Cost-effective 3D scanning and printing technologies for outer ear reconstruction: current status.

Current 3D scanning and printing technologies offer not only state-of-the-art developments in the field of medical imaging and bio-engineering, but also cost and time effective solutions for surgical reconstruction procedures. Besides tissue engineering, where living cells are used, bio-compatible polymers or synthetic resin can be applied. The combination of 3D handheld scanning devices or volumetric imaging, (open-source) image processing packages, and 3D printers form a complete workflow chain that is capable of effective rapid prototyping of outer ear replicas. This paper reviews current possibilities and latest use cases for 3D-scanning, data processing and printing of outer ear replicas with a focus on low-cost solutions for rehabilitation engineering.

Mitosis domain generalization in histopathology images - The MIDOG challenge.

The density of mitotic figures (MF) within tumor tissue is known to be highly correlated with tumor proliferation and thus is an important marker in tumor grading. Recognition of MF by pathologists is subject to a strong inter-rater bias, limiting its prognostic value. State-of-the-art deep learning methods can support experts but have been observed to strongly deteriorate when applied in a different clinical environment. The variability caused by using different whole slide scanners has been identified as one decisive component in the underlying domain shift. The goal of the MICCAI MIDOG 2021 challenge was the creation of scanner-agnostic MF detection algorithms. The challenge used a training set of 200 cases, split across four scanning systems. As test set, an additional 100 cases split across four scanning systems, including two previously unseen scanners, were provided. In this paper, we evaluate and compare the approaches that were submitted to the challenge and identify methodological factors contributing to better performance. The winning algorithm yielded an F1 score of 0.748 (CI95: 0.704-0.781), exceeding the performance of six experts on the same task.

Electromagnetic tool for the endoscopic creation of colon anastomoses-development and feasibility assessment of a novel anastomosis compression implant approach.

BACKGROUND: Colorectal anastomoses are among the most commonly performed interventions in abdominal surgery, while associated patient trauma is still high. Most recent trends of endoscopic anastomosis devices integrate magnetic components to overcome the challenges of minimally invasive surgery. However, the mutual attraction between magnetic implant halves may increase the risk of inadvertently pinching healthy structures. Thus, we present a novel anastomosis device to improve system controllability and flexibility. METHODS: A magnetic implant and an applicator with electromagnetic control units were developed. The interaction of magnetic implants with the electromagnets bears particular challenges with respect to the force-related dimensioning. Here, attraction forces must be overcome by the electromagnet actuation to detach the implant, while the attraction force between the implant halves must be sufficient to ensure a stable connection. Thus, respective forces were measured and the detachment process was reproducibly investigated. Patient hazards, associated with resistance-related heating of the coils were investigated. RESULTS: Anastomosis formation was reproducibly successful for an implant, with an attraction force of 1.53 [Formula: see text], resulting in a compression pressure of [Formula: see text]. The implant was reproducibly detachable from the applicator at the anastomosis site. Coils heated up to a maximum temperature of [Formula: see text]. Furthermore, we were able to establish a neat reconnection of intestinal bowel endings using our implant. DISCUSSION: As we achieved nearly equal compression forces with our implant as other magnetic anastomosis systems did (Magnamosis™: 1.48 N), we concluded that our approach provides sufficient holding strength to counteract the forces acting immediately postoperatively, which would eventually lead to an undesired slipping of the implant halves during the healing phase. Based on heat transfer investigations, preventive design specifications were derived, revealing that the wall thickness of a polymeric isolation is determined rather by stability considerations, than by heat shielding requirements.

[Presentation and evaluation of the haptic-visual ear surgery training system "HaptiVisT"]. / Vorstellung und Evaluation des haptisch-visuellen, ohrchirurgischen Trainingssystems "HaptiVisT".

