CBF measurements using multidelay pseudocontinuous and velocity-selective arterial spin labeling in patients with long arterial transit delays: comparison with xenon CT CBF

Purpose:

To test the theory that velocity‐selective arterial spin labeling (VSASL) is insensitive to transit delay.

Materials and Methods:

Cerebral blood flow (CBF) was measured in ten Moyamoya disease patients using xenon computed tomography (xeCT) and magnetic resonance imaging (MRI), which included multiple pseudo‐continuous ASL (pcASL) with different postlabel delays, VSASL, and dynamic susceptibility contrast (DSC) imaging. Correlation coefficient, root‐mean‐square difference, mean CBF error between ASL, and gold‐standard xeCT CBF measurements as well the dependence of this error on transit delay (TD) as estimated by DSC time‐to‐peak of the residue function (Tmax) were determined.

Results:

For pcASL with different postlabel delay time (PLD), CBF measurement with short PLD (1.5–2 sec) had the strongest correlations with xeCT; VSASL had a lower but still significant correlation with a mean coefficient of 0.55. We noted the theoretically predicted dependence of CBF error on Tmax and on PLD for pcASL; VSASL CBF measurements had the least dependence of the error on TD. We also noted effects suggesting that the location of the label decay (blood vs. tissue) impacted the measurement, which was worse for pcASL than for VSASL.

Conclusion:

We conclude that VSASL is less sensitive to TD than conventional ASL techniques and holds promise for CBF measurements in cerebrovascular diseases with slow flow. J. Magn. Reson. Imaging 2012;36:110–119. © 2012 Wiley Periodicals, Inc.     

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.     

Quantifying CBF with pulsed ASL: technical and pulse sequence factors

We summarize here current methods for the quantification of CBF using pulsed arterial spin labeling (ASL) methods. Several technical issues related to CBF quantitation are described briefly, including transit delay, signal from larger arteries, radio frequency (RF) slice profiles, magnetization transfer, tagging efficiency, and tagging geometry. Many pulsed tagging schemes have been devised, which differ in the type of tag or control pulses, and which have various advantages and disadvantages for quantitation. Several other modifications are also available that can be implemented as modules in an ASL pulse sequence, such as varying the wash-in time to estimate the transit delay. Velocity-selective ASL (VS-ASL) uses a new type of pulse labeling in which inflowing arterial spins are tagged based on their velocity rather than their spatial location. In principle, this technique may allow ASL measurement of cerebral blood flow (CBF) that is insensitive to transit delays.     

Quantifying CBF with arterial spin labeling

The basic principles of measuring cerebral blood flow (CBF) using arterial spin labeling (ASL) are reviewed. The measurement is modeled by treating the ASL method as a magnetic resonance imaging (MRI) version of a microsphere study, rather than a diffusible tracer study. This approach, particularly when applied to pulsed ASL (PASL) experiments, clarifies that absolute calibration of CBF primarily depends on global properties of blood, rather than local tissue properties such as the water partition coefficient or relaxation time. However, transit delays from the tagging region to the image voxel are a potential problem in all standard ASL methods. The key to quantitative CBF measurements that compensate for this systematic error is to create a well-defined bolus of tagged blood and to ensure that all of the bolus has been delivered to an imaging voxel at the time of measurement. Two practical technical factors considered here are 1) producing a tagged bolus with a well-defined temporal width and 2) accounting for reduction in magnitude of the tagged magnetization due to relaxation. The ASL approach has the potential to provide a robust estimation of CBF, although the timing of water exchange into tissue and the effects of pulsatile flow require further investigation.     

Quantification of cerebral arterial blood volume and cerebral blood flow using MRI with modulation of tissue and vessel (MOTIVE) signals.

