Predicting thrombolytic haemorrhage risk of acute ischemic stroke through angiogenesis/inflammation dual-targeted MR imaging

Abstract

Ischemic stroke is currently one of the biggest threats to global health due to its high mortality and disability rate. Thrombolysis with intravenous alteplase remains a primary therapy for acute ischemic stroke. Nevertheless, haemorrhage may be triggered to cause secondary victimization to the patients. On the other hand, the compensatory cerebral collaterals developing in response to ischemia stroke help preserve the penumbral area where the neurons are considered to be salvageable. In this context, precisely evaluating the collateral circulation and predicting the thrombolytic risk of stroke are extremely important not only for treatment decision making but also for a good prognosis. Aiming at identifying the ischemic penumbra and precisely predicting the possible thrombolytic haemorrhage risk prior to thrombolytic therapy, we herein report a dual-targeted magnetic resonance imaging (MRI) nanoprobe based on magnetic iron oxide nanoparticles for visualizing both cerebral collateral circulation and ischemic inflammation. Focal cerebral ischemia rat models were adopted for imaging studies on 7.0 Tesla MRI with different sequences. The imaging results revealed that the nanoprobe could target the newly formed collateral vessels and inflammatory lesions in the cerebral ischemic region, which enabled the visualization of the potential haemorrhage sites of thrombolytic therapy apart from the ischemic penumbra. The current studies therefore offer for the first time a noninvasive approach for precisely predicting potential reperfusion haemorrhage through MRI.