NMR Measurement of Perfusion Using Arterial Spin Labeling Without Saturation of Macromolecular Spins

When measuring perfusion by arterial spin labeling, saturation of tissue macromolecular spins during arterial spin labeling greatly decreases tissue water magnetization, reducing the sensitivity of the technique. In this work, a theory has been developed for perfusion measurement by arterial spin labeling without saturation of macromolecular spins. A two-coil system was used to achieve arterial spin labeling without saturation of brain tissue macromolecular spins for NMR measurement of rat cerebral perfusion. The effects of crossrelaxation on the measurement of perfusion have been studied in the absence of macromolecular spin saturation, and it is demonstrated that at 4.7 Tesla, perfusion is underestimated by approximately 17% when the effect of cross-relaxation is neglected in the calculation of perfusion. However, assuming water to be a freely diffusable tracer, the effect of cross-relaxation is predicted to be flow independent, and it can, thus, be accounted for in the calculation of perfusion. The theory and experiments are presented to estimate tissue perfusion, magnetization transfer rate constants, and spin-lattice relaxation times of water and macromolecular spins in rat brain.     

Multi-Slice MRI of Rat Brain Perfusion During Amphetamine Stimulation Using Arterial Spin Labeling

When a single coil is used to measure perfusion by arterial spin labeling, saturation of macromolecular protons occurs during the labeling period. Induced magnetization transfer contrast (MTC) effects decrease tissue water signal intensity, reducing the sensitivity of the technique. In addition, MTC effects must be properly accounted for in acquiring a control image. This forces the image to a single slice centered between the labeling plane and the control plane. In this work, a two-coil system is presented as a way to avoid saturation of macromolecular spins during arterial spin labeling. The system consists of one small surface coil for labeling the arterial water spins, and a head coil for MRI, actively decoupled from the labeling coil by using PIN diodes. It is shown that no signal loss occurs due to MTC effects when the two-coil system is used for MRI of rat brain perfusion, enabling three-dimensional perfusion imaging. Using the two-coil system, a multi-slice MRI sequence was used to study the regional effects of amphetamine on brain perfusion. Amphetamine causes significant increases in perfusion in many areas of the brain including the cortex, cingulate, and caudate putamen, in agreement with previous results using deoxyglucose uptake to monitor brain activation.     

Perfusion imaging using dynamic arterial spin labeling (DASL).

Recently, a technique based on arterial spin labeling, called dynamic arterial spin labeling (DASL (Magn Reson Med 1999;41:299-308)), has been introduced to measure simultaneously the transit time of the labeled blood from the labeling plane to the exchange site, the longitudinal relaxation time of the tissue, and the perfusion of the tissue. This technique relies on the measurement of the tissue magnetization response to a time varying labeling function. The analysis of the characteristics of the tissue magnetization response (transit time, filling time constant, and perfusion) allows for quantification of the tissue perfusion and for transit time map computations. In the present work, the DASL scheme is used in conjunction with echo planar imaging at 4.7 T to produce brain maps of perfusion and transit time in the anesthetized rat, under graded hypercapnia. The data obtained show the variation of perfusion and transit time as a function of arterial pCO2. Based on the data, CO2 reactivity maps are computed. Published 2001 Wiley-Liss, Inc.     

Reduced resolution transit delay prescan for quantitative continuous arterial spin labeling perfusion imaging

Arterial spin labeling perfusion MRI can suffer from artifacts and quantification errors when the time delay between labeling and arrival of labeled blood in the tissue is uncertain. This transit delay is particularly uncertain in broad clinical populations, where reduced or collateral flow may occur. Measurement of transit delay by acquisition of the arterial spin labeling signal at many different time delays typically extends the imaging time and degrades the sensitivity of the resulting perfusion images. Acquisition of transit delay maps at the same spatial resolution as perfusion images may not be necessary, however, because transit delay maps tend to contain little high spatial resolution information. Here, we propose the use of a reduced spatial resolution arterial spin labeling prescan for the rapid measurement of transit delay. Approaches to using the derived transit delay information to optimize and quantify higher resolution continuous arterial spin labeling perfusion images are described. Results in normal volunteers demonstrate heterogeneity of transit delay across different brain regions that lead to quantification errors without the transit maps and demonstrate the feasibility of this approach to perfusion and transit delay quantification.     

