Manganese concentration mapping in the rat brain with MRI, PET, and autoradiography
Bibliographic record
Abstract
Purpose Mn2+ is used as a contrast agent and marker for neuronal activity with magnetic resonance imaging (MRI) in rats and mice, but its accumulation is generally not assessed quantitatively. In this work, nonradioactive Mn and 52Mn are injected simultaneously in rats, and imaged with MRI, positron emission tomography (PET) and autoradiography (AR). Mn distributions are compared between modalities, to assess the potential and limitations on quantification of Mn with MRI, and to investigate the potential of multimodal measurement of Mn accumulation. Methods MRI (in vivo), PET (in vivo and post mortem), and AR (ex vivo) were acquired of rat brains, for which animals received simultaneous intraperitoneal (IP) or intracerebrovertricular (ICV)‐targeted injections containing the positron‐emitting radionuclide 52Mn and additional nonradioactive MnCl2, which acts as an MRI contrast agent. Pre and postinjection MR images were fit for the longitudinal relaxation rate (R1), coregistered, and subtracted to generate R1 difference maps, which are expected to be proportional to change in Mn concentration in tissue. AR and PET images were coregistered to smoothed R1 difference maps. Results Similar spatial distributions were seen across modalities, with Mn accumulation in the colliculus, near the injection site, and in the 4th ventricle. There was no 52Mn accumulation measurable with PET in the brain after IP injection. In areas of very highly localized and concentrated 52Mn accumulation in PET or AR, consistent increases of R1 were not seen with MRI. Scatter plots of corresponding voxel R1 difference and PET or AR signal intensity were generated and fit with least squares linear models within anatomical regions. Linear correlations were observed, particularly in regions away from very highly localized and concentrated Mn accumulation at the injection site and the 4th ventricle. Accounting for radioactive decay of 52Mn, the MnCl2 longitudinal relaxivity was between 4.0 and 5.1 s−1/mM, which is within 22% of the in vitro relaxivity. Conclusions This proof‐of‐concept study demonstrates that MR has strong potential for quantitative assessment of Mn accumulation in the brain, although local discrepancies from linear correlation suggest limitations to this use of MR in areas of inflammation or very high concentrations of Mn. These discrepancies also suggest that a combination of modalities may have additional utility for discriminating between different pools of Mn accumulation in tissue.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.001 | 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".