Reduced resolution transit delay prescan for quantitative continuous arterial spin labeling perfusion imaging

Arterial spin labeling perfusion MRI can suffer from artifacts and quantification errors when the time delay between labeling and arrival of labeled blood in the tissue is uncertain. This transit delay is particularly uncertain in broad clinical populations, where reduced or collateral flow may occur. Measurement of transit delay by acquisition of the arterial spin labeling signal at many different time delays typically extends the imaging time and degrades the sensitivity of the resulting perfusion images. Acquisition of transit delay maps at the same spatial resolution as perfusion images may not be necessary, however, because transit delay maps tend to contain little high spatial resolution information. Here, we propose the use of a reduced spatial resolution arterial spin labeling prescan for the rapid measurement of transit delay. Approaches to using the derived transit delay information to optimize and quantify higher resolution continuous arterial spin labeling perfusion images are described. Results in normal volunteers demonstrate heterogeneity of transit delay across different brain regions that lead to quantification errors without the transit maps and demonstrate the feasibility of this approach to perfusion and transit delay quantification.     

Cerebral perfusion and arterial transit time changes during task activation determined with continuous arterial spin labeling.

Perfusion imaging by arterial spin labeling (ASL) can be highly sensitive to the transit time from the labeling site to the tissue. We report the results of a study designed to separate the transit time and perfusion contributions to activation in ASL images accompanying motor and visual stimulation. Fractional transit time decreases were found to be comparable to fractional perfusion increases and the transit time change was found to be the greatest contributor to ASL signal change in ASL sequences without delayed acquisition. The implications for activation imaging with ASL and the arterial control of flow are discussed.     

Accurate,localized quantification of white matter perfusion with single‐voxel ASL

Quantification of perfusion in white matter is still difficult due to its low level, causing an often insufficiently low signal‐to‐noise ratio, and its long and inhomogeneous transit delays. Here, a technique is presented that accurately measures white matter perfusion by combining a spectroscopic single‐voxel localization technique (point‐resolved spectroscopy) with a pulsed arterial spin labeling encoding scheme (flow‐sensitive alternating inversion recovery) to specifically address the properties of white matter. The transit delay was measured by shifting the position of a slice‐selective saturation pulse between inversion and acquisition. Perfusion measurements resulted in values of 15.6 ± 3.2 mL/100 g/min in the left and 15.2 ± 4.8 mL/100 g/min in the right hemispheric white matter and 83.2 ± 15.2 mL/100 g/min in cortical gray matter. Taking dispersion of the transit times into account does not cause a significant change in the measured values. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

3D GRASE PROPELLER: Improved image acquisition technique for arterial spin labeling perfusion imaging

Arterial spin labeling is a noninvasive technique that can quantitatively measure cerebral blood flow. While traditionally arterial spin labeling employs 2D echo planar imaging or spiral acquisition trajectories, single‐shot 3D gradient echo and spin echo (GRASE) is gaining popularity in arterial spin labeling due to inherent signal‐to‐noise ratio advantage and spatial coverage. However, a major limitation of 3D GRASE is through‐plane blurring caused by T₂ decay. A novel technique combining 3D GRASE and a periodically rotated overlapping parallel lines with enhanced reconstruction trajectory (PROPELLER) is presented to minimize through‐plane blurring without sacrificing perfusion sensitivity or increasing total scan time. Full brain perfusion images were acquired at a 3 × 3 × 5 mm³ nominal voxel size with pulsed arterial spin labeling preparation sequence. Data from five healthy subjects was acquired on a GE 1.5T scanner in less than 4 minutes per subject. While showing good agreement in cerebral blood flow quantification with 3D gradient echo and spin echo, 3D GRASE PROPELLER demonstrated reduced through‐plane blurring, improved anatomical details, high repeatability and robustness against motion, making it suitable for routine clinical use. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Implementation of quantitative perfusion imaging using pulsed arterial spin labeling at ultra‐high field

This study compares the implementation of the STAR and FAIR pulsed arterial spin labeling (PASL) schemes to form quantitative perfusion maps at ultra‐high field, 7 Tesla (T), and high field, 3T. Phantom experiments were performed to compare the inversion efficiency and profile of the labeling pulses at 7T and 3T and to optimize in‐plane saturation techniques. The perfusion weighted (PW) signal was measured at a range of postlabeling delay times and quantitative perfusion maps were calculated on a voxel‐by‐voxel basis. An increase in PW signal was found with field strength, and together with the increased signal‐to‐noise ratio, this led to improved image signal‐to‐noise and quality of fit of perfusion maps at 7T. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

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.     

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.     

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.     

