David C. Alsop

Continuous flow-driven inversion for arterial spin labeling using pulsed radio frequency and gradient fields

Continuous labeling by flow‐driven adiabatic inversion is advantageous for arterial spin labeling (ASL) perfusion studies, but details of the implementation, including inefficiency, magnetization transfer, and limited support for continuous‐mode operation on clinical scanners, have restricted the benefits of this approach. Here a new approach to continuous labeling that employs rapidly repeated gradient and radio frequency (RF) pulses to achieve continuous labeling with high efficiency is characterized. The theoretical underpinnings, numerical simulations, and in vivo implementation of this pulsed continuous ASL (PCASL) method are described. In vivo PCASL labeling efficiency of 96% relative to continuous labeling with comparable labeling parameters far exceeded the 33% duty cycle of the PCASL RF pulses. Imaging at 3T with body coil transmission was readily achieved. This technique should help to realize the benefits of continuous labeling in clinical imagers. Magn Reson Med 60:1488–1497, 2008.

Reduced Transit-Time Sensitivity in Noninvasive Magnetic Resonance Imaging of Human Cerebral Blood Flow

Herein, we present a theoretical framework and experimental methods to more accurately account for transit effects in quantitative human perfusion imaging using endogenous magnetic resonance imaging (MRI) contrast. The theoretical transit time sensitivities of both continuous and pulsed inversion spin tagging experiments are demonstrated. We propose introducing a delay following continuous labeling, and demonstrate theoretically that introduction of a delay dramatically reduces the transit time sensitivity of perfusion imaging. The effects of magnetization transfer saturation on this modified continuous labeling experiment are also derived, and the assumption that the perfusion signal resides entirely within tissue rather than the arterial microvasculature is examined. We present results demonstrating the implementation of the continuous tagging experiment with delay on an echoplanar scanner for measuring cerebral blood flow (CBF) in normal volunteers. By varying the delay, we estimate transit times in the arterial system, values that are necessary for assessing the accuracy of our quantification. The effect of uncertainties in the transit time from the tagging plane to the arterial microvasculature and the transit time to the tissue itself on the accuracy of perfusion quantification is discussed and found to be small in gray matter but still potentially significant in white matter. A novel method for measuring T1, which is fast, insensitive to contamination by cerebrospinal fluid, and compatible with the application of magnetization transfer saturation, is also presented. The methods are combined to produce quantitative maps of resting and hypercarbic CBF.

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.

Magnetic resonance perfusion imaging in acute ischemic stroke using continuous arterial spin labeling.

BACKGROUND AND PURPOSE Continuous arterial spin-labeled perfusion MRI (CASL-PI) uses electromagnetically labeled arterial blood water as a diffusible tracer to noninvasively measure cerebral blood flow (CBF). We hypothesized that CASL-PI could detect perfusion deficits and perfusion/diffusion mismatches and predict outcome in acute ischemic stroke. METHODS We studied 15 patients with acute ischemic stroke within 24 hours of symptom onset. With the use of a 6-minute imaging protocol, CASL-PI was measured at 1.5 T in 8-mm contiguous supratentorial slices with a 3.75-mm in-plane resolution. Diffusion-weighted images were also obtained. Visual inspection for perfusion deficits, perfusion/diffusion mismatches, and effects of delayed arterial transit was performed. CBF in predetermined vascular territories was quantified by transformation into Talairach space. Regional CBF values were correlated with National Institutes of Health Stroke Scale (NIHSS) score on admission and Rankin Scale (RS) score at 30 days. RESULTS Interpretable CASL-PI images were obtained in all patients. Perfusion deficits were consistent with symptoms and/or diffusion-weighted imaging abnormalities. Eleven patients had hypoperfusion, 3 had normal perfusion, and 1 had relative hyperperfusion. Perfusion/diffusion mismatches were present in 8 patients. Delayed arterial transit effect was present in 7 patients; serial imaging in 2 of them showed that the delayed arterial transit area did not succumb to infarction. CBF in the affected hemisphere correlated with NIHSS and RS scores (P=0.037 and P=0.003, Spearman rank correlation). The interhemispheric percent difference in middle cerebral artery CBF correlated with NIHSS and RS scores (P=0.007 and P=0.0002, respectively). CONCLUSIONS CASL-PI provides rapid noninvasive multislice imaging in acute ischemic stroke. It depicts perfusion deficits and perfusion/diffusion mismatches and quantifies regional CBF. CASL-PI CBF asymmetries correlate with severity and outcome. Delayed arterial transit effects may indicate collateral flow.

