Reduced B0/B1 + sensitivity in velocity-selective inversion arterial spin labeling using adiabatic refocusing pulses.

PURPOSE: To mitigate the B0/B1 + sensitivity of velocity-selective inversion (VSI) pulse trains for velocity-selective arterial spin labeling (VSASL) by implementing adiabatic refocusing. This approach aims to achieve artifact-free VSI-based perfusion imaging through single-pair label-control subtractions, reducing the need for the currently required four-pair dynamic phase-cycling (DPC) technique when using a velocity-insensitive control. METHODS: We introduce a Fourier-transform VSI (FT-VSI) train that incorporates sinc-modulated hard excitation pulses with MLEV-8-modulated adiabatic hyperbolic secant refocusing pairs. We compare performance between this train and the standard composite refocusing train, including with and without DPC, for dual-module VSI VSASL. We evaluate (1) simulated velocity-selective profiles and subtraction fidelity across a broad B0/B1 + range, (2) subtraction fidelity in phantoms, and (3) image quality, artifact presence, and gray-matter perfusion heterogeneity (as measured by the spatial coefficient of variation) in healthy human subjects. RESULTS: Adiabatic refocusing significantly improves FT-VSI robustness to B0/B1 + inhomogeneity for a single label-control subtraction. Subtraction fidelity is dramatically improved in both simulation and phantoms compared with composite refocusing without DPC, and is similar compared with DPC methods. In humans, marked artifacts seen with the non-DPC composite refocusing approach are eliminated, corroborated by significantly reduced gray-matter heterogeneity (via lower spatial coefficient of variation values). CONCLUSION: A novel VSASL labeling train using adiabatic refocusing pulses for VSI was found to reduce artifacts related to B0/B1 + inhomogeneity, thereby providing an alternative to DPC and its associated limitations, which include increased vulnerability to physiological noise and motion, reduced functional MRI applicability, and suboptimal data censoring.

Direct angiographic comparison of different velocity-selective saturation, inversion, and DANTE labeling modules on cerebral arteries.

PURPOSE: This study evaluated the velocity-selective (VS) MRA with different VS labeling modules, including double refocused hyperbolic tangent, eight-segment B1-insensitive rotation, delay alternating with nutation for tailored excitation, Fourier transform-based VS saturation, and Fourier transform-based inversion. METHODS: These five VS labeling modules were evaluated first through Bloch simulations, and then using VSMRA directly on various cerebral arteries of healthy subjects. The relative signal ratios from arterial ROIs and surrounding tissues as well as relative arteria-tissue contrast ratios of different methods were compared. RESULTS: Double refocused hyperbolic tangent and eight-segment B1-insensitive rotation showed very similar labeling effects. Delay alternating with nutation for tailored excitation yielded high arterial signal but with residual tissue signal due to the spatial banding effect. Fourier transform-based VS saturation with half the time of other techniques serves as an efficient nonsubtractive VSMRA method, but the remaining tissue signal still obscured some small distal arteries that were delineated by other subtraction-based VSMRA, allowing more complete cancelation of static tissue. Fourier transform-based inversion produced the highest arterial signal in VSMRA with minimal tissue background. CONCLUSION: This is the first study that angiographically compared five different VS labeling modules. Their labeling characteristics on arteries and tissue and implications for VSMRA and VS arterial spin labeling are discussed.

Evaluating cerebrovascular reactivity measured by velocity selective inversion arterial spin labeling with different post-labeling delays: The effect of fast flow.