In vivo hadamard encoded continuous arterial spin labeling (H‐CASL)

Continuous arterial spin labeling (CASL) measurements over a range of post‐labeling delay (PLD) times can be interpreted to estimate cerebral blood flow (CBF) and arterial transit time (δa) with good spatial and temporal resolution. In this work, we present an in vivo demonstration of Hadamard‐encoded continuous arterial spin labeling (H‐CASL); an efficient method of imaging the inflow of short boli of labeled blood water in the brain at multiple PLD times. We present evidence that H‐CASL is viable for in vivo application in the rat brain and can improve the precision of δa estimation in 2/3 of the imaging time required for standard multi‐PLD CASL. Based on these findings, we propose that H‐CASL may have application as an efficient prescan for optimization of ASL imaging parameters to improve the precision of CBF estimation. Magn Reson Med 63:1111–1118, 2010. © 2010 Wiley‐Liss, Inc.     

Cardiac arterial spin labeling using segmented ECG‐gated Look‐Locker FAIR: Variability and repeatability in preclinical studies

MRI is important for the assessment of cardiac structure and function in preclinical studies of cardiac disease. Arterial spin labeling techniques can be used to measure perfusion noninvasively. In this study, an electrocardiogram‐gated Look‐Locker sequence with segmented k‐space acquisition has been implemented to acquire single slice arterial spin labeling data sets in 15 min in the mouse heart. A data logger was introduced to improve data quality by: (1) allowing automated rejection of respiration‐corrupted images, (2) providing additional prospective gating to improve consistency of acquisition timing, and (3) allowing the recombination of uncorrupted k‐space lines from consecutive data sets to reduce respiration corruption. Finally, variability and repeatability of perfusion estimation within‐session, between‐session, between‐animal, and between image rejection criteria were assessed in mice. The criterion used to reject images from the T₁ fit was shown to affect the perfusion estimation. These data showed that the between‐animal coefficient of variability (24%) was greater than the between‐session variability (17%) and within‐session variability (11%). Furthermore, the magnitude of change in perfusion required to detect differences was 30% (within‐session) and 55% (between‐session) according to Bland‐Altman repeatability analysis. These technique developments and repeatability statistics will provide a platform for future preclinical studies applying cardiac arterial spin labeling. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

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.     

Pseudo‐continuous transfer insensitive labeling technique

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

Arterial spin labeling in combination with a look-locker sampling strategy: inflow turbo-sampling EPI-FAIR (ITS-FAIR).

Arterial spin labeling (ASL) permits quantification of tissue perfusion without the use of MR contrast agents. With standard ASL techniques such as flow-sensitive alternating inversion recovery (FAIR) the signal from arterial blood is measured at a fixed inversion delay after magnetic labeling. As no image information is sampled during this delay, FAIR measurements are inefficient and time-consuming. In this work the FAIR preparation was combined with a Look-Locker acquisition to sample not one but a series of images after each labeling pulse. This new method allows monitoring of the temporal dynamics of blood inflow. To quantify perfusion, a theoretical model for the signal dynamics during the Look-Locker readout was developed and applied. Also, the imaging parameters of the new ITS-FAIR technique were optimized using an expression for the variance of the calculated perfusion. For the given scanner hardware the parameters were: temporal resolution 100 ms, 23 images, flip-angle 25.4 degrees. In a normal volunteer experiment with these parameters an average perfusion value of 48.2 +/- 12.1 ml/100 g/min was measured in the brain. With the ability to obtain ITS-FAIR time series with high temporal resolution arterial transit times in the range of -138 - 1054 ms were measured, where nonphysical negative values were found in voxels containing large vessels.     

Multislice perfusion of the kidneys using parallel imaging: Image acquisition and analysis strategies

Flow‐sensitive alternating inversion recovery arterial spin labeling with parallel imaging acquisition is used to acquire single‐shot, multislice perfusion maps of the kidney. A considerable problem for arterial spin labeling methods, which are based on sequential subtraction, is the movement of the kidneys due to respiratory motion between acquisitions. The effects of breathing strategy (free, respiratory‐triggered and breath hold) are studied and the use of background suppression is investigated. The application of movement correction by image registration is assessed and perfusion rates are measured. Postacquisition image realignment is shown to improve visual quality and subsequent perfusion quantification. Using such correction, data can be collected from free breathing alone, without the need for a good respiratory trace and in the shortest overall acquisition time, advantageous for patient comfort. The addition of background suppression to arterial spin labeling data is shown to reduce the perfusion signal‐to‐noise ratio and underestimate perfusion. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Simultaneous multislice acquisition with arterial-flow tagging (SMART) using echo planar imaging (EPI)