BACKGROUND: Operations on the temporal bone are a special challenge for ENT surgeons. The aim of the BMBF-funded project was to develop a realistic training system for ear operations in the form of a "serious game". METHODS: The presented prototype of the HaptiVisT system functions as a training system for ear surgeries with visual feedback through a glasses-free 3D monitor and feedback by means of a haptic arm simulating the drill. A variety of training options is guaranteed by three available surgical procedures (antrotomy, mastoidectomy, posterior tympanotomy). A weighted point system enables the measurability of the training success. Following the technical development of the prototype, a prospective evaluation was carried out by eight ENT physicians and four students regarding "learning content" and "user experience". A standardized questionnaire was used (ordinal scale: 1=very good to 5=very bad). RESULTS: Regarding the learning content, the aspects "strengthening anatomy (mean=1.58)", "training hand-eye coordination (1.67)", "transferability into practice (1.83)", "usefulness for practice (1.33)" yielded good to very good scores. "User experience" also showed good results for the aspects "realism (2.29)", "interaction of haptics and optics (2.33)" and "immersion in the training system (1.89)". The "motivation factor" was very high for all test subjects (1.2). CONCLUSIONS: The training system for ear surgeries "HaptiVisT" offers the possibility of immersive training. Integration into the daily clinical routine and in particular into the medical training to become an ENT specialist therefore seems to make sense.

Fast whole-slide cartography in colon cancer histology using superpixels and CNN classification.

Purpose: Automatic outlining of different tissue types in digitized histological specimen provides a basis for follow-up analyses and can potentially guide subsequent medical decisions. The immense size of whole-slide-images (WSIs), however, poses a challenge in terms of computation time. In this regard, the analysis of nonoverlapping patches outperforms pixelwise segmentation approaches but still leaves room for optimization. Furthermore, the division into patches, regardless of the biological structures they contain, is a drawback due to the loss of local dependencies. Approach: We propose to subdivide the WSI into coherent regions prior to classification by grouping visually similar adjacent pixels into superpixels. Afterward, only a random subset of patches per superpixel is classified and patch labels are combined into a superpixel label. We propose a metric for identifying superpixels with an uncertain classification and evaluate two medical applications, namely tumor area and invasive margin estimation and tumor composition analysis. Results: The algorithm has been developed on 159 hand-annotated WSIs of colon resections and its performance is compared with an analysis without prior segmentation. The algorithm shows an average speed-up of 41% and an increase in accuracy from 93.8% to 95.7%. By assigning a rejection label to uncertain superpixels, we further increase the accuracy by 0.4%. While tumor area estimation shows high concordance to the annotated area, the analysis of tumor composition highlights limitations of our approach. Conclusion: By combining superpixel segmentation and patch classification, we designed a fast and accurate framework for whole-slide cartography that is AI-model agnostic and provides the basis for various medical endpoints.

Panoramic Imaging Assessment of Different Bladder Phantoms - An Evaluation Study.

OBJECTIVE: To evaluate "panoramic image stitching" for cystoscopy, a novel technique to augment a urologist's field of view transoperatively in real-time during a cystoscopic "keyhole" procedure, 3-D bladder phantoms provide a suitable setting. Thus, the objective is the evaluation of different 3-D printed bladder phantoms with respect to their ability to be used for extended experiments of panoramic cystoscopy. MATERIALS AND METHODS: Five bladder phantoms with different geometries, surface textures, stiffness and materials were assessed with rigid 0- and 30-degree lenses and a video-cystoscope regarding suitability for image stitching. For panoramic image generation, we use an established real-time stitching approach successfully applied to retrospective cystoscopy image sequences from real clinical cases. For evaluation of the experiments two quality criteria were defined, namely 'completeness' (describing the internal area of the phantom that can be stitched), and 'extension' (how far does an acquired panorama extend beyond the assumed 'equator' of the phantom). RESULTS: Panoramas of all phantom and endoscope combinations were computed. Using landmarks (south pole, north pole, equator) in the phantoms, maximum extension of the panoramas was assessed. The computed panoramas yield maximum extensions between 270o (0-degree cystoscope) and 330o (video cystoscope). Deformable phantoms yield larger panoramas than the rigid models. CONCLUSION: In can be concluded that the stitching process works quite well with all evaluated phantoms. Nevertheless, a novel phantom would be needed, combing a deformable, elliptical geometry and real-type vascular texture in the inside, that can be filled with water.

