Imaging in Acute Anterior Circulation Ischemic Stroke: Current and Future

Abstract

Clinical trials on acute ischemic stroke have demonstrated the clinical effectiveness of revascularization treatments within an appropriate time window after stroke onset: intravenous thrombolysis (NINDS and ECASS-III) through the administration of tissue plasminogen activator within a 4.5-hour time window, endovascular thrombectomy (ESCAPE, REVASCAT, SWIFT-PRIME, MR CLEAN, EXTEND-IA) within a 6-hour time window, and extending the treatment time window up to 24 hours for endovascular thrombectomy (DAWN and DEFUSE 3). However, a substantial number of patients in these trials were ineligible for revascularization treatment, and treatments of some patients were considerably futile or sometimes dangerous in the clinical trials. Guidelines for the early management of patients with acute ischemic stroke have evolved to accept revascularization treatment as standard and include eligibility criteria for the treatment. Imaging has been crucial in selecting eligible patients for revascularization treatment in guidelines and clinical trials. Stroke specialists should know imaging criteria for revascularization treatment. Stroke imaging studies have demonstrated imaging roles in acute ischemic stroke management as follows: 1) exclusion of hemorrhage and stroke mimic disease, 2) assessment of salvageable brain, 3) localization of the site of vascular occlusion and thrombus, 4) estimation of collateral circulation, and 5) prediction of acute ischemic stroke expecting hemorrhagic transformation. Here, we review imaging methods and criteria to select eligible patients for revascularization treatment in acute anterior circulation stroke, focus on 2019 guidelines from the American Heart Association/American Stroke Association, and discuss the future direction of imaging-based patient selection to improve treatment effects.

Keywords: Acute ischemic stroke; Angiography; Collateral circulation; Computed tomography, X-ray; Magnetic resonance imaging; Perfusion.

Fig. 1.

Images at admission of an elderly patient who presented with dysarthria and right-sided weakness at 2 and half hours after last known normal state. The premorbid modified Rankin scale score of this patient was 0, and the National Institutes of Health Stroke Scale score at admission was 23. (A) Ganglionic level and (B) supraganglionic level, noncontrast computer tomography (NCCT) images show loss of gray-white matter differentiation at insula, M2, M3, M4, and M5 of the left middle cerebral artery territory, and the Alberta Stroke Program Early CT Score (ASPECTS) is 5 visually. (C) Computer-aid automated ASPECTS is 7 (RAPID, RapidAI^®, Menlo Park, CA, USA). (D) Computed tomography angiography (CTA) shows occlusion of the left internal carotid and middle cerebral arteries. (E–G) The first (E), second (F), and third phase (G) collateral images derived from multiphase CTA show a filling delay of 2 phases in the affected hemisphere with a significantly reduced number of vessels in the ischemic territory (multiphase CTA collateral score 2). (H) CT perfusion (CTP) Tmax threshold >6 seconds (Tmax >6 s) map indicates near whole left middle cerebral artery territory as penumbra (red zone). (I) Automated software (RAPID, RapidAI^®) demonstrates the volume data of core and penumbra and mismatch ratio between the penumbra and core, which are 93 mL with a threshold of CTP cerebral blood flow <30% and 132 mL with threshold of a Tmax > 6 s and 1.4, respectively. (J) Ganglionic level and (K) supraganglionic level, diffusion-weighted magnetic resonance images (DWI) obtained 10 minutes after CT scan show a large core involving the entire left middle cerebral artery territory. (L–O) Images of arterial (L), capillary (M), early venous (N), and late venous (O) phases of the collateral map derived from dynamic contrast-enhanced magnetic resonance angiography show very poor collateral perfusion status (MAC score of 0) [38] defined as collateral perfusion delay/defect more than one-half of affected middle cerebral artery territory remained until the late venous phase. DWI (J, K) and the collateral map (L–O) indicate that the core rapidly progresses to infarction. According to current guidelines, she should receive intravenous thrombolysis (IVT) after scanning NCCT (A, B). Even though the visually estimated NCCT ASPECTS is 5, it is not easy to exclude her from endovascular thrombectomy (EVT) because it is difficult to accept the NCCT ASPECTS. In addition, the automated ASPECTS is 7 (C), which is an eligible score for EVT. The result of automated software is dependent on the quality of the learning material, which is used as ground truth in deep learning. Automated ASPECTS is limited in accuracy due to the inconspicuousness of NCCT. We can see another result of the automated core size estimated with a threshold of CTP cerebral blood flow <30% (I), which is different from the results of visual and automated estimation. It is inevitably limited to measuring cores containing heterogeneous factors regarding occluded duration, collateral status, and cellular composition with different ischemic resistance as a fixed threshold value. This indirect method of core assessment is also due to the inconspicuousness of NCCT, and this is a major limitation of CT workup in acute ischemic stroke despite its availability and rapidity. However, DWI shows a far-progressed large infarction directly and clearly (J, K). We do not need to hesitate excluding her from EVT. At current guidelines, there is no basis for excluding her from IVT or for further imaging work-up except NCCT. We have no choice but to inject recombinant tissue plasminogen activator (rt-PA). However, through this case, we can understand the significant ratio of futile or dangerous treatments in current guidelines.

