PurposeTo create an inventory of image processing pipelines of arterial spin labeling (ASL) and list their main features, and to evaluate the capability, flexibility, and ease of use of publicly... Show morePurposeTo create an inventory of image processing pipelines of arterial spin labeling (ASL) and list their main features, and to evaluate the capability, flexibility, and ease of use of publicly available pipelines to guide novice ASL users in selecting their optimal pipeline.MethodsDevelopers self-assessed their pipelines using a questionnaire developed by the Task Force 1.1 of the ISMRM Open Science Initiative for Perfusion Imaging. Additionally, each publicly available pipeline was evaluated by two independent testers with basic ASL experience using a scoring system created for this purpose.ResultsThe developers of 21 pipelines filled the questionnaire. Most pipelines are free for noncommercial use (n = 18) and work with the standard NIfTI (Neuroimaging Informatics Technology Initiative) data format (n = 15). All pipelines can process standard 3D single postlabeling delay pseudo-continuous ASL images and primarily differ in their support of advanced sequences and features. The publicly available pipelines (n = 9) were included in the independent testing, all of them being free for noncommercial use. The pipelines, in general, provided a trade-off between ease of use and flexibility for configuring advanced processing options.ConclusionAlthough most ASL pipelines can process the common ASL data types, only some (namely, ASLPrep, ASLtbx, BASIL/Quantiphyse, ExploreASL, and MRICloud) are well-documented, publicly available, support multiple ASL types, have a user-friendly interface, and can provide a useful starting point for ASL processing. The choice of an optimal pipeline should be driven by specific data to be processed and user experience, and can be guided by the information provided in this ASL inventory. Show less
Tseng, C.H.; Jaspers, J.; Romero, A.M.; Wielopolski, P.; Smits, M.; Osch, M.J.P. van; Vos, F. 2023
The arterial input function (AIF) plays a crucial role in estimating quantitative perfusion properties from dynamic susceptibility contrast (DSC) MRI. An important issue, however, is that... Show moreThe arterial input function (AIF) plays a crucial role in estimating quantitative perfusion properties from dynamic susceptibility contrast (DSC) MRI. An important issue, however, is that measuring the AIF in absolute contrast-agent concentrations is challenging, due to uncertainty in relation to the measured -weighted signal, signal depletion at high concentration, and partial-volume effects. A potential solution could be to derive the AIF from separately acquired dynamic contrast enhanced (DCE) MRI data. We aim to compare the AIF determined from DCE MRI with the AIF from DSC MRI, and estimated perfusion coefficients derived from DSC data using a DCE-driven AIF with perfusion coefficients determined using a DSC-based AIF. AIFs were manually selected in branches of the middle cerebral artery (MCA) in both DCE and DSC data in each patient. In addition, a semi-automatic AIF-selection algorithm was applied to the DSC data. The amplitude and full width at half-maximum of the AIFs were compared statistically using the Wilcoxon rank-sum test, applying a 0.05 significance level. Cerebral blood flow (CBF) was derived with different AIF approaches and compared further. The results showed that the AIFs extracted from DSC scans yielded highly variable peaks across arteries within the same patient. The semi-automatic DSC–AIF had significantly narrower width compared with the manual AIFs, and a significantly larger peak than the manual DSC–AIF. Additionally, the DCE-based AIF provided a more stable measurement of relative CBF and absolute CBF values estimated with DCE–AIFs that were compatible with previously reported values. In conclusion, DCE-based AIFs were reproduced significantly better across vessels, showed more realistic profiles, and delivered more stable and reasonable CBF measurements. The DCE–AIF can, therefore, be considered as an alternative AIF source for quantitative perfusion estimations in DSC MRI. Show less
Overmars, L.M.; Kuipers, S.; Es, B. van; Bresser, J. de; Bron, E.E.; Hoefer, I.E.; ... ; Haitjema, S. 2023
