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.     

Improved pseudo‐continuous arterial spin labeling for mapping brain perfusion

Purpose:

To investigate arterial spin labeling (ASL) methods for improved brain perfusion mapping. Previously, pseudo‐continuous ASL (pCASL) was developed to overcome limitations inherent with conventional continuous ASL (CASL), but the control scan (null pulse) in the original method for pCASL perturbs the equilibrium magnetization, diminishing the ASL signal. Here, a new modification of pCASL, termed mpCASL is reported, in which the perturbation caused by the null pulse is reduced and perfusion mapping improved.

Materials and Methods:

improvements with mpCASL are demonstrated using numerical simulations and experiments. ASL signal intensity as well as contrast and reproducibility of in vivo brain perfusion images were measured in four volunteers who had MRI scans at 4 Tesla and the data compared across the labeling methods.

Results:

Perfusion maps with mpCASL showed, on average, higher ASL signal intensity and higher image contrast than those from CASL or pCASL. Furthermore, mpCASL yielded better reproducibility in repeat scans than the other methods.

Conclusion:

The experimental results are consistent with the hypothesis that the new null pulse of mpCASL leads to improved brain perfusion images. J. Magn. Reson. Imaging 2010;31:1419–1427. © 2010 Wiley‐Liss, Inc.     

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.     

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.     

MR perfusion imaging of pulmonary parenchyma using pulsed arterial spin labeling techniques: FAIRER and FAIR

Magnetic resonance imaging of pulmonary parenchyma perfusion using pulsed arterial spin labeling (ASL) techniques is presented. ASL uses magnetically labeled water as an endogenous, freely diffusible tracer. Presented are comparative results of ASL methods called Flow sensitive Alternating Inversion Recovery (FAIR), and FAIR with an Extra Radiofrequency pulse (FAIRER). Six healthy human volunteers were imaged. Perfusion-weighted images at different time delays, TI, were calculated from the subtraction of the control and tag images, which were acquired within a single breathhold. Detailed pulmonary structures can be visualized with negligible cardiac or respiratory motion artifacts. Different patterns of signal enhancement between the pulmonary vessels and parenchyma are shown in the perfusion images acquired at different TIs.     

Improved accuracy of human cerebral blood perfusion measurements using arterial spin labeling: accounting for capillary water permeability.

A two-compartment exchange model for perfusion quantification using arterial spin labeling (ASL) is presented, which corrects for the assumption that the capillary wall has infinite permeability to water. The model incorporates an extravascular and a blood compartment with the permeability surface area product (PS) of the capillary wall characterizing the passage of water between the compartments. The new model predicts that labeled spins spend longer in the blood compartment before exchange. This makes an accurate blood T(1) measurement crucial for perfusion quantification; conversely, the tissue T(1) measurement is less important and may be unnecessary for pulsed ASL experiments. The model gives up to 62% reduction in perfusion estimate for human imaging at 1.5T compared to the single compartment model. For typical human perfusion rates at 1.5T it can be assumed that the venous outflow signal is negligible. This simplifies the solution, introducing only one more parameter than the single compartment model, PS/v(bw), where v(bw) is the fractional blood water volume per unit volume of tissue. The simplified model produces an improved fit to continuous ASL data collected at varying delay time. The fitting yields reasonable values for perfusion and PS/v(bw).     

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.     

动脉自旋标记技术的临床应用进展

动脉自旋标记(ASL)是一种以动脉血内可自由扩散的水质子为内源性示踪剂的MR灌注成像技术,可以通过定量测量局部微血管的灌注,为疾病的临床诊断提供明确的客观依据。与传统注射对比剂的MR灌注成像方法相比,其不需注射外源性对比剂,可降低成本,并具有无创性、简单易行、可重复性等优点,因而有较强的临床应用潜力。就ASL的原理、分类、临床应用的现状和未来发展趋势予以综述。     

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.     

Acceleration‐selective arterial spin labeling

In this study, a new arterial spin labeling (ASL) method with spatially nonselective labeling is introduced, based on the acceleration of flowing spins, which is able to image brain perfusion with minimal contamination from venous signal. This method is termed acceleration‐selective ASL (AccASL) and resembles velocity‐selective ASL (VSASL), with the difference that AccASL is able to discriminate between arterial and venous components in a single preparation module due to the higher acceleration on the arterial side of the microvasculature, whereas VSASL cannot make this distinction unless a second labeling module is used. A difference between AccASL and VSASL is that AccASL is mainly cerebral blood volume weighted, whereas VSASL is cerebral blood flow weighted. AccASL exploits the principles of acceleration‐encoded magnetic resonance angiography by using motion‐sensitizing gradients in a T₂‐preparation module. This method is demonstrated in healthy volunteers for a range of cutoff accelerations. Additionally, AccASL is compared with VSASL and pseudo‐continuous ASL, and its feasibility in functional MRI is demonstrated. Compared with VSASL with a single labeling module, a strong and significant reduction in venous label is observed. The resulting signal‐to‐noise ratio is comparable to pseudo‐continuous ASL and robust activation of the visual cortex is observed. Magn Reson Med 71:191–199, 2014. © 2013 Wiley Periodicals, Inc.     

