Computed Tomography Perfusion imaging in acute ischemic stroke

Stroke is the most common severe neurological disorder and is associated with high levels of mortality and disability. Ischemic stroke occurs when the blood supply to a region of the brain is interrupted for a duration that is beyond the ability of brain tissue to survive. The brain is very sensitive to disruption in oxygen and glucose supply, and complete deprivation lead to tissue death within minutes. However, the brain circulation had developed mechanisms to avoid immediate cell death; collateral circulation can provide blood supply to areas beyond obstruction, compensatory increase in systemic blood pressure can occur, and local vasodilation and increased oxygen extraction allows some tissue to survive for several hours after blood supply is disrupted. This discovery that not all functionally inactive brain tissue at onset of stroke is irreversibly damaged is the basis of treatment of stroke in the acute phase. Although part of the ischemic tissue, referred to as ischemic core, is irreversibly damaged, other parts, the ischemic penumbra, can recover if blood flow is restored in a timely manner. Revascularisation therapy, using intravenous tissue plasminogen activator or mechanical thrombectomy, aims to restore blood flow as early as possible, with maximum salvage of penumbra tissue. CTP perfusion imaging can be used to identify regions of core and penumbra after an acute stroke. This information increases confidence in stroke diagnosis, and can be used to guide management and for prognostication. The use of CTP before IV thrombolysis is controversial, due to concerns about time required for scan acquisition delaying treatment, and lack of agreement on interpretation of scans. The aim of this work is to evaluate the use of CTP in assessing patients with ischemic stroke considered for revascularization therapy. We firs conducted an online study to evaluate inter-observer and intra-observer agreement on visual assessment of NCCT and CTP scans of patients with acute stroke presenting within the first 6 hours of symptom onset. Fifty seven observers, from 9 different countries, contributed to the study. Observers varied in their specialities and experience. Inter-observer agreement was moderate to almost perfect, and intra-observer agreement was moderate to substantial. Agreement on core sensitive maps (CBF and CBV) was not better than agreement on NCCT interpretation, but agreement improved for time-based maps and dichotomised maps. This agreement did not directly translate into agreement on treatment decisions. This reflects the complex nature of thrombolysis treatment decision, where imaging is only one of many factors that clinicians consider, and the lack of agreement on the use of different CTP parameters to guide IV rtPA PRACTISE is a randomised controlled multicentre clinical trial comparing to imaging strategies before IV rtPA; either NCCT alone, or NCCT with additional CTP and CTA. The trial recruited a cohort of mild to moderate strokes, with relatively small perfusion deficit. This probably reflects increased use of CTA in patients with more severe stroke, where mechanical thrombectomy is considered. The use of multimodal imaging did not increase the number of patients receiving IV rtPA, but rather gave clinicians more confidence not to give IV rtPA in patients without any radiological evidence of major artery occlusion or large perfusion deficit. Importantly, the study showed that use of multimodal imaging did not delay time to treatment. These results await confirmation in the definitive analysis of the full study results. The role of CTP in selecting patients for intra-arterial thrombectomy is not known. We explored the effect of CTP selection criteria in published trials on the number of patients potentially eligible for treatment in a pre-existing imaging database. The number of patients eligible for the IAT in our data base ranged between 3% and 53% for individual studies. Only 14% would have been eligible for 3 or more of the recent trials. In a hypothetical model, we estimated that 16% of patients admitted within the first 6 hours after symptom onset would be eligible for IAT. Whole brain Human Ischaemic Stroke Perfusion and Extended Re-canalisation-Pilot study (WHISPER-P) is a prospective observational single centre study aiming to identify the proportion of patients with ischemic stroke and salvageable brain tissue beyond the current therapeutic windows for IV thrombolysis, Finally, we conducted an observational study to assess the number of patients eligible for intra-arterial thrombectomy in an extended time window. Whole brain Human Ischaemic Stroke Perfusion and Extended Re-canalisation-Pilot study (WHISPER-P) is a prospective observational single centre study aiming to identify the proportion of patients with ischemic stroke and salvageable brain tissue beyond the current therapeutic windows for IV thrombolysis. CTP detected potentially viable tissue in about 40% of patients scanned 4.5 to 24 hours after onset of their symptoms. Penumbra was detected in 2/3 (67%) of patients scanned in the first 12 hours and 4/13 (31%) of patients scanned in the 12 to 24 hour window. Only 6% of patients met inclusion criteria for endovascular therapy