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

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

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.     

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.     

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.     

Quantitation of regional cerebral blood flow increases during motor activation: A multislice, steady-state, arterial spin tagging study.

Steady-state arterial spin tagging approaches were used to construct multislice images of relative cerebral blood flow changes during finger-tapping tasks. Statistically significant increases in cerebral blood flow were observed in primary sensorimotor cortex in all seven subjects. The mean volume of the activated region in the contralateral primary sensorimotor cortex was 0.9 cm(3), and the mean increase in cerebral blood flow in the activated area was 54% +/- 11%. Although the extended spatial coverage is advantageous for activation studies, the intrinsic sensitivity of the multislice approach is smaller than the intrinsic sensitivity of the single-slice, arterial spin tagging approach. Magn Reson Med 42:404-407, 1999. Published 1999 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.     

Noise reduction in 3D perfusion imaging by attenuating the static signal in arterial spin tagging (ASSIST)

Phase-encoded multishot SPIRAL approaches were used to acquire true 3D cerebral blood flow images of the human head using arterial spin tagging approaches. Multiple-inversion background suppression techniques, which suppress phase noise due to interacquisition fluctuations in the static magnetic field, reduced the temporal standard deviation of true 3D ΔM images acquired using arterial spin tagging approaches by ∼50%. Background suppressed arterial spin tagging (ASSIST) approaches were used to obtain high-resolution isotropic true 3D cerebral blood flow images, and to obtain true 3D activation images during cognitive (working memory) tasks. Magn Reson Med 44:92–100, 2000. Published 2000 Wiley-Liss, Inc.     

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.     

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.     

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.     

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.     

Multiphase pseudocontinuous arterial spin labeling (MP‐PCASL) for robust quantification of cerebral blood flow

Pseudocontinuous arterial spin labeling (PCASL) has been demonstrated to provide the sensitivity of the continuous arterial spin labeling method while overcoming many of the limitations of that method. Because the specification of the phases in the radiofrequency pulse train in PCASL defines the tag and control conditions of the flowing arterial blood, its tagging efficiency is sensitive to factors, such as off‐resonance fields, that induce phase mismatches between the radiofrequency pulses and the flowing spins. As a result, the quantitative estimation of cerebral blood flow with PCASL can exhibit a significant amount of error when these factors are not taken into account. In this paper, the sources of the tagging efficiency loss are characterized and a novel PCASL method that utilizes multiple phase offsets is proposed to reduce the tagging efficiency loss in PCASL. Simulations are performed to evaluate the feasibility and the performance of the proposed method. Quantitative estimates of cerebral blood flow obtained with multiple phase offset PCASL are compared to estimates obtained with conventional PCASL and pulsed arterial spin labeling. Our results show that multiple phase offset PCASL provides robust cerebral blood flow quantification while retaining much of the sensitivity advantage of PCASL. Magn Reson Med, 2010. © 2010 Wiley‐Liss, 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.     

Measurement of liver blood flow using oxygen-15 labelled water and dynamic positron emission tomography: Limitations of model description

To date no satisfactory method has been available for the quantitative in vivo measurement of the complex hepatic blood flow. In this study two modelling approaches are proposed for the analysis of liver blood flow using positron emission tomography (PET). Five experiments were performed on three foxhounds. The anaesthetised dogs were each given an intravenous bolus injection of oxygen-15 labelled water, and their livers were then scanned using PET. Radioactivity in the blood from the aorta and portal vein was measured directly and simultaneously using closed external circuits. Time-activity curves were constructed from sequential PET data. Data analysis was performed by assuming that water behaves as a freely diffusible tracer and adapting the standard one-compartment blood flow model to describe the dual blood supply of the liver. Two particular modelling approaches were investigated: the dual-input model used both directly measured input functions (i.e. using the hepatic artery and the portal vein input, determined from the radioactivity detected in the aorta and portal vein respectively) whereas the single-input model used only the measured arterial curve and predicted the corresponding portal input function. Hepatic arterial flow, portal flow and blood volume were fitted from the PET data in several regions of the liver. The resulting estimates were then compared with reference blood flow measurements, obtained using a standard microsphere technique. The microspheres were injected in a separate experiment on the same dogs immediately prior to PET scanning. Whilst neither the single- nor the dual-input models accurately reproduced the arterial reference flow values, the flow values from the single-input model were closer to the microsphere flow values. The proposed single-input model would be a good approximation for liver blood flow measurements in man. The observed discrepancies between the PET and microsphere flow values may be due to the inherent temporal and spatial heterogeneity of liver blood flow. The results presented suggest that adaptation of the standard one-compartment blood flow model to describe the dual blood supply of the liver is limited and other flow tracers have to be considered for quantitative PET measurements in the liver.     

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.     

