Search

To present a theoretical framework that rigorously defines and analyzes key concepts and quantities for velocity selective arterial spin labeling (VSASL). An expression for the VSASL arterial delivery function is derived based on (1) labeling and saturation profiles as a function of velocity and (2) physiologically plausible approximations of changes in acceleration and velocity across the vascular system. The dependence of labeling efficiency on the amplitude and effective bolus width of the arterial delivery function is defined. Factors that affect the effective bolus width are examined, and timing requirements to minimize quantitation errors are derived. The model predicts that a flow-dependent negative bias in the effective bolus width can occur when velocity selective inversion (VSI) is used for the labeling module and velocity selective saturation (VSS) is used for the vascular crushing module. The bias can be minimized by choosing a nominal labeling cutoff velocity that is lower than the nominal cutoff velocity of the vascular crushing module. The elements of the model are specified in a general fashion such that future advances can be readily integrated. The model can facilitate further efforts to understand and characterize the performance of VSASL and provide critical theoretical insights that can be used to design future experiments and develop novel VSASL approaches.

This review article provides an overview of the current status of velocity-selective arterial spin labeling (VSASL) perfusion MRI and is part of a wider effort arising from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group. Since publication of the 2015 consensus paper on arterial spin labeling (ASL) for cerebral perfusion imaging, important advancements have been made in the field. The ASL community has, therefore, decided to provide an extended perspective on various aspects of technical development and application. Because VSASL has the potential to become a principal ASL method because of its unique advantages over traditional approaches, an in-depth discussion was warranted. VSASL labels blood based on its velocity and creates a magnetic bolus immediately proximal to the microvasculature within the imaging volume. VSASL is, therefore, insensitive to transit delay effects, in contrast to spatially selective pulsed and (pseudo-) continuous ASL approaches. Recent technical developments have improved the robustness and the labeling efficiency of VSASL, making it a potentially more favorable ASL approach in a wide range of applications where transit delay effects are of concern. In this review article, we (1) describe the concepts and theoretical basis of VSASL; (2) describe different variants of VSASL and their implementation; (3) provide recommended parameters and practices for clinical adoption; (4) describe challenges in developing and implementing VSASL; and (5) describe its current applications. As VSASL continues to undergo rapid development, the focus of this review is to summarize the fundamental concepts of VSASL, describe existing VSASL techniques and applications, and provide recommendations to help the clinical community adopt VSASL.

Purpose: Spatially-selective arterial spin labeling perfusion MRI is sensitive to arterial transit times (ATT) that can result in inaccurate perfusion quantification when ATTs are long. Velocity-selective ASL is robust to this effect because blood is labeled within the imaging region, allowing immediate label delivery. However, velocity-selective ASL cannot characterize ATTs, which can provide important clinical information. Here, we introduce a novel pulse sequence, called VESPA ASL, that combines velocity-selective and pseudo-continuous ASL to simultaneously label different pools of arterial blood for robust cerebral blood flow (CBF) and ATT measurement.Methods: The VESPA ASL sequence is similar to velocity-selective ASL, but the velocity-selective labeling is made spatially-selective and pseudo-continuous ASL is added to fill the inflow time. The choice of inflow time and other sequence settings were explored. VESPA ASL was compared to multi-delay pseudo-continuous ASL and velocity-selective ASL through simulations and test-retest experiments in healthy volunteers.Results: VESPA ASL is shown to accurately measure CBF in the presence of long ATTs, while ATTs < TI can also be measured. Measurements were similar to established ASL techniques when ATT was short. When ATT was long, VESPA ASL measured CBF more accurately than multi-delay pseudo-continuous ASL, which tended to underestimate CBF.Conclusion: VESPA ASL is a novel and robust approach to simultaneously measure CBF and ATT and offers important advantages over existing methods. It fills an important clinical need for non-invasive perfusion and transit time imaging in vascular diseases with delayed arterial transit.

Purpose: To develop a generalized signal model for dual‐module velocity‐selective arterial spin labeling (dm‐VSASL) that can integrate arbitrary saturation and inversion profiles. Theory and Methods: A recently developed mathematical framework for single‐module VSASL is extended to address the increased complexity of dm‐VSASL and to model the use of realistic velocity‐selective profiles in the label‐control and vascular crushing modules. Expressions for magnetization difference, arterial delivery functions, labeling efficiency, and cerebral blood flow (CBF) estimation error are presented. Sources of error are examined and timing requirements to minimize quantification errors are derived. Results: For ideal velocity‐selective profiles, the predicted signals match those of prior work. With realistic profiles, a CBF‐dependent estimation error can occur when velocity‐selective inversion (VSI) is used for the labeling modules and velocity‐selective saturation (VSS) is used for the vascular crushing module. The error reflects a mismatch between the leading and trailing edges of the delivery function for the second bolus and can be minimized by choosing a nominal labeling cutoff velocity that is lower than the nominal saturation cutoff velocity. In the presence of B0$$ {\mathrm{B}}_0 $$ and B1$$ {\mathrm{B}}_1 $$ inhomogeneities, the labeling efficiency of dual‐module VSI is more attenuated than that of dual‐module VSS. Conclusion: The proposed signal model will enable researchers to more accurately assess and compare the performance of realistic dm‐VSASL implementations and improve the quantification of dm‐VSASL CBF measures. [ABSTRACT FROM AUTHOR]

