Network-based disease fingerprinting with neuroinflammation PET imaging
Bibliographic record
Abstract
Neuroinflammation is a hallmark of numerous neurodegenerative, psychiatric, and chronic pain disorders and can be assessed in vivo with 18 kDa translocator protein (TSPO) positron emission tomography (PET). However, conventional quantification methods of TSPO PET are limited and often overlook the spatial relationships between regional signals. The application of network-based approaches to TSPO PET imaging may provide a novel framework to capture disease-specific neuroinflammatory patterns. To address this question, here we developed a data-driven, network-based approach to generate individual brain-wide TSPO PET matrices, employing Euclidean distance to quantify inter-regional pharmacokinetics similarity. We applied this approach to a large multicenter dataset of 528 PET scans utilizing three different TSPO tracers ([11C]-PBR28, [18F]-DPA714, [11C]-PK11195), including healthy controls and patients with different diseases such as multiple sclerosis, traumatic brain injury, schizophrenia, depression, and chronic low back pain. Statistical modelling and machine learning classifiers were applied to evaluate the impact of experimental and biological factors on TSPO similarity patterns and to investigate their potential for capturing disease-specific signatures. TSPO similarity patterns demonstrated high biological specificity and reproducibility, with strong test–retest correlations (mean Spearman’s ρ = 0.84). Average precision of disease classification exceeded chance performance by 23–89% across conditions and was driven by condition-specific regional hubs whose topological distributions closely mirrored disease pathophysiology. This specificity was further supported by minimal overlap in feature importance values across conditions. Altogether, our findings show that network-based analysis of human TSPO PET data can detect disease-specific neuroinflammatory signatures. Such methodologies underscore the biological significance of TSPO PET and enhance its translational value, supporting precision medicine strategies for neuroinflammatory disorders.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".