Effect of restricted water exchange on cerebral blood flow values calculated with arterial spin tagging: a theoretical investigation.

Arterial spin tagging techniques originally used the one-compartment Kety model to describe the dynamics of tagged water in the brain. The work presented here develops a more realistic model that includes the contribution of tagged water in the capillary bed and accounts for the finite time required for water to diffuse across the blood-brain barrier. The new model was used to evaluate potential errors in cerebral blood flow values calculated using the one-compartment Kety model. The results predict that if the one-compartment Kety model is used to analyze arterial spin tagging data the observed grey matter cerebral blood flow values should be relatively insensitive to restricted diffusion of water across the capillary bed. For instance, the observed grey matter cerebral blood flow should closely approximate the true cerebral blood flow and not the product of the extraction fraction and the cerebral blood flow. This prediction is in agreement with recent experimental arterial spin tagging results.     

Perfusion imaging with compensation for asymmetric magnetization transfer effects

The effects of off-resonance radio-frequency irradiation on the intensity of the MR signal from water protons in the cat brain are asymmetric around the chemical shift of the water signal. This asymmetry, which could arise from a shift in the magnetization transfer spectrum ?1.5 ppm upfield from the solvent water signal, must be taken into account to compensate for magnetization transfer effects inherent in arterial spin tagging approaches that use a single radio-frequency coil. Two approaches that either correct for, or circumvent, the apparent upfield shift of the magnetization transfer spectrum are presented, and a perfusion image of the cat brain, using flow-induced adiabatic inversion of arterial water protons, is presented. Other problems in obtaining quantitative cerebral blood flow values using the arterial spin tagging approach are discussed.     

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.     

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.     

H(2)(15)O PET validation of steady-state arterial spin tagging cerebral blood flow measurements in humans.

Steady-state arterial spin tagging approaches can provide quantitative images of CBF, but have not been validated in humans. The work presented here compared CBF values measured using steady-state arterial spin tagging with CBF values measured in the same group of human subjects using the H(2)(15)O IV bolus PET method. Blood flow values determined by H(2)(15)O PET were corrected for the known effects of incomplete extraction of water across the blood brain barrier. For a cortical strip ROI, blood flow values determined using arterial spin tagging (64+/-12 cc/100 g/min) were not statistically different from corrected blood flow values determined using H(2)(15)O PET (67+/-13 cc/100 g/min). However, for a central white matter ROI, blood flow values determined using arterial spin tagging were significantly underestimated compared to corrected blood flow values determined using H(2)(15)O PET. This underestimation could be caused by an underestimation of the arterial transit time for white matter regions.     

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.     

Multibolus stimulated echo imaging of coronary artery flow

One limitation of traditional bolus tagging techniques for MR angiography is the small amount of blood labeled by one tagging, resulting in a limited filling of the downstream vessels. We describe a multiple bolus technique using stimulated echoes (STE) for imaging coronary flow. A series of radiofrequency (RF) pairs are given with each pair selective at the region of tagging, thus tagging consecutive volumes of blood, and a final nonselective pulse is given to “read out” all of the tagged spins. In this way, multiple boluses of tagged blood are imaged at one time.     

Spatially-confined arterial spin-labeling with FAIR

PURPOSE: To investigate the effectiveness of slab-selective inversion in pulsed arterial spin labeling with body coil excitation as a means to reduce large vessel contamination of the perfusion signal. MATERIALS AND METHODS: Studies were conducted by varying the tagging width in multislice flow-sensitive alternating inversion recovery (FAIR) in conjunction with body coil excitation on a Siemens Sonata whole-body 1.5-T scanner. The results of spatially-confined tagging were then compared with conventional nonselective tagging in the presence and absence of a bipolar gradient crusher pair in order to determine the effectiveness of suppressing vascular signal and to estimate the bolus width that reaches the capillary bed. RESULTS: It is shown in five volunteers, ages 23-38 years, that depending on the average velocity of the arterial blood flow in the tagging region, a bolus of 6-8 cm in width reaches the capillary bed at a fixed inversion time TI of 1.4 seconds, while a bolus of 11.2-16.5 cm in width enters the imaging region. Further, noticeable velocity differences have been found among the participating subjects, with averages ranging from 10.1 to 13.9 cm/second. CONCLUSION: The data suggest that it is advantageous to replace nonselective global tagging in FAIR perfusion imaging with body coil excitation by spatially-confined tagging to reduce undesired residual tagged blood in large vessels.     

QUIPSS II with thin-slice TI1 periodic saturation: a method for improving accuracy of quantitative perfusion imaging using pulsed arterial spin labeling.

