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Contrast optimization in arterial spin labeling with multiple post-labeling delays for cerebrovascular assessment
Abstract
Objective
Improving the readout for arterial spin labeling with multiple post-labeling delays (multi-PLD ASL) through a flip angle (FA) sweep towards increasing contrast-to-noise ratio for long PLD images.
Methods
Images were acquired from 20 healthy subjects and 14 patients with severe, asymptomatic carotid artery stenosis (ACAS) in a 3T MRI scanner. Multi-PLD ASL images with conventional and proposed (FA sweep) readouts were acquired. For patients, magnetic resonance angiography was used to validate the multi-PLD ASL results. Perfusion values were calculated for brain regions irrigated by the main cerebral arteries and compared by analysis of variance.
Results
For healthy subjects, better contrast was obtained for long PLDs when using the proposed multi-PLD method compared to the conventional. For both methods, no hemispheric difference of perfusion was observed. For patients, the proposed method facilitated the observation of delayed tissue perfusion, which was not visible for long PLD using the conventional multi-PLD ASL.
Conclusion
We successfully assessed brain perfusion of patients with asymptomatic CAS using multi-PLD ASL with FA sweep. We were able to show subtle individual differences. Moreover, prolonged arterial transit time in patients was observed, although they were considered asymptomatic, suggesting that it may not be an adequate term to characterize them.
... To alleviate this problem, a VFA scheme can be used such that the flip angle increases during the readout to exactly compensate for the attenuation of the preceding excitation pulses, resulting in a consistent ASL signal over time. 10,22 For a SPGR readout, where the nth excitation pulse attenuates the ASL signal by a factor of cos( (n)) and (n) is the nth flip angle, the formula for such a VFA scheme can be defined using a backward recursive formula for a given maximum flip angle at the last excitation: ...
Purpose
Dynamic angiography using arterial spin labeling (ASL) can provide detailed hemodynamic information. However, the long time‐resolved readouts require small flip angles to preserve ASL signal for later timepoints, limiting SNR. By using time‐encoded ASL to generate temporal information, the readout can be shortened. Here, the SNR improvements from using larger flip angles, made possible by the shorter readout, are quantitatively investigated.
Methods
The SNR of a conventional protocol with nine Look‐Locker readouts and a 4 × 3 time‐encoded protocol with three Look‐Locker readouts (giving nine matched timepoints) were compared using simulations and in vivo data. Both protocols were compared using readouts with constant flip angles (CFAs) and variable flip angles (VFAs), where the VFA scheme was designed to produce a consistent ASL signal across readouts. Optimization of the background suppression to minimize physiological noise across readouts was also explored.
Results
The time‐encoded protocol increased in vivo SNR by 103% and 96% when using CFAs or VFAs, respectively. Use of VFAs improved SNR compared with CFAs by 25% and 21% for the conventional and time‐encoded protocols, respectively. The VFA scheme also removed signal discontinuities in the time‐encoded data. Preliminary data suggest that optimizing the background suppression could improve in vivo SNR by a further 16%.
Conclusions
Time encoding can be used to generate additional temporal information in ASL angiography. This enables the use of larger flip angles, which can double the SNR compared with a non‐time‐encoded protocol. The shortened time‐encoded readout can also lead to improved background suppression, reducing physiological noise and further improving SNR.
Accurate assessment of cerebral perfusion is vital for understanding the hemodynamic processes involved in various neurological disorders and guiding clinical decision‐making. This guidelines article provides a comprehensive overview of quantitative perfusion imaging of the brain using multi‐timepoint arterial spin labeling (ASL), along with recommendations for its acquisition and quantification. A major benefit of acquiring ASL data with multiple label durations and/or post‐labeling delays (PLDs) is being able to account for the effect of variable arterial transit time (ATT) on quantitative perfusion values and additionally visualize the spatial pattern of ATT itself, providing valuable clinical insights. Although multi‐timepoint data can be acquired in the same scan time as single‐PLD data with comparable perfusion measurement precision, its acquisition and postprocessing presents challenges beyond single‐PLD ASL, impeding widespread adoption. Building upon the 2015 ASL consensus article, this work highlights the protocol distinctions specific to multi‐timepoint ASL and provides robust recommendations for acquiring high‐quality data. Additionally, we propose an extended quantification model based on the 2015 consensus model and discuss relevant postprocessing options to enhance the analysis of multi‐timepoint ASL data. Furthermore, we review the potential clinical applications where multi‐timepoint ASL is expected to offer significant benefits. This article is part of a series published by the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group, aiming to guide and inspire the advancement and utilization of ASL beyond the scope of the 2015 consensus article.
Background:
Multidelay arterial spin labeling (ASL) is a novel perfusion method of ASL, with arterial transit time (ATT) calculated by multiple postlabeling delays to correct cerebral blood flow (CBF). We verify the accuracy of multidelay ASL in evaluating the ischemic penumbra and perfusion levels in patients with acute ischemic stroke, compared with computed tomography perfusion (CTP).
Methods:
Patients with acute ischemic stroke with anterior circulation large vessel occlusion received baseline CTP, multidelay ASL, and diffusion-weighted imaging (DWI) in succession. Multidelay ASL image was processed to reconstruct ATT, CBF without ATT correction, and CBF corrected by ATT. The consistency of hypoperfusion and ischemic penumbra volume calculated by CTP and multidelay ASL were quantified by intraclass correlation coefficient (ICC) in 2-way mixed effects, absolute agreement, and single measure. Wilcoxon signed-rank test was used to compare the difference in penumbra volume between CTP, corrected ASL, and uncorrected ASL.
Results:
Thirty patients were included. Hypoperfusion volume based on multidelay ASL with different thresholds were 117.95 (87.77-151.49) mL for corrected relative CBF<40%, 130.29 (85.99-249.37) mL for CBF corrected by ATT<20 mL·100g-1·min-1, no statistical difference (P>0.05) compared with the volume of CTP, and consistency was almost excellent (ICC, 0.91) and substantial consistent (ICC, 0.727). The volumes of ischemic penumbra were 91.00 (42.68-125.27) mL for corrected relative CBF<40%-DWI, 108.94 (62.03-150.86) mL for CBF corrected by ATT<20 mL·100 g-1·min-1-DWI, which showed no statistical difference compared with the penumbra volume of CTP (P>0.05). The consistency was excellent (ICC, 0.822) and moderate (ICC, 0.501), respectively. The volume of uncorrected relative CBF <40%-DWI was 209.57 (123.21-292.45) mL, statistically larger than corrected relative CBF <40%-DWI (P<0.001) and CTP (P<0.001). The volume of uncorrected CBF<20 mL·100g-1·min-1-DWI was 186.23 (86.56-298.22) mL, statistically larger than CBF corrected by ATT<20 mL·100g-1·min-1-DWI (P<0.001) and CTP(P<0.001).
Conclusions:
The volume of ischemic penumbra determined by CBF/DWI mismatch based on multidelay ASL is consistent with CTP. The penumbra volume calculated by CBF adjusted by ATT is more accurate.