Purpose: To mitigate the B0/B1+ sensitivity of velocity‐selective inversion (VSI) pulse trains for velocity‐selective arterial spin labeling (VSASL) by implementing adiabatic refocusing. This approach aims to achieve artifact‐free VSI‐based perfusion imaging through single‐pair label‐control subtractions, reducing the need for the currently required four‐pair dynamic phase‐cycling (DPC) technique when using a velocity‐insensitive control. Methods: We introduce a Fourier‐transform VSI (FT‐VSI) train that incorporates sinc‐modulated hard excitation pulses with MLEV‐8‐modulated adiabatic hyperbolic secant refocusing pairs. We compare performance between this train and the standard composite refocusing train, including with and without DPC, for dual‐module VSI VSASL. We evaluate (1) simulated velocity‐selective profiles and subtraction fidelity across a broad B0/B1+ range, (2) subtraction fidelity in phantoms, and (3) image quality, artifact presence, and gray‐matter perfusion heterogeneity (as measured by the spatial coefficient of variation) in healthy human subjects. Results: Adiabatic refocusing significantly improves FT‐VSI robustness to B0/B1+ inhomogeneity for a single label‐control subtraction. Subtraction fidelity is dramatically improved in both simulation and phantoms compared with composite refocusing without DPC, and is similar compared with DPC methods. In humans, marked artifacts seen with the non‐DPC composite refocusing approach are eliminated, corroborated by significantly reduced gray‐matter heterogeneity (via lower spatial coefficient of variation values). Conclusion: A novel VSASL labeling train using adiabatic refocusing pulses for VSI was found to reduce artifacts related to B0/B1+ inhomogeneity, thereby providing an alternative to DPC and its associated limitations, which include increased vulnerability to physiological noise and motion, reduced functional MRI applicability, and suboptimal data censoring. [ABSTRACT FROM AUTHOR]

PurposeIn pulsed arterial spin labeling (PASL) methods, arterial blood is labeled by inverting a slab with uniform thickness, resulting in different temporal widths of boluses in vessels with different flow velocities. This limits the temporal resolution and signal-to-noise ratio (SNR) efficiency gains in PASL-based methods intended for high temporal resolution and SNR efficiency, such as turbo-ASL and turbo-QUASAR.Theory and methodsA novel wedge-shaped (WS) adiabatic inversion pulse is developed by adding in-plane gradient pulses to a slice-selective (SS) adiabatic inversion pulse to linearly modulate the inversion thicknesses at different locations while maintaining the adiabatic properties of the original pulse. A hyperbolic secant (HS)-based WS inversion pulse was implemented. Its performance was tested in simulations and in phantom and human experiments and compared with an SS HS inversion pulse.ResultsCompared with the SS inversion pulse, the WS inversion pulse was capable of inducing different inversion thicknesses at different locations. It could be adjusted to generate a uniform temporal width of boluses in arteries at locations with different flow velocities.ConclusionThe WS inversion pulse can be used to control the temporal widths of labeled boluses in PASL experiments. This should benefit PASL experiments by maximizing labeling duty cycle and improving temporal resolution and SNR efficiency. Magn Reson Med 76:838-847, 2016. © 2015 Wiley Periodicals, Inc.

PurposeVelocity-selective arterial spin labeling (VSASL) is theoretically insensitive to transit delay (TD) effects. However, it uses saturation instead of inversion, resulting in compromised signal to noise ratio (SNR). In this study we explore the use of multiple velocity-selective saturation (VSS) modules in VSASL (mm-VSASL) to improve SNR.MethodsTheoretical SNR efficiency improvement and optimized parameters were calculated from simulations for mm-VSASL. VSASL with two VSS modules (VSASL-2VSS) was implemented to measure cerebral blood flow in vivo, compared with conventional VSASL (VSASL-1VSS), pulsed ASL (PASL), and pseudo-continuous ASL (PCASL). TDs and bolus durations (BDs) were measured to validate the simulations and to examine the TD sensitivity of these preparations.ResultsCompared with VSASL-1VSS, VSASL-2VSS achieved a significant improvement of SNR (22.1 ± 1.9%, P = 1.7 × 10(-6) ) in vivo, consistent with a 22.7% improvement predicted from simulations. The SNR was comparable to or higher (in gray matter, P = 4.3 × 10(-3) ) than that using PCASL. VSASL was experimentally verified to have minimal TD effects.ConclusionUtilizing multiple VSS modules can improve the SNR efficiency of VSASL. Mm-VSASL may result in an SNR that is comparable to or even higher than that of PCASL in applications where long postlabeling delays are required.

