中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (5): 842-850.doi: 10.4103/1673-5374.297079

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

磁共振成像参数多元整合分析方法预测缺血性脑卒中模型猪功能的恢复

  

  • 出版日期:2021-05-15 发布日期:2020-12-29
  • 基金资助:

    美国国立卫生研究院,美国神经疾病和中风研究所拨款R01NS093314以及小型企业创新研究拨款1R43NS103596-01

An integrative multivariate approach for predicting functional recovery using magnetic resonance imaging parameters in a translational pig ischemic stroke model

Erin E. Kaiser1, 2, 3, #, J.C. Poythress4, #, Kelly M. Scheulin1, 2, 3, Brian J. Jurgielewicz1, 2, 3, Nicole A. Lazar4, Cheolwoo Park4, Steven L. Stice1, 2, 3, Jeongyoun Ahn4, #br# Franklin D. West1, 2, 3, *#br#   

  1. 1 Regenerative Bioscience Center, University of Georgia, Athens, GA, USA;  2 Neuroscience, Biomedical and Health Sciences Institute, University of Georgia, Athens, GA, USA;  3 Department of Animal and Dairy Science, College of Agricultural and Environmental Sciences, University of Georgia, Athens, GA, USA;  4 Department of Statistics, Franklin College of Arts and Sciences, University of Georgia, Athens, GA, USA
  • Online:2021-05-15 Published:2020-12-29
  • Contact: Franklin D. West, PhD, westf@uga.edu. #These two authors contributed equally to this work.
  • Supported by:
    This work was supported by the National Institutes of Health, National Institute of Neurological Disorders and Stroke grant R01NS093314 as well as Small Business Innovation Research grant 1R43NS103596-01.

摘要:

磁共振成像(MRI)经常用于评估脑卒中类型和严重程度。然而,可用于预测长期功能恢复的特定MRI生物标记物尚需进一步探讨。因此,为了解常用的MRI参数在预测猪缺血性卒中模型中的功能预后中的价值。实验以永久性大脑中动脉阻塞方法建立缺血性脑卒中猪模型。卒中后24h,MRI分析显示局部缺血性病变,扩散性降低,大脑半球肿胀和白质降解。在卒中后4周观察到猪功能缺陷,包括在旷野和新奇物体探索中的行为异常以及时空步态障碍。高斯图形模型确定了特定的MRI输出和功能恢复变量,包括白质完整性和步态表现,表现出强烈的条件依赖性。典型的相关性分析揭示了病灶体积与白质完整性以及新型对象探索和步态表现之间的预后关系。因为猪和人有许多解剖学相似性(例如白质组成),因此,研究结果对于预测慢性脑卒中患者康复的潜力有一定意义。该研究于2017年11月22日获得乔治亚大学(UGA)机构动物护理和使用委员会(IACUC;方案编号:A2014-07-021-Y3-A11和2018-01-029-Y1-A5)批准。

https://orcid.org/0000-0002-0504-7997 (Franklin D. West)

Abstract: Magnetic resonance imaging (MRI) is a clinically relevant, real-time imaging modality that is frequently utilized to assess stroke type and severity. However, specific MRI biomarkers that can be used to predict long-term functional recovery are still a critical need. Consequently, the present study sought to examine the prognostic value of commonly utilized MRI parameters to predict functional outcomes in a porcine model of ischemic stroke. Stroke was induced via permanent middle cerebral artery occlusion. At 24 hours post-stroke, MRI analysis revealed focal ischemic lesions, decreased diffusivity, hemispheric swelling, and white matter degradation. Functional deficits including behavioral abnormalities in open field and novel object exploration as well as spatiotemporal gait impairments were observed at 4 weeks post-stroke. Gaussian graphical models identified specific MRI outputs and functional recovery variables, including white matter integrity and gait performance, that exhibited strong conditional dependencies. Canonical correlation analysis revealed a prognostic relationship between lesion volume and white matter integrity and novel object exploration and gait performance. Consequently, these analyses may also have the potential of predicting patient recovery at chronic time points as pigs and humans share many anatomical similarities (e.g., white matter composition) that have proven to be critical in ischemic stroke pathophysiology. The study was approved by the University of Georgia (UGA) Institutional Animal Care and Use Committee (IACUC; Protocol Number: A2014-07-021-Y3-A11 and 2018-01-029-Y1-A5) on November 22, 2017.

Key words: behavior testing, canonical correlation analysis, gait analysis, Gaussian graphical models, ischemic stroke, magnetic resonance imaging, pig model, principal component analysis