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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 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.

Autosomal dominant Alzheimer's disease (ADAD) is a small subset of Alzheimer's disease that is genetically determined with 100% penetrance. It provides a valuable window into studying the course of pathologic processes that leads to dementia. Arterial spin labeling (ASL) MRI is a potential AD imaging marker that non-invasively measures cerebral perfusion. In this study, we investigated the relationship of cerebral blood flow measured by pseudo-continuous ASL (pCASL) MRI with measures of cerebral metabolism (FDG PET) and amyloid deposition (Pittsburgh Compound B (PiB) PET). Thirty-one participants at risk for ADAD (age 39 ± 13 years, 19 females) were recruited into this study, and 21 of them received both MRI and FDG and PiB PET scans. Considerable variability was observed in regional correlations between ASL-CBF and FDG across subjects. Both regional hypo-perfusion and hypo-metabolism were associated with amyloid deposition. Cross-sectional analyses of each biomarker as a function of the estimated years to expected dementia diagnosis indicated an inverse relationship of both perfusion and glucose metabolism with amyloid deposition during AD development. These findings indicate that neurovascular dysfunction is associated with amyloid pathology, and also indicate that ASL CBF may serve as a sensitive early biomarker for AD. The direct comparison among the three biomarkers provides complementary information for understanding the pathophysiological process of AD.

PurposeTo identify potential biomarkers of the renal impairment in lupus nephritis using a multi-parametric renal quantitative MRI (qMRI) protocol including diffusion weighted imaging (DWI), blood oxygen level dependent (BOLD), arterial spin labeling (ASL) and T1rho MRI between a cohort of healthy volunteers and lupus nephritis (LN) patients.Materials and methodsThe renal qMRI protocol was performed twice with repositioning in between on 10 LN patients and 10 matched controls at 1.5 T. Navigator-gated and breath-hold acquisitions followed by non-rigid image registration were used to control respiratory motion. The repeatability of the 4 MRI modalities was evaluated with the intra-class correlation coefficient (ICC) and within-subject coefficient of variation (wsCV). Unpaired t-test and stepwise logistic regression were carried out to evaluate qMRI parameters between the LN and control groups.ResultsThe reproducibility of the 4 qMRI modalities ranged from moderate to good (ICC=0.4-0.91, wsCV≤12%) with a few exceptions. T1rho MRI and ASL renal blood flow (RBF) demonstrated significant differences between the LN and control groups. Stepwise logistic regression yielded only one significant parameter (medullar T1rho) in differentiating LN from control groups with 95% accuracy.ConclusionA reasonable degree of test-retest repeatability and accuracy of a multi-parametric renal qMRI protocol has been demonstrated in healthy volunteers and LN subjects. T1rho and ASL RBF are promising imaging biomarkers of LN.

PurposeTo investigate the reliability and accuracy of two pseudo-continuous arterial spin labeling (pCASL) sequences, using two-dimensional (2D) gradient-echo echo planar imaging (EPI) and 3D gradient and spin echo (GRASE) as the readout, respectively.Materials and methodsEach sequence was performed twice 4 weeks apart on six normal control subjects, six elderly subjects with mild cognitive impairment (MCI), and one participant with Alzheimer's disease (AD). Eight of these subjects also underwent H2 (15) O positron emission tomography (PET) scans on the same day or proximal to their second MRI scan. The longitudinal repeatability of EPI and GRASE pCASL were evaluated with the intraclass correlation coefficient (ICC) and within-subject coefficient of variation (wsCV).ResultsThe ICCs of global perfusion measurements were 0.697 and 0.413 for GRASE and EPI based pCASL respectively. GRASE pCASL also demonstrated a higher longitudinal repeatability for regional perfusion measurements across 24 regions-of-interests (ICC = 0.707; wsCV = 10.9%) compared with EPI pCASL (ICC = 0.362; wsCV = 15.3%). When compared with PET, EPI pCASL showed a higher degree of spatial correlation with PET than GRASE pCASL, although the difference was not statistically significant.ConclusionThe 3D GRASE pCASL offers better repeatability than 2D EPI pCASL, thereby may provide a reliable imaging marker for the evaluation of disease progression and treatment effects in MCI and early AD subjects.

