Whole-brain 3D perfusion MRI at 3.0 T using CASL with a separate labeling coil.

A variety of continuous and pulsed arterial spin labeling (ASL) perfusion MRI techniques have been demonstrated in recent years. One of the reasons these methods are still not routinely used is the limited extent of the imaging region. Of the ASL methods proposed to date, continuous ASL (CASL) with a separate labeling coil is particularly attractive for whole-brain studies at high fields. This approach can provide an increased signal-to-noise ratio (SNR) in perfusion images because there are no magnetization transfer (MT) effects, and lessen concerns regarding RF power deposition at high field because it uses a local labeling coil. In this work, we demonstrate CASL whole-brain quantitative perfusion imaging at 3.0 T using a combination of strategies: 3D volume acquisition, background tissue signal suppression, and a separate labeling coil. The results show that this approach can be used to acquire perfusion images in all brain regions with good sensitivity. Further, it is shown that the method can be performed safely on humans without exceeding the current RF power deposition limits. The current method can be extended to higher fields, and further improved by the use of multiple receiver coils and parallel imaging techniques to reduce scan time or provide increased resolution.     

Steady pulsed imaging and labeling scheme for noninvasive perfusion imaging

Purpose: A steady pulsed imaging and labeling (SPIL) scheme is proposed to obtain high‐resolution multislice perfusion images of mice brain using standard preclinical MRI equipment. Theory and Methods: The SPIL scheme repeats a pulsed arterial spin labeling (PASL) module together with a short mixing time to extend the temporal duration of the generated PASL bolus to the total experimental time. Multislice image acquisition takes place during the mixing times. The mixing time is also used for magnetization recovery following image acquisition. The new scheme is able to yield multislice perfusion images rapidly. The perfusion kinetic curve can be measured by a multipulsed imaging and labeling (MPIL) scheme, i.e., acquiring single‐slice ASL signals before reaching steady‐state in the SPIL sequence. Results: When applying the SPIL method to normal mice, and to mice with unilateral ischemia, high‐resolution multislice (five slices) CBF images could be obtained in 8 min. Perfusion data from ischemic mice showed clear CBF reductions in ischemic regions. The SPIL method was also applied to postmortem mice, showing that the method is free from magnetization transfer confounds. Conclusion: The new SPIL scheme provides for robust measurement of CBF with multislice imaging capability in small animals. Magn Reson Med 75:238–248, 2016. © 2015 Wiley Periodicals, Inc.     

Transfer insensitive labeling technique (TILT): application to multislice functional perfusion imaging

Cerebral blood flow can be studied in a multislice mode with a recently proposed perfusion sequence using inversion of water spins as an endogenous tracer without magnetization transfer artifacts. The magnetization transfer insensitive labeling technique (TILT) has been used for mapping blood flow changes at a microvascular level under motor activation in a multislice mode. In TILT, perfusion mapping is achieved by subtraction of a perfusion-sensitized image from a control image. Perfusion weighting is accomplished by proximal blood labeling using two 90 degrees radiofrequency excitation pulses. For control preparation the labeling pulses are modified such that they have no net effect on blood water magnetization. The percentage of blood flow change, as well as its spatial extent, has been studied in single and multislice modes with varying delays between labeling and imaging. The average perfusion signal change due to activation was 36.9 +/- 9.1% in the single-slice experiments and 38.1 +/- 7.9% in the multislice experiments. The volume of activated brain areas amounted to 1.51 +/- 0.95 cm3 in the contralateral primary motor (M1) area, 0.90 +/- 0.72 cc in the ipsilateral M1 area, 1.27 +/- 0.39 cm3 in the contralateral and 1.42 +/- 0.75 cm3 in the ipsilateral premotor areas, and 0.71 +/- 0.19 cm3 in the supplementary motor area.     

A strategy to optimize the signal-to-noise ratio in one-coil arterial spin tagging perfusion imaging.

