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Direct CSF injection of MnCl(2) for dynamic manganese-enhanced MRI
Christina H Liu1, Helen E D'Arceuil, Alex J de Crespigny
1Department of Radiology, MGH-NMR Center, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
Abstract:
MnCl(2) was injected intrathecally through the cisterna magna in rats, allowing infusion of divalent manganese ions (Mn(++)) into the CSF space and thence into the brain, without breaking the blood-brain barrier (BBB). Mn(++) uptake and washout dynamics in the brain were measured by serial T(1)-weighted MRI and EPI T(1) and T(2) mapping for up to 3 weeks after injection. Observations within the first 6 hr after injection demonstrated anterograde and bilateral distribution of the Mn(++) within the CSF space, from the olfactory bulb and frontal cortex to the brain stem. Enhancement increased in most brain areas up to 4 days after injection, and then slowly decreased. Relaxation maps at each time point demonstrated higher concentrations of Mn in basal ganglia. Residual concentrations were still observable after 3 weeks in all brain regions. With the use of MnCl(2) calibration phantoms, the maximum Mn concentration in the brain was estimated to be approximately 27 +/- 16 microM, corresponding to changes in relaxation rates of 0.49 +/- 0.30 s(-1) for R(1) and 3.9 +/- 2.4 s(-1) for R(2). For comparison, an intrathecal GdDTPA injection was performed. This injection showed different distribution dynamics: it remained chiefly within the CSF spaces, and was largely washed out after 1 day. This method shows promise as a means of supplying Mn(++) uniformly to the whole brain for a variety of chronic functional activation studies.
Insights
Intrathecal manganese chloride (MnCl2) administration in rats effectively distributes manganese ions (Mn++) throughout the brain via cerebrospinal fluid (CSF). This method allows for chronic functional imaging studies without breaching the blood-brain barrier (BBB).
Area of Science:
- Neuroimaging
- Pharmacokinetics
- Biomedical Engineering
Background:
- The blood-brain barrier (BBB) poses a challenge for delivering contrast agents to the brain.
- Manganese ions (Mn++) have potential as MRI contrast agents due to their T1-shortening properties.
- Developing methods for sustained, whole-brain delivery of Mn++ is crucial for chronic functional studies.
Purpose of the Study:
- To evaluate the distribution and washout dynamics of intrathecally administered manganese chloride (MnCl2) in the rat brain.
- To assess the feasibility of using this method for chronic functional activation studies.
- To compare the distribution of Mn++ with a conventional contrast agent, GdDTPA.
Main Methods:
- Intrathecal injection of MnCl2 into the cisterna magna in rats.
- Serial T1-weighted MRI and EPI T1/T2 mapping for up to 3 weeks post-injection.
- Use of MnCl2 calibration phantoms to quantify brain Mn++ concentration.
Main Results:
- Mn++ distributed widely within the CSF space, reaching the olfactory bulb, frontal cortex, and brain stem within 6 hours.
- Brain enhancement increased for up to 4 days, then slowly decreased, with residual concentrations observed after 3 weeks.
- Higher Mn++ concentrations were detected in the basal ganglia, with estimated maximum concentrations around 27 microM.
- Intrathecal GdDTPA showed limited distribution within CSF spaces and rapid washout within 1 day.
Conclusions:
- Intrathecal MnCl2 administration provides a non-invasive method for sustained, whole-brain distribution of Mn++ without compromising the BBB.
- This technique is promising for chronic functional activation studies requiring uniform contrast agent delivery.
- Mn++ exhibits distinct distribution and washout kinetics compared to GdDTPA.
