Acute Stroke Imaging in the Era of the DAWN, DEFUSE 3 and WAKE-UP Study Findings

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BackgroundIn recent years, machine learning (ML) has had notable success in providing automated analyses of neuroimaging studies, and its role is likely to increase in the future. Thus, it is...

In this issue of Neurology are two articles describing further experience with magnetic resonance diffusion weighted imaging (DWI) and perfusion weighted imaging (PWI) in acute ischemic stroke.1,2 Both add to the growing body of evidence from clinical observation and animal experiments documenting that these new MRI techniques show abnormalities in regions of acute cerebral ischemia earlier than either conventional MRI or CT. We would like to discuss the use of MRI as a diagnostic test for acute ischemic stroke in the context of the practice of clinical neurology. We will not discuss the use of MRI for clinical research or treatment trials because the requirements for a diagnostic test under these circumstances are quite different. In the practice of medicine, the usual purpose of a diagnostic test is to improve the accuracy of the initial clinical diagnosis. The goal of improved diagnostic accuracy is not an end in itself, but a means to improve patient outcome by allowing selection of the most appropriate therapy. Thus, the value of a diagnostic test is determined not only by its accuracy but by demonstrating that the information it provides can be used for selecting the most effective patient management. Even in circumstances where no proven treatment exists, more accurate diagnosis can prevent the use of inappropriate treatment and provide prognostic information which is of value to patients and their families. A new diagnostic test is useful if it can replace a more invasive or expensive test or if it provides information that can be shown to improve …

Acute ischemic stroke imaging is one of the leading causes of death and disability worldwide. Neuroimaging plays a crucial role in early diagnosis and yields essential information regarding tissue integrity, a factor that remains a key therapeutic determinant. Given the widespread public health implications of stroke and central role of neuroimaging in overall management, acute stroke imaging remains a heavily debated, extensively researched, and rapidly evolving subject. There has been recent debate in the scientific community due to divided opinions on the use of CT perfusion and access-related limitations of MRI. In this paper we review and summarize recent updates relevant to acute stroke imaging and propose an imaging paradigm based on the recently available evidence.

Stroke is the most common cause of mortality and morbidity worldwide. The prognosis of stroke depends upon the area affected and its early treatment. Time is of the essence in the care of stroke patients as it is estimated that approximately 1.9 million neurons, 14 billion synapses, and 12 km myelinated nerve fibers are lost per minute. Therefore, early diagnosis and prompt treatment are necessary. The primary goal of imaging in acute stroke is to diagnose the underlying cause, estimate the area affected, predict response towards thrombolytic therapy and to exclude the conditions mimicking stroke. With advancements in radiology, multiple imaging modalities are available for diagnosis and predicting prognosis. None of them is considered alone to be perfect. In this era of multimodality imaging, the decision of choosing appropriate techniques depends upon purpose and availability. Non-Contrast Computed Tomography is time effective, and helps in excluding other causes, Trans Cranial Doppler is time-effective and cost-effective with wide availability, however, is operator dependent and less sensitive. It holds a great future in sonothrombolysis. Magnetic Resonance Imaging is so far considered to be the most superior one in terms of early diagnosis, planning for interventional treatment and predicting the response of treatment. However, it is limited due to high cost and lack of availability. The current review gives a detailed account of all imaging modalities available for imaging stroke and their associated pros and cons.

MR Perfusion Imaging in Acute Ischemic Stroke

Cerebral perfusion imaging in acute stroke assists in determining the subtype and the severity of ischemia. Recent studies in perfusion models and in healthy volunteers have shown that ultrasound perfusion imaging based on microbubble destruction can be used to assess tissue perfusion. We applied ultrasound microbubble destruction imaging (MDI) to identify perfusion deficits in patients with acute middle cerebral artery (MCA) territory stroke. Fifteen acute MCA stroke patients with sufficient transtemporal bone windows were investigated with ultrasound MDI and perfusion-weighted MRI (PWI). MDI was performed using power pulse-inversion contrast harmonic imaging. Thirty seconds after a bolus injection of the echo contrast agent SonoVue, microbubbles were destroyed using a series of high-energy pulses. Local perfusion status was analyzed in selected regions of interest by destruction curves and acoustic intensity differences (DeltaI) before and after microbubble destruction. Local perfusion status was then compared with perfusion compromise as identified on PWI. The mean differences of acoustic intensity from the ischemic MCA territory were significantly diminished compared with the normal hemisphere (DeltaI=2.52+/-1.75 versus DeltaI=13.79+/-7.31; P<0.001), resulting in lower slopes of microbubble destruction. PWI confirmed perfusion changes in the selected anatomical regions on time-to-peak maps in all 15 patients. MDI is a qualitative method that can rapidly detect perfusion changes in acute stroke. When combined with other ultrasound techniques and PWI, it may well be valuable in the care of stroke unit patients, eg, as a screening method and for follow-up assessments of perfusion deficits.