PURPOSE: Velocity selective arterial spin labeling (VSASL) quantification assumes that the labeled bolus continuously moves into the imaging voxel during the post-labeling delay (PLD). Faster blood flow could lead to a bolus duration shorter than the applied PLD of VSASL and cause underestimation of cerebral blood flow (CBF). This study aims to evaluate the performance of velocity-selective inversion (VSI) prepared arterial spin labeling (ASL) with different PLDs and pseudo-continuous ASL (PCASL) for quantification of hypercapnia-induced cerebrovascular reactivity (CVR), using phase-contrast (PC) MRI as a global reference. METHODS: We compared CVR obtained by VSI-ASL with PLD of 1520 ms (VSASL-1520), 1000 ms (VSASL-1000), and 500 ms (VSASL-500), PCASL with PLD of 1800 ms (PCASL-1800), and PC MRI on eight healthy volunteers at two sessions. RESULTS: Compared with PC MRI, VSASL-1520 produced significantly lower global CVR values, while PCASL-1800, VSASL-1000, and VSASL-500 yielded more consistent results. The reduced CVR in VSASL-1520 was more pronounced in carotid territories including frontal and temporal lobes than in vertebral territories such as the occipital lobe. This is largely caused by the underestimated perfusion during hypercapnia due to the reduced bolus duration being less than the PLD. CONCLUSION: Although VSASL offers certain advantages over spatially selective ASL due to its reduced susceptibility to delayed ATT, this technique is prone to biases when the ATT is excessively short. Therefore, a short PLD should be employed for reliable perfusion and CVR quantification in populations or conditions with fast flow.

Optimizing background suppression for dual-module velocity-selective arterial spin labeling: Without using additional background-suppression pulses.

PURPOSE: Background suppression (BS) is recommended in arterial spin labeling (ASL) for improved SNR but is difficult to optimize in existing velocity-selective ASL (VSASL) methods. Dual-module VSASL (dm-VSASL) enables delay-insensitive, robust, and SNR-efficient perfusion imaging, while allowing efficient BS, but its optimization has yet to be thoroughly investigated. METHODS: The inversion effects of the velocity-selective labeling pulses, such as velocity-selective inversion (VSI), can be used for BS, and were modeled for optimizing BS in dm-VSASL. In vivo experiments using dual-module VSI (dm-VSI) were performed to compare two BS strategies: a conventional one with additional BS pulses and a new one without any BS pulse. Their BS performance, temporal noise, and temporal SNR were examined and compared, with pulsed and pseudo-continuous ASL (PASL and PCASL) as the reference. RESULTS: The in vivo experiments validated the BS modeling. Strong positive linear correlations (r > 0.82, p < 0.0001) between the temporal noise and the tissue signal were found in PASL/PCASL and dm-VSI. Optimal BS can be achieved with and without additional BS pulses in dm-VSI; the latter improved the ASL signals by 8.5% in gray matter (p = 0.006) and 12.2% in white matter (p = 0.014) and tended to provide better temporal SNR. The dm-VSI measured significantly higher ASL signal (p < 0.016) and temporal SNR (p < 0.018) than PASL and PCASL. Complex reconstruction was found necessary with aggressive BS. CONCLUSION: Guided by modeling, optimal BS can be achieved without any BS pulse in dm-VSASL, further improving the ASL signal and the SNR performance.

Test-retest reliability of 3D velocity-selective arterial spin labeling for detecting normal variations of cerebral blood flow.

Velocity-selective inversion (VSI) based velocity-selective arterial spin labeling (VSASL) has been developed to measure cerebral blood flow (CBF) with low susceptibility to the prolonged arterial transit time and high sensitivity to brain perfusion signal. The purpose of this magnetic resonance imaging study is to evaluate the test-retest reliability of a VSI-prepared 3D VSASL protocol with whole-brain coverage to detect baseline CBF variations among cognitively normal participants in different brain regions. Coefficients of variation (CoV) of both absolute and relative CBF across scans or sessions, subjects, and gray matter regions were calculated, and corresponding intraclass correlation coefficients (ICC) were computed. The higher between-subject CoV of absolute CBF (13.4 ± 2.0%) over within-subject CoV (within-session: 3.8 ± 1.1%; between-session: 4.9 ± 0.9%) yielded moderate to excellent ICC (within-session: 0.88±0.08; between-session: 0.77±0.14) to detect normal variations of individual CBF. The higher between-region CoV of relative CBF (11.4 ± 3.0%) over within-region CoV (within-session: 2.3 ± 0.9%; between-session: 3.3 ± 1.0%) yielded excellent ICC (within-session: 0.92±0.06; between-session: 0.85±0.12) to detect normal variations of regional CBF. Age, blood pressure, end-tidal CO2, and hematocrit partially explained the variability of CBF across subjects. Together these results show excellent test-retest reliability of VSASL to detect both between-subject and between-region variations supporting its clinical utility.