Regional cerebral arterial blood volume (CBVa) and blood flow (CBF) can be quantitatively measured by modulation of tissue and vessel (MOTIVE) signals, enabling separation of tissue signal from blood. Tissue signal is selectively modulated using magnetization transfer (MT) effects. Blood signal is changed either by injection of a contrast agent or by arterial spin labeling (ASL). The measured blood volume represents CBVa because the contribution from venous blood was insignificant in our measurements. Both CBVa and CBF were quantified in isoflurane-anesthetized rats at 9.4T. CBVa obtained using a contrast agent was 1.1 +/- 0.5 and 1.3 +/- 0.6 ml/100 g tissue (N = 10) in the cortex and caudate putamen, respectively. The CBVa values determined from ASL data were 1.0 +/- 0.3 ml/100 g (N = 10) in both the cortex and the caudate putamen. The match between CBVa values determined by both methods validates the MOTIVE approach. In ASL measurements, the overestimation in calculated CBF values increased with MT saturation levels due to the decreasing contribution from tissue signals, which was confirmed by the elimination of blood with a contrast agent. Using the MOTIVE approach, accurate CBF values can also be obtained.     

Combined arterial spin label and dynamic susceptibility contrast measurement of cerebral blood flow

Dynamic susceptibility contrast (DSC) and arterial spin labeling (ASL) are both used to measure cerebral blood flow (CBF), but neither technique is ideal. Absolute DSC‐CBF quantitation is challenging due to many uncertainties, including partial‐ volume errors and nonlinear contrast relaxivity. ASL can measure quantitative CBF in regions with rapidly arriving flow, but CBF is underestimated in regions with delayed arrival. To address both problems, we have derived a patient‐specific correction factor, the ratio of ASL‐ and DSC‐CBF, calculated only in short‐arrival‐time regions (as determined by the DSC‐based normalized bolus arrival time [Tmax]). We have compared the combined CBF method to gold‐standard xenon CT in 20 patients with cerebrovascular disease, using a range of Tmax threshold levels. Combined ASL and DSC CBF demonstrated quantitative accuracy as good as the ASL technique but with improved correlation in voxels with long Tmax. The ratio of MRI‐based CBF to xenon CT CBF (coefficient of variation) was 90 ± 30% (33%) for combined ASL and DSC CBF, 43 ± 21% (47%) for DSC, and 91 ± 31% (34%) for ASL (Tmax threshold 3 sec). These findings suggest that combining ASL and DSC perfusion measurements improves quantitative CBF measurements in patients with cerebrovascular disease. Magn Reson Med 63:1548–1556, 2010. © 2010 Wiley‐Liss, Inc.     

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。     

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.     

Pseudo-continuous arterial spin labeling technique for measuring CBF dynamics with high temporal resolution.

Cerebral blood flow (CBF) can be measured noninvasively with nuclear magnetic resonance (NMR) by using arterial water as an endogenous perfusion tracer. However, the arterial spin labeling (ASL) techniques suffer from poor temporal resolution due to the need to wait for the exchange of labeled arterial spins with tissue spins to produce contrast. In this work, a new ASL technique is introduced, which allows the measurement of CBF dynamics with high temporal and spatial resolution. This novel method was used in rats to determine the dynamics of CBF changes elicited by somatosensory stimulation with a temporal resolution of 108 ms. The onset time of the CBF response was 0.6 +/- 0.4 sec (mean +/- SD) after onset of stimulation (n = 10). The peak response was observed 4.4 +/- 3.7 sec (mean +/- SD) after stimulation began. These results are in excellent agreement with previous data obtained with invasive techniques, such as laser-Doppler flowmetry and hydrogen clearance, and suggest the appropriateness of this novel technique to probe CBF dynamics in functional and pathological studies with high temporal and spatial resolution. Magn Reson Med 42:425-429, 1999.     

Perfusion Tensor Imaging

Arterial spin labeling (ASL) provides a method by which to noninvasively measure the spatial and temporal characteristics of local tissue perfusion. Standard methods employ spatial tagging schemes, but recently methods based on velocity dependent tags, called Velocity Selective ASL (VSASL), have been introduced wherein the tagging depends upon the vascular velocity profile. In this article, we point out an interesting feature of VSASL: the velocity can be encoded in any direction, thereby allowing for the measurement of perfusion with a specified angular resolution. This then facilitates the reconstruction of the local perfusion field, characterized by a perfusion tensor P, from which can be derived quantities related to the structure of the local perfusion field, such as the mean perfusion, the perfusion anisotropy, and the principal directions of flow feeding each voxel. We demonstrate this new method, Perfusion Tensor Imaging (PTI), in both the brain and skeletal muscle of normal human volunteers and discuss possible applications. Magn Reson Med 60:1284–1291, 2008. © 2008 Wiley‐Liss, Inc.     