Arterial spin labeling (ASL) is a powerful noncontrast MRI technique for evaluation of cerebral blood flow (CBF). A key parameter in single-delay ASL is the choice of postlabel delay (PLD), which refers to the timing between the labeling of arterial free water and measurement of flow into the brain. Multidelay ASL (MDASL) utilizes several PLDs to improve the accuracy of CBF calculations using arterial transit time (ATT) correction. This approach is particularly helpful in situations where ATT is unknown, including young subjects and slow-flow conditions. In this article, we discuss the technical considerations for MDASL, including labeling techniques, quantitative metrics, and technical artifacts. We then provide a practical summary of key clinical applications with real-life imaging examples in the pediatric brain, including stroke, vasculopathy, hypoxic-ischemic injury, epilepsy, migraine, tumor, infection, and metabolic disease.
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‐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.
Synopsis Arterial Spin Labeling (ASL) is a powerful technique to evaluate cerebral blood ow. To analyze hemodynamics eeects with ASL, multiples acquisitions over the time are realized, which is called multiphase ASL. In conventional multiphase ASL methods, the later phases has low contrast to noise ratio, so it becomes diicult to analyze it. This study purposes a solution to this problem, through a modulation in the acquisition ip angle. With this technique, the ip angle of all phases follows a modulation equation, so that the ASL signal over the phases becomes nearly constant. Purpose Arterial Spin Labeling (ASL) is a non-invasive method to measure perfusion quantitatively. A radiofrequency pulse labels arterial blood protons, which ow through the vascular tree and exchange water with the unlabeled brain tissue, where MR images are acquired. Usually, a single delay time (TI) between labeling and image acquisition is used. However, since arrival time varies from diierent brain regions, deening a single TI may compromise proper CBF quantiication. Multiphase ASL was proposed to overcome that issue. In this case, a set of images are acquired after diierent TIs. In conventional multiphase ASL acquisition, the contrast-to-noise ratio (CNR) decreases over the phases due the eeects of longitudinal relaxation time (T1) and multiple excitations in the image region, the contrast-to-noise ratio (CNR) decreases over the phases, so that analyzes the latter phases becomes diicult. It is especially critical to evaluate patients with cerebrovascular diseases associated with delayed arterial arrival time, such as stroke and carotid stenosis. To overcome this problem, we propose an optimization of the acquisition scheme using variable ip angle. Methods We optimized the acquisition scheme using variable ip angles determined by setting the condition that the diierence between control and labeled images were constant for all phases. In that case, ip angle for the i-th phase is given by : Simulation was performed using Matlab to investigate the eeciency of proposed method when compared to the constant ip angle implementation. Healthy adult volunteers (N=20) and patients with severe unilateral carotid stenosis (N=12) were scanned in a 3T Achieva Philips system equipped with high performance gradient system and a 32-channel head coil. Images were acquired using a GE-EPI sequence with the following parameters: TR/TE=4000/18ms, FOV=240x240mm2, matrix=64x64, slice thickness=6mm and 8 phases acquired with TIs ranging from 675ms to 2600ms and 35 ASL acquisitions.
Introduction: Patients with carotid stenosis, without history of stroke or transient ischemic attack are considered to be asymptomatic. However, many of those patients might have some degree of cognitive decline, changes in perfusion and functional connectivity that may precede clinical events suggesting a high risk for stroke. In this study, we aimed to evaluate the frequency and severity of cerebral blood flow (CBF), functional connectivity (FC) and cognitive performance abnormalities in patients with severe “asymptomatic” carotid artery stenosis (aCAS).
Methods: Fifteen patients with aCAS >70% and 15 controls were evaluated with 3T MRI, including BOLD-FMRI, Pseudo-continuous Arterial Spin Labeling and Resting-State Brain Networks. The cognitive assessment included tests for executive function, psychomotor speed, attention and memory. We used Mann-Whitney U Test to compare cognition and CBF between groups; Wilcoxon test for intragroup CBF differences; Spearman Correlation Coefficient for associations between CBF, FC and cognition.
Results: CBF maps in patients with aCAS revealed reduction in blood flow in the gray matter of temporal lobes and internal structures when compared to controls (p<0.05). The cognitive performance of patients with aCAS was lower than the control group for all measures, with significant differences in attention, mnemonic process and executive functions (p<0.05). Patients presented decreased connectivity for the fronto-temporal, salience and dorsal attentional networks (p-FDR<0.01). Additionally, we observed significant correlations (p<0.01) between salience network and the cognitive measures performed in this study.
Conclusions: Subjects with aCAS showed less expressive networks and significantly lower cognitive performance, indicating deficits in fundamental networks for the identification of relevant stimuli, neural resource coordination, and information processing. We identified preclinical abnormalities in CBF, FC and cognitive performance of patients with aCAS, suggesting that neuroimaging markers in MRI, combined with cognitive assessment, have a great potential to identify the profile of patients with high risk of stroke and cognitive decline.
Patients with asymptomatic occlusion in the internal carotid arteries (ICA) have been shown to have a better preserved hemodynamic status of the brain as compared to patients with symptoms. This study was aimed to explore the cerebral perfusion alterations in asymptomatic patients using multi-parametric arterial spin-labeling (ASL) magnetic resonance (MR) imaging. Forty-two patients diagnosed with asymptomatic ICA stenosis/occlusion were prospectively included and divided into high-grade (ultrasonographic stenosis ≥70%, N = 20) and low-grade groups (N = 22). On a 3-Tesla clinical MR scanner, pseudo-continuous ASL was performed to measure cerebral blood flow CBF, arterial transit time ATT, and flow territory. Fisher’s exact test indicates that the high-grade group has higher frequency in asymmetric ATT (p < 10⁻³) and asymmetric flow territory (p < 10⁻³) as compared to the low-grade group. The between-group difference in CBF asymmetry is marginal (p = 0.062). Logistic regression further reveals that hemispherical asymmetry in ATT and flow territory is associated with the existence of high-grade ICA stenosis (odds ratio = 12 and 21, respectively), whereas hemispherical asymmetry in CBF is not. Our data suggest that ATT and flow territory may be better predictors of asymptomatic high-grade ICA stenosis diagnosed by carotid ultrasonography than CBF.
Background and purpose:
Arterial spin-labeling MR imaging with multiple postlabeling delays has a potential to evaluate various hemodynamic parameters. To clarify whether arterial spin-labeling MR imaging can identify CBF and perfusion delay in patients with Moyamoya disease, we compared arterial spin-labeling, DSC, and (15)O-gas PET in terms of their ability to identify these parameters.
Materials and methods:
Eighteen patients with Moyamoya disease (5 men, 13 women; ages, 21-55 years) were retrospectively analyzed. CBF values of pulsed continuous arterial spin-labeling using 2 postlabeling delays (short arterial spin-labeling, 1525 ms; delayed arterial spin-labeling, 2525 ms) were compared with CBF values measured by (15)O-gas PET. All plots were divided into 2 groups by the cutoff of time-based parameters (the time of the maximum observed concentration, TTP, MTT, delay of MTT to cerebellum, and disease severity [symptomatic or not]). The ratio of 2 arterial spin-labeling CBFs (delayed arterial spin-labeling CBF to short arterial spin-labeling CBF) was compared with time-based parameters: time of the maximum observed concentration, TTP, and MTT.