Quantitative imaging of perfusion using a single subtraction, second version (QUIPSS II) is a pulsed arterial spin labeling (ASL) technique for improving the quantitation of perfusion imaging by minimizing two major systematic errors: the variable transit delay from the distal edge of the tagged region to the imaging slices, and the contamination by intravascular signal from tagged blood that flows through the imaging slices. However, residual errors remain due to incomplete saturation of spins over the slab-shaped tagged region by the QUIPSS II saturation pulse, and spatial mismatch of the distal edge of the saturation and inversion slice profiles. By replacing the original QUIPSS II saturation pulse with a train of thin-slice periodic saturation pulses applied at the distal end of the tagged region, the accuracy of perfusion quantitation is improved. Results of single and multislice studies are reported.     

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.     

Quantitative measurements of cerebral blood flow in rats using the FAIR technique: Correlation with previous lodoantipyrine autoradiographic studies

Flow-sensitive alternating inversion recovery (FAIR) is a recently introduced MRI technique for assessment of perfusion that uses blood water as an endogenous contrast agent. To characterize the FAIR signal dependency on spin tagging time (inversion time (Tl)) and to validate FAIR for cerebral blood flow (CBF) quantification, studies were conducted on the rat brain at 9.4 T using a conventional gradient-recalled echo sequence. The 7¹, of cerebral cortex and blood was found to be 1.9 and 2.2 s, respectively, and was used for CBF calculations. At short Tls (<0.8 s), the FAIR signal originates largely from vascular components with fast flows, resulting in an overestimation of CBF. For Tl > 1.5 s, the CBF calculated from FAIR is independent of the spin tagging time, suggesting that the observed FAIR signal originates predominantly from tissue/capillary components. CBF values measured by FAIR with Tl of 2.0 s were found to be in good agreement with those measured by the iodoantipyrine technique with autoradiogra-phy in rats under the same conditions of anesthesia and arterial pCO₂. The measured pCO₂ index on the parietal cortex using the FAIR technique was 6.07 ml/100 g/min per mmHg, which compares well with the pCO₂ index measured by other techniques. The FAIR technique was also able to detect the regional reduction in CBF produced by middle cerebral artery occlusion in rats.     

Quantitative imaging of perfusion using a single subtraction (QUIPSS and QUIPSS II)

In the pulsed arterial spin labeling (ASL) techniques EPISTAR, PICORE, and FAIR, subtraction of two images in which inflowing blood is first tagged and then not tagged yields a qualitative map of perfusion. An important reason this map is not quantitative is that there is a spatially varying delay in the transit of blood from the tagging region to the imaging slice that cannot be measured from a single subtraction. We introduce here two modifications of pulsed ASL (QUIPSS and QUIPSS II) that avoid this problem by applying additional saturation pulses to control the time duration of the tagged bolus, rendering the technique relatively insensitive to transit delays and improving the quantitation of perfusion.     

Perfusion analysis using dynamic arterial spin labeling (DASL).

A variety of magnetic resonance (MR) techniques have proved useful to quantify perfusion using endogenous water as a blood flow tracer. Assuming that water is a freely diffusable tracer, the model used for these techniques predicts that the quantitation of perfusion is based on three parameters, all of which can depend on blood flow. These are the longitudinal tissue relaxation time, the transit time from point of labeling to tissue, and the difference in tissue MR signal between an appropriate control and the labeled state. To measure these three parameters in parallel, a dynamic arterial spin labeling (DASL) technique is introduced based on the analysis of the tissue response to a periodic time varying degree of arterial spin labeling, called here the labeling function (LF). The LF frequency can be modulated to overdetermine parameters necessary to define the system. MR schemes are proposed to measure the tissue response to different LF frequencies efficiently. Sprague-Dawley rats were studied by DASL, using various frequencies for the LF and various arterial pCO2 levels. During data processing, the periodic behavior of the tissue response to the LF allowed for frequency filtering of periodic changes in signal intensity unrelated to perfusion and arterial spin labeling. Measures of transit time, tissue longitudinal relaxation time, and perfusion agreed well over a range of LF frequencies and with previous results. DASL shows potential for more accurately quantifying perfusion as well as measuring transit times associated with arterial spin labeling techniques.     

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-coil arterial spin-tagging for estimating cerebral blood flow as viewed from the capillary: relative contributions of intra- and extravascular signal.

