Mapping water exchange across the blood-brain barrier using 3D diffusion-prepared arterial spin labeled perfusion MRI.
ABSTRACT: PURPOSE:To present a novel MR pulse sequence and modeling algorithm to quantify the water exchange rate (kw ) across the blood-brain barrier (BBB) without contrast, and to evaluate its clinical utility in a cohort of elderly subjects at risk of cerebral small vessel disease (SVD). METHODS:A diffusion preparation module with spoiling of non-Carr-Purcell-Meiboom-Gill signals was integrated with pseudo-continuous arterial spin labeling (pCASL) and 3D gradient and spin echo (GRASE) readout. The tissue/capillary fraction of the arterial spin labeling (ASL) signal was separated by appropriate diffusion weighting (b = 50 s/mm2 ). kw was quantified using a single-pass approximation (SPA) model with total generalized variation (TGV) regularization. Nineteen elderly subjects were recruited and underwent 2 MRIs to evaluate the reproducibility of the proposed technique. Correlation analysis was performed between kw and vascular risk factors, Clinical Dementia Rating (CDR) scale, neurocognitive assessments, and white matter hyperintensity (WMH). RESULTS:The capillary/tissue fraction of ASL signal can be reliably differentiated with the diffusion weighting of b = 50 s/mm2 , given ~100-fold difference between the (pseudo-)diffusion coefficients of the 2 compartments. Good reproducibility of kw measurements (intraclass correlation coefficient = 0.75) was achieved. Average kw was 105.0 ± 20.6, 109.6 ± 18.9, and 94.1 ± 19.6 min-1 for whole brain, gray and white matter. kw was increased by 28.2%/19.5% in subjects with diabetes/hypercholesterolemia. Significant correlations between kw and vascular risk factors, CDR, executive/memory function, and the Fazekas scale of WMH were observed. CONCLUSION:A diffusion prepared 3D GRASE pCASL sequence with TGV regularized SPA modeling was proposed to measure BBB water permeability noninvasively with good reproducibility. kw may serve as an imaging marker of cerebral SVD and associated cognitive impairment.
Project description:Arterial Spin Labeling (ASL) perfusion image series have recently been utilized for functional connectivity (FC) analysis in healthy volunteers and children with autism spectrum disorders (ASD). Noise reduction by using nuisance variables has been shown to be necessary to minimize potential confounding effects of head motion and physiological signals on BOLD based FC analysis. The purpose of the present study is to systematically evaluate the effectiveness of different noise reduction strategies (NRS) using nuisance variables to improve perfusion based FC analysis in two cohorts of healthy adults using state of the art 3D background-suppressed (BS) GRASE pseudo-continuous ASL (pCASL) and dual-echo 2D-EPI pCASL sequences. Five different NRS were performed in healthy volunteers to compare their performance. We then compared seed-based FC analysis using 3D BS GRASE pCASL in a cohort of 12 children with ASD (3f/9m, age 12.8 ± 1.3 years) and 13 typically developing (TD) children (1f/12m; age 13.9 ± 3 years) in conjunction with NRS. Regression of different combinations of nuisance variables affected FC analysis from a seed in the posterior cingulate cortex (PCC) to other areas of the default mode network (DMN) in both BOLD and pCASL data sets. Consistent with existing literature on BOLD-FC, we observed improved spatial specificity after physiological noise reduction and improved long-range connectivity using head movement related regressors. Furthermore, 3D BS GRASE pCASL shows much higher temporal SNR compared to dual-echo 2D-EPI pCASL and similar effects of noise reduction as those observed for BOLD. Seed-based FC analysis using 3D BS GRASE pCASL in children with ASD and TD children showed that noise reduction including physiological and motion related signals as nuisance variables is crucial for identifying altered long-range connectivity from PCC to frontal brain areas associated with ASD. This is the first study that systematically evaluated the effects of different NRS on ASL based FC analysis. 3D BS GRASE pCASL is the preferred ASL sequence for FC analysis due to its superior temporal SNR. Removing physiological noise and motion parameters is critical for detecting altered FC in neurodevelopmental disorders such as ASD.
