American Heart Association

diagnosis and imaging

Author Interview: Seung-Hoon Lee, MD, PhD

Seung-Hoon Lee

Seung-Hoon Lee

A conversation with Seung-Hoon Lee, MD, PhD, Professor of Neurology, Seoul National University Hospital, about the role of the susceptibility vessel sign on SWI to predict stroke subtype and recanalization.

Interviewed by José G. Merino, MD, Associate Professor of Neurology, University of Maryland School of Medicine.

They will be discussing the paper, “Prediction of Stroke Subtype and Recanalization Using Susceptibility Vessel Sign on Susceptibility-Weighted Magnetic Resonance Imaging,” published in the June 2017 issue of Stroke.

Dr. Merino: Could you please briefly describe the study and summarize the key findings, putting them into context of what was known before you did the study?

Dr. Lee: I’m glad to talk about our research in this interview. Thrombi in the cerebral arteries appear hypointense on susceptibility-weighted MRI (SWMRI). We call them “the susceptibility vessel sign” (SVS). The methodological strength of this study is that SWI MRI is much more sensitive than GRE and thus can quantify the size of the SVS. In this study, we analyzed the relationship between the size of the SVS, the stroke mechanism, and whether successful recanalization occurred in patients receiving endovascular treatment. Cardiac emboli are large but fragile because they are rich in RBCs but have scant platelets. We hypothesized that because the SVS reflects the red blood cell component of the clot, patients with larger SVS are more likely to have a cardioembolic source and thus more likely to have successful recanalization. We found that as the SVS size increased, the probability of cardioembolic stroke was higher, but that SVS size did not show any positive or negative correlation with successful recanalization. This is probably due to the high recanalization rate with the stent-retrievers, irrespective of stroke etiology. No association between SVS size and recanalization can be partly explained by clot fragility in cardioembolic stroke.

Predicting Hemorrhagic Transformation Following tPA Using CT and CT Perfusion Images

Sami Al Kasab, MD

Batchelor C, Pordeli P, d’Esterre CD, Najm M, Al-Ajlan FS, Boesen ME, et al. Use of Noncontrast Computed Tomography and Computed Tomographic Perfusion in Predicting Intracerebral Hemorrhage After Intravenous Alteplase Therapy. Stroke. 2017

Intracerebral hemorrhage (ICH) is a known complication of intravenous alteplase. The rates of symptomatic intracerebral hemorrhage following intravenous alteplase administration have varied between 1-4% depending on the definition used and the study.

In this study, Drs. Connor et al analyze the association between multimodal CT imaging parameters, including NCCT hypo attenuation degree, vlCBV, impaired blood-brain barrier permeability surface product, clinical and laboratory data at baseline, early reperfusion status, and development of parenchymal hemorrhage (PH) on follow-up imaging. All patients received NCCT, CT angiography, and CT perfusion at baseline. A 24 to 48 hour scan (either NCCT or MRI) was obtained. Imaging analyses were performed by readers blinded to other imaging and patient outcomes. All NCCT were scored for ASPECTS scores, the degree of hypo attenuation within the ischemic region using a 3-point grading system. Functional parametric maps of cerebral blood flow (CBF), CBV, Tmax, and a modified CTP algorithm for permeability calculations were used.

Blood Biomarkers in Ischemic Stroke

Ilana Spokoyny, MD


Blood biomarkers are an active research interest, with the potential for predicting ischemic stroke via identification of novel risk pathways. The authors of this paper tested the associations between ischemic stroke and three blood markers: procalcitonin (PCT), copeptin, and midregional-pro-atrial natriuretic peptide (MRproANP). These biomarkers were chosen because they represent three different pathophysiological processes. Procalcitonin is associated with bacterial infections and was chosen with the hope of finding a link between infection and ischemic (especially non-cardioembolic) stroke. Copeptin is a hypothalamic stress hormone, which was chosen because chronic activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system may promote vascular risk factors. MRproANP was hypothesized to be a marker of hemodynamic dysfunction and thereby a potential marker of (especially cardioembolic) stroke.