Biological processes underlying decreased cerebral blood flow (CBF) in patients with cardiovascular disease (CVD) are largely unknown. We hypothesized that identification of protein clusters... Show moreBiological processes underlying decreased cerebral blood flow (CBF) in patients with cardiovascular disease (CVD) are largely unknown. We hypothesized that identification of protein clusters associated with lower CBF in patients with CVD may explain underlying processes. In 428 participants (74% cardiovascular diseases; 26% reference participants) from the Heart-Brain Connection Study, we assessed the relationship between 92 plasma proteins from the Olink® cardiovascular III panel and normal-appearing grey matter CBF, using affinity propagation and hierarchical clustering algorithms, and generated a Biomarker Compound Score (BCS). The BCS was related to cardiovascular risk and observed cardiovascular events within 2-year follow-up using Spearman correlation and logistic regression. Thirteen proteins were associated with CBF (ρSpearman range: −0.10 to −0.19, pFDR-corrected <0.05), and formed one cluster. The cluster primarily reflected extracellular matrix organization processes. The BCS was higher in patients with CVD compared to reference participants (pFDR-corrected <0.05) and was associated with cardiovascular risk (ρSpearman 0.42, p < 0.001) and cardiovascular events (OR 2.05, p < 0.01). In conclusion, we identified a cluster of plasma proteins related to CBF, reflecting extracellular matrix organization processes, that is also related to future cardiovascular events in patients with CVD, representing potential targets to preserve CBF and mitigate cardiovascular risk in patients with CVD. Show less
INTRODUCTIONChronic cerebral hypoperfusion is one of the assumed pathophysiological mechanisms underlying vascular cognitive impairment (VCI). We investigated the association between baseline... Show moreINTRODUCTIONChronic cerebral hypoperfusion is one of the assumed pathophysiological mechanisms underlying vascular cognitive impairment (VCI). We investigated the association between baseline cerebral blood flow (CBF) and cognitive decline after 2 years in patients with VCI and reference participants.METHODSOne hundred eighty-one participants (mean age 66.3 ± 7.4 years, 43.6% women) underwent arterial spin labeling (ASL) magnetic resonance imaging (MRI) and neuropsychological assessment at baseline and at 2-year follow-up. We determined the association between baseline global and lobar CBF and cognitive decline with multivariable regression analysis.RESULTSLower global CBF at baseline was associated with more global cognitive decline in VCI and reference participants. This association was most profound in the domain of attention/psychomotor speed. Lower temporal and frontal CBF at baseline were associated with more cognitive decline in memory.DISCUSSIONOur study supports the role of hypoperfusion in the pathophysiological and clinical progression of VCI. Show less
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
Gartner, M.; Rover, M. de; Vaclavu, L.; Scheidegger, M.; Osch, M.J.P. van; Grimm, S. 2022
Ketamine is a promising treatment option for patients with Major Depressive Disorder (MDD) and has become an important research tool to investigate antidepressant mechanisms of action. However,... Show moreKetamine is a promising treatment option for patients with Major Depressive Disorder (MDD) and has become an important research tool to investigate antidepressant mechanisms of action. However, imaging studies attempting to characterise ketamine's mechanism of action using blood oxygen level-dependent signal (BOLD) imaging have yielded inconsistent results- at least partly due to intrinsic properties of the BOLD contrast, which measures a complex signal related to neural activity. To circumvent the limitations associated with the BOLD signal, we used arterial spin labelling (ASL) as an unambiguous marker of neuronal activity-related changes in cerebral blood flow (CBF). We measured CBF in 21 MDD patients at baseline and 24 h after receiving a single intravenous infusion of subanesthetic ketamine and examined relationships with clinical outcomes. Our findings demonstrate that increase in thalamus perfusion 24 h after ketamine administration is associated with greater improvement of depressive symptoms. Furthermore, lower thalamus perfusion at baseline is associated both with larger increases in perfusion 24 h after ketamine administration and with stronger reduction of depressive symptoms. These findings indicate that ASL is not only a useful tool to broaden our understanding of ketamine's mechanism of action but might also have the potential to inform treatment decisions based on CBF-defined regional disruptions. 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