Arterial spin-labeling MR imaging measurements of timing parameters in patients with a carotid artery occlusion

BACKGROUND AND PURPOSE: Arterial spin-labeling (ASL) with image acquisition at multiple delay times can be exploited in perfusion MR imaging to visualize and quantify the temporal dynamics of arterial blood inflow. In this study, we investigated the consequences of an internal carotid artery (ICA) occlusion and collateral blood flow on regional timing parameters.MATERIALS AND METHODS: Seventeen functionally independent patients with a symptomatic ICA occlusion (15 men, 2 women; mean age, 57 years) and 29 sex- and age-matched control subjects were investigated. ASL at multiple delay times was used to quantify regional cerebral blood flow (CBF) and the transit and trailing edge times (arterial timing parameters) reflecting, respectively, the beginning and end of the labeled bolus. Intra-arterial digital subtraction angiography and MR angiography were used to grade collaterals.RESULTS: In the hemisphere ipsilateral to the ICA occlusion, the CBF was lower in the anterior frontal (31 ± 4 versus 47 ± 3 mL/min/100 g, P < .01), posterior frontal (39 ± 4 versus 55 ± 2 mL/min/100 g, P < .01), and frontal parietal region (49 ± 3 versus 61 ± 3 mL/min/100 g, P = .04) than that in control subjects. The trailing edge of the frontal-parietal region was longer in the hemisphere ipsilateral to the ICA occlusion compared with that in control subjects (2225 ± 167 versus 1593 ± 35 ms, P < .01). In patients with leptomeningeal collateral flow, the trailing edge was longer in the anterior frontal region (2436 ± 275 versus 1648 ± 201 ms, P = .03) and shorter in the occipital region (1815 ± 128 versus 2388 ± 203 ms, P = .04), compared with patients without leptomeningeal collaterals.CONCLUSION: Regional assessment of timing parameters with ASL may provide valuable information on the cerebral hemodynamic status. In patients with leptomeningeal collaterals, the most impaired territory was found in the frontal lobe.

An obstructive lesion in the internal carotid artery (ICA) causes a reduction of the perfusion pressure in the cerebral circulation. As the cerebral perfusion pressure decreases, pressure is initially maintained by a compensatory vasodilation of the arterioles, followed by an increase in the oxygen extraction fraction.¹ Regionally, the cerebral hemodynamic status depends not only on the degree of carotid obstruction but also on other factors, such as the contribution of collateral pathways.^2,3The collateral circulation can provide alternative routes for oxygenated blood to reach the brain tissue, either through the primary pathways via the circle of Willis or the secondary pathways via leptomeningeal and ophthalmic collaterals.⁴ The combination of a decreased cerebral perfusion pressure and an insufficient primary collateral blood supply may lead to hemodynamic impairment, which eventually can result in a limited clearance of emboli and ischemia.^5,6 Recruitment of the secondary collaterals is associated with further impairment, and its presence may be considered a marker of inadequacy of the primary collateral pathways.^7,8 Because the recruitment of collateral perfusion in patients with an ICA occlusion will lead to longer blood flow routes and a delayed arrival time of the blood, regional knowledge of the arrival times of arterial blood may provide additional information to characterize the collateral flow and may potentially be used to identify hemodynamically impaired regions. The most widely used methods to measure arrival times of blood use dynamic sampling of an injected bolus of contrast agent. However, due to the current concerns regarding contrast use in patients with poor renal function⁹ and ionizing radiation, an alternative without detrimental effects would be of great benefit.Recently, arterial spin-labeling (ASL) was introduced as a noninvasive method capable of assessing cerebral perfusion and the temporal dynamics of arterial blood inflow.¹⁰ The purpose of our study was, first, to investigate hemodynamic parameters in different areas of the brain in patients with an occlusion of the ICA and, second, to evaluate the effect of collateral flow on regional hemodynamics. We used an ASL MR imaging technique with image acquisition at multiple delay times to quantify regionally cerebral blood flow (CBF) and arterial timing parameters (transit and trailing edge times).     