Project description:The purpose of the present study was to present a multi-delay multi-parametric pseudo-continuous arterial spin labeling (pCASL) protocol with background suppressed 3D GRASE (gradient and spin echo) readout for perfusion imaging in acute ischemic stroke. PCASL data at 4 post-labeling delay times (PLD = 1.5, 2, 2.5, 3 s) were acquired within 4.5 min in 24 patients (mean age 79.7 ± 11.4 years; 11 men) with acute middle cerebral artery (MCA) stroke who also underwent dynamic susceptibility contrast (DSC) enhanced perfusion imaging. Arterial transit times (ATT) were estimated through the calculation of weighted delays across the 4 PLDs, which were included in the calculation of cerebral blood flow (CBF) and arterial cerebral blood volume (CBV). Mean perfusion parameters derived using pCASL and DSC were measured within MCA territories and infarct regions identified on diffusion weighted MRI. The results showed highly significant correlations between pCASL and DSC CBF measurements (r > = 0.70, p < = 0.0001) and moderately significant correlations between pCASL and DSC CBV measurements (r > = 0.45, p < = 0.027) in both MCA territories and infarct regions. ASL ATT showed correlations with DSC time to the maximum of tissue residual function (Tmax)(r = 0.66, p = 0.0005) and mean transit time (MTT)(r = 0.59, p = 0.0023) in leptomeningeal MCA territories. The present study demonstrated the feasibility for noninvasive multi-parametric perfusion imaging using ASL for acute stroke imaging.
Project description:Recent technical developments have significantly increased the signal-to-noise ratio (SNR) of arterial spin labeled (ASL) perfusion MRI. Despite this, typical ASL acquisitions still employ large voxel sizes. The purpose of this work was to implement and evaluate two ASL sequences optimized for whole-brain high-resolution perfusion imaging, combining pseudo-continuous ASL (pCASL), background suppression (BS) and 3D segmented readouts, with different in-plane k-space trajectories. Identical labeling and BS pulses were implemented for both sequences. Two segmented 3D readout schemes with different in-plane trajectories were compared: Cartesian (3D GRASE) and spiral (3D RARE Stack-Of-Spirals). High-resolution perfusion images (2 × 2 × 4?mm(3) ) were acquired in 15 young healthy volunteers with the two ASL sequences at 3 T. The quality of the perfusion maps was evaluated in terms of SNR and gray-to-white matter contrast. Point-spread-function simulations were carried out to assess the impact of readout differences on the effective resolution. The combination of pCASL, in-plane segmented 3D readouts and BS provided high-SNR high-resolution ASL perfusion images of the whole brain. Although both sequences produced excellent image quality, the 3D RARE Stack-Of-Spirals readout yielded higher temporal and spatial SNR than 3D GRASE (spatial SNR = 8.5 ± 2.8 and 3.7 ± 1.4; temporal SNR = 27.4 ± 12.5 and 15.6 ± 7.6, respectively) and decreased through-plane blurring due to its inherent oversampling of the central k-space region, its reduced effective TE and shorter total readout time, at the expense of a slight increase in the effective in-plane voxel size.
Project description:To investigate arterial spin labeling (ASL) methods for improved brain perfusion mapping. Previously, pseudo-continuous ASL (pCASL) was developed to overcome limitations inherent with conventional continuous ASL (CASL), but the control scan (null pulse) in the original method for pCASL perturbs the equilibrium magnetization, diminishing the ASL signal. Here, a new modification of pCASL, termed mpCASL is reported, in which the perturbation caused by the null pulse is reduced and perfusion mapping improved.improvements with mpCASL are demonstrated using numerical simulations and experiments. ASL signal intensity as well as contrast and reproducibility of in vivo brain perfusion images were measured in four volunteers who had MRI scans at 4 Tesla and the data compared across the labeling methods.Perfusion maps with mpCASL showed, on average, higher ASL signal intensity and higher image contrast than those from CASL or pCASL. Furthermore, mpCASL yielded better reproducibility in repeat scans than the other methods.The experimental results are consistent with the hypothesis that the new null pulse of mpCASL leads to improved brain perfusion images.
