Ultra-long-TE arterial spin labeling reveals rapid and brain-wide blood-to-CSF water transport in humans

The study of brain clearance mechanisms is an active area of research. While we know that the cerebrospinal fluid (CSF) plays a central role in one of the main existing clearance pathways, the exact processes for the secretion of CSF and the removal of waste products from tissue are under debate. CSF is thought to be created by the exchange of water and ions from the blood, which is believed to mainly occur in the choroid plexus. This exchange has not been thoroughly studied in vivo. We propose a modified arterial spin labeling (ASL) MRI sequence and image analysis to track blood water as it is transported to the CSF, and to characterize its exchange from blood to CSF. We acquired six pseudo-continuous ASL sequences with varying labeling duration (LD) and post-labeling delay (PLD) and a segmented 3D-GRASE readout with a long echo train (8 echo times (TE)) which allowed separation of the very long-T2 CSF signal. ASL signal was observed at long TEs (793 ms and higher), indicating presence of labeled water transported from blood to CSF. This signal appeared both in the CSF proximal to the choroid plexus and in the subarachnoid space surrounding the cortex. ASL signal was separated into its blood, gray matter and CSF components by fitting a triexponential function with T2s taken from literature. A two-compartment dynamic model was introduced to describe the exchange of water through time and TE. From this, a water exchange time from the blood to the CSF (Tbl->CSF) was mapped, with an order of magnitude of approximately 60 s

Combining T-2 measurements and crusher gradients into a single ASL sequence for comparison of the measurement of water transport across the blood-brain barrier

Purpose Arterial spin labeling can be used to assess the transition time of water molecules across the blood-brain barrier when combined with sequence modules, which allow a separation of intravascular from tissue signal. The bipolar gradient technique measures the intravascular fraction by removing flowing spins. The T-2-relaxation-under-spin-tagging (TRUST) technique modulates the TE to differentiate between intravascular and extravascular spins based on T-2. These modules were combined into a single time-encoded pseudo-continuous arterial spin labeling sequence to compare their mechanisms of action as well as their assessment of water transition across the blood-brain barrier.Methods This protocol was acquired on a scanner with 9 healthy volunteers who provided written, informed consent. The sequence consisted of a Hadamard-encoded pseudo-continuous arterial spin labeling module, followed by the TRUST module (effective TEs of 0, 40, and 80 ms) and bipolar flow-crushing gradients (2, 4, and infinity cm/s). An additional experiment was performed with TRUST and a 3D gradient and spin-echo readout.Results Gradients imperfectly canceled the intravascular signal, as evidenced by the presence of residual signal in the arteries at early postlabeling delays as well as the underestimation of the intravascular fraction as compared with the TRUST method. The TRUST module allowed us to detect the transport of water deeper into the vascular tree through changes in T-2 than the used crusher gradients could, with their limited b-value.Conclusion Of the implemented techniques, TRUST allowed us to follow intravascular signal deeper into the vascular tree than the approach with (relatively weak) crusher gradients when quantifying the transport time of water across the blood-brain barrier.Neuro Imaging Researc

Arterial spin labeling signal in the CSF: implications for partial volume correction and blood-CSF barrier characterization

