Pseudo‐continuous transfer insensitive labeling technique

Transfer insensitive labeling technique (TILT) was previously applied to acquire multislice cerebral blood flow maps as a pulsed arterial spin labeling (PASL) method. The magnetization transfer effect with TILT is well controlled by using concatenated radiofrequency pulses. However, use of TILT has been limited by several challenges, including slice profile errors, sensitivity to arterial transit time and intrinsic low signal‐to‐noise ratio (SNR). In this work, we propose to address these challenges by making the original TILT method into a novel pseudo‐continuous arterial spin labeling approach, named pseudo‐continuous transfer insensitive labeling technique (pTILT). pTILT improves perfusion acquisitions by (i) realizing pseudo‐continuous tagging with nonadiabatic pulses, (ii) being sensitive to slow flows in addition to fast flows, and (iii) providing flexible labeling geometries. Perfusion maps during both resting state and functional tasks are successfully demonstrated in healthy volunteers with pTILT. A comparison with typical SNR values from other perfusion techniques shows that although pTILT provides less SNR than inversion‐based pseudo‐continuous ASL techniques, the modified sequence provides similar SNR to inversion‐based PASL techniques. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Quantification of perfusion fMRI using a numerical model of arterial spin labeling that accounts for dynamic transit time effects.

A new approach to modeling the signal observed in arterial spin labeling (ASL) experiments during changing perfusion conditions is presented in this article. The new model uses numerical methods to extend first-order kinetic principles to include the changes in arrival time of the arterial tag that occur during neuronal activation. Estimation of the perfusion function from the ASL signal using this model is also demonstrated. The estimation algorithm uses a roughness penalty as well as prior information. The approach is demonstrated in numerical simulations and human experiments. The approach presented here is particularly suitable for fast ASL acquisition schemes, such as turbo continuous ASL (Turbo-CASL), which allows subtraction pairs to be acquired in less than 3 s but is sensitive to arrival time changes. This modeling approach can also be extended to other acquisition schemes.     

Whole-brain 3D perfusion MRI at 3.0 T using CASL with a separate labeling coil.

A variety of continuous and pulsed arterial spin labeling (ASL) perfusion MRI techniques have been demonstrated in recent years. One of the reasons these methods are still not routinely used is the limited extent of the imaging region. Of the ASL methods proposed to date, continuous ASL (CASL) with a separate labeling coil is particularly attractive for whole-brain studies at high fields. This approach can provide an increased signal-to-noise ratio (SNR) in perfusion images because there are no magnetization transfer (MT) effects, and lessen concerns regarding RF power deposition at high field because it uses a local labeling coil. In this work, we demonstrate CASL whole-brain quantitative perfusion imaging at 3.0 T using a combination of strategies: 3D volume acquisition, background tissue signal suppression, and a separate labeling coil. The results show that this approach can be used to acquire perfusion images in all brain regions with good sensitivity. Further, it is shown that the method can be performed safely on humans without exceeding the current RF power deposition limits. The current method can be extended to higher fields, and further improved by the use of multiple receiver coils and parallel imaging techniques to reduce scan time or provide increased resolution.     

Pediatric perfusion imaging using pulsed arterial spin labeling

PURPOSE: To test the feasibility of pediatric perfusion imaging using a pulsed arterial spin labeling (ASL) technique at 1.5 T. MATERIALS AND METHODS: ASL perfusion imaging was carried out on seven neurologically normal children and five healthy adults. The signal-to-noise ratio (SNR) of the perfusion images along with T1, M(0), arterial transit time, and the temporal fluctuation of the ASL image series were measured and compared between the two age groups. In addition, ASL perfusion magnetic resonance (MR) was performed on three children with neurologic disorder. RESULTS: In the cohort of neurologically normal children, a 70% increase in the SNR of the ASL perfusion images and a 30% increase in the absolute cerebral blood flow compared to the adult data were observed. The measures of ASL SNR, T1, and M(0) were found to decrease linearly with age. Transit time and temporal fluctuation of the ASL perfusion image series were not significantly different between the two age groups. The feasibility of ASL in the diagnosis of pediatric neurologic disease was also illustrated. CONCLUSION: ASL is a promising tool for pediatric perfusion imaging given the unique and reciprocal benefits in terms of safety and image quality.     

