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Updated: May 6, 2026
In vivo Imaging of Optic Nerve Fiber Integrity by Contrast-Enhanced MRI in Mice
Published on: July 22, 2014
Cell layers and neuropil: contrast-enhanced MRI of mouse brain in vivo
Abstract:
Contrast-enhanced T₁- and T₂-weighted MRI at 9.4 T and in-plane resolutions of 25 and 30 µm has been demonstrated to differentiate between neural tissues in mouse brain in vivo, including granule cell layers, principal cell layers, general neuropil, specialized neuropil and white matter. In T₁-weighted MRI of the olfactory bulb, hippocampus and cerebellum, contrast obtained by the intracranial administration of gadopentetate dimeglumine (Gd-DTPA) reflects the extra- and intracellular spaces of gray matter in agreement with histological data. General neuropil areas are highlighted, whereas other tissues present with lower signal intensities. The induced contrast is similar to that in plain T₂-weighted MRI, but offers a 16-30-fold higher contrast-to-noise ratio. Systemic administration of manganese chloride increases the signal-to-noise ratio in T₁-weighted MRI to a significantly greater extent in principal cell layers and specialized neuropil than in granule cell layers, whereas gadolinium-enhanced MRI indicates no larger intracellular spaces in these tissues. Granule cell layers are enhanced no more than general neuropil by manganese, whereas gadolinium-enhanced MRI indicates significantly larger intracellular spaces in the cell layers. These discrepancies suggest that the signal increase after manganese administration reflects cellular activity which is disproportionate to the intracellular space. As a result, principal cell layers and specialized neuropil become highlighted, whereas granule cell layers, general neuropil and white matter present with lower signal intensities.
Insights
High-resolution MRI using manganese chloride and gadolinium contrast agents effectively differentiates mouse brain tissues. Manganese highlights cellular activity, while gadolinium visualizes intracellular spaces, offering distinct insights into neural structures.
Area of Science:
- Neuroimaging
- Magnetic Resonance Imaging (MRI)
- Mouse Brain Anatomy
Background:
- Differentiating neural tissues in the mouse brain is crucial for understanding brain function and disease.
- Existing MRI techniques have limitations in resolving fine neural structures and distinguishing between different tissue types.
- Contrast-enhanced MRI offers potential for improved tissue characterization.
Purpose of the Study:
- To evaluate the efficacy of contrast-enhanced T₁- and T₂-weighted MRI at ultra-high field (9.4 T) with high resolution (25-30 µm) for in vivo mouse brain tissue differentiation.
- To compare the contrast mechanisms and tissue highlighting properties of gadolinium (Gd-DTPA) and manganese chloride (MnCl₂) as contrast agents.
- To investigate the relationship between contrast enhancement, intracellular spaces, and cellular activity in different neural tissues.
Main Methods:
- Acquisition of contrast-enhanced T₁- and T₂-weighted MRI data at 9.4 T with in-plane resolutions of 25 and 30 µm in mouse brains.
- Intracranial administration of gadopentetate dimeglumine (Gd-DTPA) and systemic administration of manganese chloride (MnCl₂).
- Comparison of MRI signal intensities and contrast-to-noise ratios across various brain regions, including olfactory bulb, hippocampus, and cerebellum, correlated with histological data.
Main Results:
- High-resolution MRI successfully differentiated neural tissues: granule cell layers, principal cell layers, general neuropil, specialized neuropil, and white matter.
- Gd-DTPA enhanced T₁-weighted MRI reflected extra- and intracellular spaces in gray matter, highlighting general neuropil.
- MnCl₂ administration significantly increased signal-to-noise ratio in T₁-weighted MRI, particularly in principal cell layers and specialized neuropil, suggesting enhanced cellular activity, distinct from Gd-DTPA's visualization of intracellular space.
Conclusions:
- Contrast-enhanced 9.4 T MRI with high resolution enables detailed in vivo differentiation of mouse brain neural tissues.
- Gadolinium and manganese contrast agents provide complementary information: Gd-DTPA visualizes extracellular and intracellular spaces, while MnCl₂ highlights areas of higher cellular activity.
- The observed discrepancies between manganese and gadolinium enhancement suggest that manganese-based signal increase is disproportionate to intracellular space, reflecting functional neuronal activity.
