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Updated: Jul 31, 2026
An Unbiased Approach of Sampling TEM Sections in Neuroscience
Published on: April 13, 2019
Bridging Neuroimaging and Neuropathology: A Comprehensive Workflow for Targeted Sampling of White Matter Lesions
Nadim Farhat1,2, Jinghang Li1, Jacob Berardinelli1
1Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Background And Purpose:
White matter lesions are common imaging biomarkers associated with aging and neurodegenerative diseases, yet their underlying pathology remains unclear due to limitations in imaging-based characterization. We aim to develop and validate a comprehensive workflow enabling precise MRI-guided histological sampling of white matter lesions to bridge neuroimaging and neuropathology.
Methods:
We established a workflow integrating agar-sucrose brain embedding, ultrahigh field 7 Tesla (7T) MRI acquisition, reusable three-dimensional (3D) printed cutting guides, and semiautomated MRI-blockface alignment. Left hemispheric postmortem brains were stabilized in the embedding medium and scanned using optimized MRI protocols. Coronal sectioning was guided by standardized 3D-printed cutting guides, and knife traces were digitally matched to MRI planes. White matter lesions were segmented on MRI and aligned for histopathological sampling.
Results:
The workflow enabled reproducible brain sectioning, minimized imaging artifacts, and achieved precise spatial alignment between MRI and histology. For demonstration, detailed results from two representative brains were presented in this article. Consistent, high-resolution MRI data facilitated accurate lesion detection and sampling. The use of standardized cutting guides and alignment protocols reduced variability and improved efficiency.
Conclusions:
Our cost-effective, scalable workflow reliably linked neuroimaging findings with histological analysis, enhancing the understanding of white matter lesion pathology. This framework held significant potential for advancing translational research in aging and neurodegenerative diseases.
Insights
This study presents a new workflow for precise MRI-guided brain tissue sampling, linking neuroimaging to neuropathology for better understanding of white matter lesions in aging and neurodegenerative diseases.
Area of Science:
- Neuroimaging and Neuropathology
- Translational Research in Aging and Neurodegenerative Diseases
Background:
- White matter lesions are common biomarkers in aging and neurodegenerative diseases.
- Current imaging methods have limitations in characterizing the underlying pathology of white matter lesions.
Purpose of the Study:
- To develop and validate a comprehensive workflow for precise MRI-guided histological sampling of white matter lesions.
- To bridge the gap between neuroimaging and neuropathology for a clearer understanding of lesion pathology.
Main Methods:
- Integrated agar-sucrose brain embedding, 7 Tesla (7T) MRI acquisition, and 3D-printed cutting guides.
- Employed semiautomated MRI-blockface alignment for precise spatial matching between imaging and histology.
- Utilized standardized protocols for reproducible brain sectioning and lesion sampling.
Main Results:
- The workflow demonstrated reproducible brain sectioning with minimized imaging artifacts.
- Achieved precise spatial alignment between MRI and histological samples.
- High-resolution MRI data facilitated accurate white matter lesion detection and sampling, reducing variability.
Conclusions:
- Developed a cost-effective and scalable workflow linking neuroimaging to histological analysis.
- The framework enhances the understanding of white matter lesion pathology.
- Holds significant potential for advancing translational research in aging and neurodegenerative diseases.
