Lirong Yan

Physiological origin of low‐frequency drift in blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI)

We investigated the biophysical mechanism of low‐frequency drift in blood‐oxygen‐level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) (0.00–0.01 Hz), by exploring its spatial distribution, dependence on imaging parameters, and relationship with task‐induced brain activation. Cardiac and respiratory signals were concurrently recorded during MRI scanning and subsequently removed from MRI data. It was found that the spatial distribution of low‐frequency drifts in human brain followed a tissue‐specific pattern, with greater drift magnitude in the gray matter than in white matter. In gray matter, the dependence of drift magnitudes on TE was similar to that of task‐induced BOLD signal changes, i.e., the absolute drift magnitude reached the maximum when TE approached T  2* whereas relative drift magnitude increased linearly with TE. By systematically varying the flip angle, it was found that drift magnitudes possessed a positive dependence on image intensity. In phantom experiments, the observed drift was not only much smaller than that of human brain, but also showed different dependence on TE and flip angle. In fMRI studies with visual stimulation, a strong positive correlation between drift effects at baseline and task‐induced BOLD signal changes was observed both across subjects and across activated pixels within individual participants. We further demonstrated that intrinsic, physiological drift effects are a major component of the spontaneous fluctuations of BOLD fMRI signal within the frequency range of 0.0–0.1 Hz. Our study supports brain physiology, as opposed to scanner instabilities or cardiac/respiratory pulsations, as the main source of low‐frequency drifts in BOLD fMRI. Magn Reson Med 61, 2009.

Unenhanced Dynamic MR Angiography: High Spatial and Temporal Resolution by Using True FISP–based Spin Tagging with Alternating Radiofrequency

PURPOSE To present an unenhanced four-dimensional time-resolved dynamic magnetic resonance (MR) angiography technique with true fast imaging with steady-state precession-based spin tagging with alternating radiofrequency (STAR), also called TrueSTAR. MATERIALS AND METHODS This study received Institutional Review Board approval and was HIPAA compliant. Informed consent was obtained from all study subjects. In eight healthy volunteers, the spatial and temporal resolution of the TrueSTAR technique were optimized. In another six healthy volunteers, the contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) of the TrueSTAR dynamic MR angiography images were compared with those acquired by using a standard Look-Locker echo-planar technique by using the Wilcoxon signed rank test. Finally, one patient with an arteriovenous malformation (AVM) was studied by using this technique. RESULTS The SNR and CNR of the TrueSTAR dynamic MR angiography images were 29% and 39% higher, respectively, compared with those acquired by using a standard Look-Locker echo-planar imaging sequence (both P = .028). In the AVM patient, TrueSTAR dynamic MR angiography delineated the dynamic course of labeled blood flowing through feeding arteries into the nidus and draining veins. CONCLUSION The results suggest that TrueSTAR is a promising unenhanced dynamic MR angiography technique for clinical evaluation of cerebrovascular disorders such as AVM, steno-occlusive disease, and aneurysm.

Noncontrast dynamic MRA in intracranial arteriovenous malformation (AVM), comparison with time of flight (TOF) and digital subtraction angiography (DSA).

Digital subtraction angiography (DSA) remains the gold standard to diagnose intracranial arteriovenous malformations (AVMs) but is invasive. Existing magnetic resonance angiography (MRA) is suboptimal for assessing the hemodynamics of AVMs. The objective of this study was to evaluate the clinical utility of a novel noncontrast four-dimensional (4D) dynamic MRA (dMRA) in the evaluation of intracranial AVMs through comparison with DSA and time-of-flight (TOF) MRA. Nineteen patients (12 women, mean age 26.2±10.7 years) with intracranial AVMs were examined with 4D dMRA, TOF and DSA. Spetzler-Martin grading scale was evaluated using each of the above three methods independently by two raters. Diagnostic confidence scores for three components of AVMs (feeding artery, nidus and draining vein) were also rated. Kendalls coefficient of concordance was calculated to evaluate the reliability between two raters within each modality (dMRA, TOF, TOF plus dMRA). The Wilcoxon signed-rank test was applied to compare the diagnostic confidence scores between each pair of the three modalities. dMRA was able to detect 16 out of 19 AVMs, and the ratings of AVM size and location matched those of DSA. The diagnostic confidence scores by dMRA were adequate for nidus (3.5/5), moderate for feeding arteries (2.5/5) and poor for draining veins (1.5/5). The hemodynamic information provided by dMRA improved diagnostic confidence scores by TOF MRA. As a completely noninvasive method, 4D dMRA offers hemodynamic information with a temporal resolution of 50-100 ms for the evaluation of AVMs and can complement existing methods such as DSA and TOF MRA.

Reliability of two‐dimensional and three‐dimensional pseudo‐continuous arterial spin labeling perfusion MRI in elderly populations: Comparison with 15o‐water positron emission tomography

To investigate the reliability and accuracy of two pseudo‐continuous arterial spin labeling (pCASL) sequences, using two‐dimensional (2D) gradient‐echo echo planar imaging (EPI) and 3D gradient and spin echo (GRASE) as the readout, respectively.

Complexity and synchronicity of resting state blood oxygenation level-dependent (BOLD) functional MRI in normal aging and cognitive decline.

To explore the use of approximate entropy (ApEn) as an index of the complexity and the synchronicity of resting state blood oxygenation level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) in normal aging and cognitive decline associated with familial Alzheimers disease (fAD).Purpose To explore the use of approximate entropy (ApEn) as an index of the complexity and the synchronicity of resting state BOLD fMRI in normal aging and cognitive decline associated with familial Alzheimer’s disease (fAD).

