Vascular resistance and resilience in ALS – an ultrahigh-resolution 7T MRI study of the motor cortex

ALS 中的血管阻力和弹性——运动皮层的超高分辨率 7T MRI 研究

• 批准号: 501214112
• 负责人: Dr.-Ing. Hendrik Mattern
• 金额: --
• 依托单位: Klinik für Neurologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/501214112?language=en
• 关键词: Vascular; resistance; resilience; ALS; ultrahigh

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neuromuscular disorder hallmarked by pyramidal cell degeneration of the motor cortex (M1). The underlying causes of sporadic ALS remain largely unknown, limiting its treatment options to supportive measures without any causal therapies. Even though many patients die within 3 to 5 years through respiratory insufficiency, individual ALS disease course and prognosis are highly variable. This is mirrored by distinct motor phenotypes, very long survival times of up to 10 years, and cessation or even reversal of disease progression in individual patients.In the presented proposal we hypothesize that a root cause of clinical ALS heterogeneity is a variable vascular supply of the motor cortex, which mitigates M1 pyramidal cell degeneration (“resistance”) or its impact on motor function (“resilience”). To address this question, we will prospectively examine a selected cohort of 20 ALS patients and 20 age- and sex-matched controls that will undergo 7 Tesla ultra-high field magnetic resonance imaging (MRI) applying angiographic (ToF-MRA) and anatomical sequences (MPRAGE). By visual rating two vascular patterns of M1 supply will be distinguished for the branches of the anterior cerebral artery (medial motor cortex) and middle cerebral artery (lateral motor cortex), respectively: a “single supply” pattern in which the M1 supply is provided by the terminal cortical arteries of one single branch only, or a “double supply” pattern, in which two branches feed the supplying terminal cortical arteries. We assume that a “double supply” pattern results in overlapping perfusion territories of both branches which mitigate M1 pyramidal cell degeneration or its impact on motor function. For quantitative analysis vessel distance mapping will be applied, which assigns each non-vessel voxel the distance to each of the examined arteries and thus consequently allows an approximation of the branches’ perfusion territories. Based upon mediation models the direct effects of the vascular supply patterns and perfusion territories on pyramidal cell degeneration (studied using M1 cortical thickness, global and body-part specific) will be assessed, as well as whether their severity mediates the influence of vascular supply patterns and perfusion territories upon motor function (global and body-part specific), both, at the time of the baseline MRI and longitudinally.Vascular patterns could serve as a new marker to explain the phenotypic variability in ALS, which might prove useful as an additional aspect for an individualized patient counseling regarding disease course and prognosis. Additionally the cerebral vasculature is potentially “dynamic” tissue, whose functionality can be modified through lifestyle and certain drugs. A “vascular approach to therapy” might lead to new avenues in the prevention and treatment of ALS.

肌萎缩侧索硬化症（ALS）是一种以运动皮质（M1）锥体细胞变性为特征的快速进展性神经肌肉疾病。散发性ALS的根本原因在很大程度上仍然未知，将其治疗选择限制为支持性措施，而没有任何因果疗法。尽管许多患者在3至5年内死于呼吸功能不全，但个体ALS病程和预后差异很大。这是反映了不同的运动表型，非常长的生存时间长达10年，并停止甚至逆转个别patients.In所提出的建议，我们假设，临床ALS异质性的根本原因是一个变量的运动皮层的血管供应，这减轻了M1锥体细胞变性（“阻力”）或其对运动功能的影响（“弹性”）。为了解决这个问题，我们将前瞻性地研究一个选定的20名ALS患者和20名年龄和性别匹配的对照组，这些患者将接受7特斯拉超高场磁共振成像（MRI），应用血管造影（ToF-MRA）和解剖序列（MPH）。通过视觉评级，大脑前动脉（内侧运动皮层）和大脑中动脉（外侧运动皮层）的分支将分别区分两种M1供应的血管模式：“单供应”模式，其中M1供应仅由一个单一分支的终末皮质动脉提供，或“双供应”模式，其中两个分支为供应终末皮质动脉供血。我们假设“双供应”模式导致两个分支的灌注区域重叠，从而减轻M1锥体细胞变性或其对运动功能的影响。对于定量分析，将应用血管距离映射，其为每个非血管体素分配到每个被检查动脉的距离，从而允许近似分支的灌注区域。基于中介模型，血管供应模式和灌注区域对锥体细胞变性的直接影响（使用M1皮质厚度，整体和身体部位特异性研究），以及其严重程度是否介导血管供应模式和灌注区域对运动功能的影响（整体和身体部位特异性的）血管模式可以作为解释ALS中表型变异性的新标记，这可以证明作为关于疾病过程和预后的个体化患者咨询的附加方面是有用的。此外，脑血管系统是潜在的“动态”组织，其功能可以通过生活方式和某些药物来改变。“血管治疗方法”可能会为ALS的预防和治疗开辟新的途径。