Quantification of rodent cerebral blood flow (CBF) in normal and high flow states using pulsed arterial spin labeling magnetic resonance imaging

PURPOSE: To implement a pulsed arterial spin labeling (ASL) technique in rats that accounts for cerebral blood flow (CBF) quantification errors due to arterial transit times (dt)-the time that tagged blood takes to reach the imaging slice-and outflow of the tag. MATERIALS AND METHODS: Wistar rats were subjected to air or 5% CO(2), and flow-sensitive alternating inversion-recovery (FAIR) perfusion images were acquired. For CBF calculation, we applied the double-subtraction strategy (Buxton et al., Magn Reson Med 1998;40:383-396), in which data collected at two inversion times (TIs) are combined. RESULTS: The ASL signal fell off more rapidly than expected from TI = one second onward, due to outflow effects. Inversion times for CBF calculation were therefore chosen to be larger than the longest transit times, but short enough to avoid systematic errors caused by outflow of tagged blood. Using our method, we observed a marked regional variability in CBF and dt, and a region dependent response to hypercapnia. CONCLUSION: Even when flow is accelerated, CBF can be accurately determined using pulsed ASL, as long as dt and outflow of the tag are accounted for.     

Collateral circulation imaging: MR perfusion territory arterial spin-labeling at 3T

BACKGROUND AND PURPOSE: Current knowledge of the collateral circulation remains sparse, and a noninvasive method to better characterize the role of collaterals is desirable. The aim of our study was to investigate the presence and distal flow of collaterals by using a new MR perfusion territory imaging, vessel-encoded arterial spin-labeling (VE-ASL).MATERIALS AND METHODS: Fifty-six patients with internal carotid artery (ICA) or middle cerebral artery (MCA) stenosis were identified by sonography. VE-ASL was performed to assess the presence and function of collateral flow. The perfusion information was combined with VE maps into high signal-intensity-to-noise-ratio 3-colored maps of the left carotid, right carotid, and posterior circulation territories. The presence of the anterior and posterior collateral flow was demonstrated by the color of the standard anterior cerebral artery/MCA flow territory. The distal function of collateral flow was categorized as adequate (cerebral blood flow [CBF] ≥10 mL/min/100 g) or deficient (CBF <10 mL/min/100 g). The results were compared with those of MR angiography (MRA) and intra-arterial digital subtraction angiography (DSA) in cross table, and κ coefficients were calculated to determine the agreement among different methods.RESULTS: The κ coefficients of the presence of anterior and posterior collaterals by using VE-ASL and MRA were 0.785 and 0.700, respectively. The κ coefficient of the function of collaterals by using VE-ASL and DSA was 0.726. Apart from collaterals through the circle of Willis, VE-ASL showed collateral flow via leptomeningeal anastomoses.CONCLUSIONS: In patients with ICA or MCA stenosis, VE-ASL could show the presence, the origin, and distal function of collateral flow noninvasively.

The protective effect of collateral circulation influences final clinical outcomes for patients with hemodynamically significant arterial stenosis. The principal source of collateral flow of cerebral arteries is through the arteries of the circle of Willis. Secondary collateral pathways include the external carotid artery via the ophthalmic artery and leptomeningeal anastomoses at the brain surface. However, the size and patency of these arteries are quite variable.Doppler sonography is the most common tool used to investigate the presence of collateral flows. MR angiography (MRA) can be used for determining the collaterals through the circle of Willis. However, both sonography and MRA do not show leptomeningeal collateral pathways, distal collateral flows, or the actual contribution of collateral flow to brain perfusion. Intra-arterial digital subtraction angiography (DSA) shows the presence and distal arteries of the collateral pathways.¹ However, to visualize all the collateral pathways, this technique requires an invasive and selective 3-vessel approach and is typically not performed in patients with acute stroke or cerebral arterial stenosis. Therefore, a noninvasive method that demonstrates selectively angiographic information may be desired to investigate collateral blood flow.²In MR perfusion territory arterial spin-labeling (ASL),^3–7 blood in individual or groups of feeding arteries is tagged by using ASL methodology, and images are acquired that map the vascular distribution of those feeding arteries. Recently, vessel-encoded ASL (VE-ASL) MR imaging⁸ was introduced as a more time-efficient method for mapping multiple vascular territories. The aim of our study was to investigate the presence and distal flow of collateral blood supply by using the VE-ASL technique at 3T on patients with carotid stenotic disease.     

