American Heart Association

diagnosis and imaging

Article Commentary: “Early Brain Imaging Shows Increased Severity of Acute Ischemic Strokes With Large Vessel Occlusion in COVID-19 Patients”

Burton J. Tabaac, MD

Escalard S, Chalumeau, Escalard C, Redjem H, Delvoye F, Hébert S, Smajda S, Ciccio G, Desilles J-P, Mazighi M, et al. Early Brain Imaging Shows Increased Severity of Acute Ischemic Strokes With Large Vessel Occlusion in COVID-19 Patients. Stroke. 2020.

In May of this year, amidst the sweeping COVID-19 global pandemic, the New England Journal of Medicine published a paper detailing how large vessel occlusive disease might be a presenting feature in patients with strokes secondary to the infection.1 The authors of this particular paper, cited above, build upon the NEJM observation with imaging evidence to posit that strokes secondary to COVID-19 are also more severe in nature.

Patients were selected and included to be a part of the comparative cohort if COVID-19 was diagnosed (via real-time PCR) and had documented acute large vessel occlusion between the observation and recruitment timeframe between March 15 and April 30, 2020. Two of the authors of the study were blinded to the COVID-19 status of the patient and were asked to quantify the infarct core volume for all patients with large vessel occlusion during the time period. During the study, fifteen patients with large vessel occlusion and confirmed COVID-19 infection were treated.

Looking Beyond the Primary Infarction: Remote Regional Brain Atrophy After Stroke

Lin Kooi Ong, PhD

Brodtmann A, Khlif MS, Egorova N, Veldsman M, Bird LJ, Werden E. Dynamic Regional Brain Atrophy Rates in the First Year After Ischemic Stroke. Stroke. 2020;51:e183–e192.

Brain atrophy refers to a loss of brain cells or a loss in the networks between brain cells, and is a common feature for many neurodegenerative diseases. Ischemic stroke is usually viewed as an acute cerebrovascular injury, and not as a neurodegenerative condition. Nevertheless, there is now emerging evidence demonstrating that stroke can cause persistent regional brain atrophy for months and even years after the initial event. Further, this regional brain atrophy after stroke has been linked to several late phase functional disturbances, including cognitive impairment. Notably, stroke increases the risk of developing vascular dementia.

The CANVAS study (Cognition and Neocortical Volume After Stroke) is a longitudinal study in people recruited from Melbourne hospitals, Australia, following ischemic stroke, comparing brain volume and cognitive function over 3 years with a group of healthy age- and sex-matched control participants.(1) In this article, Brodtmann and colleagues examined the trajectories of total and regional brain volume changes in the first year following stroke. Specifically, brain magnetic resonance imaging (MRI) was performed on stroke and healthy control participants, with 86 stroke participants completing testing at baseline, 125 at 3 months, and 113 participants at 12 months, as well as 40 healthy control participants. Five brain measures — hippocampal volume, thalamic volume, total brain and hemispheric brain volume, and cortical thickness — were examined to evaluate whether brain atrophy rates differed between time points and groups.

Article Commentary: “Clot-Based Radiomics Predict a Mechanical Thrombectomy Strategy for Successful Recanalization in Acute Ischemic Stroke”

Aurora Semerano, MD

Hofmeister J, Bernava G, Rosi A, Vargas MI, Carrera E, Montet X, Burgermeister S, Poletti P-A, Platon A, Lovblad K-O, Machi P. Clot-Based Radiomics Predict a Mechanical Thrombectomy Strategy for Successful Recanalization in Acute Ischemic Stroke. Stroke. 2020;51:2488–2494.

Tools for predicting the success or the failure of reperfusion treatments in the acute setting of ischemic stroke are useful both to assist treatment decision-making and to guide the selection of the best device and reperfusion strategy. Multiple biomarkers and models, including clinical, biochemical, and radiological parameters, are currently under investigations with this purpose. Recently, multimodal analyses of the occlusive clot are receiving growing interest for the potential predictive value on reperfusion outcomes.

Hofmeister et al.(1) addressed this important issue in their recent article in Stroke. More specifically, the authors aimed at identifying the radiomic features of the occlusive clot on pre-treatment non-contrast CT scan, which may predict both first-attempt successful reperfusion with thromboaspiration (defined by modified Treatment in Cerebral Ischemia, mTICI 2b-3) and the number of maneuvers required to achieve successful reperfusion.

More Than Meets the Eye: Widespread White Matter Changes After Ischemic Stroke

Charlotte Zerna, MD, MSc

Egorova N, Dhollander T, Khlif SM, Khan W, Werden E, Brodtmann. Pervasive White Matter Fiber Degeneration in Ischemic Stroke. Stroke. 2020;51:1507–1513.

