Probing silent cerebral infarct pathogenesis in sickle cell disease with cerebrovascular MRI

脑血管MRI探讨镰状细胞病无症状脑梗死发病机制

• 批准号: 10536405
• 负责人: Kristina Zvolanek
• 金额: $ 4.2万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10536405
• 关键词: 4D MRI; Acute; Address; Adult; Anatomy; Area; Arteries; Biological Markers; Blood; Blood Flow Velocity; Blood Vessels; Blood flow; Brain; Brain region; Carbon Dioxide; Cerebral Infarction; Cerebral hemisphere; Cerebrum; Child; Childhood; Circle of Willis; Clinical; Clinical Protocols; Conflict (Psychology); Coupled; Coupling; Data; Development; Distal; Fellowship; Four-dimensional; Functional disorder; Future; Goals; Health; Heterogeneity; Imaging Techniques; Impaired cognition; Impairment; Infarction; Ischemia; Lead; Learning Disabilities; Link; MRI Scans; Magnetic Resonance Imaging; Measurement; Measures; Methods; National Research Service Awards; Nervous System Trauma; Neurologic; Oxygen; Pathogenesis; Patients; Performance; Prevalence; Prevention; Preventive therapy; Process; Prospective Studies; Protocols documentation; Recording of previous events; Risk; Risk Assessment; Risk Factors; Role; Schools; Screening procedure; Sickle Cell; Sickle Cell Anemia; Source; Spatial Distribution; Stroke; Testing; Tissues; Transcranial Doppler Ultrasonography; Triage; Variant; Vascular blood supply; Vasodilator Agents; Work; blood oxygen level dependent; cell injury; cerebral artery; cerebral hemodynamics; cerebrovascular; cerebrovascular pathology; clinically relevant; cohort; cortex mapping; hemodynamics; high risk; improved; individual patient; ischemic lesion; neglect; novel; pre-doctoral; prevent; response; risk stratification; screening; stressor; stroke risk; success; ultrasound

PROJECT SUMMARY Children with sickle cell disease are at increased risk for serious cerebrovascular complications. The most prevalent of these complications are silent cerebral infarcts, focal areas of ischemic tissue damage in the brain associated with cognitive impairment and poor school performance. Despite the significant consequences of silent cerebral infarcts, they are often detected after ischemic damage has occurred. Clinical protocols to triage sickle cell patients utilize ultrasound measurements of blood velocity in large cerebral arteries, with high blood velocity indicating increased risk for stroke. However, there is conflicting evidence whether high blood velocity is a risk factor for silent cerebral infarcts. Additionally, therapies prescribed to high-risk patients may not protect against silent cerebral infarcts. We need improved understanding of the vascular impairments associated with silent cerebral infarcts in sickle cell disease to better prevent and treat this source of neurological injury. This work proposes MRI measurements of cerebrovascular reactivity as a novel source of hemodynamic information related to silent cerebral infarct formation. Cerebrovascular reactivity is the blood flow response to a dilatory stressor and is measured in smaller vessels in the cortex, making it a more local metric of vascular health than blood velocity. Previous studies have demonstrated impaired cerebrovascular reactivity in adults and children with sickle cell disease, indicating reduced ability to increase blood flow to meet oxygen demands and increased likelihood for ischemia. The aims of this proposal are to: 1) evaluate the relationship between blood velocity in large cerebral arteries and cerebrovascular reactivity in the cortex, and 2) determine if cerebrovascular reactivity is altered in brain regions close to silent cerebral infarcts. Aim 1 is a step forward from previous work, contextualizing cerebrovascular reactivity against the clinical standard for cerebrovascular risk assessment in sickle cell disease. Aim 2 determines whether this additional information improves our understanding of the spatial distribution of silent infarcts. The proposed study will provide a comprehensive assessment of cerebral hemodynamics in children with sickle cell disease and offer preliminary evidence for cerebrovascular reactivity as a hemodynamic biomarker for silent cerebral infarct occurrence. A hemodynamic biomarker that is coupled to silent cerebral infarcts could inform the treatment of sickle cell disease and aid in the development of new preventative therapies. In the long term, the imaging techniques developed in this proposal could serve as an alternative or complementary MRI screening tool to stratify for silent cerebral infarct risk more effectively.

项目概要 患有镰状细胞病的儿童发生严重脑血管并发症的风险增加。最 这些并发症中最常见的是无症状脑梗死，即大脑局部缺血组织损伤 与认知障碍和学习成绩不佳有关。尽管造成了重大后果 无症状性脑梗塞通常在缺血性损伤发生后才被发现。临床分诊方案 镰状细胞病患者利用超声测量大脑动脉中的血流速度，具有高血 速度表明中风风险增加。然而，高血流速度是否与高血流速度有关，存在相互矛盾的证据。 无症状性脑梗塞的危险因素。此外，为高危患者开出的疗法可能无法保护 对抗无症状脑梗塞。我们需要更好地了解与以下疾病相关的血管损伤 镰状细胞病中的无症状脑梗塞可以更好地预防和治疗这种神经损伤源。 这项工作提出脑血管反应性的 MRI 测量作为血流动力学的新来源 与无症状脑梗塞形成相关的信息。脑血管反应性是血流对某种物质的反应 扩张性应激源，并在皮层中的较小血管中进行测量，使其成为血管健康状况的更局部指标 比血流速度。先前的研究表明，成人和青少年的脑血管反应性受损 患有镰状细胞病的儿童，表明增加血流量以满足氧气需求的能力下降， 缺血的可能性增加。该提案的目的是：1）评估血液之间的关系 大脑动脉的速度和皮质中的脑血管反应性，2) 确定脑血管是否 靠近无症状脑梗塞的大脑区域的反应性发生改变。目标 1 比之前的工作向前迈出了一步， 将脑血管反应性与脑血管风险评估的临床标准结合起来 镰状细胞性贫血症。目标 2 确定这些附加信息是否可以提高我们对事物的理解 无症状梗塞的空间分布。 拟议的研究将对镰状细胞病儿童的脑血流动力学进行全面评估 细胞疾病，并为脑血管反应性作为沉默的血流动力学生物标志物提供初步证据 脑梗塞的发生。与无症状脑梗塞相关的血流动力学生物标志物可以告知 治疗镰状细胞病并帮助开发新的预防疗法。从长远来看， 本提案中开发的成像技术可以作为 MRI 筛查的替代或补充 更有效地对无症状脑梗塞风险进行分层的工具。