Revealing the MRI-Contrast in Optically Cleared Brains

Area of Science:

• Neuroimaging
• Biomedical Engineering
• Microscopy

Background:

• Optically-cleared tissues are generally considered unsuitable for Magnetic Resonance Imaging (MRI) due to a perceived lack of contrast.
• Previous research linked MRI contrast to lipid content, hindering multimodal imaging approaches.
• The role of lipids and the compatibility of non-delipidating clearing methods with MRI remain unclear.

Purpose of the Study:

• To investigate the relationship between MRI contrast and lipid content in optically-cleared whole brains using various tissue-clearing techniques.
• To determine if MRI contrast can be restored in lipid-free cleared tissues.
• To develop a multimodal MRI-light-microscopy (LM) imaging approach.

Main Methods:

• Assessment of MRI contrast in whole brains cleared using uDISCO, ECi, Scale, and CLARITY methods.
• Evaluation of tissue rehydration effects on MRI compatibility.
• Correlation analysis between tissue expansion, hydration levels, and MRI contrast.
• Development of a multimodal MRI-LM imaging pipeline.

Main Results:

• uDISCO and ECi-cleared brains are MRI-compatible after rehydration, despite significant lipid removal.
• Scale-cleared brains, which preserve lipids, lack MRI contrast.
• MRI contrast is successfully restored in lipid-free CLARITY-cleared brains without lipid reintroduction.
• Tissue expansion and hyperhydration are strongly associated with MRI contrast loss.

Conclusions:

• Lipids are not essential for achieving MRI contrast in cleared tissues.
• Rehydration is key to restoring MRI compatibility in cleared specimens.
• This study establishes a foundation for multimodal MRI-LM imaging, bridging micro- and mesoscale analysis.