The recent introduction of simultaneous multi-slice (SMS) acquisitions has enabled the acquisition of blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) data with significantly higher temporal sampling rates. In a parallel development, the use of multi-echo fMRI acquisitions in conjunction with a multi-echo independent component analysis (ME-ICA) approach has been introduced as a means to automatically distinguish functionally-related BOLD signal components from signal artifacts, with significant gains in sensitivity, statistical power, and specificity. In this work, we examine the gains that can be achieved with a combined approach in which data obtained with a multi-echo simultaneous multi-slice (MESMS) acquisition are analyzed with ME-ICA. We find that ME-ICA identifies significantly more BOLD-like components in the MESMS data as compared to data acquired with a conventional multi-echo single-slice acquisition. We demonstrate that the improved performance of MESMS derives from both an increase in the number of temporal samples and the enhanced ability to filter out high-frequency artifacts.

This review provides a summary statement of recommended implementations of arterial spin labeling (ASL) for clinical applications. It is a consensus of the ISMRM Perfusion Study Group and the European ASL in Dementia consortium, both of whom met to reach this consensus in October 2012 in Amsterdam. Although ASL continues to undergo rapid technical development, we believe that current ASL methods are robust and ready to provide useful clinical information, and that a consensus statement on recommended implementations will help the clinical community to adopt a standardized approach. In this review, we describe the major considerations and trade-offs in implementing an ASL protocol and provide specific recommendations for a standard approach. Our conclusion is that as an optimal default implementation, we recommend pseudo-continuous labeling, background suppression, a segmented three-dimensional readout without vascular crushing gradients, and calculation and presentation of both label/control difference images and cerebral blood flow in absolute units using a simplified model.

Tissue tolerance to ischemia can be achieved by noxious stimuli that are below a threshold to cause irreversible damage ('preconditioning'). Understanding the mechanisms underlying preconditioning may lead to the identification of novel therapeutic targets for diseases such as stroke. We here used the oxidative chain inhibitor 3-nitropropionic acid (NPA) to induce ischemia tolerance in a rat middle cerebral artery occlusion (MCAO) stroke model. Cerebral blood flow (CBF) and structural integrity were characterized by longitudinal magnetic resonance imaging (MRI) in combination with behavioral, histologic, and biochemical assessment of NPA-preconditioned animals and controls. Using this approach we show that the ischemia-tolerant state is characterized by a lower energy charge potential and lower CBF, indicating a reduced baseline metabolic demand, and therefore a cellular mechanism of neural protection. Blood vessel density and structural integrity were not altered by NPA treatment. When subjected to MCAO, preconditioned animals had a characteristic MRI signature consisting of enhanced CBF maintenance within the ischemic territory and intraischemic reversal of the initial cytotoxic edema, resulting in reduced infarct volumes. Thus, our data show that tissue protection through preconditioning occurs early during ischemia and indicate that a reduced cellular metabolism is associated with tissue tolerance to ischemia.

In blood-oxygenation-level-dependent functional magnetic resonance imaging (fMRI), current methods typically acquire ∼ 500,000 imaging voxels at each time point, and then use computer algorithms to reduce this data to the coefficients of a few hundred parcels or networks. This suggests that the amount of relevant information present in the fMRI signal is relatively small, and presents an opportunity to greatly improve the speed and signal to noise ratio (SNR) of the fMRI process. In this work, a theoretical framework is presented for calculating the coefficients of functional networks directly from highly undersampled fMRI data. Using predefined functional parcellations or networks and a compact k-space trajectory that samples data at optimal spatial scales, the problem of estimating network coefficients is reformulated to allow for direct least squares estimation, without Fourier encoding. By simulation, this approach is shown to allow for acceleration of the imaging process under ideal circumstances by nearly three orders of magnitude.

Simultaneous implementation of magnetic resonance imaging methods for Arterial Spin Labeling (ASL) and Blood Oxygenation Level Dependent (BOLD) imaging makes it possible to quantitatively measure the changes in cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO(2)) that occur in response to neural stimuli. To date, however, the range of neural stimuli amenable to quantitative analysis is limited to those that may be presented in a simple block or event related design such that measurements may be repeated and averaged to improve precision. Here we examined the feasibility of using the relationship between cerebral blood flow and the BOLD signal to improve dynamic estimates of blood flow fluctuations as well as to estimate metabolic-hemodynamic coupling under conditions where a stimulus pattern is unknown. We found that by combining the information contained in simultaneously acquired BOLD and ASL signals through a method we term BOLD Constrained Perfusion (BCP) estimation, we could significantly improve the precision of our estimates of the hemodynamic response to a visual stimulus and, under the conditions of a calibrated BOLD experiment, accurately determine the ratio of the oxygen metabolic response to the hemodynamic response. Importantly we were able to accomplish this without utilizing a priori knowledge of the temporal nature of the neural stimulus, suggesting that BOLD Constrained Perfusion estimation may make it feasible to quantitatively study the cerebral metabolic and hemodynamic responses to more natural stimuli that cannot be easily repeated or averaged.