Arterial spin labeling in small animals: methods and applications to experimental cerebral ischemia

ASL enables noninvasive, quantitative monitoring of cerebral perfusion to be performed repeatedly over a period of hours. Thus, ASL is an attractive method for basic science studies of the time evolution and pathophysiology of diseases using animal models. In particular, ASL is valuable for basic science studies of evolving tissue status and viability in stroke using animal models of acute ischemia. This study describes both pulsed (PASL) and continuous ASL (CASL) studies of quantitative cerebral perfusion in rodent models of cerebral ischemia. Some technical factors pertinent to these studies are discussed, including a method for measuring arterial blood T(1) and double-echo PASL for measuring cerebral blood flow (CBF) and volume (CBV). Investigations of the CBF response to forebrain ischemia and reperfusion, and of regional variations in CBF and arterial transit time (ATT) are also discussed.     

Arterial spin-labeling in routine clinical practice, part 1: technique and artifacts

The routine use of arterial spin-labeling (ASL) in a clinical population has led to the depiction of diverse brain pathologic features. Unique challenges in the acquisition, postprocessing, and analysis of cerebral blood flow (CBF) maps are encountered in such a population, and high-quality ASL CBF maps can be generated consistently with attention to quality control and with the use of a dedicated postprocessing pipeline. Familiarity with commonly encountered artifacts can help avoid pitfalls in the interpretation of CBF maps. The purpose of this review was to describe our experience with a heterogeneous collection of ASL perfusion cases with an emphasis on methodology and common artifacts encountered with the technique. In a period of 1 year, more than 3000 pulsed ASL cases were performed as a component of routine clinical brain MR evaluation at both 1.5 and 3T. These ASL studies were analyzed with respect to overall image quality and patterns of perfusion on final gray-scale DICOM images and color Joint Photographic Experts Group (JPEG) CBF maps, and common artifacts and their impact on final image quality were categorized.     

Absolute cerebral blood flow quantification with pulsed arterial spin labeling during hyperoxia corrected with the simultaneous measurement of the longitudinal relaxation time of arterial blood

Quantitative arterial spin labeling (ASL) estimates of cerebral blood flow (CBF) during oxygen inhalation are important in several contexts, including functional experiments calibrated with hyperoxia and studies investigating the effect of hyperoxia on regional CBF. However, ASL measurements of CBF during hyperoxia are confounded by the reduction in the longitudinal relaxation time of arterial blood (T(1a) ) from paramagnetic molecular oxygen dissolved in blood plasma. The aim of this study is to accurately quantify the effect of arbitrary levels of hyperoxia on T(1a) and correct ASL measurements of CBF during hyperoxia on a per-subject basis. To mitigate artifacts, including the inflow of fresh spins, partial voluming, pulsatility, and motion, a pulsed ASL approach was implemented for in vivo measurements of T(1a) in the rat brain at 3 Tesla. After accounting for the effect of deoxyhemoglobin dilution, the relaxivity of oxygen on blood was found to closely match phantom measurements. The results of this study suggest that the measured ASL signal changes are dominated by reductions in T(1a) for brief hyperoxic inhalation epochs, while the physiologic effects of oxygen on the vasculature account for most of the measured reduction in CBF for longer hyperoxic exposures.     

Partial volume correction of multiple inversion time arterial spin labeling MRI data

The accuracy of cerebral blood flow (CBF) estimates from arterial spin labeling (ASL) is affected by the presence of both gray matter (GM) and white matter within any voxel. Recently a partial volume (PV) correction method for ASL has been demonstrated (Asllani et al. Magn Reson Med 2008; 60:1362–1371), where PV estimates were used with a local linear regression to separate the GM and white matter ASL signal. Here a new PV correction method for multi‐inversion time ASL is proposed that exploits PV estimates within a spatially regularized kinetic curve model analysis. The proposed method exploits both PV estimates and the different kinetics of the ASL signal arising from GM and white matter. The new correction method is shown, on both simulated and real data, to provide correction of GM CBF comparable to a linear regression approach, whilst preserving greater spatial detail in the CBF image. On real data corrected GM CBF values were found to be largely independent of GM PV, implying that the correction had been successful. Increases of mean GM CBF after correction of 69–80% were observed. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Comparison of ASL and DCE MRI for the non-invasive measurement of renal blood flow: quantification and reproducibility

Objectives

To investigate the reproducibility of arterial spin labelling (ASL) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and quantitatively compare these techniques for the measurement of renal blood flow (RBF).

