Brain tumors disrupt the resting-state connectome

• Published in: NeuroImage clinical Vol. 18; pp. 279 - 289
• Main Authors: Hadjiabadi, Darian H., Pung, Leland, Zhang, Jiangyang, Ward, B.D., Lim, Woo-Taek, Kalavar, Meghana, Thakor, Nitish V., Biswal, Bharat B., Pathak, Arvind P.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.01.2018; Elsevier
• Subjects: Animals; Brain - diagnostic imaging; Brain - metabolism; Brain Neoplasms - diagnostic imaging; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Brain tumor; Cell Line, Tumor; Connectivity; Connectome; Disease Models, Animal; fMRI; Glial Fibrillary Acidic Protein - metabolism; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Humans; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Mice; Mice, SCID; Neural Pathways - diagnostic imaging; Neurovascular uncoupling; Oxygen - blood; Regular; Rest; Resting-state; Statistics, Nonparametric; Brain tumor; fMRI; Resting-state; Connectivity; Neurovascular uncoupling
• ISSN: 2213-1582; 2213-1582
• DOI: 10.1016/j.nicl.2018.01.026

Brain tumor patients often experience functional deficits that extend beyond the tumor site. While resting-state functional MRI (rsfMRI) has been used to map such functional connectivity changes in brain tumor patients, the interplay between abnormal tumor vasculature and the rsfMRI signal is still not well understood. Therefore, there is an exigent need for new tools to elucidate how the blood‑oxygenation-level-dependent (BOLD) rsfMRI signal is modulated in brain cancer. In this initial study, we explore the utility of a preclinical model for quantifying brain tumor-induced changes on the rsfMRI signal and resting-state brain connectivity. We demonstrate that brain tumors induce brain-wide alterations of resting-state networks that extend to the contralateral hemisphere, accompanied by global attenuation of the rsfMRI signal. Preliminary histology suggests that some of these alterations in brain connectivity may be attributable to tumor-related remodeling of the neurovasculature. Moreover, this work recapitulates clinical rsfMRI findings from brain tumor patients in terms of the effects of tumor size on the neurovascular microenvironment. Collectively, these results lay the foundation of a preclinical platform for exploring the usefulness of rsfMRI as a potential new biomarker in patients with brain cancer. •Brain tumors cause brain-wide alterations of resting-state networks accompanied by global attenuation of the rsfMRI signal.•Dysregulation of the neurovasculature was observed histologically and may account for some of the observed rsfMRI changes.•We replicate rsfMRI findings in brain tumor patients and lay the foundation for exploring rsfMRI as a clinical biomarker.