Dynamic and static contributions of the cerebrovasculature to the resting-state BOLD signal

Functional magnetic resonance imaging (fMRI) in the resting state, particularly fMRI based on the blood-oxygenation level-dependent (BOLD) signal, has been extensively used to measure functional connectivity in the brain. However, the mechanisms of vascular regulation that underlie the BOLD fluctuations during rest are still poorly understood. In this work, using dual-echo pseudo-continuous arterial spin labeling and MR angiography (MRA), we assess the spatio-temporal contribution of cerebral blood flow (CBF) to the resting-state BOLD signals and explore how the coupling of these signals is associated with regional vasculature. Using a general linear model analysis, we found that statistically significant coupling between resting-state BOLD and CBF fluctuations is highly variable across the brain, but the coupling is strongest within the major nodes of established resting-state networks, including the default-mode, visual, and task-positive networks. Moreover, by exploiting MRA-derived large vessel (macrovascular) volume fraction, we found that the degree of BOLD-CBF coupling significantly decreased as the ratio of large vessels to tissue volume increased. These findings suggest that the portion of resting-state BOLD fluctuations at the sites of medium-to-small vessels (more proximal to local neuronal activity) is more closely regulated by dynamic regulations in CBF, and that this CBF regulation decreases closer to large veins, which are more distal to neuronal activity.

Multiple time scale complexity analysis of resting state FMRI.

The present study explored multi-scale entropy (MSE) analysis to investigate the entropy of resting state fMRI signals across multiple time scales. MSE analysis was developed to distinguish random noise from complex signals since the entropy of the former decreases with longer time scales while the latter signal maintains its entropy due to a “self-resemblance” across time scales. A long resting state BOLD fMRI (rs-fMRI) scan with 1000 data points was performed on five healthy young volunteers to investigate the spatial and temporal characteristics of entropy across multiple time scales. A shorter rs-fMRI scan with 240 data points was performed on a cohort of subjects consisting of healthy young (age 23 ± 2 years, n = 8) and aged volunteers (age 66 ± 3 years, n = 8) to investigate the effect of healthy aging on the entropy of rs-fMRI. The results showed that MSE of gray matter, rather than white matter, resembles closely that of f−1 noise over multiple time scales. By filtering out high frequency random fluctuations, MSE analysis is able to reveal enhanced contrast in entropy between gray and white matter, as well as between age groups at longer time scales. Our data support the use of MSE analysis as a validation metric for quantifying the complexity of rs-fMRI signals.

Loss of Coherence of Low Frequency Fluctuations of BOLD FMRI in Visual Cortex of Healthy Aged Subjects

Aging effects on blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) have been studied using task induced hemodynamic responses with controversial findings. The present study systematically investigated the normal aging effect in the visual cortex using 3 indices of low frequency fluctuations of resting state BOLD fMRI, i.e., amplitude of low frequency fluctuations (ALFF), regional homogeneity (ReHo) and functional connectivity (FC). These 3 resting state measurements were compared with task induced BOLD activation in the visual cortex of 2 groups of 10 young and 10 elderly subjects. Our results showed reduced functional connectivity and regional homogeneity of low frequency fluctuations of BOLD fMRI in aged subjects as compared to young subjects. While the mean magnitude of BOLD activation and the mean amplitude of low frequency fluctuations of BOLD fMRI did not vary between the 2 age groups, larger variances were observed in both measures in aged subjects. These data suggest that normal aging may be associated with “loss of coherence” of low frequency fluctuations of resting state BOLD fMRI in the visual cortex, and may affect task induced BOLD response through increased inter- and intra-subject variability.

The pediatric template of brain perfusion

Magnetic resonance imaging (MRI) captures the dynamics of brain development with multiple modalities that quantify both structure and function. These measurements may yield valuable insights into the neural patterns that mark healthy maturation or that identify early risk for psychiatric disorder. The Pediatric Template of Brain Perfusion (PTBP) is a free and public neuroimaging resource that will help accelerate the understanding of childhood brain development as seen through the lens of multiple modality neuroimaging and in relation to cognitive and environmental factors. The PTBP uses cross-sectional and longitudinal MRI to quantify cortex, white matter, resting state functional connectivity and brain perfusion, as measured by Arterial Spin Labeling (ASL), in 120 children 7–18 years of age. We describe the PTBP and show, as a demonstration of validity, that global summary measurements capture the trajectories that demarcate critical turning points in brain maturation. This novel resource will allow a more detailed understanding of the network-level, structural and functional landmarks that are obtained during normal adolescent brain development.

Quantification of arterial cerebral blood volume using multiphase-balanced SSFP-based ASL.

A new technique is introduced in this study for in vivo measurement of arterial cerebral blood volume by combining arterial spin labeling with a segmented multiphase balanced steady‐state free precession (bSSFP) readout sequence. This technique takes advantage of the phenomenon that the longitudinal magnetization of flowing blood is not or only marginally disturbed (besides T1 relaxation) by the bSSFP ±α pulse train. When the blood water exchanges into tissue, it becomes quickly saturated by the bSSFP pulse train due to 0 velocity and reduced T1, T2 relaxation times. Therefore, labeled blood water behaves like an intravascular contrast agent in multiphase bSSFP scans, and can be used to quantify arterial cerebral blood volume in a similar way as dynamic susceptibility contrast MRI. Both Bloch equation simulation and in vivo experiments were carried out to demonstrate the feasibility for quantifying cerebral blood volume in arteries, arterioles, and capillaries using two variants of the proposed method. Functional MRI of visual cortex stimulation was further performed using multiphase bSSFP‐based arterial spin labeling and compared with vascular‐space occupancy contrast. The proposed multiphase bSSFP‐based arterial spin labeling technique may allow separation of cerebral blood volume of different vascular compartments for functional MRI studies and clinical evaluation of the cerebral vasculature. Magn Reson Med, 2012.