Optimal Atlas Registration and Resting State Functional Architecture in Patients with Glioblastoma

Abstract

Using resting-state fMRI is a challenge in patients with large tumors owing to mass effect and potentially altered representation of function, i.e., remapping. The best approach to atlas registration in tumor patients remains uncertain. In this work, we investigated the effects of alternative approaches to atlas registration on resting-state fMRI functional connectivity in glioblastoma patients and studied the impact of glioblastoma on functional brain organization. We analyzed data representing 59 glioblastoma patients and 161 age-matched healthy subjects and systemically investigated affine vs. non-linear atlas registration and two associated masking options. Outcomes were assessed both in terms of structural data match to an atlas template as well as functional connectivity (FC) match to a reference dataset. Next, we evaluated the impact of glioblastomas on the organization of brain networks accounting for the hierarchical organization of resting state networks. Our results demonstrate that non-linear atlas registration with tumor masking optimizes both structural normalization and FC mapping. The aberrancy map results, obtained with fine parcellations, are consistent with prior findings showing that FC abnormalities induced by focal lesions are widely distributed. However, the results obtained with coarse parcellations indicate that functional architecture is grossly normal in tumor patients.

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Funding declaration: Parts of this work were funded by the National Institutes of Health Grant (NIH R01 CA203861) and the Intellectual and Developmental Disabilities Research Center at Washington University award Number P50 HD103525.

Conflict of Interests: K.Y.P., J.S.S., P.H.L., A.Z.S., report the following conflict of interest. Licensing of Intellectual Property: Sora Neuroscience. C.D.H. and M.M. report the following conflicts of interest. Stock ownership: Sora Neuroscience. Licensing of Intellectual Property: Sora Neuroscience. A.S. report the following conflict of interest. Stock ownership: TheraPanacea. D.S.M. reports the following conflicts of interest: Stock ownership: Sora Neuroscience, Flywheel. Licensing of Intellectual Property: Sora Neuroscience. E.C.L. reports the following conflicts of interest. Stock ownership: Neurolutions, General Sensing, Osteovantage, Pear Therapeutics, Face to Face Biometrics, Immunovalent, Caeli Vascular, Acera, Sora Neuroscience, Inner Cosmos, Kinetrix, NeuroDev. Petal Surgical. Consultant: Monteris Medical, E15, Acera, Alcyone, Intellectual Ventures, Medtronic, Neurolutions, Osteovantage, Pear Therapeutics, Sante Ventures, Microbot. Licensing of Intellectual Property: Neurolutions, Osteovantage, Caeli Vascular, Sora Neuroscience. Washington University owns equity in Neurolutions. The other authors declare they have no competing interests.

Ethical Approval: The project meets the regulatory requirements for the protection of human subjects and was approved by the Washington University Institutional Review Board. All methods were performed in accordance with relevant guidelines and regulations.

Keywords: glioblastoma, Resting-State functional MRI, Non-linear registration, Cost function masking, Resting State Networks