The signal-to-noise ratio of the perfusion image (SNR(perfu)) in a spin-tagging experiment is shown to depend on both the degree of spin labeling (alpha) and the signal-to-noise ratio of the proton density images (SNRimage) used to calculate the perfusion image. When a single radiofrequency (RF) coil is used for both spin tagging and magnetic resonance (MR) imaging, magnetization transfer (MT) effects decrease SNRimage, and therefore SNRperfu, by an amount that depends on the strength B1 and offset deltaomega (determined by the gradient strength G(I) applied during spin tagging) of the labeling RF pulse. It is shown that by optimizing B1 and G(I), it is possible to reduce MT effects and thus increase SNRimage, while leaving alpha unchanged. As a result, SNRperfu, will be improved. An equation for calculating perfusion under general conditions of such reduced MT effects is derived and shown to give perfusion rates that are independent of the strength and offset of the labeling RF irradiation.     

Relaxation-compensated fast multislice amide proton transfer (APT) imaging of acute ischemic stroke.

Amide proton transfer (APT) imaging is a variant form of chemical exchange saturation transfer (CEST) imaging that is based on the magnetization exchange between bulk water and labile endogenous amide protons. Given that chemical exchange is pH-dependent, APT imaging has been shown capable of imaging ischemic tissue acidosis, and as such, may serve as a surrogate metabolic imaging marker complementary to perfusion and diffusion MRI. In order for APT imaging to properly diagnose heterogeneous pathologies such as stroke and cancer, fast volumetric APT imaging has to be developed. In this study the evolution of CEST contrast after RF irradiation was solved showing that although the CEST steady state is reached by the apparent longitudinal relaxation rate, the decreases of CEST contrast after irradiation is governed by the intrinsic relaxation constant. A volumetric APT imaging sequence is proposed that acquires multislice images immediately after a single long continuous wave (CW) RF irradiation, wherein the relaxation-induced loss of CEST contrast is compensated for during postprocessing. The proposed technique was verified by numerical simulation, a tissue-like dual-pH phantom, and demonstrated on an embolic stroke animal model. In summary, our study has established a fast volumetric pH-weighted APT imaging technique, allowing further investigation to fully evaluate its diagnostic power.     

Extraslice spin tagging (EST) magnetic resonance imaging for the determination of perfusion

A new magnetic resonance technique to measure perfusion is described in detail. The means by which this is done is to invert all the spins in the radiofrequency RF coil with a non-spatially selective pulse and immediately re-invert the spins in the imaging plane. The net effect is that the spins in the imaging plane experience minimal perturbation of their magnetization while the spins outside the plane (extraslice) are inverted, or tagged. Tagged spins that flow into the imaging plane before image data are acquired decrease the signal intensity in the imaging plane when compared with an image in which the inflowing spins are not tagged. This decrease in signal can be used to calculate the number of spins that have flowed into the imaging plane, i.e., can be used to calculate the perfusion in mL x 100 g(tissue)(- 1)x min(-1). The extraslice spin tagging (EST) magnetization preparation period was coupled with a fast imaging sequence to obtain perfusion maps for normal volunteers.     

Amplitude-modulated continuous arterial spin-labeling 3.0-T perfusion MR imaging with a single coil: feasibility study

Written informed consent was obtained prior to all human studies after the institutional review board approved the protocol. A continuous arterial spin-labeling technique with an amplitude-modulated control was implemented by using a single coil at 3.0 T. Adiabatic inversion efficiency at 3.0 T, comparable to that at 1.5 T, was achieved by reducing the amplitude of radiofrequency pulses and gradient strengths appropriately. The amplitude-modulated control provided a good match for the magnetization transfer effect of labeling pulses, allowing multisection perfusion magnetic resonance imaging of the whole brain. Comparison of multisection continuous and pulsed arterial spin-labeling methods at 3.0 T showed a 33% improvement in signal-to-noise ratio by using the former approach.     