Results:
The short arterial spin-labeling-CBF values were significantly correlated with the PET-CBF values (r = 0.63; P = .01). However, the short arterial spin-labeling-CBF value dropped in the regions with severe perfusion delay. The delayed arterial spin-labeling CBF overestimated PET-CBF regardless of the degree of perfusion delay. Delayed arterial spin-labeling CBF/short arterial spin-labeling CBF was well correlated with the time of the maximum observed concentration, TTP, and MTT (ρ = 0.71, 0.64, and 0.47, respectively).
Conclusions:
Arterial spin-labeling using 2 postlabeling delays may detect PET-measured true CBF and perfusion delay in patients with Moyamoya disease. Provided its theoretic basis and limitations are considered, noninvasive arterial spin-labeling could be a useful alternative for evaluating the hemodynamics of Moyamoya disease.
Carotid artery stenosis without transient ischemic attack (TIA) or stroke is considered as “asymptomatic.” However, recent studies have demonstrated that these asymptomatic carotid artery stenosis (aCAS) patients had cognitive impairment in tests of executive function, psychomotor speed, and memory, indicating that “asymptomatic” carotid stenosis may not be truly asymptomatic. In this study, when 19 aCAS patients compared with 24 healthy controls, aCAS patients showed significantly poorer performance on global cognition, memory, and executive function. By utilizing an integrated MRI including pulsed arterial spin labeling (pASL) MRI, Proton MR Spectroscopy (MRS), and resting-state functional MRI (R-fMRI), we also found that aCAS patients suffered decreased cerebral blood flow (CBF) mainly in the Left Frontal Gyrus and had decreased NAA/Cr ratio in the left hippocampus and decreased connectivity to the posterior cingulate cortex (PCC) in the anterior part of default mode network (DMN).
Background and purpose:
Multi-delay arterial spin-labeling (ASL) perfusion imaging has been used as a promising modality to evaluate cerebral perfusion. Our aim was to assess the association of leptomeningeal collateral perfusion scores based on ASL parameters with outcome of endovascular treatment in patients with acute ischemic stroke (AIS) in the middle cerebral artery (MCA) territory.
Materials and methods:
ASL data at 4 post-labeling delay (PLD) times (PLD = 1.5, 2, 2.5, 3 s) were acquired during routine clinical magnetic resonance examination on AIS patients prior to endovascular treatment. A 3-point scale of leptomeningeal collateral perfusion grade on 10 anatomic regions was determined based on arterial transit times (ATT), cerebral blood flow (CBF), and arterial cerebral blood volume (CBV), estimated by the multi-delay ASL protocol. Based on a 90-day modified Rankin Scale (mRS), the patients were dichotomized to moderate/good (mRS 0-3) and poor outcome (mRS 4-6) and the regional collateral flow scores were compared.
Results:
Fifty-five AIS patients with unilateral MCA stroke (mean 73.95±14.82 years) including 23 males were enrolled. Compared with poor outcome patients, patients with moderate to good outcomes had a significantly higher leptomeningeal collateral perfusion scores on CBV (3.01±2.11 vs. 1.82±1.51, p=0.024) but no differences on scores on CBF (2.31±1.61 vs. 1.66±1.32, p=0.231) and ATT (2.67±2.33 vs. 3.42±3.37, p=0.593).
Conclusions:
Higher leptomeningeal collateral perfusion scores on CBV images by ASL may be a specific marker of clinical outcome after endovascular treatment in patients with acute MCA ischemic stroke. Further study with larger sample size is warranted.
Arterial transit time (ATT) is most crucial for measuring absolute cerebral blood flow (CBF) by arterial spin labeling (ASL), a noninvasive magnetic resonance (MR) perfusion assessment technique, in patients with chronic occlusive cerebrovascular disease. We validated ASL-CBF and ASL-ATT maps calculated by pulsed continuous ASL (pCASL) with multiple post-label delay acquisitions in patients with occlusive cerebrovascular disease. Fifteen patients underwent MR scans, including pCASL, and positron emission tomography (PET) scans with 15O-water to obtain PET-CBF. MR acquisitions with different post-label delays (1.0, 1.5, 2.0, 2.5 and 3.0 sec) were also obtained for ATT correction. The theoretical framework of 2-compartmental model (2CM) was also used for the delay compensation. ASL-CBF and ASL-ATT were calculated based on the proposed 2CM, and the effect on the CBF values and the ATT correction characteristics were discussed. Linear regression analyses were performed both on pixel-by-pixel and region-of-interest bases in the middle cerebral artery (MCA) territory. There were significant correlations between ASL-CBF and PET-CBF both for voxel values (r = 0.74 ± 0.08, slope: 0.87 ± 0.22, intercept: 6.1 ± 4.9) and for the MCA territorial comparison in both affected (R2 = 0.67, y = 0.83x + 6.3) and contralateral sides (R2 = 0.66, y = 0.74x + 6.3). ASL-ATTs in the affected side were significantly longer than those in the contralateral side (1.51 ± 0.41 sec and 1.12 ± 0.30 sec, respectively, p <0.0005). CBF measurement using pCASL with delay compensation was feasible and fairly accurate even in altered hemodynamic states.
PurposeTo measure cerebral blood flow (CBF) using Look–Locker arterial spin labeling (ASL) in children under 1 year of age and to investigate the advantages of using subject-specific estimates of ASL model parameters in this population.Materials and Methods
Of 12 scanned infants, we successfully acquired CBF maps in 7 (postmenstrual age: 32 to 78 weeks) using a Look–Locker ASL scheme and both adult literature-derived and subject-specific model parameters. ASL global CBF measurements were compared with independent global CBF measurements obtained in the same scanning session using phase-contrast angiography.ResultsMeasured global CBF values ranged from 24 to 56 mL/100g/min in the scanned infants, increasing significantly with postmenstrual age (ρSpearman = 0.89, P-value = 0.01). Using subject-specific model parameters yielded CBF estimates in significantly better agreement with phase-contrast angiography values (P-value: 0.80) than when standard adult parameters were used (P-value: 0.04).Conclusion
Look–Locker ASL can be used to measure CBF in infants and its accuracy is improved with the use of infant-specific auxiliary parameters, particularly blood and tissue T1, which were much more variable in the imaged infants in than adults. J. Magn. Reson. Imaging 2014. © 2014 Wiley Periodicals, Inc.
The aim of this study was to systematically review CBF studies, assess their methodological quality, and identify trends in the association between task-related brain activation patterns and CBF changes in ischemic stroke (IS) patients. We searched the MEDLINE, EMBASE, CINAHL, and Web of Sciences databases for studies of functional recovery with quantification of CBF responses to brain activation paradigms after IS. Titles, abstracts and full text of articles were scrutinised according to pre-defined selection criteria. Two independent reviewers (AS, VH) undertook the methodological quality screening and data extraction of the included studies. Sixteen of the 1,521 identified studies were relevant. Studies showed weaknesses in key methodological criteria (e.g. population size, discussion of limitations), and only seven studies compared responses with a control population. Overall, there was no agreement between CBF responses in either the affected or unaffected hemisphere and prediction of post-IS recovery. Some studies have shown a higher CBF increase in the unaffected hemisphere when the affected hemisphere was stimulated compared to the healthy control responses. However, CBF responses in the affected hemisphere were inconsistent. Many post-IS CBF studies are of poor methodological quality, and do not demonstrate a consistent response post-IS or a relationship with recovery. Further longitudinal studies assessing the natural history of CBF responses to brain paradigms following IS should be undertaken to determine prognostic significance, and to inform future therapeutic strategies.