Evidence for the exchange of arterial spin-labeled water with tissue water in rat brain from diffusion-sensitized measurements of perfusion

The extraction fraction of vascular water in rat brain is investigated by means of diffusion measurements of arterial spin labeled water at varying cerebral blood flow (CBF) values. The apparent diffusion coefficient (ADC) of the difference of the proton magnetization signal in the brain acquired with and without continuous arterial spin labeling is modeled to provide a measure of the amount of arterial water in tissue and vasculature and thus of the extraction fraction. The tissue and vascular portion of the arterial spin labeled water are differentiated based on their diffusion characteristics in a manner analogous to the intravoxel incoherent motion (IVIM) method. The amount of labeled arterial water that exchanges with tissue water is determined by estimating the fraction of the total signal that is associated with the slow-decaying component of a biexponential fit to the normalized difference signal between the magnetization of brain tissue acquired with and without arterial spin labeling. The results indicate that, at normal CBF (1.15 ± 0.21 ml g^-1 min^-1), about 90% of the arterial spin labeled water diffuses with an ADC of (1.21 ± 0.37) 10^-3mm² s^-1), which is equal to tissue. At high CBF, an increasing fraction of the labeling water has a fast-pseudo-diffusion coefficient due to a decrease in water extraction fractions. The results also show that the contribution of vascular water to the measurement of perfusion by techniques that use endogenous water as a tracer can be efficiently eliminated by the use of diffusion sensitizing gradients with small effective b values (b ≈ 20 s/mm²), enabling these techniques to monitor true changes in tissue perfusion.     

Volumetric measurement of perfusion and arterial transit delay using hadamard encoded continuous arterial spin labeling

Creating images of the transit delay from the labeling location to image tissue can aid the optimization and quantification of arterial spin labeling perfusion measurements and may provide diagnostic information independent of perfusion. Unfortunately, measuring transit delay requires acquiring a series of images with different labeling timing that adds to the time cost and increases the noise of the arterial spin labeling study. Here, we implement and evaluate a proposed Hadamard encoding of labeling that speeds the imaging and improves the signal‐to‐noise ratio efficiency. Volumetric images in human volunteers confirmed the theoretical advantages of Hadamard encoding over sequential acquisition of images with multiple labeling timing. Perfusion images calculated from Hadamard encoded acquisition had reduced signal‐to‐noise ratio relative to a dedicated perfusion acquisition with either assumed or separately measured transit delays, however. Magn Reson Med 69:1014–1022, 2013. © 2012 Wiley Periodicals, Inc.     

Magnetic resonance imaging of the brain: Blood partition coefficient for water: Application to spin-tagging measurement of perfusion

We describe the use of relative proton density imaging to obtain spatially resolved measurements of the brain:blood partition coefficient for water. Values of relative proton density and apparent-T1 were calculated by performing a multidimensional nonlinear least squares fit of progressive saturation image data. Correction for magnetic field inhomogeneity was included. The partition coefficient was calculated by dividing the relative proton density of brain by the relative proton density of blood water. Results obtained from healthy volunteers demonstrate significant spatial variation in the partition coefficient in brain. Direct measurement of this parameter eliminates a source of error in the calculation of regional perfusion using arterial spin-tagging techniques.     

A strategy to optimize the signal-to-noise ratio in one-coil arterial spin tagging perfusion imaging.

