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.     

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.     

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.     

Cerebral perfusion and arterial transit time changes during task activation determined with continuous arterial spin labeling.

Perfusion imaging by arterial spin labeling (ASL) can be highly sensitive to the transit time from the labeling site to the tissue. We report the results of a study designed to separate the transit time and perfusion contributions to activation in ASL images accompanying motor and visual stimulation. Fractional transit time decreases were found to be comparable to fractional perfusion increases and the transit time change was found to be the greatest contributor to ASL signal change in ASL sequences without delayed acquisition. The implications for activation imaging with ASL and the arterial control of flow are discussed.     

Efficient sampling of early signal arrival for estimation of perfusion and transit time in whole-brain arterial spin labeling

Arterial spin labeling can be used to measure both cerebral perfusion and arterial transit time. However, accurate estimation of these parameters requires adequate temporal sampling of the arterial spin labeling difference signal. In whole-brain multislice acquisitions, two factors reduce the accuracy of the parameter estimates: saturation of labeled blood in transit and inadequate sampling of early difference signal in superior slices. Label saturation arises when slices are acquired inferior-to-superior such that slice selection in proximal slices spoils the label for a distal slice. Inadequate sampling arises when the time spent acquiring inferior slices is too long to allow early sampling of the difference signal in superior slices. A novel approach to multislice imaging is proposed to address these two issues. In round-robin arterial spin labeling, slices are acquired in a different order after every pair of control-label acquisitions. Round-robin arterial spin labeling enables the acquisitions of all slices across the same range of postlabel delays in a descending superior-to-inferior order. This eliminates the temporal sampling problem and greatly reduces label saturation. Arterial transit time estimates obtained for the whole brain with round-robin arterial spin labeling show better agreement with a single-slice acquisition than do conventional multislice acquisitions.     

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.     

Correction for vascular artifacts in cerebral blood flow values measured by using arterial spin tagging techniques

?Vascular”? artifacts can have substantial effects on human cerebral blood flow values calculated by using arterial spin tagging approaches. One vascular artifact arises from the contribution of ?tagged”? arterial water spins to the observed change in brain water MR signal. This artifact can be reduced if large bipolar gradients are used to ?crush”? the MR signal from moving arterial water spins. A second vascular artifact arises from relaxation of ?tagged”? arterial blood during transit from the tagging plane to the capillary exchange site in the imaging slice. This artifact can be corrected if the arterial transit times are measured by using ?dynamic”? spin tagging approaches. The mean transit time from the tagging plane to capillary exchange sites in a gray matter region of interest was calculated to be ～0.94 s. Cerebral blood flow values calculated for seven normal volunteers agree reasonably well with values calculated by using radioactive tracer approaches.     

Perfusion magnetic resonance imaging with continuous arterial spin labeling: methods and clinical applications in the central nervous system.

Several methods are now available for measuring cerebral perfusion and related hemodynamic parameters using magnetic resonance imaging (MRI). One class of techniques utilizes electromagnetically labeled arterial blood water as a noninvasive diffusible tracer for blood flow measurements. The electromagnetically labeled tracer has a decay rate of T1, which is sufficiently long to allow perfusion of the tissue and microvasculature to be detected. Alternatively, electromagnetic arterial spin labeling (ASL) may be used to obtain qualitative perfusion contrast for detecting changes in blood flow, similar to the use of susceptibility contrast in blood oxygenation level dependent functional MRI (BOLD fMRI) to detect functional activation in the brain. The ability to obtain blood flow maps using a non-invasive and widely available modality such as MRI should greatly enhance the utility of blood flow measurement as a means of gaining further insight into the broad range of hemodynamically related physiology and pathophysiology. This article describes the biophysical considerations pertaining to the generation of quantitative blood flow maps using a particular form of ASL in which arterial blood water is continuously labeled, termed continuous arterial spin labeling (CASL). Technical advances permit multislice perfusion imaging using CASL with reduced sensitivity to motion and transit time effects. Interpretable cerebral perfusion images can now be reliably obtained in a variety of clinical settings including acute stroke, chronic cerebrovascular disease, degenerative diseases and epilepsy. Over the past several years, the technical and theoretical foundations of CASL perfusion MRI techniques have evolved from feasibility studies into practical usage. Currently existing methodologies are sufficient to make reliable and clinically relevant observations which complement structural assessment using MRI. Future technical improvements should further reduce the acquisition times for CASL perfusion MRI, while increasing the slice coverage, resolution and stability of the images. These techniques have a broad range of potential applications in clinical and basic research of brain physiology, as well as in other organs.     

