@article{3b50e5dbab664e99b73efdb58e5c9fe3,
title = "Altered hemodynamics contribute to local but not remote functional connectivity disruption due to glioma growth",
abstract = "Glioma growth can cause pervasive changes in the functional connectivity (FC) of brain networks, which has been associated with re-organization of brain functions and development of functional deficits in patients. Mechanisms underlying functional re-organization in brain networks are not understood and efforts to utilize functional imaging for surgical planning, or as a biomarker of functional outcomes are confounded by the heterogeneity in available human data. Here we apply multiple imaging modalities in a well-controlled murine model of glioma with extensive validation using human data to explore mechanisms of FC disruption due to glioma growth. We find gliomas cause both local and distal changes in FC. FC changes in networks proximal to the tumor occur secondary to hemodynamic alterations but surprisingly, remote FC changes are independent of hemodynamic mechanisms. Our data strongly implicate hemodynamic alterations as the main driver of local changes in measurements of FC in patients with glioma.",
keywords = "Functional connectivity, glioma, hemodynamic lags, mouse model, neurovascular uncoupling",
author = "Orukari, {Inema E.} and Siegel, {Joshua S.} and Warrington, {Nicole M.} and Baxter, {Grant A.} and Bauer, {Adam Q.} and Shimony, {Joshua S.} and Rubin, {Joshua B.} and Culver, {Joseph P.}",
note = "Funding Information: We thank Sam Achilefu, Bradley Schlaggar, and Abraham Synder for critical discussions of the manuscript and the data. Lynne Marsala and Julie Prior and the Molecular Imaging Center and Oncologic Imaging Program of the Siteman Cancer Center assisted with bioluminescence imaging (BLI). Scott Beeman assisted with magnetic resonance imaging, and Ron Perez and the Hope Center Animal Surgery Core assisted with cell injections. Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported in part by National Institutes of Health Grants T32GM007200 (to IEO and JSS), R01NS078223 (to J.P.C), R01NS084028 (to JPC), R01NS099429 (to JPC), K25NS083754 (to AQB), P50CA094056 (Molecular Imaging Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine), Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under Award U54 HD087011 to the Intellectual and Developmental Disabilities Research Center at Washington University in St. Louis (to JPC and JS Shimony), and the Children{\textquoteright}s Discovery Institute (to JBR). Publisher Copyright: {\textcopyright} The Author(s) 2018.",
year = "2020",
month = jan,
day = "1",
doi = "10.1177/0271678X18803948",
language = "English",
volume = "40",
pages = "100--115",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
number = "1",
}