Predicting Stroke Recurrence in Occlusive Disease Using Noninvasive Quantitative Mapping of Cerebrovascular Reserve

HomeStrokeVol. 55, No. 3Predicting Stroke Recurrence in Occlusive Disease Using Noninvasive Quantitative Mapping of Cerebrovascular Reserve Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBPredicting Stroke Recurrence in Occlusive Disease Using Noninvasive Quantitative Mapping of Cerebrovascular Reserve Jean-Claude Baron Jean-Claude BaronJean-Claude Baron Correspondence to: Jean-Claude Baron, MD, ScD, Department of Neurology, Hôpital Sainte-Anne, GHU Paris Psychiatrie et Neurosciences, INSERM U1266, Université Paris-Cité, 1 rue Cabanis, Paris 75014, France. Email E-mail Address: [email protected] https://orcid.org/0000-0002-5264-2588 Department of Neurology, Hôpital Sainte-Anne, GHU Paris Psychiatrie et Neurosciences, FHU NeuroVasc, France. Université Paris Cité, Institut de Psychiatrie et Neurosciences de Paris, Inserm U1266, France. Originally published8 Feb 2024https://doi.org/10.1161/STROKEAHA.124.046235Stroke. 2024;55:622–624This article is a commentary on the followingIncreased Risk of Recurrent Stroke in Symptomatic Large Vessel Disease With Impaired BOLD Cerebrovascular ReactivityOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: February 8, 2024: Ahead of Print See related article, p 613Hemodynamic stroke related to chronic atherosclerotic occlusion or severe stenosis of an upstream cerebral artery is a well-defined entity characterized by its mechanism, namely reduced perfusion to a brain area not due to an acute thrombus.1 The diagnosis is based on characteristic, though nonspecific, clinical (eg, isolated upper limb paresis)1 and radiological (eg, watershed infarcts)2 features. Hemodynamic transient ischemic attacks (TIAs) are more difficult to diagnose, especially if brain imaging is normal, but some features, such as shaking-limb TIA on standing or amaurosis triggered by bright light, are very specific.3 Compromised hemodynamic reserve in the affected vascular territory as underlying pathophysiology was first documented by positron emission tomography (PET) in the form of chronic hypoperfusion with increased oxygen extraction fraction (misery perfusion)4 or, in the less severe stage, increased cerebral blood volume (reflecting autoregulatory vasodilatation).5 Reduced response to vasodilatory stimuli such as intravenously administered acetazolamide (Diamox) was subsequently documented using single-photon emission computed tomography (CT).6 Testing cerebrovascular reactivity (CVR) has become routine practice whenever hemodynamic stroke/TIA is suspected, as documenting compromised hemodynamics distal to a diseased artery confirms the diagnosis and guides patient management. Prospective studies have documented that the presence of impaired hemodynamics, and particularly of misery perfusion, carries a 4- to 12-fold higher risk of ipsilateral ischemic stroke recurrence despite best medical management.7–9 This has been the rationale behind the randomized trials of extracranial-intracranial arterial bypass, which, despite multiple reports of benefit in individual patients,10–12 have so far been neutral largely because of a high periprocedural risk of stroke,13–15 the mechanisms of which are still incompletely elucidated. Pending new trials with improved patient selection and surgical technique, extracranial-intracranial bypass is occasionally carried out as a last resort in cases of recurrent stroke despite best medical management, which should include appropriate use of antithrombotics given the likely compounding role of distal microemboli in a good fraction of hemodynamic strokes/TIAs.16 Likewise, intracranial angioplasty/stenting may be considered in specific cases despite the lack of evidence of benefit from randomized trials.Numerous techniques have been used to assess brain hemodynamics. Except perhaps in Japan, PET is not clinically available to assess brain perfusion but is the reference standard against which novel techniques have been validated. Less sophisticated perfusion imaging methods such as single-photon emission CT (initially with 133Xe and then with 99mTc-labeled tracers) or cold Xenon CT both before and after IV Diamox6 were widely used for 3 decades but largely went into disuse due to the cost of the tracers and complexity of the measurements (eg, 2 scans 24 hours apart in the case of single-photon emission CT) as well as the potential side effects of cold Xenon (confusion) or IV Diamox (TIA; possibly related to the intracranial hemodynamic steal). Transcranial Doppler with breath holding (as a proxy to CO2 administration,17 a long-known strong vasodilator) is noninvasive and easy to use, but the results are both operator and patient-dependent, and