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.     

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.     

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.     

Spin‐locked balanced steady‐state free‐precession (slSSFP)

A spin‐locked balanced steady‐state free‐precession (slSSFP) pulse sequence is described that combines a balanced gradient‐echo acquisition with an off‐resonance spin‐lock pulse for fast MRI. The transient and steady‐state magnetization trajectory was solved numerically using the Bloch equations and was shown to be similar to balanced steady‐state free‐precession (bSSFP) for a range of T₂/T₁ and flip angles, although the slSSFP steady‐state could be maintained with considerably lower radio frequency (RF) power. In both simulations and brain scans performed at 7T, slSSFP was shown to exhibit similar contrast and signal‐to‐noise ratio (SNR) efficiency to bSSFP, but with significantly lower power. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

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

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

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.     

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.     

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.     

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.     

Pseudo‐continuous arterial spin labeling at 7 T for human brain: Estimation and correction for off‐resonance effects using a Prescan

Pseudo‐continuous arterial spin labeling (ASL) can provide best signal‐to‐noise ratio efficiency with a sufficiently long tag at high fields such as 7 T, but it is very sensitive to off‐resonance fields at the tagging location. Here, a robust Prescan procedure is demonstrated to estimate the pseudo‐continuous ASL radiofrequency phase and gradients parameters required to compensate the off‐resonance effects at each vessel location. The Prescan is completed in 1–2 min and is based on acquisition of label/control pair‐wise ASL data as a function of the radiofrequency phase increment applied to the pseudo‐continuous ASL train. It is shown that this approach can be used to acquire high quality whole‐brain pseudo‐continuous ASL perfusion data of the human brain at 7 T. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Volumetric measurement of perfusion and arterial transit delay using hadamard encoded continuous arterial spin labeling

Creating images of the transit delay from the labeling location to image tissue can aid the optimization and quantification of arterial spin labeling perfusion measurements and may provide diagnostic information independent of perfusion. Unfortunately, measuring transit delay requires acquiring a series of images with different labeling timing that adds to the time cost and increases the noise of the arterial spin labeling study. Here, we implement and evaluate a proposed Hadamard encoding of labeling that speeds the imaging and improves the signal‐to‐noise ratio efficiency. Volumetric images in human volunteers confirmed the theoretical advantages of Hadamard encoding over sequential acquisition of images with multiple labeling timing. Perfusion images calculated from Hadamard encoded acquisition had reduced signal‐to‐noise ratio relative to a dedicated perfusion acquisition with either assumed or separately measured transit delays, however. Magn Reson Med 69:1014–1022, 2013. © 2012 Wiley Periodicals, Inc.     

FAIR true-FISP perfusion imaging of the kidneys.

Most arterial spin labeling (ASL) techniques apply echoplanar imaging (EPI) because this strategy provides relatively high SNR in short measuring times. Unfortunately, those techniques are very susceptible to static magnetic field inhomogeneities and perfusion signals from organs with fast transverse relaxation might decrease due to the exchange of water molecules in capillaries and organ tissue combined with relatively long echo times of EPI sequences. To overcome these problems a novel imaging technique, FAIR True-FISP, was developed. It combines a FAIR (flow-sensitive alternating inversion recovery) perfusion preparation and a true fast imaging with steady precession (True-FISP) data acquisition strategy. True-FISP was chosen since this sequence type does not show the mentioned disadvantages of EPI, but provides a similar SNR per measuring time. An important problem of this approach is that True-FISP sequences usually work in a steady state which is independent of a previous preparation of magnetization. For this reason a sequence structure had to be developed which keeps the advantages of True-FISP and makes the signal intensity sensitive to the FAIR preparation. Breathhold and nonbreathhold examinations of kidneys are presented and possible strategies to quantitative flow measurements are reported. It is shown that correction of spatially inhomogeneous receiver coil characteristics is easily feasible and leads to clinically valuable perfusion examinations of kidneys without application of potentially nephrotoxic contrast media.     

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

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

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.     

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.     

