FAIR-TrueFISP imaging of cerebral perfusion in areas of high magnetic susceptibility differences at 1.5 and 3 Tesla

PURPOSE: To estimate cerebral blood perfusion in areas of strong magnetic susceptibility changes with high spatial and temporal resolution using a flow-sensitive alternating inversion recovery (FAIR) arterial spin labeling (ASL) method. MATERIALS AND METHODS: We implemented an ASL method that is capable of imaging perfusion in areas of high magnetic susceptibility changes by combining a FAIR spin preparation with a true fast imaging in steady precession (TrueFISP) data acquisition strategy. A TrueFISP readout sequence was applied especially in regions with magnetic field inhomogeneities and compared with corresponding FAIR measurements obtained with a standard echo-planar imaging (EPI) readout. Quantitative perfusion images were obtained at 1.5 Tesla (1.5T) from eight healthy volunteers (24-42 years old) and one patient (23 years old). FAIR-TrueFISP perfusion images were compared with FAIR echo-planar images. T1 maps, which are necessary for quantitative perfusion estimation, were obtained with inversion recovery (IR) TrueFISP and IR EPI. Additionally, high-resolution perfusion measurements were performed on four volunteers at 3T. RESULTS: The two ASL perfusion imaging modalities yielded comparable diagnostic image quality in brain areas with low susceptibility differences at 1.5T. Cerebral perfusion of gray matter (GM) areas was 105.7 +/- 5.2 mL/100 g/minute for FAIR-TrueFISP and 88.8 +/- 14.6 mL/100 g/minute for FAIR-EPI at 1.5T, and 70.4 +/- 7.1 mL/100 g/minute for FAIR-TrueFISP and 63.5 +/- 6.9 mL/100 g/minute for FAIR-EPI at 3.0T. Higher perfusion values at 1.5T were due to more pronounced partial-volume effects from fast moving spins at lower spatial resolution. The FAIR-TrueFISP sequence showed no significant distortions and markedly reduced signal void artifacts in areas of high susceptibility changes (e.g., near brain-bone transitions and close to metallic clips) compared to FAIR-EPI. At 3T, highly resolved FAIR-TrueFISP perfusion images were acquired with an in-plane resolution of up to 1.3 mm. CONCLUSION: FAIR-TrueFISP allows for assessment of cerebral perfusion in areas of critically high susceptibility changes with conventional ASL methods.     

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.     

Theoretical analysis of the effect of imperfect slice profiles on tagging schemes for pulsed arterial spin labeling MRI.

Pulsed arterial spin labeling (ASL) techniques provide a noninvasive method of obtaining qualitative and quantitative perfusion images with MRI. ASL techniques employ inversion recovery and/or saturation recovery to induce perfusion weighting, and thus the performance of these techniques is dependent on the slice profiles of the inversion or saturation pulses. This article systematically examines through simulations the effects of slice profile imperfections on the perfusion signal for nine labeling schemes, including FAIR, FAIRER, and EST (UNFAIR). Each sequence is evaluated for quantitative accuracy, suppression of stationary signal, and magnitude of perfusion signal. Perfusion effects are modeled from a modified Bloch equation and experimentally determined slice profiles. The results show that FAIR, FAIRER, and EST have excellent tissue suppression. The magnitude of the perfusion signal is comparable for FAIR and FAIRER, with EST providing a slightly weaker signal. For quantitative measurements, all three methods underestimate the perfusion signal by more than 20%. Of the additional six ASL techniques examined, only one performed well in this model. This method, which combines inversion and saturation recovery, yields improved signal accuracy (<15% difference from the theoretical value) and tissue suppression similar to that of FAIR and its variants, but has only half the signal. Magn Reson Med 46:141-148, 2001.     

Modeling and optimization of Look-Locker spin labeling for measuring perfusion and transit time changes in activation studies taking into account arterial blood volume.

