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Updated: Jun 26, 2026
Functional Neuroimaging Using Ultrasonic Blood-brain Barrier Disruption and Manganese-enhanced MRI
Published on: July 12, 2012
Accounting for nonspecific enhancement in neuronal tract tracing using manganese enhanced magnetic resonance imaging
Kai-Hsiang Chuang1, Alan P Koretsky
1Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. chuangk@ninds.nih.gov
Abstract:
Manganese enhanced MRI (MEMRI) is an emerging technique for tracing neuronal pathways in vivo. However, manganese may leak into blood vessels or cerebrospinal fluid (CSF) after local injection and can be circulated to and taken up by brain regions that may not have connections to the targeted pathways. Comparing enhancement time courses after intranasal injection with intravenous infusion of MnCl(2) in rats, the early enhancements in the pituitary gland (Pit) and hippocampus indicate the contrasts in those regions in the olfactory tract-tracing experiment were caused by such systemic effects. Since the Pit has easy access to manganese from the blood and its signal is proportional to other brain regions after intravenous infusion, it was used as an internal reference for the systemic effects. Applying intensity normalization by the Pit signal to tract-tracing data from the olfactory bulb led to reduced contrast in the hippocampus. These results demonstrate that nonspecific enhancements in MEMRI tract-tracing studies may have to be taken into account and that normalization by the Pit signal can compensate these effects.
Insights
Manganese enhanced MRI (MEMRI) can inaccurately trace neuronal pathways due to manganese leakage. Normalizing signals using the pituitary gland (Pit) effectively corrects for these systemic effects in tract-tracing studies.
Area of Science:
- Neuroscience
- Medical Imaging
Background:
- Manganese-enhanced MRI (MEMRI) is a valuable in vivo technique for mapping neuronal connections.
- Systemic manganese distribution can lead to false positives in tract-tracing experiments.
Purpose of the Study:
- To investigate and quantify systemic manganese distribution effects in MEMRI tract-tracing.
- To develop a normalization method to correct for non-specific signal enhancements.
Main Methods:
- Comparison of intranasal and intravenous manganese chloride (MnCl2) administration in rats.
- Analysis of enhancement time courses in various brain regions, including the pituitary gland (Pit) and hippocampus.
- Intensity normalization using the Pit signal as an internal reference for systemic manganese uptake.
Main Results:
- Early manganese enhancement in the pituitary and hippocampus after intranasal injection suggests systemic circulation.
- The pituitary gland signal correlated with other brain regions after intravenous infusion, validating its use as a reference.
- Pituitary signal normalization reduced non-specific hippocampal contrast in olfactory bulb tract-tracing data.
Conclusions:
- Systemic manganese uptake can confound MEMRI tract-tracing results.
- Pituitary signal normalization is an effective strategy to compensate for non-specific MEMRI enhancements.
- Accurate neuronal pathway tracing with MEMRI requires accounting for and correcting systemic effects.
