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Updated: Aug 11, 2026
A Magnetic Resonance Imaging Protocol for Stroke Onset Time Estimation in Permanent Cerebral Ischemia
Published on: September 16, 2017
Reversal of early diffusion-weighted magnetic resonance imaging abnormalities does not necessarily reflect tissue
T M Ringer1, T Neumann-Haefelin, R A Sobel
1Department of Neurosurgery, Stanford University, CA, USA.
Background And Purpose:
Diffusion-weighted MRI (DWI) can detect early ischemic changes and is sometimes used as a surrogate neurological end point in clinical trials. Recent experimental stroke studies have shown that with brief periods of ischemia, some DWI lesions transiently reverse, only to recur later. This study examined the histological condition of the tissue during the period of DWI reversal.
Methods:
Rats underwent 30 minutes of middle cerebral artery occlusion followed by reperfusion. DWI images were obtained during ischemia and 3 to 5 hours, 1 day, and 7 days later. MRI scans were compared with histology (5 hours, n=5; 7 days, n=5) with the use of neuronal (microtubule-associated protein 2 [MAP2]) and astrocytic (glial fibrillary acidic protein [GFAP]) markers and heat-shock protein 72 (HSP72).
Results:
DWI abnormalities reversed 3 to 5 hours after ischemia onset but recurred at 1 day. Four animals showed complete reversal of the initial DWI hyperintensity, and 6 showed partial reversal. When the 5-hour DWI was completely normal, there was significant loss of MAP2 immunoreactivity, comprising approximately 30% of the initial DWI lesion. However, GFAP staining revealed morphologically normal astrocytes. HSP72 immunoreactivity at 5 hours was extensive and corresponded to the initial DWI lesion.
Conclusions:
After brief ischemic periods, normalization of the DWI does not necessarily imply that the tissue is normal. Neurons already exhibit evidence of structural damage and stress. Normal GFAP staining suggests that other nonneuronal cell populations may partially compensate for altered fluid balances at the time of DWI reversal despite the presence of neuronal injury. These observations suggest that caution is warranted when relying solely on DWI for assessment of ischemic damage.
Insights
Diffusion-weighted MRI (DWI) lesions may temporarily disappear after brief strokes, but tissue damage persists. Neuronal injury is evident even when DWI appears normal, indicating caution is needed when assessing stroke severity with DWI alone.
Area of Science:
- Neuroscience
- Medical Imaging
- Pathology
Background:
- Diffusion-weighted MRI (DWI) detects early ischemic changes and is used in clinical trials.
- Experimental stroke studies show transient DWI lesion reversal followed by recurrence.
- The histological state of tissue during DWI reversal requires examination.
Purpose of the Study:
- To investigate the histological condition of brain tissue during the period of DWI reversal after transient ischemia.
- To determine if normalized DWI accurately reflects tissue health post-ischemia.
Main Methods:
- Rats underwent 30-minute middle cerebral artery occlusion and reperfusion.
- DWI was performed during ischemia and at 3-5 hours, 1 day, and 7 days post-reperfusion.
- Histology used neuronal (MAP2) and astrocytic (GFAP) markers, and heat-shock protein 72 (HSP72) at 5 hours and 7 days.
Main Results:
- DWI abnormalities reversed by 3-5 hours but recurred at 1 day.
- At 5 hours, despite normal DWI in some cases, significant neuronal damage (MAP2 loss) was observed.
- Astrocytes (GFAP) appeared normal, while HSP72 was elevated, indicating cellular stress.
Conclusions:
- Normalized DWI after transient ischemia does not guarantee tissue normality.
- Neurons show structural damage and stress even when DWI findings reverse.
- Non-neuronal cells may influence fluid balance during DWI reversal, masking underlying neuronal injury.