This work describes a new compartmental model with step-wise temporal analysis for a Look-Locker (LL)-flow-sensitive alternating inversion-recovery (FAIR) sequence, which combines the FAIR arterial spin labeling (ASL) scheme with a LL echo planar imaging (EPI) measurement, using a multireadout EPI sequence for simultaneous perfusion and T*(2) measurements. The new model highlights the importance of accounting for the transit time of blood through the arteriolar compartment, delta, in the quantification of perfusion. The signal expected is calculated in a step-wise manner to avoid discontinuities between different compartments. The optimal LL-FAIR pulse sequence timings for the measurement of perfusion with high signal-to-noise ratio (SNR), and high temporal resolution at 1.5, 3, and 7T are presented. LL-FAIR is shown to provide better SNR per unit time compared to standard FAIR. The sequence has been used experimentally for simultaneous monitoring of perfusion, transit time, and T*(2) changes in response to a visual stimulus in four subjects. It was found that perfusion increased by 83 +/- 4% on brain activation from a resting state value of 94 +/- 13 ml/100 g/min, while T*(2) increased by 3.5 +/- 0.5%.     

MR perfusion imaging of pulmonary parenchyma using pulsed arterial spin labeling techniques: FAIRER and FAIR

Magnetic resonance imaging of pulmonary parenchyma perfusion using pulsed arterial spin labeling (ASL) techniques is presented. ASL uses magnetically labeled water as an endogenous, freely diffusible tracer. Presented are comparative results of ASL methods called Flow sensitive Alternating Inversion Recovery (FAIR), and FAIR with an Extra Radiofrequency pulse (FAIRER). Six healthy human volunteers were imaged. Perfusion-weighted images at different time delays, TI, were calculated from the subtraction of the control and tag images, which were acquired within a single breathhold. Detailed pulmonary structures can be visualized with negligible cardiac or respiratory motion artifacts. Different patterns of signal enhancement between the pulmonary vessels and parenchyma are shown in the perfusion images acquired at different TIs.     

Ventilation-perfusion ratio of signal intensity in human lung using oxygen-enhanced and arterial spin labeling techniques.

This study investigates the distribution of ventilation-perfusion (V/Q) signal intensity (SI) ratios using oxygen-enhanced and arterial spin labeling (ASL) techniques in the lungs of 10 healthy volunteers. Ventilation and perfusion images were simultaneously acquired using the flow-sensitive alternating inversion recovery (FAIR) method as volunteers alternately inhaled room air and 100% oxygen. Images of the T(1) distribution were calculated for five volunteers for both selective (T(1f)) and nonselective (T(1)) inversion. The average T(1) was 1360 ms +/- 116 ms, and the average T(1f) was 1012 ms +/- 112 ms, yielding a difference that is statistically significant (P < 0.002). Excluding large pulmonary vessels, the average V/Q SI ratios were 0.355 +/- 0.073 for the left lung and 0.371 +/- 0.093 for the right lung, which are in agreement with the theoretical V/Q SI ratio. Plots of the V/Q SI ratio are similar to the logarithmic normal distribution obtained by multiple inert gas elimination techniques, with a range of ratios matching ventilation and perfusion. This MRI V/Q technique is completely noninvasive and does not involve ionized radiation. A limitation of this method is the nonsimultaneous acquisition of perfusion and ventilation data, with oxygen administered only for the ventilation data.     

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

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

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.     

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.     

A protocol for assessing subtraction errors of arterial spin-tagging perfusion techniques in human brain.

