This review article provides an overview of a range of recent technical developments in advanced arterial spin labeling (ASL) methods that have been developed or adopted by the community since the... Show moreThis review article provides an overview of a range of recent technical developments in advanced arterial spin labeling (ASL) methods that have been developed or adopted by the community since the publication of a previous ASL consensus paper by Alsop et al. It is part of a series of review/recommendation papers from the International Society for Magnetic Resonance in Medicine Perfusion Study Group. Here, we focus on advancements in readouts and trajectories, image reconstruction, noise reduction, partial volume correction, quantification of nonperfusion parameters, fMRI, fingerprinting, vessel selective ASL, angiography, deep learning, and ultrahigh field ASL. We aim to provide a high level of understanding of these new approaches and some guidance for their implementation, with the goal of facilitating the adoption of such advances by research groups and by MRI vendors. Topics outside the scope of this article that are reviewed at length in separate articles include velocity selective ASL, multiple-timepoint ASL, body ASL, and clinical ASL recommendations. Show less
Barbour, S.J.; Coppo, R.; Zhang, H.; Liu, Z.H.; Suzuki, Y.; Matsuzaki, K.; ... ; Int IgA Nephropathy Network 2022
The International IgA Nephropathy (IgAN) Prediction Tool is the preferred method in the 2021 KDIGO guidelines to predict, at the time of kidney biopsy, the risk of a 50% drop in estimated... Show moreThe International IgA Nephropathy (IgAN) Prediction Tool is the preferred method in the 2021 KDIGO guidelines to predict, at the time of kidney biopsy, the risk of a 50% drop in estimated glomerular filtration rate or kidney failure. However, it is not known if the Prediction Tool can be accurately applied after a period of observation post-biopsy. Using an international multi-ethnic derivation cohort of 2,507 adults with IgAN, we updated the Prediction Tool for use one year after biopsy, and externally validated this in a cohort of 722 adults. The original Prediction Tool applied at one-year without modification had a coefficient of variation (R-2) of 55% and 54% and four-year concordance (C statistic) of 0.82 but poor calibration with under-prediction of risk (integrated calibration index (ICI) 1.54 and 2.11, with and without race, respectively). Our updated Prediction Tool had a better model fit with higher R2 (61% and 60%), significant increase in four-year C-statistic (0.87 and 0.86) and better four-year calibration with lower ICI (0.75 and 0.35). On external validation, the updated Prediction Tool had similar R-2 (60% and 58%) and four-year C-statistics (both 0.85) compared to the derivation analysis, with excellent four-year calibration (ICI 0.62 and 0.56). This updated Prediction Tool had similar prediction performance when used two years after biopsy. Thus, the original Prediction Tool should be used only at the time of biopsy whereas our updated Prediction Tool can be used for risk stratification one or two years post-biopsy. Show less
Combining arterial spin-labeling MRA with contrast-enhanced time-resolved MRA holds promise as an alternative to DSA for confirmation of obliteration following gamma knife radiosurgery for brain... Show moreCombining arterial spin-labeling MRA with contrast-enhanced time-resolved MRA holds promise as an alternative to DSA for confirmation of obliteration following gamma knife radiosurgery for brain AVMs, having provided 100% sensitivity and specificity in the study.BACKGROUND AND PURPOSE:Intra-arterial DSA has been traditionally used for confirmation of cure following gamma knife radiosurgery for AVMs. Our aim was to evaluate whether 4D arterial spin-labeling MRA and contrast-enhanced time-resolved MRA in combination can be an alternative to DSA for confirmation of AVM obliteration following gamma knife radiosurgery.MATERIALS AND METHODS:In this prospective study, 30 patients undergoing DSA for confirmation of obliteration following gamma knife radiosurgery for AVMs (criterion standard) also underwent MRA, including arterial spin-labeling MRA and contrast-enhanced time-resolved MRA. One dataset was technically unsatisfactory, and the case was excluded. The DSA and MRA datasets of 29 patients were independently and blindly evaluated by 2 observers regarding the presence/absence of residual AVMs.RESULTS:The mean time between gamma knife radiosurgery and follow-up DSA/MRA was 53?months (95% CI, 42?64 months; range, 22?168 months). MRA total scanning time was 9 minutes and 17 seconds. Residual AVMs were detected on DSA in 9 subjects (obliteration rate = 69%). All residual AVMs were detected on at least 1 MRA sequence. Arterial spin-labeling MRA and contrast-enhanced time-resolved MRA showed excellent specificity and positive predictive values individually (100%). However, their sensitivity and negative predictive values were suboptimal due to 1 false-negative with arterial spin-labeling MRA and 2 with contrast-enhanced time-resolved MRA (sensitivity = 88% and 77%, negative predictive values = 95% and 90%, respectively). Both sensitivity and negative predictive values increased to 100% if a composite assessment of both MRA sequences was performed. Diagnostic accuracy (receiver operating characteristic) and agreement (?) are maximized using arterial spin-labeling MRA and contrast-enhanced time-resolved MRA in combination (area under receiver operating characteristic curve?= 1, P??=?1, P? Show less