Studies have shown that ischemic stroke does not only lead to focal tissue destruction, but can also result in the remote loss of gray matter and disruption of functional connectivity. However, less is known about the remote and regional white matter degeneration after ischemic stroke. Prior studies have been limited by using diffusion-tensor imaging metrics that are non-specific voxel-averaged measures and can lead to erroneous interpretations in locations where white matter fibers are crossing. The objective of the study by Egorova et al. was, therefore, to examine white matter degeneration in a cohort of participants at 3 months post-infarct using a novel fixel-based analysis (fiber population within an MRI voxel). This method allowed the authors to assess complex microstructural fiber geometry in greater detail.

Participants with ischemic stroke (confirmed both clinically and radiologically) were recruited within 6 weeks of their index event at 3 hospitals in Melbourne, Australia. Both patients with first ever (85.6%) and recurrent ischemic stroke (14.4%) in any vascular territory and of any etiology were considered. Age-matched controls (that were also comparable in sex and education status) were selected from a database of volunteers who had previously undertaken MRI research at one of the recruiting hospitals. Of the 165 recruited participants who completed scanning at 3 months, complete usable MRI diffusion data were available for 104 stroke and 40 control participants and could be used for analysis after successfully undergoing pre-processing.

Article Commentary: “Cerebral Blood Flow Predicts the Infarct Core”

Adeola Olowu, MD

Amukotuwa S, Straka M, Aksoy D, Fischbein N, Desmond P, Albers G, et al. Cerebral Blood Flow Predicts the Infarct Core: New Insights From Contemporaneous Diffusion and Perfusion Imaging. Stroke. 2019;50:2783–2789.

The purpose of this study was to assess if cerebral blood flow (CBF) from perfusion studies could accurately estimate infarct core size in ischemic stroke patients during acute stroke management for appropriate thrombectomy triage. Relative cerebral blood flow (rCBF) accuracy would be determined by comparing infarct size to DWI of MRI.

Imaging data was assessed from the DEFUSE 2 and SENSE 3 studies. DEFUSE 2 (Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evaluation) evaluated if MRI can be used to determine which patients would most likely benefit from endovascular reperfusion. SENSE 3 (Sensitivity Encoding) compared DWI and CT perfusion to reliably detect ischemic core tissue, at risk tissue, and tissue at risk of hemorrhagic transformation. Between the two studies, 119 patients had both DWI and perfusion studies within 24 hours of symptoms onset. 

Relative CBF (rCBF) was divided into 12 thresholds (0.20-0.44), and each of those thresholds were compared to the corresponding DWI. rCBF threshold of 0.32 provided the best prediction of infarct core estimate with DWI. When applying an infarct core limit of 70 mL for thrombectomy, approximately 94% of patients were correctly triaged to the appropriate therapy.

Figure 1. Coregistered diffusion-weighted imaging (DWI) and processed perfusion-weighted imaging (PWI) images from a 66-year old man who had an acute right MCA M1 segment occlusion.
Figure 1. Coregistered diffusion-weighted imaging (DWI) and processed perfusion-weighted imaging (PWI) images from a 66-year old man who had an acute right MCA M1 segment occlusion.

FLAIR-rSI is Time, and Time is Brain, so FLAIR-rSI is Brain?

Lina Palaiodimou, MD

Cheng B, Boutitie F, Nickel A, Wouters A, Cho T-H, Ebinger M, et al. Quantitative Signal Intensity in Fluid-Attenuated Inversion Recovery and Treatment Effect in the WAKE-UP Trial. Stroke. 2019.

Advanced neuroimaging has already changed the scene in acute stroke treatment, allowing patients with unknown or extended time windows to receive recanalization therapies (intravenous thrombolysis, mechanical thrombectomy). The cornerstone of this recent breakthrough is the demonstration of viable brain tissue regardless of time elapsed since stroke onset. That was also the case in the WAKE-UP trial, which proved clinical benefit in alteplase-treated acute stroke patients with unknown time of onset, but clearly presenting salvageable brain tissue, as was demonstrated by diffusion-weighted imaging (DWI) – fluid-attenuated inversion recovery (FLAIR) mismatch.   

The study by Cheng et al. presents a post-hoc analysis of the WAKE-UP trial with the aim to associate quantitatively measured relative signal intensity in FLAIR (rSI-FLAIR) with the clinical outcomes of the treated patients. The objective of this study was rationalized by previous studies, which correlated rSI-FLAIR with time elapsed since stroke onset. That correlation was linear; higher rSI-FLAIR corresponded to longer time since stroke onset and, actually, when the clock was ticking, FLAIR was glowing. Consequently, Cheng et al. moved to the next logical reasoning that, since rSI-FLAIR is associated with time and time is associated with clinical outcomes, rSI-FLAIR may relate to clinical outcomes of alteplase-treated patients. 