A number of two-compartment models have been developed for the analysis of arterial spin labeling (ASL) data, from which both cerebral blood flow (CBF) and capillary permeability-surface product (PS) can be estimated. To derive values of PS, the volume fraction of the ASL signal arising from the intravascular space (v(bw)) must be known a priori. We examined the use of diffusion-weighted imaging (DWI) and subsequent analysis using the intravoxel incoherent motion model to determine v(bw) in the human brain. These data were then used in a two-compartment ASL model to estimate PS. Imaging was performed in 10 healthy adult subjects, and repeated in five subjects to test reproducibility. In gray matter (excluding large arteries), mean voxel-wise v(bw) was 2.3±0.2 mL blood/100 g tissue (all subjects mean±s.d.), and CBF and PS were 44±5 and 108±2 mL per 100 g per minute, respectively. After spatial smoothing using a 6-mm full width at half maximum Gaussian kernel, the coefficient of repeatability of CBF, v(bw) and PS were 8 mL per 100 g per minute, 0.4 mL blood/100 g tissue, and 13 mL per 100 g per minute, respectively. Our results show that the combined use of ASL and DWI can provide a new, noninvasive methodology for estimating v(bw) and PS directly, with reproducibility that is sufficient for clinical use.Journal of Cerebral Blood Flow & Metabolism advance online publication, 19 September 2012; doi:10.1038/jcbfm.2012.125.
To compare arterial transit time estimates from two efficient transit time mapping techniques using arterial spin labeling (ASL)-flow encoded arterial spin tagging (FEAST) and Look-Locker ASL (LL-ASL). The effects of bipolar gradients and label location were investigated.
Six healthy subjects were scanned with pseudo-continuous ASL (pCASL) FEAST and pulsed (PASL) and pCASL variants of LL-ASL at different labeling locations with and without bipolar gradients. Application of transit time mapping was demonstrated in a clinical case.
Mean (±SD) macrovascular transit times were 363 ± 39, 676 ± 73 and 908 ± 170 ms for LL-PASL, LL-pCASL with labeling offsets of 60 and 90 mm respectively, showing linear dependence on labeling locations. Mean microvascular transit time for LL-pCASL was 1,463±135 ms, in good agreement with the FEAST estimate of 1,444 ± 128 ms. Data acquired from a patient with stroke demonstrate how transit time and CBF maps provide complementary information for clinical diagnosis.
Both FEAST and LL-ASL provide transit time information in clinically acceptable scan times. Bipolar gradients can be used to tailor transit time estimates for different experimental and clinical situations.
Our purpose was to use multiple inflow pulsed ASL to investigate whether hemodynamic AAT information is sensitive to hemispheric asymmetry in acute ischemia. The cohorts included 15 patients with acute minor stroke or TIA and 15 age-matched controls. Patients were scanned by using a stroke MR imaging protocol at a median time of 74 hours. DWI lesion volumes were small and functional impairment was low; however, perfusion abnormalities were evident. Prolonged AAT values were more likely to reside in the affected hemisphere (significant when compared with controls, P < .048). An advantage of this ASL technique is the ability to use AAT information in addition to CBF to characterize ischemia.
Relative mean transit time (MTT) is readily obtainable from dynamic susceptibility contrast MRI of the brain. While it has received much attention in acute ischemic stroke as a possible means to identify patients for reperfusion therapies, little has been done to determine if it has clinical significance outside the acute setting. To determine if relative MTT could be used to identify patients who are at high risk for subsequent stroke, we analyzed data from the St. Louis Carotid Occlusion Study. This prospective study was carried out from 1992-1997 to determine if PET measurement of oxygen extraction fraction could identify medically treated patients with recently symptomatic carotid artery occlusion at high risk for subsequent stroke. Sixty-eight of the participants in the study had quantitative PET measurements of cerebral blood flow (CBF) and cerebral blood volume (CBV). From these we calculated the MTT (CBV/CBF) in each middle cerebral artery territory and determined the MTT ratio of the ipsilateral to the contralateral hemisphere (I/C MTT ratio). Nine of the 68 participants had a subsequent ipsilateral ischemic stroke during mean follow-up of 2.6 years (range .5 - 5 years). The I/C MTT ratio was significantly associated with subsequent stroke as a continuous variable by Cox regression analysis (HR 65, 95%CI 7-613, p < .001). The maximum combination of sensitivity (.778) and specificity (.763) was obtained with a cutpoint of ≥ 1.387 which identified 7/9 subsequent strokes (PPV .333, NPV .957). Relative MTT shows great promise as a means to identify patients with large artery disease who are at high risk for subsequent stoke. These results need to be confirmed using MRI in a cohort receiving contemporary medical management.
Purpose:
Applications of intravoxel incoherent motion (IVIM) imaging in the brain are scarce, whereas it has been successfully applied in other organs with promising results. To better understand the cerebral IVIM signal, the diffusion properties of the arterial blood flow within different parts of the cerebral vascular tree (i.e., different generations of the branching pattern) were isolated and measured by employing an arterial spin labeling (ASL) preparation module before an IVIM readout.
Methods:
ASL preparation was achieved by T1 -adjusted time-encoded pseudo-continuous ASL (te-pCASL). The IVIM readout module was achieved by introducing bipolar gradients immediately after the excitation pulse. The results of ASL-IVIM were compared with those of conventional IVIM to improve our understanding of the signal generation process of IVIM.
Results:
The pseudo-diffusion coefficient D* as calculated from ASL-IVIM data was found to decrease exponentially for postlabeling delays (PLDs) between 883 ms and 2176 ms, becoming relatively stable for PLDs longer than 2176 ms. The fast compartment of the conventional IVIM-experiment shows comparable apparent diffusion values to the ASL signal with PLDs between 1747 ms and 2176 ms. At the longest PLDs, the observed D* values (4.0 ± 2.8 × 10(-3) mm(2) /s) are approximately 4.5 times higher than the slow compartment (0.90 ± 0.05 × 10(-3) mm(2) /s) of the conventional IVIM experiment.
Conclusion:
This study showed much more complicated diffusion properties of vascular signal than the conventionally assumed single D* of the perfusion compartment in the two-compartment model of IVIM (biexponential behavior). Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine.
Background:
Intracranial arterial stenosis (ICAS) is a predominant cause of ischemic stroke in Asia. Changes in the signal intensities (SIs) across ICAS lesions on time-of-flight magnetic resonance angiography (TOF-MRA) have been indicated to partially reflect the hemodynamic significance of the lesions, which we aimed to verify by correlating it with cerebral perfusion features provided by CT perfusion (CTP) imaging.