A nested case-control study was performed among initially stroke-free patients enrolled in the Northern Manhattan Study (NOMAS). 172 cases of first ischemic stroke were compared to 344 randomly selected controls. Primary endpoint (occurrence of first ischemic stroke) was detected using phone calls and prospective monitoring of hospital admissions and discharges. Patients with intracerebral hemorrhage were excluded.

PCT levels in the blood may reflect ongoing subclinical inflammatory processes triggered by bacterial endotoxins. It is unclear why there was an association of PCT with specifically small vessel stroke subtype. MRproANP was associated with cardioembolic stroke subtype, which may represent cardiac pathology (which has also been linked to ANP) causing cardioembolic strokes. Interventions based on these associations must be validated in prospective clinical trials, but this is a strong first step in developing better risk models and blood-based diagnostic tools for ischemic stroke. If these are validated and incorporated into clinical practice, one could imagine using MRproANP to help distinguish cardioembolic from non-cardioembolic sources of cryptogenic stroke, or using procalcitonin as one of the factors helping to distinguish mild strokes or TIAs from mimics. 
The adjusted hazard ratios for new ischemic stroke comparing the highest to lowest quartiles of PCT and MRproANP were 1.9 (1.0-3.8) and 3.5 (1.6-7.5), respectively. Stroke etiology was determined using based on the TOAST criteria. High PCT levels (top quartile) were associated with small vessel stroke (HR 5.1, 1.4-18.7) and high MRproANP levels (top quartile) were associated with cardioembolic stroke (HR 16.3, 3.7-70.9). 


Relevance of Carotid Plaque Characteristics for Ischemic Stroke and Coronary Heart Disease


Citing the systemic nature of atherosclerosis, the authors of this paper studied the association between extracranial carotid atherosclerosis features and prior ischemic stroke (IS) and coronary heart disease (CHD). 

Patients were selected from the Rotterdam Study. Participants with at least 2.5mm of carotid intima media thickness (IMT) were eligible for this study. Of 3,795 eligible participants, 1,982 underwent MRI of bilateral carotid arteries. MRI was performed on 1.5-Tesla scanners with a carotid artery protocol. All plaques of at least 2mm of thickness were assessed for intraplaque hemorrhage (IPH), lipid core, and calcification. Additionally, wall thickness and degree of stenosis were determined. Participants’ history was queried for prior IS and CHD (non-fatal MI or myocardial revascularization). Covariates were age, sex, smoking status, lipid measurements, BMI, diabetes, and hypertension.

Binomial logistic regression was used to determine the association between individual plaque characteristics and history of IS and CHD. Men and women were examined separately.

One thousand seven hundred thirty-one participants were ultimately included. The mean age was 73 years, and 55% were male. A majority of patients had a history of smoking. IS and CHD were much more common in men, as were vascular risk factors. The mean carotid wall thickness was 3.6mm, and the mean degree of stenosis was 13%. IPH was present in 35%, lipid core in 41%, and calcification in 82%. In terms of outcomes, 105 had a history of IS, and 199 had a history of CHD.

In the overall population, in multivariate analysis, only degree of stenosis was associated with IS. For men, stenosis and IPH were associated with IS. In both the overall population and when stratified by sex, only carotid stenosis was associated with CHD. 

The key finding is that whereas plaque thickness or stenosis were associated with both IS and CHD, IPH was only associated with IS (in men). The dependence on prevalence data and the lack of clinical data (e.g. stroke laterality or mechanism) limit the conclusions that can be drawn from this study. However, this work may foreshadow and stimulate prospective, mechanistically enlightening studies that capitalize on the granularity of MRI data.