Prostate perfusion mapping using Fourier-transform based velocity-selective arterial spin labeling: Choice of cutoff velocity and comparison with brain.

PURPOSE: To develop velocity selective arterial spin labeling (VSASL) protocols for prostate blood flow (PBF) and prostate blood volume (PBV) mapping. METHODS: Fourier-transform based velocity-selective inversion and saturation pulse trains were utilized in VSASL sequences to obtain blood flow and blood volume weighted perfusion signal, respectively. Here four cutoff velocities (Vcut = 0.25, 0.50, 1.00, and 1.50 cm/s) for PBF and PBV mapping sequences were evaluated with a parallel implementation in brain for measuring cerebral blood flow (CBF) and cerebral blood volume (CBV) with identical 3D readout. This study was performed at 3T on eight young and middle-aged healthy subjects comparing both perfusion weighted signal (PWS) and temporal SNR (tSNR). RESULTS: In contrast to CBF and CBV, the PWS of PBF and PBV were rather unobservable at Vcut of 1.00 or 1.50 cm/s and both PWS and tSNR of PBF and PBV considerably increased at the lower Vcut , indicating that blood moves much slower in prostate than in brain. Similar to the brain results, the tSNR of PBV-weighted signal was about two to four times over the corresponding values of PBF-weighted signal. The results also suggested a trend of reduced vascularity within prostate during aging. CONCLUSION: For prostate, a low Vcut of 0.25-0.50 cm/s seemed necessary for both PBF and PBV measurements to obtain adequate perfusion signal. As in brain, PBV mapping yielded a higher tSNR than PBF.

Comparison and optimization of pCASL and VSASL for rat thoracolumbar spinal cord MRI at 9.4 T.

PURPOSE: To evaluate pseudo-continuous arterial spin labeling (pCASL) and velocity-selective arterial spin labeling (VSASL) for quantification of spinal cord blood flow (SCBF) in the rat thoracolumbar spinal cord. METHODS: Labeling efficiency (LE) was compared between pCASL and three VSASL variants in simulations and both phantom and in vivo experiments at 9.4 T. For pCASL, the effects of label plane position and shimming were systematically evaluated. For VSASL, the effects of composite pulses and phase cycling were evaluated to reduce artifacts. Additionally, vessel suppression, respiratory, and cardiac gating were evaluated to reduce motion artifacts. pCASL and VSASL maps of spinal cord blood flow were acquired with the optimized protocols. RESULTS: LE of the descending aorta was larger in pCASL compared to VSASL variants. In pCASL, LE off-isocenter was improved by local shimming positioned at the label plane and the anatomical level of labeling for the thoracic cord was only viable at the level of the T10 vertebra. Cardiac gating was essential to reduce motion artifacts. Both pCASL and VSASL successfully demonstrated comparable SCBF values in the thoracolumbar cord. CONCLUSION: pCASL demonstrated high and consistent LE in the thoracic aorta, and VSASL was also feasible, but with reduced efficiency. A combination of cardiac gating and recording of actual post-label delays was important for accurate SCBF quantification. These results highlight the challenges and solutions to achieve sufficient ASL labeling and contrast at high field in organs prone to motion.

Evaluation of 3D stack-of-spiral turbo FLASH acquisitions for pseudo-continuous and velocity-selective ASL-derived brain perfusion mapping.