Quantification of blood flow in brain tumors: comparison of arterial spin labeling and dynamic susceptibility-weighted contrast-enhanced MR imaging

PURPOSE: To implement an arterial spin labeling technique that is feasible in routine examinations and to test the method and compare it with dynamic susceptibility-weighted contrast material-enhanced magnetic resonance (MR) imaging for evaluation of tumor blood flow (TBF) in patients with brain tumors. MATERIALS AND METHODS: Thirty-six patients with histologically proven brain tumors were examined at 1.5 T. A second version of quantitative imaging of perfusion by using a single subtraction with addition of thin-section periodic saturation after inversion and a time delay (Q2TIPS) technique of pulsed arterial spin labeling in the multisection mode was implemented. After arterial spin labeling, a combined T2- and T2*-weighted first-pass bolus perfusion study (gadopentetate dimeglumine, 0.2 mmol/kg) was performed by using a double-echo echo-planar imaging sequence. In regions of interest, maps of absolute and relative cerebral blood flow were computed and analyzed with arterial spin labeling and dynamic susceptibility-weighted contrast-enhanced MR imaging, respectively. RESULTS: Both techniques yielded the highest perfusion values in imaging of glioblastomas and the lowest values in imaging of two low-grade gliomas that both showed strong gadopentetate dimeglumine enhancement. There was a close linear correlation between dynamic susceptibility-weighted contrast-enhanced MR imaging and arterial spin labeling in the tumor region of interest (linear regression coefficient, R = 0.83; P <.005). Blood flow is underestimated with arterial spin labeling at low flow rates. High- and low-grade gliomas can be distinguished at the same level of significance with both methods. Absolute TBF is less important for tumor grading than is the ratio of TBF to age-dependent mean brain perfusion. CONCLUSION: Arterial spin labeling is a suitable method for assessment of microvascular perfusion and allows distinction between high- and low-grade gliomas.     

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.     

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 approximately 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.     

Arterial spin labeling MRI study of age and gender effects on brain perfusion hemodynamics

Normal aging is associated with diminished brain perfusion measured as cerebral blood flow (CBF), but previously it is difficult to accurately measure various aspects of perfusion hemodynamics including: bolus arrival times and delays through small arterioles, expressed as arterial-arteriole transit time. To study hemodynamics in greater detail, volumetric arterial spin labeling MRI with variable postlabeling delays was used together with a distributed, dual-compartment tracer model. The main goal was to determine how CBF and other perfusion hemodynamics vary with aging. Twenty cognitive normal female and 15 male subjects (age: 23-84 years old) were studied at 4 T. Arterial spin labeling measurements were performed in the posterior cingulate cortex, precuneus, and whole brain gray matter. CBF declined with advancing age (P < 0.001). Separately from variations in bolus arrival times, arterial-arteriole transit time increased with advancing age (P < 0.01). Finally, women had overall higher CBF values (P < 0.01) and shorter arterial-arteriole transit time (P < 0.01) than men, regardless of age. The findings imply that CBF and blood transit times are compromised in aging, and these changes together with differences between genders should be taken into account when studying brain perfusion.     

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.     

In vivo measurement of the longitudinal relaxation time of arterial blood (T1a) in the mouse using a pulsed arterial spin labeling approach.

A novel method for measuring the longitudinal relaxation time of arterial blood (T1a) is presented. Knowledge of T1a is essential for accurately quantifying cerebral perfusion using arterial spin labeling (ASL) techniques. The method is based on the flow-sensitive alternating inversion recovery (FAIR) pulsed ASL (PASL) approach. We modified the standard FAIR acquisition scheme by incorporating a global saturation pulse at the beginning of the recovery period. With this approach the FAIR tissue signal difference has a simple monoexponential dependence on the recovery time, with T1a as the time constant. Therefore, FAIR measurements performed over a range of recovery times can be fitted to a monoexponential recovery curve and T1a can be calculated directly. This eliminates many of the difficulties associated with the measurement of T1a. Experiments performed in vivo in the mouse at 2.35T produced a mean value of 1.51 s for T1a, consistent with previously published values.     

Pulsed arterial spin labeling parameter optimization for an elderly population

PURPOSE: To optimize pulsed arterial spin labeling (PASL) parameters for the elderly to take into account possible perfusion changes that occur in the brain with age. MATERIALS AND METHODS: Healthy young (N = 14, age range = 21-27 years) and elderly (N = 12, age range = 61-67 years) subjects were scanned using Q2TIPS (QUIPSS II with thin-slice TI, periodic saturation) with varying inversion times (TI(2)) at 1.5T. The difference signal (DeltaM), transit time (deltat), and cerebral blood flow (CBF) were calculated in segmented gray matter (GM). RESULTS: The young displayed more perfusion-weighted signal difference than the elderly at all TI(2)'s. The peak DeltaM occurred at TI(2) approximately 1300 msec and 1500 msec in the young and elderly groups, respectively. Qualitatively, intravascular signal was minimal in the younger group by TI(2) = 1500 msec, whereas a longer TI(2) of 1800 msec was needed to minimize this signal in the elderly. The transit time was approximately 100 msec longer in the elderly, and CBF was in the range of literature values. CONCLUSION: For acquiring perfusion-weighted images with minimal intravascular signal and adequate tissue signal for PASL studies of cerebral perfusion in the elderly, a longer inversion time is advantageous.     

