Feature article

Using MRI of the brain to prevent stroke

By: Sridhar Nadamuni

Advances in magnetic resonance imaging (MRI) such as high-resolution vessel-wall imaging may be used in stroke prevention by identifying atherosclerotic plaques leading to ischemic stroke.[1] Imaging findings associated with plaque pathology in patients strongly indicated for treatment, suggest that high-resolution magnetic resonance imaging (HR-MRI) can be used to elucidate parameters of plaque inflammation that can be used as stand-alone predictors of stroke recurrence.[2]

High-resolution intracranial vessel-wall MRI: 3.0T versus 7.0T, a research system

Seven-tesla MRI has been found to exhibit the highest potential in determining the total impact of intracranial atherosclerosis through research, especially in elderly populations.[3] Although large differences in lesions were observed at both field strengths, the 7.0T MRI resulted in significantly higher number of visible lesions on the intracranial vessel wall compared with 3.0T MRI. In fact, most of the lesions in the walls of cerebral arteries were visible with 7.0T MRI. The lesions showed contrast enhancement. The increased signal-to-noise (SNR) and contrast-to-noise ratios (CNR) at higher field strengths provide a higher spatial resolution to highlight the arterial vessel walls.[4] This feature is important because intracranial atherosclerosis is considered as one of the primary etiological factors underlying ischemic stroke and transient ischemic attack (TIA), and has been shown to increase the risk of recurrent stroke.[5]

Non-invasive imaging modalities such as computed tomography (CT) angiography only highlight the lumen of the blood vessels rather than the vessel wall, which may underestimate the role of intracranial atherosclerosis in stroke.[6] By contrast, HR-MRI facilitates the detection of defects in intracranial vessel wall even before the luminal narrowing occurs. In fact, using a combination of high-resolution carotid MRI and 18F- fluorodeoxyglucose (FDG)-positron emission tomography (PET), it was possible to detect American Heart Association (AHA) type VI lesions in cryptogenic stroke occurring on the same side of the body.[7] HR-MRI has been used to reveal stroke induced by stenosis, for instance, occlusion of the middle cerebral or basilar artery in branch atheromatous disease, which is usually caused by non-stenotic atherosclerotic plaques that are hidden from the usual imaging techniques based on lumenography.[8]

HR-MRI is invaluable in delineating unstable and vulnerable plaques. Advanced imaging methodologies can identify patients at risk of stroke based on plaque features, lipid composition, and new blood vessel formation, for appropriate therapeutic intervention. HR-MRI can be used clinically for vessel-wall imaging and is considered as a dependable, non-invasive marker of unstable atherosclerotic plaques occurring extra- and intracranially.1

MRI-based triage for acute stroke therapy: Recent advances

In addition to elucidating stroke pathophysiology involving the ischemic center, perfusion, collaterals, clot, and blood–brain barrier, MRI has now been used to predict patients’ response to early endovascular thrombectomy (EVT), and to identify candidates for delayed intervention.[9]

According to the 2018 Stroke Management Guidelines, computed tomography perfusion (CTP) or diffusion-weighted imaging/magnetic resonance perfusion (DWI/MRP) scans are indicated for patients presenting more than 6 h after their ischemic event, and those with large vessel occlusion (LVO), for prompt intervention of all eligible patients with EVT.[10] Compared with non-contrast computed tomography (CT), computed tomography angiography (CTA) and computed tomography perfusion (CTP), advances in MRI have led to short (less than 7 min) acquisition time with automated and rapid post-processing. A triage based on MRI has been shown to increase the efficacy of EVT, even in ineligible patients, for instance, those with wake-up strokes. MRI in which fluid attenuation inversion recovery (FLAIR) sequences were combined with DWI have been used to ascertain lesion age and a DWI-positive/FLAIR-negative mismatch in patients within 4.5 h of stroke onset involving the middle cerebral artery, with strongly predictive values and enhanced functional outcomes.[11],[12] If MRI revealed healthy collaterals, the 7-day infarct growth and the 90-day modified Rankin score presented a favorable outcome for the patient.[13]

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Implications for stroke screening

Compared with CTP that requires additional imaging and post-processing time, a rapid MRI based on DWI, FLAIR, gradient echo, and MR angiography, and MRP can be performed in 6 min, which is comparable to any CT intervention for acute stroke screening.[14]

In addition to revealing a perfusion-diffusion mismatch and highlighting regions in the penumbra and those containing irreversible lesions, MRI provides comprehensive information of the blood–brain barrier (BBB), collaterals, age of the lesion, and clot.1

Given the risk of treatment complications arising from poor collaterals, a prospective observational study (Clinical trials identifier NCT02668627) is currently testing the feasibility of MRI-based collateral imaging to predict the response to EVT in patients with acute ischemic stroke. Early infarct grow rate and eligibility are under investigation depending on the MRI-based collateral grades determined prior to treatment.

