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Resting state neurovascular coupling patterns estimated using advanced multiband multi-echo BOLD/ASL imaging1Radiology, Medical College of Wisconsin, Milwaukee, WI, United States
Synopsis
Keywords: Arterial spin labelling, Data Analysis, Coupling, Simultaneous BOLD/ASL
Impaired neurovascular coupling (NVC) plays a critical role in many neurovascular pathological processes. Several resting state fMRI methods have been used to estimate NVC including BOLD/CBF coupling and, to a lesser extent, ALFF and fALFF. In this study, resting state BOLD/CBF coupling was evaluated using advanced multiband multi-echo BOLD/ASL sequence and correlated with ALFF and fALFF in healthy volunteers. Significant correlation between BOLD/CBF coupling and ALFF and fALFF was seen in major brain network hubs. These results indicate MBME BOLD/ASL may provide similar, but complimentary measures of NVC compared to traditional RS metrics.
Introduction
Neurovascular coupling (NVC), where acute localized blood flow increases following neural activity, is the basis for the BOLD response in fMRI1. Impaired NVC plays a critical role in a number of neurovascular pathological processes. Recent technical developments have combined a multiband acquisition with four total echoes with a pseudocontinuous arterial spin labelling (pCASL) approach to simultaneously collect BOLD and cerebral blood flow (CBF) data2. This sequence can be used to measure BOLD/CBF coupling as an estimate of NVC. In addition, traditional resting state metrics such as ALFF and fALFF can be measured with the same acquisition. These metrics have been suggested as potential surrogates for NVC. The relationship between BOLD/CBF coupling and these RSFC metrics is largely unknown. In this study, resting state BOLD/CBF coupling was evaluated and correlated with ALFF and fALFF in a group of healthy volunteers.Methods
Twenty-nine healthy volunteer subjects (Mean Age=28.0 Range 20 – 46, 9 Male, 20 Female) participated in this study. Imaging was performed on a 3T scanner. Each subject underwent a multiband multi-echo BOLD/ASL resting state fMRI acquisition2,3 with the following parameters: TR/TE=3500/11,30,49,67ms, FOV=24cm, matrix size=80x80 with slice thickness=3mm (3x3x3mm voxel size), 11 slices with multiband factor=4 (44 total slices), FA=90°, and partial Fourier factor=0.85. The sequence also incorporated an unbalanced pCASL labeling scheme with labeling time=1.5s and PLD=1.0s. Resting state scans used a single shot EPI readout with in-plane acceleration (R)=2 and lasted six minutes resulting in 103 volumes.Data was analyzed using a combination of AFNI4,5, and FSL6. First, the anatomical MPRAGE image was coregistered to Montreal Neurological Institute (MNI) space. Then, the first-echo functional data was volume-registered to the first volume. Subsequent echoes were registered using the transformation matrices from the first echo. For the BOLD data, the four echoes were combined using the -weighted approach7 and denoised using multi-echo independent component analysis (ME-ICA)8-10 by regressing non-BOLD independent components out of the combined ME data. The denoised MBME dataset was then registered to the MPRAGE image and then to MNI space using the anatomical transformations computed above. Finally, the denoised data was bandpass filtered with 0.01 < f < 0.071Hz corresponding to 1/(4*TR). A perfusion-weighted (PW) timeseries was generated by highpass filtering the first echo at f > 0.071Hz followed by demodulation11.
The BOLD/CBF coupling was assessed by correlating the signals from the BOLD and PW datasets on a voxelwise basis using Pearson correlation with 3dTcorrelate in AFNI. The BOLD time series was time-shifted from -2TR to +2TR (-7.0 – 7.0s) with steps of 1 TR. The voxelwise maximum correlation within this range was defined as rmax. ALFF and fALFF were computed using 3dRSFC in AFNI for the BOLD data. To examine the relationship between BOLD/CBF coupling and the traditional RS metrics, rmax was correlated with ALFF and fALFF on a voxelwise basis across subjects using 3dTcorrelate in AFNI with Pearson correlation. The resulting correlation maps were thresholded at p < 0.05 with cluster size correction for multiple comparisons.
Results
Individual subject and group-averaged BOLD/CBF coupling results are shown in Figure 1. Heightened coupling was widespread, with coupling highest in the parietal, frontal and visual regions. Group averaged ALFF and fALFF metrics are shown in Figure 2. The results of the correlation between BOLD/CBF coupling (rmax) and traditional resting state metrics (ALFF and fALFF) are shown in Figure 3. Significant correlation between BOLD/CBF coupling and ALFF was seen mainly in the visual cortex and motor cortex. Similar results were seen for the correlation between BOLD/CBF coupling and fALFF, however significant correlation was more widespread including more parietal and frontal areas.Discussion/Conclusions
The group average for BOLD/CBF coupling showed stronger coupling in similar areas as previous studies including default mode network (DMN), visual cortex and frontal areas12,13. In order to tease apart the relationship between BOLD/CBF coupling and NVC, coupling was correlated with traditional RS metrics including ALFF and fALFF. ALFF has been shown to correlate with cerebrovascular reactivity (CVR) a measure of vascular health that has been used to estimate NVC14,15. The CBF/ALFF ratio has also been shown to be altered in disease16 as has the CBF/fALFF ratio17. Finally, Tak et al found coupling correlated with RSFC strength in the DMN18. Our findings showed BOLD/CBF coupling was significantly correlated with traditional RS metrics including ALFF, and fALFF in major network hubs indicating coupling may provide similar, but complimentary measures of NVC compared to traditional RS metrics. The multiband multi-echo BOLD/ASL approach could provide a useful tool for estimating NVC in translational neuroscience research, however studies in pathological conditions are needed.Acknowledgements
No acknowledgement found.References
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Figures
Figure 1. BOLD/CBF coupling for a representative individual subject (left) and averaged across the entire group (right).
Figure 2. ALFF (left) and fALFF (right) averaged across the group.
Figure 3. Spatial correlation of BOLD/CBF coupling (rmax) with mALFF (left) and fALFF (right). Similar regions were observed for both metrics, while fALFF correlations were more widespread.