Artificial Intelligence-Based Polyp Detection in Colonoscopy: Where Have We Been, Where Do We Stand, and Where Are We Headed?

BACKGROUND: In the past, image-based computer-assisted diagnosis and detection systems have been driven mainly from the field of radiology, and more specifically mammography. Nevertheless, with the availability of large image data collections (known as the "Big Data" phenomenon) in correlation with developments from the domain of artificial intelligence (AI) and particularly so-called deep convolutional neural networks, computer-assisted detection of adenomas and polyps in real-time during screening colonoscopy has become feasible. SUMMARY: With respect to these developments, the scope of this contribution is to provide a brief overview about the evolution of AI-based detection of adenomas and polyps during colonoscopy of the past 35 years, starting with the age of "handcrafted geometrical features" together with simple classification schemes, over the development and use of "texture-based features" and machine learning approaches, and ending with current developments in the field of deep learning using convolutional neural networks. In parallel, the need and necessity of large-scale clinical data will be discussed in order to develop such methods, up to commercially available AI products for automated detection of polyps (adenoma and benign neoplastic lesions). Finally, a short view into the future is made regarding further possibilities of AI methods within colonoscopy. KEY MESSAGES: Research of image-based lesion detection in colonoscopy data has a 35-year-old history. Milestones such as the Paris nomenclature, texture features, big data, and deep learning were essential for the development and availability of commercial AI-based systems for polyp detection.

Force-feedback assisted and virtual fixtures based K-wire drilling simulation.

One common method to fix fractures of the human hand after an accident is an osteosynthesis with Kirschner wires (K-wires) to stabilize the bone fragments. The insertion of K-wires is a delicate minimally invasive surgery, because surgeons operate almost without a sight. Since realistic training methods are time consuming, costly and insufficient, a virtual-reality (VR) based training system for the placement of K-wires was developed. As part of this, the current work deals with the real-time bone drilling simulation using a haptic force-feedback device. To simulate the drilling, we introduce a virtual fixture based force-feedback drilling approach. By decomposition of the drilling task into individual phases, each phase can be handled individually to perfectly control the drilling procedure. We report about the related finite state machine (FSM), describe the haptic feedback of each state and explain, how to avoid jerking of the haptic force-feedback during state transition. The usage of the virtual fixture approach results in a good haptic performance and a stable drilling behavior. This was confirmed by 26 expert surgeons, who evaluated the virtual drilling on the simulator and rated it as very realistic. To make the system even more convincing, we determined real drilling feed rates through experimental pig bone drilling and transferred them to our system. Due to a constant simulation thread we can guarantee a precise drilling motion. Virtual fixtures based force-feedback calculation is able to simulate force-feedback assisted bone drilling with high quality and, thus, will have a great potential in developing medical applications.

Co-staining of microRNAs and their target proteins by miRNA in situ hybridization and immunohistofluorescence on prostate cancer tissue microarrays.

The co-expression of miRNAs and their target proteins was studied on tissue microarrays from different prostate cancer (PCa) patients. PCa of primary Gleason pattern 4 (GP4), lymph node metastases of GP4, distant metastases, and normal tissue from the transitional and peripheral zones were co-stained by fluorescent miRNA in situ hybridization (miRisH) and protein immunohistofluorescence (IHF). The miRNAs and corresponding target proteins include the pairs miR-145/ERG, miR-143/uPAR, and miR-375/SEC23A. The fluorescence-stained and scanned tissue microarrays (TMAs) were evaluated by experienced uropathologists. The pair miR-145/ERG showed an exclusive staining for miR-145 in the nuclei of stromal cells, both in tumor and normal tissue, and for ERG in the cytoplasm with/without co-expression in the nucleus of tumor cells. The pair miR-143/uPAR revealed a clear distinction between miR-143 in the nuclei of stromal cells and uPAR staining in the cytoplasm of tumor cells. Metastases (lymph node and distant) however, showed tumor cells with cytoplasmic staining for miR-143/uPAR. In normal tissues, beside the nuclei of the stroma cells, gland cells could also express miR-143 and uPAR in the cytoplasm. miR-375 showed particular staining in the nucleoli of GP4 and metastatic samples, suggesting that nucleoli play a special role in sequestering proteins and miRNAs. Combined miRisH/IHF allows for the study of miRNA expression patterns and their target proteins at the single-cell level.

