Design and validation of a medical robotic device system to control two collaborative robots for ultrasound-guided needle insertions.

The percutaneous biopsy is a critical intervention for diagnosis and staging in cancer therapy. Robotic systems can improve the efficiency and outcome of such procedures while alleviating stress for physicians and patients. However, the high complexity of operation and the limited possibilities for robotic integration in the operating room (OR) decrease user acceptance and the number of deployed robots. Collaborative systems and standardized device communication may provide approaches to overcome named problems. Derived from the IEEE 11073 SDC standard terminology of medical device systems, we designed and validated a medical robotic device system (MERODES) to access and control a collaborative setup of two KUKA robots for ultrasound-guided needle insertions. The system is based on a novel standard for service-oriented device connectivity and utilizes collaborative principles to enhance user experience. Implementing separated workflow applications allows for a flexible system setup and configuration. The system was validated in three separate test scenarios to measure accuracies for 1) co-registration, 2) needle target planning in a water bath and 3) in an abdominal phantom. The co-registration accuracy averaged 0.94 ± 0.42 mm. The positioning errors ranged from 0.86 ± 0.42 to 1.19 ± 0.70 mm in the water bath setup and from 1.69 ± 0.92 to 1.96 ± 0.86 mm in the phantom. The presented results serve as a proof-of-concept and add to the current state of the art to alleviate system deployment and fast configuration for percutaneous robotic interventions.

Analysis of the paraspinal muscle morphology of the lumbar spine using a convolutional neural network (CNN).

PURPOSE: This single-center study aimed to develop a convolutional neural network to segment multiple consecutive axial magnetic resonance imaging (MRI) slices of the lumbar spinal muscles of patients with lower back pain and automatically classify fatty muscle degeneration. METHODS: We developed a fully connected deep convolutional neural network (CNN) with a pre-trained U-Net model trained on a dataset of 3,650 axial T2-weighted MRI images from 100 patients with lower back pain. We included all qualities of MRI; the exclusion criteria were fractures, tumors, infection, or spine implants. The training was performed using k-fold cross-validation (k = 10), and performance was evaluated using the dice similarity coefficient (DSC) and cross-sectional area error (CSA error). For clinical correlation, we used a simplified Goutallier classification (SGC) system with three classes. RESULTS: The mean DSC was high for overall muscle (0.91) and muscle tissue segmentation (0.83) but showed deficiencies in fatty tissue segmentation (0.51). The CSA error was small for the overall muscle area of 8.42%, and fatty tissue segmentation showed a high mean CSA error of 40.74%. The SGC classification was correctly predicted in 75% of the patients. CONCLUSION: Our fully connected CNN segmented overall muscle and muscle tissue with high precision and recall, as well as good DSC values. The mean predicted SGC values of all available patient axial slices showed promising results. With an overall Error of 25%, further development is needed for clinical implementation. Larger datasets and training of other model architectures are required to segment fatty tissue more accurately.

Robot-Assisted Image-Guided Interventions.

Image guidance is a common methodology of minimally invasive procedures. Depending on the type of intervention, various imaging modalities are available. Common imaging modalities are computed tomography, magnetic resonance tomography, and ultrasound. Robotic systems have been developed to enable and improve the procedures using these imaging techniques. Spatial and technological constraints limit the development of versatile robotic systems. This paper offers a brief overview of the developments of robotic systems for image-guided interventions since 2015 and includes samples of our current research in this field.

Mathematical model for the thermal enhancement of radiation response: thermodynamic approach.

Radiotherapy can effectively kill malignant cells, but the doses required to cure cancer patients may inflict severe collateral damage to adjacent healthy tissues. Recent technological advances in the clinical application has revitalized hyperthermia treatment (HT) as an option to improve radiotherapy (RT) outcomes. Understanding the synergistic effect of simultaneous thermoradiotherapy via mathematical modelling is essential for treatment planning. We here propose a theoretical model in which the thermal enhancement ratio (TER) relates to the cell fraction being radiosensitised by the infliction of sublethal damage through HT. Further damage finally kills the cell or abrogates its proliferative capacity in a non-reversible process. We suggest the TER to be proportional to the energy invested in the sensitisation, which is modelled as a simple rate process. Assuming protein denaturation as the main driver of HT-induced sublethal damage and considering the temperature dependence of the heat capacity of cellular proteins, the sensitisation rates were found to depend exponentially on temperature; in agreement with previous empirical observations. Our findings point towards an improved definition of thermal dose in concordance with the thermodynamics of protein denaturation. Our predictions well reproduce experimental in vitro and in vivo data, explaining the thermal modulation of cellular radioresponse for simultaneous thermoradiotherapy.

