Myelin Damage in Relapsing Multiple Sclerosis Is Associated with Decreased N-Acetylaspartate and Creatine Concentrations (P4.181)
Bibliographic record
Abstract
Objective: To determine whether the levels of N-acetylaspartate (NAA) and total creatine (tCr; creatine and phosphocreatine) in normal-appearing white matter are correlated with myelin water fraction (MWF) in patients with relapsing multiple sclerosis (RMS) and healthy controls (HC). Background: Brain MRI offers a non-invasive measure of myelin content through the MWF. Magnetic resonance spectroscopy (MRS) measures tCr, which is involved in energy storage, and NAA, which supports myelin lipid synthesis. Given the roles of tCr and NAA in mitochondrial function and myelin production, we hypothesized that tCr and/or NAA would correlate with myelin content in the brain. Methods: A total of 25 patients recruited for an MRI substudy of a Phase III, randomized clinical trial of ocrelizumab versus interferon β-1a (OPERA II; NCT01412333) and 44 age- and gender-matched HC were scanned at 3T. MRS was measured from a 6.5x4.5x1.8cm³ white matter voxel and fit with LCModel v6.3. NAA, N-acetyl-aspartylglutamate, tCr, choline, myo-inositol and glutamate concentrations were calculated relative to the water peak and corrected for voxel compartmentation and relaxation. MWF was measured using a 32 echo gradient and spin echo imaging sequence to sample the water T2 decay curve, which was modelled with multiple exponential components. MRS voxels were mapped to MWF maps to extract the mean MWF in the voxel. Results: tCr (r²=0.24; p=0.01) and NAA (r²=0.16; p=0.05) both positively correlated with the mean voxel MWF in the RMS group. There were no correlations between MWF and any metabolite in the HC group or when both RMS and HC groups were included. Conclusions: The presence of positive, though weak, relationships between tCr and NAA with myelin content in the RMS cohort suggests that decreased mitochondrial function, as evidenced by reduced tCr and NAA, may be linked to loss of myelin in patients with RMS. Supported by F. Hoffmann-La Roche
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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 | 0.000 | 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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".