Multimodal control of neck muscles for vestibular mediated head oscillation damping during walking: a pilot study.

PURPOSE: It is still in question whether head oscillation damping during walking forms a part of the vestibular function. The anatomical pathway from the vestibular system to the neck muscles via the medial vestibulospinal tract (MVST) is well known but there is a lack of knowledge of the exact influence and modulation of each other in daily life activities. METHODS: (I) We fixed a head-neck unit of a human cadaver specimen in a steal frame to determine the required pitch-torque for a horizontal head position. The mean value of the acquired pitch-torque was 0.54 Nm. (II) On a motorized treadmill we acquired kinematic data of the head, the sternum and both feet by wireless 3D IMUs for seven asymptomatic volunteers. Subsequently three randomized task conditions were performed. Condition 1 was walking without any irritation. Condition 2 imitated a sacculus irritation using a standardized cVEMP signal. The third condition used an electric neck muscle-irritation (TENS). The data were analyzed by the simulation environment software OpenSim 4.0. RESULTS: 8 neck muscle pairs were identified. By performing three different conditions we observed some highly significant deviations of the neck muscle peak torques. Analysing Euler angles, we found during walking a LARP and RALP head pendulum, which also was strongly perturbated. CONCLUSION: Particularly the pitch-down head oscillation damping is the most challenging one for neck muscles, especially under biomechanical concerns. Mainly via MVST motor activity of neck muscles  might be modulated by vestibular motor signals. Two simultaneous proprioceptor effects might optimize head oscillation damping. One might be a proprioceptive feedback loop to the vestibular nucleus. Another might trigger the cervicocollic reflex (CCR).

Angiopoietin-2 stimulation of endothelial cells induces alphavbeta3 integrin internalization and degradation.

The angiopoietins (Ang-1 and Ang-2) have been identified as agonistic and antagonistic ligands of the endothelial receptor tyrosine kinase Tie2, respectively. Both ligands have been demonstrated to induce translocation of Tie2 to cell-cell junctions. However, only Ang-1 induces Tie2-dependent Akt activation and subsequent survival signaling and endothelial quiescence. Ang-2 interferes negatively with Ang-1/Tie2 signaling, thereby antagonizing the Ang-1/Tie2 axis. Here, we show that both Ang-1 and Ang-2 recruit beta3 integrins to Tie2. This co-localization is most prominent in cell-cell junctions. However, only Ang-2 stimulation resulted in complex formation among Tie2, alphavbeta3 integrin, and focal adhesion kinase as evidenced by co-immunoprecipitation experiments. Focal adhesion kinase was phosphorylated in the FAT domain at Ser(910) upon Ang-2 stimulation and the adaptor proteins p130Cas and talin dissociated from alphavbeta3 integrin. The alphavbeta3 integrin was internalized, ubiquitinylated, and gated toward lysosomes. Taken together, the experiments define Tie2/alphavbeta3 integrin association-induced integrin internalization and degradation as mechanistic consequences of endothelial Ang-2 stimulation.

Peripheral Vestibular Disorders: An Epidemiologic Survey in 70 Million Individuals.

BACKGROUND: Dizziness is a common complaint in medicine. Nevertheless, there is a lack of valid data concerning the age and gender distribution of dizziness disorders within a larger population. Therefore, the aim of the present study is to undertake a representative epidemiological survey that examines all age groups of an entire population and describes the age and gender distribution of the most common peripheral vestibular disorders. METHODS: A population-based epidemiological survey based on confirmed ICD-10 codes, of an entire national population was performed. The population-based data of 70,315,919 patients were leveraged, as provided by 123 statutory health insurance companies in Germany. Patients of all age groups were analyzed. Outcome measures were age and gender distribution and the prevalence of unspecific vertigo, Meniere's disease, benign paroxysmal positional vertigo, vestibular neuritis, and other peripheral vestibular disorders. RESULTS: The prevalence among the recorded diagnoses was 6.5% (6,461/100,000 individuals), with women (N = 2,973,323; 65.4%) being significantly more frequently affected by vertigo than men (N = 1,570,240; 34.6%; p < 0.001). Vertigo is rare in childhood (i.e., up to 10-14 yr of age). Subsequently, the prevalence of the analyzed diseases increases with age, up to a peak between 74 and 94 years. CONCLUSIONS: The results demonstrate that peripheral vestibular disorders are common in a developed country, across all age groups and a specific distribution of these disorders can be identified for every age group and gender. The impact of these disorders on the German healthcare system is currently underestimated.

A spherical harmonics intensity model for 3D segmentation and 3D shape analysis of heterochromatin foci.

The genome is partitioned into regions of euchromatin and heterochromatin. The organization of heterochromatin is important for the regulation of cellular processes such as chromosome segregation and gene silencing, and their misregulation is linked to cancer and other diseases. We present a model-based approach for automatic 3D segmentation and 3D shape analysis of heterochromatin foci from 3D confocal light microscopy images. Our approach employs a novel 3D intensity model based on spherical harmonics, which analytically describes the shape and intensities of the foci. The model parameters are determined by fitting the model to the image intensities using least-squares minimization. To characterize the 3D shape of the foci, we exploit the computed spherical harmonics coefficients and determine a shape descriptor. We applied our approach to 3D synthetic image data as well as real 3D static and real 3D time-lapse microscopy images, and compared the performance with that of previous approaches. It turned out that our approach yields accurate 3D segmentation results and performs better than previous approaches. We also show that our approach can be used for quantifying 3D shape differences of heterochromatin foci.

True four-dimensional analysis of thoracic aortic displacement and distension using model-based segmentation of computed tomography angiography.