For better quantification of perfusion with arterial spin labeling (ASL), partial volume correction (PVC) is used to disentangle the signals from gray matter (GM) and white matter within any voxel. Based on physiological considerations, PVC algorithms typically assume zero signal in the cerebrospinal fluid (CSF). Recent measurements, however, have shown that CSF-ASL signal can exceed 10% of GM signal, even when using recommended ASL labeling parameters. CSF signal is expected to particularly affect PVC results in the choroid plexus. This study aims to measure the impact of CSF signal on PVC perfusion measurements, and to investigate the potential use of PVC to retrieve pure CSF-ASL signal for blood-CSF barrier characterization. In vivo imaging included six pCASL sequences with variable label duration and post-labeling delay (PLD), and an eight-echo 3D-GRASE readout. A dataset was simulated to estimate the effect of CSF-PVC with known ground-truth parameters. Differences between the results of CSF-PVC and non-CSF-PVC were estimated for regions of interest (ROls) based on GM probability, and a separate ROI isolating the choroid plexus. In vivo, the suitability of PVC-CSF signal as an estimate of pure CSF was investigated by comparing its time course with the long-TE CSF signal. Results from both simulation and in vivo data indicated that including the CSF signal in PVC improves quantification of GM CBF by approximately 10%. In simulated data, this improvement was greater for multi-PLD (model fitting) quantification than for single PLD (similar to 1-5% difference). In the choroid plexus, the difference between CSF-PVC and non-CSF-PVC was much larger, averaging around 30%. Long-TE (pure) CSF signal could not be estimated from PVC CSF signal as it followed a different time course, indicating the presence of residual macrovascular signal in the PVC. The inclusion of CSF adds value to PVC for more accurate measurements of GM perfusion, and especially for quantification of perfusion in the choroid plexus and study of the glymphatic system.Radiolog

A split-label design for simultaneous measurements of perfusion in distant slices by pulsed arterial spin labeling

Purpose Multislice arterial spin labeling (ASL) MRI acquisitions are currently challenging in skeletal muscle because of long transit times, translating into low-perfusion SNR in distal slices when large spatial coverage is required. However, fiber type and oxidative capacity vary along the length of healthy muscles, calling for multislice acquisitions in clinical studies. We propose a new variant of flow alternating inversion recovery (FAIR) that generates sufficient ASL signal to monitor exercise-induced perfusion changes in muscle in two distant slices.Methods Label around and between two 7-cm distant slices was created by applying the presaturation/postsaturation and selective inversion modules selectively to each slice (split-label multislice FAIR). Images were acquired using simultaneous multislice EPI. We validated our approach in the brain to take advantage of the high resting-state perfusion, and applied it in the lower leg muscle during and after exercise, interleaved with a single-slice FAIR as a reference.Results We show that standard multislice FAIR leads to an underestimation of perfusion, while the proposed split-label multislice approach shows good agreement with separate single-slice FAIR acquisitions in brain, as well as in muscle following exercise.Conclusion Split-label FAIR allows measuring muscle perfusion in two distant slices simultaneously without losing sensitivity in the distal slice.Cardiovascular Aspects of RadiologyNeuro Imaging Researc

Optimized cervical spinal cord perfusion MRI after traumatic injury in the rat

Despite the potential to guide clinical management of spinal cord injury and disease, noninvasive methods of monitoring perfusion status of the spinal cord clinically remain an unmet need. In this study, we optimized pseudo-continuous arterial spin labeling (pCASL) for the rodent cervical spinal cord and demonstrate its utility in identifying perfusion deficits in an acute contusion injury model. High-resolution perfusion sagittal images with reduced imaging artifacts were obtained with optimized background suppression and imaging readout. Following moderate contusion injury, perfusion was clearly and reliably decreased at the site of injury. Implementation of time-encoded pCASL confirmed injury site perfusion deficits with blood flow measurements corrected for variability in arterial transit times. The noninvasive protocol of pCASL in the spinal cord can be utilized in future applications to examine perfusion changes after therapeutic interventions in the rat and translation to patients may offer critical implications for patient management.Neuro Imaging Researc

Ultra-long-TE arterial spin labeling reveals rapid and brain-wide blood-to-CSF water transport in humans