ASL技术在中枢神经系统中的应用进展

动脉自旋标记(ASL)是通过射频脉冲标记动脉血来进行脑血流的无创评估,属于绝对定量灌注。ASL无需使用对比剂且没有电离辐射,可在短期内对病人重复评价,其衍生技术在中枢神经系统中的应用越来越广泛。介绍ASL的成像原理、衍生技术,并对比分析多种灌注技术。同时就ASL技术在缺血性疾病、脑肿瘤、癫、神经退行性疾病、线粒体脑肌病伴高乳酸血症和脑卒中样发作(MELAS)综合征、脑炎等疾病中的应用进展予以综述。     

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 T(1) 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.     

动脉自旋标记MRI技术在烟雾病中的应用

烟雾病（MMD）是一种发生在Willis环附近的慢性、进行性脑血管狭窄或闭塞性疾病。病人脑血管阻塞程度、侧支循环开放和脑灌注情况常影响预后和治疗决策。动脉自旋标记（ASL）MRI技术以动脉血中的水分子为内源性示踪剂进行灌注成像,可以无创性地提供脑血流动力学信息。就ASL成像原理以及常规、多期延迟、长延迟ASL,ASL-4D MR血管成像（MRA）及加速度选择性-ASL MRA等各种ASL成像技术在MMD中的临床应用进行综述。     

Comparison of first-pass Gd-DOTA and FAIRER MR perfusion imaging in a rabbit model of pulmonary embolism

PURPOSE: To compare the sensitivity of contrast-enhanced magnetic resonance imaging (MRI) and arterial spin labeling to perfusion deficits in the lung. MATERIALS AND METHODS: A rabbit model of pulmonary embolism was imaged with both flow-sensitive alternating inversion recovery with an extra radiofrequency pulse (FAIRER) arterial spin labeling and Gd-DOTA enhanced MRI. The signal-to-noise ratio (SNR) was measured in the area of the perfusion deficit and the normal lung for both techniques. RESULTS: The defect was readily visible in all images. The normal lung had an average of 3.8 +/- 1.2 times the SNR of the unperfused lung with the arterial spin labeling technique, and approximately 13.7 +/- 3.3 times the SNR with the contrast-enhanced technique. CONCLUSION: Gd-DOTA enhanced MRI provides higher SNR in pulmonary perfusion imaging; however, arterial spin labeling is also adequate and may be used when repeated studies are indicated.     

Can arterial spin labeling detect white matter perfusion signal?

Since the invention of arterial spin labeling (ASL) it has been acknowledged that ASL does not allow reliable detection of a white matter (WM) perfusion signal. However, recent developments such as pseudo‐continuous labeling and background suppression have improved the quality. The goal of this research was to study the ability of these newer ASL sequences to detect WM perfusion signal. Background suppressed pseudo‐continuous ASL was implemented at 3T with multislice 2D readout after 1525 ms. In five volunteers it was shown that 10 min scanning resulted in significant perfusion signal in 70% of WM voxels. Increasing the labeling and delay time did not lead to a higher percentage. In 27 normal volunteers it was found that 35 averages are necessary to detect significant WM signal, but 150 averages are needed to detect signal in the deep WM. Finally, it was shown in a patient with a cerebral arteriovenous malformation that pseudo‐continuous ASL enabled the depiction of hypointense WM perfusion signal, although dynamic susceptibility contrast MRI showed that this region was merely showing delayed arrival of contrast agent than hypoperfusion. It can be concluded that, except within the deep WM, ASL is sensitive enough to detect WM perfusion signal and perfusion deficits. Magn Reson Med, 2009. © 2009 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 .     

