Functional Magnetic Resonance Imaging Activation Optimization in the Setting of Brain Tumor-Induced Neurovascular Uncoupling Using Resting-State Blood Oxygen Level-Dependent Amplitude of Low Frequency Fluctuations

Abstract

The goal of this study was to demonstrate that a novel resting state BOLD ALFF (amplitude of low frequency fluctuations)-based correction method can substantially enhance the detectability of motor task activation in the presence of tumor-induced neurovascular uncoupling (NVU). Twelve de novo brain tumor patients who underwent comprehensive clinical BOLD fMRI exams including task fMRI and resting state fMRI (rsfMRI) were evaluated. Each patient displayed decreased/absent task fMRI activation in the ipsilesional primary motor cortex in the absence of corresponding motor deficit or suboptimal task performance, consistent with NVU. Z-score maps for the motor tasks were obtained from general linear model (GLM) analysis (reflecting motor activation vs. rest). ALFF maps were calculated from rsfMRI data. Precentral and postcentral gyri in contralesional (CL) and ipsilesional (IL) hemispheres were parcellated using an Automated Anatomical Labeling (AAL) template for each patient. A novel ALFF-based correction method was used to identify the NVU affected voxels in the ipsilesional primary motor cortex (PMC), and a correction factor was applied to normalize the baseline Z-scores for these voxels. In all cases, substantially greater activation was seen on post-ALFF correction motor activation maps within the ipsilesional precentral gyri than in the pre-ALFF correction activation maps. We have demonstrated the feasibility of a new resting state ALFF-based technique for effective correction of brain tumor-related NVU in the primary motor cortex.

Keywords: frequency domain metrics ALFF (amplitude of low frequency fluctuations); motor activation; neurovascular uncoupling; presurgical mapping.

FIG. 1.

Patient 1 with a left hemispheric WHO grade IV glioblastoma (Patient 8 in Table 1) performed bilateral simultaneous sequential finger tapping task. This case displays severe NVU affecting the sensorimotor network. Suprathreshold voxels (Z-score >2.5) in the expected hand representation area of the primary motor cortex are highlighted in the pre-correction map on one axial slice. Post-correction and difference maps resulting from subtraction of the pre-correction map from the post-correction map are also displayed. The difference map shows the newly detectable BOLD activation (arrow) in the NVU-affected primary sensorimotor cortex following application of the correction algorithm. Patient 2 with a grade II oligodendroglioma performed bilateral simultaneous sequential finger tapping task and Patient 3 with grade IV glioma performed tongue movement task (Patient No. 11 and 6 in Table 1, respectively). Patient 2 is a moderate NVU case, and Patient 3 is a mild NVU case. Pre- and post-correction motor maps for each patient are provided. Suprathreshold voxels (Z-score >2.5) in the primary motor cortex are highlighted in the pre-correction map. Difference maps resulting from subtraction of pre-correction maps from post-correction maps are also displayed. The difference map shows the newly detectable BOLD activation (arrow) in the NVU-affected primary sensorimotor cortex following application of the correction. In addition, BH CVR maps are also displayed for each case in the last column on the right, overlaid on T1-weighted anatomic images. Statistical thresholds used for the severe, moderate, and mild NVU cases are 0.30, 0.40, and 0.20 BOLD percentage signal changes, respectively. Note the IL reduction in CVR compared with the CL hemisphere; in the setting of preserved motor function, these findings are indicative of lesion-induced NVU. BH CVR, breath-hold cerebrovascular reactivity; BOLD, blood oxygen level dependent; CL, contralesional; IL, ipsilesional; NVU, neurovascular uncoupling; WHO, World Health Organization. Color images are available online.

FIG. 2.

The average fMRI time courses of sensorimotor cortex in CL and IL hemispheres in three cases displaying severe NVU, moderate NVU, and mild NVU, respectively, are plotted. “Amplitude” refers to the intensity of the BOLD signal (in a.u.) extracted from the IL and CL ROIs. The time course of “CL” represents an average time course of all of the activated, that is, suprathreshold voxels in the CL sensorimotor cortex and “IL Difference” represents an average time course of all newly detected “active” voxels in the IL sensorimotor cortex obtained following application of the ALFF correction algorithm. The bold black vertical dashed lines in the “CL” and “IL Difference” plots separate successive cycles of task and rest epochs in the fMRI paradigm. Note that the task fMRI paradigm includes three cycles. Light gray dotted lines highlight the baseline and maximal BOLD signals in each time course. The difference between maximal signal and baseline in each time course is designated as the BOLD amplitude (A) for each “CL” and “IL Difference” time course. Note the similarity of the “CL” and “IL Difference” time courses in terms of periodicity in each patient, as well as the relatively low amplitude of IL BOLD signal compared with CL signal, reflecting the effects of NVU on the voxels that were selected for correction. ALFF, amplitude of low frequency fluctuations; a.u., arbitrary units; ROI, region of interest. Color images are available online.

FIG. 3.

The average fMRI time courses of Heschl's gyrus (a key component of the auditory network) in CL and IL hemispheres in three cases displaying severe NVU, moderate NVU, and mild NVU, respectively, are plotted in blue (CL) and red (IL), respectively. Note the randomness of both the “CL” and “IL” BOLD signal time courses, that is, absence of task-correlated periodicity, in each patient. Also, in the last column, the BOLD signal time course post-ALFF correction in IL is also plotted (black-colored line) along with pre-ALFF-corrected IL time course (in red). Note the same random BOLD signal fluctuations following correction that we have seen pre-correction in the IL ROI. Color images are available online.