Laura M. Parkes

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.

Localizing human visual gamma-band activity in frequency, time and space

Neuronal gamma-band (30-100 Hz) synchronization subserves fundamental functions in neuronal processing. However, different experimental approaches differ widely in their success in finding gamma-band activity. We aimed at linking animal and human studies of gamma-band activity and at preparing optimized methods for an in-depth investigation of the mechanisms and functions of gamma-band activity and gamma-band coherence in humans. In the first step described here, we maximized the signal-to-noise ratio with which we can observe visually induced gamma-band activity in human magnetoencephalographic recordings. We used a stimulus and task design that evoked strong gamma-band activity in animals and combined it with multi-taper methods for spectral analysis and adaptive spatial filtering for source analysis. With this approach, we found human visual gamma-band activity very reliably across subjects and across multiple recording sessions of a given subject. While increases in gamma-band activity are typically accompanied by decreases in alpha- and beta-band activity, the gamma-band enhancement was often the spectral component with the highest signal-to-noise ratio. Furthermore, some subjects demonstrated two clearly separate visually induced gamma bands, one around 40 Hz and another between 70 and 80 Hz. Gamma-band activity was sustained for the entire stimulation period, which was up to 3 s. The sources of gamma-band activity were in the calcarine sulcus in all subjects. The results localize human visual gamma-band activity in frequency, time and space and the described methods allow its further investigation with great sensitivity.

Normal cerebral perfusion measurements using arterial spin labeling: reproducibility, stability, and age and gender effects.

Before meaningful conclusions can be drawn from clinical measures of cerebral blood perfusion, the precision of the measurement must be determined and set in the context of inter‐ and intrasubject sources of variability. This work establishes the reproducibility of perfusion measurements using the noninvasive MRI technique of continuous arterial spin labeling (CASL). Perfusion was measured in 34 healthy normal subjects. Intersubject variability was assessed, and age and gender contributions were estimated. Intersubject variation was found to be large, with up to 100% perfusion difference for subjects of the same age and gender. Repeated measurements in one subject showed that perfusion remains remarkably stable in the short term when compared with intersubject variation and the large capacity for perfusion change in the brain. A significant decrease in the ratio of gray‐matter to white‐matter perfusion was found with increasing age (0.79% per year (P < 0.0005)). This appears to be due mainly to a reduction in gray‐matter perfusion, which was found to decrease by 0.45% per year (P = 0.04). Regional analysis suggested that the gray‐matter age‐related changes were predominantly localized in the frontal cortex. Whole‐brain perfusion was 13% higher (P = 0.02) in females compared to males. Magn Reson Med 51:736–743, 2004.

Improved accuracy of human cerebral blood perfusion measurements using arterial spin labeling: accounting for capillary water permeability

A two‐compartment exchange model for perfusion quantification using arterial spin labeling (ASL) is presented, which corrects for the assumption that the capillary wall has infinite permeability to water. The model incorporates an extravascular and a blood compartment with the permeability surface area product (PS) of the capillary wall characterizing the passage of water between the compartments. The new model predicts that labeled spins spend longer in the blood compartment before exchange. This makes an accurate blood T1 measurement crucial for perfusion quantification; conversely, the tissue T1 measurement is less important and may be unecessary for pulsed ASL experiments. The model gives up to 62% reduction in perfusion estimate for human imaging at 1.5T compared to the single compartment model. For typical human perfusion rates at 1.5T it can be assumed that the venous outflow signal is negligible. This simplifies the solution, introducing only one more parameter than the single compartment model, PS/vbw, where vbw is the fractional blood water volume per unit volume of tissue. The simplified model produces an improved fit to continuous ASL data collected at varying delay time. The fitting yields reasonable values for perfusion and PS/vbw. Magn Reson Med 48:27–41, 2002.

Multivoxel fMRI analysis of color tuning in human primary visual cortex

We use multivoxel pattern analysis (MVPA) to study the spatial clustering of color-selective neurons in the human brain. Our main objective was to investigate whether MVPA reveals the spatial arrangements of color-selective neurons in human primary visual cortex (V1). We measured the distributed fMRI activation patterns for different color stimuli (Experiment 1: cardinal colors (to which the LGN is known to be tuned), Experiment 2: perceptual hues) in V1. Our two main findings were that (i) cone-opponent cardinal color modulations produce highly reproducible patterns of activity in V1, but these were not unique to each color. This suggests that V1 neurons with tuning characteristics similar to those found in LGN are not spatially clustered. (ii) Unique activation patterns for perceptual hues in V1 support current evidence for a spatially clustered hue map. We believe that our work is the first to show evidence of spatial clustering of neurons with similar color preferences in human V1.

Quantifying the spatial resolution of the gradient echo and spin echo BOLD response at 3 Tesla

The blood oxygen level dependent (BOLD) response, as measured with fMRI, offers good spatial resolution compared to other non‐invasive neuroimaging methods. The use of a spin echo technique rather than the conventional gradient echo technique may further improve the resolution by refocusing static dephasing effects around the larger vessels, so sensitizing the signal to the microvasculature. In this work the width of the point spread function (PSF) of the BOLD response at a field strength of 3 Tesla is compared for these two approaches. A double echo EPI pulse sequence with simultaneous collection of gradient echo and spin echo signal allows a direct comparison of the techniques. Rotating multiple‐wedge stimuli of different spatial frequencies are used to estimate the width of the BOLD response. Waves of activation are created on the surface of the visual cortex, which begin to overlap as the wedge separation decreases. The modulation of the BOLD response decreases with increasing spatial frequency in a manner dependent on its width. The spin echo response shows a 13% reduction in the width of the PSF, but at a cost of at least 3‐fold reduction in contrast to noise ratio. Magn Reson Med, 2005.

