A method to image brain tissue frozen at autopsy

Area of Science:

• Biomedical Imaging
• Histopathology
• Molecular Biology

Background:

• Postmortem Magnetic Resonance Imaging (MRI) aids histopathological studies by locating pathological regions in fixed tissues.
• Imaging frozen tissue at extraction is challenging, limiting its use in preserving sample integrity for molecular analyses.
• Existing methods often compromise tissue integrity, hindering downstream applications like transcriptomics.

Purpose of the Study:

• To develop and validate a cold postmortem MRI technique for imaging frozen human tissue.
• To preserve tissue integrity and enable targeted molecular techniques such as transcriptomics.
• To optimize imaging parameters for clear visualization of brain tissue structures and lesions.

Main Methods:

• Assessed RNA integrity number (RIN) to determine biomolecular degradation rates in mouse brains at various temperatures (-20°C to +20°C).
• Developed a cold MRI protocol using 2-methylbutane immersion and a recirculating chiller for human autopsy tissue.
• Optimized imaging temperature to -7°C, balancing RIN stability, MRI signal, and tissue contrast using MPRAGE sequences.

Main Results:

• Optimal imaging temperature of -7°C maintained RIN stability for over 12 hours with minimal degradation.
• Magnetization-prepared rapid gradient echo (MPRAGE) MRI at -7°C provided good gray-white matter contrast and visualized lesions.
• No significant changes in RIN were observed before and after MRI, confirming tissue integrity preservation.

Conclusions:

• Cold postmortem MRI effectively preserves frozen tissue integrity, crucial for downstream molecular analyses like transcriptomics.
• The developed technique enhances the efficiency of histopathological studies by enabling targeted analysis of intact frozen samples.
• Sub-zero temperature MRI imaging may advance the understanding of MRI signal compartment specificity in biological tissues.