Computed tomography perfusion imaging in acute stroke requires further validation. We aimed to establish the optimal computed tomography perfusion parameters defining the infarct core and critically hypoperfused tissue. Sub-6-h computed tomography perfusion and 24-h magnetic resonance imaging were analysed from 314 consecutive patients with ischaemic stroke. Diffusion-weighted imaging lesion volume at 24 h was used to define the extent of critically hypoperfused tissue (in patients without reperfusion between acute and 24-h time points), and infarct core (in patients with major reperfusion at 24 h). Pixel-based analysis of co-registered computed tomography perfusion and diffusion-weighted imaging was then used to define the optimum computed tomography perfusion thresholds for critically hypoperfused at-risk tissue and infarct core. These optimized acute computed tomography perfusion threshold-based lesion volumes were then compared with 24-h diffusion-weighted imaging infarct volume, as well as 24-h and 90-day clinical outcomes for validation. Relative delay time >2 s was the most accurate computed tomography perfusion threshold in predicting the extent of critically hypoperfused tissue with both receiver operating curve analysis (area under curve 0.86), and the volumetric validation (mean difference between computed tomography perfusion and 24-h diffusion-weighted imaging lesions = 2 cm(2), 95% confidence interval 0.5-3.2 cm(2)). Cerebral blood flow <40% (of contralateral) within the relative delay time >2 s perfusion lesion was the most accurate computed tomography perfusion threshold at defining infarct core with both receiver operating characteristic analysis (area under curve = 0.85) and the volumetric validation. Using these thresholds, the extent of computed tomography perfusion mismatch tissue (the volume of 'at-risk' tissue between the critically hypoperfused and core thresholds) salvaged from infarction correlated with clinical improvement at 24 h (R(2) = 0.59, P = 0.04) and 90 days (R(2) = 0.42, P = 0.02). Patients with larger baseline computed tomography perfusion infarct core volume (>25 ml) also had poorer recovery at Day 90 (P = 0.039). Computed tomography perfusion can accurately identify critically hypoperfused tissue that progresses to infarction without early reperfusion, and the computed tomography perfusion cerebral blood flow infarct core closely predicts the final volume of infarcted tissue in patients who do reperfuse. The computed tomography perfusion infarct core and at-risk measures identified are also strong predictors of clinical outcome.

IntroductionAustralia has fortunately had a low prevalence coronavirus disease 2019 (COVID‐19), and our healthcare system has not been overwhelmed. We aimed to determine whether, despite this, a decline in acute stroke presentations, imaging and intervention occurred during the pandemic at a busy stroke centre.MethodsThe number of ‘code stroke’ activations, multimodal CTs and endovascular clot retrievals (ECRs) performed during the pandemic period (3/1/2020–5/10/2020) at a large comprehensive stroke centre was compared against the pre‐pandemic period (3/1/2019–1/31/2019) using Z‐statistics. Year‐on‐year comparison of the number of patients with large vessel occlusions (LVOs) and ECRs performed per month was also made.ResultsThe number of ‘code stroke’ activations and patients undergoing multimodal CT per month decreased significantly (P < 0.0025) following lockdown on 29th March. The number of ECRs also decreased (P = 0.165). The nadir in the weekly number of CTs coincided with lockdown and the peak of new COVID‐19 cases. The number of patients with LVOs and ECRs increased by 15% and 14%, respectively, in March but decreased by 55% and 48%, respectively, in April.ConclusionsThe significant decrease in volume of ‘code stroke’ activations and acute stroke imaging following lockdown was accompanied by a concomitant decrease in patients with LVOs and ECRs. The decrease in imaging was therefore not driven purely by patients with mild strokes and stroke mimics, but also included those with severe strokes. Since Australia had a low prevalence of COVID‐19, this observed decrease cannot be attributed to hospital congestion and is instead likely driven by patient fear.

