White matter changes and gait decline in cerebral small vessel disease.

The relation between progression of cerebral small vessel disease (SVD) and gait decline is uncertain, and diffusion tensor imaging (DTI) studies on gait decline are lacking. We therefore investigated the longitudinal associations between (micro) structural brain changes and gait decline in SVD using DTI. 275 participants were included from the Radboud University Nijmegen Diffusion tensor and Magnetic resonance imaging Cohort (RUN DMC), a prospective cohort of participants with cerebral small vessel disease aged 50-85 years. Gait (using GAITRite) and magnetic resonance imaging measures were assessed during baseline (2006-2007) and follow-up (2011 - 2012). Linear regression analysis was used to investigate the association between changes in conventional magnetic resonance and diffusion tensor imaging measures and gait decline. Tract-based spatial statistics analysis was used to investigate region-specific associations between changes in white matter integrity and gait decline. 56.2% were male, mean age was 62.9 years (SD8.2), mean follow-up duration was 5.4 years (SD0.2) and mean gait speed decline was 0.2 m/s (SD0.2). Stride length decline was associated with white matter atrophy (ß = 0.16, p = 0.007), and increase in mean white matter radial diffusivity and mean diffusivity, and decrease in mean fractional anisotropy (respectively, ß = - 0.14, p = 0.009; ß = - 0.12, p = 0.018; ß = 0.10, p = 0.049), independent of age, sex, height, follow-up duration and baseline stride length. Tract-based spatial statistics analysis showed significant associations between stride length decline and fractional anisotropy decrease and mean diffusivity increase (primarily explained by radial diffusivity increase) in multiple white matter tracts, with the strongest associations found in the corpus callosum and corona radiata, independent of traditional small vessel disease markers. White matter atrophy and loss of white matter integrity are associated with gait decline in older adults with small vessel disease after 5 years of follow-up. These findings suggest that progression of SVD might play an important role in gait decline.

Reduced functional connectivity within the primary motor cortex of patients with brachial plexus injury.

This study aims at the effects of traumatic brachial plexus lesion with root avulsions (BPA) upon the organization of the primary motor cortex (M1). Nine right-handed patients with a right BPA in whom an intercostal to musculocutaneous (ICN-MC) nerve transfer was performed had post-operative resting state fMRI scanning. The analysis of empirical functional correlations between neighboring voxels revealed faster correlation decay as a function of distance in the M1 region corresponding to the arm in BPA patients as compared to the control group. No differences between the two groups were found in the face area. We also investigated whether such larger decay in patients could be attributed to a gray matter diminution in M1. Structural imaging analysis showed no difference in gray matter density between groups. Our findings suggest that the faster decay in neighboring functional correlations without significant gray matter diminution in BPA patients could be related to a reduced activity in intrinsic horizontal connections in M1 responsible for upper limb motor synergies.

Diffusion tensor imaging of the hippocampus predicts the risk of dementia; the RUN DMC study.

INTRODUCTION: Cerebral small vessel disease is one of the most important risk factors for dementia, and has been related to hippocampal atrophy, which is among the first observed changes on conventional MRI in patients with dementia. However, these volumetric changes might be preceded by loss of microstructural integrity of the hippocampus for which conventional MRI is not sensitive enough. Therefore, we investigated the relation between the hippocampal diffusion parameters and the risk of incident dementia, using diffusion tensor imaging, independent of hippocampal volume. METHODS: The RUNDMC study is a prospective study among 503 elderly with small vessel disease, without dementia, with 5 years follow-up in 2012 (99.6% response-rate). Cox regression analysis was performed to calculate hazard ratios for dementia, of fractional anisotropy and mean diffusivity within the hippocampus, adjusted for demographics, hippocampal volume, and white matter. This was repeated in participants without evident hippocampal volume loss, because in these participants the visible damage might not yet have already started, whereas damage might have started on a microstructural level. RESULTS: 43 participants developed dementia (8.6%), resulting in a 5.5-year cumulative risk of 11.1% (95%CI 7.7-14.6). Higher mean diffusivity was associated with an increased 5-year risk of dementia. In the subgroup of participants with the upper half hippocampal volume, higher hippocampal mean diffusivity, more than doubled the 5-year risk of dementia. CONCLUSION: This is the first prospective study showing a relation between a higher baseline hippocampal mean diffusivity and the risk of incident dementia in elderly with small vessel disease at 5-year follow-up, independent of hippocampal volume and white matter volume.

