Jiongjiong Wang

A Theoretical and Experimental Investigation of the Tagging Efficiency of Pseudocontinuous Arterial Spin Labeling

Arterial spin labeling (ASL) is capable of noninvasively measuring blood flow by magnetically tagging the protons in arterial blood, which has been conventionally achieved using instantaneous (PASL) or continuous (CASL) RF pulses. As an intermediate method, pseudocontinuous ASL (pCASL) utilizes a train of discrete RF pulses to mimic continuous tagging that is often unavailable on imagers due to the requirement of continuous RF transmit capabilities. In the present study, we implemented two versions of pCASL (balanced and unbalanced gradient waveforms in tag and control scans) for both transmit/receive coils and array receivers. Experimental data show a 50% ± 4% increase of signal‐to‐noise ratio (SNR) compared with PASL and a higher tagging efficiency than amplitude‐modulated (AM) CASL (80% vs. 68%). Computer simulations predict an optimal tagging efficiency of 85% for flow velocities from 10 to 60 cm/s. It is theoretically and experimentally demonstrated that the tagging efficiency of pCASL is dependent upon the resonance offset and flip angle of the RF pulse train. We conclude that pCASL has the potential of combining the merits of PASL, including less hardware demand and higher tagging efficiency, and CASL, which includes a longer tagging bolus and thus higher SNR. These improvements provide a better balance between tagging efficiency and SNR. Magn Reson Med 58:1020–1027, 2007.

Comparison of quantitative perfusion imaging using arterial spin labeling at 1.5 and 4.0 Tesla

High‐field arterial spin labeling (ASL) perfusion MRI is appealing because it provides not only increased signal‐to‐noise ratio (SNR), but also advantages in terms of labeling due to the increased relaxation time T1 of labeled blood. In the present study, we provide a theoretical framework for the dependence of the ASL signal on the static field strength, followed by experimental validation in which a multislice pulsed ASL (PASL) technique was carried out at 4T and compared with PASL and continuous ASL (CASL) techniques at 1.5T, both in the resting state and during motor activation. The resting‐state data showed an SNR ratio of 2.3:1.4:1 in the gray matter and a contrast‐to‐noise ratio (CNR) of 2.7:1.1:1 between the gray and white matter for the difference perfusion images acquired using 4T PASL, 1.5T CASL, and 1.5T PASL, respectively. However, the functional data acquired using 4T PASL did not show significantly improved sensitivity to motor cortex activation compared with the 1.5T functional data, with reduced fractional perfusion signal change and increased intersubject variability. Possible reasons for these experimental results, including susceptibility effects and physiological noise, are discussed. Magn Reson Med 48:242–254, 2002.

Limbic Activation to Cigarette Smoking Cues Independent of Nicotine Withdrawal: A Perfusion fMRI Study

Exposure to cigarette smoking cues can trigger physiological arousal and desire to smoke. The brain substrates of smoking cue-induced craving (CIC) are beginning to be elucidated; however, it has been difficult to study this state independent of the potential contributions of pharmacological withdrawal from nicotine. Pharmacological withdrawal itself may have substantial effects on brain activation to cues, either by obscuring or enhancing it, and as CIC is not reduced by nicotine replacement strategies, its neuro-anatomical substrates may differ. Thus, characterizing CIC is critical for developing effective interventions. This study used arterial spin-labeled (ASL) perfusion fMRI, and newly developed and highly appetitive, explicit smoking stimuli, to examine neural activity to cigarette CIC in an original experimental design that strongly minimizes contributions from pharmacological withdrawal. Twenty-one smokers (12 females) completed smoking and nonsmoking cue fMRI sessions. Craving self-reports were collected before and after each session. SPM2 software was employed to analyze data. Blood flow (perfusion) in a priori-selected regions was greater during exposure to smoking stimuli compared to nonsmoking stimuli (p<0.01; corrected) in ventral striatum, amygdala, orbitofrontal cortex, hippocampus, medial thalamus, and left insula. Perfusion positively correlated with intensity of cigarette CIC in both the dorsolateral prefrontal cortex (r2=0.54) and posterior cingulate (r2=0.53). This pattern of activation that includes the ventral striatum, a critical reward substrate, and the interconnected amygdala, cingulate and OFC, is consistent with decades of animal research on the neural correlates of conditioned drug reward.

Arterial spin labeling perfusion fMRI with very low task frequency

Functional magnetic resonance imaging (fMRI) has become the most widely used modality for visualizing regional brain activation in response to sensorimotor or cognitive tasks. While the majority of fMRI studies have used blood oxygenation level‐dependent (BOLD) contrast as a marker for neural activation, baseline drift effects result in poor sensitivity for detecting slow variations in neural activity. By contrast, drift effects are minimized in arterial spin labeling (ASL) perfusion contrast, primarily as a result of successive pairwise subtraction between images acquired with and without labeling. Recent data suggest that ASL contrast shows stable noise characteristics over the entire frequency spectrum, which makes it suitable for studying low‐frequency events in brain function. The present study investigates the relative sensitivities of ASL and BOLD contrast in detecting changes in motor cortex activation over a spectrum of frequencies of experimental design, where the alternating period between the resting state and activation is varied from 30 s up to 24 hr. The results demonstrate that 1) ASL contrast can detect differences in motor cortex activation over periods of minutes, hours, and even days; 2) the functional sensitivity of ASL contrast becomes superior to that of BOLD contrast when the alternating period between the resting state and activation is greater than a few minutes; and 3) task activation measured by ASL tends to have less intersubject variability than BOLD contrast. The improved sensitivity of the ASL contrast for low task frequency and longitudinal studies, along with its superior power in group analysis, is expected to extend the range of experimental designs that can be studied using fMRI. Magn Reson Med 49:796–802, 2003.

