Erroneous Resting-State fMRI Connectivity Maps Due to Prolonged Arterial Arrival Time and How to Fix Them.

In resting-state functional MRI (rs-fMRI), functional networks are assessed utilizing the temporal correlation between spontaneous blood oxygen level-dependent signal fluctuations of spatially remote brain regions. Recently, several groups have shown that temporal shifts are present in rs-fMRI maps in patients with cerebrovascular disease due to spatial differences in arterial arrival times, and that this can be exploited to map arrival times in the brain. This suggests that rs-fMRI connectivity mapping may be similarly sensitive to such temporal shifts, and that standard rs-fMRI analysis methods may fail to identify functional connectivity networks. To investigate this, we studied the default mode network (DMN) in Moyamoya disease patients and compared it with normal healthy volunteers. Our results show that using standard independent component analysis (ICA) and seed-based approaches, arterial arrival delays lead to inaccurate incomplete characterization of functional connectivity within the DMN in Moyamoya disease patients. Furthermore, we propose two techniques to correct these errors, for seed-based and ICA methods, respectively. Using these methods, we demonstrate that it is possible to mitigate the deleterious effects of arterial arrival time on the assessment of functional connectivity of the DMN. As these corrections have not been applied to the vast majority of >200 prior rs-fMRI studies in patients with cerebrovascular disease, we suggest that they be interpreted with great caution. Correction methods should be applied in any rs-fMRI connectivity study of subjects expected to have abnormally delayed arterial arrival times.