An investigation into the functional and structural connectivity of the Default Mode Network.

Connectivity analyses based on both resting-state (rs-)fMRI and diffusion weighted imaging studies suggest that the human brain contains regions that act as hubs for the entire brain, and that elements of the Default Mode Network (DMN) play a pivotal role in this network. In the present study, the detailed functional and structural connectivity of the DMN was investigated. Resting state fMRI (35 minute duration) and Diffusion Weighted Imaging (DWI) data (256 directions) were acquired from forty-seven healthy subjects at 3 T. Tractography was performed on the DWI data. The resting state data were analysed using a combination of Independent Component Analysis, partial correlation analysis and graph theory. This forms a data driven approach for examining the connectivity of the DMN. ICA defined regions of interest were used as a basis for a partial correlation analysis. The resulting partial correlation coefficients were used to compute graph theoretical measures. This was performed on a single subject basis, and combined to compute group results depicting the spatial distribution of betweenness centrality within the DMN. Hubs with high betweenness centrality were frequently found in association areas of the brain. This approach makes it possible to distinguish the hubs in the DMN as belonging to different anatomical association systems. The start and end points of the fibre tracts coincide with hubs found using the resting state analysis.

The European Federation of Organisations for Medical Physics Policy Statement No 14: the role of the Medical Physicist in the management of safety within the magnetic resonance imaging environment: EFOMP recommendations.

This European Federation of Organisations for Medical Physics (EFOMP) Policy Statement outlines the way in which a Safety Management System can be developed for MRI units. The Policy Statement can help eliminate or at least minimize accidents or incidents in the magnetic resonance environment and is recommended as a step towards harmonisation of safety of workers, patients, and the general public regarding the use of magnetic resonance imaging systems in diagnostic and interventional procedures.

Microstructural integrity of the cingulum is related to verbal memory performance in elderly with cerebral small vessel disease: the RUN DMC study.

BACKGROUND: Cerebral small vessel disease (SVD) is related to verbal memory failures. It is suggested that early white matter damage, is located, among others, in the (posterior) cingulum at an early stage in neurodegeneration. Changes in the microstructural integrity of the cingulum assessed with diffusion tensor imaging (DTI), beyond detection with conventional MRI, may precede macrostructural changes and be related to verbal memory failures. OBJECTIVE: To investigate the relation between cingular microstructural integrity and verbal memory performance in 503 non-demented elderly with cerebral SVD. METHODS: The RUN DMC study is a prospective cohort study in elderly (50-85 years) with cerebral SVD. All participants underwent T1 MPRAGE, FLAIR and DTI scanning and the Rey Auditory Verbal Learning Test. Mean diffusivity (MD) and fractional anisotropy (FA) were assessed in six different cingular regions of interests (ROIs). Linear regression analysis was used to assess the relation between verbal memory performance and cingular DTI parameters, with appropriate adjustments. Furthermore a TBSS analysis of the whole brain was performed to investigate the specificity of our findings. RESULTS: Both our ROI-based and TBSS analysis showed that FA was positively related to immediate memory, delayed recall, delayed recognition and overall verbal memory performance of the cingulum, independent of confounders. A similar distribution was seen for the inverse association with MD and verbal memory performance with TBSS analysis. No significant relations were found with psychomotor speed, visuospatial memory and MMSE. When stratified on hippocampal integrity, the MD and FA values of the cingular ROIs differed significantly between participants with a good and poor hippocampal integrity. CONCLUSION: Microstructural integrity of the cingulum, assessed by DTI, is specifically related to verbal memory performance, in elderly with SVD. Furthermore we found that when the integrity of the hippocampus is disrupted, the cingulum integrity is impaired as well.

Observation of ground-state quantum beats in atomic spontaneous emission.

