Pulsatility Index in the Basal Ganglia Arteries Increases with Age in Elderly with and without Cerebral Small Vessel Disease.

BACKGROUND AND PURPOSE: Cerebral small vessel disease contributes to stroke and cognitive impairment and interacts with Alzheimer disease pathology. Because of the small dimensions of the affected vessels, in vivo characterization of blood flow properties is challenging but important to unravel the underlying mechanisms of the disease. MATERIALS AND METHODS: A 2D phase-contrast sequence at 7T MR imaging was used to assess blood flow velocity and the pulsatility index of the perforating basal ganglia arteries. We included patients with cerebral amyloid angiopathy (n = 8; identified through the modified Boston criteria), hypertensive arteriopathy (n = 12; identified through the presence of strictly deep or mixed cerebral microbleeds), and age- and sex-matched controls (n = 28; no cerebral microbleeds). RESULTS: Older age was related to a greater pulsatility index, irrespective of cerebral small vessel disease. In hypertensive arteriopathy, there was an association between lower blood flow velocity of the basal ganglia and the presence of peri-basal ganglia WM hyperintensities. CONCLUSIONS: Our results suggest that age might be the driving factor for altered cerebral small vessel hemodynamics. Furthermore, this study puts cerebral small vessel disease downstream pathologies in the basal ganglia region in relation to blood flow characteristics of the basal ganglia microvasculature.

Characterization of Cerebellar Atrophy and Resting State Functional Connectivity Patterns in Sporadic Adult-Onset Ataxia of Unknown Etiology (SAOA).

Sporadic adult-onset ataxia of unknown etiology (SAOA) is a non-genetic neurodegenerative disorder of the cerebellum of unknown cause which manifests with progressive ataxia without severe autonomic failure. Although SAOA is associated with cerebellar degeneration, little is known about the specific cerebellar atrophy pattern in SAOA. Thirty-seven SAOA patients and 49 healthy controls (HCs) were included at two centers. We investigated the structural and functional characteristics of SAOA brains using voxel-based morphometry (VBM) and resting-state functional imaging (rs-fMRI). In order to examine the functional consequence of structural cerebellar alterations, the amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) were analyzed, and then assessed their relation with disease severity, disease duration, and age of onset within these regions. Group differences were investigated using two-sample t tests, controlling for age, gender, site, and the total intracranial volume. The VBM analysis revealed a significant, mostly bilateral reduction of local gray matter (GM) volume in lobules I-V, V, VI, IX, X, and vermis VIII a/b in SAOA patients, compared with HCs. The GM volume loss in these regions was significantly associated with disease severity, disease duration, and age of onset. The disease-related atrophy regions did not show any functional alternations compared with HCs but were functionally characterized by high ALFF and poor DC compared with intact cerebellar regions. Our data revealed volume reduction in SAOA in cerebellar regions that are known to be involved in motor and somatosensory processing, corresponding with the clinical phenotype of SAOA. Our data suggest that the atrophy occurs in those cerebellar regions which are characterized by high ALFF and poor DC. Further studies have to show if these findings are specific for SAOA, and if they can be used to predict disease progression.

Contribution of iron and protein contents from rat brain subcellular fractions to MR phase imaging.