PurposeThe goal of this study was to introduce a new noncontrast enhanced 4D dynamic MR angiography (dMRA) technique termed multibolus TrueFISP-based spin tagging with alternating radiofrequency (TrueSTAR).MethodsMultibolus TrueFISP-based spin tagging with alternating radiofrequency was developed by taking advantage of the phenomenon that the steady-state signal of TrueFISP is minimally disturbed by periodically inserted magnetization preparations (e.g., spin tagging) that are sandwiched by two α/2 RF pulses. Both theoretical analysis and experimental studies were carried out to optimize the proposed method which was compared with both pulsed and pseudo-continuous arterial spin labeling-based dMRA in healthy volunteers. Optimized multibolus dMRA was also applied in a patient with arteriovenous malformation to demonstrate its potential clinical utility.ResultsMultibolus dMRA offered a prolonged tagging bolus compared to the standard single-bolus dMRA, and allowed improved visualization of the draining veins in the arteriovenous malformation patient. Compared to pseudo-continuous arterial spin labeling-based dMRA, multibolus dMRA provided visualization of the full passage of the labeled blood with the flexibility for both static and dynamic magnetic resonance angiography.ConclusionBy combining the benefits of pulsed and pseudo-continuous arterial spin labeling-based dMRA, multibolus TrueFISP-based spin tagging with alternating radiofrequency can prolong and enhance the tagging bolus without sacrificing imaging speed or temporal resolution.

Resistance training is a promising strategy to promote healthy cognitive aging; however, the brain mechanisms by which resistance training benefits cognition have yet to be determined. Here, we examined the effects of a 12-week resistance training program on resting brain activity and cerebrovascular function in 20 healthy older adults (14 females, mean age 69.1 years). In this single group clinical trial, multimodal 3 T magnetic resonance imaging was performed at 3 time points: baseline (preceding a 12-week control period), pre-intervention, and post-intervention. Along with significant improvements in fluid cognition (d = 1.27), 4 significant voxelwise clusters were identified for decreases in resting brain activity after the intervention (Cerebellum, Right Middle Temporal Gyrus, Left Inferior Parietal Lobule, and Right Inferior Parietal Lobule), but none were identified for changes in resting cerebral blood flow. Using a separate region of interest approach, we provide estimates for improved cerebral blood flow, compared with declines over the initial control period, in regions associated with cognitive impairment, such as hippocampal blood flow (d = 0.40), and posterior cingulate blood flow (d = 0.61). Finally, resistance training had a small countermeasure effect on the age-related progression of white matter lesion volume (rank-biserial = −0.22), a biomarker of cerebrovascular disease. These proof-of-concept data support larger trials to determine whether resistance training can attenuate or even reverse salient neurodegenerative processes. [ABSTRACT FROM AUTHOR]

Purpose: To optimize pseudo‐continuous arterial spin labeling (pCASL) for 7 T, and to further improve the labeling efficiency with parallel RF transmission transmit B1 (B1+) shimming. Methods: pCASL parameters were optimized based on B1+/B0 field distributions at 7 T with simulation. To increase labeling efficiency, the B1+ amplitude at inflowing arteries was increased with parallel RF transmission B1+ shimming. The "indv‐shim" with shimming weights calculated for each individual subject, and the "univ‐shim" with universal weights calculated on a group of 12 subjects, were compared with circular polarized (CP) shim. The optimized pCASL sequences with three B1+ shimming modes (indv‐shim, univ‐shim, and CP‐shim) were evaluated in 6 subjects who underwent two repeated scans 24 hours apart, along with a pulsed ASL sequence. Quantitative metrics including mean B1+ amplitude, perfusion, and intraclass correlation coefficient were calculated. The optimized 7T pCASL was compared with standard 3T pCASL on 5 subjects, using spatial SNR and temporal SNR. Results: The optimal pCASL parameter set (RF duration/gap = 300/250 us, Gave=0.6mT/m,gRatio=10) achieved robust perfusion measurement in the presence of B1+/B0 inhomogeneities. Both indv‐shim and univ‐shim significantly increased B1+ amplitude compared with CP‐shim in simulation and in vivo experiment (P <.01). Compared with CP‐shim, perfusion signal was increased by 9.5% with indv‐shim (P <.05) and by 5.3% with univ‐shim (P =.35). All three pCASL sequences achieved fair to good repeatability (intraclass correlation coefficient ≥ 0.5). Compared with 3T pCASL, the optimized 7T pCASL achieved 78.3% higher spatial SNR and 200% higher temporal SNR. Conclusion: The optimized pCASL achieved robust perfusion imaging at 7 T, while both indv‐shim and univ‐shim further increased labeling efficiency. [ABSTRACT FROM AUTHOR]