Assessment of cerebral blood flow in Alzheimer's disease by spin‐labeled magnetic resonance imaging

To evaluate the utility of arterial spin‐labeled blood flow magnetic resonance imaging for the detection of cerebral blood flow abnormalities in Alzheimers disease, arterial spin‐labeled blood flow images in 16 contiguous 5‐mm axial sections were acquired in 18 patients diagnosed with probable Alzheimers disease and 11 age‐matched controls. Blood flow images from all subjects were transformed to a standard anatomical space for voxel‐by‐voxel statistical analysis. High quality blood flow images were obtained from all but 1 subject. Statistical analysis demonstrated significant flow decreases relative to control subjects in temporal, parietal, frontal, and posterior cingulate cortices. Increased severity of disease, as measured by Mini‐Mental State Examination, correlated with posterior parietal and posterior cingulate decreases but not temporal decreases. Arterial spin‐labeled magnetic resonance imaging was found to be an effective tool for characterizing flow decreases accompanying Alzheimers disease. The absence of ionizing radiation or injection and the ability to obtain high quality anatomical images within the same scanning session make arterial spin labeling an attractive technique for the study of Alzheimers disease, for the evaluation of pharmacological therapies, and, possibly, for early diagnosis. Ann Neural 2000; 47:93–100

Comparison of quantitative perfusion imaging using arterial spin labeling at 1.5 and 4.0 Tesla

High‐field arterial spin labeling (ASL) perfusion MRI is appealing because it provides not only increased signal‐to‐noise ratio (SNR), but also advantages in terms of labeling due to the increased relaxation time T1 of labeled blood. In the present study, we provide a theoretical framework for the dependence of the ASL signal on the static field strength, followed by experimental validation in which a multislice pulsed ASL (PASL) technique was carried out at 4T and compared with PASL and continuous ASL (CASL) techniques at 1.5T, both in the resting state and during motor activation. The resting‐state data showed an SNR ratio of 2.3:1.4:1 in the gray matter and a contrast‐to‐noise ratio (CNR) of 2.7:1.1:1 between the gray and white matter for the difference perfusion images acquired using 4T PASL, 1.5T CASL, and 1.5T PASL, respectively. However, the functional data acquired using 4T PASL did not show significantly improved sensitivity to motor cortex activation compared with the 1.5T functional data, with reduced fractional perfusion signal change and increased intersubject variability. Possible reasons for these experimental results, including susceptibility effects and physiological noise, are discussed. Magn Reson Med 48:242–254, 2002.

An fMRI study of sex differences in regional activation to a verbal and a spatial task.

Sex differences in cognitive performance have been documented, women performing better on some phonological tasks and men on spatial tasks. An earlier fMRI study suggested sex differences in distributed brain activation during phonological processing, with bilateral activation seen in women while men showed primarily left-lateralized activation. This blood oxygen level-dependent fMRI study examined sex differences (14 men, 13 women) in activation for a spatial task (judgment of line orientation) compared to a verbal-reasoning task (analogies) that does not typically show sex differences. Task difficulty was manipulated. Hypothesized ROI-based analysis documented the expected left-lateralized changes for the verbal task in the inferior parietal and planum temporal regions in both men and women, but only men showed right-lateralized increase for the spatial task in these regions. Image-based analysis revealed a distributed network of cortical regions activated by the tasks, which consisted of the lateral frontal, medial frontal, mid-temporal, occipitoparietal, and occipital regions. The activation was more left lateralized for the verbal and more right for the spatial tasks, but men also showed some left activation for the spatial task, which was not seen in women. Increased task difficulty produced more distributed activation for the verbal and more circumscribed activation for the spatial task. The results suggest that failure to activate the appropriate hemisphere in regions directly involved in task performance may explain certain sex differences in performance. They also extend, for a spatial task, the principle that bilateral activation in a distributed cognitive system underlies sex differences in performance.