Methods:
Ischemic stroke or transient ischemic attack patients with unilateral symptomatic stenosis (≥50%) of intracranial internal carotid artery or middle cerebral artery (MCA) were included in this study. Change of SIs across an ICAS lesion on TOF-MRA was calculated by the distal and proximal SI ratio (SIR). Cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) within the MCA territory of ipsilateral and contralateral hemispheres were evaluated on the CTP images at the basal ganglia level. Relative CBV, CBF and MTT were defined as ratios of the values obtained from ipsilateral and contralateral hemispheres. The relationships between SIR and CTP parameters were analyzed.
Results:
Fifty subjects (74% male, mean age 62) were recruited. Overall, the mean SIR was 0.77 ± 0.17. SIR of ICAS was significantly, linearly and negatively correlated with ipsilateral CBV (r = -0.335, p = 0.017), ipsilateral MTT (r = -0.301, p = 0.034), and ipsilateral/contralateral MTT ratio (r = -0.443, p = 0.001).
Conclusions:
Diminished SIs distal to ICAS on TOF-MRA might be associated with delayed ipsilateral cerebral perfusion. Changes of the SIs across ICAS lesions on TOF-MRA may be a simple marker to reflect cerebral perfusion changes in patients with symptomatic ICAS.
Atherosclerosis carotid stenosis is associated with stroke and cognitive impairment. Progressive cognitive decline may be an even greater problem than stroke, but it has not been widely recognized and therefore must be adequately addressed. Although both Carotid Endarterectomy (CEA) and Carotid Artery Stenting (CAS) have been proven can prevent future stroke in patients with atherosclerotic carotid stenosis, the influence of CEA and CAS on cognitive function is not clear. In the first part of this review, we evaluated the literature concerning carotid stenosis and the risk of cognitive impairment. Studies have suggested that both symptomatic and asymptomatic carotid stenosis are associated with cognitive impairment. In the second part, we reviewed the impact of CEA and CAS on cognitive function, some studies have shown benefits, but others have not.
Background:
Mean transit time (MTT) measurements to assess cerebral hemodynamics are easily obtained by computed tomography and magnetic resonance imaging. We reviewed hemodynamic and clinical outcome data from the St. Louis Carotid Occlusion Study to determine if increased MTT was associated with an increased risk of stroke in patients with symptomatic complete carotid artery occlusion.
Methods:
Positron emission tomography (PET) studies of cerebral blood volume-to-cerebral blood flow ratios were used to calculate MTTs. Mean ipsilateral (side of the occluded internal carotid artery)-to-contralateral ratios of MTTs in the middle cerebral artery territories were determined. MTT was tested as a predictor of stroke risk using Cox regression analysis. Receiver operating characteristic curves for stroke risk prediction were generated by varying the mean ispilateral-to-contralateral MTT ratio to identify an optimal cutpoint.
Results:
Increased MTT ratio was associated with an increased risk of ipsilateral stroke (P < .001). The maximum combination of sensitivity (.778) and specificity (.763) was obtained at a cutpoint ratio of 1.387 or higher. Subjects with a MTT ratio of 1.387 or higher had a 29.3% 2-year risk of ipsilateral stroke compared to 4.6% for those without (P < .001).
Conclusions:
PET relative MTT ratio identified patients with symptomatic complete internal artery occlusion who were at high risk for subsequent ipsilateral stroke. Confirmation using measurements of relative MTT from other imaging modalities in a patient cohort receiving contemporary medical management is needed.
Purpose:
Walsh ordering of Hadamard encoding-matrices and an additional averaging strategy are proposed for Hadamard-encoded pseudocontinuous arterial spin labeling (H-pCASL). In contrast to conventional H-pCASL the proposed method generates more perfusion-weighted images which are accessible already during a running experiment and even from incomplete sets of encoded images.
Theory:
Walsh-ordered Hadamard matrices consist of fully decodable Hadamard submatrices. At any time during a measurement these submatrices may yield perfusion-weighted images, even at runtime and with incomplete datasets. The usage of an additional so-called mirrored matrix for averaging leads to more decodable subboli.
Methods:
Perfusion-weighted images (five healthy volunteers) are generated using both a Walsh-ordered and a corresponding mirrored Hadamard matrix. To test their correctness they are compared with equivalent images from conventional multi postlabeling-delay (PLD) pCASL-measurements.
Results:
All predicted perfusion-weighted images could be generated and correlated very well with multi-PLD images. Already small subsets of encoded images, acquired early during the measurement, yielded perfusion-weighted images. The mirrored matrix generates more perfusion-weighted images without time penalty.
Conclusion:
Early access to perfusion-weighted images despite incomplete datasets allows dynamic adaptation of parameters and increases robustness against artifacts. Thus, the approach may be well suited for clinical applications, where pathologies demand rapid parameter adaptation and increase the chance of artifacts. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.
Background:
Perfusion magnetic resonance image with arterial spin labeling (ASL) provides a completely noninvasive measurement of cerebral blood flow (CBF). However, arterial transient times can have a marked effect on the ASL signal. For example, a single postlabeling delay (PLD) of 1.5 seconds underestimates the slowly streaming collateral pathways that maintain the cerebrovascular reserve (CVR). To overcome this limitation, we developed a dual PLD method.
Subjects and methods:
A dual PLD method of 1.5 and 2.5 seconds was compared with (123)I-iodoamphetamine single-photon emission computed tomography with acetazolamide loading to assess CVR in 10 patients with steno-occlusive cerebrovascular disease.
Results:
In 5 cases (Group A), dual PLD-ASL demonstrated low CBF with 1.5-second PLD in the target area, whereas CBF was improved with 2.5-second PLD. In the other 5 cases (Group B), dual PLD-ASL depicted low CBF with 1.5-second PLD, and no improvement in CBF with 2.5-second PLD in the target area was observed. On single-photon emission computed tomography, CVR was maintained in Group A but decreased in Group B.
Conclusions:
Although dual PLD methods may not be a completely alternative test for (123)I-iodoamphetamine single-photon emission computed tomography with acetazolamide loading, it is a feasible, simple, noninvasive, and repeatable technique for assessing CVR, even when employed in a routine clinical setting.
Information on the water-transport across the blood-brain-barrier can be determined from the T2 of the arterial spin labeling (ASL) signal. However, the current approach of using separate acquisitions of multiple inversion times is too time-consuming for clinical (research) applications. The aim of this study was to improve the time-efficiency of this method by combining it with time encoded pseudo Continuous ASL (te-pCASL). Furthermore, the hemodynamic properties of the border zone regions in the brains of healthy, young volunteers were characterized as an example-application. The use of te-pCASL instead of multi-TI pCASL significantly reduced the total scan duration, while providing a higher temporal resolution. A significantly lower cerebral blood flow (CBF) was found in the border zone regions compared with the central regions, in both the posterior and the middle cerebral artery (MCA) flow territory. The arterial transit time (ATT) was almost two times longer in the border-zone regions than in the central regions (p<0.05), with an average delay in ATT of 382ms in the posterior and 539ms in the MCA flow territory. When corrected for the ATT, the change in T2 over time was not significantly different for the border-zones as compared to the central regions. In conclusion, te-pCASL-TRUST provided a time efficient method to distinguish spin compartments based on their T2. The ATT in the border zone is significantly longer than in the central region. However, the exchange of the label from the arterial to the tissue compartment appears to be at a similar rate.