Regional effects of magnetization dispersion on quantitative perfusion imaging for pulsed and continuous arterial spin labeling

Most experiments assume a global transit delay time with blood flowing from the tagging region to the imaging slice in plug flow without any dispersion of the magnetization. However, because of cardiac pulsation, nonuniform cross‐sectional flow profile, and complex vessel networks, the transit delay time is not a single value but follows a distribution. In this study, we explored the regional effects of magnetization dispersion on quantitative perfusion imaging for varying transit times within a very large interval from the direct comparison of pulsed, pseudo‐continuous, and dual‐coil continuous arterial spin labeling encoding schemes. Longer distances between tagging and imaging region typically used for continuous tagging schemes enhance the regional bias on the quantitative cerebral blood flow measurement causing an underestimation up to 37% when plug flow is assumed as in the standard model. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Xenon CT cerebral blood flow in patients with head injury: influence of pulmonary trauma on the input function

The noninvasive xenon-enhanced CT (Xe CT) cerebral blood flow (CBF) method has been used in patients with severe traumatic brain injury (TBI) to identify the blood-flow thresholds for the development of irreversible ischaemia or infarction following severe TBI. Quantitative regional CBF (rCBF) estimates are based on the assumption of identity between the end-tidal xenon concentration curve, used as the input function, and the arterial xenon concentration curve, being the true input function to the brain. Accordingly, rCBF data addressing the issue of ischaemia should be viewed in relation to possible deviations between the end-tidal and arterial xenon concentration curves. To evaluate this possible source of error, we studied five patients with severe TBI (Glasgow coma score ≤ 7) who also had pulmonary trauma. CBF was studied with the Xe CT CBF method and flow rates were determined by fitting the Kety equation to each CT voxel using either the end-tidal or the arterial xenon curve as input function. In all patients rCBF estimates were lower using the end-tidal xenon curve than with the arterial xenon curve; the mean underestimation was 20.3 % in gray metter and 17.3 % in white matter. The deviation between the end-tidal and arterial xenon concentration curves should be considered as a source of error when defining critical flow values according to the flow thresholds of tissue viability Received: 1 June 1999/Accepted: 23 July 1999     

Model-free arterial spin labeling quantification approach for perfusion MRI.

In this work a model-free arterial spin labeling (ASL) quantification approach for measuring cerebral blood flow (CBF) and arterial blood volume (aBV) is proposed. The method is based on the acquisition of a train of multiple images following the labeling scheme. Perfusion is obtained using deconvolution in a manner similar to that of dynamic susceptibility contrast (DSC) MRI. Local arterial input functions (AIFs) can be estimated by subtracting two perfusion-weighted images acquired with and without crusher gradients, respectively. Furthermore, by knowing the duration of the bolus of tagged arterial blood, one can estimate the aBV on a voxel-by-voxel basis. The maximum of the residue function obtained from the deconvolution of the tissue curve by the AIF is a measure of CBF after scaling by the locally estimated aBV. This method provides averaged gray matter (GM) perfusion values of 38 +/- 2 ml/min/100 g and aBV of 0.93% +/- 0.06%. The average CBF value is 10% smaller than that obtained on the same data set using the standard general kinetic model (42 +/- 2 ml/min/100 g). Monte Carlo simulations were performed to compare this new methodology with parametric fitting by the conventional model.     

Effects of CBV,CBF, and blood‐brain barrier permeability on accuracy of PASL and VASO measurement

Cerebral blood flow, cerebral blood volume (CBV), and water permeability through blood‐brain barrier are important hemodynamic parameters in brain physiology. Pulsed arterial spin labeling and vascular‐space occupancy techniques have been used to measure regional cerebral blood flow and CBV, respectively. However, these techniques generally ignore the effects of one hemodynamic parameter on the measurement of others. For instance, the influences of CBV changes on arterial spin labeling or the permeability effects on vascular‐space occupancy typically were not accounted for in the quantification of blood flow or volume. In the current work, the biophysical effects of CBV on pulsed arterial spin labeling and permeability on vascular‐space occupancy signals are evaluated using a general two‐compartment model. The dependence of these effects on the T₁ at various field strengths is also assessed by simulations. Results indicate that CBV has negligible to small influences on pulsed arterial spin labeling signal (<6.6% at 3 T) and permeability effects are negligible on vascular‐space occupancy signal (<0.1% at 3 T) under normal physiologic conditions. In addition, CBV effect on pulsed arterial spin labeling is further diminished at high field strengths, but residual blood contamination in vascular‐space occupancy signal may be enhanced at high fields due to the reduced difference between extra‐ and intravascular T₁ values. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

A two‐stage approach for measuring vascular water exchange and arterial transit time by diffusion‐weighted perfusion MRI

Changes in the exchange rate of water across the blood‐brain barrier, denoted k_w, may indicate blood‐brain barrier dysfunction before the leakage of large‐molecule contrast agents is observable. A previously proposed approach for measuring k_w is to use diffusion‐weighted arterial spin labeling to measure the vascular and tissue fractions of labeled water, because the vascular‐to‐tissue ratio is related to k_w. However, the accuracy of diffusion‐weighted arterial spin labeling is affected by arterial blood contributions and the arterial transit time (τ_a). To address these issues, a two‐stage method is proposed that uses combinations of diffusion‐weighted gradient strengths and post‐labeling delays to measure both τ_a and k_w. The feasibility of this method was assessed by acquiring diffusion‐weighted arterial spin labeling data from seven healthy volunteers. Repeat measurements and Monte Carlo simulations were conducted to determine the precision and accuracy of the k_w estimates. Average grey and white matter k_w values were 110 ± 18 and 126 ± 18 min^?1, respectively, which compare favorably to blood‐brain barrier permeability measurements obtained with positron emission tomography. The intrasubject coefficient of variation was 26% ± 23% in grey matter and 21% ± 17% in white matter, indicating that reproducible k_w measurements can be obtained. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.