Neural population modeling, including the role of neural attractors, is a promising tool for understanding many aspects of brain function. We propose a modeling framework to connect the abstract variables used in modeling to recent cellular-level estimates of the bioenergetic costs of different aspects of neural activity, measured in ATP consumed per second per neuron. Based on recent work, an empirical reference for brain ATP use for the awake resting brain was estimated as ~2 x 109 ATP/s-neuron across several mammalian species. The energetics framework was applied to the Wilson-Cowan (WC) model of two interacting populations of neurons, one excitatory (E) and one inhibitory (I). Attractors were considered to exhibit steady-state behavior and limit cycle behavior, both of which end when the excitatory stimulus ends, and sustained activity that persists after the stimulus ends. The energy cost of limit cycles, with oscillations much faster than the average neuronal firing rate of the population, is tracked more closely with the firing rate than the limit cycle frequency. Self-sustained firing driven by recurrent excitation, though, involves higher firing rates and a higher energy cost. As an example of a simple network in which each node is a WC model, a combination of three nodes can serve as a flexible circuit element that turns on with an oscillating output when input passes a threshold and then persists after the input ends (an "on-switch"), with moderate overall ATP use. The proposed framework can serve as a guide for anchoring neural population models to plausible bioenergetics requirements. [ABSTRACT FROM AUTHOR]

It has been recently proposed that the local cerebral blood volume change during brain activation can be measured by a series of images whose contrast is dependent on vascular space occupancy (VASO). VASO takes advantage of the inversion recovery sequence to acquire images when the longitudinal magnetization ([M.sub.z]) of blood is relaxing through zero. The degree of blood suppression, however, is not always well controlled as a consequence of spatial variations in inversion efficiency and blood [T.sub.1]. Furthermore, while blood is eliminated, the [M.sub.z] of other tissues is also small, which makes the contrast-to-noise ratio inherently low in VASO. In this paper, diffusion gradients were applied to demonstrate residual intravascular signal in the original VASO. An alternative VASO-weighted imaging was then proposed using a longer inversion time at which the [M.sub.z] difference between blood and gray matter was optimized. A global saturation immediately after image acquisition was employed to eliminate the [M.sub.z] disparity between inflowing blood and the residual in-plane blood from previous acquisition. Feasibility was evaluated by numerical simulation and functional experiments. In human visual cortex, the fractional VASO signal and cerebral blood volume changes were found to be -0.6% and 44%, respectively (voxel size = 3.4 x 3.4 x 5.0 [mm.sup.3]). As compared to the original VASO, the presented method provided a largely comparable activation map and hemodynamic curve but was not confounded by the existence of blood. Results also demonstrated its advantages of 1.6-fold higher CNR and insensitivity to variant tissue/blood [T.sub.1] as well as inversion efficiency. Index Terms--Brain activation, cerebral blood volume (CBV), functional magnetic resonance imaging, vascular space occupancy (VASO).

The blood in the carotid arteries exhibits time-varying flow velocity as a function of cardiac phases. Despite this flow velocity variation, most current methods set forth for the analysis of arterial spin labeling (ASL) data have assumed that the tagged blood is delivered from the tagging region to the imaging region via simple plug flow, i.e., a single transit delay (6t). In this study, we used a pulse oximeter to synchronize image acquisition at systole and diastole separately. The [delta]t dispersion was modeled with a Gaussian distribution and the effect of cardiac pulsation upon the ASL signal was evaluated on five healthy volunteers. ASL signals were collected at a series of inflow times (TI) using PICORE QUIPSS II: TR/TE/T[I.sub.1] = 2400/3.2/700 ms, TI = {300,500,700,900, 1100, 1300, 1500} ms, matrix size = 64 x 64, repetition = 100. Transit delay was found significantly shorter in systolic tag than diastolic tag (paired student's t-test, p < 0.001; mean difference across subjects : 54 ms). When the tag was applied in late systole, the ASL signal arrived in the target brain slice earlier, and was higher by 16% with TI = 700 ms. Intervoxel dispersion (~350 ms) dominated over intravoxel dispersion ( Index Terms--Arterial spin labeling, cardiac pulsation, flow dispersion, magnetic resonance imaging.