Sensitive and specific biomarkers of myelin can help define baseline brain health and development, identify and monitor disease pathology, and evaluate response to treatment where myelin content is affected. Diffusion measures such as radial diffusivity (RD) are commonly used to assess myelin content, but are not specific to myelin. Inhomogeneous magnetization transfer (ihMT) and multicomponent driven equilibrium single-pulse observation of T1 and T2 (mcDESPOT) offer quantitative parameters (qihMT and myelin volume fraction/VF, respectively) which are suggested to have improved sensitivity to myelin. We compared RD, qihMT, and VF in a cohort of 23 healthy children aged 8-13 years to evaluate the similarities and differences across these measures. All 3 measures were significantly related across brain voxels, but VF and qihMT were significantly more strongly correlated (qihMT-VF r = 0.89) than either measure was with RD (RD-qihMT r = -0.66, RD-VF r = -0.74; all p < 0.001). Mean parameters differed in several regions, especially in subcortical gray matter. These differences can likely be explained by unique sensitivities of each measure to non-myelin factors, such as crossing fiber geometry, axonal packing, fiber orientation, glial density, or magnetization transfer effects in a voxel. We also observed an orientation dependence of qihMT in white matter, such that qihMT decreased as fiber orientation went from parallel to perpendicular to B. All measures appear to be sensitive to myelin content, though qihMT and VF appear to be more specific to it than RD. Scan time, noise tolerance, and resolution requirements may inform researchers of the appropriate measure to choose for a specific application.
BackgroundArterial spin labeling (ASL) can be confounded by varying arterial transit times (ATT) across the brain and with disease. Hadamard encoding schemes can be applied to 3D pseudocontinuous ASL (pCASL) to acquire ASL data with multiple postlabeling delays (PLDs) to estimate ATT and then correct cerebral blood flow (CBF).PurposeTo assess the longitudinal reproducibility of 3D pCASL with Hadamard‐encoded multiple PLDs.Study TypeProspective, longitudinal.PopulationFifty‐two healthy, right‐handed male subjects who underwent imaging at four timepoints over 45 days.Field Strength/SequenceA Hadamard‐encoded 3D pCASL sequence was acquired at 3.0T with seven PLDs from 1.0–3.7 sec.AssessmentATT and corrected CBF (cCBF) were computed. Conventional uncorrected CBF (unCBF) was also estimated. Within‐ and between‐subject coefficient of variation (wCV and bCV, respectively) and intraclass correlation coefficient (ICC) were evaluated across four time intervals: 7, 14, 30, and 45 days, in gray matter and 17 independent regions of interest (ROIs). A power analysis was also conducted.Statistical TestsA repeated‐measures analysis of variance (ANOVA) was used to compare ATT, cCBF, and unCBF across the four scan sessions. A paired two‐sample t‐test was used to compare cCBF and unCBF. Pearson's correlation was used to examine the relationship between the cCBF and unCBF difference and ATT. Power calculations were completed using both the cCBF and unCBF variances.ResultsATT showed the lowest wCV and bCV (3.3–4.4% and 6.0–6.3%, respectively) compared to both cCBF (10.5–11.7% and 20.6–22.2%, respectively) and unCBF (12.0–13.6% and 22.7–23.7%, respectively). wCV and bCV were lower for cCBF vs. unCBF. A significant difference between cCBF and unCBF was found in most regions (P = 5.5 × 10‐5–3.8 × 10‐4 in gray matter) that was highly correlated with ATT (R2 = 0.79–0.86). A power analysis yielded acceptable power at feasible sample sizes using cCBF.Data ConclusionATT and ATT‐corrected CBF were longitudinally stable, indicating that ATT and CBF changes can be reliably evaluated with Hadamard‐encoded 3D pCASL with multiple PLDs.Level of Evidence: 1Technical Efficacy Stage: 2J. Magn. Reson. Imaging 2020;51:1846–1853.
A novel sequence has been introduced that combines multiband imaging with a multi-echo acquisition for simultaneous high spatial resolution pseudo-continuous arterial spin labeling (ASL) and blood-oxygenation-level dependent (BOLD) echo-planar imaging (MBME ASL/BOLD). Resting-state connectivity in healthy adult subjects was assessed using this sequence. Four echoes were acquired with a multiband acceleration of four, in order to increase spatial resolution, shorten repetition time, and reduce slice-timing effects on the ASL signal. In addition, by acquiring four echoes, advanced multi-echo independent component analysis (ME-ICA) denoising could be employed to increase the signal-to-noise ratio (SNR) and BOLD sensitivity. Seed-based and dual-regression approaches were utilized to analyze functional connectivity. Cerebral blood flow (CBF) and BOLD coupling was also evaluated by correlating the perfusion-weighted timeseries with the BOLD timeseries. These metrics were compared between single echo (E2), multi-echo combined (MEC), multi-echo combined and denoised (MECDN), and perfusion-weighted (PW) timeseries. Temporal SNR increased for the MECDN data compared to the MEC and E2 data. Connectivity also increased, in terms of correlation strength and network size, for the MECDN compared to the MEC and E2 datasets. CBF and BOLD coupling was increased in major resting-state networks, and that correlation was strongest for the MECDN datasets. These results indicate our novel MBME ASL/BOLD sequence, which collects simultaneous high-resolution ASL/BOLD data, could be a powerful tool for detecting functional connectivity and dynamic neurovascular coupling during the resting state. The collection of more than two echoes facilitates the use of ME-ICA denoising to greatly improve the quality of resting state functional connectivity MRI.
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