This article 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 article we describe the major considerations and tradeoffs in implementing an ASL protocol, and provide specific recommendations for a standard approach. Our conclusions are that, as an optimal default implementation we recommend: pseudo-continuous labeling, background suppression, a segmented 3D 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.

Measurement of tissue perfusion is important for the functional assessment of organs in vivo. Here we report the use of 1H NMR imaging to generate perfusion maps in the rat brain at 4.7 T. Blood water flowing to the brain is saturated in the neck region with a slice-selective saturation imaging sequence, creating an endogenous tracer in the form of proximally saturated spins. Because proton T1 times are relatively long, particularly at high field strengths, saturated spins exchange with bulk water in the brain and a steady state is created where the regional concentration of saturated spins is determined by the regional blood flow and regional T1. Distal saturation applied equidistantly outside the brain serves as a control for effects of the saturation pulses. Average cerebral blood flow in normocapnic rat brain under halothane anesthesia was determined to be 105 +/- 16 cc.100 g-1.min-1 (mean +/- SEM, n = 3), in good agreement with values reported in the literature, and was sensitive to increases in arterial pCO2. This technique allows regional perfusion maps to be measured noninvasively, with the resolution of 1H MRI, and should be readily applicable to human studies.

A technique has been developed for proton magnetic resonance imaging (MRI) of perfusion, using water as a freely diffusable tracer, and its application to the measurement of cerebral blood flow (CBF) in the rat is demonstrated. The method involves labeling the inflowing water proton spins in the arterial blood by inverting them continuously at the neck region and observing the effects of inversion on the intensity of brain MRI. Solution to the Bloch equations, modified to include the effects of flow, allows regional perfusion rates to be measured from an image with spin inversion, a control image, and a T, image. Continuous spin inversion labeling the arterial blood water was accomplished, using principles of adiabatic fast passage by applying continuous-wave radiofrequency power in the presence of a magnetic field gradient in the direction of arterial flow. In the detection slice used to measure perfusion, whole brain CBF averaged 1.39 ± 0.19 ml'g'1 min-' (mean ± SEM, n = 5). The technique's sensitivity to changes in CBF was measured by using graded hypercarbia, a condition that is known to increase brain perfusion. CBF vs.PCO2 data yield a best-fit straight line described by CBF (ml-g'-minin) = [19F]trifluoromethane (7-9), and chelated gadolinium contrast agents (10), have led to measurements of tissue perfusion.Here we describe an alternative technique for proton magnetic resonance imaging (MRI) of perfusion rates in the brain by using endogenous water as a diffusable tracer. The method involves labeling the water proton nuclear spins in the arterial blood by continuously inverting them in the neck region before they enter the brain. Continuous inversion is accomplished adiabatically, taking advantage of the linear bulk motion of the blood (11). Proton MRI is used to monitor the effects of perfusion delivering the spin-labeled water to the brain. Solutions to the Bloch equations, which describe the time dependence of magnetization, modified to include the effects of flow, allow regional perfusion rates to be calculated from a set of three images. These are an image with spin inversion, a control image, and a T1 image. We apply this technique to the measurement ofrat brain cerebral blood flow (CBF). To assess the technique's sensitivity to changes in perfusion, we have determined CBF under graded hypercarbia, a condition that is known to increase CBF (12). Finally, by generating perfusion images of a freeze-injured rat brain, we demonstrate that the technique can detect abnormalities in regional CBF. MATERIALS AND METHODSAnimal Preparation. Male Sprague-Dawley rats (200-300 g; Taconic Farms) were anesthetized with 5% halothane, orally intubated, and ventilated on 1% halothane and a 1:1 N20/02 mixture. A femoral arterial line was used for monitoring blood pressure and to sample blood for blood gas determinations. The core temperature of the rats was maintained at 37 ± 1PC by using a circulating water pad. Arterial pCO2 was altered by adding various amounts of CO2 to the ventilator gas mixture up to a...

Glutamate (Glu) exhibits a pH and concentration dependent chemical exchange saturation transfer effect (CEST) between its -amine group and bulk water, here termed GluCEST. GluCEST asymmetry is observed at ~3 parts per million downfield from bulk water. Following middle cerebral artery occlusion in the rat brain, an approximately 100% elevation of GluCEST in the ipsilateral side compared to the contralateral side was observed, and is predominantly due to pH changes. In a rat brain tumor model with blood brain barrier disruption, intravenous Glu injection resulted in a clear elevation of GluCEST and a comparable increase in the proton magnetic resonance spectroscopy signal of Glu. GluCEST maps from healthy human brain at 7T were also obtained. These results demonstrate the feasibility and potential of GluCEST for mapping relative changes in Glu concentration as well as pH in vivo. Potential contributions from other brain metabolites to the GluCEST effect are also discussed.

Herein, we present a theoretical framework and experimental methods to more accurately account for transit effects in quantitative human perfusion imaging using endogenous magnetic resonance imaging (MRI) contrast. The theoretical transit time sensitivities of both continuous and pulsed inversion spin tagging experiments are demonstrated. We propose introducing a delay following continuous labeling, and demonstrate theoretically that introduction of a delay dramatically reduces the transit time sensitivity of perfusion imaging. The effects of magnetization transfer saturation on this modified continuous labeling experiment are also derived, and the assumption that the perfusion signal resides entirely within tissue rather than the arterial microvasculature is examined. We present results demonstrating the implementation of the continuous tagging experiment with delay on an echoplanar scanner for measuring cerebral blood flow (CBF) in normal volunteers. By varying the delay, we estimate transit times in the arterial system, values that are necessary for assessing the accuracy of our quantification. The effect of uncertainties in the transit time from the tagging plane to the arterial microvasculature and the transit time to the tissue itself on the accuracy of perfusion quantification is discussed and found to be small in gray matter but still potentially significant in white matter. A novel method for measuring T1, which is fast, insensitive to contamination by cerebrospinal fluid, and compatible with the application of magnetization transfer saturation, is also presented. The methods are combined to produce quantitative maps of resting and hypercarbic CBF.

Working memory refers to a system for temporary storage and manipulation of information in the brain, a function critical for a wide range of cognitive operations. It has been proposed that working memory includes a central executive system (CES) to control attention and information flow to and from verbal and spatial short-term memory buffers. Although the prefrontal cortex is activated during both verbal and spatial passive working memory tasks, the brain regions involved in the CES component of working memory have not been identified. We have used functional magnetic resonance imaging (fMRI) to examine brain activation during the concurrent performance of two tasks, which is expected to engage the CES. Activation of the prefrontal cortex was observed when both tasks are performed together, but not when they are performed separately. These results support the view that the prefrontal cortex is involved in human working memory.

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. © 2014 Wiley Periodicals, Inc.

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.