Complex‐valued analysis of arterial spin labeling–based functional magnetic resonance imaging signals

Cerebral blood flow‐dependent phase differences between tagged and control arterial spin labeling images are reported. A biophysical model is presented to explain the vascular origin of this difference. Arterial spin labeling data indicated that the phase difference is largest when the arterial component of the signals is preserved but is greatly reduced as the arterial contribution is suppressed by postinversion delays or flow‐crushing gradients. Arterial vasculature imaging by saturation data of activation and hypercapnia conditions showed increases in phase accompanying blood flow increases. An arterial spin labeling functional magnetic resonance imaging study yielded significant activation by magnitude‐only, phase‐only, and complex analyses when preserving the whole arterial spin labeling signal. After suppression of the arterial signal by postinversion delays, magnitude‐only and complex models yielded similar activation levels, but the phase‐only model detected nearly no activation. When flow crushers were used for arterial suppression, magnitude‐only activation was slightly lower and fluctuations in phase were dramatically higher than when postinversion delays were used. Although the complex analysis performed did not improve detection, a simulation study indicated that the complex‐valued activation model exhibits combined magnitude and phase detection power and thus maximizes sensitivity under ideal conditions. This suggests that, as arterial spin labeling imaging and image correction methods develop, the complex‐valued detection model may become helpful in signal detection. Magn Reson Med, 2009. © 2009 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.     

Application of variable‐rate selective excitation pulses for spin labeling in perfusion MRI

Arterial spin labeling offers great potential in clinical applications for noninvasive measurement of cerebral blood flow. Arterial spin labeling tagging methods such as the flow sensitive alternating inversion recovery technique require efficient spatial inversion pulses with high inversion accuracy and sharp transition zones between inverted and noninverted magnetization, i.e., require a high performance inversion pulse. This work presents a comprehensive comparison of the advantages offered by a variable‐rate selective excitation variant of the hyperbolic secant pulse against the widely used conventional hyperbolic secant pulse and the frequency offset corrected inversion pulses. Pulses were compared using simulation and experimental measurement in phantoms before being used in a flow sensitive alternating inversion recovery‐arterial spin labeling perfusion measurement in normal volunteers. Both the hyperbolic secant and frequency offset corrected inversion pulses have small variations in inversion profiles that may lead to unwanted subtraction errors in arterial spin labeling at a level where the residual signal is comparable to the desired perfusion contrast. The variable‐rate selective excitation pulse is shown to have improved inversion efficiency indicating its potential in perfusion MRI. The variable‐rate selective excitation pulse variant also showed greatest tolerance to radiofrequency variation and off‐resonance conditions, making it a robust choice for in vivo arterial spin labeling measurement. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

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.     

Reduction of errors in ASL cerebral perfusion and arterial transit time maps using image de‐noising

In this work, the performance of image de‐noising techniques for reducing errors in arterial spin labeling cerebral blood flow and arterial transit time estimates is investigated. Simulations were used to show that the established arterial spin labeling cerebral blood flow quantification method exhibits the bias behavior common to nonlinear model estimates, and as a result, the reduction of random errors using image de‐noising can improve accuracy. To assess the effect on precision, multiple arterial spin labeling data sets acquired from the rat brain were processed using a variety of common de‐noising methods (Wiener filter, anisotropic diffusion filter, gaussian filter, wavelet decomposition, and independent component analyses). The various de‐noising schemes were also applied to human arterial spin labeling data to assess the possible extent of structure degradation due to excessive spatial smoothing. The animal experiments and simulated data show that noise reduction methods can suppress both random and systematic errors, improving both the precision and accuracy of cerebral blood flow measurements and the precision of transit time maps. A number of these methods (and particularly independent component analysis) were shown to achieve this aim without compromising image contrast. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Measurement of deep gray matter perfusion using a segmented true–fast imaging with steady‐state precession (True‐FISP) arterial spin‐labeling (ASL) method at 3T

Purpose

To study the feasibility of using the MRI technique of segmented true–fast imaging with steady‐state precession arterial spin‐labeling (True‐FISP ASL) for the noninvasive measurement and quantification of local perfusion in cerebral deep gray matter at 3T.

Materials and Methods

A flow‐sensitive alternating inversion‐recovery (FAIR) ASL perfusion preparation was used in which the echo‐planar imaging (EPI) readout was replaced with a segmented True‐FISP data acquisition strategy. The absolute perfusion for six selected regions of deep gray matter (left and right thalamus, putamen, and caudate) were calculated in 11 healthy human subjects (six male, five female; mean age = 35.5 years ± 9.9).