We report ground-state quantum beats in spontaneous emission from a continuously driven atomic ensemble. Beats are visible only in an intensity autocorrelation and evidence spontaneously generated coherence in radiative decay. Our measurement realizes a quantum eraser where a first photon detection prepares a superposition and a second erases the "which path" information in the intermediate state.

Very high-resolution three-dimensional functional MRI of the human visual cortex with elimination of large venous vessels.

We propose a very high-resolution, three-dimensional (3D) gradient-echo technique with a twofold parallel imaging acceleration using a specialized occipital receiver coil at 3 T to perform functional MRI (fMRI) of the visual cortex. This configuration makes it possible to acquire 3D fMRI data within a timescale compatible with a block design. Without further processing, the functional maps at an isotropic 3D resolution of 0.42 microL (0.75 mm voxel size) and near-isotropic resolution of 1.2 microL (1 mm voxel size) show very robust activation in visual areas, but with clear contamination from larger veins. As this technique allows direct identification of veins in the functional scan, it permits removal of their effect from the activation maps. In our study, elimination of veins qualitatively improves the spatial specificity of activation maps, while reducing the activated volume by about 25%. The proposed technique provides functional information at the resolution of anatomical scans, is localized to gray matter, and facilitates functional to anatomical co-registration because of minimal distortions.

3D diffusion tensor imaging with 2D navigated turbo spin echo.

A Cartesian two-dimensional navigator with variable orientation for online motion correction is introduced. It corrects for all possible zeroth- and first-order phase errors due to rigid-body motion of a subject during the diffusion-weighting preparation. The technique is developed for the application of three-dimensional (3D) imaging sequences, which offer the opportunity of high-resolution diffusion-weighted imaging, or diffusion tensor imaging (DTI) with isotropic voxel resolution. The navigator was applied to a displaced 3D turbo spin-echo sequence with an ECG-gated diffusion preparation to avoid phase errors due to gross brain pulsation. Online and offline corrected in vivo images acquired with this sequence are compared to investigate the advantages of online correction. Also eigenvector maps of the diffusion tensor are presented with an isotropic resolution of 1 mm3, which indicate that this new navigator technique is a promising approach for high-resolution DTI.

Online motion correction for diffusion-weighted segmented-EPI and FLASH imaging.

This paper explores the application of online motion correction using navigator echoes to the segmented-EPI and FLASH techniques. In segmented EPI this has the advantage over post-acquisition correction that the position in k-space of each segment is no longer subject to arbitrary shifts caused by rotation. In diffusion-weighted FLASH it has the advantage that the full magnetisation can be utilised in comparison to other methods of eliminating the sensitivity to bulk motion, in which the sensitivity is halved. Healthy subjects were investigated on a 3 T whole-body system in which the hardware has been modified so that navigator echoes can be recorded on a personal computer which generates the necessary magnetic field gradient correction pulses and shifts in the Larmor frequency within 800 micros. ECG triggering was used to avoid the period of non-rigid-body brain motion. Two orthogonal navigator echoes were employed. For segmented EPI it was found essential to minimise the T2* weighting of the navigator echoes to about 10 ms to obtain reliable results. High quality images were obtained for both methods examined. Online motion correction brings direct benefits to both the diffusion-weighted segmented-EPI and FLASH techniques.

The irrelevant sound effect: what needs modelling, and a tentative model.

This paper reviews the literature on the irrelevant sound effect and concludes that, contrary to some claims, the data consistently show that irrelevant sound and articulatory suppression are not functionally equivalent. We evaluate the contribution of Larsen and Baddeley (2003 in this issue) and briefly discuss additional data in support of their position. We perform an error analysis on data from their third experiment and simulate detailed aspects of those data using our primacy model of immediate serial recall. Our model is briefly related to a number of findings in the literature on irrelevant sound.

A qualitative test of the balloon model for BOLD-based MR signal changes at 3T.

