Estimation of the uncertainty of elastic image registration with the demons algorithm.

The accuracy of elastic image registration is limited. We propose an approach to detect voxels where registration based on the demons algorithm is likely to perform inaccurately, compared to other locations of the same image. The approach is based on the assumption that the local reproducibility of the registration can be regarded as a measure of uncertainty of the image registration. The reproducibility is determined as the standard deviation of the displacement vector components obtained from multiple registrations. These registrations differ in predefined initial deformations. The proposed approach was tested with artificially deformed lung images, where the ground truth on the deformation is known. In voxels where the result of the registration was less reproducible, the registration turned out to have larger average registration errors as compared to locations of the same image, where the registration was more reproducible. The proposed method can show a clinician in which area of the image the elastic registration with the demons algorithm cannot be expected to be accurate.

A stochastic approach to estimate the uncertainty involved in B-spline image registration.

Uncertainties in image registration may be a significant source of errors in anatomy mapping as well as dose accumulation in radiotherapy. It is, therefore, essential to validate the accuracy of image registration. Here, we propose a method to detect areas where mono modal B-spline registration performs well and to distinguish those from areas of the same image, where the registration is likely to be less accurate. It is a stochastic approach to automatically estimate the uncertainty of the resulting displacement vector field. The coefficients resulting from the B-spline registration are subject to moderate and randomly performed variations. A quantity is proposed to characterize the local sensitivity of the similarity measure to these variations. We demonstrate the statistical dependence between the local image registration error and this quantity by calculating their mutual information. We show the significance of the statistical dependence with an approach based on random redistributions. The proposed method has the potential to divide an image into subregions which differ in the magnitude of their average registration error.

Six-minute walking-induced systemic inflammation and oxidative stress in muscle-wasted COPD patients.

BACKGROUND: Systemic inflammation and oxidative stress are potential mechanisms for muscle wasting in COPD patients. Six-minute walking testing (6MWT) has been suggested as simple and valid exercise test in COPD that is well tolerated, and reflective of activities of daily living. The present study investigated physiologic and systemic immunologic responses to a 6MWT in muscle-wasted patients with COPD and compared them with maximal cardiopulmonary exercise testing (CPET). METHODS: Ten patients with muscle-wasted COPD were included (fat-free mass index [FFMI]: men, < 16 kg/m2; women, < 15 kg/m2). 6MWT and CPET were performed in random order. The physiologic response was followed by a mobile oxycon. Arterial blood was obtained at rest and after exercise to measure blood gases and markers of systemic inflammation and oxidative stress. RESULTS: In these patients (FEV1 55 +/- 4% of predicted [mean +/- SE]), the 6MWT was a submaximal, albeit intense, exercise as reflected by oxygen uptake (VO2), minute ventilation, heart rate, and lactate values. Leukocytosis was less intense after 6MWT compared to CPET. Contrary, the increase in interleukin-6, free radical release by neutrophils, oxidation of proteins and lipids, and the reduction in antioxidant capacity were similar after both exercises. FFMI was inversely related to 6MWT-induced increases in protein and lipid peroxidation. CONCLUSIONS: This study shows that a 6MWT induces a systemic immunologic response in muscle-wasted patients with COPD, which is comparable to CPET-induced responses. The correlation between systemic oxidative stress and the degree of muscle wasting supports a possible causal relation between systemic inflammation, oxidative stress, and muscle wasting.

Exercise-induced systemic effects in muscle-wasted patients with COPD.