Adults and children processing music: An fMRI study

The present study investigates the functional neuroanatomy of music perception with functional magnetic resonance imaging (fMRI). Three different subject groups were investigated to examine developmental aspects and effects of musical training: 10-year-old children with varying degrees of musical training, adults without formal musical training (nonmusicians), and adult musicians. Subjects made judgements on sequences that ended on chords that were music-syntactically either regular or irregular. In adults, irregular chords activated the inferior frontal gyrus, orbital frontolateral cortex, the anterior insula, ventrolateral premotor cortex, anterior and posterior areas of the superior temporal gyrus, the superior temporal sulcus, and the supramarginal gyrus. These structures presumably form different networks mediating cognitive aspects of music processing (such as processing of musical syntax and musical meaning, as well as auditory working memory), and possibly emotional aspects of music processing. In the right hemisphere, the activation pattern of children was similar to that of adults. In the left hemisphere, adults showed larger activations than children in prefrontal areas, in the supramarginal gyrus, and in temporal areas. In both adults and children, musical training was correlated with stronger activations in the frontal operculum and the anterior portion of the superior temporal gyrus.

Sleep-dependent motor memory plasticity in the human brain

Growing evidence indicates a role for sleep in off-line memory processing, specifically in post-training consolidation. In humans, sleep has been shown to trigger overnight learning on a motor-sequence memory task, while equivalent waking periods produce no such improvement. But while the behavioral characteristics of sleep-dependent motor learning become increasingly well characterized, the underlying neural basis remains unknown. Here we present functional magnetic resonance imaging data demonstrating a change in the representation of a motor memory after a night of sleep. Subjects trained on a motor-skill memory and 12 hours later, after either sleep or wake, were retested during functional magnetic resonance imaging. Following sleep relative to wake, regions of increased activation were expressed in the right primary motor cortex, medial prefrontal lobe, hippocampus and left cerebellum; changes that can support faster motor output and more precise mapping of key-press movements. In contrast, signal decreases were identified in parietal cortices, the left insular cortex, temporal pole and fronto-polar region, reflecting a reduced need for conscious spatial monitoring and a decreased emotional task burden. This evidence of an overnight, systems-level change in the representation of a motor memory holds important implications for acquiring real-life skills and in clinical rehabilitation following brain trauma, such as stroke.

Perfusion magnetic resonance imaging with continuous arterial spin labeling: methods and clinical applications in the central nervous system

Several methods are now available for measuring cerebral perfusion and related hemodynamic parameters using magnetic resonance imaging (MRI). One class of techniques utilizes electromagnetically labeled arterial blood water as a noninvasive diffusible tracer for blood flow measurements. The electromagnetically labeled tracer has a decay rate of T1, which is sufficiently long to allow perfusion of the tissue and microvasculature to be detected. Alternatively, electromagnetic arterial spin labeling (ASL) may be used to obtain qualitative perfusion contrast for detecting changes in blood flow, similar to the use of susceptibility contrast in blood oxygenation level dependent functional MRI (BOLD fMRI) to detect functional activation in the brain. The ability to obtain blood flow maps using a non-invasive and widely available modality such as MRI should greatly enhance the utility of blood flow measurement as a means of gaining further insight into the broad range of hemodynamically related physiology and pathophysiology. This article describes the biophysical considerations pertaining to the generation of quantitative blood flow maps using a particular form of ASL in which arterial blood water is continuously labeled, termed continuous arterial spin labeling (CASL). Technical advances permit multislice perfusion imaging using CASL with reduced sensitivity to motion and transit time effects. Interpretable cerebral perfusion images can now be reliably obtained in a variety of clinical settings including acute stroke, chronic cerebrovascular disease, degenerative diseases and epilepsy. Over the past several years, the technical and theoretical foundations of CASL perfusion MRI techniques have evolved from feasibility studies into practical usage. Currently existing methodologies are sufficient to make reliable and clinically relevant observations which complement structural assessment using MRI. Future technical improvements should further reduce the acquisition times for CASL perfusion MRI, while increasing the slice coverage, resolution and stability of the images. These techniques have a broad range of potential applications in clinical and basic research of brain physiology, as well as in other organs.