PURPOSE: The most-used 3D acquisitions for ASL are gradient and spin echo (GRASE)- and stack-of-spiral (SOS)-based fast spin echo, which require multiple shots. Alternatively, turbo FLASH (TFL) allows longer echo trains, and SOS-TFL has the potential to reduce the number of shots to even single-shot, thus improving the temporal resolution. Here we compare the performance of 3D SOS-TFL and 3D GRASE for ASL at 3T. METHODS: The 3D SOS-TFL readout was optimized with respect to fat suppression and excitation flip angles for pseudo-continuous ASL- and velocity-selective (VS)ASL-derived cerebral blood flow (CBF) mapping as well as for VSASL-derived cerebral blood volume (CBV) mapping. Results were compared with 3D GRASE readout on healthy volunteers in terms of perfusion quantification and temporal SNR (tSNR) efficiency. CBF and CBV mapping derived from 3D SOS-TFL-based ASL was demonstrated on one stroke patient, and the potential for single-shot acquisitions was exemplified. RESULTS: SOS-TFL with a 15° flip angle resulted in adequate tSNR efficiency with negligible image blurring. Selective water excitation was necessary to eliminate fat-induced artifacts. For pseudo-continuous ASL- and VSASL-based CBF and CBV mapping, compared to the employed four-shot 3D GRASE with an acceleration factor of 2, the fully sampled 3D SOS-TFL delivered comparable performance (with a similar scan time) using three shots, which could be further undersampled to achieve single-shot acquisition with higher tSNR efficiency. SOS-TFL had reduced CSF contamination for VSASL-CBF. CONCLUSION: 3D SOS-TFL acquisition was found to be a viable substitute for 3D GRASE for ASL with sufficient tSNR efficiency, minimal relaxation-induced blurring, reduced CSF contamination, and the potential of single-shot, especially for VSASL.

Velocity-selective arterial spin labeling perfusion MRI: A review of the state of the art and recommendations for clinical implementation.

This review article provides an overview of the current status of velocity-selective arterial spin labeling (VSASL) perfusion MRI and is part of a wider effort arising from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group. Since publication of the 2015 consensus paper on arterial spin labeling (ASL) for cerebral perfusion imaging, important advancements have been made in the field. The ASL community has, therefore, decided to provide an extended perspective on various aspects of technical development and application. Because VSASL has the potential to become a principal ASL method because of its unique advantages over traditional approaches, an in-depth discussion was warranted. VSASL labels blood based on its velocity and creates a magnetic bolus immediately proximal to the microvasculature within the imaging volume. VSASL is, therefore, insensitive to transit delay effects, in contrast to spatially selective pulsed and (pseudo-) continuous ASL approaches. Recent technical developments have improved the robustness and the labeling efficiency of VSASL, making it a potentially more favorable ASL approach in a wide range of applications where transit delay effects are of concern. In this review article, we (1) describe the concepts and theoretical basis of VSASL; (2) describe different variants of VSASL and their implementation; (3) provide recommended parameters and practices for clinical adoption; (4) describe challenges in developing and implementing VSASL; and (5) describe its current applications. As VSASL continues to undergo rapid development, the focus of this review is to summarize the fundamental concepts of VSASL, describe existing VSASL techniques and applications, and provide recommendations to help the clinical community adopt VSASL.

Cerebrovascular reactivity measurements using simultaneous 15O-water PET and ASL MRI: Impacts of arterial transit time, labeling efficiency, and hematocrit.