Copyright © 2015. Published by Elsevier Inc.
In acute ischemic stroke, critical hypoperfusion is a frequent cause of hypoxic tissue injury: As cerebral blood flow (CBF) falls below the ischemic threshold of 20 mL/100 mL/min, neurological symptoms develop and hypoxic tissue injury evolves within minutes or hours unless the oxygen supply is restored. But is ischemia the only hemodynamic source of hypoxic tissue injury?
Reanalyses of the equations we traditionally use to describe the relation between CBF and tissue oxygenation suggest that capillary flow patterns are crucial for the efficient extraction of oxygen: without close capillary flow control, “functional shunts” tend to form and some of the blood’s oxygen content in effect becomes inaccessible to tissue.
This phenomenon raises several questions: Are there in fact two hemodynamic causes of tissue hypoxia: Limited blood supply (ischemia) and limited oxygen extraction due to capillary dysfunction? If so, how do we distinguish the two, experimentally and in patients? Do flow-metabolism coupling mechanisms adjust CBF to optimize tissue oxygenation when capillary dysfunction impairs oxygen extraction downstream?
Cardiovascular risk factors such as age, hypertension, diabetes, hypercholesterolemia, and smoking increase the risk of both stroke and dementia. The capillary dysfunction phenomenon therefore forces us to consider whether changes in capillary morphology or blood rheology may play a role in the etiology of some stroke subtypes and in Alzheimer’s disease.
Here, we discuss whether certain disease characteristics suggest capillary dysfunction rather than primary flow-limiting vascular pathology and how capillary dysfunction may be imaged and managed.
Arterial spin labeling (ASL) is an MRI perfusion imaging method from which quantitative cerebral blood flow (CBF) can be calculated. We present a multi-TI ASL method (multi-TI integrated ASL) in which variable post-labeling delays and variable TRs are used to improve the estimation of arterial transit time (ATT) and CBF while shortening the scan time by 41% compared to the conventional methods. Variable bolus widths allow for T1 and M0 estimation from raw ASL data. Multi-TI integrated pseudo-continuous ASL images were collected at 7 TI times ranging 100-4300ms. Voxel-wise T1 and M0 maps were estimated, then CBF and ATT maps were created using the estimated T1 tissue map. All maps were consistent with physiological values reported in the literature. Based on simulations and in vivo comparisons, this method demonstrates higher CBF and ATT estimation efficiency than other ATT acquisition methods and fits the perfusion model better. It produces CBF maps with reduced sensitivity to errors from ATT and tissue T1 variations. The estimated M0, T1, and ATT maps also have potential clinical utility. The method requires a single scan acquired within a clinically acceptable scan time (under 6 minutes) and with low sensitivity to motion.
Background and purpose:
Because of a low prevalence of severe carotid stenosis in the general population, screening for presence of asymptomatic carotid artery stenosis (ACAS) is not warranted. Possibly, for certain subgroups, screening is worthwhile. The present study aims to develop prediction rules for the presence of ACAS (>50% and >70%).
Methods:
Individual participant data from 4 population-based cohort studies (Malmö Diet and Cancer Study, Tromsø Study, Carotid Atherosclerosis Progression Study, and Cardiovascular Health Study; totaling 23 706 participants) were pooled. Multivariable logistic regression was performed to determine which variables predict presence of ACAS (>50% and >70%). Calibration and discrimination of the models were assessed, and bootstrapping was used to correct for overfitting.
Results:
Age, sex, history of vascular disease, systolic and diastolic blood pressure, total cholesterol/high-density lipoprotein ratio, diabetes mellitus, and current smoking were predictors of stenosis (>50% and >70%). The calibration of the model was good confirmed by a nonsignificant Hosmer and Lemeshow test for moderate (P=0.59) and severe stenosis (P=0.07). The models discriminated well between participants with and without stenosis, with an area under the receiver operating characteristic curve corrected for over optimism of 0.82 (95% confidence interval, 0.80-0.84) for moderate stenosis and of 0.87 (95% confidence interval, 0.85-0.90) for severe stenosis. The regression coefficients of the predictors were converted into a score chart to facilitate practical application.
Conclusions:
A clinical prediction rule was developed that allows identification of subgroups with high prevalence of moderate (>50%) and severe (>70%) ACAS. When confirmed in comparable cohorts, application of the prediction rule may lead to a reduction in the number needed to screen for ACAS.
Measurement of the cerebral blood flow (CBF) with whole-brain coverage is challenging in terms of both acquisition and quantitative analysis. In order to fit arterial spin labeling-based perfusion kinetic curves, an empirical three-parameter model which characterizes the effective impulse response function (IRF) is introduced, which allows the determination of CBF, the arterial transit time (ATT) and T1,eff . The accuracy and precision of the proposed model were compared with those of more complicated models with four or five parameters through Monte Carlo simulations. Pseudo-continuous arterial spin labeling images were acquired on a clinical 3-T scanner in 10 normal volunteers using a three-dimensional multi-shot gradient and spin echo scheme at multiple post-labeling delays to sample the kinetic curves. Voxel-wise fitting was performed using the three-parameter model and other models that contain two, four or five unknown parameters. For the two-parameter model, T1,eff values close to tissue and blood were assumed separately. Standard statistical analysis was conducted to compare these fitting models in various brain regions. The fitted results indicated that: (i) the estimated CBF values using the two-parameter model show appreciable dependence on the assumed T1,eff values; (ii) the proposed three-parameter model achieves the optimal balance between the goodness of fit and model complexity when compared among the models with explicit IRF fitting; (iii) both the two-parameter model using fixed blood T1 values for T1,eff and the three-parameter model provide reasonable fitting results. Using the proposed three-parameter model, the estimated CBF (46 ± 14 mL/100 g/min) and ATT (1.4 ± 0.3 s) values averaged from different brain regions are close to the literature reports; the estimated T1,eff values (1.9 ± 0.4 s) are higher than the tissue T1 values, possibly reflecting a contribution from the microvascular arterial blood compartment.
Carotid artery atherosclerosis may cause increased intima-media thickness (IMT), plaque formation, and vessel stenosis or occlusion. However, the association between carotid artery atherosclerosis and cognitive impairment remains uncertain. This study explored the effects of IMT and carotid artery stenosis on cognitive function in an elderly Chinese non-stroke population. A total of 2015 patients were recruited. The IMT of carotid arteries and the presence of plaques and stenosis in carotid arteries were assessed with B-mode ultrasound examination. Cognitive performance was evaluated with neuropsychological tests. The cross-sectional relationships between cognitive performance and carotid wall characteristics were analyzed. Carotid artery atherosclerosis (IMT>1.0) and stenosis were found in 86% and 51% of patients, respectively. Cognitive impairment was found in 356 (17.7%) patients. After adjustment for possible confounders, IMT (odds ratio [OR]=1.96; 95% confidence interval [CI] 1.23-3.16) and hyperdense plaque (OR=4.72; 95% CI 2.56-11.2) were associated with poor cognitive performance. Patients with severe (⩾70%) carotid artery stenosis had a lower Mini-Mental State Examination score compared with the mild to modest (40-70%) carotid artery stenosis group. Cognitive performance differed between patients with left and right carotid artery stenosis, but no differences were observed between patients with severe left and right carotid artery stenosis. This study indicates that carotid artery atherosclerosis is correlated with cognitive impairment in the elderly Chinese population. A larger sample size across multiple centers and a longitudinal study are required to further explore the impact of carotid artery atherosclerosis on cognition in the elderly population.