PURPOSE: Physical exercise is known to induce an acute inflammatory response and oxidative stress in healthy subjects and patients with chronic obstructive pulmonary disease (COPD). Increasing evidence associates systemic inflammation and oxidative stress with muscle wasting and muscle dysfunction in COPD. In the present study, it was hypothesized that exercise-induced systemic inflammatory and oxidative responses in muscle-wasted COPD patients are increased compared with non-muscle-wasted patients and healthy subjects. METHODS: Pulmonary function, body composition, and quadriceps muscle strength were measured in 10 muscle-wasted (fat-free mass index (FFMI) < 16 kg x m(-2) (men), < 15 kg x m(-2) (women)), 10 non-muscle-wasted COPD patients, and 10 healthy subjects. Systemic inflammation (C-reactive protein (CRP), leukocytes, cytokines) and oxidative stress (production of reactive oxygen species (ROS) by neutrophils, plasma antioxidant capacity, protein oxidation, lipid peroxidation, oxidized to reduced glutathione ratio (GSSG/GSH)) were determined before and after maximal and submaximal (50% of maximal work rate) cycle ergometry. RESULTS: Low-grade systemic inflammation was significantly (P < 0.05) elevated in all COPD patients and tended to be highest in muscle-wasted patients. A decreased antioxidant status (plasma antioxidant capacity, P < 0.05; GSH, P < 0.05) and increased protein oxidation (P < 0.001) reflected increased basal oxidative stress in muscle-wasted COPD patients compared with both other groups. Both maximal and submaximal exercise caused increased inflammatory (IL-6, +1.1 pg. x mL(-1) vs rest, P < 0.05) and oxidative responses (ROS release by neutrophils, + 32%; GSSG/GSH + 29%; lipid peroxidation, + 30% vs rest) in muscle-wasted COPD patients, which were less pronounced or not observed in non-muscle-wasted patients and healthy subjects. CONCLUSIONS: These data indicate that both maximal and submaximal exercise induce increased systemic inflammatory and oxidative responses in muscle-wasted COPD patients compared with non-muscle-wasted patients and healthy subjects.

Supplemental oxygen prevents exercise-induced oxidative stress in muscle-wasted patients with chronic obstructive pulmonary disease.

RATIONALE: Although oxygen therapy is of clear benefit in patients with severe chronic obstructive pulmonary disease (COPD), recent studies have shown that short-term supplementary oxygen may increase oxidative stress and inflammation within the airways. OBJECTIVE: We investigated whether systemic inflammation and oxidative stress at rest and during exercise in patients with COPD are influenced by supplemental oxygen. METHODS: Nine normoxemic, muscle-wasted patients with moderate to very severe COPD were studied. Plasma markers of systemic inflammation (leukocyte counts, interleukin 6 [IL-6]) and oxidative stress (lipid peroxidation, protein oxidation, antioxidant capacity) were measured after treatment with either supplemental oxygen (nasal, 4 L . min(-1)) or compressed air, both at rest (1 h treatment) and after submaximal exercise (40 W, constant work rate). In addition, free-radical production by neutrophils and ATP-degradation products were determined before and after exercise. RESULTS: Short-term oxygen breathing at rest did not influence systemic low-grade inflammation and oxidative stress. The IL-6 response to exercise was attenuated during cycling with supplemental oxygen. Exercise-induced lipid and protein oxidation were prevented by treatment with supplemental oxygen. This was associated with both decreased free-radical production by neutrophils and reduced formation of (hypo)xanthine and uric acid. CONCLUSION: Short-term supplementary oxygen does not affect basal systemic inflammation and oxidative stress but prevents exercise-induced oxidative stress in normoxemic, muscle-wasted patients with COPD, and attenuates plasma IL-6 response. Inhibition of neutrophil activation and ATP degradation appears to be involved in this effect.

An application framework for computer-aided patient positioning in radiation therapy.

The importance of exact patient positioning in radiation therapy increases with the ongoing improvements in irradiation planning and treatment. Therefore, new ways to overcome precision limitations of current positioning methods in fractionated treatment have to be found. The Department of Medical Physics at the German Cancer Research Centre (DKFZ) follows different video-based approaches to increase repositioning precision. In this context, the modular software framework FIVE (Fast Integrated Video-based Environment) has been designed and implemented. It is both hardware- and platform-independent and supports merging position data by integrating various computer-aided patient positioning methods. A highly precise optical tracking system and several subtraction imaging techniques have been realized as modules to supply basic video-based repositioning techniques. This paper describes the common framework architecture, the main software modules and their interfaces. An object-oriented software engineering process has been applied using the UML, C + + and the Qt library. The significance of the current framework prototype for the application in patient positioning as well as the extension to further application areas will be discussed. Particularly in experimental research, where special system adjustments are often necessary, the open design of the software allows problem-oriented extensions and adaptations.