Reliability and sensitivity to alterered hemodynamics measured with resting-state fMRI metrics: Comparison with (123) I-IMP SPECT

Blood oxygenation level-dependent (BOLD) contrast is sensitive to local hemodynamic changes and thus is applicable to imaging perfusion or vascular reactivity. However, knowledge about its measurement characteristics compared to reference standard perfusion imaging is limited. This study longitudinally evaluated perfusion in patients with steno-occlusive disease using resting-state functional MRI (rsfMRI) acquired before and within nine days of anterior circulation revascularization in patients with large cerebral artery steno-occlusive diseases. The reliability and sensitivity to longitudinal changes of rsfMRI temporal correlation (Rc) and time delay (TDc) relative to the cerebellar signal were examined voxel-wise in comparison with single-photon emission CT (SPECT) cerebral blood flow (CBF) using the within-subject standard deviation (Sw) and intraclass correlation coefficients (ICCs). For statistical comparisons, the standard deviation (SD) of longitudinal changes within the cerebellum, the number of voxels with significant changes in the left middle cerebral artery territory ipsilateral to surgery, and their average changes relative to the cerebellar SD were evaluated. The test-retest reliability of the fMRI met-rics was also similarly evaluated using the human connectome project (HCP) healthy young adult dataset. The test-retest time interval was 31 +/- 18 days. Test-retest reliability was significantly higher for SPECT (cerebellar SD: -2.59 +/- 0.20) than for fMRI metrics (cerebellar SD: Rc, - 2.34 +/- 0.24, p = 0.04; TDc, - 2.19 +/- 0.21, p = 0.003). Sensitivity to postoperative changes, which was evaluated as the number of voxels, was significantly higher for fMRI TDc (8.78 +/- 0.72) than for Rc (7.42 +/- 1.48, p = 0.03) or SPECT CBF (6.88 +/- 0.67, p < 0.001). The ratio between the average Rc, TDc, and SPECT CBF changes within the left MCA target region and cerebellar SD was also significantly higher for fMRI TDc (1.21 +/- 0.79) than Rc (0.48 +/- 0.94, p = 0.006) or SPECT CBF (0.23 +/- 0.57, p = 0.001). The measurement variability of time delay was also larger than that of temporal correlation in HCP data within the cerebellum ( t = -8.7, p < 0.001) or in the whole-brain ( t = -27.4, p < 0.001) gray matter. These data suggest that fMRI time delay is more sensitive to the hemodynamic changes than SPECT CBF, although the reliability is lower. The implication for fMRI connectivity studies is that temporal correlation can be significantly decreased due to altered hemodynamics, even in cases with normal CBF.