Cerebrovascular reactivity (CVR) reflects the capacity of the brain to meet changing physiological demands and can predict the risk of cerebrovascular diseases. CVR can be obtained by measuring the change in cerebral blood flow (CBF) during a brain stress test where CBF is altered by a vasodilator such as acetazolamide. Although the gold standard to quantify CBF is PET imaging, the procedure is invasive and inaccessible to most patients. Arterial spin labeling (ASL) is a non-invasive and quantitative MRI method to measure CBF, and a consensus guideline has been published for the clinical application of ASL. Despite single post labeling delay (PLD) pseudo-continuous ASL (PCASL) being the recommended ASL technique for CBF quantification, it is sensitive to variations to the arterial transit time (ATT) and labeling efficiency induced by the vasodilator in CVR studies. Multi-PLD ASL controls for the changes in ATT, and velocity selective ASL is in theory insensitive to both ATT and labeling efficiency. Here we investigate CVR using simultaneous 15O-water PET and ASL MRI data from 19 healthy subjects. CVR and CBF measured by the ASL techniques were compared using PET as the reference technique. The impacts of blood T1 and labeling efficiency on ASL were assessed using individual measurements of hematocrit and flow velocity data of the carotid and vertebral arteries measured using phase-contrast MRI. We found that multi-PLD PCASL is the ASL technique most consistent with PET for CVR quantification (group mean CVR of the whole brain = 42±19% and 40±18% respectively). Single-PLD ASL underestimated the CVR of the whole brain significantly by 15±10% compared with PET (p<0.01, paired t-test). Changes in ATT pre- and post-acetazolamide was the principal factor affecting ASL-based CVR quantification. Variations in labeling efficiency and blood T1 had negligible effects.

Systematic evaluation of velocity-selective arterial spin labeling settings for placental perfusion measurement.

PURPOSE: Placental function is key for successful human pregnancies. Perfusion may be a sensitive marker for the in vivo assessment of placental function. Arterial spin labeling (ASL) MRI enables noninvasive measurement of tissue perfusion and it was recently suggested that ASL with velocity-selective (VS) labeling could be advantageous in the placenta. We systematically evaluated essential VS-ASL sequence parameters to determine optimal settings for efficient placental perfusion measurements. METHODS: Eleven pregnant women were scanned at 3T using VS-ASL with 2D multislice echo planar imaging (EPI)-readout. One reference VS-ASL scan was acquired in all subjects; within subgroups the following parameters were systematically varied: cutoff velocity, velocity encoding direction, and inflow time. Visual evaluation and region of interest analyses were performed to compare perfusion signal differences between acquisitions. RESULTS: In all subjects, a perfusion pattern with clear hyperintense focal regions was observed. Perfusion signal decreased with inflow time and cutoff velocity. Subject-specific dependence on velocity encoding direction was observed. High temporal signal-to-noise ratios with high contrast on the perfusion images between the hyperintense regions and placental tissue were seen at ~1.6 cm/s cutoff velocity and ~1000 ms inflow time. Evaluation of measurements at multiple inflow times revealed differences in blood flow dynamics between placental regions. CONCLUSION: Placental perfusion measurements are feasible at 3T using VS-ASL with 2D multislice EPI-readout. A clear dependence of perfusion signal on VS labeling parameters and inflow time was demonstrated. Whereas multiple parameter combinations may advance the interpretation of placental circulation dynamics, this study provides a basis to select an effective set of parameters for the observation of placenta perfusion natural history and its potential pathological changes.

Improved multislice perfusion imaging with velocity-selective arterial spin labeling.

PURPOSE: To improve the multislice performance of velocity-selective arterial spin labeling (VS-ASL) imaging for cerebral blood flow (CBF) measurement such that it might be routinely applied for clinical applications with whole brain coverage. MATERIALS AND METHODS: VS-ASL was performed with improvements such as timing optimization, stimulated echo removal, and slice profile sharpening. Each improvement was evaluated in volunteers by measuring temporal noise in the CBF measurement. VS-ASL with all these improvements was performed in 20 patients with Moyamoya disease some of whom also underwent xenon-enhanced CT (xeCT) imaging which was the reference standard for CBF measurement. RESULTS: Sequence timing optimization and inter-slice crosstalk reduction using stimulated echo removal and slice profile sharpening all contributed to reduction of temporal noise. VS-ASL imaging with all these improvements performed in Moyamoya disease patients showed significant reduction of temporal noise (P < 0.0001) and increased correlation coefficient with xeCT CBF imaging (from 0.07 to 0.62). CONCLUSION: We demonstrated that timing optimization, stimulated echo removal, and slice profile improvement have a large effect on image quality and robustness of VS-ASL in clinical imaging applications.

