Uwe Mittag

On the combined effects of normobaric hypoxia and bed rest upon bone and mineral metabolism: Results from the PlanHab study

Bone losses are common as a consequence of unloading and also in patients with chronic obstructive pulmonary disease (COPD). Although hypoxia has been implicated as an important factor to drive bone loss, its interaction with unloading remains unresolved. The objective therefore was to assess whether human bone loss caused by unloading could be aggravated by chronic hypoxia. In a cross-over designed study, 14 healthy young men underwent 21-day interventions of bed rest in normoxia (NBR), bed rest in hypoxia (HBR), and hypoxic ambulatory confinement (HAmb). Hypoxic conditions were equivalent to 4000m altitude. Bone metabolism (NTX, P1NP, sclerostin, DKK1) and phospho-calcic homeostasis (calcium and phosphate serum levels and urinary excretion, PTH) were assessed from regular blood samples and 24-hour urine collections, and tibia and femur bone mineral content was assessed by peripheral quantitative computed tomography (pQCT). Urinary NTX excretion increased (P<0.001) to a similar extent in NBR and HBR (P=0.69) and P1NP serum levels decreased (P=0.0035) with likewise no difference between NBR and HBR (P=0.88). Serum total calcium was increased during bed rest by 0.059 (day D05, SE 0.05mM) to 0.091mM (day D21, P<0.001), with no additional effect by hypoxia during bed rest (P=0.199). HAmb led, at least temporally, to increased total serum calcium, to reduced serum phosphate, and to reduced phosphate and calcium excretion. In conclusion, hypoxia did not aggravate bed rest-induced bone resorption, but led to changes in phospho-calcic homeostasis likely caused by hyperventilation. Whether hyperventilation could have mitigated the effects of hypoxia in this study remains to be established.

Diameter Measurement of Vascular Structures in Ultrasound Video Sequences

Abstract Today, computer aided assessment of ultrasound video sequences is considered the gold standard. Ultrasound analysis forms an integral part of the medical research studies performed at the DLR. Currently, two studies are being performed that obtain ultrasound measurements of vascular structures. In this project, a software is developed that supports these and future studies in providing a framework for ultrasound analysis. Furthermore a method for obtaining assessment of diameter measurements from vascular structures in ultrasound video material is provided. Following the problem analysis based on scenarios and tasks the use cases were constructed and used for an system design. A virtual window was derived from the requirements specification—use cases. After consulting the customer with the virtual window, it was later realized by implementing the GUI. The developed software is clearly structured and focuses on extensibility. To be able to achieve this goal, the softwares main components clearly separated by integrating the model view controller pattern into the software’s architecture. The facade pattern is utilized to provide easy access to the frameworks interface models and hides the complexity. In the approach of developing the image processing, the image material was examined in depth and characteristics defined. The approach for determining the edges on the vessel walls for diameter measurement is to differentiate the image with a first order derivate of a Gaussian filter. The edges are then detected by analyzing the differentiated image. Diameter measurement between the edges follows certain assumptions that have been made. The diameter measurement algorithm was later evaluated. The evaluation of the diameter measurement algorithm showed that there is considerable variability between the gold standard of manual measurement and the software results. Furthermore, it was shown that the video quality and the definition of the region of interest have an impact on measurement accuracy. Concluding the software developed here delivers a framework for ultrasound image analysis and enables the further refinement of the measurement algorithm and flexible implementation into future ultrasound applications.

Hypoxia Aggravates Inactivity-Related Muscle Wasting

Poor musculoskeletal state is commonly observed in numerous clinical populations such as chronic obstructive pulmonary disease (COPD) and heart failure patients. It, however, remains unresolved whether systemic hypoxemia, typically associated with such clinical conditions, directly contributes to muscle deterioration. We aimed to experimentally elucidate the effects of systemic environmental hypoxia upon inactivity-related muscle wasting. For this purpose, fourteen healthy, male participants underwent three 21-day long interventions in a randomized, cross-over designed manner: (i) bed rest in normoxia (NBR; PiO2 = 133.1 ± 0.3 mmHg), (ii) bed rest in normobaric hypoxia (HBR; PiO2 = 90.0 ± 0.4 mmHg) and ambulatory confinement in normobaric hypoxia (HAmb; PiO2 = 90.0 ± 0.4 mmHg). Peripheral quantitative computed tomography and vastus lateralis muscle biopsies were performed before and after the interventions to obtain thigh and calf muscle cross-sectional areas and muscle fiber phenotype changes, respectively. A significant reduction of thigh muscle size following NBR (-6.9%, SE 0.8%; P < 0.001) was further aggravated following HBR (-9.7%, SE 1.2%; P = 0.027). Bed rest-induced muscle wasting in the calf was, by contrast, not exacerbated by hypoxic conditions (P = 0.47). Reductions in both thigh (-2.7%, SE 1.1%, P = 0.017) and calf (-3.3%, SE 0.7%, P < 0.001) muscle size were noted following HAmb. A significant and comparable increase in type 2× fiber percentage of the vastus lateralis muscle was noted following both bed rest interventions (NBR = +3.1%, SE 2.6%, HBR = +3.9%, SE 2.7%, P < 0.05). Collectively, these data indicate that hypoxia can exacerbate inactivity-related muscle wasting in healthy active participants and moreover suggest that the combination of both, hypoxemia and lack of activity, as seen in COPD patients, might be particularly harmful for muscle tissue.

SOLEUS: Ankle Foot Orthosis for Space Countermeasure with Immersive Virtual Reality

This paper presents the SOLEUS project, which aims to design innovative countermeasure for astronauts in space, based on the development of an active foot orthosis and immersive virtual reality technologies. The paper introduces the problematics of space countermeasure and describes the expected benefits of the proposed technology. It provides details on the system architecture, components and the simulation tool that has been used to support the design process. Finally, the scientific evaluation strategy for the validation of the system is introduced.

Musculoskeletal Simulation of SOLEUS Ankle Exoskeleton for Countermeasure Exercise in Space

SOLEUS system aims at providing efficient countermeasure exercises focused on the lower legs. The final product is foreseen to be based on an orthotics structure allowing exercising the ankle joint and muscle groups, even in microgravity. In order to test the pedal-pulling scenario for the operation of the system, multibody dynamics based musculoskeletal simulation has been performed. The result of the simulation shows the profile of the ankle plantar flexion torque by muscles with the given exoskeleton’s actuator force and motion conditions. Also the muscle activation patterns could be retrieved.

Partially Rigid 3D Registration of Flexible Tissues in High Resolution Anatomical MRI

This contribution introduces a method for partially rigid 3D registration of high resolution magnetic resonance (MR) images of the eye globes (EG) and the optic nerve sheaths (ONS) based on the reconstruction of their 3D models. Conventional registration methods do not preserve anatomical structures in such a way that quantitative anatomical comparisons could be computed. Therefore, iterative closest points (ICP) registration method has been extended to enable partial rigid registration (PICP) of flexible tissue structures within certain spatially limited areas. The results of the proposed approach are compared with the non-linear registration method ART. It was shown that PICP approach considerably improved the matching quality of local tissue and preserved anatomical structure at the same time.