Arterial spin labeling (ASL) permits quantification of tissue perfusion without the use of MR contrast agents. With standard ASL techniques such as flow-sensitive alternating inversion recovery (FAIR) the signal from arterial blood is measured at a fixed inversion delay after magnetic labeling. As no image information is sampled during this delay, FAIR measurements are inefficient and time-consuming. In this work the FAIR preparation was combined with a Look-Locker acquisition to sample not one but a series of images after each labeling pulse. This new method allows monitoring of the temporal dynamics of blood inflow. To quantify perfusion, a theoretical model for the signal dynamics during the Look-Locker readout was developed and applied. Also, the imaging parameters of the new ITS-FAIR technique were optimized using an expression for the variance of the calculated perfusion. For the given scanner hardware the parameters were: temporal resolution 100 ms, 23 images, flip-angle 25.4°. In a normal volunteer experiment with these parameters an average perfusion value of 48.2 ± 12.1 ml/100 g/min was measured in the brain. With the ability to obtain ITS-FAIR time series with high temporal resolution arterial transit times in the range of −138 − 1054 ms were measured, where nonphysical negative values were found in voxels containing large vessels. Magn Reson Med 46:974–984, 2001. © 2001 Wiley-Liss, Inc.
Measurement of tissue perfusion is important for the functional assessment of organs in vivo. Here we report the use of 1H NMR imaging to generate perfusion maps in the rat brain at 4.7 T. Blood water flowing to the brain is saturated in the neck region with a sliceselective saturation imaging sequence, creating an endogenous tracer in the form of proximally saturated spins. Because proton T1 times are relatively long, particularly at high field strengths, saturated spins exchange with bulk water in the brain and a steady state is created where the regional concentration of saturated spins is determined by the regional blood flow and regional T1. Distal saturation applied equidistantly outside the brain serves as a control for effects of the saturation pulses. Average cerebral blood flow in normocapnic rat brain under halothane anesthesia was determined to be 105 ± 16 cc. 100 g−1. min−1 (mean ± SEM, n = 3), in good agreement with values reported in the literature, and was sensitive to increases in arterial pCO2. This technique allows regional perfusion maps to be measured noninvasively, with the resolution of 1H MRI, and should be readily applicable to human studies. © 1992 Academic Press, Inc.
Variational Bayes (VB) has been proposed as a method to facilitate calculations of the posterior distributions for linear models, by providing a fast method for Bayesian inference by estimating the parameters of a factorized approximation to the posterior distribution. Here a VB method for nonlinear forward models with Gaussian additive noise is presented. In the case of noninformative priors the parameter estimates obtained from this VB approach are identical to those found via nonlinear least squares. However, the advantage of the VB method lies in its Bayesian formulation, which permits prior information to be included in a hierarchical structure and measures of uncertainty for all parameter estimates to be obtained via the posterior distribution. Unlike other Bayesian methods VB is only approximate in comparison with the sampling method of MCMC. However, the VB method is found to be comparable and the assumptions made about the form of the posterior distribution reasonable. Practically, the VB approach is substantially faster than MCMC as fewer calculations are required. Some of the advantages of the fully Bayesian nature of the method are demonstrated through the extension of the noise model and the inclusion of automatic relevance determination (ARD) within the VB algorithm.
The regional distribution, laterality, and reliability of volumetric pulsed continuous arterial spin labeling (PCASL) measurements of cerebral blood flow (CBF) in cortical, subcortical, and cerebellar regions were determined in 10 normal volunteers studied on two occasions separated by 3 to 7 days. Regional CBF, normalized for global perfusion, was highly reliable when measured on separate days. Several regions showed significant lateral asymmetry; notably, in frontal regions CBF was greater in the right than left hemisphere, whereas left was greater than right in posterior regions. There was considerable regional variability across the brain, whereby the posterior cingulate and central and posterior precuneus cortices had the highest perfusion and the globus pallidus the lowest gray matter perfusion. The latter may be due to iron-induced T1 shortening affecting labeled spins and computed CBF signal. High CBF in the posterior cingulate and posterior and central precuneus cortices in this task-free acquisition suggests high activity in these principal nodes of the "default mode network."
FSL (the FMRIB Software Library) is a comprehensive library of analysis tools for functional, structural and diffusion MRI brain imaging data, written mainly by members of the Analysis Group, FMRIB, Oxford. For this NeuroImage special issue on "20 years of fMRI" we have been asked to write about the history, developments and current status of FSL. We also include some descriptions of parts of FSL that are not well covered in the existing literature. We hope that some of this content might be of interest to users of FSL, and also maybe to new research groups considering creating, releasing and supporting new software packages for brain image analysis.
Changes in the exchange rate of water across the blood-brain barrier, denoted k(w), may indicate blood-brain barrier dysfunction before the leakage of large-molecule contrast agents is observable. A previously proposed approach for measuring k(w) is to use diffusion-weighted arterial spin labeling to measure the vascular and tissue fractions of labeled water, because the vascular-to-tissue ratio is related to k(w). However, the accuracy of diffusion-weighted arterial spin labeling is affected by arterial blood contributions and the arterial transit time (τ(a)). To address these issues, a two-stage method is proposed that uses combinations of diffusion-weighted gradient strengths and post-labeling delays to measure both τ(a) and k(w). The feasibility of this method was assessed by acquiring diffusion-weighted arterial spin labeling data from seven healthy volunteers. Repeat measurements and Monte Carlo simulations were conducted to determine the precision and accuracy of the k(w) estimates. Average grey and white matter k(w) values were 110 ± 18 and 126 ± 18 min(-1), respectively, which compare favorably to blood-brain barrier permeability measurements obtained with positron emission tomography. The intrasubject coefficient of variation was 26% ± 23% in grey matter and 21% ± 17% in white matter, indicating that reproducible k(w) measurements can be obtained.
Continuous arterial spin labeling (CASL) measurements over a range of post-labeling delay (PLD) times can be interpreted to estimate cerebral blood flow (CBF) and arterial transit time (deltaa) with good spatial and temporal resolution. In this work, we present an in vivo demonstration of Hadamard-encoded continuous arterial spin labeling (H-CASL); an efficient method of imaging the inflow of short boli of labeled blood water in the brain at multiple PLD times. We present evidence that H-CASL is viable for in vivo application in the rat brain and can improve the precision of deltaa estimation in 2/3 of the imaging time required for standard multi-PLD CASL. Based on these findings, we propose that H-CASL may have application as an efficient prescan for optimization of ASL imaging parameters to improve the precision of CBF estimation.