Alzheimer's disease (AD) is the leading cause of cognitive impairment and dementia in elderly individuals. According to the current biomarker framework for "unbiased descriptive classification",... Show moreAlzheimer's disease (AD) is the leading cause of cognitive impairment and dementia in elderly individuals. According to the current biomarker framework for "unbiased descriptive classification", biomarkers of neurodegeneration, "N", constitute a critical component in the tri-category "A/T/N" system. Current biomarkers of neurodegeneration suffer from potential drawbacks such as requiring invasive lumbar puncture, involving ionizing radiation, or representing a late, irreversible marker. Recent human studies have suggested that reduced brain oxygen metabolism may be a new functional marker of neurodegeneration in AD, but the heterogeneity and the presence of mixed pathology in human patients did not allow a full understanding of the role of oxygen extraction and metabolism in AD. In this report, global brain oxygen metabolism and related physiological parameters were studied in two AD mouse models with relatively pure pathology, using advanced MRI techniques including T-2-relaxation-under-spin-tagging (TRUST) and phase contrast (PC) MRI. Additionally, regional cerebral blood flow (CBF) was determined with pseudocontinuous arterial spin labeling. Reduced global oxygen extraction fraction (by -18.7%, p = 0.008), unit-mass cerebral metabolic rate of oxygen (CMRO2) (by -17.4%, p = 0.04) and total CMRO2 (by -30.8%, p < 0.001) were observed in Tau4R Delta K mice-referred to as the tau AD model-which manifested pronounced neurodegeneration, as measured by diminished brain volume (by -15.2%, p < 0.001). Global and regional CBF in these mice were not different from those of wild-type mice (p > 0.05), suggesting normal vascular function. By contrast, in B6;SJL-Tg [APPSWE]2576Kha (APP) mice-referred to as the amyloid AD model-no brain volume reduction, as well as relatively intact brain oxygen extraction and metabolism, were found (p > 0.05). Consistent with the imaging data, behavioral measures of walking distance were impaired in Tau4R Delta K mice (p = 0.004), but not in APP mice (p = 0.88). Collectively, these findings support the hypothesis that noninvasive MRI measurement of brain oxygen metabolism may be a promising biomarker of neurodegeneration in AD. Show less
In patients with sickle cell disease (SCD), cerebral blood flow (CBF) is elevated to counteract anemia and maintain oxygen supply to the brain. This may exhaust the vasodilating capacity of the... Show moreIn patients with sickle cell disease (SCD), cerebral blood flow (CBF) is elevated to counteract anemia and maintain oxygen supply to the brain. This may exhaust the vasodilating capacity of the vessels, possibly increasing the risk of silent cerebral infarctions (SCI). To further investigate cerebrovascular hemodynamics in SCD patients, we assessed CBF, arterial transit time (ATT), cerebrovascular reactivity of CBF and ATT (CVRCBF and CVRATT) and oxygen delivery in patients with different forms of SCD and matched healthy controls. We analyzed data of 52 patients with severe SCD (HbSS and HbS beta(0)-thal), 20 patients with mild SCD (HbSC and HbS beta(+)-thal) and 10 healthy matched controls (HbAA and HbAS). Time-encoded arterial spin labeling (ASL) scans were performed before and after a vasodilatory challenge using acetazolamide (ACZ). To identify predictors of CBF and ATT after vasodilation, regression analyses were performed. Oxygen delivery was calculated and associated with hemoglobin and fetal hemoglobin (HbF) levels. At baseline, severe SCD patients showed significantly higher CBF and lower ATT compared to both the mild SCD patients and healthy controls. As CBFpostACZ was linearly related to CBFpreACZ, CVRCBF decreased with disease severity. CVRATT was also