PURPOSE: Investigation of magnetic susceptibility and chemical exchange as sources of MRI phase contrast between gray and white matter resulting from protein and iron content from subcellular fractions. METHODS: This study analyzes the iron and macromolecule content of different subcellular fractions from rat brain and their relation to the water-resonance frequency by NMR spectroscopy. Additionally, the contributions of susceptibility and exchange were determined with different NMR reference substances. RESULTS: Only weak correlations between iron (r = 0.4318, P = 0.76) or protein content (r = 0.4704, P = 0.70) and frequency shift were observed. After membrane depletion, the correlation for iron increased to r = -0.9006 (P = 0.0009), whereas the shift relative to protein content increased much less (r = -0.4982, P = 0.64). Exchange-driven frequency shifts were 1.283 ppb/(mg/ml) for myelin and 0.775 ppb/(mg/ml) for synaptosomes; susceptibility-driven shifts were -1.209 ppb/(mg/ml) for myelin and -0.368 ppb/(mg/ml) for synaptosomes. The ratios between susceptibility and exchange differ significantly from simple protein solutions. CONCLUSIONS: As a result of counteracting susceptibility and exchange and increased relative shifts in membrane-depleted fractions, we conclude that tissue microstructure accounts more for the in vivo phase contrast than in the situation of homogenized tissue. Thus, membranes may generate much of the in vivo MR phase contrast resulting from anisotropy. Magn Reson Med 77:2028-2039, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Perceptual Experience of Visual Motion Activates hMT+ Independently From the Physical Reality: fMRI Insights From the Looming Pinna Figure.

The human motion processing area, hMT+, has been labeled the critical neural area for processing of real and illusory visual motion in radial 2D patterns. However, the activation in hMT+ during perception of illusory rotation in the looming double-circular Pinna Figure (PF) generated in 3D space has not been observed yet. To do so, an optic-flow like motion of rings (looming) in PF was generated on a computer screen. A psychophysically precise nulling procedure allowed quantifying the individual amount of the perceived illusory rotation in PF (PI) for each participant. The interpolation of the individual illusory motion parameters created a subjectively non-rotating PF and a physically rotating control stimulus of identical rotary strength as the PI. The physically rotating control was a double-circular figure which diverged from PF only in its arrangement of luminance gradients. In a 3-Tesla scanner, participants were presented with a random order of rotating and non-rotating figures (illusory, real, no rotation, and nulled PI). Both types, illusory and real rotation, when equal in perceptual strength for the observer, were found to be processed by hMT+.

Motion correction in MRI of the brain.

Subject motion in MRI is a relevant problem in the daily clinical routine as well as in scientific studies. Since the beginning of clinical use of MRI, many research groups have developed methods to suppress or correct motion artefacts. This review focuses on rigid body motion correction of head and brain MRI and its application in diagnosis and research. It explains the sources and types of motion and related artefacts, classifies and describes existing techniques for motion detection, compensation and correction and lists established and experimental approaches. Retrospective motion correction modifies the MR image data during the reconstruction, while prospective motion correction performs an adaptive update of the data acquisition. Differences, benefits and drawbacks of different motion correction methods are discussed.

The role of blood vessels in high-resolution volume conductor head modeling of EEG.

Reconstruction of the electrical sources of human EEG activity at high spatio-temporal accuracy is an important aim in neuroscience and neurological diagnostics. Over the last decades, numerous studies have demonstrated that realistic modeling of head anatomy improves the accuracy of source reconstruction of EEG signals. For example, including a cerebro-spinal fluid compartment and the anisotropy of white matter electrical conductivity were both shown to significantly reduce modeling errors. Here, we for the first time quantify the role of detailed reconstructions of the cerebral blood vessels in volume conductor head modeling for EEG. To study the role of the highly arborized cerebral blood vessels, we created a submillimeter head model based on ultra-high-field-strength (7T) structural MRI datasets. Blood vessels (arteries and emissary/intraosseous veins) were segmented using Frangi multi-scale vesselness filtering. The final head model consisted of a geometry-adapted cubic mesh with over 17×10(6) nodes. We solved the forward model using a finite-element-method (FEM) transfer matrix approach, which allowed reducing computation times substantially and quantified the importance of the blood vessel compartment by computing forward and inverse errors resulting from ignoring the blood vessels. Our results show that ignoring emissary veins piercing the skull leads to focal localization errors of approx. 5 to 15mm. Large errors (>2cm) were observed due to the carotid arteries and the dense arterial vasculature in areas such as in the insula or in the medial temporal lobe. Thus, in such predisposed areas, errors caused by neglecting blood vessels can reach similar magnitudes as those previously reported for neglecting white matter anisotropy, the CSF or the dura - structures which are generally considered important components of realistic EEG head models. Our findings thus imply that including a realistic blood vessel compartment in EEG head models will be helpful to improve the accuracy of EEG source analyses particularly when high accuracies in brain areas with dense vasculature are required.