The signal-to-noise ratio of the perfusion image (SNR(perfu)) in a spin-tagging experiment is shown to depend on both the degree of spin labeling (alpha) and the signal-to-noise ratio of the proton density images (SNRimage) used to calculate the perfusion image. When a single radiofrequency (RF) coil is used for both spin tagging and magnetic resonance (MR) imaging, magnetization transfer (MT) effects decrease SNRimage, and therefore SNRperfu, by an amount that depends on the strength B1 and offset deltaomega (determined by the gradient strength G(I) applied during spin tagging) of the labeling RF pulse. It is shown that by optimizing B1 and G(I), it is possible to reduce MT effects and thus increase SNRimage, while leaving alpha unchanged. As a result, SNRperfu, will be improved. An equation for calculating perfusion under general conditions of such reduced MT effects is derived and shown to give perfusion rates that are independent of the strength and offset of the labeling RF irradiation.     

Robust method for 3D arterial spin labeling in mice

Arterial spin labeling is a versatile perfusion quantification methodology, which has the potential to provide accurate characterization of cerebral blood flow (CBF) in mouse models. However, a paucity of physiological data needed for accurate modeling, more stringent requirements for gradient performance, and strong artifacts introduced by magnetization transfer present special challenges for accurate CBF mapping in the mouse. This article describes robust mapping of CBF over three-dimensional brain regions using amplitude-modulated continuous arterial spin labeling. To provide physiological data for CBF modeling, the carotid artery blood velocity distribution was characterized using pulsed-wave Doppler ultrasound. These blood velocity measurements were used in simulations that optimize inversion efficiency for parameters meeting MRI gradient duty cycle constraints. A rapid slice positioning algorithm was developed and evaluated to provide accurate positioning of the labeling plane. To account for enhancement of T(1) due to magnetization transfer, a binary spin bath model of magnetization transfer was used to provide a more accurate estimate of CBF. Finally, a study of CBF was conducted on 10 mice with findings of highly reproducible inversion efficiency (mean ± standard-error-of-the-mean, 0.67 ± 0.03), statistically significant variation in CBF over 12 brain regions (P < 0.0001) and a mean ± standard-error-of-the-mean whole brain CBF of 219 ± 6 mL/100 g/min.     

Single-shot 3D imaging techniques improve arterial spin labeling perfusion measurements.

Arterial spin labeling (ASL) can be used to measure perfusion without the use of contrast agents. Due to the small volume fraction of blood vessels compared to tissue in the human brain (typ. 3-5%) ASL techniques have an intrinsically low signal-to-noise ratio (SNR). In this publication, evidence is presented that the SNR can be improved by using arterial spin labeling in combination with single-shot 3D readout techniques. Specifically, a single-shot 3D-GRASE sequence is presented, which yields a 2.8-fold increase in SNR compared to 2D EPI at the same nominal resolution. Up to 18 slices can be acquired in 2 min with an SNR of 10 or more for gray matter perfusion. A method is proposed to increase the reliability of perfusion quantification using QUIPSS II derivates by acquiring low-resolution maps of the bolus arrival time, which allows differentiation between lack of perfusion and delayed arrival of the labeled blood. For arterial spin labeling, single-shot 3D imaging techniques are optimal in terms of efficiency and might prove beneficial to improve reliability of perfusion quantitation in a clinical setup.     

Multislice perfusion of the kidneys using parallel imaging: Image acquisition and analysis strategies

Flow‐sensitive alternating inversion recovery arterial spin labeling with parallel imaging acquisition is used to acquire single‐shot, multislice perfusion maps of the kidney. A considerable problem for arterial spin labeling methods, which are based on sequential subtraction, is the movement of the kidneys due to respiratory motion between acquisitions. The effects of breathing strategy (free, respiratory‐triggered and breath hold) are studied and the use of background suppression is investigated. The application of movement correction by image registration is assessed and perfusion rates are measured. Postacquisition image realignment is shown to improve visual quality and subsequent perfusion quantification. Using such correction, data can be collected from free breathing alone, without the need for a good respiratory trace and in the shortest overall acquisition time, advantageous for patient comfort. The addition of background suppression to arterial spin labeling data is shown to reduce the perfusion signal‐to‐noise ratio and underestimate perfusion. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Magnetic resonance elastography of liver in healthy asians: Normal liver stiffness quantification and reproducibility assessment

