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Updated: Jun 22, 2026
Whole-Brain Single-Cell Imaging and Analysis of Intact Neonatal Mouse Brains Using MRI, Tissue Clearing, and Light-Sheet Microscopy
Published on: August 1, 2022
MRI of cellular layers in mouse brain in vivo
Susann Boretius1, Lars Kasper, Roland Tammer
1Biomedizinische NMR Forschungs GmbH am Max-Planck-Institut für biophysikalische Chemie, 37070 Göttingen, Germany. sboreti@gwdg.de
Abstract:
Noninvasive imaging of the brain of animal models demands the detection of increasingly smaller structures by in vivo MRI. The purpose of this work was to elucidate the spatial resolution and structural contrast that can be obtained for studying the brain of C57BL/6J mice by optimized T2-weighted fast spin-echo MRI at 9.4 T. As a prerequisite for high-resolution imaging in vivo, motion artifacts were abolished by combining volatile anesthetics and positive pressure ventilation with a specially designed animal bed for fixation. Multiple substructures in the cortex, olfactory bulb, hippocampus, and cerebellum were resolved at 30 to 40 microm in-plane resolution and 200 to 300 microm section thickness as well as for relatively long echo times of 65 to 82 ms. In particular, the approach resulted in the differentiation of up to five cortical layers. In the olfactory bulb the images unraveled the mitral cell layer which has a thickness of mostly single cells. In the hippocampus at least five substructures could be separated. The molecular layer, Purkinje layer, and granular layer of the cerebellum could be clearly differentiated from the white matter. In conclusion, even without the use of a contrast agent, suitable adjustments of a widely available T2-weighted MRI sequence at high field allow for structural MRI of living mice at near single-cell layer resolution.
Insights
High-resolution magnetic resonance imaging (MRI) can now visualize near single-cell layers in mouse brains. Optimized T2-weighted fast spin-echo MRI at 9.4 T achieves this without contrast agents.
Area of Science:
- Neuroimaging
- Magnetic Resonance Imaging (MRI)
- Animal Models
Background:
- In vivo MRI of animal models requires detecting smaller brain structures.
- Advancements in MRI are crucial for understanding brain anatomy and function in research settings.
Purpose of the Study:
- To determine the spatial resolution and structural contrast achievable for C57BL/6J mouse brains using optimized T2-weighted fast spin-echo MRI at 9.4 T.
- To establish high-resolution in vivo imaging protocols for small animal brains.
Main Methods:
- Utilized optimized T2-weighted fast spin-echo MRI at 9.4 T.
- Minimized motion artifacts using volatile anesthetics, positive pressure ventilation, and a specialized animal fixation bed.
- Acquired images with 30-40 microm in-plane resolution and 200-300 microm section thickness, using echo times of 65-82 ms.
Main Results:
- Resolved multiple cortical, olfactory bulb, hippocampal, and cerebellar substructures.
- Differentiated up to five cortical layers.
- Visualized the mitral cell layer in the olfactory bulb (single-cell thickness) and separated at least five hippocampal substructures.
- Clearly distinguished cerebellar layers (molecular, Purkinje, granular) from white matter.
Conclusions:
- Optimized T2-weighted MRI sequences at high field strength enable structural imaging of living mouse brains at near single-cell layer resolution.
- This technique is effective even without contrast agents.
- The method provides detailed anatomical insights for neuroscience research.