Innovations in functional MR imaging of the brain: arterial spin labeling and diffusion

The standard technique for brain activation functional MRI (fMRI) is the BOLD sequence. Two new techniques have emerged: arterial spin labeling (ASL) MRI and diffusion MRI. Both have the theoretical advantage of more accurately directly demonstrating neuronal activation compared to BOLD imaging, resulting in improved spatial and temporal resolution. ASL is a perfusion sequence using labeled arterial protons as an endogenous perfusion agent. In spite of methodological difficulties, quantitative CBF measurements are possible. ASL is less susceptible to venous contamination than BOLD and more reproducible. Diffusion MRI evaluates neuronal activation at the cellular level with the prospect of excellent spatial resolution. The main limitations for both techniques are the technical difficulties in the acquisition and the low SNR. AS such, ASL is not widely used clinically and diffusion remains in the field of research. However, the increasing availability of 3T MR systems coupled with multi-channel surface coils and improved postprocessing techniques should improve the detection of the brain activation signal. It is thus possible that these techniques could become clinically available either in complement to or as a replacement for BOLD imaging.     

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.     

Selective arterial spin labeling (SASL): perfusion territory mapping of selected feeding arteries tagged using two-dimensional radiofrequency pulses.

To date, most perfusion magnetic resonance imaging (MRI) methods using arterial spin labeling (ASL) have employed slab-selective inversion pulses or continuous labeling within a plane in order to obtain maps derived from all major blood vessels entering the brain. However, there is great potential for gaining additional information on the territories perfused by the major vessels if individual feeding arteries could be tagged. This study demonstrates noninvasive arterial perfusion territory maps obtained using two-dimensional (2D) selective inversion pulses. This method is designated "selective ASL" (SASL). The SASL method was used to tag the major arteries below the circle of Willis. A combination of 2D selective tagging and multislice readout allows perfusion territories to be clearly visualized, with likely applications to cerebrovascular disease and stroke.     

3D Pseudocontinuous arterial spin labeling in routine clinical practice: A review of clinically significant artifacts

Arterial spin labeling (ASL) is a completely noninvasive magnetic resonance imaging (MRI) perfusion method for quantitatively measuring cerebral blood flow utilizing magnetically labeled arterial water. Advances in the technique have enabled the major MRI vendors to make the sequence available to the clinical neuroimaging community. Consequently, ASL is being increasingly incorporated into the routine neuroimaging protocol. Although a variety of ASL techniques are available, the ISMRM Perfusion Study Group and the European ASL in Dementia Consortium have released consensus guidelines recommending standardized implementation of 3D pseudocontinuous ASL with background suppression. The purpose of this review, aimed at the large number of neuroimaging clinicians who have either no or limited experience with this 3D pseudocontinuous ASL, is to discuss the common and clinically significant artifacts that may be encountered with this technique. While some of these artifacts hinder accurate interpretation of studies, either by degrading the images or mimicking pathology, there are other artifacts that are of clinical utility, because they increase the conspicuity of pathology. Cognizance of these artifacts will help the physician interpreting ASL to avoid potential diagnostic pitfalls, and increase their level of comfort with the technique. J. MAGN. RESON. IMAGING 2016;43:11–27.     

Modeling and optimization of Look-Locker spin labeling for measuring perfusion and transit time changes in activation studies taking into account arterial blood volume.

This work describes a new compartmental model with step-wise temporal analysis for a Look-Locker (LL)-flow-sensitive alternating inversion-recovery (FAIR) sequence, which combines the FAIR arterial spin labeling (ASL) scheme with a LL echo planar imaging (EPI) measurement, using a multireadout EPI sequence for simultaneous perfusion and T*(2) measurements. The new model highlights the importance of accounting for the transit time of blood through the arteriolar compartment, delta, in the quantification of perfusion. The signal expected is calculated in a step-wise manner to avoid discontinuities between different compartments. The optimal LL-FAIR pulse sequence timings for the measurement of perfusion with high signal-to-noise ratio (SNR), and high temporal resolution at 1.5, 3, and 7T are presented. LL-FAIR is shown to provide better SNR per unit time compared to standard FAIR. The sequence has been used experimentally for simultaneous monitoring of perfusion, transit time, and T*(2) changes in response to a visual stimulus in four subjects. It was found that perfusion increased by 83 +/- 4% on brain activation from a resting state value of 94 +/- 13 ml/100 g/min, while T*(2) increased by 3.5 +/- 0.5%.     

