Neural Regeneration Research ›› 2021, Vol. 16 ›› Issue (5): 842-850.doi: 10.4103/1673-5374.297079

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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.

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