American Heart Association

diagnosis and imaging

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.

Article Commentary: “Resting-State Functional Connectivity Magnetic Resonance Imaging and Outcome after Acute Stroke”

Alexis N. Simpkins, MD, PhD

Puig J, Blasco G, Alberich-Bayarri A, Schlaug G, Deco G, Biarnes C, et al. Resting-State Functional Connectivity Magnetic Resonance Imaging and Outcome After Acute Stroke. Stroke. 2018

Many ischemic stroke patients will have residual disability from their stroke even if they receive thrombolysis or endovascular therapy. In fact, stroke is and is projected to continue to be one of the leading causes of long-term disability in adults. Identifying tools that can be used to accurately predict expected stroke recovery can change the way the patient is medically managed and can be used as an outcome measure in clinical trials. Changes in NIHSS, infarct volume, and stroke lesion have been shown to predict early neurologic outcome, but there are still limitations with each of these predictors. As a result, there are continued efforts to provide more sensitive and specific predictive models. Here, the authors assessed whether resting state-functional MRI (rs-fMRI) is associated with projected neurologic outcome at 90 days and can be combined with other frequently used predictors to improve accuracy. The selection of rs-fMRI was supported by previous studies that demonstrated an association between resting state and task-oriented functional connectivity and previous reports of the role of interhemispheric connectivity in stroke recovery.

Collaterals vs. Time in the Natural History of Acute Ischemic Stroke

Raffaele Ornello, MD

Vagal A, Aviv R, Sucharew H, Reddy M, Hou Q, Michel P, et al. Collateral clock is more important than time clock for tissue fate – A natural history study of acute ischemic strokes. Stroke. 2018

The endovascular treatment of ischemic stroke is beneficial up to 24 hours from symptom onset, provided that neuroimaging studies show the presence of ischemic penumbra, i.e., the hypoperfused brain region which has not progressed to infarction. Over time, the ischemic penumbra progresses to infarction, thus limiting the possibility of treating ischemic stroke; however, current literature suggests that the presence of robust collateral vessels delays that progression.

Tick Tock Goes the Collateral Clock

Houman Khosravani, MD, PhD

Vagal A, Aviv R, Sucharew H, Reddy M, Hou Q, Michel P, et al. Collateral Clock Is More Important Than Time Clock for Tissue Fate: A Natural History Study of Acute Ischemic Strokes. Stroke. 2018

“We hold these truths to be self-evident” is stated in the Declaration of Independence, and some say that with the passage of time, all becomes self-evident. Thus, what is the impact of time, and what is the truth behind the function and abundance of collateral circulation? These answers are critical to the late-window management of acute stroke. The topic will be one that keeps on giving, and an important contribution to this topic comes from a recent paper by Vagal et al.

In both early and extended time-windows brought about by DAWN and DEFUSE 3, the presence and functional capacity of robust collaterals has become uniquely important. The ischemic penumbra can persist for prolonged periods of time (up to 48 hrs), and its survival rests in part with the collateral circulation. The ability to assess this important aspect of tissue health is key in the evolution of thinking that is taking place: a move from time-window to tissue-health window. At the forefront of this assessment is perfusion imaging — in the case of this research, using CT perfusion. Understanding how time affects the natural history of the penumbra stands to inform assessment and decision-making in the era of EVT for patients within 24 hrs of symptom onset. Vagal et al. explore time from stroke onset and infarct growth in untreated acute ischemic stroke patients within this time window with the purpose of understanding how collaterals affect this evolution. However, it is important to note that data in this study were collected in the era of TPA first up to 3 hrs, then up to 4.5 hrs, and IA-TPA up to six hours (spanning 2003-2011) — thus, prior to the current EVT era. Nonetheless, patients who met inclusion criteria did not receive any therapy allowing for assessment of the penumbra’s natural history.

Ischemic Penumbra and the Race Against Time. Or Is It?

Kara Jo Swafford, MD

Vagal A, Aviv R, Sucharew H, Reddy M, Hou Q, Michel P, et al. Collateral Clock Is More Important Than Time Clock for Tissue Fate: A Natural History Study of Acute Ischemic Strokes. Stroke. 2018

The ischemic penumbra represents hypo-perfused tissue at risk of infarction if cerebral blood flow is not restored and may persist for hours after onset of ischemia. Progression from penumbra to infarction may be delayed due to the presence of collateral circulation. The 2018 American Heart Association acute ischemic stroke guidelines, in part based on the results of the DAWN and DEFUSE 3 trials, support the use of perfusion imaging for identifying patients with potentially salvageable tissue to help in selecting appropriate candidates for mechanical thrombectomy. Limited data exists on penumbra characteristics in patients with untreated acute ischemic stroke compared to those receiving reperfusion therapy within a delayed time window (i.e., up to 24 hours after stroke onset). Vagal et al designed a multicenter retrospective cross-sectional study to investigate how time from stroke onset may affect penumbral salvage and infarct growth in untreated acute ischemic stroke patients within the first 24 hours, including the role of collaterals.

More Than Meets the MRI: Texture Analysis Shows Normal Appearing White Matter is Not So Normal in SVD, Predicts Cognitive Impairment and Decline

Danny R. Rose, Jr., MD

Tozer DJ, Zeestraten E, Lawrence AJ, Barrick TR, Markus HS. Texture Analysis of T1-Weighted and Fluid-Attenuated Inversion Recovery Images Detects Abnormalities That Correlate With Cognitive Decline in Small Vessel Disease. Stroke. 2018

Cerebral small vessel disease (SVD) is a well-established but relatively poorly understood cause of lacunar stroke and vascular dementia. While the complex structural changes underpinning this disease process have yet to be fully elucidated, several MRI imaging markers have been identified in association with SVD, including white matter hyperintensities (WMH), cerebral microbleeds, and evidence of lacunar infarction. While these imaging markers have been useful in assessing severity of disease, they are less strongly associated with cognitive impairment. One particular area of interest as further imaging research into SVD has progressed is the so-called “normal appearing white matter” (NAWM), specifically the areas of white matter on traditional MRI that do not show the typical T2/FLAIR hyperintense changes.