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Updated: Jan 25, 2026

Application of Granger Causality Analysis of the Directed Functional Connection in Alzheimer's Disease and Mild Cognitive Impairment
Published on: August 7, 2017
Dynamic-flip-angle ECG-gating with nuisance signal regression improves resting-state BOLD functional connectivity
Chenxi Hu1, Fuyuze Tokoglu1, Dustin Scheinost1
1Department of Radiology and Biomedical Imaging, Yale School of Medicine, Yale University, New Haven, Conneticut.
Purpose:
To investigate an ECG-gated dynamic-flip-angle BOLD sequence with improved robustness against cardiogenic noise in resting-state fMRI.
Methods:
ECG-gating minimizes the cardiogenic noise but introduces T1 -dependent signal variation, which is minimized by combination of a dynamic-flip-angle technique and retrospective nuisance signal regression (NSR) using signals of white matter, CSF, and global average. The technique was studied with simulations in a wide range of T1 and B1 fields and phantom imaging with pre-programmed TR variations. Resting-state fMRI of 20 healthy subjects was acquired with non-gated BOLD (NG), ECG-gated constant-flip-angle BOLD (GCFA), ECG-gated BOLD with retrospective T1 -correction (GRC), and ECG-gated dynamic-flip-angle BOLD (GDFA), all processed by the same NSR method. GDFA was compared to alternative methods over temporal SNR (tSNR), seed-based connectivity, and whole-brain voxelwise connectivity based on intrinsic connectivity distribution (ICD). A previous large-cohort data set (N = 100) was used as a connectivity gold standard.
Results:
Simulations and phantom imaging show substantial reduction of the T1 -dependent signal variation with GDFA alone, and further reduction with NSR. The resting-state study shows improved tSNR in the basal brain, comparing GDFA to NG, after both processed with NSR. Furthermore, GDFA significantly improved subcortical-subcortical and cortical-subcortical connectivity for several representative seeds and significantly improved ICD in the brainstem, thalamus, striatum, and prefrontal cortex, compared to the other 3 approaches.
Conclusion:
GDFA with NSR improves mapping of the resting-state functional connectivity of the basal-brain regions by reducing cardiogenic noise.
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