Abnormalities of cerebral perfusion in multiple sclerosis

Background: Measuring perfusion provides a potential indication of metabolic activity in brain tissue. Studies in multiple sclerosis (MS) have identified areas of decreased perfusion in grey matter (GM) and white matter (WM), but the pattern in clinical subgroups is unclear. Objectives: This study investigated perfusion changes in differing MS clinical subgroups on or off β-interferon therapy using a non-invasive MRI technique (continuous arterial spin labelling) to investigate whether different clinical MS subtypes displayed perfusion changes and whether this could give a further insight into the pathological mechanisms involved. Methods: Sixty patients (21 relapsing remitting, 14 secondary progressive, 12 primary progressive, 13 benign) and 34 healthy controls were compared. Statistical parametric mapping (SPM ’99) was used to investigate regional variations in perfusion in both GM and WM. Global WM perfusion was derived by segmenting WM from images using T1 relaxation times. Results: Regions of lower perfusion in predominantly GM were observed in the primary and secondary progressive cohorts, particularly in the thalamus. Increased WM perfusion was seen in relapsing remitting and secondary progressive cohorts. Conclusions: Low GM perfusion could reflect decreased metabolism secondary to neuronal and axonal loss or dysfunction with a predilection for progressive forms of MS. Increased WM perfusion may indicate increased metabolic activity possibly due to increased cellularity and inflammation. Improved methodology and longitudinal studies may enable further investigation of regional and temporal changes, and their relationship with physical and cognitive impairment.

Combining EEG and fMRI to investigate the post-movement beta rebound.

The relationship between synchronous neuronal activity as measured with EEG and the blood oxygenation level dependent (BOLD) signal as measured during fMRI is not clear. This work investigates the relationship by combining EEG and fMRI measures of the strong increase in beta frequency power following movement, the so-called post-movement beta rebound (PMBR). The time course of the PMBR, as measured by EEG, was included as a regressor in the fMRI analysis, allowing identification of a region of associated BOLD signal increase in the sensorimotor cortex, with the most significant region in the post-central sulcus. The increase in the BOLD signal suggests that the number of active neurons and/or their synaptic rate is increased during the PMBR. The duration of the BOLD response curve in the PMBR region is significantly longer than in the activated motor region, and is well fitted by a model including both motor and PMBR regressors. An intersubject correlation between the BOLD signal amplitude associated with the PMBR regressor and the PMBR strength as measured with EEG provides further evidence that this region is a source of the PMBR. There is a strong intra-subject correlation between the BOLD signal amplitude in the sensorimotor cortex during movement and the PMBR strength as measured by EEG, suggesting either that the motor activity itself, or somatosensory inputs associated with the motor activity, influence the PMBR. This work provides further evidence for a BOLD signal change associated with changes in neuronal synchrony, so opening up the possibility of studying other event-related oscillatory changes using fMRI.

Dynamic contrast-enhanced imaging techniques: CT and MRI

Over the last few decades there has been considerable research into quantifying the cerebral microvasculature with imaging, for use in studies of the human brain and various pathologies including cerebral tumours. This review highlights key issues in dynamic contrast-enhanced CT, dynamic contrast-enhanced MRI and arterial spin labelling, the various applications of which are considered elsewhere in this special issue of the British Journal of Radiology.

Depressive Disorders: Focally Altered Cerebral Perfusion Measured with Arterial Spin-labeling MR Imaging

PURPOSE To assess focal cerebral perfusion in patients with refractory depressive disorder (RDD), patients with nonrefractory depressive disorder (NDD), and healthy control subjects by using arterial spin-labeling (ASL) magnetic resonance (MR) imaging. MATERIALS AND METHODS This study was approved by the local ethical committee, and written informed consent was obtained from all participants. Twenty-four patients with RDD, 37 patients with NDD, and 42 healthy control subjects were included. From February 2006 to July 2007, all participants were imaged with a 3-T MR system. ASL and echo-planar images were subtracted and averaged to give perfusion-weighted images. Voxel-based analysis was performed. Region-of-interest analysis was applied to the bilateral hippocampi, thalami, and lentiform nuclei. RESULTS Patients with NDD showed reduced perfusion in the left prefrontal cortex versus control subjects and increased perfusion mainly in the limbic-striatal areas (P < .05). In contrast, patients with RDD had decreased perfusion predominantly in the bilateral frontal and bilateral thalamic regions (P < .05). Compared with patients with RDD, patients with NDD showed higher perfusion mainly in the limbic-striatal areas (P < .05). In region-of-interest analysis, the NDD group showed higher regional cerebral blood flow than both RDD and control groups in the left hippocampus (P = .045), right hippocampus (P = .001), and right lentiform nucleus (P = .049). CONCLUSION This study revealed alterations of regional perfusion in the brains of patients with RDD that differed from those in patients with NDD. These results are consistent with the concept that RDD is associated with decreased activity of the bilateral prefrontal areas; and NDD, with decreased activity of left frontal areas in conjunction with overactivity of the bilateral limbic system.