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Updated: May 16, 2026
Functional Neuroimaging Using Ultrasonic Blood-brain Barrier Disruption and Manganese-enhanced MRI
Published on: July 12, 2012
Regional specificity of manganese accumulation and clearance in the mouse brain: implications for manganese-enhanced
B Grünecker1, S F Kaltwasser, A C Zappe
1Max Planck Institute of Psychiatry, Munich, Germany.
Abstract:
Manganese-enhanced MRI has recently become a valuable tool for the assessment of in vivo functional cerebral activity in animal models. As a result of the toxicity of manganese at higher dosages, fractionated application schemes have been proposed to reduce the toxic side effects by using lower concentrations per injection. Here, we present data on regional-specific manganese accumulation during a fractionated application scheme over 8 days of 30 mg/kg MnCl2 , as well as on the clearance of manganese chloride over the course of several weeks after the termination of the whole application protocol supplying an accumulative dose of 240 mg/kg MnCl2 . Our data show most rapid accumulation in the superior and inferior colliculi, amygdala, bed nucleus of the stria terminalis, cornu ammonis of the hippocampus and globus pallidus. The data suggest that no ceiling effects occur in any region using the proposed application protocol. Therefore, a comparison of basal neuronal activity differences in different animal groups based on locally specific manganese accumulation is possible using fractionated application. Half-life times of manganese clearance varied between 5 and 7 days, and were longest in the periaqueductal gray, amygdala and entorhinal cortex. As the hippocampal formation shows one of the highest T1 -weighted signal intensities after manganese application, and manganese-induced memory impairment has been suggested, we assessed hippocampus-dependent learning as well as possible manganese-induced atrophy of the hippocampal volume. No interference of manganese application on learning was detected after 4 days of Mn(2+) application or 2 weeks after the application protocol. In addition, no volumetric changes induced by manganese application were found for the hippocampus at any of the measured time points. For longitudinal measurements (i.e. repeated manganese applications), a minimum of at least 8 weeks should be considered using the proposed protocol to allow for sufficient clearance of the paramagnetic ion from cerebral tissue.
Insights
Fractionated manganese application allows for safe assessment of brain activity using manganese-enhanced MRI (MEMRI). This method shows regional accumulation and clearance, with no observed impact on hippocampus-dependent learning or volume.
Area of Science:
- Neuroscience
- Biomedical Imaging
- Pharmacology
Background:
- Manganese-enhanced MRI (MEMRI) is a key technique for studying in vivo brain function in animal models.
- High manganese doses can be toxic, leading to the development of fractionated application schemes to mitigate side effects.
Purpose of the Study:
- To investigate regional manganese accumulation and clearance patterns using a fractionated application protocol.
- To assess potential manganese-induced effects on hippocampus-dependent learning and hippocampal volume.
Main Methods:
- Administered fractionated doses of manganese chloride (MnCl2) over 8 days (30 mg/kg/day) for a total dose of 240 mg/kg.
- Monitored manganese accumulation and clearance in specific brain regions using MRI.
- Evaluated hippocampus-dependent learning and hippocampal volume at various time points post-application.
Main Results:
- Rapid manganese accumulation was observed in the superior/inferior colliculi, amygdala, bed nucleus of the stria terminalis, hippocampus (cornu ammonis), and globus pallidus.
- Manganese clearance half-life ranged from 5 to 7 days, with the longest retention in the periaqueductal gray, amygdala, and entorhinal cortex.
- No significant interference with hippocampus-dependent learning or volumetric changes in the hippocampus was detected.
Conclusions:
- Fractionated manganese application enables safe and effective assessment of regional brain activity via MEMRI without significant toxicity.
- The proposed protocol allows for comparisons of basal neuronal activity across different animal groups.
- A minimum 8-week interval is recommended between repeated manganese applications for adequate clearance.