Automated polyp detection in the colorectum: a prospective study (with videos).

BACKGROUND AND AIMS: Adenoma detection is a highly personalized task that differs markedly among endoscopists. Technical advances are therefore desirable for the improvement of the adenoma detection rate (ADR). An automated computer-driven technology would offer the chance to objectively assess the presence of colorectal polyps during colonoscopy. We present here the application of a real-time automated polyp detection software (APDS) under routine colonoscopy conditions. METHODS: This was a prospective study at a university hospital in Germany. A prototype of a novel APDS ("KoloPol," Fraunhofer IIS, Erlangen, Germany) was used for automated image-based polyp detection. The software functions by highlighting structures of possible polyp lesions in a color-coded manner during real-time colonoscopy procedures. Testing the feasibility of APDS deployment under real-time conditions was the primary goal of the study. APDS polyp detection rates (PDRs) were defined as secondary endpoints provided that endoscopists' detection served as criterion standard. RESULTS: The APDS was applied in 55 routine colonoscopies without the occurrence of any clinically relevant adverse events. Endoscopists' PDRs and ADRs were 56.4% and 30.9%, respectively. The PDRs and ADRs of the APDS were 50.9% and 29.1%, respectively. The APDS detected 55 of 73 polyps (75.3%). Smaller polyp size and flat polyp morphology were correlated with insufficient polyp detection by the APDS. CONCLUSION: Computer-assisted automated low-delay polyp detection is feasible during real-time colonoscopy. Efforts should be undertaken to improve the APDS with respect to smaller and flat shaped polyps. (Clinical trial registration number: NCT02838888.).

IFN-γ-response mediator GBP-1 represses human cell proliferation by inhibiting the Hippo signaling transcription factor TEAD.

Interferon-gamma (IFN-γ) is a pleiotropic cytokine that exerts important functions in inflammation, infectious diseases, and cancer. The large GTPase human guanylate-binding protein 1 (GBP-1) is among the most strongly IFN-γ-induced cellular proteins. Previously, it has been shown that GBP-1 mediates manifold cellular responses to IFN-γ including the inhibition of proliferation, spreading, migration, and invasion and through this exerts anti-tumorigenic activity. However, the mechanisms of GBP-1 anti-tumorigenic activities remain poorly understood. Here, we elucidated the molecular mechanism of the human GBP-1-mediated suppression of proliferation by demonstrating for the first time a cross-talk between the anti-tumorigenic IFN-γ and Hippo pathways. The α9-helix of GBP-1 was found to be sufficient to inhibit proliferation. Protein-binding and molecular modeling studies revealed that the α9-helix binds to the DNA-binding domain of the Hippo signaling transcription factor TEA domain protein (TEAD) mediated by the 376VDHLFQK382 sequence at the N-terminus of the GBP-1-α9-helix. Mutation of this sequence resulted in abrogation of both TEAD interaction and suppression of proliferation. Further on, the interaction caused inhibition of TEAD transcriptional activity associated with the down-regulation of TEAD-target genes. In agreement with these results, IFN-γ treatment of the cells also impaired TEAD activity, and this effect was abrogated by siRNA-mediated inhibition of GBP-1 expression. Altogether, this demonstrated that the α9-helix is the proliferation inhibitory domain of GBP-1, which acts independent of the GTPase activity through the inhibition of the Hippo transcription factor TEAD in mediating the anti-proliferative cell response to IFN-γ.

Using automated texture features to determine the probability for masking of a tumor on mammography, but not ultrasound.