Technological advances in MRI measurement of brain perfusion

Measurement of brain perfusion using arterial spin labeling (ASL) or dynamic susceptibility contrast (DSC) based MRI has many potential important clinical applications. However, the clinical application of perfusion MRI has been limited by a number of factors, including a relatively poor spatial resolution, limited volume coverage, and low signal-to-noise ratio (SNR). It is difficult to improve any of these aspects because both ASL and DSC methods require rapid image acquisition. In this report, recent methodological developments are discussed that alleviate some of these limitations and make perfusion MRI more suitable for clinical application. In particular, the availability of high magnetic field strength systems, increased gradient performance, the use of RF coil arrays and parallel imaging, and increasing pulse sequence efficiency allow for increased image acquisition speed and improved SNR. The use of parallel imaging facilitates the trade-off of SNR for increases in spatial resolution. As a demonstration, we obtained DSC and ASL perfusion images at 3.0 T and 7.0 T with multichannel RF coils and parallel imaging, which allowed us to obtain high-quality images with in-plane voxel sizes of 1.5 x 1.5 mm(2).     

Improved perfusion-weighted MRI by a novel double inversion with proximal labeling of both tagged and control acquisitions.

A novel pulsed arterial spin labeling (PASL) technique for multislice perfusion-weighted imaging is proposed that compensates for magnetization transfer (MT) effects without sacrificing tag efficiency, and balances transient magnetic field effects (eddy currents) induced by pulsed field gradients. Improved compensation for MT is demonstrated using a phantom. Improvement in perfusion measurement was compared to other PASL techniques by acquiring perfusion images from 13 healthy volunteers (nine women and four men; age range 29-64 years; mean age 45 +/- 14 years) and second-order image texture analysis. The main improvements with the new method were significantly higher image contrast, higher mean signal intensity, and better signal uniformity across slices. In conclusion, this new PASL method should provide improved accuracy in measuring brain perfusion.     

Pulsed arterial spin labeling using TurboFLASH with suppression of intravascular signal.

Accurate quantification of perfusion with the ADC techniques requires the suppression of the majority of the intravascular signal. This is normally achieved with the use of diffusion gradients. The TurboFLASH sequence with its ultrashort repetition times is not readily amenable to this scheme. This report demonstrates the implementation of a modified TurboFLASH sequence for FAIR imaging. Intravascular suppression is achieved with a modified preparation period that includes a driven equilibrium Fourier transform (DEFT) combination of 90 degrees-180 degrees-90 degrees hard RF pulses subsequent to the inversion delay. These pulses rotate the perfusion-prepared magnetization into the transverse plane where it can experience the suitably placed diffusion gradients before being returned to the longitudinal direction by the second 90 degrees pulse. A value of b = 20-30 s/mm(2) was thereby found to suppress the majority of the intravascular signal. For single-slice perfusion imaging, quantification is only slightly modified. The technique can be readily extended to multislice acquisition if the evolving flow signal after the DEFT preparation is considered. An advantage of the modified preparation scheme is evident in the multislice FAIR images by the preservation of the sign of the magnetization difference.     

Continuous ASL (CASL) perfusion MRI with an array coil and parallel imaging at 3T.

The purpose of this work was to assess the feasibility and efficacy of using an array coil and parallel imaging in continuous arterial spin labeling (CASL) perfusion MRI. An 8-channel receive-only array head coil was used in conjunction with a surrounding detunable volume transmit coil. The signal to noise ratio (SNR), temporal stability, cerebral blood flow (CBF), and perfusion image coverage were measured from steady state CASL scans using: a standard volume coil, array coil, and array coil with 2- and 3-fold accelerated parallel imaging. Compared to the standard volume coil, the array coil provided 3 times the average SNR increase and higher temporal stability for the perfusion weighted images, even with threefold acceleration. Although perfusion images of the array coil were affected by the inhomogeneous coil sensitivities, this effect was invisible in the quantitative CBF images, which showed highly reproducible perfusion values compared to the standard volume coil. The unfolding distortions of parallel imaging were suppressed in the perfusion images by pairwise subtraction, though they sharply degraded the raw EPI images. Moreover, parallel imaging provided the potential of acquiring more slices due to the shortened acquisition time and improved coverage in brain regions with high static field inhomogeneity. Such results highlight the potential utility of array coils and parallel imaging in ASL perfusion MRI.     

