Multiple Sclerosis Lesion Magnetic Susceptibility Activity

多发性硬化症病变磁化率活性

• 批准号: 9922392
• 负责人: Yi Wang
• 金额: $ 36.74万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9922392
• 关键词: Accounting; Address; Age; Autopsy; Back; Biological Markers; Blood - brain barrier anatomy; Brain; Chronic; Cicatrix; Confusion; Data; Demyelinations; Deposition; Development; Diagnosis; Disease; Financial compensation; Gadolinium; Goals; Image; Imaging Techniques; Immunohistochemistry; Inflammation; Inflammatory; Iron; Lesion; Longitudinal Studies; Longitudinal prospective study; Macrophage Activation; Magnetic Resonance Imaging; Magnetism; Maps; Measurement; Measures; Methods; Microglia; Modeling; Monitor; Motion; Multiple Sclerosis; Multiple Sclerosis Lesions; Myelin; Nerve Degeneration; Neurologic Deficit; Outcomes Research; Pathogenicity; Pathologic; Patients; Phase; Play; Predisposition; Process; Property; Reference Standards; Reproducibility; Research; Research Project Grants; Resolution; Retrospective Studies; Role; Scanning; Signal Transduction; Source; Specificity; Specimen; Structure; Techniques; Testing; Time; Tissue Sample; Tissues; base; blood-brain barrier disruption; clinical practice; data acquisition; healing; imaging biomarker; improved; interest; multiple sclerosis patient; prevent; public health relevance; recruit; remyelination; spatiotemporal; tool; white matter

 DESCRIPTION (provided by applicant): The long term objective of this project is to improve the capability to monitor the inflammatory and neurodegenerative processes in Multiple Sclerosis (MS) for effective diagnosis and treatment. The specific goal of this research is to establish the time course of magnetic susceptibility of lesions as a sensitive probe of demyelination and iron content associated with inflammatory processes. Currently, gadolinium enhancement in conventional magnetic resonance imaging (MRI) is widely used to map inflammation caused by blood brain barrier (BBB) disruption during MS lesion formation. However, there is still inflammation in the brain after the BBB heals and currently there is no method in clinical practice to detect this inflammation behind the BBB. Our preliminary data demonstrates that the time course of lesion magnetic susceptibility as measured by quantitative susceptibility mapping (QSM) can detect lesion activity after the resolution of gadolinium enhancement. Accordingly, this proposed research will try to establish the existence of and gain a basic understanding of the time course of MS lesion susceptibility by carrying out three specific aims: Aim 1: Improve QSM scanning robustness and processing accuracy for reliable longitudinal measurement of susceptibility time course. We hypothesize that QSM can be improved to high reproducibility and accuracy of 0.01ppm (parts per million, susceptibility unit). Aim 2: Define the MS lesion magnetic susceptibility time course through prospective longitudinal study of the susceptibility of lesions at all ages, with spatiotemporal correlation of gadolinium enhancement measured by conventional MRI. We hypothesize that lesion susceptibility changes dynamically over time, even after inflammatory activity, as measured by conventional MRI, has subsided. Aim 3: Define the immunohistochemical correlates of MS lesion magnetic susceptibility using autopsied brain specimens from MS patients and controls. We hypothesize that the QSM signal of an MS lesion correlates in part with microglia/macrophages activation (i.e. inflammatory activity) and that the QSM value of a fully demyelinated lesion is determined by iron.

 描述（由申请人提供）：该项目的长期目标是提高监测多发性硬化症（MS）炎症和神经退行性过程的能力，以进行有效的诊断和治疗。这项研究的具体目标是建立病变磁化率的时间过程，作为与炎症过程相关的脱髓鞘和铁含量的敏感探针。目前，传统磁共振成像（MRI）中的钆增强被广泛用于绘制多发性硬化症病变形成过程中血脑屏障（BBB）破坏引起的炎症图谱。然而，BBB愈合后大脑中仍然存在炎症，目前临床上还没有方法检测BBB后面的这种炎症。我们的初步数据表明，通过定量磁化率图（QSM）测量的病灶磁化率的时间过程可以检测钆增强分辨率后的病灶活动。因此，本项研究将尝试通过实现三个具体目标来确定 MS 病变敏感性时间过程的存在并获得对 MS 病变敏感性时间过程的基本了解： 目标 1：提高 QSM 扫描鲁棒性和处理精度，以实现可靠的敏感性时间过程纵向测量。我们假设 QSM 可以提高到 0.01ppm（百万分之一，磁化率单位）的高再现性和准确度。目标 2：通过对所有年龄段病变磁化率的前瞻性纵向研究，以及传统 MRI 测量的钆增强的时空相关性，定义 MS 病变磁化率时程。我们假设，即使在传统 MRI 测量的炎症活动消退之后，病变易感性也会随着时间动态变化。目标 3：使用多发性硬化症患者和对照的尸检脑标本确定多发性硬化症病变磁化率的免疫组织化学相关性。我们假设 MS 病变的 QSM 信号部分与小胶质细胞/巨噬细胞激活（即炎症活动）相关，并且完全脱髓鞘病变的 QSM 值由铁决定。

项目成果

The Role of Astrocytes in Multiple Sclerosis.

• DOI: 10.3389/fimmu.2018.00217
• 发表时间: 2018
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Ponath G;Park C;Pitt D
• 通讯作者: Pitt D

Estimation of Multiple Sclerosis lesion age on magnetic resonance imaging.

• DOI: 10.1016/j.neuroimage.2020.117451
• 发表时间: 2021-01-15
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Sweeney EM;Nguyen TD;Kuceyeski A;Ryan SM;Zhang S;Zexter L;Wang Y;Gauthier SA
• 通讯作者: Gauthier SA

Significance and In Vivo Detection of Iron-Laden Microglia in White Matter Multiple Sclerosis Lesions.

• DOI: 10.3389/fimmu.2018.00255
• 发表时间: 2018
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Gillen KM;Mubarak M;Nguyen TD;Pitt D
• 通讯作者: Pitt D

Diagnostic accuracy of semiautomatic lesion detection plus quantitative susceptibility mapping in the identification of new and enhancing multiple sclerosis lesions.

• DOI: 10.1016/j.nicl.2018.01.013
• 发表时间: 2018
• 期刊: NeuroImage. Clinical
• 作者: Zhang S;Nguyen TD;Zhao Y;Gauthier SA;Wang Y;Gupta A
• 通讯作者: Gupta A