MRI has been used to evaluate clots with increased specificity and accuracy better than CT images. Images showing blooming artifacts in gradient-echo images have been linked to cardioembolic stroke.[15]

BBB defects can be detected based on MRI permeability images, which facilitate the screening of patients at risk of bleeding in stroke, with high specificity and such images can be used in clinical practice.[16]

Machine-learning strategies have facilitated the integration of information obtained from several MRI sequences to improve the triage for early vascularization. For example, in addition to combining DWI and FLAIR data for effective screening of patients within hours of symptom onset, machine learning has been shown to enhance the accuracy of prediction of symptom onset based on collaterals or perfusion.[17]

Conclusion

Advances in multimodal MRI suggest that physicians can leverage cutting-edge technologies such as HR-MRI for rapid data acquisition and automated post-processing independently or in conjunction with machine learning and artificial intelligence-based decision algorithms, for stroke prevention. However, appropriate and controlled clinical studies are still needed before the image-based algorithms can be incorporated into routine clinical practice for early revascularization of patients with stroke.

 

 

REFERENCES

[1] Recent Advances in Primary and Secondary Prevention of Atherosclerotic Stroke.Journal of Stroke.doi:10.5853/jos.2018.00773. Accessed August 16, 2018.

[2] Abstract 147: Plaque Inflammation is Associated with Early Cerebral Ischemic Events in Symptomatic Carotid Stenosis. Stroke. 2018;49:A147. Accessed August 16, 2018

[3] High-resolution Intracranial Vessel Wall MRI in an Elderly Asymptomatic Population: Comparison of 3T and 7T. European Radiology.doi:10.1007/s00330-016-4483-3.Accessed August 16, 2018.

[4] Multicontrast-Weighted Magnetic Resonance Imaging of Atherosclerotic Plaques at 3.0 and 1.5 Tesla: Ex-vivo Comparison with Histopathologic Correlation. European Radiology. https://link.springer.com/article/10.1007%2Fs00330-006-0265-7.Accessed August 16, 2018.

[5] Intracranial Atherosclerosis. Lancet. doi: 10.1016/S0140-6736(13)61088-0. Accessed August 16, 2018.

[6] Evaluating Intracranial Atherosclerosis rather than Intracranial Stenosis. Stroke. doi: 10.1161/STROKEAHA.113.002491. Accessed August 16, 2018.

[7] High-Risk Plaque Features can be Detected in Non-stenotic Carotid Plaques of Patients with Ischaemic Stroke Classified as Cryptogenic using Combined (18)F-FDG PET/MR imaging. European Journal of Nuclear Medicine and Molecular Imaging.doi: 10.1007/s00259-015-3201-8. Accessed August 16, 2018.

[8] Intracranial Atherosclerosis: From Microscopy to High-Resolution Magnetic Resonance Imaging.

Journal of Stroke.doi: 10.5853/jos.2016.01956.

[9] Multimodal MRI-Based Triage for Acute Stroke Therapy: Challenges and Progress.Frontiers in Neurology.doi:10.3389/fneur.2018.00586.Accessed August 16, 2018.

[10] 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.

Stroke. doi: 10.1161/STR.0000000000000158.Accessed August 16, 2018.

[11] Negative Fluid-Attenuated Inversion Recovery Imaging Identifies Acute Ischemic Stroke at 3 hours or less. Annals of Neurology.doi: 10.1002/ana.21651.Accessed August 16, 2018.

[12] DWI-FLAIR Mismatch for the Identification of Patients with Acute Ischaemic Stroke within 4·5 h of Symptom Onset (PRE-FLAIR): a Multicentre Observational Study. The Lancet Neurology. doi: 10.1016/S1474-4422(11)70192-2. Accessed August 16, 2018.

[13] A Novel Magnetic Resonance Imaging Approach to Collateral Flow Imaging in Ischemic stroke. Annals of Neurology. doi: 10.1002/ana.24211.Accessed August 16, 2018.

[14] Six-minute Magnetic Resonance Imaging Protocol for Evaluation of Acute Ischemic Stroke: Pushing the Boundaries. Stroke. doi: 10.1161/STROKEAHA.114.005305.August 16, 2018.

[15] Prediction of Stroke Subtype and Recanalization Using Susceptibility Vessel Sign on Susceptibility-Weighted Magnetic Resonance Imaging.Stroke. doi: 10.1161/STROKEAHA.116.016217. Accessed August 16, 2018.

[16] Multi-center Prediction of Hemorrhagic Transformation in Acute Ischemic Stroke using Permeability Imaging Features. Magnetic Resonance Imaging. doi: 10.1016/j.mri.2013.03.013. Accessed August 16, 2018.

[17] Prediction of Stroke Onset Is Improved by Relative Fluid-Attenuated Inversion Recovery and Perfusion Imaging Compared to the Visual Diffusion-Weighted Imaging/Fluid-Attenuated Inversion Recovery Mismatch.Stroke. doi: 10.1161/STROKEAHA.116.013903.Accessed August 16, 2018.