Luis Hernandez-Garcia

Recommended implementation of arterial spin-labeled Perfusion mri for clinical applications: A consensus of the ISMRM Perfusion Study group and the European consortium for ASL in dementia

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. Magn Reson Med 73:102–116, 2015.

Challenges to attention: A continuous arterial spin labeling (ASL) study of the effects of distraction on sustained attention

Maintaining attention and performance over time is an essential part of many activities, and effortful cognitive control is required to avoid vigilance decrements and interference from distraction. Regions at or near right middle frontal gyrus (Brodmanns area (BA) 9), as well as in other prefrontal and parietal areas, are often activated in studies of sustained attention (e.g., Cabeza and Nyberg, 2000; Kim et al., 2006; Lim et al., 2010). This activation has often been interpreted as representing the engagement of cognitive control processes. However, such studies are typically implemented at one level of task difficulty, without an experimental manipulation of control demands. The present study used the distractor condition sustained attention task (dSAT), which has been used extensively in animals to determine the role of neuromodulator systems in attentional performance, to test the hypotheses that BA 9 is sensitive to changes in the demand for cognitive control and that this sensitivity reflects an increased engagement of attentional effort. Continuous arterial spin labeling (ASL) was used to measure neural activity in sixteen healthy, young adults performing a sustained attention task under standard conditions and under a distraction condition that provided an experimental manipulation of demands on cognitive control. The distractor impaired behavioral performance and increased activation in right middle frontal gyrus. Larger increases in right middle frontal gyrus activity were associated with greater behavioral vulnerability to the distractor. These findings indicate that while right middle frontal gyrus regions are sensitive to demands for attentional effort and control, they may not be sufficient to maintain performance under challenge. In addition, they demonstrate the sensitivity of ASL methods to variations in task demands, and suggest that the dSAT may be a useful tool for translational cross-species and clinical research.

Estimation efficiency and statistical power in arterial spin labeling fMRI.

Arterial spin labeling (ASL) data are typically differenced, sometimes after interpolation, as part of preprocessing before statistical analysis in fMRI. While this process can reduce the number of time points by half, it simplifies the subsequent signal and noise models (i.e., smoothed box-car predictors and white noise). In this paper, we argue that ASL data are best viewed in the same data analytic framework as BOLD fMRI data, in that all scans are modeled and colored noise is accommodated. The data are not differenced, but the control/label effect is implicitly built into the model. While the models using differenced data may seem easier to implement, we show that differencing models fit with ordinary least squares either produce biased estimates of the standard errors or suffer from a loss in efficiency. The main disadvantage to our approach is that non-white noise must be modeled in order to yield accurate standard errors, however, this is a standard problem that has been solved for BOLD data, and the very same software can be used to account for such autocorrelated noise.

Neural effects of short-term training on working memory

Working memory training has been the focus of intense research interest. Despite accumulating behavioral work, knowledge about the neural mechanisms underlying training effects is scarce. Here, we show that 7 days of training on an n-back task led to substantial performance improvements in the trained task; furthermore, the experimental group showed cross-modal transfer, as compared with an active control group. In addition, there were two neural effects that emerged as a function of training: first, increased perfusion during task performance in selected regions, reflecting a neural response to cope with high task demand; second, increased blood flow at rest in regions where training effects were apparent. We also found that perfusion at rest was correlated with task proficiency, probably reflecting an improved neural readiness to perform. Our findings are discussed within the context of the available neuroimaging literature on n-back training.

B0 field inhomogeneity considerations in pseudo-continuous arterial spin labeling (pCASL): effects on tagging efficiency and correction strategy

Pseudo‐continuous arterial spin labeling (pCASL) is a very powerful technique to measure cerebral perfusion, which circumvents the problems affecting other continuous arterial spin labeling schemes, such as magnetization transfer and duty cycle. However, some variability in the tagging efficiency of the pCASL technique has been reported. This article investigates the effect of B0 field inhomogeneity on the tagging efficiency of the pCASL pulse sequence as a possible cause of this variability. Both theory and simulated data predict that the efficiency of pseudo‐continuous labeling pulses can be degraded in the presence of off‐resonance effects. These findings are corroborated by human in vivo measurements of tagging efficiency. On the basis of this theoretical framework, a method utilizing B0 field map information is proposed to correct for the possible loss in tagging efficiency of the pCASL pulse sequence. The efficiency of the proposed correction method is evaluated using numerical simulations and in vivo implementation. The data show that the proposed method can effectively recover the lost tagging efficiency and signal‐to‐noise ratio of pCASL caused by off‐resonance effects. Copyright

Vascular dynamics and BOLD fMRI: CBF level effects and analysis considerations.

