title: DWI and complex brain network analysis predicts vascular cognitive impairment in spontaneous hypertensive rats undergoing executive function tests.
abstract: The identification of biomarkers of vascular cognitive impairment is urgent for its early diagnosis. The aim of this study was to detect and monitor changes in brain structure and connectivity, and to correlate them with the decline in executive function. We examined the feasibility of early diagnostic magnetic resonance imaging (MRI) to predict cognitive impairment before onset in an animal model of chronic hypertension: Spontaneously Hypertensive Rats. Cognitive performance was tested in an operant conditioning paradigm that evaluated learning, memory, and behavioral flexibility skills. Behavioral tests were coupled with longitudinal diffusion weighted imaging acquired with 126 diffusion gradient directions and 0.3 mm(3) isometric resolution at 10, 14, 18, 22, 26, and 40 weeks after birth. Diffusion weighted imaging was analyzed in two different ways, by regional characterization of diffusion tensor imaging (DTI) indices, and by assessing changes in structural brain network organization based on Q-Ball tractography. Already at the first evaluated times, DTI scalar maps revealed significant differences in many regions, suggesting loss of integrity in white and gray matter of spontaneously hypertensive rats when compared to normotensive control rats. In addition, graph theory analysis of the structural brain network demonstrated a significant decrease of hierarchical modularity, global and local efficacy, with predictive value as shown by regional three-fold cross validation study. Moreover, these decreases were significantly correlated with the behavioral performance deficits observed at subsequent time points, suggesting that the diffusion weighted imaging and connectivity studies can unravel neuroimaging alterations even overt signs of cognitive impairment become apparent.
authors.affiliation: Experimental 7T MRI Unit, IDIBAPS, Institut d'Investigacions Biomèdiques August Pi i Sunyer Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: López-Gil
authors.affiliation: Expert Ymaging S.L. Barcelona, Spain.
authors.forename: Iván
authors.initials: I
authors.lastname: Amat-Roldan
authors.affiliation: Experimental 7T MRI Unit, IDIBAPS, Institut d'Investigacions Biomèdiques August Pi i Sunyer Barcelona, Spain ; Group of Biomedical Imaging of the University of Barcelona, CIBER de Bioingenieria, Biomateriales y Nanomedicina Barcelona, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Tudela
authors.affiliation: Department of Neurochemistry and Neuropharmacology, Institut d'Investigacions Biomèdiques de Barcelona (IIBB-CSIC) Barcelona, Spain ; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII Madrid, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Castañé
authors.affiliation: Human Anatomy and Embryology Unit, Laboratory of Surgical NeuroAnatomy, Facultat de Medicina, Universitat de Barcelona Barcelona, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Prats-Galino
authors.affiliation: Department of Brain Ischemia and Neurodegeneration, Institut d'Investigacions Biomèdiques de Barcelona (IIBB-CSIC) Barcelona, Spain.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Planas
authors.affiliation: Department of Experimental Neurology, Center for Stroke Research Berlin Charité, Berlin, Germany.
authors.forename: Tracy D
authors.initials: TD
authors.lastname: Farr
authors.affiliation: Experimental 7T MRI Unit, IDIBAPS, Institut d'Investigacions Biomèdiques August Pi i Sunyer Barcelona, Spain ; Group of Biomedical Imaging of the University of Barcelona, CIBER de Bioingenieria, Biomateriales y Nanomedicina Barcelona, Spain.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Soria
keywords: DTI; DWI; animal models; connectomics; executive function; hypertension; in-vivo MRI; vascular cognitive impairment
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