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MRI-Based evaluation of locus and extent of neurotoxic lesions in monkeys
L Málková1, C K Lex, M Mishkin
1Department of Pharmacology, Georgetown University Medical Center, Washington, DC, USA. malkoval@georgetown.edu
Abstract:
To minimize the variability in the extent of lesions made by injections of the excitotoxin ibotenic acid in rhesus monkeys, we developed and validated an MRI-based method to determine the efficacy of the injections soon after surgery. T2-weighted MR images were obtained 6-11 days after surgery from 17 brain hemispheres of monkeys that had received bilateral lesions of either the hippocampal formation (HF), perirhinal cortex, or parahippocampal cortex. The extent of lesion estimated from the hypersignal that appeared in and outside of the targeted area on these MR images was compared with the extent of damage assessed histologically after survival periods ranging from 120-370 days. Highly significant correlations (r values between 0.85-0.99) were found between these two measures for several regions in the medial temporal lobe. Based on this finding, lack of hypersignal in the targeted area of some Ss was followed by successful reinjection of the neurotoxin to create more complete cell loss prior to the postoperative phase of the study. We also assessed the relationship between a postoperative reduction in HF volume, measured from T1-weighted MR images, and the extent of damage determined histologically in 14 hemispheres of monkeys with bilateral excitotoxic HF lesions. The HF volume decreases sharply after surgery until 40-50 days postoperatively, after which there is only a minor further decrease. Based on this finding, we obtained T1-weighted MR images at least 44 days but in most cases close to 1 year after surgery. A highly significant positive correlation (r = 0.95, P < 0.001) was found between neuronal damage and volume reduction, with nearly complete neuronal damage (96-99%) corresponding to a volume reduction of 68-79%. These MRI-based methods thus provide an accurate in vivo evaluation of the locus and extent of neurotoxic lesions. Application of these methods can ensure that each animal in the experiment is used effectively.
Insights
We developed MRI methods to accurately assess neurotoxin-induced brain lesions in rhesus monkeys. This technique ensures effective use of animals in research by confirming lesion extent and guiding further interventions.
Area of Science:
- Neuroscience
- Medical Imaging
- Primate Research
Background:
- Excitotoxic lesions are used in primate models to study brain function.
- Variability in lesion extent can compromise experimental outcomes.
- Accurate post-operative assessment of lesion efficacy is crucial.
Purpose of the Study:
- To develop and validate MRI-based methods for assessing neurotoxin-induced brain lesions in rhesus monkeys.
- To minimize variability in lesion extent and ensure experimental efficacy.
- To provide an accurate in vivo evaluation of lesion locus and extent.
Main Methods:
- T2-weighted MRI was used 6-11 days post-surgery to assess lesion-induced hypersignal.
- Histological analysis was performed after 120-370 days to compare lesion extent.
- T1-weighted MRI was used to measure hippocampal formation (HF) volume reduction at least 44 days post-surgery.
Main Results:
- High correlations (r=0.85-0.99) were found between MRI-estimated and histological lesion extent in medial temporal lobe regions.
- MRI hypersignal guided successful reinjection of neurotoxin for more complete lesions.
- A strong positive correlation (r=0.95) existed between HF volume reduction and neuronal damage (96-99% damage correlated with 68-79% volume reduction).
Conclusions:
- MRI provides an accurate in vivo method for evaluating the locus and extent of neurotoxic lesions.
- These methods improve experimental design by ensuring lesion efficacy and optimizing animal use.
- The validated MRI techniques enhance the reliability of primate models in neuroscience research.