Results

Preliminary measurements of the average absolute perfusion values at the six selected regions of deep gray matter are in agreement with published values for mean absolute cerebral blood flow (CBF) baselines acquired from healthy volunteers using positron emission tomography (PET).

Conclusion

Segmented True‐FISP ASL is a practical and quantitative technique suitable to measure local tissue perfusion in cerebral deep gray matter at a high spatial resolution without the susceptibility artifacts commonly associated with EPI‐based methods of ASL. J. Magn. Reson. Imaging 2009;29:1425–1431. © 2009 Wiley‐Liss, 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.     

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.     

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.     

NMR Measurement of Perfusion Using Arterial Spin Labeling Without Saturation of Macromolecular Spins

When measuring perfusion by arterial spin labeling, saturation of tissue macromolecular spins during arterial spin labeling greatly decreases tissue water magnetization, reducing the sensitivity of the technique. In this work, a theory has been developed for perfusion measurement by arterial spin labeling without saturation of macromolecular spins. A two-coil system was used to achieve arterial spin labeling without saturation of brain tissue macromolecular spins for NMR measurement of rat cerebral perfusion. The effects of crossrelaxation on the measurement of perfusion have been studied in the absence of macromolecular spin saturation, and it is demonstrated that at 4.7 Tesla, perfusion is underestimated by approximately 17% when the effect of cross-relaxation is neglected in the calculation of perfusion. However, assuming water to be a freely diffusable tracer, the effect of cross-relaxation is predicted to be flow independent, and it can, thus, be accounted for in the calculation of perfusion. The theory and experiments are presented to estimate tissue perfusion, magnetization transfer rate constants, and spin-lattice relaxation times of water and macromolecular spins in rat brain.     

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.     

Acceleration‐selective arterial spin labeling

In this study, a new arterial spin labeling (ASL) method with spatially nonselective labeling is introduced, based on the acceleration of flowing spins, which is able to image brain perfusion with minimal contamination from venous signal. This method is termed acceleration‐selective ASL (AccASL) and resembles velocity‐selective ASL (VSASL), with the difference that AccASL is able to discriminate between arterial and venous components in a single preparation module due to the higher acceleration on the arterial side of the microvasculature, whereas VSASL cannot make this distinction unless a second labeling module is used. A difference between AccASL and VSASL is that AccASL is mainly cerebral blood volume weighted, whereas VSASL is cerebral blood flow weighted. AccASL exploits the principles of acceleration‐encoded magnetic resonance angiography by using motion‐sensitizing gradients in a T₂‐preparation module. This method is demonstrated in healthy volunteers for a range of cutoff accelerations. Additionally, AccASL is compared with VSASL and pseudo‐continuous ASL, and its feasibility in functional MRI is demonstrated. Compared with VSASL with a single labeling module, a strong and significant reduction in venous label is observed. The resulting signal‐to‐noise ratio is comparable to pseudo‐continuous ASL and robust activation of the visual cortex is observed. Magn Reson Med 71:191–199, 2014. © 2013 Wiley Periodicals, Inc.     

Measurement of rat brain perfusion by NMR using spin labeling of arterial water: In vivo determination of the degree of spin labeling

In vivo NMR experiments are performed to determine the degree of spin labeling for measurement of tissue perfusion by NMR using spin labeling of arterial water by adiabatic fast passage. Arterial water spins are labeled using flow in the presence of a field gradient and B₁ irradiation to fulfill the conditions for adiabatic fast passage spin inversion. It is demonstrated that the NMR-measured tissue perfusion is not affected by changing the degree of spin labeling as long as the degree of spin labeling is determined and accounted for according to the model used for calculating perfusion. By measuring the degree of spin labeling with different arterial blood flow velocities induced by different arterial pCO₂, it is also demonstrated that, when spin labeling is carried out by adiabatic fast passage, the degree of spin labeling is not affected by changes in arterial blood flow velocity over a broad range.     

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.     

