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In vivo Imaging of Optic Nerve Fiber Integrity by Contrast-Enhanced MRI in Mice
Published on: July 22, 2014
In vivo 3D MRI staining of mouse brain after subcutaneous application of MnCl2
Takashi Watanabe1, Oliver Natt, Susann Boretius
1Biomedizinische NMR Forschungs GmbH am Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany.
Abstract:
Follow-up T(1)-weighted 3D gradient-echo MRI (2.35 T) of murine brain in vivo (N = 5) at 120 microm isotropic resolution revealed spatially distinct signal increases 6-48 hr after subcutaneous application of MnCl(2) (20 mg/kg). The effects result from a shortening of the water proton T(1) relaxation time due to the presence of unchelated paramagnetic Mn(2+) ions, which access the brain by systemic circulation and crossing of the blood-brain barrier (BBB). A pronounced Mn(2+)-induced signal enhancement was first seen in structures without a BBB, such as the choroid plexus, pituitary gland, and pineal gland. Within 24 hr after administration, Mn(2+) contrast highlighted the olfactory bulb, inferior colliculi, cerebellum, and the CA3 subfield of the hippocampus. The affinity of Mn(2+) to various brain systems suggests the neuronal uptake of Mn(2+) ions from the extracellular space and subsequent axonal transport. Thus, at least part of the Mn(2+) contrast reflects a functional brain response of behaving animals, for example, in the olfactory system. In vivo MRI staining of the brain by systemic administration of MnCl(2) may contribute to phenotyping mutant mice with morphologic and functional alterations of the central nervous system.
Insights
Manganese chloride (MnCl2) injected into mice enhances MRI signals in the brain by affecting water relaxation times. This manganese (Mn2+) contrast highlights brain structures and may aid in studying neurological conditions.
Area of Science:
- Neuroimaging
- Biomedical Engineering
- Pharmacology
Background:
- Magnetic Resonance Imaging (MRI) is a crucial tool for visualizing brain structure and function.
- Contrast agents can enhance MRI signal but require careful consideration of their distribution and effects.
- Paramagnetic ions, like manganese (Mn2+), can alter water proton relaxation times, influencing MRI signal intensity.
Purpose of the Study:
- To investigate the in vivo effects of systemically administered manganese chloride (MnCl2) on murine brain MRI.
- To assess the distribution and temporal dynamics of Mn2+ in the brain using T1-weighted MRI.
- To explore the potential of Mn2+ as an MRI contrast agent for neuroimaging and phenotyping.
Main Methods:
- T1-weighted 3D gradient-echo MRI was performed on mice (N=5) at 2.35 T with 120 microm isotropic resolution.
- Mice received subcutaneous injections of MnCl2 (20 mg/kg).
- Brain imaging was conducted at various time points (6-48 hours) post-injection to track Mn2+ distribution.
Main Results:
- Spatially distinct signal increases were observed in the murine brain 6-48 hours after MnCl2 administration.
- Enhanced signal was initially prominent in structures lacking a blood-brain barrier (BBB), such as the choroid plexus, pituitary, and pineal glands.
- Within 24 hours, Mn2+ contrast highlighted the olfactory bulb, inferior colliculi, cerebellum, and hippocampal CA3 subfield, suggesting neuronal uptake and axonal transport.
Conclusions:
- Systemic administration of MnCl2 acts as an effective in vivo MRI contrast agent in the murine brain.
- The observed Mn2+ distribution suggests both passive diffusion into areas without a BBB and active neuronal uptake.
- Mn2+ enhanced MRI may serve as a valuable tool for phenotyping mutant mice with central nervous system alterations.