Purpose: Characterizing vessel territories can provide crucial information for evaluation of cerebrovascular disorders. In this study, we present a novel postprocessing pipeline for vascular territorial imaging of cerebral arteries based on a noncontrast enhanced time‐resolved 4D magnetic resonance angiography (MRA). Methods: Eight healthy participants, 1 Moyamoya patient, and 1 arteriovenous malformations patient were recruited. Territorial segmentation and relative blood flow rate calculations of cerebral arteries including left and right middle cerebral arteries and left and right posterior cerebral arteries were carried out based on the 4D MRA‐derived arterial arrival time maps of intracranial vessels. Results: Among healthy young subjects, the average relative blood flow rate values corresponding to left and right middle cerebral arteries and left and right posterior cerebral arteries were 35.9 ± 5.9%, 32.9 ± 7.5%, 15.4 ± 3.8%, and 15.9 ± 2.5%, respectively. Excellent agreement was observed between relative blood flow rate values obtained from the proposed 4D MRA‐based method and reference 2D phase contrast MRI. Abnormal cerebral circulations were visualized and quantified on both patients using the developed technique. Conclusion: The vascular territorial imaging technique developed in this study allowed for the generation of territorial maps with user‐defined level of details within a clinically feasible scan time, and as such may provide useful information to assess cerebral circulation balance in different pathologies. [ABSTRACT FROM AUTHOR]

Cerebral small vessel disease (cSVD) affects arterioles, capillaries, and venules and can lead to cognitive impairments and clinical symptomatology of vascular cognitive impairment and dementia (VCID). VCID symptoms are similar to Alzheimer's disease (AD) but the neurophysiologic alterations are less well studied, resulting in no established biomarkers. The purpose of this study was to evaluate cerebral blood flow (CBF) measured by 3D pseudo-continuous arterial spin labeling (pCASL) as a potential biomarker of VCID in a cohort of elderly Latinx subjects at risk of cSVD. Forty-five elderly Latinx subjects (12 males, 69 ± 7 years) underwent repeated MRI scans ∼6 weeks apart. CBF was measured using 3D pCASL in the whole brain, white matter and 4 main vascular territories (leptomeningeal anterior, middle, and posterior cerebral artery (leptoACA, leptoMCA, leptoPCA), as well as MCA perforator). The test-retest repeatability of CBF was assessed by intra-class correlation coefficient (ICC) and within-subject coefficient of variation (wsCV). Absolute and relative CBF was correlated with gross cognitive measures and domain specific assessment of executive and memory function, vascular risks, and Fazekas scores and volumes of white matter hyperintensity (WMH). Neurocognitive evaluations were performed using Montreal Cognitive Assessment (MoCA) and neuropsychological test battery in the Uniform Data Set v3 (UDS3). Good to excellent test-retest repeatability was achieved (ICC = 0.77–0.85, wsCV 3–9%) for CBF measurements in the whole brain, white matter, and 4 vascular territories. Relative CBF normalized by global mean CBF in the leptoMCA territory was positively correlated with the executive function composite score, while relative CBF in the leptoMCA and MCA perforator territory was positively correlated with MoCA scores, controlling for age, gender, years of education, and testing language. Relative CBF in WM was negatively correlated with WMH volume and MoCA scores, while relative leptoMCA CBF was positively correlated with WMH volume. Reliable 3D pCASL CBF measurements were achieved in the cohort of elderly Latinx subjects. Relative CBF in the leptomeningeal and perforator MCA territories were the most likely candidate biomarker of VCID. These findings need to be replicated in larger cohorts with greater variability of stages of cSVD. [ABSTRACT FROM AUTHOR]

