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... Show moreThis 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. Show less
Plas, M.C.E. van der; Craig, M.; Schmid, S.; Chappell, M.A.; Osch, M.J.P. van 2021
Purpose In this paper, the ability to quantify cerebral blood flow by arterial spin labeling (ASL) was studied by investigating the separation of the macrovascular and tissue component using a 2... Show morePurpose In this paper, the ability to quantify cerebral blood flow by arterial spin labeling (ASL) was studied by investigating the separation of the macrovascular and tissue component using a 2-component model. Underlying assumptions of this model, especially the inclusion of dispersion in the analysis, were studied, as well as the temporal resolution of the ASL datasets. Methods Four different datasets were acquired: (1) 4D ASL angiography to characterize the macrovascular component and to study dispersion modeling within this component, (2) high temporal resolution ASL data to investigate the separation of the 2 components and the effect of dispersion modelling on this separation, (3) low temporal resolution ASL dataset to study the effect of the temporal resolution on the separation of the 2 components, and (4) low temporal resolution ASL data with vascular crushing. Results The model that included a gamma dispersion kernel had the best fit to the 4D ASL angiography. For the high temporal resolution ASL dataset, inclusion of the gamma dispersion kernel led to more signal included in the arterial blood volume map, which resulted in decreased cerebral blood flow values. The arterial blood volume and cerebral blood flow maps showed overall higher arterial blood volume values and lower cerebral blood flow values for the high temporal resolution dataset compared to the low temporal resolution dataset. Conclusion Inclusion of a gamma dispersion kernel resulted in better fitting of the model to the data. The separation of the macrovascular and tissue component is affected by the inclusion of a gamma dispersion kernel and the temporal resolution of the ASL dataset. Show less
Plas, M.C.E. van der; Schmid, S.; Versluis, M.J.; Okell, T.W.; Osch, M.J.P. van 2021
The objective of the current study was to combine a time-encoded pseudocontinuous arterial spin labeling (te-pCASL) scheme with a golden angle radial readout for simultaneous acquisition of... Show moreThe objective of the current study was to combine a time-encoded pseudocontinuous arterial spin labeling (te-pCASL) scheme with a golden angle radial readout for simultaneous acquisition of angiography and perfusion images from one single dataset, both in a highly flexible single-slice approach as well as within a multislice setting. A te-pCASL preparation and the golden angle radial readout were both used as a temporal resolution tool to retrospectively choose the temporal window for the reconstruction of both angiography and perfusion images from a single-slice dataset. The temporal window could be chosen retrospectively and adjusted to the hemodynamics of the volunteer on the scanner for the single-slice dataset. Angiographic images were reconstructed at a minimum temporal resolution of 69 ms. For the perfusion phase, only the densely sampled center of k-space was included in the reconstruction. For a multislice acquisition, the golden angle radial readout allowed reconstruction of images with different spatial resolutions to provide angiographic and perfusion information over 10 slices. The te-pCASL preparation was used as the only source for dynamic information. The multislice acquisition shows the ability of the golden angle radial readout to display the inflow of the labeled blood into the arteries as well as the perfusion in the tissue with full brain coverage. By combining a te-pCASL preparation with a golden angle radial readout, single-slice high temporal resolution angiography and good quality perfusion images were reconstructed in a flexible manner from a single dataset. Optimizing the golden angle radial readout for reconstructions at multiple spatial resolutions allows for multislice acquisition. Show less