Methods

Sixteen healthy volunteers were examined on two different occasions. ASL was performed using a multi-TI FAIR labelling scheme with a segmented 3D-GRASE imaging module. DCE MRI was performed using a 3D-FLASH pulse sequence. A Bland-Altman analysis was used to assess repeatability of each technique, and determine the degree of correspondence between the two methods.

Results

The overall mean cortical renal blood flow (RBF) of the ASL group was 263?±?41 ml min^?1 [100 ml tissue]^?1, and using DCE MRI was 287?±?70 ml min^?1 [100 ml tissue]^?1. The group coefficient of variation (CV_g) was 18 % for ASL and 28 % for DCE-MRI. Repeatability studies showed that ASL was more reproducible than DCE with CV_gs of 16 % and 25 % for ASL and DCE respectively. Bland-Altman analysis comparing the two techniques showed a good agreement.

Conclusions

The repeated measures analysis shows that the ASL technique has better reproducibility than DCE-MRI. Difference analysis shows no significant difference between the RBF values of the two techniques.

Key Points

? Reliable non-invasive monitoring of renal blood flow is currently clinically unavailable. ? Renal arterial spin labelling MRI is robust and repeatable. ? Renal dynamic contrast-enhanced MRI is robust and repeatable. ? ASL blood flow values are similar to those obtained using DCE-MRI.     

Measuring the neural response to continuous intramuscular infusion of hypertonic saline by perfusion MRI

Purpose:

To determine the extent to which arterial spin labeling (ASL), a functional magnetic resonance imaging technique that directly measures cerebral blood flow (CBF), is able to measure the neural activation associated with prolonged experimental muscle pain.

Materials and Methods:

Hypertonic saline (HS) (5% NaCl) was infused into the brachioradialis muscle of 19 healthy volunteers for 15 min. The imaging volume extended from the dorsal side of the pons to the primary somatosensory cortices, covering most of the cortical and subcortical regions associated with pain perception.

Results:

Using a numerical scale from 0 to 10, ratings of pain intensity peaked at 5.9 ± 0.5 (mean ± SE). Group activation maps showed that the slow infusion of HS evoked CBF increases primarily in bilateral insula, with additional activation in right frontal regions. In the activated areas, CBF gradually increased at the onset of HS infusion and was maintained at relatively constant levels throughout the remainder of the infusion period. However, the level and extent of activation were smaller than observed in previous studies involving acute muscle pain.

Conclusion:

This study demonstrates the ability of ASL to measure changes in CBF over extended periods of time and that the neural activation caused by muscle pain is paradigm specific. J. Magn. Reson. Imaging 2012;35:669‐677. © 2011 Wiley‐Liss, Inc.     

Effects of the apparent transverse relaxation time on cerebral blood flow measurements obtained by arterial spin labeling.

Previous modeling studies have predicted that a significant fraction of the signal in arterial spin labeling (ASL) experiments originates from labeled water in the capillaries. Provided that the relaxation times in blood and tissue are similar, ASL data can still be analyzed with the conventional one-compartment Kety model. Such studies have primarily focused on T1 differences and have neglected any differences in transverse relaxation times (T2 and T2*). This is reasonable for studies at lower fields; however, it may not be valid at higher fields due to the stronger susceptibility effects of deoxygenated blood. In this study a tracer kinetic model was developed that includes T2* differences between capillary blood and tissue. The model predicts that a reduction in blood T2* at higher fields will attenuate the capillary contribution to the ASL signal. This in turn causes an underestimation of CBF when ASL data are analyzed with the one-compartment Kety model. We confirmed this prediction by comparing ASL data collected at 1.5 and 4 T, and at multiple gradient echoes (19, 32, 45, and 58 ms). A decrease in resting-state CBF with echo time (TE) was observed at 4 T, but not at 1.5 T. These results suggest that at higher fields AST data should be collected using gradient-echo techniques with short TEs, or with spin-echo techniques. Furthermore, the sensitivity of the CBF measurements to venous T2* may affect the interpretation of concurrent ASL/BOLD studies.