Detecting conversion from mild cognitive impairment to Alzheimer’s disease using FLAIR MRI biomarkers
Bibliographic record
Abstract
Mild cognitive impairment (MCI) is the prodromal phase of Alzheimer's disease (AD) and while it presents as an imperative intervention window, it is difficult to detect which subjects convert to AD (cMCI) and which ones remain stable (sMCI). The objective of this work was to investigate fluid-attenuated inversion recovery (FLAIR) MRI biomarkers and their ability to differentiate between sMCI and cMCI subjects in cross-sectional and longitudinal data. Three types of biomarkers were investigated: volume, intensity and texture. Volume biomarkers included total brain volume, cerebrospinal fluid volume (CSF), lateral ventricular volume, white matter lesion volume, subarachnoid CSF, and grey matter (GM) and white matter (WM), all normalized to intracranial volume. The mean intensity, kurtosis, and skewness of the GM and WM made up the intensity features. Texture features quantified homogeneity and microstructural tissue changes of GM and WM regions. Composite indices were also considered, which are biomarkers that represent an aggregate sum (z-score normalization and summation) of all biomarkers. The FLAIR MRI biomarkers successfully identified high-risk subjects as significant differences (p < 0.05) were found between the means of the sMCI and cMCI groups and the rate of change over time for several individual biomarkers as well as the composite indices for both cross-sectional and longitudinal analyses. Classification accuracy and feature importance analysis showed volume biomarkers to be most predictive, however, best performance was obtained when complimenting the volume biomarkers with the intensity and texture features. Using all the biomarkers, accuracy of 86.2 % and 69.2 % was achieved for normal control-AD and sMCI-cMCI classification respectively. Survival analysis demonstrated that the majority of the biomarkers showed a noticeable impact on the AD conversion probability 4 years prior to conversion. Composite indices were the top performers for all analyses including feature importance, classification, and survival analysis. This demonstrated their ability to summarize various dimensions of disease into single-valued metrics. Significant correlation (p < 0.05) with phosphorylated-tau and amyloid-beta CSF biomarkers was found with all the FLAIR biomarkers. The proposed biomarker system is easily attained as FLAIR is routinely acquired, models are not computationally intensive and the results are explainable, thus making this pipeline easily integrated into clinical workflow.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".