Previous analyses of aortic displacement and distension using computed tomography angiography (CTA) were performed on double-oblique multi-planar reformations and did not consider through-plane motion. The aim of this study was to overcome this limitation by using a novel computational approach for the assessment of thoracic aortic displacement and distension in their true four-dimensional extent. Vessel segmentation with landmark tracking was executed on CTA of 24 patients without evidence of aortic disease. Distension magnitudes and maximum displacement vectors (MDV) including their direction were analyzed at 5 aortic locations: left coronary artery (COR), mid-ascending aorta (ASC), brachiocephalic trunk (BCT), left subclavian artery (LSA), descending aorta (DES). Distension was highest for COR (2.3 ± 1.2 mm) and BCT (1.7 ± 1.1 mm) compared with ASC, LSA, and DES (p < 0.005). MDV decreased from COR to LSA (p < 0.005) and was highest for COR (6.2 ± 2.0 mm) and ASC (3.8 ± 1.9 mm). Displacement was directed towards left and anterior at COR and ASC. Craniocaudal displacement at COR and ASC was 1.3 ± 0.8 and 0.3 ± 0.3 mm. At BCT, LSA, and DES no predominant displacement direction was observable. Vessel displacement and wall distension are highest in the ascending aorta, and ascending aortic displacement is primarily directed towards left and anterior. Craniocaudal displacement remains low even close to the left cardiac ventricle.

3D morphometry using automated aortic segmentation in native MR angiography: an alternative to contrast enhanced MRA?

INTRODUCTION: Native-MR angiography (N-MRA) is considered an imaging alternative to contrast enhanced MR angiography (CE-MRA) for patients with renal insufficiency. Lower intraluminal contrast in N-MRA often leads to failure of the segmentation process in commercial algorithms. This study introduces an in-house 3D model-based segmentation approach used to compare both sequences by automatic 3D lumen segmentation, allowing for evaluation of differences of aortic lumen diameters as well as differences in length comparing both acquisition techniques at every possible location. METHODS AND MATERIALS: Sixteen healthy volunteers underwent 1.5-T-MR Angiography (MRA). For each volunteer, two different MR sequences were performed, CE-MRA: gradient echo Turbo FLASH sequence and N-MRA: respiratory-and-cardiac-gated, T2-weighted 3D SSFP. Datasets were segmented using a 3D model-based ellipse-fitting approach with a single seed point placed manually above the celiac trunk. The segmented volumes were manually cropped from left subclavian artery to celiac trunk to avoid error due to side branches. Diameters, volumes and centerline length were computed for intraindividual comparison. For statistical analysis the Wilcoxon-Signed-Ranked-Test was used. RESULTS: Average centerline length obtained based on N-MRA was 239.0±23.4 mm compared to 238.6±23.5 mm for CE-MRA without significant difference (P=0.877). Average maximum diameter obtained based on N-MRA was 25.7±3.3 mm compared to 24.1±3.2 mm for CE-MRA (P<0.001). In agreement with the difference in diameters, volumes obtained based on N-MRA (100.1±35.4 cm(3)) were consistently and significantly larger compared to CE-MRA (89.2±30.0 cm(3)) (P<0.001). CONCLUSIONS: 3D morphometry shows highly similar centerline lengths for N-MRA and CE-MRA, but systematically higher diameters and volumes for N-MRA.

Segmentation and quantification of the aortic arch using joint 3D model-based segmentation and elastic image registration.

Accurate quantification of the morphology of vessels is important for diagnosis and treatment of cardiovascular diseases. We introduce a new joint segmentation and registration approach for the quantification of the aortic arch morphology that combines 3D model-based segmentation with elastic image registration. With this combination, the approach benefits from the robustness of model-based segmentation and the accuracy of elastic registration. The approach can cope with a large spectrum of vessel shapes and particularly with pathological shapes that deviate significantly from the underlying model used for segmentation. The performance of the approach has been evaluated on the basis of 3D synthetic images, 3D phantom data, and clinical 3D CTA images including pathologies. We also performed a quantitative comparison with previous approaches.

Model-based segmentation and motion analysis of the thoracic aorta from 4D ECG-gated CTA images.

Pathologies of the thoracic aorta can alter the shape and motion pattern of the aorta throughout the cardiac cycle. For diagnosis and therapy planning, determination of the aortic shape and motion is important. We introduce a new approach for segmentation and motion analysis of the thoracic aorta from 4D ECG-CTA images, which combines spatial and temporal tracking, motion determination by intensity-based matching, and 3D fitting of vessel models. The approach has been successfully applied to 30 clinically relevant 4D CTA image sequences. We have also performed a quantitative evaluation of the segmentation accuracy.

Combined model-based segmentation and elastic registration for accurate quantification of the aortic arch.

Accurate quantification of the morphology of vessels is important for diagnosis and treatment of cardiovascular diseases. We introduce a new approach for the quantification of the aortic arch morphology that combines 3D model-based segmentation with elastic image registration. The performance of the approach has been evaluated using 3D synthetic images and clinically relevant 3D CTA images including pathologies. We also performed a comparison with a previous approach.

Hybrid spline-based multimodal registration using local measures for joint entropy and mutual information.

We introduce a new hybrid approach for spline-based elastic registration of multimodal medical images. The approach uses point landmarks as well as intensity information based on local analytic measures for joint entropy and mutual information. The information-theoretic similarity measures are computationally efficient and can be optimized independently for each voxel. We have applied our approach to synthetic images, brain phantom images, as well as clinically relevant multimodal medical images. We also compared our measures with previous measures.