Value of Frequency Domain Resting-State Functional Magnetic Resonance Imaging Metrics Amplitude of Low-Frequency Fluctuation and Fractional Amplitude of Low-Frequency Fluctuation in the Assessment of Brain Tumor-Induced Neurovascular Uncoupling

Abstract

The aim of this study was to explore whether the phenomenon of brain tumor-related neurovascular uncoupling (NVU) in resting-state blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) (rsfMRI) may also affect the resting-state fMRI (rsfMRI) frequency domain metrics the amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF). Twelve de novo brain tumor patients, who underwent clinical fMRI examinations, including task-based fMRI (tbfMRI) and rsfMRI, were included in this Institutional Review Board-approved study. Each patient displayed decreased/absent tbfMRI activation in the primary ipsilesional (IL) sensorimotor cortex in the absence of a corresponding motor deficit or suboptimal task performance, consistent with NVU. Z-score maps for the motor tasks were obtained from general linear model analysis (reflecting motor activation vs. rest). Seed-based correlation analysis (SCA) maps of sensorimotor network, ALFF, and fALFF were calculated from rsfMRI data. Precentral and postcentral gyri in contralesional (CL) and IL hemispheres were parcellated using an automated anatomical labeling template for each patient. Region of interest (ROI) analysis was performed on four maps: tbfMRI, SCA, ALFF, and fALFF. Voxel values in the CL and IL ROIs of each map were divided by the corresponding global mean of ALFF and fALFF in the cortical brain tissue. Group analysis revealed significantly decreased IL ALFF (p = 0.02) and fALFF (p = 0.03) metrics compared with CL ROIs, consistent with similar findings of significantly decreased IL BOLD signal for tbfMRI (p = 0.0005) and SCA maps (p = 0.0004). The frequency domain metrics ALFF and fALFF may be markers of lesion-induced NVU in rsfMRI similar to previously reported alterations in tbfMRI activation and SCA-derived resting-state functional connectivity maps.

Keywords: frequency domain metrics ALFF (amplitude of low-frequency fluctuation) and fALFF (fractional ALFF); motor activation; neurovascular uncoupling; presurgical mapping; resting-state fMRI.

FIG. 1.

Patient with a grade II oligodendroglioma. Top row shows tongue motor fMRI activation map (tbfMRI) (Z-score >4.0) overlaid on T1-weighted structural images. Second, third, and bottom rows show SCA, ALFF, and fALFF maps (SCA >1.0, ALFF >0.4 and fALFF >0.36) from rsfMRI. Blue contours display ROIs from automatically parcellated combined precentral and postcentral gyri. Notice in all maps that there is abnormally decreased signal in the IL perirolandic ROIs compared with the normal CL perirolandic ROIs. In the setting of preserved clinical motor function and excellent task performance, these findings are indicative of tumor-induced NVU. ALFF, amplitude of low-frequency fluctuations; CL, contralesional; fALFF, fractional ALFF; fMRI, functional magnetic resonance imaging; IL, ipsilesional; NVU, neurovascular uncoupling; ROI, region of interest; rsfMRI, resting-state fMRI; SCA, seed correlation analysis; tbfMRI, task-based functional MRI. Color images available online at www.liebertpub.com/brain