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Correlation of diffusion MRI and heat shock protein in a rat embolic stroke model
J A Detre1, E L Zager, D C Alsop
1Department of Neurology, University of Pennsylvania, Philadelphia 19104, USA. detre@mail.med.upenn.edu
Abstract:
The expression of 70 kDa heat shock protein (HSP-70) in focal ischemia occurs in regions that sustain sub-lethal ischemic injury, and may therefore be considered as a biological marker of the ischemic penumbra. In a rat embolic stroke model, using fibrin-rich emboli, we correlated the expression of HSP-70 mRNA with diffusion magnetic resonance imaging (MRI) to determine if HSP-70 mRNA expression was associated with alterations in the apparent diffusion coefficient (ADC) of brain tissue water, a putative early marker of cytotoxic injury that is readily measured in vivo. Serial ADC measurements were made for 120 min following embolic infarction in the right carotid artery territory. HSP-70 mRNA expression was observed at the boundaries of the densely ischemic zone, as judged by diffusion imaging. ADC values observed in HSP-70 mRNA-positive regions were intermediate between those observed in the ischemic core or in control regions. In addition, the volume of HSP-70 mRNA-positive tissue correlated positively with the volume of tissue showing intermediate ADC values at 120 min. These findings suggest that intermediate ADC values occur in penumbral regions. Heterogeneity of ischemic cellular injury is suggested as the basis for the intermediate ADC values observed in these regions.
Insights
70 kDa heat shock protein (HSP-70) mRNA expression in focal ischemia may indicate the ischemic penumbra. This study correlated HSP-70 mRNA with diffusion MRI, suggesting intermediate apparent diffusion coefficient (ADC) values reflect penumbral regions.
Area of Science:
- Neuroscience
- Biochemistry
- Medical Imaging
Background:
- 70 kDa heat shock protein (HSP-70) expression is linked to sub-lethal ischemic injury.
- HSP-70 is a potential biological marker for the ischemic penumbra.
Purpose of the Study:
- To correlate HSP-70 mRNA expression with diffusion MRI apparent diffusion coefficient (ADC) changes in a rat stroke model.
- To investigate if HSP-70 mRNA expression is associated with early cytotoxic injury markers.
Main Methods:
- A rat embolic stroke model using fibrin-rich emboli was employed.
- Serial apparent diffusion coefficient (ADC) measurements were taken for 120 minutes post-infarction.
- HSP-70 mRNA expression was analyzed in relation to diffusion imaging findings.
Main Results:
- HSP-70 mRNA expression was detected at the boundaries of the densely ischemic zone.
- ADC values in HSP-70 mRNA-positive regions were intermediate between the ischemic core and control regions.
- A positive correlation was found between the volume of HSP-70 mRNA-positive tissue and tissue with intermediate ADC values.
Conclusions:
- Intermediate ADC values likely occur in the ischemic penumbra.
- HSP-70 mRNA expression may serve as a marker for penumbral regions.
- Heterogeneity in ischemic cellular injury may explain intermediate ADC values.