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Routine clinical evaluation of cerebrovascular reserve capacity using carbogen in patients with intracranial stenosis.

ABSTRACT: A promising method for identifying hemodynamic impairment that may serve as a biomarker for stroke risk in patients with intracranial stenosis is cerebrovascular reactivity (CVR) mapping using noninvasive MRI. Here, abilities to measure CVR safely in the clinic using hypercarbic hyperoxic (carbogen) gas challenges, which increase oxygen delivery to tissue, are investigated.In sequence with structural and angiographic imaging, blood oxygenation level-dependent carbogen-induced CVR scans were performed in patients with symptomatic intracranial stenosis (n=92) and control (n=10) volunteers, with a subgroup of patients (n=57) undergoing cerebral blood flow-weighted pseudocontinuous arterial spin labeling CVR. Subjects were stratified for 4 substudies to evaluate relationships between (1) carbogen and hypercarbic normoxic CVR in healthy tissue (n=10), (2) carbogen cerebral blood flow CVR and blood oxygenation level-dependent CVR in intracranial stenosis patients (n=57), (3) carbogen CVR and clinical measures of disease in patients with asymmetrical intracranial atherosclerotic (n=31) and moyamoya (n=29) disease, and (4) the CVR scan and immediate and longer-term complications (n=92).Noninvasive blood oxygenation level-dependent carbogen-induced CVR values correlate with (1) lobar hypercarbic normoxic gas stimuli in healthy tissue (R=0.92; P<0.001), (2) carbogen-induced cerebral blood flow CVR in patients with intracranial stenosis (R=0.30-0.33; P<0.012), and (3) angiographic measures of disease severity both in atherosclerotic and moyamoya patients after appropriate processing. No immediate stroke-related complications were reported in response to carbogen administration; longer-term neurological events fell within the range for expected events in this patient population.Carbogen-induced CVR elicited no added adverse events and provided a surrogate marker of cerebrovascular reserve consistent with intracranial vasculopathy.

SUBMITTER: Donahue MJ

PROVIDER: S-EPMC4118584 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Routine clinical evaluation of cerebrovascular reserve capacity using carbogen in patients with intracranial stenosis.

Donahue Manus J MJ Dethrage Lindsey M LM Faraco Carlos C CC Jordan Lori C LC Clemmons Paul P Singer Robert R Mocco J J Shyr Yu Y Desai Aditi A O'Duffy Anne A Riebau Derek D Hermann Lisa L Connors John J Kirshner Howard H Strother Megan K MK

Stroke 20140617 8

<h4>Background and purpose</h4>A promising method for identifying hemodynamic impairment that may serve as a biomarker for stroke risk in patients with intracranial stenosis is cerebrovascular reactivity (CVR) mapping using noninvasive MRI. Here, abilities to measure CVR safely in the clinic using hypercarbic hyperoxic (carbogen) gas challenges, which increase oxygen delivery to tissue, are investigated.<h4>Methods</h4>In sequence with structural and angiographic imaging, blood oxygenation level ...[more]

PMID: 24938845

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Project description:PurposeTo project and compare the lifetime health benefits, health care costs, and incremental cost-effectiveness of a decision rule based on assessment of cerebrovascular reserve (CVR) compared with medical therapy and immediate revascularization in asymptomatic patients with carotid artery stenosis for prevention of stroke.Materials and methodsThe three strategies compared included immediate revascularization (carotid endarterectomy) and ongoing medical therapy (with antiplatelet, statin, and antihypertensive agents plus lifestyle modification), medical therapy-based treatment with revascularization only for patients who progressed, and use of a CVR-based decision rule for treatment in which patients with CVR impairment undergo immediate revascularization and all others receive medical therapy. A decision analytic model was developed to project lifetime quality-adjusted life years (QALYs) and costs for asymptomatic patients with carotid stenosis with 70%-89% carotid luminal narrowing at presentation. Risks of clinical events, costs, and quality-of-life values were estimated on the basis of those in published sources. The analysis was conducted from a health care system perspective, with health and cost outcomes discounted at 3%. Results Total costs per person and lifetime QALYs were lowest for the medical therapy-based strategy ($14 597, 9.848 QALYs), followed by CVR testing ($16 583, 9.934 QALYs) and immediate revascularization ($20 950, 9.940 QALYs). The incremental cost-effectiveness ratio for the CVR-based strategy compared with the medical therapy-based strategy was $23 000 per QALY and for the immediate revascularization versus the CVR-based strategy was $760 000 per QALY.Resultswere sensitive to variations in model inputs for revascularization costs and complication risks and baseline stroke risk.ConclusionCVR testing can be a cost-effective tool to identify asymptomatic patients with carotid stenosis who are most likely to benefit from revascularization.

Project description:Background and purposeLoss of hemodynamic reserve in intracranial cerebrovascular disease reduces blood oxygenation level-dependent activation by fMRI and increases asymmetry in MTT measured by provocative DSC perfusion MR imaging before and after vasodilation with intravenous acetazolamide. The concordance for detecting hemodynamic reserve integrity has been compared.Materials and methodsPatients (n = 40) with intracranial cerebrovascular disease and technically adequate DSA, fMRI and provocative DSC perfusion studies were retrospectively grouped into single vessels proximal to and distal from the circle of Willis, multiple vessels, and Moyamoya disease. The vascular territories were classified as having compromised hemodynamic reserve if the expected fMRI blood oxygenation level-dependent activation was absent or if MTT showed increased asymmetry following vasodilation. Concordance was examined in compromised and uncompromised vascular territories of each group with the Fischer exact test and proportions of agreement.ResultsExtensive leptomeningeal collateral circulation was present in all cases. Decreased concordance between the methods was found in vascular territories with stenosis distal to but not proximal to the circle of Willis. Multivessel and Moyamoya diseases also showed low concordance. A model of multiple temporally displaced arterial inputs from leptomeningeal collateral flow demonstrated that the resultant lengthening MTT mimicked compromised hemodynamic reserve despite being sufficient to support blood oxygenation level-dependent contrast.ConclusionsDecreased concordance between the 2 methods for assessment of hemodynamic reserve for vascular disease distal to the circle of Willis is posited to be due to well-developed leptomeningeal collateral circulation providing multiple temporally displaced arterial input functions that bias the perfusion analysis toward hemodynamic reserve compromise while blood oxygenation level-dependent activation remains detectable.

Dataset Information

Routine clinical evaluation of cerebrovascular reserve capacity using carbogen in patients with intracranial stenosis.

Publications

Routine clinical evaluation of cerebrovascular reserve capacity using carbogen in patients with intracranial stenosis.

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