Intracranial Atherosclerosis and Coronary Atherosclerosis: Two Twigs from the Same Vascular Branch

Peggy Nguyen, MD

Chung J-W, Bang OY, Lee MJ, Hwang J, Cha J, Choi J-H, et al. Echoing Plaque Activity of the Coronary and Intracranial Arteries in Patients With Stroke. Stroke. 2016

Atherosclerosis is a diffuse process that can affect both the coronary and carotid arteries, but while previous studies have suggested a strong correlation between coronary atherosclerosis and extracranial carotid atherosclerosis, the correlation with intracranial atherosclerosis is less clear. Whereas the mechanism of myocardial infarction from coronary atherosclerosis is likely more similar to ischemic stroke caused by extracranial atherosclerosis, ischemic stroke caused by intracranial atherosclerosis typically falls into two etiologies: branch occlusive disease-type (B-type), where atherosclerosis occludes a perforating artery, versus coronary-type plaque rupture of plaque (C-type), where the atherosclerotic plaque ruptures, causing a shower of multiple embolic infarcts distally. This study attempts to characterize intracranial plaque phenotypes and correlate asymptomatic coronary artery disease (CAD) with intracranial atherosclerotic disease (ICAD) burden.


A total of 81 patients were included the final analysis, drawn from a population of patients admitted within 7 days of symptom onset for treatment of acute ischemic stroke with intracranial atherosclerosis. Patients who had known histories of coronary artery disease were excluded. B-type ICAS was differentiated from C-type ICAS in both anterior and posterior territory strokes. An ICAD score was calculated on the basis of intracranial atherosclerotic burden, with 0 points given for stenosis less than 50%, 1 point for stenosis of 50-99% and 2 points for an occlusion, with all involved intracranial vessels summed for a total score

Asymptomatic CAD was quite common, with a prevalence of just over 80% in the study population. The prevalence of asymptomatic CAD was relatively similar in both B-type and C-type ICAS groups (48% vs 52%) and, as might be expected, the burden of ICAD was positively correlated with the burden of CAD, although non-calcified coronary artery plaque morphology was independently associated with C-type ICAS. As non-calcified coronary plaque increased, remodeling also increased in the symptomatic arteries of patients with ICAS.

This study provides evidence of a positive relationship between coronary and intracranial atherosclerotic burden, and that coronary artery plaque composition (calcified vs non-calcified) might predict intracranial atherosclerosis morphology. The investigators suggest that this should prompt us as clinician to take a more holistic approach to the entire vascular system, rather than solely focus on, for example, the cerebral vasculature, or the coronary arteries. Certainly this might prompt the clinician to, when faced with a stroke patient with C-type ICAS, be more cognizant of the type of likely associated CAD burden, but a study evaluating whether this might also be predictive of acute coronary syndrome, would be of additional benefit.

Fractional Anisotropy Change in Acute Phase of Stroke and its Correlation with Motor Recovery at 3 Months

Qing Hao, MD, PhD


“Doctor, will my father move his right arm again? How much do you think he can recover from this stroke?” As stroke neurologists, we are often asked about the prognosis after the stroke and most time the answer would be, “I am not exactly sure”.
Neuroimaging, especially MRI brain, has been very helpful in prognostication. Previous studies performed on chronic stroke patients demonstrated integrity/ atrophy of cortical spinal tract (CST) and signals indicative Wallerian degeneration (WD) on MRI in the chronic phase closely correlated with motor outcome.

Any neuroimaging markers in the acute phase of stroke can predict motor outcome? CST lesion load (based on initial motor impairment, lesion size and location) and CST integrity still played important roles. When talking about CST integrity, we can’t ignore fractional anisotropy (FA), an imaging marker derived from diffusion tensor imaging, which quantifies the organization (e.g. degree of alignment) and integrity of white matter tracts.
In this article, the author focused on FA in acute phase—they sought to investigate if FA difference in acute phase can be detected and how it predict motor outcome measured by upper extremity Fugl-Meyer score at 3 months.

Retrospective analyses were performed on a prospectively collected cohort of 58 patients with first time ischemic hemispheric stroke. MRI was done within 80 hours after stroke onset. FA values were determined in two regions of interest for 50 patients: cerebral peduncle and a stretch of the CST caudal to each stroke lesion (Nearest-5-Slice – N5S).
The authors were able to detect subtle asymmetry of FA changes (lower FA in the ipsilesional CST), most significantly in the slice that was closest to the ischemic lesion, not in the cerebral peduncle. The slope of the FA laterality index for the nearest-5-slices showed a weak but significant prediction (R2=0.11, p=0,022) for 3-month UE-FM score in univariate analysis, not in multivariate analysis. Not surprisingly, initial UE-FM, weighted CTS lesion load and days of therapy were stronger predictors (R2 =0.69, 0.71 and 0.249 respectively, p< 0.001) for 3-months UE-FM score.
CST integrity may be a dynamic change and its predictive value for motor recovery may be different at various stages after stroke. We look forward to more precise prediction models that would help us answer those challenging prognostication questions.