Implementation of quantitative FAIR perfusion imaging with a short repetition time in time-course studies.

Flow-sensitive alternating inversion recovery (FAIR) is a pulsed arterial spin labeling magnetic resonance imaging method for perfusion quantification. In its standard implementation for quantification with full longitudinal relaxation between acquisitions, its use in time-course investigations of rapidly changing flow values is limited. The time efficiency can be improved by decreasing the repetition time but quantification becomes problematic. This situation is further complicated if a whole-body radiofrequency transmit coil is not used since fresh blood spins will flow in from outside the coil. To alleviate these problems, the use of global pre-saturation is proposed. The resulting expression for the flow signal depends on the relationship between the imaging parameters and the coil inflow time and can be significantly simplified under certain combinations of these parameters. With this implementation of FAIR, quantitative flow maps of gerbil brains were obtained with a 3 minute time resolution in a study of the effects of reperfusion. The pre-occlusion flow measurements were in good agreement with values obtained by the standard FAIR implementation and by other techniques, but the low values following occlusion were underestimated due to the increased transit times.     

Effect of lung inflation on arterial spin labeling signal in MR perfusion imaging of human lung

The effect of lung inflation on arterial spin-labeling signal in lung perfusion is investigated. Arterial spin-labeling schemes, called alternation of selective inversion pulse (ASI) and its hybrid (HASI), which uses blood water as an endogenous, freely diffusible tracer, were applied to magnetic resonance (MR) perfusion imaging of the lung. Perfusion-weighted images of the lung from nine healthy volunteers were obtained at different time delays. There was a significant signal difference in ASI images acquired at different respiratory phases. Greater signal enhancement has been observed when the volunteers performed breath holding on end expiration than on end inspiration. This is in agreement with the normal physiologic effect of lung inflation on the pressure-flow relationship of pulmonary vasculature. ASI and HASI perfusion-weighted images show similar lung features and image quality. Preliminary results from pulmonary embolism patients indicate that arterial spin labeling is sensitive for the detection of areas of perfusion deficit. J. Magn. Reson. Imaging 2001;13:954-959.     

Determination of spin compartment in arterial spin labeling MRI

A major difference between arterial‐spin‐labeling MRI and gold‐standard radiotracer blood flow methods is that the compartment localization of the labeled spins in the arterial‐spin‐labeling image is often ambiguous, which may affect the quantification of cerebral blood flow. In this study, we aim to probe whether the spins are located in the vascular system or tissue by using T2 of the arterial‐spin‐labeling signal as a marker. We combined two recently developed techniques, pseudo‐continuous arterial spin labeling and T2‐Relaxation‐Under‐Spin‐Tagging, to determine the T2 of the labeled spins at multiple postlabeling delay times. Our data suggest that the labeled spins first showed the T2 of arterial blood followed by gradually approaching and stabilizing at the tissue T2. The T2 values did not decrease further toward the venous T2. By fitting the experimental data to a two‐compartment model, we estimated gray matter cerebral blood flow, arterial transit time, and tissue transit time to be 74.0 ± 10.7 mL/100g/min (mean ± SD, N = 10), 938 ± 156 msec, and 1901 ± 181 msec, respectively. The arterial blood volume was calculated to be 1.18 ± 0.21 mL/100 g. A postlabeling delay time of 2 s is sufficient to allow the spins to completely enter the tissue space for gray matter but not for white matter. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

磁共振3 D－ASL灌注成像在不强化小脑病变鉴别诊断中的应用价值

目的：在无强化小脑病变患者中应用三维动脉自旋标记成像（3DASL）技术，探讨其在无强化小脑病变鉴别诊断中的价值。方法分析15例临床诊断明确的小脑病变患者的3 DASL检查结果。15例患者均为行常规MRI平扫发现小脑异常信号且增强扫描无强化者，所有患者均进一步行3DASL扫描，测量病灶区的CBF值，根据病理及临床随诊结果，分析3DASL对无强化小脑病变的诊断价值。结果15例患者常规MRI平扫均可见长T 1长T2为主的异常信号，增强扫描均无强化，常规扫描无特异性表现。15例患者中小脑梗死11例，3 DASL均呈低灌注；胶质瘤3例，3DASL呈等高灌注；淋巴瘤1例，3DASL呈等灌注；3DASL结果具有一定的特异性。结论作为一项无创性磁共振灌注成像新技术，3 DASL成像能够为小脑无强化病灶提供有价值的诊断依据。