The aim of this study was to adapt the balloon model for BOLD-based MR signal changes to a magnetic field strength of 3T and to examine its validity. The simultaneous measurement of BOLD and diffusion-weighted BOLD responses was performed. The amplitude of the BOLD peak was found to be similar for all subjects when a short visual stimulus of 6 sec was used. The rise-time to the BOLD peak and the shape and depth of the poststimulus undershoot varied significantly. A fit of the experimental BOLD responses was found to be possible by use of parameters within a reasonable physiological range. The relations between these parameters and their influence on the modeled BOLD responses is discussed. A prediction of the balloon model is the occurrence of a BOLD overshoot, i.e., a lag between the changes of the blood volume and the blood flow after the start of the stimulation. Experimental evidence for the existence of a BOLD overshoot is presented.

Characterization of cerebral small vessel disease by proton spectroscopy and morphological magnetic resonance.

This study sought to investigate whether clinical and neuropsychological impairment in cerebral small vessel disease (CSVD) can be evaluated by proton spectroscopy ((1)H-MRS) and structural magnetic resonance (MR) imaging. Sixteen patients with CSVD and 15 healthy age-matched controls participated in the study. In addition to spectroscopic and structural MR examination all patients underwent a comprehensive clinical and neuropsychological investigation. Significant differences in between patients and controls were revealed by (1)H-MRS in the parietal white matter: decreased metabolic ratios of N-acetyl aspartate to choline (NAA/Cho; patients: 1.37 +/- 0.17, control: 1.72 +/- 0.25, p < 0.001) and of N-acetyl aspartate to creatin (NAA/Cr; patients: 1.41 +/- 0.15, control: 1.66 +/- 0.2, p < 0.01) indicated a pathological state. Evaluation of spectroscopic and neuropsychological data revealed a close relation between attentional impairment, i.e. delayed cerebral transmission time and decreased NAA/Cho and NAA/Cr (r = 0.62, p = 0.014). In sum, (1)H-MRS allowed a clear discrimination between patients with CSVD and age-matched normal controls. Moreover, comparisons of (1)H-MRS and neuropsychological data suggested that NAA metabolic levels, and particularly the delay in cerebral transmission time, could be potential predictors of the severeness of attentional impairment.

Online motion correction for diffusion-weighted imaging using navigator echoes: Application to RARE imaging without sensitivity loss.

This article describes the first application of true online motion correction to diffusion-weighted RARE imaging. Two orthogonal navigator echoes were acquired and zeroth and first-order phase corrections applied in less than 8 ms between a diffusion-weighted magnetization preparation and data acquisition using the RARE sequence. The zeroth-order phase correction was realized by pulsing the system's B(0)-coil: the first-order error corrected with appropriate magnetic field gradient pulses. Online correction ensured that no irreversible signal loss could occur in the imaging experiment. Diffusion-weighted images of the brain were obtained from healthy volunteers. EGG-triggered acquisition was applied at 400 ms after the R-wave. Data were acquired on a matrix of 256 x 256 with a RARE factor of 16 and a b-value of 804 smm(-2). The images obtained with online motion correction showed a remarkably high image quality, while those acquired without motion correction were severely degraded by artifacts.

The effects of microscopic tissue parameters on the diffusion weighted magnetic resonance imaging experiment.

This review examines the way in which microscopic tissue parameters can affect MR experiments which are sensitive to diffusion. The interaction between the intra- and extravascular as well as that between the intra- and extracellular spaces is examined. Susceptibility gradients due to the presence of deoxyhemoglobin can cause diffusion-induced signal losses which are significant in functional magnetic resonance experiments, particularly at higher main magnetic field strengths. This is also true of the fast response that manifests itself as an early negative signal change in functional magnetic resonance experiments. The fields surrounding paramagnetic vessels are described and the way in which diffusion in these fields contributes to functional signal changes is examined. Flow in the capillary bed can be a confounding factor in experiments which aim to examine the diffusion characteristics of extravascular water. It is potentially also a method for assessing capillary perfusion. The intravoxel incoherent motion experiment is described in terms of how significantly this effect can influence diffusion attenuation curves from water. The major models for describing water diffusion in tissue are presented, as are the main experimental results that have contributed to an understanding of the mechanisms of diffusion contrast. The widely accepted view that changes in the diffusion characteristics are caused by a shift of water to the intracellular space and a concomitant change in extracellular tortuosity is examined critically. More recent experiments that indicate that a reduction in the intracellular diffusion may occur simultaneously with the cell swelling are described and their compatibility with existing models discussed.