Non-contrast free-breathing liver perfusion imaging using velocity selective ASL combined with prospective motion compensation.

PURPOSE: To apply velocity selective arterial spin labeling (VSASL) combined with a navigator-based (NAV) prospective motion compensation method for a free-breathing liver perfusion measurement without contrast agent. METHODS: Sinc-modulated Velocity Selective Inversion (sinc-VSI) pulses were applied as labeling and control pulses. In order to account for respiratory motion, a navigator was employed in the form of a single gradient-echo projection readout, located at the diaphragm along the inferior-superior direction. Prior to each transverse imaging slice of the spin-echo EPI based readouts, navigator and fat suppression were incorporated. Motion data was obtained from the navigator and transmitted back to the sequence, allowing real-time adjustments to slice positioning. The sinc-VSI without velocity-selective gradients during the control condition but with velocity-selective gradients along all three directions during labeling was chosen for the VSASL. The VSASL was compared with pseudo-continuous ASL (pCASL) methods, which selectively tagged the moving spins using a tagging plane placed at the portal vein and hepatic artery. RESULTS: The motion caused by respiratory activity was effectively computed using the navigator signal. The coefficients of variation (CoV) of average liver voxel in NAV were significantly decreased when compared to breath-hold (BH), with an average reduction of 29.4 ±â€¯18.44% for control images, and 29.89 ±â€¯20.83% for label images (p < 0.001). The resulting maps of normalized ASL signal (normalized to M0) showed significantly higher perfusion weightings in the NAV-compensated VSASL, when compared to the NAV-compensated pCASL techniques. CONCLUSIONS: This study demonstrates the feasibility of using a navigator-based prospective motion compensation technique in conjunction with VSASL for the measurement of liver perfusion without the use of contrast agents while allowing for free-breathing.

Velocity-Selective Arterial Spin Labeling Perfusion in Monitoring High Grade Gliomas Following Therapy: Clinical Feasibility at 1.5T and Comparison with Dynamic Susceptibility Contrast Perfusion.

MR perfusion imaging is important in the clinical evaluation of primary brain tumors, particularly in differentiating between true progression and treatment-induced change. The utility of velocity-selective ASL (VSASL) compared to the more commonly utilized DSC perfusion technique was assessed in routine clinical surveillance MR exams of 28 patients with high-grade gliomas at 1.5T. Using RANO criteria, patients were assigned to two groups, one with detectable residual/recurrent tumor ("RT", n = 9), and the other with no detectable residual/recurrent tumor ("NRT", n = 19). An ROI was drawn to encompass the largest dimension of the lesion with measures normalized against normal gray matter to yield rCBF and tSNR from VSASL, as well as rCBF and leakage-corrected relative CBV (lc-rCBV) from DSC. VSASL (rCBF and tSNR) and DSC (rCBF and lc-rCBV) metrics were significantly higher in the RT group than the NRT group allowing adequate discrimination (p < 0.05, Mann-Whitney test). Lin's concordance analyses showed moderate to excellent concordance between the two methods, with a stronger, moderate correlation between VSASL rCBF and DSC lc-rCBV (r = 0.57, p = 0.002; Pearson's correlation). These results suggest that VSASL is clinically feasible at 1.5T and has the potential to offer a noninvasive alternative to DSC perfusion in monitoring high-grade gliomas following therapy.

Arterial spin labeling in neuroimaging.

Arterial spin labeling (ASL) is a magnetic resonance imaging technique for measuring tissue perfusion using a freely diffusible intrinsic tracer. As compared with other perfusion techniques, ASL offers several advantages and is now available for routine clinical practice in many institutions. Its noninvasive nature and ability to quantitatively measure tissue perfusion make ASL ideal for research and clinical studies. Recent technical advances have increased its sensitivity and also extended its potential applications. This review focuses on some basic knowledge of ASL perfusion, emerging techniques and clinical applications in neuroimaging.