Arterial spin tagging techniques have been used to image tissue perfusion in MR without contrast injection or ionizing radiation. Currently, spin tagging studies are performed primarily using single-slice imaging sequences, which are time consuming. This note reports a multislice echo-planar arterial spin tagging technique (Simultaneous Multislice Acquisition with aRterial-flow Tagging, or “SMART”). Multiband RF encoding (Hadamard) is used to provide simultaneous multislice acquisition capability for spin tagging techniques (such as echo planar imaging signal targeting with alternating radio frequency and flow-sensitive alternative inversion recovery). The method is illustrated with a two-slice pulse sequence that was implemented using the FAIR technique to generate two perfusion weighted images simultaneously. Compared with single-slice sequences, this two-slice sequence provided similar image quality, signal-to-noise ratio, and twice the spatial coverage compared with the single-slice technique within the same scan time.     

Multislice imaging of quantitative cerebral perfusion with pulsed arterial spin labeling

A method is presented for multislice measurements of quantitative cerebral perfusion based on magnetic labeling of arterial spins. The method combines a pulsed arterial inversion, known as the FAIR (Flow-sensitive Alternating Inversion Recovery) experiment, with a fast spiral scan image acquisition. The short duration (22 ms) of the spiral data collection allows simultaneous measurement of up to 10 slices per labeling period, thus dramatically increasing efficiency compared to current single slice acquisition protocols. Investigation of labeling efficiency, suppression of unwanted signals from stationary as well as intraarterial spins, and the FAIR signal change as a function of inversion delay are presented. The assessment of quantitative cerebral blood flow (CBF) with the new technique is demonstrated and shown to require measurement of arterial transit time as well as suppression of intraarterial spin signals. CBF values measured on normal volunteers are consistent with results obtained from H₂O¹⁵ positron emission tomography (PET) studies and other radioactive tracer approaches. In addition, the new method allows detection of activation-related perfusion changes in a finger-tapping experiment, with locations of activation corresponding well to those observed with blood oxygen level dependent (BOLD) fMRI.     

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.     

Noninvasive measurement of arterial cerebral blood volume using Look-Locker EPI and arterial spin labeling.

This paper describes a method of noninvasively measuring regional arterial cerebral blood volume fractions (CBV(a)) in vivo using the combination of Look-Locker echo-planar imaging (LL-EPI) with arterial spin labeling (ASL). Using this technique the arterial inflow curve is rapidly sampled and the regional CBV(a) is measured, while tissue perfusion signals are suppressed. Two methods of spin labeling (LL-EPI flow-sensitive alternating inversion recovery (LL-EPI-FAIR) and LL-EPI signal targeting using alternating radiofrequency (LL-EPI-STAR)) are assessed and their advantages discussed. The application of vascular crushing to LL-EPI-FAIR is described and used to validate the insensitivity of the sequence to the perfusion difference signal. LL-EPI-STAR is used to assess changes in CBV(a) in response to a finger-tapping task. LL-EPI-STAR signal difference curves are shown to have a shortened vascular transit delay and increased peak signal change on activation. A 33 +/- 14% increase in CBV(a) on activation is found. CBV(a) is measured with a 6-s temporal resolution and the temporal response is compared with the BOLD signal change. CBV(a) is shown to increase more rapidly and return to baseline significantly faster than the BOLD signal change, which supports the suggestion that a change in CBV(a) is an input to the BOLD response.     

A fast,effective filtering method for improving clinical pulsed arterial spin labeling MRI

Purpose

To evaluate the effectiveness of a fully automated postprocessing filter algorithm in pulsed arterial spin labeling (PASL) MRI perfusion images in a large clinical population.

Materials and Methods

A mean and standard deviation‐based filter was implemented to remove outliers in the set of perfusion‐weighted images (control – label) before being averaged and scaled to quantitative cerebral blood flow (CBF) maps. Filtered and unfiltered CBF maps from 200 randomly selected clinical cases were assessed by four blinded raters to evaluate the effectiveness of the filter.

Results

The filter salvaged many studies deemed uninterpretable as a result of motion artifacts, transient gradient, and/or radiofrequency instabilities, and unexpected disruption of data acquisition by the technologist to communicate with the patient. The filtered CBF maps contained significantly (P < 0.05) fewer artifacts and were more interpretable than unfiltered CBF maps as determined by one‐tail paired t‐test.

Conclusion

Variations in MR perfusion signal related to patient motion, system instability, or disruption of the steady state can introduce artifacts in the CBF maps that can be significantly reduced by postprocessing filtering. Diagnostic quality of the clinical perfusion images can be improved by performing selective averaging without a significant loss in perfusion signal‐to‐noise ratio. J. Magn. Reson. Imaging 2009;29:1134–1139. © 2009 Wiley‐Liss, Inc.