CT perfusion assessment of treatment response and complications in acute ischemic stroke

An acute ischemic stroke is caused by the sudden occlusion of a large blood vessel to a part of the brain. Current treatment options are to dissolve the clot with the injection of a solvent into a vein or to physically remove the clot with an interventional radiology procedure.

A major complication that can occur after stroke is a bleeding inside the infarcted area. This complication can occur with or without treatment but the risk is higher with treatment. Being able to predict which patients will develop a bleeding is important because if the risk is too high it would be better to withhold treatment.

Another major complication is the development of severe brain swelling. The only treatment for this complication is surgical removal of part of the skull to give the brain more space to swell. If this is done before the severe swelling starts the results are better, so being able to predict which patient will develop this swelling could help with treatment decisions.

In this thesis the relation between two important imaging variables (reperfusion and blood-brain barrier permeability (BBBP)) and the two major complications was investigated. The two imaging variables are obtained with dynamic contrast enhanced CT, called CT perfusion (CTP). Reperfusion and BBBP have both been associated with bleeding and brain swelling. It is however unclear what combination of factors leads to these complications. Reperfusion, blood-brain barrier damage and the effect of the clot solvent may all play their part.

The results of the thesis show that recanalization and reperfusion are strongly associated but not always equivalent. Complete reperfusion can be predicted by the total ischemic area on admission CTP. The results did not show an association between reperfusion and the occurrence of bleeding. The results suggest that the delivery of recombinant tissue Plasminogen Activator (rtPA) to the ischemic area with possible direct injury to the BBB results in bleeding. Permeability measurements showed a positive association with the occurrence of bleeding. They did however not improve prediction of bleeding compared to using age and neurological status on admission. In patients with large MCA infarcts on follow-up, the obtained results suggest that patients who develop severe swelling already have a proximal clot and poor collaterals on admission, which leads to a larger affected area and increased permeability. In addition, permeability improves prediction of swelling and thereby has the potential to improve outcome by earlier selection of patients for treatment with partial skull removal.

The main challenge remains to identify which patients are at a higher risk with treatment, so more individualized treatment regimens can be developed.