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Published on: May 19, 2015
Comparative analysis of in situ and ex situ postmortem brain MRI: Evaluating volumetry, DTI, and relaxometry
Dominique Neuhaus1,2, Thomas Rost2, Tanja Haas3
1Institute of Forensic Medicine, Department of Biomedical Engineering, University of Basel, Basel, Switzerland.
Purpose:
To compare postmortem in situ with ex situ MRI parameters, including volumetry, diffusion tensor imaging (DTI), and relaxometry for assessing methodology-induced alterations, which is a crucial prerequisite when performing MRI biomarker validation.
Methods:
MRI whole-brain scans of five deceased patients with amyotrophic lateral sclerosis were performed at 3 T. In situ scans were conducted within 32 h after death (SD 18 h), and ex situ scans after brain extraction and 3 months of formalin fixation. The imaging protocol included MP2RAGE, DTI, and multi-contrast spin-echo and multi-echo gradient-echo sequences. Volumetry, fractional anisotropy, mean diffusivity, T1, T2, and have been assessed for specific brain regions.
Results:
When comparing ex situ to in situ values, the following results were obtained. Deep gray matter as well as the thalamus and the hippocampus showed a reduced volume. Fractional anisotropy was reduced in the cortex and the whole brain. Mean diffusivity was decreased in white matter and deep gray matter. T1 and T2 were reduced in all investigated structures, whereas was increased in the cortex.
Conclusion:
The results of this study show that the volumes and MRI parameters of several brain regions are potentially affected by tissue extraction and subsequent formalin fixation, suggesting that methodological alterations are present in ex situ MRI. To avoid overlap of indistinguishable methodological and disease-related changes, we recommend performing in situ postmortem MRI as an additional intermediate step for in vivo MRI biomarker validation.
Insights
Postmortem MRI reveals that brain extraction and formalin fixation significantly alter MRI parameters, impacting volumetric and diffusion tensor imaging (DTI) measures. In situ MRI is recommended for accurate in vivo biomarker validation.
Area of Science:
- Neuroimaging
- Biomarker Validation
- Postmortem Studies
Background:
- Accurate in vivo MRI biomarker validation requires understanding methodology-induced alterations.
- Postmortem MRI offers a method to assess these changes.
Purpose of the Study:
- To compare in situ and ex situ MRI parameters (volumetry, DTI, relaxometry) in postmortem brains.
- To identify methodology-induced alterations from tissue extraction and fixation.
Main Methods:
- Whole-brain MRI at 3 T was performed on five deceased patients (amyotrophic lateral sclerosis).
- In situ scans were acquired within 32 hours postmortem; ex situ scans after extraction and 3 months fixation.
- MP2RAGE, DTI, and multi-contrast sequences were used; volumetry, fractional anisotropy, mean diffusivity, T1, T2, and R2* were assessed.
Main Results:
- Ex situ MRI showed reduced volumes in deep gray matter, thalamus, and hippocampus.
- Fractional anisotropy and mean diffusivity decreased in various brain regions.
- T1 and T2 values were reduced, while R2* increased in the cortex.
Conclusions:
- Tissue extraction and formalin fixation significantly alter brain volumes and MRI parameters.
- Methodological alterations in ex situ MRI can confound disease-related changes.
- In situ postmortem MRI is recommended as an intermediate step for in vivo biomarker validation.