Arterial spin labeling MRI: Clinical applications in the brain

Visualization of cerebral blood flow (CBF) has become an important part of neuroimaging for a wide range of diseases. Arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) sequences are increasingly being used to provide MR‐based CBF quantification without the need for contrast administration, and can be obtained in conjunction with a structural MRI study. ASL MRI is useful for evaluating cerebrovascular disease including arterio‐occlusive disease, vascular shunts, for assessing primary and secondary malignancy, and as a biomarker for neuronal metabolism in other disorders such as seizures and neurodegeneration. In this review we briefly outline the various ASL techniques including advantages and disadvantages of each, methodology for clinical interpretation, and clinical applications with specific examples. J. Magn. Reson. Imaging 2015;41:1165–1180. © 2014 Wiley Periodicals, Inc.     

Brain perfusion territory imaging: methods and clinical applications of selective arterial spin-labeling MR imaging

The ability to visualize perfusion territories in the brain is important for many clinical applications. The aim of this overview is to highlight the possibilities of selective arterial spin-labeling (ASL) magnetic resonance (MR) imaging techniques in the assessment of the perfusion territories of the cerebral arteries. In the past decade, the optimization of selective ASL MR techniques to image the cerebral perfusion territories has resulted in numerous labeling approaches and an increasing number of clinical applications. In this article, the methods and clinical applications of selective ASL MR imaging are described and the importance of perfusion territory information in studying cerebral hemodynamic changes in patients with cerebrovascular disease is shown. In specific patient groups with cerebrovascular disease, such as acute stroke, large artery steno-occlusive disease, and arteriovenous malformation, selective ASL MR imaging provides valuable hemodynamic information when added to current MR protocols. As a noninvasive tool for perfusion territory measurements, selective ASL may contribute to a better understanding of the relation between the vasculature, perfusion, and brain function.     

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.     

Arterial spin labeling: validity testing and comparison studies

Arterial spin labeling (ASL) is a potential means of obtaining quantitative images of cerebral blood flow (CBF). However, few validation studies of ASL have been performed in animal models using gold-standard CBF methods. Other methods that use radiolabeled water as a tracer underestimate CBF in high flow states, but this effect has not been evident in ASL studies. In this study the accuracy of ASL measurements of CBF were modeled and experimentally validated, with particular attention paid to high flow rates. The ASL signal as modeled included the contributions from intravascular labeled spins. The modeling demonstrated linearity of the ASL signal with respect to baseline flow, and linearity of ASL signal changes with respect to changes in flow, including high-flow conditions. Validation studies using quantitative autoradiography (QAR) to image flow in a rat model of unilateral cerebral ischemia showed that ASL systematically overestimated CBF by 34%. A similar overestimation was also predicted by modeling. These results indicate that ASL signals are linear with respect to flow (even high flow), but ASL-CBF measurements are systematically overestimated.     

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。     

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。     

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. © 2014 Wiley Periodicals, Inc.     

Masthead,Volume 73, Issue 1

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.     

Quantification of cerebral perfusion using arterial spin labeling: two-compartment models

One of the advantages of arterial spin labeling (ASL) techniques over other techniques for measuring cerebral perfusion is that with ASL it is possible to achieve accurate quantification. This is particularly useful in the field of functional imaging, where accurate measurements of perfusion change can help untangle the complex physiological changes that occur following neuronal activation. However, the linearity of the perfusion estimate over a wide range of perfusion values may be more important than absolute values. For several years, single-compartment models have dominated the literature, and it has been assumed that the labeled water diffuses freely throughout the tissue voxel. However, recent work, as summarized in this review, has shown that this assumption is inaccurate and leads to an overestimation of perfusion at low perfusion rates, and an underestimation at high rates. The inclusion of restricted permeability of the capillary wall to water in a two-compartment model offers improved quantification.     