Explicit Diagnostic Criteria: Gaining Ground in the Perpetual Struggle to Elucidate TIA

Matthew Maximillian Padrick, MD, BA

Dolmans LS, Lebedeva ER, Veluponnar D, van Dijk EJ, Nederkoorn PJ, Hoes AW, et al. Diagnostic Accuracy of the Explicit Diagnostic Criteria for Transient Ischemic Attack: A Validation Study. Stroke. 2019;50:2080–2085

The diagnosis of Transient Ischemic Attack (TIA) has remained one of the murkier diagnoses a physician can encounter, and yet it yields a disproportionately large impact on patient wellbeing. Diagnoses can be given haphazardly, say in a busy emergency department, for brief dizziness, confusion, tingling, or just not feeling quite right. I have seen a patient who was given the diagnosis after less than a minute of isolated whole body shivering. ED neurology consults are a luxury, not the rule, and “follow up with neuro” discharge action plans may never materialize.

With the growing acceptance and implementation of the POINT and CHANCE trials, these TIA diagnoses carry significant weight. Patients with no clear indication may suddenly find themselves on dual antiplatelet therapy, which is certainly not without risk. On the other end of the spectrum, missing the diagnosis significantly increases our patients’ risk of stroke within 6 months. There have been multiple scales created to help with risk stratification, and the quest for reliable biomarkers is well underway. 

White Matter Hyperintensity and Brain Atrophy — A New Imaging Measure of Cognitive Impairment

Kristina Shkirkova, BSc

Wyss A, Dawson J, Arba F, Wardlaw JM, Dickie DA, on behalf of the VISTA-Prevention Collaborators. “Combining Neurovascular and Neurodegenerative Magnetic Resonance Imaging Measures in Stroke.” Stroke. 2019; 50:1136-1139.

To characterize age and stroke-related tissue damage, the total small vessel disease score and the brain health index have recently been developed for clinical use. The total small vessel disease score combines presence of lacunes, microbleeds, and moderate to severe white matter hyperintensities (WMH) by visual scoring based on clinical imaging. The brain health index uses automatic processing of MRI scans to quantify visible injury from small vessel disease and brain atrophy. However, the total small vessel disease score is prone to granularity and measurement limitations, whereas the brain health index requires high-resolution T1, T2, T2 gradient echo, and fluid attenuated inversion recovery scans, which are not often available in routine clinical imaging.

The study by Wyss et al. argues that individual markers of cerebral small vessel disease and brain atrophy have limited potential to explain high proportion of variance in neurovascular and neurodegenerative disease. The authors propose to combine markers of white matter hyperintensity and cerebral atrophy, represented by cerebrospinal fluid (CSF) volume, into a single measure capable of more accurate predictions of cognitive impairment.

Infarct Growth in the Early Time Windows: The Time Paradox

Ravinder-Jeet Singh, MBBS, DM

Broocks G, Rajput F, Hanning U, Faizy TD, Leischner H, Schön G, et al. Highest Lesion Growth Rates in Patients With Hyperacute Stroke: When Time Is Brain Particularly Matters. Stroke. 2018;50:189–192.

Infarct growth has become a topic of intense discussion in the current endovascular era, mainly due to its likely impact on stroke care models. A core theme of these models is decision to transport or treat eligible patients immediately, but also to limit futile transfers (drip-and-ship patient) and futile recanalization (mothership patient). The big question is: Which patient will grow their infarct during transfer and thus become ineligible for intervention on arrival to a comprehensive stroke center (futile transfers), and who will grow their infarct after imaging to derive no or minimal benefit from recanalization (futile recanalization)? Various clinical and imaging predictors have been proposed to predict infarct growth, including age, time, collateral status, etc. The study by Broocks et al. suggests that time is an important determinant of infarct growth, but its relation to lesion growth is rather counterintuitive, with early presenters having higher infarct growth compared to late presenters.

A New Tool to Quantify Severity, Extent and Course of Focal Cerebral Arteriopathy of Childhood Could Be Used for Treatment Trials

Alejandro Fuerte, MD

Fullerton H, Stence N, Hills N, Jiang B, Amlie-Lefond C, Bernard T, et al. Focal Cerebral Arteriopathy of Childhood: Novel Severity Score and Natural History. Stroke. 2018

Focal cerebral arteriopathy (FCA) of childhood is an acute disease causing unilateral stenosis of the cerebral arteries. It appears to be caused by an inflammatory process, and corticosteroids are used in its treatment in the absence of clinical trial data. Because it is one of the most common causes of arterial ischemic stroke (AIS) in healthy children and it increases the risk of recurrent stroke, a Delphi consensus identified this issue as the highest priority for a clinical trial in the field of childhood stroke.

The main goal of Fullerton et al. was to develop a severity score for this disease (Focal Arteriopathy Childhood Severity Score; FCASS). For this they used data from the VIPS study (Vascular Effects of Infection in Pediatric Stroke), a large, international, prospective cohort study that enrolled 355 children (29 days to 18 years of age) with AIS and collected clinical, imaging data and serum samples.