A protocol for assessing signal contributions from static tissue (subtraction errors) in perfusion images acquired with arterial spin-labeling (ASL) techniques in human brain is proposed. The method exploits the reduction of blood T(1) caused by the clinically available paramagnetic contrast agent, gadopentetate dimeglumine (Gd-DTPA). The protocol is demonstrated clinically with multislice FAIR images acquired before, during, and after Gd-DTPA administration using a range of selective inversion widths. Perfusion images acquired postcontrast for selective inversion widths large enough (threshold) to avoid interaction with the imaging slice had signal intensities reduced to noise level, as opposed to subtraction errors manifested on images acquired using inversion widths below the threshold. The need for these experiments to be performed in vivo is further illustrated by comparison with phantom results. The protocol allows a one-time calibration of relevant ASL parameters (e.g., selective inversion widths) in vivo, which may otherwise cause subtraction errors. Magn Reson Med 43:896-900, 2000. Published 2000 Wiley-Liss, Inc.     

In vivo measurement of the longitudinal relaxation time of arterial blood (T1a) in the mouse using a pulsed arterial spin labeling approach.

A novel method for measuring the longitudinal relaxation time of arterial blood (T1a) is presented. Knowledge of T1a is essential for accurately quantifying cerebral perfusion using arterial spin labeling (ASL) techniques. The method is based on the flow-sensitive alternating inversion recovery (FAIR) pulsed ASL (PASL) approach. We modified the standard FAIR acquisition scheme by incorporating a global saturation pulse at the beginning of the recovery period. With this approach the FAIR tissue signal difference has a simple monoexponential dependence on the recovery time, with T1a as the time constant. Therefore, FAIR measurements performed over a range of recovery times can be fitted to a monoexponential recovery curve and T1a can be calculated directly. This eliminates many of the difficulties associated with the measurement of T1a. Experiments performed in vivo in the mouse at 2.35T produced a mean value of 1.51 s for T1a, consistent with previously published values.     

Application of selective saturation to image the dynamics of arterial blood flow during brain activation using magnetic resonance imaging.

A saturation-based approach is proposed to image the arterial blood flow signal with temporal resolution of 1 to 2 s and in-plane spatial resolution of a few millimeters. Using a saturation approach to suppress the undesired background stationary signal allows the blood water that enters the slice to be imaged at some specified later time. Since the blood protons that are being imaged are not restricted to the intravascular space, this technique is also sensitive to tissue perfusion signal contributions. The signal uptake characteristics of the saturation method proposed were used to study the different signal contributions as a function of the acquisition parameters. A typical perfusion acquisition (FAIR) was also used for comparison. The proposed method was demonstrated in a functional motor activation experiment and the observed signal changes were smaller than those obtained using the FAIR acquisition. The dynamics of the saturation method and FAIR temporal signal changes were investigated and time constants between 2 and 44 s were estimated. The tissue signal contribution to the saturation method's signal was small over the range of acquisition parameters that sensitized it to the arterial compartment.     

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.     

Evaluation of systematic quantification errors in velocity-selective arterial spin labeling of the brain.

Velocity-selective (VS) sequences potentially permit arterial spin labeling (ASL) perfusion imaging with labeling applied very close to the tissue. In this study the effects of cerebrospinal fluid (CSF) motion, radiofrequency (RF) field imperfections, and sequence timing parameters on the appearance and quantitative perfusion values obtained with VS-ASL were evaluated. Large artifacts related to CSF motion were observed with moderate velocity weighting, which were removed by inversion recovery preparation at the cost of increased imaging time. Imperfect refocusing and excitation pulses resulting from nonuniform RF fields produced systematic errors in the ASL subtraction images. A phase cycling scheme was introduced to eliminate these errors. Quantitative perfusion images were obtained with CSF suppression and phase cycling. Gray matter blood flow of 27.7 ml 100 g(-1) min(-1), approximately half the value reported in studies using spatially-selective ASL, was measured. Potential sources for this underestimation are discussed.     

