The Application of Novel Positron Emission Tomography (PET) Radioligands as Imaging Biomarkers of Neurochemical Changes in the Brain: Relevance in Schizophrenia and Alzheimer's disease
Bibliographic record
Abstract
The work of the thesis consists of five studies evaluating two Positron Emission Tomography (PET) radioligands and their molecular targets as imaging biomarkers of neurobiological abnormalities that occur in normal ageing and psychiatric illnesses. The first part of the thesis evaluated the use of [11C]-(+)-PHNO, which has affinity to dopamine D2/3 receptors, as an imaging biomarker of dopamine function. In the first study, [11C]-(+)-PHNO was used to evaluate the effect of personality differences on inter-individual variations of dopamine response to stress. In the second study, [11C]-(+)-PHNO was used to examine whether abnormalities in D2/3 receptor density could be present in the early phase of psychosis, specifically in individuals who have clinical high risk to develop psychosis and in antipsychotic- naïve patients with schizophrenia. The second part of the thesis evaluated the use of a novel second-generation Translocator protein 18kDa (TSPO) radioligand, [18F]-FEPPA, as an imaging biomarker of neuroinflammation. Although biomarker abnormalities may not be sufficient to produce an illness, the presence of biomarker abnormalities in non-affected healthy individuals may represent a biological vulnerability that may lead to an eventual development of a disease. In the third study of the thesis, I used [18F]-FEPPA to examine whether abnormalities in neuroinflammation can be detected in cognitively normal elderly individuals. The fourth study focused on a novel application of [18F]-FEPPA as an imaging biomarker of neuroinflammation in the white matter regions in healthy volunteers across normal adult life span. In this study, the caveats and limitations of [18F]-FEPPA quantification in the white matter regions were also explored. Finally, in the fifth study, [18F]-FEPPA was evaluated as an imaging biomarker of neuroinflammation in a clinical population by comparing the binding of [18F]-FEPPA in cognitively intact healthy control subjects and patients with Alzheimer's disease (AD) in both grey and white matter regions. The impact of neuroinflammation on cognitive function was evaluated by examining associations between several cognitive measures and [18F]-FEPPA binding in participants with AD. Collectively, these five studies demonstrate that PET radioligands can be used as imaging biomarkers to evaluate neurochemical changes that are present in both health and disease.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| 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".