• Cellular swelling (cytotoxic edema) with resultant restricted diffusion is the first histologic change to be observed.
• Subsequently in the course of stroke evolution, the cytotoxic edema is replaced by vasogenic edema (interstitial edema). Inflammatory cells start to clean up the damaged cells and replace the lost neuronal tissue with gliosis.

Cytotoxic and interstitial edema

Diffusion Weighted MRI and Conventional MRI
prediction of histopathologic changes

• DWI (Diffusion Weighted Imaging) and ADC (Apparent Diffusion Coefficient) MRI sequences are very sensitive to diffusion restriction and cytotoxic edema.
• Diffusion restriction is bright on DWI and dark on ADC map.
• DWI signal intensity is calculated from the following formula:

  

• This equation indicates that DWI signal has T2 contrast as part of the total signal.
• ADC map is a more accurate image to predict the diffusion restriction as it represents the distribution of ADC throughout the brain without the influence of T2 signal.

Evolution of infarction based on DWI, ADC map

• Changes on diffusion-weighted images and ADC map become apparent within half to one hour of ictus.
• DWI SI peaks in 3-4 days while ADC map signal is lowest in 2-3 days.
• Lovblad et al reported an 88% stroke detection sensitivity using DWI within 6 hours. This contradicts the prior reported sensitivity which approached 100%.
• Normalization of ADC signal by visual inspection after infarction indicates an approximately 10 day old infarct with 88% sensitivity and 90% specificity.
• The higher the SI is on DWI and the lower the intensity is on ADC in hyperacute stroke (in the first few hours), the more severe the neuronal injury.
• The majority of stroke lesions increase in volume on DWI with the maximum volume achieved at 2–3 days.

Reversibility of diffusion restriction signal on DWI and ADC map
The initial reversible cytotoxic edema is a very brief period. There are very few cases mentioned in the literature describing a positive DWI stroke in which the DWI signal reversed to normal following thrombolytic treatment.

Pitfalls of Diffusion Restriction Imaging:

1. False negative DWI/ ADC
   Ranges between 2-11%. This is related to early scanning during which there is hemodynamic derangement, but cytotoxic edema has not yet developed. These patients are the ones which will benefit most from early thrombolytic treatment. In these situations PWI is more accurate than DWI/ADC.
2. False positive DWI/ ADC
   This is related to causes of diffusion restriction other than vascular disease and ischemia, including viral encephalitis in which intracellular viruses cause cellular derangement and cytotoxic edema.

Conventional T2 and FLAIR (Fluid Attenuation Inversion Recovery)

These sequences are very sensitive to free extracellular (ECF) water. They are excellent for imaging interstitial (vasogenic) edema and will depict any hemorrhagic changes in the infarction, along with T1 sequence.

The vasogenic edema gradually progresses after the cytotoxic edema with associated increase in T2 signal.

Lesions with SI FLAIR ratio relative to contralateral symmetrical area of less than 1.37 have been found to be 36 hours old or less, with 91% sensitivity and 83% specificity.