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.     

A theoretical and experimental comparison of continuous and pulsed arterial spin labeling techniques for quantitative perfusion imaging

Under ideal conditions, continuous arterial spin labeling (ASL) techniques are higher in SNR than pulsed ASL techniques by a factor of e. Presented here is a direct theoretical and experimental comparison of continuous ASL and pulsed ASL, using versions of both that are amenable to multislice imaging and insensitive to variations in transit times (continuous ASL with a delay before imaging, and QUIPSS II (Quantitative Imaging of Perfusion Using a Single Subtraction–second version)). Perfusion image quality for comparable imaging time was nearly identical for both single-slice and multislice imaging. The measured raw signal was approximately 25% higher with continuous ASL, but the SNR per unit time was identical.     

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.     

Pediatric perfusion imaging using pulsed arterial spin labeling

PURPOSE: To test the feasibility of pediatric perfusion imaging using a pulsed arterial spin labeling (ASL) technique at 1.5 T. MATERIALS AND METHODS: ASL perfusion imaging was carried out on seven neurologically normal children and five healthy adults. The signal-to-noise ratio (SNR) of the perfusion images along with T1, M(0), arterial transit time, and the temporal fluctuation of the ASL image series were measured and compared between the two age groups. In addition, ASL perfusion magnetic resonance (MR) was performed on three children with neurologic disorder. RESULTS: In the cohort of neurologically normal children, a 70% increase in the SNR of the ASL perfusion images and a 30% increase in the absolute cerebral blood flow compared to the adult data were observed. The measures of ASL SNR, T1, and M(0) were found to decrease linearly with age. Transit time and temporal fluctuation of the ASL perfusion image series were not significantly different between the two age groups. The feasibility of ASL in the diagnosis of pediatric neurologic disease was also illustrated. CONCLUSION: ASL is a promising tool for pediatric perfusion imaging given the unique and reciprocal benefits in terms of safety and image quality.     

Perfusion imaging using dynamic arterial spin labeling (DASL).

Recently, a technique based on arterial spin labeling, called dynamic arterial spin labeling (DASL (Magn Reson Med 1999;41:299-308)), has been introduced to measure simultaneously the transit time of the labeled blood from the labeling plane to the exchange site, the longitudinal relaxation time of the tissue, and the perfusion of the tissue. This technique relies on the measurement of the tissue magnetization response to a time varying labeling function. The analysis of the characteristics of the tissue magnetization response (transit time, filling time constant, and perfusion) allows for quantification of the tissue perfusion and for transit time map computations. In the present work, the DASL scheme is used in conjunction with echo planar imaging at 4.7 T to produce brain maps of perfusion and transit time in the anesthetized rat, under graded hypercapnia. The data obtained show the variation of perfusion and transit time as a function of arterial pCO2. Based on the data, CO2 reactivity maps are computed. Published 2001 Wiley-Liss, Inc.     

Pittfalls of MRI measurement of white matter perfusion based on arterial spin labeling.

Although arterial spin labeling (ASL) MRI has been successfully applied to measure gray matter (GM) perfusion in vivo, accurate detection of white matter (WM) perfusion has proven difficult. Reported literature values are not consistent with each other or with perfusion measured with other modalities. In this work, the cause of these inconsistencies is investigated. The results suggest that WM perfusion values are substantially affected by the limited image resolution and by signal losses caused by the long transit times in WM, which significantly affect the label. From gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) bolus-tracking experiments (N=6), it is estimated that the transit time can be several seconds long in deep WM. Furthermore, simulations show that even at a spatial resolution of 7 microl voxel size, contamination by the GM signals can exceed 40% of the actual WM signal. From 10-min long flow-sensitive alternating inversion recovery ASL (FAIR-ASL) measurements at 3T in normal subjects (N=7), using highly sensitive detectors, it is shown that single-voxel (7 mul) deep WM perfusion values have an signal-to-noise ratio (SNR) less than 1. The poor sensitivity and heterogeneous transit time limit the applicability of ASL for measurement of perfusion in WM.     

