Developing a novel reference region for [18F]PI-2620-PET imaging to facilitate the assessment of 4-repeat tauopathies
Bibliographic record
Abstract
PURPOSE: Progressive supranuclear palsy (PSP) is a fatal 4-repeat (4R) tauopathy with progressive movement phenotypes. In-vivo 4R tau biomarkers are therefore crucial for PSP diagnosis, monitoring, and treatment evaluation. The tau-PET tracer [18F]PI-2620 binds to 4R tau and shows increased uptake in PSP-associated regions (e.g., globus pallidus), and is therefore a candidate 4R tau biomarker. However, commonly used cerebellar tau-PET reference regions show regional proximity to cerebellar 4R tau deposits in PSP, confounding semiquantitative [18F]PI-2620 assessments. Therefore, we employed bias-free image-derived input function (IDIF) PET quantification to identify an optimized data-driven reference region for assessing 4R tau in PSP. METHODS: Dynamic [18F]PI-2620 PET (60 min) was acquired in 58 PSP-Richardson Syndrome (PSP-RS) and 18 healthy controls (HC). IDIF-modelling with carotid timeseries derived total distribution volume (VT). Iteratively normalizing VT images to atlas-based white matter (WM), we identified reference candidates maximizing PSP-RS vs. HC pallidum differences. The best-performing WM references were combined to a temporo-orbital WM reference, validated in PSP-nonRS (n = 54), HC (n = 18), and disease controls (α-synucleinopathies, n = 21; Alzheimer’s disease (AD, n = 22) using VT-ratios (VTr) and 20-40min static standardized uptake value ratios (SUVr). RESULTS: Using the data-driven temporo-orbital WM reference, PSP patients showed significantly higher basal ganglia [18F]PI-2620 signal vs. HC compared to cerebellar normalization. Receiver operating curve (ROC) analysis confirmed higher diagnostic accuracy using the temporo-orbital WM reference. Pallidum [18F]PI-2620 showed significant associations with clinical disease severity exclusively when using the novel temporo-orbital WM reference. CONCLUSIONS: A data-driven temporo-orbital WM reference optimizes [18F]PI-2620 PET assessment for PSP diagnosis, outperforming conventional cerebellar references used in tau-PET imaging.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".