Small‐tip fast recovery imaging using non‐slice‐selective tailored tip‐up pulses and radiofrequency‐spoiling

Small‐tip fast recovery (STFR) imaging is a new steady‐state imaging sequence that is a potential alternative to balanced steady‐state free precession. Under ideal imaging conditions, STFR may provide comparable signal‐to‐noise ratio and image contrast as balanced steady‐state free precession, but without signal variations due to resonance offset. STFR relies on a tailored “tip‐up,” or “fast recovery,” radiofrequency pulse to align the spins with the longitudinal axis after each data readout segment. The design of the tip‐up pulse is based on the acquisition of a separate off‐resonance (B0) map. Unfortunately, the design of fast (a few ms) slice‐ or slab‐selective radiofrequency pulses that accurately tailor the excitation pattern to the local B0 inhomogeneity over the entire imaging volume remains a challenging and unsolved problem. We introduce a novel implementation of STFR imaging based on “non‐slice‐selective” tip‐up pulses, which simplifies the radiofrequency pulse design problem significantly. Out‐of‐slice magnetization pathways are suppressed using radiofrequency‐spoiling. Brain images obtained with this technique show excellent gray/white matter contrast, and point to the possibility of rapid steady‐state T₂/T₁‐weighted imaging with intrinsic suppression of cerebrospinal fluid, through‐plane vessel signal, and off‐resonance artifacts. In the future, we expect STFR imaging to benefit significantly from parallel excitation hardware and high‐order gradient shim systems. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Comparing model‐based and model‐free analysis methods for QUASAR arterial spin labeling perfusion quantification

Amongst the various implementations of arterial spin labeling MRI methods for quantifying cerebral perfusion, the QUASAR method is unique. By using a combination of labeling with and without flow suppression gradients, the QUASAR method offers the separation of macrovascular and tissue signals. This permits local arterial input functions to be defined and “model‐free” analysis, using numerical deconvolution, to be used. However, it remains unclear whether arterial spin labeling data are best treated using model‐free or model‐based analysis. This work provides a critical comparison of these two approaches for QUASAR arterial spin labeling in the healthy brain. An existing two‐component (arterial and tissue) model was extended to the mixed flow suppression scheme of QUASAR to provide an optimal model‐based analysis. The model‐based analysis was extended to incorporate dispersion of the labeled bolus, generally regarded as the major source of discrepancy between the two analysis approaches. Model‐free and model‐based analyses were compared for perfusion quantification including absolute measurements, uncertainty estimation, and spatial variation in cerebral blood flow estimates. Major sources of discrepancies between model‐free and model‐based analysis were attributed to the effects of dispersion and the degree to which the two methods can separate macrovascular and tissue signal. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

3D steady‐state diffusion‐weighted imaging with trajectory using radially batched internal navigator echoes (TURBINE)

While most diffusion‐weighted imaging (DWI) is acquired using single‐shot diffusion‐weighted spin‐echo echo‐planar imaging, steady‐state DWI is an alternative method with the potential to achieve higher‐resolution images with less distortion. Steady‐state DWI is, however, best suited to a segmented three‐dimensional acquisition and thus requires three‐dimensional navigation to fully correct for motion artifacts. In this paper, a method for three‐dimensional motion‐corrected steady‐state DWI is presented. The method uses a unique acquisition and reconstruction scheme named trajectory using radially batched internal navigator echoes (TURBINE). Steady‐state DWI with TURBINE uses slab‐selection and a short echo‐planar imaging (EPI) readout each pulse repetition time. Successive EPI readouts are rotated about the phase‐encode axis. For image reconstruction, batches of cardiac‐synchronized readouts are used to form three‐dimensional navigators from a fully sampled central k‐space cylinder. In vivo steady‐state DWI with TURBINE is demonstrated in human brain. Motion artifacts are corrected using refocusing reconstruction and TURBINE images prove less distorted compared to two‐dimensional single‐shot diffusion‐weighted‐spin‐EPI. Magn Reson Med, 2010. © 2009 Wiley‐Liss, Inc.     

Single-shot 3D imaging techniques improve arterial spin labeling perfusion measurements.

Arterial spin labeling (ASL) can be used to measure perfusion without the use of contrast agents. Due to the small volume fraction of blood vessels compared to tissue in the human brain (typ. 3-5%) ASL techniques have an intrinsically low signal-to-noise ratio (SNR). In this publication, evidence is presented that the SNR can be improved by using arterial spin labeling in combination with single-shot 3D readout techniques. Specifically, a single-shot 3D-GRASE sequence is presented, which yields a 2.8-fold increase in SNR compared to 2D EPI at the same nominal resolution. Up to 18 slices can be acquired in 2 min with an SNR of 10 or more for gray matter perfusion. A method is proposed to increase the reliability of perfusion quantification using QUIPSS II derivates by acquiring low-resolution maps of the bolus arrival time, which allows differentiation between lack of perfusion and delayed arrival of the labeled blood. For arterial spin labeling, single-shot 3D imaging techniques are optimal in terms of efficiency and might prove beneficial to improve reliability of perfusion quantitation in a clinical setup.