BACKGROUND: Tumors in radiologically dense breast were overlooked on mammograms more often than tumors in low-density breasts. A fast reproducible and automated method of assessing percentage mammographic density (PMD) would be desirable to support decisions whether ultrasonography should be provided for women in addition to mammography in diagnostic mammography units. PMD assessment has still not been included in clinical routine work, as there are issues of interobserver variability and the procedure is quite time consuming. This study investigated whether fully automatically generated texture features of mammograms can replace time-consuming semi-automatic PMD assessment to predict a patient's risk of having an invasive breast tumor that is visible on ultrasound but masked on mammography (mammography failure). METHODS: This observational study included 1334 women with invasive breast cancer treated at a hospital-based diagnostic mammography unit. Ultrasound was available for the entire cohort as part of routine diagnosis. Computer-based threshold PMD assessments ("observed PMD") were carried out and 363 texture features were obtained from each mammogram. Several variable selection and regression techniques (univariate selection, lasso, boosting, random forest) were applied to predict PMD from the texture features. The predicted PMD values were each used as new predictor for masking in logistic regression models together with clinical predictors. These four logistic regression models with predicted PMD were compared among themselves and with a logistic regression model with observed PMD. The most accurate masking prediction was determined by cross-validation. RESULTS: About 120 of the 363 texture features were selected for predicting PMD. Density predictions with boosting were the best substitute for observed PMD to predict masking. Overall, the corresponding logistic regression model performed better (cross-validated AUC, 0.747) than one without mammographic density (0.734), but less well than the one with the observed PMD (0.753). However, in patients with an assigned mammography failure risk >10%, covering about half of all masked tumors, the boosting-based model performed at least as accurately as the original PMD model. CONCLUSION: Automatically generated texture features can replace semi-automatically determined PMD in a prediction model for mammography failure, such that more than 50% of masked tumors could be discovered.

Analysis of Corynebacterium diphtheriae macrophage interaction: Dispensability of corynomycolic acids for inhibition of phagolysosome maturation and identification of a new gene involved in synthesis of the corynomycolic acid layer.

Corynebacterium diphtheriae is the causative agent of diphtheria, a toxin mediated disease of upper respiratory tract, which can be fatal. As a member of the CMNR group, C. diphtheriae is closely related to members of the genera Mycobacterium, Nocardia and Rhodococcus. Almost all members of these genera comprise an outer membrane layer of mycolic acids, which is assumed to influence host-pathogen interactions. In this study, three different C. diphtheriae strains were investigated in respect to their interaction with phagocytic murine and human cells and the invertebrate infection model Caenorhabditis elegans. Our results indicate that C. diphtheriae is able to delay phagolysosome maturation after internalization in murine and human cell lines. This effect is independent of the presence of mycolic acids, as one of the strains lacked corynomycolates. In addition, analyses of NF-κB induction revealed a mycolate-independent mechanism and hint to detrimental effects of the different strains tested on the phagocytic cells. Bioinformatics analyses carried out to elucidate the reason for the lack of mycolates in one of the strains led to the identification of a new gene involved in mycomembrane formation in C. diphtheriae.

Using simulated fluorescence cell micrographs for the evaluation of cell image segmentation algorithms.

BACKGROUND: Manual assessment and evaluation of fluorescent micrograph cell experiments is time-consuming and tedious. Automated segmentation pipelines can ensure efficient and reproducible evaluation and analysis with constant high quality for all images of an experiment. Such cell segmentation approaches are usually validated and rated in comparison to manually annotated micrographs. Nevertheless, manual annotations are prone to errors and display inter- and intra-observer variability which influence the validation results of automated cell segmentation pipelines. RESULTS: We present a new approach to simulate fluorescent cell micrographs that provides an objective ground truth for the validation of cell segmentation methods. The cell simulation was evaluated twofold: (1) An expert observer study shows that the proposed approach generates realistic fluorescent cell micrograph simulations. (2) An automated segmentation pipeline on the simulated fluorescent cell micrographs reproduces segmentation performances of that pipeline on real fluorescent cell micrographs. CONCLUSION: The proposed simulation approach produces realistic fluorescent cell micrographs with corresponding ground truth. The simulated data is suited to evaluate image segmentation pipelines more efficiently and reproducibly than it is possible on manually annotated real micrographs.