Rojas-Villabona, A.; Sokolska, M.; Solbach, T.; Grieve, J.; Rega, M.; Torrealdea, F.; ... ; Jager, H.R. 2021
PurposeIntra-arterial Digital Subtraction Angiography (DSA) is the gold standard technique for radiosurgery target delineation in brain Arterio-Venous Malformations (AVMs). This study aims to... Show morePurposeIntra-arterial Digital Subtraction Angiography (DSA) is the gold standard technique for radiosurgery target delineation in brain Arterio-Venous Malformations (AVMs). This study aims to evaluate whether a combination of three Magnetic Resonance Angiography sequences (triple-MRA) could be used for delineation of brain AVMs for Gamma Knife Radiosurgery (GKR).MethodsFifteen patients undergoing DSA for GKR targeting of brain AVMs also underwent triple-MRA: 4D Arterial Spin Labelling based angiography (ASL-MRA), Contrast-Enhanced Time-Resolved MRA (CE-MRA) and High Definition post-contrast Time-Of-Flight angiography (HD-TOF). The arterial phase of the AVM nidus was delineated on triple-MRA by an interventional neuroradiologist and a consultant neurosurgeon (triple-MRA volume). Triple-MRA volumes were compared to AVM targets delineated by the clinical team for delivery of GKR using the current planning paradigm, i.e., stereotactic DSA and volumetric MRI (DSA volume). Difference in size, degree of inclusion (DI) and concordance index (CcI) between DSA and triple-MRA volumes are reported.ResultsAVM target volumes delineated on triple-MRA were on average 9.8% smaller than DSA volumes (95%CI:5.6-13.9%; SD:7.14%; p = .003). DI of DSA volume in triple-MRA volume was on average 73.5% (95%CI:71.2-76; range: 65-80%). The mean percentage of triple-MRA volume not included on DSA volume was 18% (95%CI:14.7-21.3; range: 7-30%).ConclusionThe technical feasibility of using triple-MRA for visualisation and delineation of brain AVMs for GKR planning has been demonstrated. Tighter and more precise delineation of AVM target volumes could be achieved by using triple-MRA for radiosurgery targeting. However, further research is required to ascertain the impact this may have in obliteration rates and side effects. Show less
In the 1980's some of the earliest studies of arterial spin labeling (ASL) MRI have demonstrated its ability to generate MR angiography (MRA) images. Thanks to many technical improvements, ASL has... Show moreIn the 1980's some of the earliest studies of arterial spin labeling (ASL) MRI have demonstrated its ability to generate MR angiography (MRA) images. Thanks to many technical improvements, ASL has been success-fully moving its position from the realm of research into the clinical area, albeit more known as perfusion imaging than as MRA. For MRA imaging, other techniques such as time-of-flight, phase contrast MRA and contrast-enhanced (CE) MRA are more popular choices for clinical applications. In the last decade, however, ASL-MRA has been experiencing a remarkable revival, especially because of its non-invasive nature, i.e. the fact that it does not rely on the use of contrast agent. Very importantly, there are additional benefits of using ASL for MRA. For example, its higher flexibility to achieve both high spatial and temporal resolution than CE dynamic MRA, and the capability of vessel specific visualization, in which the vascular tree arising from a selected artery can be exclusively visualized. In this article, the implementation and recent developments of ASI,-based MRA are discussed; not only focusing on the basic sequences based upon pulsed ASL or pseudo-continuous ASL, but also including more recent labeling approaches, such as vessel-selective labeling, velocity-selective ASL, vessel-encoded ASL and time-encoded ASL. Although these ASL techniques have been already utilized in perfusion imaging and their usefulness has been suggested by many studies, some additional considerations should be made when employing them for MRA, since there is something more than the difference of the spatial resolution of the readout sequence. Moreover, extensive discussion is included on what readout sequence to use, especially by highlighting how to achieve high spatial resolution while keeping scan-time reasonable such that the ASL-MRA sequence can easily be included into a clinical examination. 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
Barbour, S.J.; Coppo, R.; Zhang, H.; Liu, Z.H.; Suzuki, Y.; Matsuzaki, K.; ... ; Int IgA Nephropathy Network 2019