The purpose of this study was to establish a normal range for the arterial arrival time (AAT) in whole-brain pulsed arterial spin labeling (PASL) cerebral perfusion MRI. Healthy volunteers (N = 36, range: 20 to 35 years) provided informed consent to participate in this study. AAT was assessed in multiple brain regions, using three-dimensional gradient and spin echo (GRASE) pulsed arterial spin labeling at 3.0 T, and found to be 641 +/- 95, 804 +/- 91, 802 +/- 126, and 935 +/- 108 ms in the temporal, parietal, frontal, and occipital lobes, respectively. Mean gray matter AAT was found to be 694 +/- 89 ms for females (N = 15), which was significantly shorter than for men, 814 +/- 192 ms (N = 21; P < 0.0003), and significant after correcting for brain volume (P < 0.001). Significant AAT sex differences were also found using voxelwise permutation testing. An atlas of AAT values across the healthy brain is presented here and may be useful for future experiments that aim to quantify cerebral blood flow from ASL data, as well as for clinical comparisons where disease pathology may lead to altered AAT. Pulsed arterial spin labeling signals were simulated using an identical sampling scheme as the empiric study and revealed AAT can be estimated robustly when simulated arrival times are well beyond the normal range.
When modelling FMRI and other MRI time-series data, a Bayesian approach based on adaptive spatial smoothness priors is a compelling alternative to using a standard generalized linear model (GLM) on presmoothed data. Another benefit of the Bayesian approach is that biophysical prior information can be incorporated in a principled manner; however, this requirement for a fixed non-spatial prior on a parameter would normally preclude using spatial regularization on that same parameter. We have developed a Gaussian-process-based prior to apply adaptive spatial regularization while still ensuring that the fixed biophysical prior is correctly applied on each voxel. A parameterized covariance matrix provides separate control over the variance (the diagonal elements) and the between-voxel correlation (due to off-diagonal elements). Analysis proceeds using evidence optimization (EO), with variational Bayes (VB) updates used for some parameters. The method can also be applied to non-linear forward models by using a linear Taylor expansion centred on the latest parameter estimates. Applying the method to FMRI with a constrained haemodynamic response function (HRF) shape model shows improved fits in simulations, compared to using either the non-spatial or spatial-smoothness prior alone. We also analyse multi-inversion arterial spin labelling data using a non-linear perfusion model to estimate cerebral blood flow and bolus arrival time. By combining both types of prior information, this new prior performs consistently well across a wider range of situations than either prior alone, and provides better estimates when both types of prior information are relevant.
A technique has been developed for proton magnetic resonance imaging (MRI) of perfusion, using water as a freely diffusable tracer, and its application to the measurement of cerebral blood flow (CBF) in the rat is demonstrated. The method involves labeling the inflowing water proton spins in the arterial blood by inverting them continuously at the neck region and observing the effects of inversion on the intensity of brain MRI. Solution to the Bloch equations, modified to include the effects of flow, allows regional perfusion rates to be measured from an image with spin inversion, a control image, and a T1 image. Continuous spin inversion labeling the arterial blood water was accomplished, using principles of adiabatic fast passage by applying continuous-wave radiofrequency power in the presence of a magnetic field gradient in the direction of arterial flow. In the detection slice used to measure perfusion, whole brain CBF averaged 1.39 +/- 0.19 ml.g-1.min-1 (mean +/- SEM, n = 5). The technique's sensitivity to changes in CBF was measured by using graded hypercarbia, a condition that is known to increase brain perfusion. CBF vs. pCO2 data yield a best-fit straight line described by CBF (ml.g-1.min-1) = 0.052pCO2 (mm Hg) - 0.173, in excellent agreement with values in the literature. Finally, perfusion images of a freeze-injured rat brain have been obtained, demonstrating the technique's ability to detect regional abnormalities in perfusion.
Recently, several implementations of arterial spin labeling (ASL) techniques have been developed for producing MRI images sensitive to local tissue perfusion. For quantitation of perfusion, both pulsed and continuous labeling methods potentially suffer from a number of systematic errors. In this study, a general kinetic model for the ASL signal is described that can be used to assess these errors. With appropriate assumptions, the general model reduces to models that have been used previously to analyze ASL data, but the general model also provides a way to analyze the errors that result if these assumptions are not accurate. The model was used for an initial assessment of systematic errors due to the effects of variable transit delays from the tagging band to the imaging voxel, the effects of capillary/tissue exchange of water on the relaxation of the tag, and the effects of incomplete water extraction. In preliminary experiments with a human subject, the model provided a good description of pulsed ASL data during a simple sensorimotor activation task.
Regional perfusion imaging (RPI) has recently been introduced as a potentially powerful technique to map the perfusion territories of patients with vascular diseases in a fully noninvasive manner. However, this technique suffers from the problems of the transfer insensitive labeling technique upon which it is based. In particular, RPI is very sensitive to magnetic field inhomogeneities, and therefore the definition of the labeled bolus can deteriorate at field strength higher than 1.5 T. Furthermore, the slab-selective triple-pulse postsaturation sequence used originally will also be impaired due to the same problem, rendering RPI unusable at higher field. In this work, an adiabatic-based signal targeting with alternating radiofrequency pulses sequence is proposed as a labeling scheme to solve the problems related to variations in local magnetic field, together with an improved four-pulse water suppression enhanced through T(1) effects technique as a presaturation scheme.
This work describes a new compartmental model with step-wise temporal analysis for a Look-Locker (LL)-flow-sensitive alternating inversion-recovery (FAIR) sequence, which combines the FAIR arterial spin labeling (ASL) scheme with a LL echo planar imaging (EPI) measurement, using a multireadout EPI sequence for simultaneous perfusion and T*(2) measurements. The new model highlights the importance of accounting for the transit time of blood through the arteriolar compartment, delta, in the quantification of perfusion. The signal expected is calculated in a step-wise manner to avoid discontinuities between different compartments. The optimal LL-FAIR pulse sequence timings for the measurement of perfusion with high signal-to-noise ratio (SNR), and high temporal resolution at 1.5, 3, and 7T are presented. LL-FAIR is shown to provide better SNR per unit time compared to standard FAIR. The sequence has been used experimentally for simultaneous monitoring of perfusion, transit time, and T*(2) changes in response to a visual stimulus in four subjects. It was found that perfusion increased by 83 +/- 4% on brain activation from a resting state value of 94 +/- 13 ml/100 g/min, while T*(2) increased by 3.5 +/- 0.5%.
- M Jenkinson
- C F Beckmann
- T E Behrens
- M W Woolrich
- S M Smith
Jenkinson M, Beckmann CF, Behrens TE, Woolrich MW, Smith
SM (2012) Fsl. Neuroimage 62(2):782-790
ASL contrast optimization in multiphase STAR labeling using variable flip angle
- A M Paschoal
- R F Leoni
- A C Santos
- B U Foerster
- F F Paiva
Paschoal AM, Leoni RF, Santos AC, Foerster BU, Paiva FF (2015)
ASL contrast optimization in multiphase STAR labeling using
variable flip angle. In: 21st annual meeting of the organization
for human brain mapping, Honolulu, p 1857
Impairments in brain perfusion, metabolites, functional connectivity, and cognition in severe asymptomatic carotid stenosis patients: an integrated MRI study
- T Wang
- Xiao F Wu
- G Fang
- J Sun
- Z Feng
- H Zhang
- J Xu