Perfusion MRI in Perinatal Stroke

Russell Mitesh Cerejo, MD

Watson CG, Dehaes M, Gagoski BA, Grant PE, Rivkin MJ. Arterial Spin Labeling Perfusion Magnetic Resonance Imaging Performed in Acute Perinatal Stroke Reveals Hyperperfusion Associated With Ischemic Injury. Stroke. 2016


In their paper, the authors described a novel method to assess perfusion in perinatal strokes in the ischemic as well as penumbra tissue. 
They included subjects less than 28 days old at time of diagnosis, and included both arterial and venous infarcts. MRI was carried out on 3T scanners with arterial spin labeling (ASL) techniques used for non-contrast perfusion imaging. Out of 25 neonates that participated, 16 were males (64%). Median gestational age at birth was 38.7 weeks (range: 35.7-41.9), median (estimated) age at stroke was 1 day (i.e., second day of life) (range: 0-8), and median age at MRI was 3 days (range: 0-16). The median time from symptom onset to MRI acquisition was 2 days (range: 0-8).

Arterial ischemic stroke was present in 11 (44%), while venous infarction was found in 9 (36%). Five patients (20%) had both arterial and venous stroke. Hyperperfusion was seen in 73% of arterial ischemic strokes, 11% with venous stroke, and 80% with both. Hypoperfusion was observed in 33% with venous and none with arterial stroke. Perfusion was normal in 45% with venous and 20% with both. In nearly all patients presenting with clinical or electrographic seizures, EEG abnormalities were present in the same hemisphere as the stroke; this clinical feature did not differ by stroke type.

This study demonstrates that perfusion imaging can be obtained in neonates with acute stroke, and often reveals hyperperfusion in the infarct core. Penumbra in arterial infarcts is seldom found. Hyperperfusion may be due to post-stroke reperfusion or to neuronal hyperexcitability of stroke-associated seizure.

FLAIR Vascular Hyperintensities in Bordezone Strokes

Allison E. Arch, MD

Kim and colleagues investigated the clinical significance of FLAIR vascular hyperintensities in watershed strokes, and they tried to predict poor prognosis using these FLAIR changes as a marker of impaired hemodynamics.


Watershed, or borderzone, strokes represent 10% of all ischemic infarcts. The authors of this study defined 2 types of borderzone strokes: internal borderzone infarcts (IBZ), which are lesions between the deep and superficial perforating arterial territories of the MCA, and cortical borderzone infarcts (CBZ), which are between the MCA/ACA or the MCA/PCA territories. A patient was then considered FLAIR-positive he had 2 or more FLAIR vascular hyperintensities in his MCA territory on MRI, which were thought to have occurred prior to the stroke.

Eighty-seven consecutive patients with acute borderzone strokes were identified, 62 with CBZ and 55 with IBZ. Thirty of all included stroke patients were considered FLAIR-positive. The authors found that FLAIR vascular hyperintensities were associated with a more severe clinical presentation and a poorer clinical prognosis in patients with CBZ strokes, but not in patients with IBZ strokes. They concluded the presence of FLAIR vascular hyperintensities, “may help to identify CBZ-infarcted patients who require close observation and hemodynamic control.”
Their findings are interesting. The authors noted that the presumed pathogenesis of watershed strokes is microembolization in combination with hemodynamic disturbance. However, in patients with FLAIR vascular hyperintensities on MRI, there may be an additional hemodynamic-compromised insult during the stroke, which then leads to poorer outcomes. Kim and colleagues pointed out that in the CBZ group, those who had FLAIR vascular hyperintensities had similar sized DWI lesions to those patients who did not have FLAIR lesions. However, there were significant perfusion differences between the FLAIR-positive and FLAIR-negative groups, lending support to the concept that FLAIR vascular hyperintensities on MRI may signify that the patient is more influenced by hemodynamic instability than his FLAIR-negative counterpart.