The study of brain clearance mechanisms is an active area of research. While we know that the cerebrospinal fluid (CSF) plays a central role in one of the main existing clearance pathways, the exact processes for the secretion of CSF and the removal of waste products from tissue are under debate. CSF is thought to be created by the exchange of water and ions from the blood, which is believed to mainly occur in the choroid plexus. This exchange has not been thoroughly studied in vivo.We propose a modified arterial spin labeling (ASL) MRI sequence and image analysis to track blood water as it is transported to the CSF, and to characterize its exchange from blood to CSF. We acquired six pseudo-continuous ASL sequences with varying labeling duration (LD) and post-labeling delay (PLD) and a segmented 3D-GRASE readout with a long echo train (8 echo times (TE)) which allowed separation of the very long-T-2 CSF signal. ASL signal was observed at long TEs (793 ms and higher), indicating presence of labeled water transported from blood to CSF. This signal appeared both in the CSF proximal to the choroid plexus and in the subarachnoid space surrounding the cortex. ASL signal was separated into its blood, gray matter and CSF components by fitting a triexponential function with T(2)s taken from literature. A two-compartment dynamic model was introduced to describe the exchange of water through time and TE. From this, a water exchange time from the blood to the CSF (Tbl->CSF) was mapped, with an order of magnitude of approximately 60 s.Neuro Imaging Researc

ISMRM Open Science Initiative for Perfusion Imaging (OSIPI): ASL pipeline inventory

Purpose: To create an inventory of image processing pipelines of arterial spin labeling (ASL) and list their main features, and to evaluate the capability, flexibility, and ease of use of publicly available pipelines to guide novice ASL users in selecting their optimal pipeline. Methods: Developers self-assessed their pipelines using a questionnaire developed by the Task Force 1.1 of the ISMRM Open Science Initiative for Perfusion Imaging. Additionally, each publicly available pipeline was evaluated by two independent testers with basic ASL experience using a scoring system created for this purpose. Results: The developers of 21 pipelines filled the questionnaire. Most pipelines are free for noncommercial use (n = 18) and work with the standard NIfTI (Neuroimaging Informatics Technology Initiative) data format (n = 15). All pipelines can process standard 3D single postlabeling delay pseudo-continuous ASL images and primarily differ in their support of advanced sequences and features. The publicly available pipelines (n = 9) were included in the independent testing, all of them being free for noncommercial use. The pipelines, in general, provided a trade-off between ease of use and flexibility for configuring advanced processing options. Conclusion: Although most ASL pipelines can process the common ASL data types, only some (namely, ASLPrep, ASLtbx, BASIL/Quantiphyse, ExploreASL, and MRICloud) are well-documented, publicly available, support multiple ASL types, have a user-friendly interface, and can provide a useful starting point for ASL processing. The choice of an optimal pipeline should be driven by specific data to be processed and user experience, and can be guided by the information provided in this ASL inventory

Dependency of R-2 and R-2* relaxation on Gd-DTPA concentration in arterial blood: influence of hematocrit and magnetic field strength

Dynamic susceptibility contrast (DSC) MRI is clinically used to measure brain perfusion by monitoring the dynamic passage of a bolus of contrast agent through the brain. For quantitative analysis of the DSC images, the arterial input function is required. It is known that the original assumption of a linear relation between the R-2((*)) relaxation and the arterial contrast agent concentration is invalid, although the exact relation is as of yet unknown. Studying this relation in vitro is time-consuming, because of the widespread variations in field strengths, MRI sequences, contrast agents, and physiological conditions. This study aims to simulate the R-2((*)) versus contrast concentration relation under varying physiological and technical conditions using an adapted version of an open-source simulation tool. The approach was validated with previously acquired data in human whole blood at 1.5 T by means of a gradient-echo sequence (proof-of-concept). Subsequently, the impact of hematocrit, field strength, and oxygen saturation on this relation was studied for both gradient-echo and spin-echo sequences. The results show that for both gradient-echo and spin-echo sequences, the relaxivity increases with hematocrit and field strength, while the hematocrit dependency was nonlinear for both types of MRI sequences. By contrast, oxygen saturation has only a minor effect. In conclusion, the simulation setup has proven to be an efficient method to rapidly calibrate and estimate the relation between R-2((*)) and gadolinium concentration in whole blood. This knowledge will be useful in future clinical work to more accurately retrieve quantitative information on brain perfusion.Cardiovascular Aspects of Radiolog