Purpose Velocity-selective arterial spin labeling (VSASL) has been proposed for renal perfusion imaging to mitigate planning challenges and effects of arterial transit time (ATT) uncertainties. In... Show morePurpose Velocity-selective arterial spin labeling (VSASL) has been proposed for renal perfusion imaging to mitigate planning challenges and effects of arterial transit time (ATT) uncertainties. In VSASL, label generation may shift in the vascular tree as a function of cutoff velocity. Here, we investigate label dynamics and especially the ATT of renal VSASL and compared it with a spatially selective pulsed arterial spin labeling technique, flow alternating inversion recovery (FAIR).Methods Arterial spin labeling data were acquired in 7 subjects, using free-breathing dual VSASL and FAIR with five postlabeling delays: 400, 800, 1200, 2000, and 2600 ms. The VSASL measurements were acquired with cutoff velocities of 5, 10, and 15 cm/s, with anterior-posterior velocity-encoding direction. Cortical perfusion-weighted signal, temporal SNR, quantified renal blood flow, and arterial transit time were reported.Results In contrast to FAIR, renal VSASL already showed fairly high signal at the earliest postlabeling delays, for all cutoff velocities. The highest VSASL signal and temporal SNR was obtained with a cutoff velocity of 10 cm/s at postlabeling delay = 800 ms, which was earlier than for FAIR at 1200 ms. Fitted ATT on VSASL was <= 0 ms, indicating ATT insensitivity, which was shorter than for FAIR (189 +/- 79 ms, P < .05). Finally, the average cortical renal blood flow measured with cutoff velocities of 5 cm/s (398 +/- 84 mL/min/100 g) and 10 cm/s (472 +/- 160 mL/min/100 g) were similar to renal blood flow measured with FAIR (441 +/- 84 mL/min/100 g) (P > .05) with good correlations on subject level.Conclusion Velocity-selective arterial spin labeling in the kidney reduces ATT sensitivity compared with the recommended pulsed arterial spin labeling method, as well as if cutoff velocity is increased to reduce spurious labeling due to motion. Thus, VSASL has potential as a method for time-efficient, single-time-point, free-breathing renal perfusion measurements, despite lower tSNR than FAIR. Show less
Franklin, S.L.; Bones, I.K.; Harteveld, A.A.; Hirschler, L.; Stralen, M. van; Qin, Q.; ... ; Schmid, S. 2020
Purpose Flow-based arterial spin labeling (ASL) techniques provide a transit-time insensitive alternative to the more conventional spatially selective ASL techniques. However, it is not clear which... Show morePurpose Flow-based arterial spin labeling (ASL) techniques provide a transit-time insensitive alternative to the more conventional spatially selective ASL techniques. However, it is not clear which flow-based ASL technique performs best and also, how these techniques perform outside the brain (taking into account eg, flow-dynamics, field-inhomogeneity, and organ motion). In the current study we aimed to compare 4 flow-based ASL techniques (ie, velocity selective ASL, acceleration selective ASL, multiple velocity selective saturation ASL, and velocity selective inversion prepared ASL [VSI-ASL]) to the current spatially selective reference techniques in brain (ie, pseudo-continuous ASL [pCASL]) and kidney (ie, pCASL and flow alternating inversion recovery [FAIR]).Methods Brain (n = 5) and kidney (n = 6) scans were performed in healthy subjects at 3T. Perfusion-weighted signal (PWS) maps were generated and ASL techniques were compared based on temporal SNR (tSNR), sensitivity to perfusion changes using a visual stimulus (brain) and robustness to respiratory motion by comparing scans acquired in paced-breathing and free-breathing (kidney).Results In brain, all flow-based ASL techniques showed similar tSNR as pCASL, but only VSI-ASL showed similar sensitivity to perfusion changes. In kidney, all flow-based ASL techniques had comparable tSNR, although all lower than FAIR. In addition, VSI-ASL showed a sensitivity to B-1-inhomogeneity. All ASL techniques were relatively robust to respiratory motion.Conclusion In both brain and kidney, flow-based ASL techniques provide a planning-free and transit-time insensitive alternative to spatially selective ASL techniques. VSI-ASL shows the most potential overall, showing similar performance as the golden standard pCASL in brain. However, in kidney, a reduction of B-1-sensitivity of VSI-ASL is necessary to match the performance of FAIR. Show less
Petitclerc, L.; Schmid, S.; Hirschler, L.; Osch, M.J.P. van 2020