Velocity-selective arterial spin labeling.

In pathologies in which slow or collateral flow conditions may exist, conventional arterial spin labeling (ASL) methods that apply magnetic tags based on the location of arterial spins may not provide robust measures of cerebral blood flow (CBF), as the transit delay for the delivery of blood to target tissues may far exceed the relaxation time of the tag. Here we describe current methods for ASL with velocity-selective (VS) tags (termed VSASL) that do not require spatial selectivity and can thus provide quantitative measures of CBF under slow and collateral flow conditions. The implementation of a robust multislice VSASL technique is described in detail, and data obtained with this technique are compared with those obtained with conventional pulsed ASL (PASL). The technical considerations described here include the design of VS pulses, background suppression, anisotropy with respect to velocity-encoding directions, and CBF quantitation issues.     

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.     

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.     

Functional perfusion imaging using continuous arterial spin labeling with separate labeling and imaging coils at 3 T.

Functional perfusion imaging with a separate labeling coil located above the common carotid artery was demonstrated in human volunteers at 3 T. A helmet resonator and a spin-echo echo-planar imaging (EPI) sequence were used for imaging, and a circular surface coil of 6 cm i.d. was employed for labeling. The subjects performed a finger-tapping task. Signal differences between the condition of finger tapping and the resting state were between -0.5% and -1.1 % among the subjects. The imaging protocol included a long post-label delay (PLD) to reduce transit time effects. Labeling was applied for all repetitions of the functional run to reduce the sampling interval.     

Comparison of quantitative perfusion imaging using arterial spin labeling at 1.5 and 4.0 Tesla.

High-field arterial spin labeling (ASL) perfusion MRI is appealing because it provides not only increased signal-to-noise ratio (SNR), but also advantages in terms of labeling due to the increased relaxation time T(1) of labeled blood. In the present study, we provide a theoretical framework for the dependence of the ASL signal on the static field strength, followed by experimental validation in which a multislice pulsed ASL (PASL) technique was carried out at 4T and compared with PASL and continuous ASL (CASL) techniques at 1.5T, both in the resting state and during motor activation. The resting-state data showed an SNR ratio of 2.3:1.4:1 in the gray matter and a contrast-to-noise ratio (CNR) of 2.7:1.1:1 between the gray and white matter for the difference perfusion images acquired using 4T PASL, 1.5T CASL, and 1.5T PASL, respectively. However, the functional data acquired using 4T PASL did not show significantly improved sensitivity to motor cortex activation compared with the 1.5T functional data, with reduced fractional perfusion signal change and increased intersubject variability. Possible reasons for these experimental results, including susceptibility effects and physiological noise, are discussed.     

Quantitative perfusion measurements using pulsed arterial spin labeling: effects of large region-of-interest analysis

PURPOSE: To study arterial spin labeling (ASL) MRI techniques and to investigate various problematic issues that still hinder the accurate and robust quantitative analysis of ASL data. MATERIALS AND METHODS: A pulsed-ASL (PASL) sequence was implemented on a 3-T imaging system and a protocol was developed for the measurement of perfusion based on fitting to a standard kinetic model. Both numerical simulations and multi-inversion time MRI data were analyzed. The effect of fitting a kinetic curve to a large region of interest (ROI) with a distribution of arterial transit times was compared to a pixel-by-pixel (PBP) method. RESULTS: It was found that a significant underestimation of perfusion of approximately 17+/-6% (P<0.001) occurs in gray matter, when comparing an ROI with a PBP analysis over a group of 12 healthy subjects. CONCLUSION: Analysis of ASL data based on a large ROI may suffer from inaccuracies arising from a distribution of transit times, implying that averaging of ASL kinetic data over such regions should therefore be avoided. When possible, a PBP fit should be performed.     