Diffuse optical measurement of blood flow, blood oxygenation, and metabolism in a human brain during sensorimotor cortex activation

We combine diffuse optical and correlation spectroscopies to simultaneously measure the oxyhemoglobin and deoxyhemoglobin concentration and blood flow in an adult human brain during sensorimotor stimulation. The observations permit calculation of the relative cerebral metabolic rate of oxygen in the human brain, for the first time to our knowledge, by use of all-optical methods. The feasibility for noninvasive optical measurement of blood flow through the skull of an adult brain is thus demonstrated, and the clinical potential of this hybrid, all-optical noninvasive, methodology can now be explored.

Technical aspects and utility of fMRI using BOLD and ASL

Functional magnetic resonance imaging (fMRI) is an emerging methodology which provides various approaches to visualizing regional brain activity non-invasively. Although the exact mechanisms underlying the coupling between neural function and fMRI signal changes remain unclear, fMRI studies have been successful in confirming task-specific activation in a variety of brain regions, providing converging evidence for functional localization. In particular, fMRI methods based on blood oxygenation level dependent (BOLD) contrast and arterial spin labeling (ASL) perfusion contrast have enabled imaging of changes in blood oxygenation and cerebral blood flow (CBF). While BOLD contrast has been widely used as the surrogate marker for neural activation and can provide reliable information on the neuroanatomy underlying transient sensorimotor and cognitive functions, recent evidence suggests perfusion contrast is suitable for studying relatively long term effects on CBF both at rest or during activation. New developments in combining or simultaneously measuring the electrophysiological and fMRI signals allow a new class of studies that capitalize on dynamic imaging with high spatiotemporal resolution. This article reviews the biophysical bases and methodologies of fMRI and its applications to the clinical neurosciences, with emphasis on the spatiotemporal resolution of fMRI and its coupling with neurophysiology under both normal and pathophysiological conditions.

Arterial transit time imaging with flow encoding arterial spin tagging (FEAST)

Arterial spin labeling (ASL) perfusion imaging provides direct and absolute measurement of cerebral blood flow (CBF). Arterial transit time is a related physiological parameter reflecting the duration for the labeled spins to reach the brain region of interest. Most of the existing ASL approaches to assess arterial transit time rely on multiple measurements at various postlabeling delay times, and thus are vulnerable to motion artifact as well as computational error. We describe the use of flow encoding arterial spin tagging (FEAST) technique to measure tissue transit time, which can be derived from the ratio between the ASL signals measured with and without appropriate bipolar gradients. In the present study, we provided a theoretical framework and carried out an experimental validation during steady‐state imaging. The global mean tissue transit time was ∼1100 and 1400 ms for two conditions of bipolar gradients with specific encoding velocity (Venc) of 29 and 8 mm/sec, respectively. The mean tissue transit time measured within cerebral vascular territories was shortest in the deep middle cerebral artery (MCA) territory. Application of the FEAST technique in two patients with cerebrovascular disease demonstrated prolonged tissue transit times in the affected vascular territories which were consistent with results from other MR imaging modalities. Magn Reson Med 50:599–607, 2003.

Pediatric Perfusion Imaging Using Pulsed Arterial Spin Labeling

To test the feasibility of pediatric perfusion imaging using a pulsed arterial spin labeling (ASL) technique at 1.5 T.

Arterial spin-labeled perfusion MRI in basic and clinical neuroscience

Purpose of reviewArterial spin labeling (ASL) provides an endogenous and completely noninvasive tracer for the quantification of regional cerebral blood flow (CBF) with magnetic resonance imaging (MRI). Although the measurement of CBF has obvious utility in cerebrovascular disorders, because CBF is closely coupled to neural metabolism, ASL perfusion MRI has a broad range of potential applications as a biomarker of regional brain function in basic and clinical neuroscience. Recent findingsOver the past few years, ASL technology has improved considerably and the utility of ASL perfusion MRI as a diagnostic and research tool has been demonstrated. This review briefly covers ASL methodologies and clinical applications, while expanding on the use of ASL in human neuroscience research to elucidate patterns of resting brain function that correlate with genotype or phenotype (trait effects), or in response to exogenous manipulations of brain function with pharmacological agents or psychological tasks (state effects). SummaryASL perfusion MRI provides a versatile biomarker of regional brain function that can be acquired as part of a multimodal MRI examination. Because ASL quantifies a physiological parameter, it should be useful for multisite or longitudinal studies.

Validation of diffuse correlation spectroscopy for muscle blood flow with concurrent arterial spin labeled perfusion MRI

Calf blood flow was measured simultaneously in healthy human subjects (n = 7) during cuff inflation and deflation using near-infrared diffuse correlation spectroscopy (DCS) and arterial spin labeled perfusion MRI (ASL-MRI). The DCS and ASL-MRI data exhibited highly correlated absolute and relative dynamic flow responses in each individual (p < 0.001). Peak flow variations during hyperemia were also significantly correlated, though more for relative (p = 0.003) than absolute (p = 0.016) flow. Repeated measurement variation was less than 8% for both modalities. The results provide much needed quantitative blood flow validation of the diffuse optical correlation method in humans.