The single‐capillary model was applied to the exchange microvessels for water in the cerebral parenchyma and used to calculate blood‐to‐brain flux of water; the theory of the steady‐state arterial spin‐tagging (AST) technique for estimating cerebral blood flow (CBF) was revised to incorporate the presence of both extravascular (tissue) and capillary signal. A crucial element of the single‐coil AST experiment is that magnetization transfer (MT) shortens the effective T₁ of the extravascular water, making it one‐quarter that of the T₁ of capillary blood. Furthermore, the mean capillary transit time is on the order of the T₁ of the extravascular water. The single‐coil AST experiment is distinguished from other methods which use water as an indicator for measurement of CBF in that the (flow‐dependent) populations of inverted protons in the intra‐ and extravascular compartments can be nearly equal for normal physiological conditions. The following questions are considered: Is single‐coil AST contrast linear in resting CBF? Is contrast in the single‐coil AST technique likely to be linear under changes in CBF in normal tissue? Is the contrast likely to be linear in such common pathologies as stroke and cerebral tumor? We demonstrate that, if the population of inverted protons in the microvessels is included in the experiment, the voxel population of inverted protons will be approximately linear with flow across a broad range of flow values. We predict that the single‐coil AST experiment will systematically overestimate resting CBF for flows in the normal range, that changes in CBF in normal tissue will produce an approximately linear response in AST measurement, and, finally, we predict the operating characteristics of the measurement in common cerebral pathologies. Magn Reson Med 46:465–475, 2001. © 2001 Wiley‐Liss, Inc.     

Perfusion imaging of the human brain at 1.5 T using a single-shot EPI spin tagging approach

Single-shot echo planar imaging (EPI) techniques have been applied, in conjunction with arterial spin tagging approaches, to obtain images of cerebral blood flow in a single axial slice in the human brain. Serial studies demonstrate that cerebral blood flow images acquired in 8 min are reproducible, with a statistical precision of approximately ±10 cc/100 g/min. The average value of cerebral blood flow in the slice is 51 ±11 cc/100 g/min for six normal subjects. The cerebral blood flow images contain two types of artifact, probably due to arterial and venous blood volume contributions, which must be overcome before the arterial spin tagging approach can be used for routine clinical studies.     

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.     

Intraportal venous flow distribution: evaluation with single breath-hold ECG-triggered three-dimensional half-Fourier fast spin-echo MR imaging and a selective inversion-recovery tagging pulse.

OBJECTIVE: The purpose of this study was to evaluate the intraportal blood flow distribution from splenic and superior mesenteric veins with an unenhanced MR angiographic technique using single breath-hold ECG-triggered three-dimensional (3D) half-Fourier fast spin-echo sequence and selective inversion-recovery tagging pulse. SUBJECTS AND METHODS: Seventeen healthy volunteers were included in this prospective study. After obtaining regular single breath-hold ECG-triggered 3D half-Fourier fast spin-echo images without applying a tagging pulse, we placed the selective inversion-recovery tagging pulse on the superior mesenteric vein (TAG-A), the splenic vein (TAG-B), or on both (TAG-C) to study the inflow correlation of tagged or marked blood into the portal vein. MR images were evaluated subjectively by three reviewers. RESULTS: On MR images obtained using the TAG-A pulse to suppress the signal flow from the superior mesenteric vein into the portal vein, the most common pattern of signal loss was observed on the right half of the main portal vein (8/17 subjects). Conversely, on the MR images obtained using the TAG-B pulse, signal loss of the left half of the main portal vein was the most common pattern (11/17 subjects). Signal reduction from the splenic venous flow in the left portal vein was significantly greater than that from the superior mesenteric venous flow (p<0.05). CONCLUSION: The unenhanced MR angiographic technique using single breath-hold ECG-triggered 3D half-Fourier fast spin echo with selective inversion-recovery tagging pulse has the potential to assess the intraportal blood flow distribution from the splenic and superior mesenteric veins.     

MR angiography using spin-lock flow tagging.

A method for MR angiography using an RF labeling technique is suggested. The method utilizes a slice-selective spin-lock pulse sequence for tagging the spins of inflowing blood. The pulse sequence begins with a spatially selective 90 degrees (x) RF pulse, followed by a nonselective composite locking pulse of 135 degrees (y) - n[360 degrees (y)]-135 degrees (y) and by a 90 degrees (-x) pulse. A spoiler gradient is then applied. A rapid imaging stage, which yields a T(1)rho-weighted signal from the tagged spins, completes the sequence. Untagged spins are thoroughly dephased and consequently suppressed in the image. Thus, contrast is obtained without an injection of a contrast material or image subtraction. Furthermore, the flow of the tagged bolus can be visualized. The sequence was implemented on phantoms and on human volunteers using a 1.5T scanner. The results indicate the feasibility of the suggested sequence.     

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.