Characterizing Hemodynamic Compensation and Stroke Risk in Stenosis Patients

描述（由申请人提供）：本研究的总体目的是评估症状性颅内（IC）狭窄闭塞性疾病患者卒中风险与血流动力学补偿策略之间的关系，使用新型3.0 T MRI方案进行测量。最近的研究表明，有症状的IC动脉狭窄患者的2年缺血性卒中发生率较高。IC狭窄患者的治疗包括血管成形术、IC支架植入术或旁路术的血运重建，然而，识别最有可能从这些更积极的干预中获益的患者，而不是单独的医疗管理，一直存在问题。可能需要准确测量血流动力学损害，以更好地定义卒中风险并指导治疗决策。具体而言，在脑灌注压（CPP）受损的IC狭窄患者中，血流动力学受损的程度反映了血管系统增加动脉脑血容量（aCBV）和/或形成侧支以补充脑血流量（CBF）的自动调节能力。CBF侧支化和aCBV自动调节的流行被假设为与卒中风险唯一相关;然而，这种相关性的程度一直存在争议。对卒中风险进行分层的关键障碍在于缺乏i）测量具有高特异性的多种血流动力学因素的方法和（ii）能够监测损伤纵向进展的无创方法。我们已经证明了相对较新的无创MRI方法在评估脑血管反应性（CVR）、aCBV和侧支CBF方面的临床实用性。我们假设通过对这些参数的集体测量可以更全面地显示中风风险。因此，我们建议实施一种新的、经验证的血流动力学MRI方案，以评估IC狭窄患者的组织水平损伤和补偿策略。使用一种集体方法，结合测量多个脑区的侧支CBF、aCBV和CVR，结合将上述变量作为可能的预后因素的统计模型，我们将量化两年卒中风险与血流动力学代偿机制相关的程度。本研究的非侵入性和多方面的范围旨在扩大诊断卒中的基础设施，并阐明这一高危人群中卒中的新血流动力学预后指标。 公共卫生相关性：最近的研究表明颅内动脉狭窄患者的卒中发生率较高，但关于如何最好地管理这些患者的报告相互矛盾。为了更好地了解这些患者的卒中风险，我们建议应用新的非侵入性磁共振成像方法，以获得更全面的测量组织活力和血管代偿策略在这一高危人群中的流行程度。这项研究的结果预计将提供有关大脑补偿动脉狭窄的机制的新信息，并描述这些机制与中风风险之间的关系，以减少中风和长期残疾的过度目标。

DESCRIPTION (provided by applicant): The overall aim of this work is to assess the relationship between stroke risk and hemodynamic compensation strategies, as measured using a novel 3.0 Tesla MRI protocol, in patients with symptomatic intracranial (IC) steno-occlusive disease. Recent studies have shown high two-year ischemic stroke rates in symptomatic patients with IC arterial stenosis. Therapy for IC stenosis patients includes revascularization with angioplasty, IC stenting, or bypass, however identification of patients most likely to benefit from these more aggressive interventions, rather than medical management alone, has been problematic. Accurate measurements of hemodynamic compromise are likely required to better define stroke risk and guide treatment decisions. Specifically, in IC stenosis patients with compromised cerebral perfusion pressure (CPP), the extent of hemodynamic compromise reflects the autoregulatory capacity of vasculature to increase arterial cerebral blood volume (aCBV) and/or develop collaterals to supplement cerebral blood flow (CBF). The prevalence of CBF collateralization and aCBV autoregulation has been hypothesized to correlate uniquely with stroke risk; however the extent of this correlation has been debated. The critical barrier to stratifying stroke risk rests with a lack of i) methodology for measuring multiple hemodynamic factors with high specificity and (ii) noninvasive approaches capable of monitoring longitudinal progression of impairment. We have demonstrated the clinical utility of relatively new, noninvasive MRI approaches for assessing cerebrovascular reactivity (CVR), aCBV, and collateral CBF. We hypothesize that stroke risk can be more completely evinced from collective measurements of these parameters. Therefore, we propose to implement a novel, validated hemodynamic MRI protocol to assess tissue-level impairment and compensation strategies in patients with IC stenosis. Using a collective approach combining measurements of collateral CBF, aCBV and CVR in multiple brain regions, in conjunction with a statistical model incorporating the above variables as possible prognostic factors, we will quantify the extent to which two-year stroke risk is associated with hemodynamic compensation mechanisms. The noninvasive and multi-faceted scope of this investigation is intended to expand the diagnostic stroke infrastructure and elucidate new hemodynamic prognostic indicators of stroke in this high-risk population. PUBLIC HEALTH RELEVANCE: Recent studies have shown high stroke rates in patients with intracranial arterial stenosis, however conflicting reports regarding how best to manage these patients. To better understand stroke risk in these patients, we propose to apply novel, noninvasive magnetic resonance imaging approaches to obtain a more comprehensive measure of tissue viability and the prevalence of vascular compensation strategies in this at-risk population. Results from this study are anticipated to provide new information regarding the mechanisms by which the brain compensates for arterial stenosis and to describe the relationship between these mechanisms and stroke risk with the overreaching aims of reducing stroke and long-term disability.