[Neurofunctional MRI at high magnetic fields]. / Neurofunktionelle MRT bei hohen Feldern.

CLINICAL/METHODICAL ISSUE: Functional magnetic resonance imaging (fMRI) examinations are limited in their sensitivity due to the low activation-induced signal change. Within short tolerable scan times the spatial resolution is thus limited. STANDARD RADIOLOGICAL METHODS: fMRI is a reliable tool in neuroscience as well as for clinical applications such as presurgical mapping of brain function. METHODICAL INNOVATIONS: The fMRI sensitivity improves greatly (more than linearly) with increasing magnetic field strengths. For many years this was the main driving force in the push towards higher field strengths, such as 7 T. PERFORMANCE: The sensitivity gain is greatest for high spatial resolution and fMRI with very high sub-millimeter resolution becomes feasible. Current results demonstrate that the localization of the blood oxygenation level dependent (BOLD) signal is better than previously assumed. ACHIEVEMENTS: High-field fMRI not only allows quantitative improvements but also opens the way to new information content, such as columnar and layer-dependent functional structures of the cortex. This may pave the way for further information, e.g. the directionality of cortico-cortical connections; however, these possibilities also pose new challenges. New methods for processing such high resolution data are required which do not require spatial smoothing and preserve the high information content. PRACTICAL RECOMMENDATIONS: Common spatial resolutions of 2-3 mm are still very well suited for examinations at 3 T where they benefit from the low signal void, lower geometrical distortion and reduced acoustic noise. To achieve higher resolution at 7 T parallel imaging and geometric distortion correction are essential and permit the best congruence with structural data. The echo time at 7 T should be adjusted to about 20-25 ms. Data processing for single subjects or patients should be performed with little or no smoothing to retain resolution. Group studies could achieve good correlation with local normalization. New methods for information extraction, such as multivariate pattern analysis may allow combination of group data without the need for voxel-based congruence.

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.

SAR simulations for high-field MRI: how much detail, effort, and accuracy is needed?

Accurate prediction of specific absorption rate (SAR) for high field MRI is necessary to best exploit its potential and guarantee safe operation. To reduce the effort (time, complexity) of SAR simulations while maintaining robust results, the minimum requirements for the creation (segmentation, labeling) of human models and methods to reduce the time for SAR calculations for 7 Tesla MR-imaging are evaluated. The geometric extent of the model required for realistic head-simulations and the number of tissue types sufficient to form a reliable but simplified model of the human body are studied. Two models (male and female) of the virtual family are analyzed. Additionally, their position within the head-coil is taken into account. Furthermore, the effects of retuning the coils to different load conditions and the influence of a large bore radiofrequency-shield have been examined. The calculation time for SAR simulations in the head can be reduced by 50% without significant error for smaller model extent and simplified tissue structure outside the coil. Likewise, the model generation can be accelerated by reducing the number of tissue types. Local SAR can vary up to 14% due to position alone. This must be considered and sets a limit for SAR prediction accuracy. All these results are comparable between the two body models tested.

The impact of physiological noise correction on fMRI at 7 T.