Project description:BACKGROUND:Placenta influences the health of both a woman and her fetus during pregnancy. Maternal blood supply to placenta can be measured noninvasively using arterial spin labeling (ASL). PURPOSE:To present a multidelay pseudocontinuous arterial spin labeling (pCASL) combined with a fast 3D inner-volume gradient- and spin-echo (GRASE) imaging technique to simultaneously measure placental blood flow (PBF) and arterial transit time (ATT), and to study PBF and ATT evolution with gestational age during the second trimester. The PBF values were compared with uterine arterial Doppler ultrasound to assess its potential clinical utility. STUDY TYPE:This was a prospective study. SUBJECTS:Thirty-four pregnant women. FIELD STRENGTH/SEQUENCE:Multidelay 3D inner-volume GRASE pCASL sequence on 3T MR scanners. ASSESSMENT:Subjects underwent two longitudinal MRI scans within the second trimester, conducted between 14-16 and 19-22 weeks of gestational age, respectively. Placental perfusion was measured using the free-breathing pCASL sequence at three postlabeling delays (PLDs), followed by offline motion correction and model fitting for estimation of PBF and ATT. STATISTICAL TESTS:A paired t-test was conducted to evaluate the significance of PBF/ATT variations with placental development. A two-sample t-test was conducted to evaluate the significance of PBF difference in subjects with and without early diastolic notch. RESULTS:The mean PBF and ATT for the second trimester were 111.4 ± 26.7 ml/100g/min and 1387.5 ± 88.0 msec, respectively. The average PBF increased by 10.4% (P < 0.05), while no significant change in ATT (P = 0.72) was found along gestational ages during the second trimester. PBF decreased 20.3% (P < 0.01) in subjects with early diastolic notches in ultrasound flow waveform patterns. DATA CONCLUSION:Multidelay pCASL with inner-volume 3D GRASE is promising for noninvasive assessment of PBF during pregnancy. Its clinical use for the detection of aberrations in placental function and prediction of fetal developmental disorders awaits evaluation. LEVEL OF EVIDENCE:1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1667-1676.
Project description:Resting-state brain activity has been widely investigated using blood oxygenation level dependent (BOLD) contrast techniques. However, BOLD signal changes reflect a combination of the effects of cerebral blood flow (CBF), cerebral blood volume (CBV), as well as the cerebral metabolic rate of oxygen (CMRO2). In this study, resting-state brain activation was detected and compared using the following techniques: (a) BOLD, using a gradient-echo echo planar imaging (GE-EPI) sequence; (b) CBV-weighted signal, acquired using gradient and spin echo (GRASE) based vascular space occupancy (VASO); and (c) CBF, using pseudo-continuous arterial spin labeling (pCASL). Reliable brain networks were detected using VASO and ASL, including sensorimotor, auditory, primary visual, higher visual, default mode, salience and left/right executive control networks. Differences between the resting-state activation detected with ASL, VASO and BOLD could potentially be due to the different temporal signal-to-noise ratio (tSNR) and the short post-labeling delay (PLD) in ASL, along with differences in the spin-echo readout of VASO. It is also possible that the dynamics of spontaneous fluctuations in BOLD, CBV and CBF could differ due to biological reasons, according to their location within the brain.
Project description:Arterial spin labeling (ASL) sequences that incorporate multiple postlabeling delay (PLD) times allow estimation of when arterial blood signal arrives within a region of interest. Sequences that account for such variability may improve the reliability of ASL and therefore make the technique well suited for future clinical and experimental investigations of cerebral perfusion. This study assessed the within- and between-session reproducibility of an optimized pseudo-continuous ASL (pCASL) functional magnetic resonance imaging (FMRI) sequence that incorporates multiple postlabeling delays (multi-PLD pCASL). Healthy subjects underwent four identical scans separated by 30?minutes, 1 week, and 1 month using multi-PLD pCASL to image absolute perfusion (cerebral blood flow (CBF) and arterial arrival time (AAT)) during both rest and a visual-cued motor task. We show good test-retest reliability, with strong consistency across subjects and sessions during rest (inter-session within-subject coefficient of variation: gray matter (GM) CBF=6.44%; GM AAT=2.20%). We also report high sensitivity and reproducibility during the functional task, where we show robust task-related decreases in AAT corresponding with regions of increased CBF. Importantly, these results give insight into optimal PLD selection for future investigations using single-PLD ASL to image different brain regions, and highlight the necessity of multi-PLD ASL when imaging perfusion in the whole brain.
