American Heart Association

diagnosis and imaging

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.

The Association of C-Reactive Protein and Amyloid Blood Biomarkers with Advanced Imaging Markers

Lin Kooi Ong, PhD

Hilal S, Ikram A, Verbeek MM, Franco OH, Stoops E, Vanderstichele H, et al. C-Reactive Protein, Plasma Amyloid-β Levels, and Their Interaction With Magnetic Resonance Imaging Markers. Stroke. 2018

The Rotterdam Study is a population-based prospective cohort study among middle age and elderly persons living in the Ommoord district in the city of Rotterdam, the Netherlands. In this study, Hilal et al. examined whether the levels of plasma C-reactive protein (CRP), an inflammation marker, are associated with Magnetic Resonance Imaging (MRI) markers such as lacunes, white matter hyperintensities, cerebral microbleeds, perivascular spaces, and atrophy of brain structures in a population of 2814 participants. Hilal and colleagues then measured the levels of plasma amyloid- β (Aβ) isoforms in a subsample of 736 individuals, and examined their interaction with CRP levels and MRI markers. The team observed higher levels of plasma CRP were associated with higher lacunar counts, larger volume of white matter hyperintensities, changes in microbleed counts, enlarged perivascular space and reduced gray matter volume. Further, the team found that effects such as lacunar counts, enlarged perivascular space and microbleed counts were augmented by an interaction between CRP and Aβ levels.

Stroke Mechanism Suggested by Thrombus Permeability on CT Angiography

Kara Jo Swafford, MD

Berndt M, Friedrich B, Maegerlein C, Moench S, Hedderich D, Lehm M, et al. Thrombus Permeability in Admission Computed Tomographic Imaging Indicates Stroke Pathogenesis Based on Thrombus Histology. Stroke. 2018

Mechanical thrombectomy for treatment of an acute ischemic stroke caused by a large vessel occlusion provides the possibility of histological study of the thrombus, which is composed of fibrin, platelets, red blood cells and white blood cells. Higher fibrin content is associated with a cardiogenic origin. Clot permeability or perviousness depends on its constituents and can be assessed by the quantity of contrast present within the thrombus on CT angiography (CTA).

Berndt et al. assessed the correlation between the histological composition of clot retrieved by mechanical thrombectomy and the perviousness of the clot on CTA. They hypothesized that clot perviousness could assist in determining the stroke pathogenesis, guiding clinical decisions related to secondary stroke prevention. They found that permeable thrombi consist of mainly fibrin-platelet conglomerations and fewer red blood cells and were associated with cardioembolic stroke. Conversely, they found that lower perviousness was associated with thrombi containing mostly red blood cells and were most likely of noncardioembolic origin.

In Search of an IV-tPA Biomarker for LVO

Richard Jackson, MD

Yoo J, Baek J-H, Park H, Song D, Kim K, Hwang IG, et al. Thrombus Volume as a Predictor of Nonrecanalization After Intravenous Thrombolysis in Acute Stroke. Stroke. 2018

Now that endovascular thrombectomy has been shown to be beneficial in large vessel occlusions, there is a question of distribution of resources and triage of patients. Yoo et al. recognized this need and began to look at a possible imaging biomarker for response to IV-tPA.

They began with a retrospective analysis of a CT-based thrombus cohort of 214 patients from three university hospitals between 2006 and 2009. Mean thrombus volume was found to be 129mm3 and density 53.5 HU with a median time to tPA of 52 minutes. Of the 214 patients, 162 (76%) failed to re-canalize, which was defined as TICI grade 1-2a. Using statistical analysis, the upper range of the calculated reference range was 181.9 mm3 thrombus volume, and, therefore, a cut-off volume of 200mm3 was determined to be optimal to predict non-recanalization.