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Updated: Jul 10, 2026
Functional Neuroimaging Using Ultrasonic Blood-brain Barrier Disruption and Manganese-enhanced MRI
Published on: July 12, 2012
Fractionated manganese-enhanced MRI
Nicholas A Bock1, Fernando F Paiva, Afonso C Silva
1Cerebral Microcirculation Unit/Laboratory of Functional and Molecular Imaging/National Institute of Neurological Disorders and Stroke/National Institutes of Health, Bethesda, MD 20892-1065, USA. bockn@mail.nih.gov
Abstract:
We investigated the use of manganese-enhanced MRI (MEMRI) with fractionated doses as a way to retain the unique properties of manganese as a neuronal contrast agent while lessening its toxic effects in animals. First, we followed the signal enhancement on T1-weighted images of the brains of rats receiving 30 mg/kg fractions of MnCl2 . 4H2O every 48 h and found that the signal increased in regions with consecutive fractionated doses and ultimately saturated. Second, we used T1 mapping to test whether the amount of MRI-visible manganese that accumulated depended on the concentration of manganese in the fractions. For a fixed cumulative dose of 180 mg/kg MnCl2 . 4H2O, increasing fraction doses of 6 x 30 mg/kg, 3 x 60 mg/kg, 2 x 90 mg/kg and 1 x 180 mg/kg produced progressively shorter T1 values. The adverse systemic health effects, including complications at the injection site and poor animal well-being, also rose with the fraction dose. Thus, fractionated MEMRI can be used to balance the properties of manganese as a contrast agent in animals against its toxic effects.
Insights
Fractionated manganese-enhanced MRI (MEMRI) uses smaller, repeated doses of manganese chloride to enhance brain imaging signals in rats. This method balances manganese
Area of Science:
- Neuroimaging
- Biomedical Engineering
- Pharmacology
Background:
- Manganese-enhanced MRI (MEMRI) utilizes manganese chloride as a neuronal contrast agent.
- High doses of manganese can cause toxicity, limiting its use.
- Fractionated dosing strategies are explored to mitigate manganese toxicity.
Purpose of the Study:
- To investigate fractionated dosing of manganese chloride for MEMRI in animal models.
- To balance the contrast-enhancing properties of manganese with its potential toxic effects.
- To optimize manganese delivery for improved neuronal imaging.
Main Methods:
- Rats received fractionated doses of manganese chloride (MnCl2·4H2O) every 48 hours.
- T1-weighted imaging was used to monitor signal enhancement in the brain.
- T1 mapping assessed manganese accumulation and its relationship to fraction dose and concentration.
Main Results:
- Signal enhancement increased with consecutive fractionated doses and eventually saturated.
- Lower T1 values (indicating higher manganese concentration) were observed with increasing fraction doses for a fixed cumulative dose.
- Adverse systemic health effects and injection site complications increased with higher fraction doses.
Conclusions:
- Fractionated MEMRI allows for controlled manganese accumulation, retaining its contrast properties.
- This approach offers a method to mitigate manganese toxicity in animal studies.
- Fractionated dosing provides a viable strategy for balancing efficacy and safety in manganese-enhanced neuroimaging.