Continuous flow‐driven inversion for arterial spin labeling using pulsed radio frequency and gradient fields

Continuous labeling by flow‐driven adiabatic inversion is advantageous for arterial spin labeling (ASL) perfusion studies, but details of the implementation, including inefficiency, magnetization transfer, and limited support for continuous‐mode operation on clinical scanners, have restricted the benefits of this approach. Here a new approach to continuous labeling that employs rapidly repeated gradient and radio frequency (RF) pulses to achieve continuous labeling with high efficiency is characterized. The theoretical underpinnings, numerical simulations, and in vivo implementation of this pulsed continuous ASL (PCASL) method are described. In vivo PCASL labeling efficiency of 96% relative to continuous labeling with comparable labeling parameters far exceeded the 33% duty cycle of the PCASL RF pulses. Imaging at 3T with body coil transmission was readily achieved. This technique should help to realize the benefits of continuous labeling in clinical imagers. Magn Reson Med 60:1488–1497, 2008. © 2008 Wiley‐Liss, Inc.     

Brain MR perfusion‐weighted imaging with alternate ascending/descending directional navigation

In this study, a new arterial spin labeling technique that requires no separate spin preparation pulse was developed. Sequential two‐dimensional slices were acquired in ascending and descending orders by turns using balanced steady state free precession for pair‐wise subtraction. Simulation studies showed this new technique, alternate ascending/descending directional navigation (ALADDIN), has high sensitivity to both slow‐ (1–10 cm/sec) and fast‐moving (>10 cm/sec) blood because of the presence of multiple labeling planes proximal to imaging planes and sensitivity of balanced steady state free precession to initial magnetization differences. ALADDIN provided high‐resolution multislice perfusion‐weighted images in ～3 min. About 80–90% of signals in a slice were ascribed to spins saturated in the four prior slices. Three to five edge slices on each side of imaging group were affected by transient magnetization transfer effects and incomplete T₁ recovery between successive acquisitions. ALADDIN signals were dependent on many imaging parameters, implying room for improvement. Sagittal and coronal ALADDIN images demonstrated perfusion direction in gray matter regions was mostly from center to lateral, anterior, or posterior, whereas that in some white matter regions was reversed. ALADDIN is likely useful for many studies requiring perfusion‐weighted imaging with short scan time, insensitiveness to arterial transit time, directional information, high resolution, and/or wide coverage. Magn Reson Med, 2011. © 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.     

Improved perfusion quantification in FAIR imaging by offset correction.

Perfusion quantification using pulsed arterial spin labeling has been shown to be sensitive to the RF pulse slice profiles. Therefore, in Flow-sensitive Alternating-Inversion Recovery (FAIR) imaging the slice selective (ss) inversion slab is usually three to four times thicker than the imaging slice. However, this reduces perfusion sensitivity due to the increased transit delay of the incoming blood with unperturbed spins. In the present article, the dependence of the magnetization on the RF pulse slice profiles is inspected both theoretically and experimentally. A perfusion quantification model is presented that allows the use of thinner ss inversion slabs by taking into account the offset of RF slice profiles between ss and nonselective inversion slabs. This model was tested in both phantom and human studies. Magn Reson Med 46:193-197, 2001.     

In vivo assessment of absolute perfusion in the murine skeletal muscle with spin labeling MRI. Magnetic resonance imaging

PURPOSE: To assess absolute perfusion in the skeletal muscle of mice in vivo with spin labeling magnetic resonance imaging (MRI) under normal and stress conditions. MATERIALS AND METHODS: Absolute perfusion in the skeletal muscle of 27 C57BL/6 mice was assessed in vivo non-invasively by spin labeling MRI at 7.05 T. This technique was based on the acquisition of T1 maps with global and slice-selective spin inversion in separate acquisitions. T1 mapping was performed by inversion recovery snapshot fast low angle shot imaging. To guarantee proper spin inversion within the whole mouse, a dedicated radiofrequency (RF) coil combination was constructed. A birdcage resonator was used for transmission, while detection of the MRI signal was achieved by a surface coil. RESULTS: Basal perfusion in the hindlimbs was determined to be 94 +/- 10 mL (100 g x minute)(-1) (mean +/- standard error of the mean [SEM], N = 27). This value is in good agreement with perfusion values determined by invasive techniques such as microspheres. A subgroup of six animals received a constant dose of 4 mg (kg x minute)(-1) of the vasodilator adenosine by an intraperitoneal catheter. In this case, perfusion was significantly increased to 179 +/- 56 mL (100 g x minute)(-1) (mean +/- SEM, N = 6, P < 0.02). Mean basal perfusion in this subgroup was 96 +/- 26 mL (100 g x minute)(-1). CONCLUSION: Spin labeling MRI is a well-suited technique for the in vivo assessment of absolute perfusion in the murine skeletal muscle.     