Arterial spin labeling (ASL) methods allow for quantitative mapping of tissue perfusion in absolute units, without the use of contrast agents. In this technique, the magnetization of arterial blood water is labeled by magnetic inversion or saturation, and the delivery of labeled blood water to tissues is observed. In this review three classes of labeling methods for ASL are described and compared: continuous, pulsed, and velocity‐selective. The quantification of perfusion from ASL data is discussed, and methods for the extraction of new types of information using ASL and related techniques, such as mapping of vascular territories or venous oxygenation, are described. J. Magn. Reson. Imaging 2014;40:1–10 . © 2014 Wiley Periodicals, Inc .     

Comparing model‐based and model‐free analysis methods for QUASAR arterial spin labeling perfusion quantification

Amongst the various implementations of arterial spin labeling MRI methods for quantifying cerebral perfusion, the QUASAR method is unique. By using a combination of labeling with and without flow suppression gradients, the QUASAR method offers the separation of macrovascular and tissue signals. This permits local arterial input functions to be defined and “model‐free” analysis, using numerical deconvolution, to be used. However, it remains unclear whether arterial spin labeling data are best treated using model‐free or model‐based analysis. This work provides a critical comparison of these two approaches for QUASAR arterial spin labeling in the healthy brain. An existing two‐component (arterial and tissue) model was extended to the mixed flow suppression scheme of QUASAR to provide an optimal model‐based analysis. The model‐based analysis was extended to incorporate dispersion of the labeled bolus, generally regarded as the major source of discrepancy between the two analysis approaches. Model‐free and model‐based analyses were compared for perfusion quantification including absolute measurements, uncertainty estimation, and spatial variation in cerebral blood flow estimates. Major sources of discrepancies between model‐free and model‐based analysis were attributed to the effects of dispersion and the degree to which the two methods can separate macrovascular and tissue signal. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Improved perfusion quantification in FAIR imaging by offset correction.

Perfusion quantification using pulsed arterial spin labeling has been shown to be sensitive to the RF pulse slice profiles. Therefore, in Flow-sensitive Alternating-Inversion Recovery (FAIR) imaging the slice selective (ss) inversion slab is usually three to four times thicker than the imaging slice. However, this reduces perfusion sensitivity due to the increased transit delay of the incoming blood with unperturbed spins. In the present article, the dependence of the magnetization on the RF pulse slice profiles is inspected both theoretically and experimentally. A perfusion quantification model is presented that allows the use of thinner ss inversion slabs by taking into account the offset of RF slice profiles between ss and nonselective inversion slabs. This model was tested in both phantom and human studies. Magn Reson Med 46:193-197, 2001.     

Crossed cerebellar hyperperfusion after MELAS attack followed up by whole brain continuous arterial spin labeling perfusion imaging

Crossed cerebellar hyperperfusion (CCH) is detected in patients with epilepsy by brain perfusion studies including single photon emission computed tomography and positron emission tomography. In addition, brain perfusion can be studied with arterial spin labeling (ASL), which is a non-invasive MRI perfusion method that quantitatively measures cerebral blood flow per unit tissue mass. We followed up a 47-year-old patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) by continuous arterial spin labeling technique, which showed crossed cerebellar hyperperfusion after acute stroke-like episode. This cerebellar hyperperfusion normalized in the follow-up.     