Cognitive neuroimaging studies typically require fast whole brain image acquisition with maximal sensitivity to small BOLD signal changes. To increase the sensitivity, higher field strengths are often employed, since they provide an increased image signal-to-noise ratio (SNR). However, as image SNR increases, the relative contribution of physiological noise to the total time series noise will be greater compared to that from thermal noise. At 7 T, we studied how the physiological noise contribution can be best reduced for EPI time series acquired at three different spatial resolutions (1.1 mm × 1.1 mm × 1.8 mm, 2 mm × 2 mm × 2 mm and 3 mm × 3 mm × 3 mm). Applying optimal physiological noise correction methods improved temporal SNR (tSNR) and increased the numbers of significantly activated voxels in fMRI visual activation studies for all sets of acquisition parameters. The most dramatic results were achieved for the lowest spatial resolution, an acquisition parameter combination commonly used in cognitive neuroimaging which requires high functional sensitivity and temporal resolution (i.e. 3mm isotropic resolution and whole brain image repetition time of 2s). For this data, physiological noise models based on cardio-respiratory information improved tSNR by approximately 25% in the visual cortex and 35% sub-cortically. When the time series were additionally corrected for the residual effects of head motion after retrospective realignment, the tSNR was increased by around 58% in the visual cortex and 71% sub-cortically, exceeding tSNR ~140. In conclusion, optimal physiological noise correction at 7 T increases tSNR significantly, resulting in the highest tSNR per unit time published so far. This tSNR improvement translates into a significant increase in BOLD sensitivity, facilitating the study of even subtle BOLD responses.

Frontostriatal activation in patients with obsessive-compulsive disorder before and after cognitive behavioral therapy.

BACKGROUND: Cognitive behavioral therapy (CBT) with exposure and response prevention (ERP) is the psychotherapeutic treatment of choice for obsessive-compulsive disorder (OCD). However, little is known about the impact of CBT on frontostriatal dysfunctioning, known to be the neuronal correlate of OCD. METHOD: A probabilistic reversal learning (RL) task probing adaptive strategy switching capabilities was used in 10 unmedicated patients with OCD and 10 healthy controls during an event-related functional magnetic resonance imaging (fMRI) experiment. Patients were scanned before and after intensive CBT, controls twice at comparable intervals. RESULTS: Strategy change within the RL task involved activity in a broad frontal network in patients and controls. No significant differences between the groups or in group by time interactions were detected in a whole-brain analysis corrected for multiple comparisons. However, a reanalysis with a more lenient threshold revealed decreased responsiveness of the orbitofrontal cortex and right putamen during strategy change before treatment in patients compared with healthy subjects. A group by time effect was found in the caudate nucleus, demonstrating increased activity for patients over the course of time. Patients with greater clinical improvement, reflected by greater reductions in Yale-Brown Obsessive Compulsive Scale (YBOCS) scores, showed more stable activation in the pallidum. CONCLUSIONS: Although these findings are preliminary and need to be replicated in larger samples, they indicate a possible influence of psychotherapy on brain activity in core regions that have been shown to be directly involved both in acquisition of behavioral rules and stereotypes and in the pathophysiology of OCD, the caudate nucleus and the pallidum.

High field FMRI reveals thalamocortical integration of segregated cognitive and emotional processing in mediodorsal and intralaminar thalamic nuclei.

Thalamocortical loops, connecting functionally segregated, higher order cortical regions, and basal ganglia, have been proposed not only for well described motor and sensory regions, but also for limbic and prefrontal areas relevant for affective and cognitive processes. These functions are, however, more specific to humans, rendering most invasive neuroanatomical approaches impossible and interspecies translations difficult. In contrast, non-invasive imaging of functional neuroanatomy using fMRI allows for the development of elaborate task paradigms capable of testing the specific functionalities proposed for these circuits. Until recently, spatial resolution largely limited the anatomical definition of functional clusters at the level of distinct thalamic nuclei. Since their anatomical distinction seems crucial not only for the segregation of cognitive and limbic loops but also for the detection of their functional interaction during cognitive-emotional integration, we applied high resolution fMRI on 7 Tesla. Using an event-related design, we could isolate thalamic effects for preceding attention as well as experience of erotic stimuli. We could demonstrate specific thalamic effects of general emotional arousal in mediodorsal nucleus and effects specific to preceding attention and expectancy in intralaminar centromedian/parafascicular complex. These thalamic effects were paralleled by specific coactivations in the head of caudate nucleus as well as segregated portions of rostral or caudal cingulate cortex and anterior insula supporting distinct thalamo-striato-cortical loops. In addition to predescribed effects of sexual arousal in hypothalamus and ventral striatum, high resolution fMRI could extent this network to paraventricular thalamus encompassing laterodorsal and parataenial nuclei. We could lend evidence to segregated subcortical loops which integrate cognitive and emotional aspects of basic human behavior such as sexual processing.