Digital Mapping of the Urinary Bladder: Potential for Standardized Cystoscopy Reports.

OBJECTIVE: To develop a standardized digital reporting tool for cystoscopy of the urinary bladder using panoramic imaging. MATERIALS AND METHODS: An image processing and stitching software (Endorama) was developed to generate panoramic images from cystoscopy data. In a processing phase, algorithms were modulated and refined by reference to cystoscopy sequences (n = 30). Subsequently, standard systematic cystoscopies (n = 12) were recorded in patients undergoing transurethral resection of a bladder tumor to create panoramic images. RESULTS: All sequences were applicable for the development and refinements of the software. Processing increasingly allowed the creation of images illustrating large parts of the bladder and relevant anatomic landmarks in different locations. The pathway covered by the endoscope during the intervention was illustrated as a route in the respective digital image. During the application phase, panoramic images were successfully created in 10 out of 12 cases. The resolution of the images was 4096 × 2048 pixels and the images required a median digital memory of 3.9 MB (3.4-5.7). The panoramic images illustrated 22 relevant findings of which 7 were papillary tumors. CONCLUSION: High-quality digital panoramic maps of the urinary bladder were created using specifically processed data of videocystoscopy. In this preliminary series, relevant findings were illustrated in the respective image. Our tool may help improve standardization of cystoscopy reports and reduce interobserver variability.

Semi-automated delineation of breast cancer tumors and subsequent materialization using three-dimensional printing (rapid prototyping).

OBJECTIVE: Three-dimensional (3D) printing has become widely available, and a few cases of its use in clinical practice have been described. The aim of this study was to explore facilities for the semi-automated delineation of breast cancer tumors and to assess the feasibility of 3D printing of breast cancer tumors. METHODS: In a case series of five patients, different 3D imaging methods-magnetic resonance imaging (MRI), digital breast tomosynthesis (DBT), and 3D ultrasound-were used to capture 3D data for breast cancer tumors. The volumes of the breast tumors were calculated to assess the comparability of the breast tumor models, and the MRI information was used to render models on a commercially available 3D printer to materialize the tumors. RESULTS: The tumor volumes calculated from the different 3D methods appeared to be comparable. Tumor models with volumes between 325 mm3 and 7,770 mm3 were printed and compared with the models rendered from MRI. The materialization of the tumors reflected the computer models of them. CONCLUSION: 3D printing (rapid prototyping) appears to be feasible. Scenarios for the clinical use of the technology might include presenting the model to the surgeon to provide a better understanding of the tumor's spatial characteristics in the breast, in order to improve decision-making in relation to neoadjuvant chemotherapy or surgical approaches. J. Surg. Oncol. 2017;115:238-242. © 2016 Wiley Periodicals, Inc.

The Tax-Inducible Actin-Bundling Protein Fascin Is Crucial for Release and Cell-to-Cell Transmission of Human T-Cell Leukemia Virus Type 1 (HTLV-1).