Background: Arterial spin labeling (ASL) based-noncontrast-enhanced 4D MR angiography (NCE 4D MRA) shows potential in characterizing cerebrovascular hemodynamics in cerebrovascular disorders. Ultrahigh-field theoretically benefits ASL signal with increased inherent signal-to-noise ratio (SNR) and prolonged blood T1 , which may provide improved delineation of vasculature in 4D MRA.Purpose: To investigate the feasibility of NCE 4D MRA using 3D Cartesian trajectory and stack-of-stars (SOS) golden angle radial trajectory at 7T.Study Type: A prospective study.Subjects: Six normal volunteers and eight patients with arteriovenous malformation (AVM).Field Strength/sequence: NCE 4D MRA with Cartesian and radial trajectories were performed at 3T and 7T.Assessment: Subjective image quality of 4D MRA was evaluated using a 4-point scale by two experienced neuroradiologists. The characterization of AVM components with 4D MRA and DSA was also graded using the Spetzler-Martin grading scale.Statistical Tests: Cohen's kappa coefficient was calculated to evaluate the agreement between two readers within each 4D MRA technique (Cartesian and Radial). A Wilcoxon signed-rank test was performed to compare the subjective image quality scores of 4D MRA between Cartesian and radial trajectories, and between 7T and 3T, respectively.Results: Good-to-excellent image quality was achieved in 4D MRA with both Cartesian (3.83 ± 0.41) and radial (3.42 ± 0.49) acquisitions in healthy volunteers at 7T. However, markedly reduced scan time was needed with radial acquisition. 4D MRA at 7T (3.31 ± 0.59) shows better delineation of AVM lesion features, especially the vein drainage, compared with that of 3T (2.83 ± 0.75), although no statistical significance was achieved (P = 0.180).Data Conclusion: The feasibility of ASL based 4D MRA at 7T with Cartesian and SOS golden angle radial acquisition was demonstrated. The clinical evaluation of 4D MRA in AVMs between 3T and 7T suggested 7T 4D MRA images acquired with radial acquisition demonstrate excellent delineation of AVM features, especially the draining veins.Level Of Evidence: 2 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2017. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the feasibility and performance of compressed sensing (CS) with magnitude subtraction regularization in accelerating non-contrast-enhanced dynamic intracranial MR angiography (NCE-dMRA). Methods A CS algorithm was introduced in NCE-dMRA by exploiting the sparsity of the magnitude difference of the control and label images. The NCE-dMRA data were acquired using golden-angle stack-of-stars trajectory on six healthy volunteers and one patient with arteriovenous fistula. Images were reconstructed using (i) the proposed magnitude-subtraction CS (MS-CS); (ii) complex-subtraction CS; (iii) independent CS; and (iv) view-sharing with k-space weighted image contrast (KWIC). The dMRA image quality was compared across the four reconstruction strategies. The proposed MS-CS method was further compared with KWIC for temporal fidelity of depicting dynamic flow. Results The proposed MS-CS method was able to reconstruct NCE-dMRA images with detailed vascular structures and clean background. It provided better subjective image quality than the other two CS strategies ( P < 0.05). Compared with KWIC, MS-CS showed similar image quality, but reduced temporal blurring in delineating the fine distal arteries. Conclusions The MS-CS method is a promising CS technique for accelerating NCE-dMRA acquisition without compromising image quality and temporal fidelity. Magn Reson Med 79:867-878, 2018. © 2017 International Society for Magnetic Resonance in Medicine. [ABSTRACT FROM AUTHOR]

A new technique is introduced in this study for in vivo measurement of arterial cerebral blood volume by combining arterial spin labeling with a segmented multiphase balanced steady-state free precession (bSSFP) readout sequence. This technique takes advantage of the phenomenon that the longitudinal magnetization of flowing blood is not or only marginally disturbed (besides T1 relaxation) by the bSSFP ±α pulse train. When the blood water exchanges into tissue, it becomes quickly saturated by the bSSFP pulse train due to 0 velocity and reduced T1, T2 relaxation times. Therefore, labeled blood water behaves like an intravascular contrast agent in multiphase bSSFP scans, and can be used to quantify arterial cerebral blood volume in a similar way as dynamic susceptibility contrast MRI. Both Bloch equation simulation and in vivo experiments were carried out to demonstrate the feasibility for quantifying cerebral blood volume in arteries, arterioles, and capillaries using two variants of the proposed method. Functional MRI of visual cortex stimulation was further performed using multiphase bSSFP-based arterial spin labeling and compared with vascular-space occupancy contrast. The proposed multiphase bSSFP-based arterial spin labeling technique may allow separation of cerebral blood volume of different vascular compartments for functional MRI studies and clinical evaluation of the cerebral vasculature. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

