 with MCI, and 165 with AD. The hippocampus and amygdala were segmented based on the DKT-Atlas, with additional subdivisions guided by probabilistic atlases from Freesurfer. Then radiomic features (n=120) were extracted from 38 hippocampal subregions and 18 amygdala nuclei using PyRadiomics. Various feature selection techniques, including ANOVA, PCA, Chi-square, and LASSO, were applied alongside nine machine learning classifiers. Results The Multi-Layer Perceptron (MLP) model combined with LASSO demonstrated excellent classification performance: ROC AUC of 0.957 for CN vs. AD, ROC AUC of 0.867 for MCI vs. AD, and ROC AUC of 0.782 for CN vs. MCI. Key regions, including the accessory basal nucleus, presubiculum head, and CA4 head, were identified as critical biomarkers. Features including GLRLM (Long Run Emphasis) and Small Dependence Emphasis (GLDM) showed strong diagnostic potential, reflecting subtle metabolic and microstructural changes often preceding anatomical alterations. Conclusion Specific hippocampal and amygdala subregions and their four radiomic features were found to have a significant role in the early diagnosis of AD, its staging, and its severity assessment by capturing subtle shifts in metabolic patterns. Furthermore, these features offer potential insights into the disease’s underlying mechanisms and model interpretability.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".