磁共振ASL灌注成像及其在脑疾病诊断中的临床应用

磁共振动脉血质子自旋标记(ASL)灌注成像是将动脉血作为内源性示踪剂、无创性的观测血流灌注情况的磁共振检查技术,可以提供相应血流动力学方面的信息。笔者查阅了今年来相关文献,主要综述了ASL的基本原理、检查方法及其在脑血管疾病中的应用价值和发展趋势。     

Four-phase single-capillary stepwise model for kinetics in arterial spin labeling MRI.

An extended model for extracting measures of brain perfusion from pulsed arterial spin labeling (ASL) data while considering transit effects and restricted permeability of capillaries to blood water is proposed. We divided the time course of the signal difference between control and labeled images into four phases with respect to the arrival time of labeled blood water at the voxel of interest (t(A)), transit time through the arteries in the voxel (t(ex)), and duration of the bolus of labeled spins (tau). Dividing the labeled slab of blood water into many discrete segments, and adapting numerical integration methods allowed us to conveniently model restricted capillary-tissue exchange based on a modified distributed parameter model. We compared this four-phase single-capillary stepwise (FPSCS) model with models that treat water as a freely diffusible tracer, using both simulations and experimental ASL brain imaging data at 1.5T from eight healthy subjects (24-80 years old). The FPSCS model yielded less errors in the least-squares sense in fitting brain ASL data in comparison with freely diffusible tracer models of water (P = 0.055). These results imply that restricted permeability of capillaries to water should be considered when brain ASL data are analyzed.     

Estimation of perfusion and arterial transit time in myocardium using free‐breathing myocardial arterial spin labeling with navigator‐echo

Arterial spin labeling (ASL) provides noninvasive measurement of tissue blood flow, but sensitivity to motion has limited its application to imaging of myocardial blood flow. Although different cardiac phases can be synchronized using electrocardiography triggering, breath holding is generally required to minimize effects of respiratory motion during ASL scanning, which may be challenging in clinical populations. Here a free‐breathing myocardial ASL technique with the potential for reliable clinical application is presented, by combining ASL with a navigator‐gated, electrocardiography‐triggered TrueFISP readout sequence. Dynamic myocardial perfusion signals were measured at multiple delay times that allowed simultaneous fitting of myocardial blood flow and arterial transit time. With the assist of a nonrigid motion correction program, the estimated mean myocardial blood flow was 1.00 ± 0.55 mL/g/min with a mean transit time of ∼400 msec. The intraclass correlation coefficient of repeated scans was 0.89 with a mean within subject coefficient of variation of 22%. Perfusion response during mild to moderate stress was further measured. The capability for noninvasive, free‐breathing assessment of myocardial blood flow using ASL may offer an alternative approach to first‐pass perfusion MRI for clinical evaluation of patients with coronary artery disease. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Single-shot quantitative perfusion imaging of the human lung.

The major drawback to quantitative perfusion imaging using arterial spin labeling (ASL) techniques is the need to acquire two images (tag and control), which must be subtracted in order to obtain a perfusion-weighted image. This can potentially result in misregistration artifacts, especially in lung imaging, due to varying lung inflation levels in different breath-holds. In this work a double inversion recovery (DIR) imaging technique that yields perfusion-weighted images of the human lung in a single shot is presented. This technique ensures the complete suppression of background tissue while it preserves signal from the blood. Furthermore, the perfusion-weighted images and an additional (independent) acquired reference scan can be used to obtain quantitative perfusion information from the lungs.     

A theoretical and experimental comparison of continuous and pulsed arterial spin labeling techniques for quantitative perfusion imaging

Under ideal conditions, continuous arterial spin labeling (ASL) techniques are higher in SNR than pulsed ASL techniques by a factor of e. Presented here is a direct theoretical and experimental comparison of continuous ASL and pulsed ASL, using versions of both that are amenable to multislice imaging and insensitive to variations in transit times (continuous ASL with a delay before imaging, and QUIPSS II (Quantitative Imaging of Perfusion Using a Single Subtraction–second version)). Perfusion image quality for comparable imaging time was nearly identical for both single-slice and multislice imaging. The measured raw signal was approximately 25% higher with continuous ASL, but the SNR per unit time was identical.