Single-voxel MRS with prospective motion correction and retrospective frequency correction.

Subject motion during MRS investigations is a factor limiting the quality and the diagnostic value of the spectra. The possibility of using external motion tracking data to correct for artefacts in MR imaging has been demonstrated previously. In this paper the utility of prospective motion correction for single-voxel proton MRS is investigated. The object motion data are used in real time to update the position of the spectroscopy voxel during the acquisition prior to every sequence repetition cycle. It is not, however, sufficient to update the voxel position alone due to shim changes accompanying subject motion. Adverse effects of frequency shifts induced by subject motion are effectively suppressed by the interleaved reference scan method.

Human 7T MRI: First Clinical and Neuroscientific Applications.

After many years of development and niche applications in a very limited number of laboratories, human 7T magnetic resonance imaging systems are becoming available to a number of clinical and neuroscientific researchers. The spectrum of available methods and their robustness is increasing and the first studies are underway to evaluate the potential applications and benefits for larger clinical studies or even clinical diagnosis. A number of technical and methodological challenges currently limit the application mainly to examinations of the brain. Some of the current possibilities of ultra-high field systems and examples of first applications in patient and research studies are demonstrated to give the reader an overview.

fMRI evidence for sensorimotor transformations in human cortex during smooth pursuit eye movements.

Smooth pursuit eye movements (SP) are driven by moving objects. The pursuit system processes the visual input signals and transforms this information into an oculomotor output signal. Despite the object's movement on the retina and the eyes' movement in the head, we are able to locate the object in space implying coordinate transformations from retinal to head and space coordinates. To test for the visual and oculomotor components of SP and the possible transformation sites, we investigated three experimental conditions: (I) fixation of a stationary target with a second target moving across the retina (visual), (II) pursuit of the moving target with the second target moving in phase (oculomotor), (III) pursuit of the moving target with the second target remaining stationary (visuo-oculomotor). Precise eye movement data were simultaneously measured with the fMRI data. Visual components of activation during SP were located in the motion-sensitive, temporo-parieto-occipital region MT+ and the right posterior parietal cortex (PPC). Motor components comprised more widespread activation in these regions and additional activations in the frontal and supplementary eye fields (FEF, SEF), the cingulate gyrus and precuneus. The combined visuo-oculomotor stimulus revealed additional activation in the putamen. Possible transformation sites were found in MT+ and PPC. The MT+ activation evoked by the motion of a single visual dot was very localized, while the activation of the same single dot motion driving the eye was rather extended across MT+. The eye movement information appeared to be dispersed across the visual map of MT+. This could be interpreted as a transfer of the one-dimensional eye movement information into the two-dimensional visual map. Potentially, the dispersed information could be used to remap MT+ to space coordinates rather than retinal coordinates and to provide the basis for a motor output control. A similar interpretation holds for our results in the PPC region.

Magnetic resonance lymphangiography in Klippel-Trénaunay syndrome.

To date, lymphoscintigraphy and conventional, direct lymphography have been the favoured imaging modalities in assessing the lymphatic system in patients with Klippel-Trénaunay syndrome. We report on the first patient suffering from Klippel-Trénaunay syndrome whose lymphatic vasculature of the lower limbs was evaluated with MR lymphangiography.