significantly affected in severe SCD patients compared to mild SCD patients and healthy controls. Considering all groups, women showed higher CBFpostACZ than men (p < 0.01) independent of baseline CBF. Subsequently, post ACZ oxygen delivery was also higher in women (p < 0.05). Baseline, but not post ACZ, GM oxygen delivery increased with HbF levels. Our data showed that baseline CBF and ATT and CVRCBF and CVRATT are most affected in severe SCD patients and to a lesser extent in patients with milder forms of SCD compared to healthy controls. Cerebrovascular vasoreactivity was mainly determined by baseline CBF, sex and HbF levels. The higher vascular reactivity observed in women could be related to their lower SCI prevalence, which remains an area of future work. Beneficial effects of HbF on oxygen delivery reflect changes in oxygen dissociation affinity from hemoglobin and were limited to baseline conditions suggesting that high HbF levels do not protect the brain upon a hemodynamic challenge, despite its positive effect on hemolysis. Show less
Vlastra, W.; Nieuwkerk, A.C. van; Bronzwaer, A.S.G.T.; Versteeg, A.; Bron, E.E.; Niessen, W.J.; ... ; Delewi, R. 2020
BACKGROUND Transcatheter aortic valve implantation (TAVI) is a minimally invasive, life-saving treatment for patients with severe aortic valve stenosis that improves quality of life. We examined... Show moreBACKGROUND Transcatheter aortic valve implantation (TAVI) is a minimally invasive, life-saving treatment for patients with severe aortic valve stenosis that improves quality of life. We examined cardiac output and cerebral blood flow in patients undergoing TAVI to test the hypothesis that improved cardiac output after TAVI is associated with an increase in cerebral blood flow. DESIGN Prospective cohort study. SETTING European high-volume tertiary multidisciplinary cardiac care. PARTICIPANTS Thirty-one patients (78.3 +/- 4.6 years; 61% female) with severe symptomatic aortic valve stenosis. MEASUREMENTS Noninvasive prospective assessment of cardiac output (L/min) by inert gas rebreathing and cerebral blood flow of the total gray matter (mL/100 g per min) using arterial spin labeling magnetic resonance imaging in resting state less than 24 hours before TAVI and at 3-month follow-up. Cerebral blood flow change was defined as the difference relative to baseline. RESULTS On average, cardiac output in patients with severe aortic valve stenosis increased from 4.0 +/- 1.1 to 5.4 +/- 2.4 L/min after TAVI (P= .003). The increase in cerebral blood flow after TAVI strongly varied between patients (7% +/- 24%;P= .41) and related to the increase in cardiac output, with an 8.2% (standard error = 2.3%;P= .003) increase in cerebral blood flow per every additional liter of cardiac output following the TAVI procedure. CONCLUSION Following TAVI, there was an association of increase in cardiac output with increase in cerebral blood flow. These findings encourage future larger studies to determine the influence of TAVI on cerebral blood flow and cognitive function. Show less
Purpose To determine whether sacrificing part of the scan time of pseudo-continuous arterial spin labeling (PCASL) for measurement of the labeling efficiency and blood T1 is beneficial in terms of... Show morePurpose To determine whether sacrificing part of the scan time of pseudo-continuous arterial spin labeling (PCASL) for measurement of the labeling efficiency and blood T1 is beneficial in terms of CBF quantification reliability.Methods In a simulation framework, 5-minute scan protocols with different scan time divisions between PCASL data acquisition and supporting measurements were evaluated in terms of CBF estimation variability across both noise and ground truth parameter realizations taken from the general population distribution. The entire simulation experiment was repeated for a single-post-labeling delay (PLD), multi-PLD, and free-lunch time-encoded (te-FL) PCASL acquisition strategy. Furthermore, a real data study was designed for preliminary validation.Results For the considered population statistics, measuring the labeling efficiency and the blood T1 proved beneficial in terms of CBF estimation variability for any distribution of the 5-minute scan time compared to only acquiring ASL data. Compared to single-PLD PCASL without support measurements as recommended in the consensus statement, a 26%, 33%, and 42% reduction in relative CBF estimation variability was found for optimal combinations of supporting measurements with single-PLD, free-lunch, and multi-PLD PCASL data acquisition, respectively. The benefit of taking the individual variation of blood T1 into account was also demonstrated in the real data experiment.Conclusions Spending time to measure the labeling efficiency and the blood T1 instead of acquiring more averages of the PCASL data proves to be advisable for robust CBF quantification in the general population. Show less
