Demonstration of Brain Tumor-Induced Neurovascular Uncoupling in Resting-State fMRI at Ultrahigh Field

Abstract

To demonstrate in a small case series for the first time the phenomenon of brain tumor-related neurovascular uncoupling (NVU) in resting-state blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) at ultrahigh field (7T). Two de novo (i.e., untreated) brain tumor patients underwent both BOLD resting-state fMRI (rsfMRI) on a 7T MRI system and motor task-based BOLD fMRI at 3T. Ipsilesional (i.e., ipsilateral to tumor or IL) and contralesional (i.e., contralateral to tumor or CL) region of interest (ROI) analysis was performed on both 3T motor task-related general linear model-derived activation maps and on 7T rsfMRI independent component analysis (ICA)-derived sensorimotor network maps for each case. Asymmetry scores (ASs) were computed based on numbers of suprathreshold voxels in the IL and CL ROIs. In each patient, ASs derived from ROI analysis of suprathreshold voxels in IL and CL ROIs in task-related activation maps and rsfMRI ICA-derived sensorimotor component maps indicate greater number of suprathreshold voxels in contralesional than ipsilesional sensorimotor cortex in both maps. In patient 1, an AS of 0.2 was obtained from the suprathreshold Z-score spectrum (voxels with Z-scores >5.0) of the task-based activation map and AS of 1.0 was obtained from the suprathreshold Z-score spectrum (Z-scores >5.0) of the ICA-derived sensorimotor component map. Similarly, in patient 2, an AS of 1.0 was obtained from the suprathreshold Z-score spectrum (Z-scores >5.0) of the task-based activation map and an AS of 1.0 was obtained from the suprathreshold Z-score spectrum (Z-scores >5.0) of the ICA-derived sensorimotor component map. Overall, decreased BOLD signal was noted in IL compared with CL ROIs on both task-based activation maps and ultrahigh field resting-state maps, indicating the presence of NVU. We have demonstrated evidence of NVU on ultrahigh field 7T rsfMRI comparable with the findings on standard 3T motor task-based fMRI in both cases.

The Resting-State Functional Magnetic Resonance Imaging Regional Homogeneity Metrics—Kendall's Coefficient of Concordance-Regional Homogeneity and Coherence-Regional Homogeneity—Are Valid Indicators of Tumor-Related Neurovascular Uncoupling

“…Very recently, a few publications (Agarwal et al, 2016a(Agarwal et al, , 2016bMallela et al, 2016) have demonstrated similar impaired BOLD responses in rsfMRI due to brain tumor-induced NVU. Studies by Agarwal et al (2016b) have demonstrated that tumor-related NVU can adversely affect the restingstate BOLD signal similar to its effect on task-based BOLD activation.…”

“…Another study demonstrated that brain tumor-related NVU may also similarly affect rsfMRI at ultrahigh field (7 Tesla) despite the higher signal-to-noise ratio afforded by higher field strength (Agarwal et al, 2016a). Mallela et al (2016) have examined the correlation of rsfMRI data with tumor characteristics and clinical information to characterize functional reorganization of resting-state networks (RSNs) and the limitations of this method in high-grade gliomas due to NVU.…”

Limitations of Resting-State Functional MR Imaging in the Setting of Focal Brain Lesions

“…51 Because of its easy implementation and less stringent requirements for patient compliance, rsfMRI has been attracting wide attention for use as a preoperative mapping tool. 52,53 However, rsfMRI also suffers from similar important clinical limitations of false negative BOLD signals due to brain-tumor related NVU; 54–56 thus, to use rsfMRI as a reliable pre-surgical tool, it becomes all the more important to study NVU in cases of focal resectable brain lesions such as tumors to evaluate its effects on rsfMRI.…”

“…In another study, they further assessed brain tumor-related NVU in rsfMRI at ultrahigh field (7T) and demonstrated that the higher SNR at 7T does not fully mitigate the effects of such NVU. 56 Mallela and colleagues examined the correlation of rsfMRI data with tumor characteristics and clinical information to characterize functional reorganization of RSNs and the limitations of rsfMRI in high-grade gliomas due to NVU. 54 …”

Real‐time presurgical resting‐state fMRI in patients with brain tumors: Quality control and comparison with task‐fMRI and intraoperative mapping

“…A recent study in patients with brain tumors demonstrated only moderate group level rsfMRI versus tfMRI language network concordance with substantial subject‐level variability (Sair et al, ). Infiltration and abnormal neurovascular coupling, generally greater with higher tumor grade but also present in low‐grade gliomas (Pak et al, ), may compromise blood oxygenation level dependent (BOLD) contrast, both in rsfMRI and tfMRI (Hou et al, ; Jiang et al, ; Holodny et al, ; Agarwal et al, ).…”