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.

项目摘要 镰状细胞疾病的儿童患严重脑血管并发症的风险增加。最多 这些并发症的普遍是无声的脑梗塞，大脑缺血组织损伤的焦点区域 与认知障碍和学校表现不佳有关。尽管有重大后果 沉默的脑梗塞，经常在发生缺血性损害后检测到它们。分类的临床方案 镰状细胞患者利用大脑动脉的血液速度的超声测量 速度表明中风的风险增加。但是，有相互矛盾的证据是否高血速度是 无声脑梗塞的危险因素。此外，向高危患者开处方的疗法可能无法保护 反对无声的脑梗塞。我们需要对与相关的血管障碍的理解有所改善 镰状细胞疾病中的无声脑梗塞可更好地预防和治疗这种神经系统损伤的根源。 这项工作提出了MRI测量的脑血管反应性，作为新型血流动力学来源 与无声脑梗塞形成有关的信息。脑血管反应性是对A的血流反应 扩张胁迫源，并在皮质中的较小血管中进行测量，使其成为血管健康的局部度量标准 比血液速度。先前的研究表明，成人的脑血管反应性受损 患有镰状细胞疾病的儿童，表明增加血液流动以满足氧气需求的能力降低，并且 缺血的可能性增加。该提议的目的是：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）确定脑血管是否是否 在接近无声脑梗塞的大脑区域中的反应性改变了。 AIM 1是以前的工作迈出的一步 对脑血管反应性的情境化针对临床标准的脑血管反应性，以评估脑血管风险评估 镰状细胞性贫血症。 AIM 2确定此附加信息是否可以提高我们对 无声梗塞的空间分布。 拟议的研究将对患有镰刀儿童的脑血液动力学进行全面评估 细胞疾病并提供脑血管反应性的初步证据，作为沉默的血流动力学生物标志物 大脑梗塞的发生。与沉默的脑梗塞相连的血液动力学生物标志物可以告知 治疗镰状细胞疾病并有助于开发新的预防疗法。从长远来看 该提案中开发的成像技术可以用作替代或互补的MRI筛选 更有效地分层以确定无声脑梗塞的风险。