Exploring a weighted composite score for harmonization of 18F‐MK6240 and 18F‐ Flortaucipir: linearity and correlations with cognitive measures in a head‐to‐head tau PET dataset – The HEAD Study
Bibliographic record
Abstract
Abstract Background Harmonization of the two most commonly used Tau PET tracers, 18F‐Flortaucipir and 18F‐MK6240 has proven to be complex. Unlike the centiloid scale for amyloid tracers, Tau PET SUVRs of the two tracers are not linearly comparable and vary markedly in dynamic range and sensitivity. Method Tau PET SUVRs for Braak stage (1‐6) in 18F‐MK6240 and 18F‐Flortaucipir were obtained from the Longitudinal multicenter head‐to‐head harmonization of tau‐PET tracers (HEAD) project. For training, we used 13 amyloid confirmed AD, 24 amyloid confirmed MCI and 66 amyloid negative controls. To assess linearity and correlations with neuropsychological tests, we included the training data as well as 74 subjects of unknown or inconsistent amyloid status. Two methods of generating outcome measures were used. (1) As a stand‐in for Tau load, similar to the centiloid scale, a score of 100, 50 or 0 was given to participants of the training set by multiplying CDR score by 100. Hierarchical and ridge regression were performed for each tracer using PET‐Braak SUVRs as predictive variables. Regression coefficients were used to calculate an outcome measure for all participants. (2) Principal component analysis (PCA) was applied for each tracer to the vectors of PET‐Braak regional SUVR of the training subset. Projections along the principal axis were calculated for both modalities Result Hierarchical, ridge regression and PCA all yielded composite measures with good linear dependence between the two tracers (r2 for hierarchical, ridge and PCA were 0.84, 0.80, 0.80, respectively). Regions remaining in the hierarchical regression analyses varied between tracers: predictive regions for 18F‐MK6240 were PET‐Braak 1, 4 and 5, while 18F‐Flortaucipir used only PET‐Braak 1 and 5. Composite measures correlated well with MMSE and total MOCA score with all composite measures r < ‐0.61. Conclusion While both tracers may have different sensitivities to regional Tau distributions and disease stages, weighting multiple regions differently for each tracer gives a composite score linearly comparable across tracers that correlates with neuropsychological measures. This study is limited by the low total tau load and impairment level of all participants and would benefit from the inclusion of patients with more disease progression.
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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 | 0.015 | 0.022 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".