Fig. 2.

Images of an elderly patient who developed left-sided weakness 2 hours prior. (A) Diffusion-weighted magnetic resonance imaging at admission shows a core involving the whole right middle cerebral artery territory. (B) Time-of-flight magnetic resonance angiography (TOF-MRA) and (C) computed tomography angiography (CTA) show occlusion from the right proximal internal carotid artery (ICA) to the ipsilateral middle cerebral artery. (D) Early phase image of dynamic contrast-enhanced magnetic resonance angiography (DCE-MRA) shows the same finding as that of TOF-MRA and CTA. (E) More delayed phase image than (D) of DCE-MRA reveals delayed flow of the ICA reaching the cavernous segment (white arrows). (F) Catheter digital subtraction angiography reveals the patent right proximal ICA (black arrows) and occlusion of the C1 segment of the right ICA (*).

Fig. 3.

Images of a middle aged patient who developed left-sided weakness 30 minutes prior. Her premorbid modified Rankin scale score was 0, and the National Institutes of Health Stroke Scale score at admission was 11. She underwent intravenous thrombolysis followed by intraarterial thrombectomy, but recanalization of the occluded arteries was not achieved, as shown by a modified Thrombolysis in Cerebral Infarction scale score of 2a. (A) Noncontrast computed tomography image at admission shows less distinction of the right basal ganglia than the left basal ganglia. (B) Diffusion-weighted magnetic resonance imaging (DWI) at admission shows a core involving the insula, caudate nucleus, basal ganglia, internal capsule, M1, cortical area of M2 and M3, and some periventricular white matter of M3 on the right middle cerebral artery territory. (C) Dynamic contrast-enhanced magnetic resonance angiography (DCE-MRA) at admission shows occlusion of the right internal carotid and middle cerebral arteries. (D) MR perfusion Tmax threshold >6 seconds (Tmax >6 s) map at admission shows penumbra (white zone) matched with the core. (E) DWI on Day 1 shows a significantly increased extent of the core on DWI at admission due to reperfusion failure. (F–J) Images of arterial (F), capillary (G), early venous (H), late venous (I), and delay (J) phases of collateral map derived from DCE-MRA show intermediate to poor collateral perfusion status (MAC score of 2) [38] defined as collateral perfusion delay/defect more than one-half of affected middle cerebral artery territory in the capillary phase and equal to or less than one-half in the early venous phase. Because there was no target mismatch on Tmax >6 s (D), despite no penumbra on Tmax >6 s, the extent of the baseline core increased as much as the hypoperfused area on the capillary phase of the collateral map at admission, and the extent of the baseline core coincided with the hypoperfused area in the early venous phase.

Fig. 4.

Images of an elderly patient who developed left-sided weakness 4 hours prior. His premorbid modified Rankin scale score was 0, and the National Institutes of Health Stroke Scale score at admission was 10. He was ineligible for IVT because he was taking an oral anticoagulant for arterial fibrillation. (A) Diffusion-weighted magnetic resonance imaging (DWI) at admission shows the core mainly involving more than one-third of the right middle cerebral artery (MCA) territory. (B) Dynamic contrast-enhanced magnetic resonance angiography (DCE-MRA) at admission shows partial occlusion at the first bifurcation of the right MCA. (C) MR perfusion Tmax threshold >6 seconds (Tmax 7>6 s) map at admission shows penumbra (white zone) larger than the core representing target mismatch. Catheter digital subtraction angiography performed prior to endovascular thrombectomy (EVT) revealed distal migration of fragmented thrombi to the M3 and M4 branches of the right MCA, so EVT did not undergo. (D) DWI on Day 1 shows that most of the baseline DWI lesions were reversed except for two tiny infarct signals. (E–I) Images of arterial (E), capillary (F), early venous (G), late venous (H), and delay (I) phases of collateral map derived from DCE-MRA show good collateral perfusion status (MAC score of 4) [38] defined as collateral perfusion delay equal to or less than one-half of affected MCA territory in the capillary phase and no or a small delay in the early venous phase.