Clinical Application of 3D Arterial Spin-Labeled Brain Perfusion Imaging for Alzheimer Disease: Comparison with Brain Perfusion SPECT

BACKGROUND AND PURPOSE:Alzheimer disease is the most common neurodegenerative disorder with dementia, and a practical and economic biomarker for diagnosis of Alzheimer disease is needed. Three-dimensional arterial spin-labeling, with its high signal-to-noise ratio, enables measurement of cerebral blood flow precisely without any extrinsic tracers. We evaluated the performance of 3D arterial spin-labeling compared with SPECT, and demonstrated the 3D arterial spin-labeled imaging characteristics in the diagnosis of Alzheimer disease.MATERIALS AND METHODS:This study included 68 patients with clinically suspected Alzheimer disease who underwent both 3D arterial spin-labeling and SPECT imaging. Two readers independently assessed both images. Kendall W coefficients of concordance (K) were computed, and receiver operating characteristic analyses were performed for each reader. The differences between the images in regional perfusion distribution were evaluated by means of statistical parametric mapping, and the incidence of hypoperfusion of the cerebral watershed area, referred to as “borderzone sign” in the 3D arterial spin-labeled images, was determined.RESULTS:Readers showed K = 0.82/0.73 for SPECT/3D arterial spin-labeled imaging, and the respective areas under the receiver operating characteristic curve were 0.82/0.69 for reader 1 and 0.80/0.69 for reader 2. Statistical parametric mapping showed that the perisylvian and medial parieto-occipital perfusion in the arterial spin-labeled images was significantly higher than that in the SPECT images. Borderzone sign was observed on 3D arterial spin-labeling in 70% of patients misdiagnosed with Alzheimer disease.CONCLUSIONS:The diagnostic performance of 3D arterial spin-labeling and SPECT for Alzheimer disease was almost equivalent. Three-dimensional arterial spin-labeled imaging was more influenced by hemodynamic factors than was SPECT imaging.

Alzheimer disease (AD) is the most common neurodegenerative disorder with dementia and is becoming a social problem in most developed countries. A practical and economic biomarker for diagnosis of AD is needed. CBF is commonly accepted as a physiologic correlate of brain function.¹ AD is associated with regional decreases in CBF, so the ability of CBF to differentiate between individuals affected by AD and healthy individuals has been evaluated with the use of SPECT.²Arterial spin-labeling (ASL) enables measurement of CBF without any extrinsic tracers by use of magnetically labeled arterial blood water as a diffusible tracer. ASL MR imaging has 2 major modalities: pulsed ASL³ and continuous ASL.⁴ The continuous ASL technique uses continuous adiabatic inversion, whereas pulsed ASL uses a single inversion pulse. The recently developed pulsed-continuous ASL imaging protocol based on 3D stack-of-spirals readouts⁵ is an intermediate method between the conventional pulsed ASL and continuous ASL methods, in that pulsed-continuous offers a longer tag bolus than does pulsed ASL and a higher labeling efficiency than does the amplitude-modulated continuous ASL.^6,7 Each section acquired with 2D ASL experiences a slightly different inflow time; thus, it is difficult to estimate a precise transit time when multiple sections are acquired. The use of 3D acquisition techniques overcomes many of these limitations, allowing both whole-brain coverage and simultaneous acquisition to ensure a unified mean transit time. The SNR of 3D acquisitions can be greater than that of 2D multisection methods. Although ASL has inherently low SNR, mainly because of the relatively small amount of labeled spins in the tissue, pulsed-continuous can provide a better balance between labeling efficiency and SNR than conventional ASL methods. This can improve the accuracy of quantified CBF estimates. Many AD studies by use of ASL have been reported, which indicates that ASL MR imaging is an indispensable technique for studying AD.^8–12 CBF measured with ASL MR imaging can detect regional hypoperfusion in the AD precuneus and bilateral parietal cortex and discriminate individuals with AD from normal subjects. Recent research with the use of pulsed-continuous reported that 3D ASL can evaluate the severity of cognitive impairment as measured by the correlation of CBF with cognition.¹³SPECT is now commonly used for CBF assessment in the diagnosis of AD, so we considered that it was important to evaluate the differences in CBF distribution in perfusion images obtained with both SPECT and ASL by use of similarly behaved diffusible tracers and to demonstrate the characteristics of ASL in comparison with SPECT. To the best of our knowledge, the evaluation of brain perfusion imaging by use of both ASL and SPECT in the same subjects with clinically suspected AD to discriminate the AD group from the non-AD group has not been reported. We used whole-brain 3D ASL MR imaging with pulsed-continuous labeling for CBF measurement in the diagnosis of AD because of its high SNR and the possibilities for improving image quality.In this study, we evaluated the detectability of reduced regional cerebral perfusion in AD by use of 3D ASL compared with brain perfusion SPECT and demonstrated the characteristics of perfusion images obtained by means of 3D ASL.