Estimation of perfusion and arterial transit time in myocardium using free‐breathing myocardial arterial spin labeling with navigator‐echo

Arterial spin labeling (ASL) provides noninvasive measurement of tissue blood flow, but sensitivity to motion has limited its application to imaging of myocardial blood flow. Although different cardiac phases can be synchronized using electrocardiography triggering, breath holding is generally required to minimize effects of respiratory motion during ASL scanning, which may be challenging in clinical populations. Here a free‐breathing myocardial ASL technique with the potential for reliable clinical application is presented, by combining ASL with a navigator‐gated, electrocardiography‐triggered TrueFISP readout sequence. Dynamic myocardial perfusion signals were measured at multiple delay times that allowed simultaneous fitting of myocardial blood flow and arterial transit time. With the assist of a nonrigid motion correction program, the estimated mean myocardial blood flow was 1.00 ± 0.55 mL/g/min with a mean transit time of ∼400 msec. The intraclass correlation coefficient of repeated scans was 0.89 with a mean within subject coefficient of variation of 22%. Perfusion response during mild to moderate stress was further measured. The capability for noninvasive, free‐breathing assessment of myocardial blood flow using ASL may offer an alternative approach to first‐pass perfusion MRI for clinical evaluation of patients with coronary artery disease. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Vessel‐encoded dynamic magnetic resonance angiography using arterial spin labeling

A new noninvasive MRI method for vessel‐selective angiography is presented. The technique combines vessel‐encoded pseudocontinuous arterial spin labeling with a two‐dimensional dynamic angiographic readout and was used to image the cerebral arteries in healthy volunteers. Time‐of‐flight angiograms were also acquired prior to vessel‐selective dynamic angiography acquisitions in axial, coronal, and/or sagittal planes, using a 3‐T MRI scanner. The latter consisted of a vessel‐encoded pseudocontinuous arterial spin labeling pulse train of 300 or 1000 ms followed by a two‐dimensional thick‐slab flow‐compensated fast low‐angle shot readout combined with a segmented Look‐Locker sampling strategy (temporal resolution = 55 ms). Selective labeling was performed at the level of the neck to generate individual angiograms for both right and left internal carotid and vertebral arteries. Individual vessel angiograms were reconstructed using a bayesian inference method. The vessel‐selective dynamic angiograms obtained were consistent with the time‐of‐flight images, and the longer of the two vessel‐encoded pseudocontinuous arterial spin labeling pulse train durations tested (1000 ms) was found to give better distal vessel visibility. This technique provides highly selective angiograms quickly and noninvasively that could potentially be used in place of intra‐arterial x‐ray angiography for larger vessels. 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.     

Vessel‐encoded dynamic magnetic resonance angiography using arterial spin labeling

A new noninvasive MRI method for vessel selective angiography is presented. The technique combines vessel‐encoded pseudocontinuous arterial spin labeling with a two‐dimensional dynamic angiographic readout and was used to image the cerebral arteries in healthy volunteers. Time‐of‐flight angiograms were also acquired prior to vessel‐selective dynamic angiography acquisitions in axial, coronal, and/or sagittal planes, using a 3‐T MRI scanner. The latter consisted of a vessel‐encoded pseudocontinuous arterial spin labeling pulse train of 300 or 1000 ms followed by a two‐dimensional thick‐slab flow‐compensated fast low angle shot readout combined with a segmented Look‐Locker sampling strategy (temporal resolution = 55 ms). Selective labeling was performed at the level of the neck to generate individual angiograms for both right and left internal carotid and vertebral arteries. Individual vessel angiograms were reconstructed using a bayesian inference method. The vessel‐selective dynamic angiograms obtained were consistent with the time‐of‐flight images, and the longer of the two vessel‐encoded pseudocontinuous arterial spin labeling pulse train durations tested (1000 ms) was found to give better distal vessel visibility. This technique provides highly selective angiograms quickly and noninvasively that could potentially be used in place of intra‐arterial x‐ray angiography for larger vessels. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Crossed cerebellar hyperperfusion after MELAS attack followed up by whole brain continuous arterial spin labeling perfusion imaging

Crossed cerebellar hyperperfusion (CCH) is detected in patients with epilepsy by brain perfusion studies including single photon emission computed tomography and positron emission tomography. In addition, brain perfusion can be studied with arterial spin labeling (ASL), which is a non-invasive MRI perfusion method that quantitatively measures cerebral blood flow per unit tissue mass. We followed up a 47-year-old patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) by continuous arterial spin labeling technique, which showed crossed cerebellar hyperperfusion after acute stroke-like episode. This cerebellar hyperperfusion normalized in the follow-up.