[Visual rating of T2'-blood-oxygen-level-dependent magnetic resonance imaging in acute stroke patients--a pilot study]. / T2'-Blood-Oxygen-Level-Dependent-Magnetresonanz-Bildgebung beim akuten Schlaganfall--eine Pilotstudie.

PURPOSE: Delineation of brain tissue that is at risk but not yet infarcted (penumbra) continues to be a major challenge for stroke imaging. Metabolic characterization of the penumbra might be able to be achieved using blood-oxygen-level-dependent (BOLD) imaging. MATERIALS AND METHODS: We analyzed MRI data from 20 patients within the first 6 hours after stroke onset and after 5-8 days. Among other sequences, the MRI protocol consisted of diffusion-weighted (DWI/ADC = apparent diffusion coefficient) and quantitative T2 and T2* imaging (qT2, qT2*). BOLD images (T2') were calculated using 1/T2' = 1/qT2* - 1/qT2. BOLD lesions were rated by two blinded observers. RESULTS: Based on the primary blinded reading of the BOLD images, the lesion side was rated correctly by observers 1 and 2 in 80/50 % of the cases, incorrectly in 5/40 % of the cases, and rated as not visible in 15/10 % of the cases. After unblinding the observers, the visibility was rated in 45/45 % of the cases as good, in 35/40 % of the cases as reasonable, and in 20/15 % of the cases as insufficient for diagnostic purposes. The sensitivity for subsequent infarct growth was 0.88 (95 % confidence interval, CI 0.47 to 0.99), the specificity was 0.33 (95 % CI 0.07 to 0.70), the positive predictive value (PPV) was 0.54 (95 % CI 0.25 to 0.81), and the negative predictive value (NPV) was 0.75 (95 % CI 0.19 to 0.99). The odds ratio for subsequent infarct growth was 3.5 (95 % CI 0.20 to 115.53). CONCLUSION: Hypo-intense lesions in BOLD imaging were visible and exceeded the lesion in diffusion-weighted imaging in most of the stroke patients. The encouraging results justify further testing of the hypothesis that BOLD lesions, when larger than DWI lesions, are associated with infarct growth from initial DWI to final infarct.

Prospective real-time slice-by-slice motion correction for fMRI in freely moving subjects.

Subject motion is still the major source of data quality degradation in functional magnetic resonance imaging (fMRI) studies. Established methods correct motion between successive repetitions based on the acquired imaging volumes either retrospectively or prospectively. A fast, highly accurate, and prospective real-time correction method for fMRI using external optical motion tracking has been implemented. The head position is determined by means of an optical stereoscopic tracking system. The method corrects motion during the acquisition of an fMRI time series on a slice-by-slice basis by continuously updating the imaging volume position to follow the motion of the head. This method allows the measurement of fMRI data in the presence of significant motion during the acquisition of a single volume. Even without intentional motion, fMRI signal stability is maintained and higher sensitivity to detect activation is achieved without reducing specificity. With significant motion, only the proposed approach allowed detection of brain activation. The results show that the new method is superior to image-based correction methods, which fail in the case of fast or excessive motion.

Magnetic resonance imaging of freely moving objects: prospective real-time motion correction using an external optical motion tracking system.

Subject motion and associated artefacts limit the applicability of MRI and the achievable quality of the images acquired. In this paper, a fully integrated method for prospective correction of arbitrary rigid body motion employing an external motion tracking device is demonstrated for the first time. The position of the imaging volume is updated prior to every excitation of the spin system. The performance of the available tracking hardware and its connection to the MR imager is analyzed in detail. With the introduction of a novel calibration procedure the accuracy of motion correction is improved compared to previous approaches. Together with the high geometry update rate even freely moving objects can be imaged without motion related artefacts. The high performance and image quality improvement in case of subject motion are demonstrated for various imaging techniques such as gradient and spin echo, as well as echo planar imaging.