Purpose To compare cerebral blood flow (CBF) and cerebrovascular reserve (CVR) quantification from Turbo-QUASAR (quantitative signal targeting with alternating radiofrequency labeling of arterial... Show morePurpose To compare cerebral blood flow (CBF) and cerebrovascular reserve (CVR) quantification from Turbo-QUASAR (quantitative signal targeting with alternating radiofrequency labeling of arterial regions) arterial spin labeling (ASL) and single post-labeling delay pseudo-continuous ASL (PCASL). Methods A model-based method was developed to quantify CBF and arterial transit time (ATT) from Turbo-QUASAR, including a correction for magnetization transfer effects caused by the repeated labeling pulses. Simulations were performed to assess the accuracy of the model-based method. Data from an in vivo experiment conducted on a healthy cohort were retrospectively analyzed to compare the CBF and CVR (induced by acetazolamide) measurement from Turbo-QUASAR and PCASL on the basis of global and regional differences. The quality of the two ASL data sets was examined using the coefficient of variation (CoV). Results The model-based method for Turbo-QUASAR was accurate for CBF estimation (relative error was 8% for signal-to-noise ratio = 5) in simulations if the bolus duration was known. In the in vivo experiment, the mean global CVR estimated by Turbo-QUASAR and PCASL was between 63% and 64% and not significantly different. Although global CBF values of the two ASL techniques were not significantly different, regional CBF differences were found in deep gray matter in both pre- and postacetazolamide conditions. The CoV of Turbo-QUASAR data was significantly higher than PCASL. Conclusion Both ASL techniques were effective for quantifying CBF and CVR, despite the regional differences observed. Although CBF estimated from Turbo-QUASAR demonstrated a higher variability than PCASL, Turbo-QUASAR offers the advantage of being able to measure and control for variation in ATT. 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
The cerebral blood flow (CBF) is a potential biomarker for neurological disease. However, the arterial transit time (ATT) of the labeled blood is known to potentially affect CBF quantification.... Show moreThe cerebral blood flow (CBF) is a potential biomarker for neurological disease. However, the arterial transit time (ATT) of the labeled blood is known to potentially affect CBF quantification. Furthermore, ATT could be an interesting biomarker in itself, as it may reflect underlying macro and microvascular pathologies. Currently, no optimized magnetic resonance imaging (MRI) sequence exists to measure ATT in mice. Recently, time-encoded labeling schemes have been implemented in rats and humans, enabling ATT mapping with higher signal-to-noise ratio (SNR) and shorter scan time than multi-delay arterial spin labeling (ASL). In this study, we show that time-encoded pseudo-continuous arterial spin labeling (te-pCASL) also enables transit time measurements in mice. As an optimal design that takes the fast blood flow in mice into account, time encoding with 11 sub-boli of 50 ms is proposed to accurately probe the inflow of labeled blood. For perfusion imaging, a separate, traditional pCASL scan was employed. From the six studied brain regions, the hippocampus showed the shortest ATT (169 +/- 11 ms) and the auditory/visual cortex showed the longest (284 +/- 16 ms). Furthermore, ATT was found to be preserved in old wild-type mice. In a mouse with an induced carotid artery occlusion, prolongation of ATT was shown. In conclusion, this study shows the successful implementation of te-pCASL in mice, making it possible, for the first time, to measure ATT in mice in a time-efficient manner. Show less