ImportanceAlthough IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, there is no validated tool to predict disease progression. This limits patient-specific risk... Show moreImportanceAlthough IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, there is no validated tool to predict disease progression. This limits patient-specific risk stratification and treatment decisions, clinical trial recruitment, and biomarker validation. ObjectiveTo derive and externally validate a prediction model for disease progression in IgAN that can be applied at the time of kidney biopsy in multiple ethnic groups worldwide. Design, Setting, and ParticipantsWe derived and externally validated a prediction model using clinical and histologic risk factors that are readily available in clinical practice. Large, multi-ethnic cohorts of adults with biopsy-proven IgAN were included from Europe, North America, China, and Japan. Main Outcomes and MeasuresCox proportional hazards models were used to analyze the risk of a 50% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease, and were evaluated using the R-D(2) measure, Akaike information criterion (AIC), C statistic, continuous net reclassification improvement (NRI), integrated discrimination improvement (IDI), and calibration plots. ResultsThe study included 3927 patients; mean age, 35.4 (interquartile range, 28.0-45.4) years; and 2173 (55.3%) were men. The following prediction models were created in a derivation cohort of 2781 patients: a clinical model that included eGFR, blood pressure, and proteinuria at biopsy; and 2 full models that also contained the MEST histologic score, age, medication use, and either racial/ethnic characteristics (white, Japanese, or Chinese) or no racial/ethnic characteristics, to allow application in other ethnic groups. Compared with the clinical model, the full models with and without race/ethnicity had better R-D(2) (26.3% and 25.3%, respectively, vs 20.3%) and AIC (6338 and 6379, respectively, vs 6485), significant increases in C statistic from 0.78 to 0.82 and 0.81, respectively (Delta C, 0.04; 95% CI, 0.03-0.04 and Delta C, 0.03; 95% CI, 0.02-0.03, respectively), and significant improvement in reclassification as assessed by the NRI (0.18; 95% CI, 0.07-0.29 and 0.51; 95% CI, 0.39-0.62, respectively) and IDI (0.07; 95% CI, 0.06-0.08 and 0.06; 95% CI, 0.05-0.06, respectively). External validation was performed in a cohort of 1146 patients. For both full models, the C statistics (0.82; 95% CI, 0.81-0.83 with race/ethnicity; 0.81; 95% CI, 0.80-0.82 without race/ethnicity) and R-D(2) (both 35.3%) were similar or better than in the validation cohort, with excellent calibration. Conclusions and RelevanceIn this study, the 2 full prediction models were shown to be accurate and validated methods for predicting disease progression and patient risk stratification in IgAN in multi-ethnic cohorts, with additional applications to clinical trial design and biomarker research. Show less
Suzuki, Y.; Okell, T.W.; Fujima, N.; Osch, M.J.P. van 2019
Purpose: The recently introduced "Acquisition of ConTRol and labEled imaging in the Same Shot" (ACTRESS) approach was designed to halve the scan time of arterial spin labeling (ASL) -based 4D-MRA... Show morePurpose: The recently introduced "Acquisition of ConTRol and labEled imaging in the Same Shot" (ACTRESS) approach was designed to halve the scan time of arterial spin labeling (ASL) -based 4D-MRA by obtaining both labeled and control images in a single Look-Locker readout. However, application for vessel-selective labeling remains difficult. The aim of this study was to achieve a combination of ACTRESS and vessel-selective labeling to halve the scan time of vessel-selective 4D-MRA.Methods: By Bloch equation simulations, Look-I,ocker pseudocontinuous-ASE, (pCASL) was optimized to achieve constant static tissue signal across the multidelay readout, which is essential for the ACTRESS approach. Additionally, a new subtraction scheme was proposed to achieve visualization of the inflow phase even when labeled blood will have already arrived in the distal arteries during the first phase acquisition due to the long duration of the pCASL labeling module. In vivo studies were performed to investigate the signal variation of the static tissue, as well as to assess image quality of vessel-selective 4D-MRA with ACTRESS.Results: in in vivo studies, the mean signal variation of the static tissue was 8.98% over the Look-Locker phases, thereby minimizing the elevation of background signal. This allowed visualization of peripheral arteries and slowly arriving arterial blood with image quality as good as conventional pCASL, within half the acquisition time. Vesselselective pCASL-ACTRESS enabled the separated visualization of vessels arising from internal and external carotid arteries within this shortened acquisition time.Conclusion: By combining vessel-selective pCASL and ACTRESS approach, 4D-MRA of a single targeted arterial tree was achieved in a few minutes. Show less
