Danny J.J. Wang

Recommended implementation of arterial spin-labeled Perfusion mri for clinical applications: A consensus of the ISMRM Perfusion Study group and the European consortium for ASL in dementia

This review provides a summary statement of recommended implementations of arterial spin labeling (ASL) for clinical applications. It is a consensus of the ISMRM Perfusion Study Group and the European ASL in Dementia consortium, both of whom met to reach this consensus in October 2012 in Amsterdam. Although ASL continues to undergo rapid technical development, we believe that current ASL methods are robust and ready to provide useful clinical information, and that a consensus statement on recommended implementations will help the clinical community to adopt a standardized approach. In this review, we describe the major considerations and trade‐offs in implementing an ASL protocol and provide specific recommendations for a standard approach. Our conclusion is that as an optimal default implementation, we recommend pseudo‐continuous labeling, background suppression, a segmented three‐dimensional readout without vascular crushing gradients, and calculation and presentation of both label/control difference images and cerebral blood flow in absolute units using a simplified model. Magn Reson Med 73:102–116, 2015.

Applications of Arterial Spin Labeled MRI in the Brain

Perfusion provides oxygen and nutrients to tissues and is closely tied to tissue function while disorders of perfusion are major sources of medical morbidity and mortality. It has been almost two decades since the use of arterial spin labeling (ASL) for noninvasive perfusion imaging was first reported. While initial ASL magnetic resonance imaging (MRI) studies focused primarily on technological development and validation, a number of robust ASL implementations have emerged, and ASL MRI is now also available commercially on several platforms. As a result, basic science and clinical applications of ASL MRI have begun to proliferate. Although ASL MRI can be carried out in any organ, most studies to date have focused on the brain. This review covers selected research and clinical applications of ASL MRI in the brain to illustrate its potential in both neuroscience research and clinical care. J. Magn. Reson. Imaging 2012;35:1026‐1037.

Test-retest reliability of arterial spin labeling with common labeling strategies.

To compare the test–retest reproducibility of three variants of arterial spin labeling (ASL): pseudo‐continuous (pCASL), pulsed (PASL) and continuous (CASL).

The Value of Arterial Spin-Labeled Perfusion Imaging in Acute Ischemic Stroke: Comparison With Dynamic Susceptibility Contrast-Enhanced MRI

Background and Purpose— The purpose of this study was to evaluate the potential clinical value of arterial spin-labeled (ASL) perfusion MRI in acute ischemic stroke (AIS) through comparison with dynamic susceptibility contrast (DSC) enhanced perfusion MRI. Methods— Pseudocontinuous ASL with 3-dimensional background-suppressed gradient and spin echo readout was applied with DSC perfusion MRI on 26 patients with AIS. ASL cerebral blood flow and multiparametric DSC perfusion maps were rated for image quality and lesion severity/conspicuity. Mean ASL cerebral blood flow and DSC perfusion values were obtained in main vascular territories. Kendall coefficient of concordance was calculated to evaluate the reliability of ratings. Spearman correlation coefficients were calculated to compare ratings and quantitative perfusion values between ASL and DSC perfusion maps. Results— ASL cerebral blood flow and DSC perfusion maps provided largely consistent results in delineating hypoperfused brain regions in AIS. Hyperemic lesions, which also appeared frequently in the AIS cases studied, were more conspicuous on ASL cerebral blood flow than on DSC cerebral blood flow, mean transit time and time to the maximum of the tissue residual function maps. Conclusions— As a rapid, noninvasive, and quantitative technique, ASL has clinical use in detecting blood flow abnormalities in patients with AIS.

Multi-delay multi-parametric arterial spin-labeled perfusion MRI in acute ischemic stroke — Comparison with dynamic susceptibility contrast enhanced perfusion imaging

The purpose of the present study was to present a multi-delay multi-parametric pseudo-continuous arterial spin labeling (pCASL) protocol with background suppressed 3D GRASE (gradient and spin echo) readout for perfusion imaging in acute ischemic stroke. PCASL data at 4 post-labeling delay times (PLD = 1.5, 2, 2.5, 3 s) were acquired within 4.5 min in 24 patients (mean age 79.7 ± 11.4 years; 11 men) with acute middle cerebral artery (MCA) stroke who also underwent dynamic susceptibility contrast (DSC) enhanced perfusion imaging. Arterial transit times (ATT) were estimated through the calculation of weighted delays across the 4 PLDs, which were included in the calculation of cerebral blood flow (CBF) and arterial cerebral blood volume (CBV). Mean perfusion parameters derived using pCASL and DSC were measured within MCA territories and infarct regions identified on diffusion weighted MRI. The results showed highly significant correlations between pCASL and DSC CBF measurements (r > = 0.70, p < = 0.0001) and moderately significant correlations between pCASL and DSC CBV measurements (r > = 0.45, p < = 0.027) in both MCA territories and infarct regions. ASL ATT showed correlations with DSC time to the maximum of tissue residual function (Tmax)(r = 0.66, p = 0.0005) and mean transit time (MTT)(r = 0.59, p = 0.0023) in leptomeningeal MCA territories. The present study demonstrated the feasibility for noninvasive multi-parametric perfusion imaging using ASL for acute stroke imaging.