Arterial transit time effects in pulsed arterial spin labeling CBF mapping: Insight from a PET and MR study in normal human subjects

Arterial transit time (ATT), a key parameter required to calculate absolute cerebral blood flow in arterial spin labeling (ASL), is subject to much uncertainty. In this study, ASL ATTs were estimated on a per‐voxel basis using data measured by both ASL and positron emission tomography in the same subjects. The mean ATT increased by 260 ± 20 (standard error of the mean) ms when the imaging slab shifted downwards by 54 mm, and increased from 630 ± 30 to 1220 ± 30 ms for the first slice, with an increase of 610 ± 20 ms over a four‐slice slab when the gap between the imaging and labeling slab increased from 20 to 74 mm. When the per‐slice ATTs were employed in ASL cerebral blood flow quantification and the in‐slice ATT variations ignored, regional cerebral blood flow could be significantly different from the positron emission tomography measures. ATT also decreased with focal activation by the same amount for both visual and motor tasks (～80 ms). These results provide a quantitative relationship between ATT and the ASL imaging geometry and yield an assessment of the assumptions commonly used in ASL imaging. These findings should be considered in the interpretation of, and comparisons between, different ASL‐based cerebral blood flow studies. The results also provide spatially specific ATT data that may aid in optimizing the ASL imaging parameters. Magn Reson Med, 2010. © 2009 Wiley‐Liss, Inc.     

BASE imaging: A new spin labeling technique for measuring absolute perfusion changes

A new technique for magnetic resonance imaging of absolute perfusion changes that uses magnetically labeled tissue water proton spins as a freely diffusible tracer is described. It consists of unprepared basis (BA) images that serve as a reference and selective (SE) inversion prepared images that are sensitive to perfusion changes. In the present study, the BASE technique was applied to functional neuroimaging. BA and SE images were alternatingly and repeatedly acquired during periods of visual stimulation and control. Visual stimulation was achieved with an alternating black/white checkerboard operating at a frequency of 8 Hz. Maps of the absolute cerebral blood flow changes (ACBF) were calculated from the image intensities of the corresponding BA and SE images. The individual mean values of ACBF measured in five healthy volunteers ranged from 69 ± 18 to 99 ± 26 ml/min/100 g. Since the BASE technique does not require nonselective spin inversion, it can be used with small transmit/receive head coils (e.g., surface coils). In addition, the BASE technique is robust against a mismatch of the inversion and detection slice profiles.     

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.     

Simultaneous measurement of cerebral blood flow and transit time with turbo dynamic arterial spin labeling (Turbo-DASL): application to functional studies

A turbo dynamic arterial spin labeling method (Turbo-DASL) was developed to simultaneously measure cerebral blood flow (CBF) and blood transit time with high temporal resolution. With Turbo-DASL, images were repeatedly acquired with a spiral readout after small-angle excitations during pseudocontinuous arterial spin labeling and control periods. Turbo-DASL experiments at 9.4 T without and with diffusion gradients were performed on rats anesthetized with isoflurane or α-chloralose. We determined blood transit times from carotid arteries to cortical arterial vessels (TT(a) ) from data obtained without diffusion gradients and to capillaries (TT(c) ) from data obtained with diffusion gradients. Cerebral arterial blood volume (CBV(a) ) was also calculated. At the baseline condition, both CBF and CBV(a) in the somatosensory cortical area were 40-50% less in rats with α-chloralose than in rats with isoflurane, while TT(a) and TT(c) were similar for both anesthetics. Absolute CBF and CBV(a) were positively correlated, while CBF and TT(c) were slightly negatively correlated. During forepaw stimulation, CBF increase was 15 ± 3% (n = 7) vs. 60 ± 7% (n = 5), and CBV(a) increase was 19 ± 9% vs. 46 ± 17% under isoflurane vs. α-chloralose anesthesia, respectively; CBF vs. CBV(a) changes were highly correlated. However, TT(a) and TT(c) were not significantly changed during stimulation. Our results support that arterial CBV increase plays a major role in functional CBF changes.