The delta-retrovirus Human T-cell leukemia virus type 1 (HTLV-1) preferentially infects CD4+ T-cells via cell-to-cell transmission. Viruses are transmitted by polarized budding and by transfer of viral biofilms at the virological synapse (VS). Formation of the VS requires the viral Tax protein and polarization of the host cytoskeleton, however, molecular mechanisms of HTLV-1 cell-to-cell transmission remain incompletely understood. Recently, we could show Tax-dependent upregulation of the actin-bundling protein Fascin (FSCN-1) in HTLV-1-infected T-cells. Here, we report that Fascin contributes to HTLV-1 transmission. Using single-cycle replication-dependent HTLV-1 reporter vectors, we found that repression of endogenous Fascin by short hairpin RNAs and by Fascin-specific nanobodies impaired gag p19 release and cell-to-cell transmission in 293T cells. In Jurkat T-cells, Tax-induced Fascin expression enhanced virus release and Fascin-dependently augmented cell-to-cell transmission to Raji/CD4+ B-cells. Repression of Fascin in HTLV-1-infected T-cells diminished virus release and gag p19 transfer to co-cultured T-cells. Spotting the mechanism, flow cytometry and automatic image analysis showed that Tax-induced T-cell conjugate formation occurred Fascin-independently. However, adhesion of HTLV-1-infected MT-2 cells in co-culture with Jurkat T-cells was reduced upon knockdown of Fascin, suggesting that Fascin contributes to dissemination of infected T-cells. Imaging of chronically infected MS-9 T-cells in co-culture with Jurkat T-cells revealed that Fascin's localization at tight cell-cell contacts is accompanied by gag polarization suggesting that Fascin directly affects the distribution of gag to budding sites, and therefore, indirectly viral transmission. In detail, we found gag clusters that are interspersed with Fascin clusters, suggesting that Fascin makes room for gag in viral biofilms. Moreover, we observed short, Fascin-containing membrane extensions surrounding gag clusters and clutching uninfected T-cells. Finally, we detected Fascin and gag in long-distance cellular protrusions. Taken together, we show for the first time that HTLV-1 usurps the host cell factor Fascin to foster virus release and cell-to-cell transmission.

Shading correction for endoscopic images using principal color components.

PURPOSE: Inhomogeneous illumination often causes significant shading and vignetting effects in images captured by an endoscope. Most of the established shading correction methods are designed for gray-level images. Only few papers have been published about how to compensate for shading in color images. For endoscopic images with a distinct red coloring, these methods tend to produce color artifacts. METHOD: A color shading correction algorithm for endoscopic images is proposed. Principal component analysis is used to calculate an appropriate estimate of the shading effect so that a one-channel shading correction can be applied without producing undesired artifacts. RESULTS: The proposed method is compared to established YUV and HSV color-conversion-based approaches. It produces superior results both on simulated and on real endoscopic images. Example images of using the proposed shading correction for endoscopic image mosaicking are presented. CONCLUSION: A new method for shading correction is presented which is tailored to images with distinct coloring. It is beneficial for the visual impression and further image analysis tasks.

The killing of macrophages by Corynebacterium ulcerans.

Corynebacterium ulcerans is an emerging pathogen transmitted by a zoonotic pathway with a very broad host spectrum to humans. Despite rising numbers of infections and potentially fatal outcomes, data on the molecular basis of pathogenicity are scarce. In this study, the interaction of 2 C. ulcerans isolates - one from an asymptomatic dog, one from a fatal case of human infection - with human macrophages was investigated. C. ulcerans strains were able to survive in macrophages for at least 20 hours. Uptake led to delay of phagolysosome maturation and detrimental effects on the macrophages as deduced from cytotoxicity measurements and FACS analyses. The data presented here indicate a high infectious potential of this emerging pathogen.

A new ex vivo beating heart model to investigate the application of heart valve performance tools with a high-speed camera.

High-speed camera examination of heart valves is an established technique to examine heart valve prosthesis. The aim of this study was to examine the possibility to transmit new tools for high-speed camera examination of heart valve behavior under near-physiological conditions in a porcine ex vivo beating heart model. After explantation of the piglet heart, main coronary arteries were cannulated and the heart was reperfused with the previously collected donor blood. When the heart started beating in sinus rhythm again, the motion of the aortic and mitral valve was recorded using a digital high-speed camera system (recording rate 2,000 frames/sec). The image sequences of the mitral valve were analyzed, and digital kymograms were calculated at different angles for the exact analysis of the different closure phases. The image sequence of the aortic valve was analyzed, and several snakes were performed to analyze the effective orifice area over the time. Both processing tools were successfully applied to examine heart valves in this ex vivo beating heart model. We were able to investigate the exact open and closure time of the mitral valve, as well as the projected effective orifice area of the aortic valve over the time. The high-speed camera investigation in an ex vivo beating heart model of heart valve behavior is feasible and also reasonable because of using processing feature such as kymography for exact analysis. These analytical techniques might help to optimize reconstructive surgery of the mitral valve and the development of heart valve prostheses in future.