Project description:For ASL perfusion imaging in clinical settings the current guidelines recommends pseudo-continuous arterial spin labeling with segmented 3D readout. This combination achieves the best signal to noise ratio with reasonable resolution but is prone to motion artifacts due to the segmented readout. Motion robust single-shot 3D acquisitions suffer from image blurring due to the T2 decay of the sampled signals during the long readout. To tackle this problem, we propose an accelerated 3D-GRASE sequence with a time-dependent 2D-CAIPIRINHA sampling pattern. This has several advantages: First, the single-shot echo trains are shortened by the acceleration factor; Second, the temporal incoherence between measurements is increased; And third, the coil sensitivity maps can be estimated directly from the averaged k-space data. To obtain improved perfusion images from the undersampled time series, we developed a variational image reconstruction approach employing spatio-temporal total-generalized-variation (TGV) regularization. The proposed ASL-TGV method reduced the total acquisition time, improved the motion robustness of 3D ASL data, and the image quality of the cerebral blood flow (CBF) maps compared to those by a standard segmented approach. An evaluation was performed on 5 healthy subjects including intentional movement for 2 subjects. Single-shot whole brain CBF-maps with high resolution 3.1?×?3.1?×?3 mm and image quality can be acquired in 1min 46sec. Additionally high quality CBF- and arterial transit time (ATT) -maps from single-shot multi-post-labeling delay (PLD) data can be gained with the proposed method. This method may improve the robustness of 3D ASL in clinical settings, and may be applied for perfusion fMRI.
Project description:Arterial spin labeling (ASL) perfusion-weighted imaging (PWI) by magnetic resonance imaging (MRI) has been shown to be useful for identifying asphyxiated newborns at risk of developing brain injury, whether or not therapeutic hypothermia was administered. However, this technique has been only rarely used in newborns until now, because of the challenges to obtain sufficient signal-to-noise ratio (SNR) and spatial resolution in newborns.To compare two methods of ASL-PWI (i.e., single inversion-time pulsed arterial spin labeling [single TI PASL], and pseudo-continuous arterial spin labeling [pCASL]) to assess brain perfusion in asphyxiated newborns treated with therapeutic hypothermia and in healthy newborns.We conducted a prospective cohort study of term asphyxiated newborns meeting the criteria for therapeutic hypothermia; four additional healthy term newborns were also included as controls. Each of the enrolled newborns was scanned at least once during the first month of life. Each MRI scan included conventional anatomical imaging, as well as PASL and pCASL PWI-MRI. Control and labeled images were registered separately to reduce the effect of motion artifacts. For each scan, the axial slice at the level of the basal ganglia was used for comparisons. Each scan was scored for its image quality. Quantification of whole-slice cerebral blood flow (CBF) was done afterwards using previously described formulas.A total number of 61 concomitant PASL and pCASL scans were obtained in nineteen asphyxiated newborns treated with therapeutic hypothermia and four healthy newborns. After discarding the scans with very poor image quality, 75% (46/61) remained for comparison between the two ASL methods. pCASL images presented a significantly superior image quality score compared to PASL images (p < 0.0001). Strong correlation was found between the CBF measured by PASL and pCASL (r = 0.61, p < 0.0001).This study demonstrates that both ASL methods are feasible to assess brain perfusion in healthy and sick newborns. However, pCASL might be a better choice over PASL in newborns, as pCASL perfusion maps had a superior image quality that allowed a more detailed identification of the different brain structures.
Project description:Arterial spin labeling (ASL) is a noninvasive method to measure cerebral blood flow (CBF). Arterial spin labeling is susceptible to artifact generated by head motion; this artifact is propagated through the subtraction procedure required to calculate CBF. We introduce a novel strategy for mitigating this artifact based on weighting tag/control volumes according to a noise estimate. We evaluated this strategy (DVARS weighting) in application to both pulsed ASL (PASL) and pseudo-continuous ASL (pCASL) in a cohort of normal adults (N=57). Application of DVARS weighting significantly improved test-retest repeatability as assessed by the intra-class correlation coefficient. Before the application of DVARS weighting, mean gray matter intra-class correlation (ICC) between subsequent ASL runs was 0.48 and 0.51 in PASL and pCASL, respectively. With weighting, ICC was significantly improved to 0.63 and 0.58.