It is unclear why this would be on the case in CBZ strokes but not in IBZ strokes. Further investigations are needed to help elucidate the importance of hemodynamics in borderzone strokes. 

Genetic Factors that Impact White Matter Hyperintensities Increase Risk of Lacunar Stroke

Jay Shah, MD

Traylor M, Rutten-Jacobs LCA,Thijs V, Holliday EG, Levi C, Bevan S, et al. Genetic Associations With White Matter Hyperintensities Confer Risk of Lacunar Stroke. Stroke. 2016

Small vessel disease (SVD) can lead to various pathologies including lacunar infarcts, hemorrhage and microbleeds but the underlying pathophysiological mechanism remains unknown. White matter hyperintensities (WMH) are increased in lacunar stroke suggesting a shared pathological mechanism. Furthermore, WMH and lacunar infarcts co-exist in patients with inherited forms of SVD such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Genome-wide association studies (GWAS) have identified multiple genetic variants associated with WMH. In this study, the authors evaluated the impact of common genetic variants associated with WMH on the risk of lacunar stroke in patients with lacunar strokes and controls.
The authors used a genetic risk score approach to determine if SNPs associated with WMH were associated with lacunar strokes along with cardioembolic and large vessel infarcts. Each subgroup included approximately 1300 patients and 9000 controls. Secondly, lacunar strokes were separated into WMH (n = 568) and without WMH (n=787) to test for association. WMH genetic risk score was associated with lacunar stroke in patients regardless of WMH status but not with cardioembolic or large vessel strokes. However, none of the WMH-associated SNPs met significance for association with lacunar stroke.

This study supports the known belief that features of cerebral SVD share pathophysiology. Interestingly, the risk of lacunar stroke remained in patients without significant WMH. This could potentially be to the effect of “time”, in that patients without WMH could possibly be younger and have not had accumulated SVD damage. Another possibility is that patients without WMH have an unknown protective mechanism that protects against WMH but not lacunar stroke. The latter would be interesting in that it would suggest differing pathological mechanism. The study had large number of patients and controls but a potential confounding variable is that control patients did not have MRI images raising the possibility that controls had lacunar strokes and/or WMH as such pathology can potentially be clinically “silent”. Nonetheless, this study highlights a shared pathophysiological process that underlies various manifestations of CVD. 


What Makes a Lacune?

Peggy Nguyen, MD

The lacune, often used interchangeably with the definition of a stroke of small vessel atherosclerotic etiology, is traditionally based on a size definition of no greater than 15 mm. It is a classic feature of cerebral small vessel disease. However, despite its prolific use in the stroke literature, the exact characteristics and morphological features of a lacune are not well defined. Here, the authors analyzed the shape of incident lacunes in CADASIL, a genetically inherited small vessel arteriopathy, to better define the lacune’s morphological features.

Fifty-seven CADASIL patients with incident lacunes were included in the study, encompassing 88 incident lacunes, only 18 of which were associated with symptoms. The most common locations for lacunes were in the centrum semiovale (n=30) and the basal ganglia (n=27). In spectral shape analysis, elongation and planarity were found to be the primary determinants of lacune shape and tended to align along perforating arteries. Although 15 mm is traditionally used as the upper size limit of a lacune, about 10% of lacunes, particularly when evaluated in planes other than axial, exceeded this size, whereas only 1 lacune was larger than 15 mm in the axial plane.

Not all lacunes are created the same, but there are certainly similarities, and this may have to do with the mechanisms by which they develop. The findings in this study confirm some generalizations of lacunes, such as the common locations, but also refutes some others, for instance, the size of lacunes, particularly when viewed in non-axial planes. These findings are also suggestive of a mechanism in which lacunes of chronic small vessel diseases develop secondary to factors related to vascular anatomy, rather than tract degeneration.