GATOR: connecting integrated operating room solutions based on the IEEE 11073 SDC and ORiN standards.

PURPOSE: Medical device interoperability in operating rooms (OR) provides advantages for both, patients and physicians. Several approaches were made to provide standards for successful device integration. However, with high heterogeneity of standards in the market, device vendors may reject these approaches. The aim of this work is therefore to provide a proof of concept for the connection of two promising integration solutions OR.NET and SCOT to increase vendor interest. METHODS: The connection of devices between both domains is targeted by implementing an application to map device capabilities between the IEEE 11073 SDC and ORiN standards. Potential properties of the respective architectures are defined. The connection was evaluated by latency measurements in a demonstrator setup utilizing an OR light as an exemplary device. RESULTS: The latency measurements resulted in a similar transmission speed of the GATOR (53.0 ms) and direct SDC-to-SDC (38.0 ms) communication. Direct proprietary ORiN-to-ORiN communication was faster in any case (8.0 ms). CONCLUSION: A connection between both standards was successfully achieved via the GATOR application. The results show comparable magnitudes of the communication between the standards compared to the direct standard-internal communication.

Distribution and Interaction of Murine Pulmonary Phagocytes in the Naive and Allergic Lung.

The division of labor between pulmonary phagocytic subsets [macrophage/monocyte and dendritic cell (DC) subpopulations] has been described at the functional level. However, whether these lung phagocytes also display unique spatial distribution remains unclear. Here, to analyze cellular distribution in lung compartments and contacts between phagocyte subpopulations, we established an immunohistochemistry (IHC)-based method to clearly identify murine lung phagocyte subsets in situ based on differential expression of CD11c, CD11b, MHC-II, Langerin and mPDCA-1. Furthermore, we investigated subset-specific functional differences in antigen uptake and spatial changes upon allergic sensitization. Our staining allowed the distinction between alveolar macrophages (AMs), interstitial macrophage (IM) subpopulations, CD11b+ DC subpopulations, CD103+ DCs, and plasmacytoid DCs (pDCs). We identified interstitial regions between airways and around airways as regions of IM/CD11b+ DC/CD103+ DC clusters, where a subset of IMs (IM2) and CD103+ DCs formed intense contacts that decreased upon allergic sensitization. These data indicate functional interactions between both cell types either in steady state or after antigen encounter affecting the development of allergies or tolerance. Furthermore, we observed major antigen uptake in AMs and IMs rather than DC subpopulations that was not restricted to airways and adjacent areas. This will enable to focus future studies to immunologically relevant cellular interactions and to unravel which cells are tipping the balance between pro-inflammatory immune responses or tolerance.

Monitoring C3aR Expression Using a Floxed tdTomato-C3aR Reporter Knock-in Mouse.

C3a exerts multiple biologic functions through activation of its cognate C3a receptor. C3-/- and C3aR-/- mice have been instrumental in defining important roles of the C3a/C3aR axis in the regulation of acute and chronic inflammatory diseases, including ischemia/reperfusion injury, allergic asthma, autoimmune nephritis, and rheumatoid arthritis. Surprisingly little is known about C3aR expression and function in immune and stromal cells. To close this gap, we generated a floxed tandem-dye Tomato (tdTomato)-C3aR reporter knock-in mouse, which we used to monitor C3aR expression in cells residing in the lung, airways, lamina propria (LP) of the small intestine, brain, visceral adipose tissue, bone marrow (BM), spleen, and the circulation. We found a strong expression of tdTomato-C3aR in the brain, lung, LP, and visceral adipose tissue, whereas it was minor in the spleen, blood, BM, and the airways. Most macrophage and eosinophil populations were tdTomato-C3aR+ Interestingly, most tissue eosinophils and some macrophage populations expressed C3aR intracellularly. BM-derived dendritic cells (DCs), lung-resident cluster of differentiation (CD) 11b+ conventional DCs (cDCs) and monocyte-derived DCs, LP CD103+, and CD11b+ cDCs but not pulmonary CD103+ cDCs and splenic DCs were tdTomato-C3aR+ Surprisingly, neither BM, blood, lung neutrophils, nor mast cells expressed C3aR. Similarly, all lymphoid-derived cells were tdTomato-C3aR-, except some LP-derived type 3 innate lymphoid cells. Pulmonary and LP-derived epithelial cells expressed at best minor levels of C3aR. In summary, we provide novel insights into the expression pattern of C3aR in mice. The floxed C3aR knock-in mouse will help to reliably track and conditionally delete C3aR expression in experimental models of inflammation.