A novel denoising algorithm termed k-space weighted image average (KWIA) was proposed to improve the signal-to-noise ratio (SNR) of dynamic MRI, such as arterial spin labeling (ASL)-based dynamic magnetic resonance angiography (dMRA) and perfusion imaging. KWIA divides the k-space of each time frame into multiple rings, the central ring of the k-space remains intact to preserve the image contrast and temporal resolution, while outer rings are progressively averaged with neighboring time frames to increase SNR. Simulations and in-vivo dMRA and multi-delay ASL studies were performed to evaluate the performance of KWIA under various MRI acquisition conditions. SNR ratios and temporal signal errors between KWIA-processed and the original data were measured. Visualization of dynamic blood flow signals as well as quantitative parametric maps were evaluated for KWIA-processed images as compared to the original images. KWIA achieved a SNR ratio of 1.73 for dMRA and 2.0 for multi-delay ASL respectively, which were in accordance with the theoretical predictions. Improved visualization of dynamic blood flow signals was demonstrated using KWIA in distal small vessels in dMRA and small brain structures in multi-delay ASL. Approximately 5% temporal errors were observed in both KWIA-processed dMRA and ASL signals. Fine anatomical features were revealed in the quantitative parametric maps of dMRA, and the residuals of model fitting were reduced for multi-delay ASL. Compared to other conventional denoising methods, KWIA is a flexible denoising algorithm that improves the SNR of ASL-based dMRA and perfusion MRI by up to 2-fold without compromising spatial and temporal resolution or quantification accuracy. • KWIA is a simple and fast post-processing denoising algorithm used for dynamic MRI. • The SNR of ASL-based dMRA and perfusion MRI can be improved by up to 2-fold. • The improved SNR enabled better visualization of dynamic blood flow signals in small vessels and fine brain structures. • KWIA was able to retain the spatial and temporal resolution and quantification accuracy. [ABSTRACT FROM AUTHOR]

• Zoomed 3D ASL technique at 7T for laminar perfusion imaging. • Quantitative CBF measurements both at baseline and during task activation. • Laminar profiles of ATT and CBF consistent with cortical microvascular density. • Two-peak CBF finger tapping activation in human motor cortex. • Predominant CBF increase in deep layers by visual spatial attention. Laminar fMRI based on BOLD and CBV contrast at ultrahigh magnetic fields has been applied for studying the dynamics of mesoscopic brain networks. However, the quantitative interpretations of BOLD/CBV fMRI results are confounded by different baseline physiology across cortical layers. Here we introduce a novel 3D zoomed pseudo-continuous arterial spin labeling (pCASL) technique at 7T that offers the capability for quantitative measurements of laminar cerebral blood flow (CBF) both at rest and during task activation with high spatial specificity and sensitivity. We found arterial transit time in superficial layers is ∼100 ms shorter than in middle/deep layers revealing the time course of labeled blood flowing from pial arteries to downstream microvasculature. Resting state CBF peaked in the middle layers which is highly consistent with microvascular density measured from human cortex specimens. Finger tapping induced a robust two-peak laminar profile of CBF increases in the superficial (somatosensory and premotor input) and deep (spinal output) layers of M1, while finger brushing task induced a weaker CBF increase in superficial layers (somatosensory input). This observation is highly consistent with reported laminar profiles of CBV activation on M1. We further demonstrated that visuospatial attention induced a predominant CBF increase in deep layers and a smaller CBF increase on top of the lower baseline CBF in superficial layers of V1 (feedback cortical input), while stimulus driven activity peaked in the middle layers (feedforward thalamic input). With the capability for quantitative CBF measurements both at baseline and during task activation, high-resolution ASL perfusion fMRI at 7T provides an important tool for in vivo assessment of neurovascular function and metabolic activities of neural circuits across cortical layers. [Display omitted] [ABSTRACT FROM AUTHOR]