3D GRASE PROPELLER: Improved image acquisition technique for arterial spin labeling perfusion imaging

Arterial spin labeling is a noninvasive technique that can quantitatively measure cerebral blood flow. While traditionally arterial spin labeling employs 2D echo planar imaging or spiral acquisition trajectories, single‐shot 3D gradient echo and spin echo (GRASE) is gaining popularity in arterial spin labeling due to inherent signal‐to‐noise ratio advantage and spatial coverage. However, a major limitation of 3D GRASE is through‐plane blurring caused by T₂ decay. A novel technique combining 3D GRASE and a periodically rotated overlapping parallel lines with enhanced reconstruction trajectory (PROPELLER) is presented to minimize through‐plane blurring without sacrificing perfusion sensitivity or increasing total scan time. Full brain perfusion images were acquired at a 3 × 3 × 5 mm³ nominal voxel size with pulsed arterial spin labeling preparation sequence. Data from five healthy subjects was acquired on a GE 1.5T scanner in less than 4 minutes per subject. While showing good agreement in cerebral blood flow quantification with 3D gradient echo and spin echo, 3D GRASE PROPELLER demonstrated reduced through‐plane blurring, improved anatomical details, high repeatability and robustness against motion, making it suitable for routine clinical use. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Improved perfusion-weighted MRI by a novel double inversion with proximal labeling of both tagged and control acquisitions.

A novel pulsed arterial spin labeling (PASL) technique for multislice perfusion-weighted imaging is proposed that compensates for magnetization transfer (MT) effects without sacrificing tag efficiency, and balances transient magnetic field effects (eddy currents) induced by pulsed field gradients. Improved compensation for MT is demonstrated using a phantom. Improvement in perfusion measurement was compared to other PASL techniques by acquiring perfusion images from 13 healthy volunteers (nine women and four men; age range 29-64 years; mean age 45 +/- 14 years) and second-order image texture analysis. The main improvements with the new method were significantly higher image contrast, higher mean signal intensity, and better signal uniformity across slices. In conclusion, this new PASL method should provide improved accuracy in measuring brain perfusion.     

Arterial spin labeling in combination with a look-locker sampling strategy: inflow turbo-sampling EPI-FAIR (ITS-FAIR).

Arterial spin labeling (ASL) permits quantification of tissue perfusion without the use of MR contrast agents. With standard ASL techniques such as flow-sensitive alternating inversion recovery (FAIR) the signal from arterial blood is measured at a fixed inversion delay after magnetic labeling. As no image information is sampled during this delay, FAIR measurements are inefficient and time-consuming. In this work the FAIR preparation was combined with a Look-Locker acquisition to sample not one but a series of images after each labeling pulse. This new method allows monitoring of the temporal dynamics of blood inflow. To quantify perfusion, a theoretical model for the signal dynamics during the Look-Locker readout was developed and applied. Also, the imaging parameters of the new ITS-FAIR technique were optimized using an expression for the variance of the calculated perfusion. For the given scanner hardware the parameters were: temporal resolution 100 ms, 23 images, flip-angle 25.4 degrees. In a normal volunteer experiment with these parameters an average perfusion value of 48.2 +/- 12.1 ml/100 g/min was measured in the brain. With the ability to obtain ITS-FAIR time series with high temporal resolution arterial transit times in the range of -138 - 1054 ms were measured, where nonphysical negative values were found in voxels containing large vessels.     

Multislice perfusion and perfusion territory imaging in humans with separate label and image coils.

An arterial spin labeling technique using separate RF labeling and imaging coils was used to obtain multislice perfusion images of the human brain at 3 T. Continuous RF irradiation at a peak power of 0.3 W was applied to the carotid arteries to adiabatically invert spins. Labeling was achieved without producing magnetization transfer effects since the B1 field of the labeling coil did not extend into the imaging region or couple significant power into the imaging coil. Eliminating magnetization transfer allowed the acquisition of multislice perfusion images of arbitrary orientation. Combining surface coil labeling with a reduced RF duty cycle permitted significantly lower SAR than single coil approaches. The technique was also found to allow selective labeling of blood in either carotid, providing an assessment of the artery's perfusion territory. In normal subjects, these territories were well-defined and localized to the ipsilateral hemisphere.