Multi-organ comparison of flow-based arterial spin labeling techniques: spatially non-selective labeling for cerebral and renal perfusion imaging

Purpose Flow-based arterial spin labeling (ASL) techniques provide a transit-time insensitive alternative to the more conventional spatially selective ASL techniques. However, it is not clear which flow-based ASL technique performs best and also, how these techniques perform outside the brain (taking into account eg, flow-dynamics, field-inhomogeneity, and organ motion). In the current study we aimed to compare 4 flow-based ASL techniques (ie, velocity selective ASL, acceleration selective ASL, multiple velocity selective saturation ASL, and velocity selective inversion prepared ASL [VSI-ASL]) to the current spatially selective reference techniques in brain (ie, pseudo-continuous ASL [pCASL]) and kidney (ie, pCASL and flow alternating inversion recovery [FAIR]).Methods Brain (n = 5) and kidney (n = 6) scans were performed in healthy subjects at 3T. Perfusion-weighted signal (PWS) maps were generated and ASL techniques were compared based on temporal SNR (tSNR), sensitivity to perfusion changes using a visual stimulus (brain) and robustness to respiratory motion by comparing scans acquired in paced-breathing and free-breathing (kidney).Results In brain, all flow-based ASL techniques showed similar tSNR as pCASL, but only VSI-ASL showed similar sensitivity to perfusion changes. In kidney, all flow-based ASL techniques had comparable tSNR, although all lower than FAIR. In addition, VSI-ASL showed a sensitivity to B-1-inhomogeneity. All ASL techniques were relatively robust to respiratory motion.Conclusion In both brain and kidney, flow-based ASL techniques provide a planning-free and transit-time insensitive alternative to spatially selective ASL techniques. VSI-ASL shows the most potential overall, showing similar performance as the golden standard pCASL in brain. However, in kidney, a reduction of B-1-sensitivity of VSI-ASL is necessary to match the performance of FAIR.Neuro Imaging Researc

Waist circumference and risk of elevated blood pressure in children: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Increasing childhood obesity has become a major health threat. This cross-sectional study reports associations between schoolchildren's waist circumference (WC) and risk of elevated blood pressure.</p> <p>Methods</p> <p>We measured height, weight, neck and waist circumference, and blood pressure in regular health examinations among children in grade 1 (ages 6-7 years) at six elementary schools in Taipei County, Taiwan. Elevated blood pressure was defined in children found to have mean systolic or diastolic blood pressure greater than or equal to the gender-, age-, and height-percentile-specific 95th-percentile blood pressure value.</p> <p>Results</p> <p>All 2,334 schoolchildren were examined (response rate was 100% in the six schools). The mean of systolic and diastolic blood pressure increased as WC quartiles increased (p < 0.0001). The prevalence of elevated blood pressure for boys and girls within the fourth quartile of waist circumference was 38.9% and 26.8%, respectively. In the multivariate logistic regression analyses, the adjusted odds ratios of elevated blood pressure were 1.78 (95% confidence interval [CI] = 1.13-2.80), 2.45 (95% CI = 1.56-3.85), and 6.03 (95% CI = 3.59-10.1) for children in the second, third, and fourth waist circumference quartiles compared with the first quartile. The odds ratios for per-unit increase and per increase of standard deviation associated with elevated blood pressure were 1.14 (95% CI = 1.10-1.18) and 2.22 (95% CI = 1.76-2.78), respectively.</p> <p>Conclusions</p> <p>Elevated blood pressure in children was associated with waist circumference. Not only is waist circumference easier to measure than blood pressure, but it also provides important information on metabolic risk. Further research is needed on effective interventions to identify and monitor children with increased waist circumference to reduce metabolic and blood pressure risks.</p