Potentials and Challenges for Arterial Spin Labeling in Pharmacological Magnetic Resonance Imaging

Pharmacological magnetic resonance imaging (phMRI) is increasingly being used in drug discovery and development to speed the translation from the laboratory to the clinic. The two primary methods in phMRI include blood-oxygen-level-dependent (BOLD) contrast and arterial spin-labeled (ASL) perfusion MRI. BOLD contrast has been widely applied in existing phMRI studies. However, because of the lack of absolute quantification and poor reproducibility over time scales longer than hours or across scanning sessions, BOLD fMRI may not be suitable to track oral and other long-term drug effects on baseline brain function. As an alternative method, ASL provides noninvasive, absolute quantification of cerebral blood flow both at rest and during task activation. ASL perfusion measurements have been shown to be highly reproducible over minutes and hours to days and weeks. These two characteristics make ASL an ideal tool for phMRI for studying both intravenous and oral drug action as well as understanding drug effects on baseline brain function and brain activation to cognitive or sensory processing. When ASL is combined with BOLD fMRI, drug-induced changes in cerebral metabolic rate of oxygen may also be inferred. Representative phMRI studies using ASL perfusion MRI on caffeine, remifentanil, and metoclopramide (dopamine antagonist) are reviewed here, with an emphasis on the methodologies used to control for potentially confounding vascular and systemic effects. Both the potentials and limitations of using ASL as an imaging marker of drug action are discussed.

Longitudinal Reproducibility and Accuracy of Pseudo-Continuous Arterial Spin–labeled Perfusion MR Imaging in Typically Developing Children

PURPOSE To evaluate the longitudinal repeatability and accuracy of cerebral blood flow (CBF) measurements by using pseudo-continuous arterial spin-labeled (pCASL) perfusion magnetic resonance (MR) imaging in typically developing children. MATERIALS AND METHODS Institutional review board approval with HIPAA compliance and informed consent were obtained. Twenty-two children aged 7-17 years underwent repeated pCASL examinations 2-4 weeks apart with a 3-T MR imager, along with in vivo blood T1 and arterial transit time measurements. Phase-contrast (PC) MR imaging was performed as the reference standard for global blood flow volume. Intraclass correlation coefficient (ICC) and within-subject coefficient of variation (wsCV) were used to evaluate accuracy and repeatability. RESULTS The accuracy of pCASL against the reference standard of PC MR imaging increased on incorporating subjectwise in vivo blood T1 measurement (ICC: 0.32 vs 0.58). The ICC further increased to 0.65 by using a population-based model of blood T1. Additionally, CBF measurements with use of pCASL demonstrated a moderate to good level of longitudinal repeatability in whole brain (ICC = 0.61, wsCV = 15%), in gray matter (ICC = 0.65, wsCV = 14%), and across 16 brain regions (mean ICC = 0.55, wsCV = 17%). The mean arterial transit time was 1538 msec ± 123 (standard deviation) in the pediatric cohort studied, which showed an increasing trend with age (P = .043). CONCLUSION Incorporating developmental changes in blood T1 is important for improving the accuracy of pCASL CBF measurements in children and adolescents; the noninvasive nature, accuracy, and longitudinal repeatability should facilitate the use of pCASL perfusion MR imaging in neurodevelopmental studies.

Quantitative characterization of nuclear overhauser enhancement and amide proton transfer effects in the human brain at 7 tesla.

This study aimed to quantitatively investigate two main magnetization transfer effects at low B1: the nuclear Overhauser enhancement (NOE) and amide proton transfer in the human brain at 7 T.

In vivo venous blood T1 measurement using inversion recovery true-FISP in children and adults

A time‐efficient method is described for in vivo venous blood T1 measurement using multiphase inversion‐recovery‐prepared balanced steady‐state free precession imaging. Computer simulations and validation experiments using a flow phantom were carried out to demonstrate the accuracy of the proposed method for measuring blood T1 by taking advantage of the continuous inflow of fresh blood with longitudinal magnetization undisturbed by previous radiofrequency pulses. In vivo measurement of venous blood T1 in the sagittal sinus was carried out in 26 healthy children and adults aged 7–39 years. The measured venous blood T1 values decreased with age as a whole (P = 0.006) and were higher in females than males (P = 0.013), matching the expected developmental changes and gender differences in human hematocrit level. The estimated mean blood T1 values were highly correlated with normal hematocrit levels across age and gender groups (Spearmans r = 0.93, P = 0.008). The longitudinal repeatability of this technique was 4.0% as measured by the within‐subject coefficient of variation. The proposed multiphase inversion recovery‐prepared balanced steady‐state free precession imaging method is a feasible technique for fast (<1 min) and reliable in vivo venous blood T1 measurement and may serve as an index of hematocrit level in individual subjects. Magn Reson Med, 2010.

Quantification issues in arterial spin labeling perfusion magnetic resonance imaging.

Arterial spin labeling (ASL) perfusion magnetic resonance imaging has gained wide acceptance for its value in clinical and neuroscience applications during recent years. Its capability for noninvasive and absolute perfusion quantification is a key characteristic that makes ASL attractive for many clinical applications. In the present review, we discuss the main parameters or factors that affect the reliability and accuracy of ASL perfusion measurements. Our secondary goal was to outline potential solutions that may improve the reliability and accuracy of ASL in clinical settings. It was found that, through theoretical analyses, flow quantification is most sensitive to tagging efficiency and estimation of the equilibrium magnetization of blood signal (M0b). Variations of blood T1 have a greater effect on perfusion quantification than variations of tissue T1. Arterial transit time becomes an influential factor when it is longer than the postlabeling delay time. The T2s of blood and tissue impose minimal effects on perfusion calculation at field strengths equal to or lower than 3.0 T. Subsequently, we proposed various approaches for in vivo estimation or calibration of the above parameters, such as the use of phase-contrast magnetic resonance imaging for calibration of the labeling efficiency as well as the use of inversion recovery TrueFISP (true fast imaging with steady-state precession) sequence for blood T1 mapping. We also list representative clinical cases in which implicit assumptions for ASL perfusion quantification may be violated, such as the venous outflow effect in children with sickle cell disease. Finally, an optimal imaging protocol including in vivo measurements of several critical parameters was recommended for clinical ASL studies.