Purpose Arterial spin labeling can be used to assess the transition time of water molecules across the blood-brain barrier when combined with sequence modules, which allow a separation of... Show morePurpose Arterial spin labeling can be used to assess the transition time of water molecules across the blood-brain barrier when combined with sequence modules, which allow a separation of intravascular from tissue signal. The bipolar gradient technique measures the intravascular fraction by removing flowing spins. The T-2-relaxation-under-spin-tagging (TRUST) technique modulates the TE to differentiate between intravascular and extravascular spins based on T-2. These modules were combined into a single time-encoded pseudo-continuous arterial spin labeling sequence to compare their mechanisms of action as well as their assessment of water transition across the blood-brain barrier.Methods This protocol was acquired on a scanner with 9 healthy volunteers who provided written, informed consent. The sequence consisted of a Hadamard-encoded pseudo-continuous arterial spin labeling module, followed by the TRUST module (effective TEs of 0, 40, and 80 ms) and bipolar flow-crushing gradients (2, 4, and infinity cm/s). An additional experiment was performed with TRUST and a 3D gradient and spin-echo readout.Results Gradients imperfectly canceled the intravascular signal, as evidenced by the presence of residual signal in the arteries at early postlabeling delays as well as the underestimation of the intravascular fraction as compared with the TRUST method. The TRUST module allowed us to detect the transport of water deeper into the vascular tree through changes in T-2 than the used crusher gradients could, with their limited b-value.Conclusion Of the implemented techniques, TRUST allowed us to follow intravascular signal deeper into the vascular tree than the approach with (relatively weak) crusher gradients when quantifying the transport time of water across the blood-brain barrier. Show less
Background: More people on immunosuppression live in or wish to travel to yellow fever virus (YFV)-endemic areas. Data on the safety and immunogenicity of yellow fever vaccination (YFVV) during... Show moreBackground: More people on immunosuppression live in or wish to travel to yellow fever virus (YFV)-endemic areas. Data on the safety and immunogenicity of yellow fever vaccination (YFVV) during immunosuppression are scarce. The aim of this study was to compare the safety and immunogenicity of a primary YFVV between travellers on methotrexate and controls.Methods: We conducted a prospective multi-centre controlled observational study from 2015 to 2017 in six Swiss travel clinics. 15 adults (nine with rheumatic diseases, five with dermatologic conditions and one with a gastroenterological disease) on low-dose methotrexate (<= 20 mg/week) requiring a primary YFVV and 15 age and sex-matched controls received a YFVV. Solicited/unsolicited adverse reactions were recorded, YFV-RNA was measured in serum samples on Days 3, 7, 10, 14, 28 and neutralizing antibodies on Days 0, 7, 10, 14, 28.Results: Patients' and controls' median ages were 53 and 52 years; 9 patients and 10 controls were female. 43% of patients and 33% of controls showed local side effects (P = 0.71); 86% of patients and 66% of controls reported systemic reactions (P = 0.39). YFV-RNA was detected in patients and controls on Day 3-10 post-vaccination and was never of clinical significance. Slightly more patients developed YFV-RNAaemia (Day 3: n= 5 vs n= 2, Day 7: n= 9 vs n= 7, Day 10: n= 3 vs n= 2, all P > 0.39). No serious reactions occurred. On Day 10, a minority of vaccinees was seroprotected (patients: n= 2, controls: n= 6). On Day 28, all vaccinees were seroprotected.Conclusions: First-time YFVV was safe and immunogenic in travellers on low-dose methotrexate. Larger studies are needed to confirm these promising results. Show less
Caffo, O.; Wissing, M.; Bianchini, D.; Bergman, A.; Thomsen, F.B.; Schmid, S.; ... ; CASTOR Study Investigators 2020