BackgroundThe Hemiptera (aphids, cicadas, and true bugs) are a key insect order, with high diversity for feeding ecology and excellent experimental tractability for molecular genetics. Building... Show moreBackgroundThe Hemiptera (aphids, cicadas, and true bugs) are a key insect order, with high diversity for feeding ecology and excellent experimental tractability for molecular genetics. Building upon recent sequencing of hemipteran pests such as phloem-feeding aphids and blood-feeding bed bugs, we present the genome sequence and comparative analyses centered on the milkweed bug Oncopeltus fasciatus, a seed feeder of the family Lygaeidae.ResultsThe 926-Mb Oncopeltus genome is well represented by the current assembly and official gene set. We use our genomic and RNA-seq data not only to characterize the protein-coding gene repertoire and perform isoform-specific RNAi, but also to elucidate patterns of molecular evolution and physiology. We find ongoing, lineage-specific expansion and diversification of repressive C2H2 zinc finger proteins. The discovery of intron gain and turnover specific to the Hemiptera also prompted the evaluation of lineage and genome size as predictors of gene structure evolution. Furthermore, we identify enzymatic gains and losses that correlate with feeding biology, particularly for reductions associated with derived, fluid nutrition feeding.ConclusionsWith the milkweed bug, we now have a critical mass of sequenced species for a hemimetabolous insect order and close outgroup to the Holometabola, substantially improving the diversity of insect genomics. We thereby define commonalities among the Hemiptera and delve into how hemipteran genomes reflect distinct feeding ecologies. Given Oncopeltus's strength as an experimental model, these new sequence resources bolster the foundation for molecular research and highlight technical considerations for the analysis of medium-sized invertebrate genomes. Show less
Suzuki, Y.; Okell, T.W.; Chappell, M.A.; Osch, M.J.P. van 2019
Purpose: When using simultaneous multi-slice (SMS) EPI for background suppressed (BGS) arterial spin labeling (ASL), correction of through-plane motion could introduce artefacts, because the slices... Show morePurpose: When using simultaneous multi-slice (SMS) EPI for background suppressed (BGS) arterial spin labeling (ASL), correction of through-plane motion could introduce artefacts, because the slices with most effective BGS are adjacent to slices with the least BGS. In this study, a new framework is presented to correct for such artefacts.Methods: The proposed framework consists of 3 steps: (1) homogenization of the static tissue signal over the different slices to eliminate most inter-slice differences because of different levels of BGS, (2) application of motion correction, and (3) extraction of a perfusion-weighted signal using a general linear model. The proposed framework was evaluated by simulations and a functional ASL study with intentional head motion.Results: Simulation studies demonstrated that the strong signal differences between slices with the most and least effective BGS caused sub-optimal estimation of motion parameters when through-plane motion was present. Although use of the M-0 image as the reference for registration allowed 82% improvement of motion estimation for through-plane motion, it still led to residual subtraction errors caused by different static tissue signal between control and label because of different BGS levels. By using our proposed framework, those problems were minimized, and the accuracy of CBF estimation was improved. Moreover, the functional ASL study showed improved detection of visual and motor activation when applying the framework as compared to conventional motion correction, as well as when motion correction was completely omitted.Conclusion: When combining BGS-ASL with SMS-EPI, particular attention is needed to avoid artefacts introduced by motion correction. With the proposed framework, these issues are minimized. Show less
For many cerebrovascular diseases, visualization of blood flow through the large vasculature, as well as quantitative information on tissue perfusion, is very important. Arterial Spin labelling ... Show moreFor many cerebrovascular diseases, visualization of blood flow through the large vasculature, as well as quantitative information on tissue perfusion, is very important. Arterial Spin labelling (ASL) magnetic resonance (MR) imaging enables the visualization of arterial flow by labelling the magnetization of arterial blood using radiofrequency pulses. The labelled arterial blood acts as an endogenous tracer and allows, which can avoid the reliance on the use of contrast agents. In this doctoral thesis, several new techniques for dynamic MR angiography and perfusion imaging were developed based on ASL techniques, which include pulsed ASL, pseudo-continuous ASL (pCASL), vessel-encoded pCASL, time-encoded pCASL as well as simultaneous multi-slice pCASL. The underlying motivation of these development is to reduce the burden on patients by employing non-invasive ASL techniques as potential alternatives to X-ray digital subtraction angiography, contrast-enhanced MR angiography and perfusion imaging. In each study, the optimum ASL techniques was carefully chosen by considering the pros and cons of the technique to achieve better clinical usability, while improving robustness against potential artifacts. Show less
Osch, M.J.P. van; Teeuwisse, W.M.; Chen, Z.S.; Suzuki, Y.; Helle, M.; Schmid, S. 2018