Multi-Slice MRI of Rat Brain Perfusion During Amphetamine Stimulation Using Arterial Spin Labeling

When a single coil is used to measure perfusion by arterial spin labeling, saturation of macromolecular protons occurs during the labeling period. Induced magnetization transfer contrast (MTC) effects decrease tissue water signal intensity, reducing the sensitivity of the technique. In addition, MTC effects must be properly accounted for in acquiring a control image. This forces the image to a single slice centered between the labeling plane and the control plane. In this work, a two-coil system is presented as a way to avoid saturation of macromolecular spins during arterial spin labeling. The system consists of one small surface coil for labeling the arterial water spins, and a head coil for MRI, actively decoupled from the labeling coil by using PIN diodes. It is shown that no signal loss occurs due to MTC effects when the two-coil system is used for MRI of rat brain perfusion, enabling three-dimensional perfusion imaging. Using the two-coil system, a multi-slice MRI sequence was used to study the regional effects of amphetamine on brain perfusion. Amphetamine causes significant increases in perfusion in many areas of the brain including the cortex, cingulate, and caudate putamen, in agreement with previous results using deoxyglucose uptake to monitor brain activation.     

Pseudo-continuous arterial spin labeling at very high magnetic field (11.75 T) for high-resolution mouse brain perfusion imaging

With the increasing number of transgenic mouse models of human brain diseases, there is a need for a sensitive method that allows assessing quantitative whole brain perfusion within a reasonable scan time. Arterial spin labeling (ASL), an MRI technique that permits the noninvasive quantification of cerebral blood flow, has been used to assess rodents brain perfusion. For mice, the reported experiments performed with continuous or pulsed ASL were challenged by poor multislice capability, limited sensitivity, or quantification issues. Here, the recently proposed pseudo-continuous ASL strategy, which has shown great promise for human studies, was investigated for mouse brain perfusion imaging at 11.75 T. Pseudo-continuous ASL was experimentally optimized and compared with a standard flow-sensitive alternating inversion recovery sequence for sensitivity, robustness, absolute quantification, and multislice imaging capability. A sensitivity gain up to 40% and clear advantages for multislice imaging are obtained with pseudo-continuous ASL.     

EPISTAR MRI: Multislice mapping of cerebral blood flow

A method is described for multislice EPISTAR that perfectly compensates magnetization transfer effects. lnflowing arterial spins are labeled with a 360° adiabatic pulse. Two control tags are applied sequentially at the same location as the labeling pulse, each with a 180° adiabatic pulse so the total RF irradiation, frequency shift, and bandwidth of the labeling and control pulses are identical. Therefore, magnetization transfer effects are the same as for the labeling pulse and cancel with image subtraction for all slices. The method also eliminates tagging of venous spins and concern about asymmetric magnetization transfer effects.     

Assessment of collateral supply by two-coil continuous arterial spin labeling after coil occlusion of the internal carotid artery

A patient undergoing coil occlusion of a left internal carotid artery aneurysm was investigated by continuous arterial spin labeling MR imaging to evaluate perfusion territory mapping. Labeling was restricted to the left- or right-sided carotid artery by use of a separate neck coil. Before embolization, perfusion contrast was largely restricted to the labeled hemisphere. After embolization, perfusion contrast was created symmetrically in both hemispheres on labeling the right side, verifying sufficient collateral supply.