Underestimation of cerebral perfusion on flow-sensitive alternating inversion recovery image: semiquantitative evaluation with time-to-peak values

BACKGROUND AND PURPOSE: We assessed the underestimation of cerebral perfusion measured by the flow-sensitive alternating inversion recovery (FAIR) technique in patients with carotid stenosis and compared the technique with dynamic susceptibility contrast (DSC) MR images. MATERIALS AND METHODS: We studied 42 areas of decreased cerebral blood flow (CBF) using 3 FAIR images with different inversion times (TIs) in 42 consecutive patients with unilateral carotid stenosis of more than 50%. The width of decreased CBF area (wCBF) was qualitatively assessed. We analyzed the ratio of CBF (rCBF) and the time-to-peak (TTP) difference (dTTP) between the ipsilateral hemisphere to carotid stenosis and contralateral normal area using regions of interest (ROIs) at the same location. RESULTS: In the areas with more prolonged TTP (dTTP > or =3.2 s), the wCBF obtained from the FAIR images with TI of 1600 ms was smaller than those from the FAIR images with a TI of 800 ms and 1200 ms in all cases. The mean rCBF obtained from the FAIR images with a TI of 1200 ms was significantly lower than that obtained from the FAIR images with a TI of 1600 ms (P < .01) in the areas with more prolonged TTP. In the areas with less prolonged TTP (dTTP <3.2 s), the wCBF and mean rCBF were not significantly different between the 2 FAIR images (TI, 1200 and 1600 ms). CONCLUSION: If TTP is delayed significantly (dTTP > or =3.2 s), the FAIR with intermediate or short TI showed underestimation of perfusion in the same area with delay in TTP.     

Quantification of renal allograft perfusion using arterial spin labeling MRI: initial results

Objective  

To quantify renal allograft perfusion in recipients with stable allograft function and acute decrease in allograft function using nonenhanced flow-sensitive alternating inversion recovery (FAIR)-TrueFISP arterial spin labeling (ASL) MR imaging.     

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

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

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.     

What levels of precision are achievable for quantification of perfusion and capillary permeability surface area product using ASL?

We examine the use of arterial spin labeling (ASL) in normal brains of rats and humans to measure perfusion (F) and capillary permeability surface area product (PS) using a previously described two-compartment model. We investigate the experimental limits on F and PS quantification using simulations and experimental verification in rat brain at 9.4T. A sensitivity analysis on the two-compartment model is presented to estimate optimal experimental inversion times (TIs) for F and PS quantification and indicate how sensitive the model would be to changes in F and PS. We present the expected error on flow-sensitive alternating inversion recovery (FAIR)-based F and PS measurements and quantify the precision with which these parameters could be estimated at various signal-to-noise ratios (SNRs). Perfusion was measured in four rat brains using FAIR ASL, and we conclude that perfusion could be quantified with an acceptable level of precision using this technique. However, we found that to measure PS with even a 100% coefficient of variation (CV) would require an SNR increase of approximately 2 orders of magnitude over our acquired data. We conclude that with current MR capabilities and with the experimental approach used in this study, acceptable levels of precision in the measurement of PS are not possible.     

The effect of B1 field inhomogeneity and the nonselective inversion profile on the kinetics of FAIR-based perfusion MRI.

Perfusion imaging with pulsed arterial spin labeling techniques, like flow-sensitive alternating inversion recovery (FAIR), may suffer from inflow of fresh, i.e., unlabeled, spins. Inflow of fresh spins is caused by the arrival of unlabeled spins in the image slice and can lead to underestimation of the perfusion if not taken into account. In this study it was shown that a decrease in B(1) field strength toward the edge of the transmit coil and the consequent reduction in the inversion efficiency leads to a narrowing of the arterial delivery function and a reduction in FAIR signal. Increasing the B(1) amplitude of the adiabatic inversion pulse from 2.3 to 5.7 times its minimum amplitude requirement resulted in an observed increase of 40 to 80% in the rat brain FAIR signal at inflow times longer than 0.65 s. For coils with limited dimensions and significant B(1) inhomogeneity over the perfusion labeling slab, the application of an excessively large B(1) amplitude in combination with adiabatic inversion is recommended to optimize the FAIR perfusion contrast.