Purpose: In this study, the influence of the cardiac cycle on the amount of label produced by a velocity-selective (VSASL) and acceleration-selective arterial spin labeling (AccASL) module was... Show morePurpose: In this study, the influence of the cardiac cycle on the amount of label produced by a velocity-selective (VSASL) and acceleration-selective arterial spin labeling (AccASL) module was investigated.Methods: A short-PLD sequence was developed where a single VSASL- or AccASL-module was preceded by pCASL labeling to isolate the arterial blood pool. ASL subtraction was performed with label/control images with similar cardiac phase and time-of-measurement, followed by retrospective binning in 10 cardiac phase bins. ASL signal variation over the heart cycle was evaluated and tested for significance using a permutation test.Results: VSASL and AccASL showed significant arterial signal fluctuations over the cardiac cycle of up to similar to 36% and similar to 64%, respectively, mainly in areas containing large arteries. pCASL also showed significant signal fluctuations, of up to similar to 25% in arteries. Raw label/control images confirmed that the observed signal fluctuations were caused by the amount of label produced during the cardiac cycle, rather than inflow-effects, because the raw images did not all show equal cardiac phase dependence. No significant effects of the cardiac cycle were found on the gray matter ASL-signal.Conclusion: Significant influence of the cardiac cycle on the generated label was found for spatially nonselective ASL-sequences. Hence, to become independent of the cardiac cycle, sufficient averages need to be taken. Alternatively, these findings could be highly interesting for the purpose of quantifying pulsatility more distally in the vascular tree. Show less
Plas, M.C.E. van der; Teeuwisse, W.M.; Schmid, S.; Chappell, M.; Osch, M.J.P. van 2019
Purpose: The goal of this study was to achieve high temporal resolution, multi-time point pseudo-continuous arterial spin labeling (pCASL) MRI in a time-efficient manner, while maintaining whole... Show morePurpose: The goal of this study was to achieve high temporal resolution, multi-time point pseudo-continuous arterial spin labeling (pCASL) MRI in a time-efficient manner, while maintaining whole-brain coverage.Methods: A Hadamard 8-matrix was used to dynamically encode the pCASL labeling train, thereby providing the first source of temporal information. The second method for obtaining dynamic arterial spin labeling (ASL) signal consisted of a Look-Locker (LL) readout of 4 phases that are acquired with a flip-angle sweep to maintain constant sensitivity over the phases. To obtain whole-brain coverage in the short LL interval, 4 slices were excited simultaneously by multi-banded radiofrequency pulses. After subtraction according to the Hadamard scheme, the ASL signal was corrected for the use of the flip-angle sweep and background suppression pulses. The BASIL toolkit of the Oxford Centre for FMRIB was used to quantify the ASL signal.Results: By combining a time-encoded pCASL labeling scheme with an LL readout and simultaneous multi-slice acquisition, 28 time points of 16 slices with a 75- or 150-ms time resolution were acquired in a total scan time of 10 minutes 20 seconds, from which cerebral blood flow (CBF) maps, arterial transit time maps, and arterial blood volume could be determined.Conclusion: Whole-brain ASL images were acquired with a 75-ms time resolution for the angiography and 150-ms resolution for the perfusion phase by combining the proposed techniques. Reducing the total scan time to 1 minute 18 seconds still resulted in reasonable CBF maps, which demonstrates the feasibility of this approach for practical studies on brain hemodynamics. Show less
Osch, M.J.P. van; Teeuwisse, W.M.; Chen, Z.S.; Suzuki, Y.; Helle, M.; Schmid, S. 2018
In this thesis I have described the introduction and validation of a new spatially non-selective arterial spin labeling (SNS-ASL) method in healthy subjects. Acceleration selective ASL (AccASL... Show moreIn this thesis I have described the introduction and validation of a new spatially non-selective arterial spin labeling (SNS-ASL) method in healthy subjects. Acceleration selective ASL (AccASL) was compared with pseudo continuous ASL (pCASL), a traditional ASL method, as well as other spatially non-selective ASL methods (velocity selective ASL, as introduced by Wong et al with two velocity-selective blocks, and using only a single labeling module), and with [15O]-H2O PET as the gold standard for brain perfusion imaging. By combining an AccASL with VSASL labeling module, the location of label origin in the vascular tree was assessed. Furthermore, time-encoded pCASL was explored in combination with SNS-ASL labeling modules to obtain insight into labeling at multiple post labeling delays (PLD). Finally, te-pCASL was combined with T2-Relaxation-under-Spin-Tagging (TRUST) to provide a time efficient method to distinguish spin compartments based on their T2-values. Show less
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