Implications of bulk motion for diffusion-weighted imaging experiments: effects, mechanisms, and solutions.

This review article describes the effect of bulk motion on diffusion-weighted imaging experiments, and examines methods for correcting the resulting artifacts. The emphasis throughout the article is on two-dimensional imaging of the brain. The effects of translational and rotational motion on the MR signal are described, and the literature concerning pulsatile brain motion is examined. Methods for ameliorating motion effects are divided into three generic categories. The first is methods that should be intrinsically insensitive to macroscopic motion. These include motion-compensated diffusion-weighting schemes, single-shot EPI, projection reconstruction, and line scanning. Of these, only single-shot EPI and projection reconstruction methods can obtain high-quality images without compromising on sensitivity. The second category of methods is those that can be made insensitive to bulk motion. The methods examined here are FLASH and RARE. It is shown that for both sequences motion insensitivity is in general attained only at the cost of a 50% reduction in sensitivity. The final set of methods examined are those that correct for motion, primarily navigator echoes. The properties and limitations of the navigator echo approach are presented, as are those of methods which attempt to correct the acquired data by minimizing image artifacts. The review concludes with a short summary in which the current status of diffusion imaging in the presence of bulk motion is examined.

An assessment of eddy current sensitivity and correction in single-shot diffusion-weighted imaging.

Artefacts caused by eddy currents are a major problem in diffusion weighted imaging. This is particularly acute in experiments in which a number of images with differing degrees of diffusion weighting and/or differently oriented diffusion-weighting gradients need to be combined. The echo-planar imaging sequence is particularly sensitive to the effects of residual eddy currents, especially due to the low bandwidth in the phase-encoding direction. Two published schemes are investigated regarding the effectiveness of eddy current correction. That of Jezzard et al (1998 Magn. Reson. Med. 39 801-12) requires the acquisition of additional experimental data in order to perform a post-acquisition correction, whereas that of Wider et al (1994 J. Magn. Reson. A 108 255-8) attempts to reduce the eddy currents directly. It is found that the latter experiment gives a somewhat superior performance and a combination of the two approaches results in an almost complete elimination of artefact. An alternative single-shot imaging experiment to echo-planar imaging is given by sequences based on fast spin-echo methods, which should be insensitive to the effects of constant eddy currents. It is shown that the intrinsic eddy-current-related artefact level in such experiments is indeed low, residual artefacts being attributed to eddy current decay during the echo train. In situations of poor main magnetic field homogeneity or large eddy currents such sequences may be gainfully used instead of echo-planar imaging.

Cortical reafferentation following left subcortical hemorrhage: a serial functional MR study.

A 48-year-old patient who had aphasia due to a left subcortical hemorrhage underwent three follow-up examinations to assess MR signal changes accompanying recovery. A word classification task was applied. During the 6-month follow-up period, we observed a dynamic change from negative toward positive blood oxygenation level-dependent MR signals, i.e., task-related reafferentation of eloquent cortices occurred. Clinical improvement from aphasia paralleled the MR signal changes.

Reduced power multislice MDEFT imaging.

A novel method is presented for acquiring multislice T1-weighted images. The method utilizes non-slice-selective inversion pulses followed by a series of slice-selective excitations. k-space is divided into a number of segments equal to the number of slices. Successive segments of k-space are assigned to successive slice-selective pulses, and the order in which the slices are excited is manipulated to ensure that images of each slice have identical contrast and point spread function (PSF). This method is applied to the MDEFT experiment, a particular version of the inversion recovery experiment. The implications of this acquisition scheme on the PSF are examined, and it is shown that, provided the k-space modulation function does not change sign, a good PSF is achieved. For a given maximum number of slices, the total experimental duration depends only on TR and the number of phase-encoding steps. A method of accelerating the experiment by multiply exciting each slice is described. An experimental demonstration of the proposed sequences is given by imaging the human head at 3 T.