the technique does not provide 3-dimensional maps of CVR. CT-based perfusion imaging measures the dynamic transit of an iodinated intravascular contrast agent and is widely used to assess CVR, most commonly using cerebral blood volume or mean transit time (or its derivatives), which has been validated against PET.18 Magnetic resonance imaging (MRI)-based perfusion-weighted imaging, which implements the same approach as CT-based perfusion but uses noniodinated contrast agents, has been validated against PET in acute stroke19 but not formally yet in hemodynamic ischemia. Of note, the contrast agents used in CT-based perfusion or perfusion-weighted imaging may be contraindicated in case of allergy or renal failure. More recent noninvasive imaging techniques include MR-based noncontrast arterial spin labeling,20 which like oxygen-15 PET uses labeled water as a nearly ideal perfusion tracer, produces perfusion maps in absolute units of cerebral blood flow, has been validated against PET,21 and can be repeated after Diamox within minutes of baseline imaging. Awaiting formal validation for routine clinical application, another MR-based noninvasive technique, quantitative MR angiography, appears particularly promising to assess the posterior circulation.9Blood oxygen level-dependent (BOLD) MRI with CO2 challenge has recently emerged as a particularly attractive, easy-to-implement noninvasive method that has potentially wide clinical applications given the availability of MRI in routine practice and of the BOLD sequence on commercial scanners. It is based on the principle that changes in the BOLD signal reflect mismatching between perfusion and oxygen consumption and hence the oxygen extraction fraction. Using a vasodilatory challenge (inhaled CO2 most often), this technique has been shown to allow the assessment of the CVR in patients suspected of hemodynamic stroke and has been validated against PET in this context.22 This technique is particularly attractive as it produces high-resolution whole-brain (ie, including both the anterior and posterior circulations) 3-dimensional quantitative maps of CVR in %BOLD signal change/mm Hg CO2. Furthermore, controlling the CO2 challenge limits intersubject variability in response to CO2 inhalation and thus in eventual Paco2, which in turn permits reliable quantification of the CVR.22In the present issue of Stroke, van Niftrik et al23 report a novel study in a large sample (n=130) of patients with symptomatic anterior-circulation large-vessel disease that applied BOLD MRI with a device that enables a consistent vasoactive stimulus. Significantly impaired CVR was determined based on a cutoff derived from a sample of age-matched healthy subjects. Using this approach, they found that BOLD MRI was able to predict the risk of ischemic stroke recurrence. The adjusted hazard ratio for ischemic stroke recurrence was 10.7 in patients with versus without significantly impaired CVR, consistent with previous findings derived from more standard techniques.7–9 Although retrospective and hence potentially affected by hidden biases, this study elegantly demonstrates that BOLD-CVR MRI with standardized CO2 challenge is a clinically applicable technique to evaluate the risk of stroke recurrence in large-vessel occlusive disease and may advantageously replace techniques currently used in clinical routine. Licensing for routine clinical use the device used to standardize the CO2 stimulus is a necessary preliminary step.Disclosures NoneFootnotesFor Disclosures, see page 623.The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Correspondence to: Jean-Claude Baron, MD, ScD, Department of Neurology, Hôpital Sainte-Anne, GHU Paris Psychiatrie et Neurosciences, INSERM U1266, Université Paris-Cité, 1 rue Cabanis, Paris 75014, France. Email jean-claude.baron@inserm.frREFERENCES1. Klijn CJ, Kappelle LJ. Haemodynamic stroke: clinical features, prognosis, and management.Lancet Neurol. 2010; 9:1008–1017. doi: 10.1016/S1474-4422(10)70185-XCrossrefMedlineGoogle Scholar2. Momjian-Mayor I, Baron JC. The pathophysiology of watershed infarction in internal carotid artery disease: review of cerebral perfusion studies.Stroke. 2005; 36:567–577. doi: 10.1161/01.STR.0000155727.82242.e1LinkGoogle Scholar3. Persoon S, Kappelle LJ, Klijn CJ. 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Stroke. 2024;55:613-621 March 2024Vol 55, Issue 3 Advertisement Article InformationMetrics © 2024 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.124.046235PMID: 38328925 Originally publishedFebruary 8, 2024 KeywordsEditorialshemodynamicsischemic strokemagnetic resonance imagingpositron emission tomographyperfusionPDF download Advertisement SubjectsClinical StudiesHemodynamicsIschemiaMagnetic Resonance Imaging (MRI)