Complicated Carotid Artery Plaques and Risk of Recurrent Ischemic Stroke or TIA

Stroke is a leading cause of mortality and disability worldwide, with 15 million people having a stroke annually. Given that it is very difficult to distinguish an ischemic from a...

Complicated Carotid Artery Plaques as a Cause of Cryptogenic Stroke

Introduction: Diagnosis and treatment of acute stroke depends upon imaging, namely non-contrast CT (NCCT), CT angiography (CTA), CT perfusion (CTP), and MRI. We sought to i) examine available data from around the world on six categories related to acute stroke imaging: utilization, time to imaging, radiation exposure, contrast dose, availability, and cost, and ii) compare that information with similar data from our province (Alberta). Methods: Using a scoping review methodology, six categories related to acute stroke diagnostic imaging were examined: utilization, time to imaging, radiation exposure, contrast dose, availability, and cost. Metadata for these categories in Alberta were collected from Alberta Health Services administrative records for comparison. Results: A total of 6693 articles/documents were initially identified through database searches, of which 83 were included for analysis. CT (range = 55-100%) was used more frequently than MRI (range = 23.6-94.0%) in acute stroke, with high CTA use in Alberta (55.7%) compared to other centres (range = 8.6-36.0%; Table 1). CT time to imaging was &lt; 25 min (target time) in most centres, but not in Alberta (mean = 3.2 hr, median = 2.0 hr). MRI was not used urgently in most centres (mean = 0.4-21.0 hr), including Alberta (mean = 15.4 hr, median = 13.0 hr). CTA radiation exposure was greater in Alberta compared to other centres (5.7 mSv vs 2.8-5.4 mSv) whereas it was similar for NCCT and CTP. Contrast doses for CTA and CTP were similar between Alberta (CTA = 50-70 mL, CTP = 45 mL) and other centres (CTA = 40-150 mL, CTP = 30-60 mL). Lastly, the number of CT and MRI scanners per million population and cost of operating them was similar worldwide. Conclusions: In conclusion, no studies were identified that provide a comprehensive overview of all six factors relevant to diagnostic imaging in acute stroke. The Alberta metadata fills in this literature gap, specifically in the context of Canadian stroke care.

pH change is often considered a hallmark of metabolic disruption in diseases such as ischemic stroke and cancer. Chemical exchange saturation transfer (CEST) MRI, particularly amide proton transfer (APT), has emerged as a noninvasive pH imaging approach. However, there are changes in multipool CEST effects besides APT MRI. Our study investigated radiofrequency (RF) amplitude-based ratiometric CEST pH imaging in acute stroke. Briefly, adult male Wistar rats underwent CEST MRI under two RF saturation (B1 ) levels of 0.75 and 1.5 μT following middle cerebral artery occlusion. Magnetization transfer (MT), direct water saturation, CEST at 2ppm (CEST@2ppm), amine (2.75 ppm), and APT (3.5ppm) effects were resolved with the multipool Lorentzian fitting approach. The ratiometric analysis was measured in the ischemic lesion and the contralateral normal area, which was also correlated with pH-specific MT and the relaxation normalized APT (MRAPT) index. MT, amine CEST effect, and their respective ratiometric indices did not show significant changes in ischemic regions (p> 0.05), as expected. Whereas APT decreased in the ischemic lesion for B1 of 1.5 μT (p< 0.01), the correlation between the amide ratio with MRAPT index was moderate (r = 0.52, p= 0.02). By comparison, the ischemic tissue showed a significantly increased CEST@2ppm for both saturation levels from the contralateral normal area (p≤0.01). Importantly, the CEST@2ppm ratio decreased in the ischemic lesion (p< 0.01), which highly correlated with the MRAPT index (r = 0.93, p< 0.001). To summarize, our study demonstrated the feasibility of endogenous CEST@2ppm ratiometric imaging of pH upon acute stroke, promising to detect pH changes in metabolic diseases.

Acute stroke imaging has developed from intraarterial angiography and native, unenhanced CT to highly elaborated tools with the access to a variety of pathophysiological variables ahead of therapy. Despite enduring unresolved problems, we can now obtain a comprehensive view on the individual patient's disease and act fast and specifically under consideration of chances and risks of different therapies. The stroke neuroradiologist is the decisive partner of engaged clinical disciplines and should own a leading role in future acute stroke trials. Weighing the different modalities against each other, there is an established advantage of acute stroke MRI over CT based on diffusion-weighted imaging and the possibility to obtain even more functional information on stroke pathophysiology.