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Postmortem interval alters the water relaxation and diffusion properties of rat nervous tissue--implications for MRI
Timothy M Shepherd1, Jeremy J Flint, Peter E Thelwall
1Department of Radiology and Biomedical Imaging, University of California-San Francisco, San Francisco, CA 94143-0628, USA. tim.shepherd@radiology.ucsf.edu
Abstract:
High-resolution imaging of human autopsy tissues may improve our understanding of in vivo MRI findings, but interpretation is complicated because samples are obtained by immersion fixation following a postmortem interval (PMI). This study tested the hypotheses that immersion fixation and PMI's from 0-24 h would alter the water relaxation and diffusion properties in rat cortical slice and spinal cord models of human nervous tissue. Diffusion data collected from rat cortical slices at multiple diffusion times (10-60 ms) and b-values (7-15,000 s/mm(2)) were analyzed using a two-compartment model with exchange. Rat spinal cords were characterized with standard diffusion tensor imaging (21 directions, b=1250 s/mm(2)). Switching from perfusion- to immersion-fixation at 0 h PMI altered most MRI properties of rat cortical slices and spinal cords, including a 22% decrease in fractional anisotropy (P<0.001). After 4 h PMI, cortical slice T(1) and T(2) increased 22% and 65% respectively (P<0.001), transmembrane water exchange decreased 23% (P<0.001) and intracellular proton fraction increased 25% (P=0.002). After 6 h PMI, spinal cord white matter fractional anisotropy had decreased 38% (P<0.001). MRI property changes were observed for PMIs up to 24 h. The MRI changes correlated with protease activity and histopathological signs of autolysis. Thus, immersion fixation and/or even short PMIs (4-6 h) altered the MRI properties of rat nervous tissue. This suggests comparisons between in vivo clinical MRI and MRI data from human autopsy tissues should be interpreted with caution.
Insights
Immersion fixation and postmortem intervals (PMI) significantly alter MRI properties in nervous tissue. Even short PMIs (4-6 hours) change water relaxation and diffusion, cautioning against direct comparison with in vivo MRI findings.
Area of Science:
- Neuroimaging
- Biomedical Engineering
- Pathology
Background:
- High-resolution MRI of human autopsy tissues aids in vivo MRI understanding.
- Interpretation is challenging due to immersion fixation and postmortem intervals (PMI).
Purpose of the Study:
- To investigate how immersion fixation and PMIs (0-24h) affect MRI properties in rat nervous tissue models.
- To test if these factors alter water relaxation and diffusion characteristics.
Main Methods:
- Diffusion data from rat cortical slices analyzed with a two-compartment model with exchange.
- Rat spinal cords imaged using diffusion tensor imaging.
- MRI properties assessed after switching fixation methods and at various PMIs.
Main Results:
- Immersion fixation at 0h PMI altered most MRI properties, decreasing fractional anisotropy by 22%.
- After 4h PMI, cortical T1/T2 increased, water exchange decreased, and intracellular proton fraction rose.
- Spinal cord white matter fractional anisotropy decreased by 38% after 6h PMI.
Conclusions:
- Immersion fixation and short PMIs (4-6h) significantly alter MRI properties of nervous tissue.
- Observed MRI changes correlate with protease activity and autolysis.
- Comparisons between in vivo clinical MRI and autopsy tissue MRI require careful interpretation.