Changes in the cerebral blood flow (CBF) baseline produce significant changes to the hemodynamic response. This work shows that increases in the baseline blood flow level produce blood oxygenation-level dependent (BOLD) and blood flow responses that are slower and lower in amplitude, while decreases in the baseline blood flow level produce faster and higher amplitude hemodynamic responses. This effect was characterized using a vascular model of the hemodynamic response that separated arterial blood flow response from the venous blood volume response and linked the input stimulus to the vascular response. The model predicted the baseline blood flow level effects to be dominated by changes in the arterial vasculature. Specifically, it predicted changes in the arterial blood flow time constant and venous blood volume time constant parameters of +294% and -24%, respectively, for a 27% increase in the baseline blood flow. The vascular model performance was compared to an empirical model of the hemodynamic response. The vascular and empirical hemodynamic models captured most of the baseline blood flow level effects observed and can be used to correct for these effects in fMRI data. While the empirical hemodynamic model is easy to implement, it did not incorporate any explicit physiological information.

Fast, pseudo‐continuous arterial spin labeling for functional imaging using a two‐coil system

A fast, two‐coil, pseudo‐continuous labeling scheme is presented. This new scheme permits the collection of a multislice subtraction pair in <3 s, depending on the subjects arterial transit times. The method consists of acquiring both control and tag images immediately after a labeling period that matches the arterial transit time. The theoretical basis of the technique, and simulations of the signal during changes in both transit time and perfusion are presented. Experimental data from functional imaging experiments were collected to demonstrate the technique and its characteristics. Magn Reson Med 51:577–585, 2004.

Temporal summation of heat pain in humans: Evidence supporting thalamocortical modulation

&NA; Noxious cutaneous contact heat stimuli (48 °C) are perceived as increasingly painful when the stimulus duration is extended from 5 to 10 s, reflecting the temporal summation of central neuronal activity mediating heat pain. However, the sensation of increasing heat pain disappears, reaching a plateau as stimulus duration increases from 10 to 20 s. We used functional magnetic resonance imaging (fMRI) in 10 healthy subjects to determine if active central mechanisms could contribute to this psychophysical plateau. During heat pain durations ranging from 5 to 20 s, activation intensities in the bilateral orbitofrontal cortices and the activation volume in the left primary (S1) somatosensory cortex correlated only with perceived stimulus intensity and not with stimulus duration. Activation volumes increased with both stimulus duration and perceived intensity in the left lateral thalamus, posterior insula, inferior parietal cortex, and hippocampus. In contrast, during the psychophysical plateau, both the intensity and volume of thalamic and cortical activations in the right medial thalamus, right posterior insula, and left secondary (S2) somatosensory cortex continued to increase with stimulus duration but not with perceived stimulus intensity. Activation volumes in the left medial and right lateral thalamus, and the bilateral mid‐anterior cingulate, left orbitofrontal, and right S2 cortices also increased only with stimulus duration. The increased activity of specific thalamic and cortical structures as stimulus duration, but not perceived intensity, increases is consistent with the recruitment of a thalamocortical mechanism that participates in the modulation of pain‐related cortical responses and the temporal summation of heat pain.

Quantitative analysis of arterial spin labeling FMRI data using a general linear model

Arterial spin labeling techniques can yield quantitative measures of perfusion by fitting a kinetic model to difference images (tagged-control). Because of the noisy nature of the difference images investigators typically average a large number of tagged versus control difference measurements over long periods of time. This averaging requires that the perfusion signal be at a steady state and not at the transitions between active and baseline states in order to quantitatively estimate activation induced perfusion. This can be an impediment for functional magnetic resonance imaging task experiments. In this work, we introduce a general linear model (GLM) that specifies Blood Oxygenation Level Dependent (BOLD) effects and arterial spin labeling modulation effects and translate them into meaningful, quantitative measures of perfusion by using standard tracer kinetic models. We show that there is a strong association between the perfusion values using our GLM method and the traditional subtraction method, but that our GLM method is more robust to noise.

Numerical Analysis and Design of Single-Source Multicoil TMS for Deep and Focused Brain Stimulation

Transcranial magnetic stimulation (TMS) is a tool for noninvasive stimulation of neuronal tissue used for research in cognitive neuroscience and to treat neurological disorders. Many TMS applications call for large electric fields to be sharply focused on regions that often lie deep inside the brain. Unfortunately, the fields generated by present-day TMS coils diffuse and decay rapidly as they penetrate into the head. As a result, they tend to stimulate relatively large regions of tissue near the brain surface. Earlier studies suggested that a focused TMS excitation can be attained using multiple nonuniformly fed coils in a multichannel array. We propose a systematic, genetic algorithm-based technique for synthesizing multichannel arrays that minimize the volume of the excited region required to achieve a prescribed penetration depth and maintain realistic values for the input driving currents. Because multichannel arrays are costly to build, we also propose a method to convert the multichannel arrays into single-channel ones while minimally materially deteriorating performance. Numerical results show that the new multi- and single-channel arrays stimulate tissue 2.4 cm into the head while exciting 3.0 and 2.6 times less volume than conventional Figure-8 coils, respectively.