American Heart Association

diagnosis and imaging

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.

In Search for a Potential Biomarker for Small Vessel Disease: Is Plasma Aβ Level the Answer?

Shashank Shekhar, MD, MS
@Artofstroke

van Leijsen EMC, Kuiperij HB, Kersten I, Bergkamp MI, van Uden IWM, Vanderstichele H, et al. Plasma Aβ (Amyloid-β) Levels and Severity and Progression of Small Vessel Disease. Stroke. 2018

Leukoaraiosis, along with microbleeds and lacunes, are one of the most commonly encountered findings after a brain imaging in patients with multiple vascular risk factors. These changes are a result of small vessel disease (SVD). White matter disease is considered as a potential imaging marker for the development of dementia. Apart from traditional risk factors, e.g., hypertension, diabetes, etc., Aβ (amyloid β) has been proposed as an additional contributor to SVD. To investigate the association of plasma Aβ levels with severity and progression of SVD, the authors studied 487 participants in a prospective cohort RUN DMC study (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort).

Using MRI-based Techniques for Easier Recognition of Hemodynamic Failure in Chronic Cerebrovascular Steno-Occlusive Disease

Gurmeen Kaur, MBBS
@kaurgurmeen

Fierstra J, van Niftrik C, Warnock G, Wegener S, Piccirelli M, Pangalu A, et al. Staging Hemodynamic Failure With Blood Oxygen-Level–Dependent Functional Magnetic Resonance Imaging Cerebrovascular Reactivity: A Comparison Versus Gold Standard (15O-)H2O-Positron Emission Tomography. Stroke. 2018

A major challenge faced by vascular neurologists and neuro-radiologists is accurately identifying the subset of patients with chronic cerebrovascular steno-occlusive disease, predicting those that have a propensity to develop hemodynamic failure and, as a result, have an increased risk of stroke.

Over the past few years, with development of imaging technology, multiple CT and MRI-based techniques have been developed to assess the degree of hemodynamic failure. Cerebral blood flow measurement using 15O PET scan has been recognized as the gold standard. There is a baseline measurement followed by a second scan with acetazolamide (Diamox) challenge.

Large Core at Presentation Does Not Essentially Translate Into Poor Outcomes, May Be Amenable to Treatment in Select Patients

Kaustubh Limaye, MD
@kaustubhslimaye

Gautheron V, Xie Y, Tisserand M, Raoult H, Soize S, Naggara O, et al. Outcome After Reperfusion Therapies in Patients With Large Baseline Diffusion-Weighted Imaging Stroke Lesions: A THRACE Trial (Mechanical Thrombectomy After Intravenous Alteplase Versus Alteplase Alone After Stroke) Subgroup Analysis. Stroke. 2018

The treatment landscape of acute ischemic stroke secondary to large vessel occlusion changed significantly in 2015 with the publication of 5 clinical trials that compared intravenous alteplase (IV t-pA) with IV t-pA and intra-arterial therapy (IAT). These clinical trials showed unequivocal benefit in reducing morbidity with the ESCAPE trial even showing mortality benefit. A similar trial conducted at 26 centers in France, THRACE (mechanical thrombectomy after intravenous alteplase versus alteplase alone after stroke) randomized 414 acute stroke patients with large vessel occlusion in either arm (IV t-PA vs IV tPA + IAT). 42 % of patients (IV tPA alone) vs. 53% (IV tPA +IAT) achieved functional independence [OR-1.55,95%CI 1.05-2.30; p-0.028], supporting data from the previous clinical trials. As this study was designed before the results of the IMS-III were published, it included patients treated within 4 hours of symptom onset. Other inclusion criteria were age 18-80 years, NIHSS 10-25, both anterior and posterior circulation and initiation of IAT within 5 hours.

Optical Coherence Tomography: New Insights into Cerebral Vasculature

Aristeidis H. Katsanos, MD

Chen CJ, Kumar JS, Chen SH, Ding D, Buell TJ, Sur S, et al. Optical Coherence Tomography: Future Applications in Cerebrovascular Imaging. Stroke. 2018

Optical coherence tomography (OCT) uses low-coherence interferometry to produce two-dimensional images of optical scattering with promising clinical and research applications in the evaluation of vasculature in different regions and settings. Despite an imaging depth of only a few millimeters, OCT can produce significantly higher resolution images than ultrasound due to the inherent properties of light waves to provide higher quality transverse imaging compared to sonic waves.