@article{ConradGenzelCvetkovicetal.2017, author = {Conrad, Tim and Genzel, Martin and Cvetkovic, Nada and Wulkow, Niklas and Vybiral, Jan and Kutyniok, Gitta and Sch{\"u}tte, Christof}, title = {Sparse Proteomics Analysis - a compressed sensing-based approach for feature selection and classification of high-dimensional proteomics mass spectrometry data}, volume = {18}, journal = {BMC Bioinformatics}, number = {160}, doi = {10.1186/s12859-017-1565-4}, pages = {1 -- 20}, year = {2017}, abstract = {Motivation: High-throughput proteomics techniques, such as mass spectrometry (MS)-based approaches, produce very high-dimensional data-sets. In a clinical setting one is often interested how MS spectra dier between patients of different classes, for example spectra from healthy patients vs. spectra from patients having a particular disease. Machine learning algorithms are needed to (a) identify these discriminating features and (b) classify unknown spectra based on this feature set. Since the acquired data is usually noisy, the algorithms should be robust to noise and outliers, and the identied feature set should be as small as possible. Results: We present a new algorithm, Sparse Proteomics Analysis (SPA), based on the theory of Compressed Sensing that allows to identify a minimal discriminating set of features from mass spectrometry data-sets. We show how our method performs on artificial and real-world data-sets.}, language = {en} } @article{SeeberConradHoppeetal.2017, author = {Seeber, L. and Conrad, Tim and Hoppe, Christian and Obermeier, Patrick and Chen, X. and Karsch, K. and Muehlhans, S. and Tief, Franziska and Boettcher, Sindy and Diedrich, S. and Schweiger, Brunhilde and Rath, Barbara}, title = {Educating parents about the vaccination status of their children: A user-centered mobile application}, volume = {5}, journal = {Preventive Medicine Reports}, doi = {10.1016/j.pmedr.2017.01.002}, pages = {241 -- 250}, year = {2017}, abstract = {Parents are often uncertain about the vaccination status of their children. In times of vaccine hesitancy, vaccination programs could benefit from active patient participation. The Vaccination App (VAccApp) was developed by the Vienna Vaccine Safety Initiative, enabling parents to learn about the vaccination status of their children, including 25 different routine, special indication and travel vaccines listed in the WHO Immunization Certificate of Vaccination (WHO-ICV). Between 2012 and 2014, the VAccApp was validated in a hospital-based quality management program in Berlin, Germany, in collaboration with the Robert Koch Institute. Parents of 178 children were asked to transfer the immunization data of their children from the WHO-ICV into the VAccApp. The respective WHO-ICV was photocopied for independent, professional data entry (gold standard). Demonstrating the status quo in vaccine information reporting, a Recall Group of 278 parents underwent structured interviews for verbal immunization histories, without the respective WHO-ICV. Only 9\% of the Recall Group were able to provide a complete vaccination status; on average 39\% of the questions were answered correctly. Using the WHO-ICV with the help of the VAccApp resulted in 62\% of parents providing a complete vaccination status; on average 95\% of the questions were answered correctly. After using the VAccApp, parents were more likely to remember key aspects of the vaccination history. User-friendly mobile applications empower parents to take a closer look at the vaccination record, thereby taking an active role in providing accurate vaccination histories. Parents may become motivated to ask informed questions and to keep vaccinations up-to-date.}, language = {en} } @misc{AmbellanLameckervonTycowiczetal.2019, author = {Ambellan, Felix and Lamecker, Hans and von Tycowicz, Christoph and Zachow, Stefan}, title = {Statistical Shape Models - Understanding and Mastering Variation in Anatomy}, issn = {1438-0064}, doi = {10.1007/978-3-030-19385-0_5}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-72699}, year = {2019}, abstract = {In our chapter we are describing how to reconstruct three-dimensional anatomy from medical image data and how to build Statistical 3D Shape Models out of many such reconstructions yielding a new kind of anatomy that not only allows quantitative analysis of anatomical variation but also a visual exploration and educational visualization. Future digital anatomy atlases will not only show a static (average) anatomy but also its normal or pathological variation in three or even four dimensions, hence, illustrating growth and/or disease progression. Statistical Shape Models (SSMs) are geometric models that describe a collection of semantically similar objects in a very compact way. SSMs represent an average shape of many three-dimensional objects as well as their variation in shape. The creation of SSMs requires a correspondence mapping, which can be achieved e.g. by parameterization with a respective sampling. If a corresponding parameterization over all shapes can be established, variation between individual shape characteristics can be mathematically investigated. We will explain what Statistical Shape Models are and how they are constructed. Extensions of Statistical Shape Models will be motivated for articulated coupled structures. In addition to shape also the appearance of objects will be integrated into the concept. Appearance is a visual feature independent of shape that depends on observers or imaging techniques. Typical appearances are for instance the color and intensity of a visual surface of an object under particular lighting conditions, or measurements of material properties with computed tomography (CT) or magnetic resonance imaging (MRI). A combination of (articulated) statistical shape models with statistical models of appearance lead to articulated Statistical Shape and Appearance Models (a-SSAMs).After giving various examples of SSMs for human organs, skeletal structures, faces, and bodies, we will shortly describe clinical applications where such models have been successfully employed. Statistical Shape Models are the foundation for the analysis of anatomical cohort data, where characteristic shapes are correlated to demographic or epidemiologic data. SSMs consisting of several thousands of objects offer, in combination with statistical methods ormachine learning techniques, the possibility to identify characteristic clusters, thus being the foundation for advanced diagnostic disease scoring.}, language = {en} } @misc{AmbellanTackEhlkeetal.2019, author = {Ambellan, Felix and Tack, Alexander and Ehlke, Moritz and Zachow, Stefan}, title = {Automated Segmentation of Knee Bone and Cartilage combining Statistical Shape Knowledge and Convolutional Neural Networks: Data from the Osteoarthritis Initiative}, issn = {1438-0064}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-72704}, year = {2019}, abstract = {We present a method for the automated segmentation of knee bones and cartilage from magnetic resonance imaging (MRI) that combines a priori knowledge of anatomical shape with Convolutional Neural Networks (CNNs).The proposed approach incorporates 3D Statistical Shape Models (SSMs) as well as 2D and 3D CNNs to achieve a robust and accurate segmentation of even highly pathological knee structures.The shape models and neural networks employed are trained using data from the Osteoarthritis Initiative (OAI) and the MICCAI grand challenge "Segmentation of Knee Images 2010" (SKI10), respectively. We evaluate our method on 40 validation and 50 submission datasets from the SKI10 challenge.For the first time, an accuracy equivalent to the inter-observer variability of human readers is achieved in this challenge.Moreover, the quality of the proposed method is thoroughly assessed using various measures for data from the OAI, i.e. 507 manual segmentations of bone and cartilage, and 88 additional manual segmentations of cartilage. Our method yields sub-voxel accuracy for both OAI datasets. We make the 507 manual segmentations as well as our experimental setup publicly available to further aid research in the field of medical image segmentation.In conclusion, combining localized classification via CNNs with statistical anatomical knowledge via SSMs results in a state-of-the-art segmentation method for knee bones and cartilage from MRI data.}, language = {en} } @article{ObermeierHeimBiereetal.2018, author = {Obermeier, Patrick and Heim, A. and Biere, Barbara and Hage, E. and Alchikh, Maren and Conrad, Tim and Schweiger, Brunhilde and Rath, Barbara}, title = {Clinical characteristics and disease severity associated with adenovirus infections in infants and children - discovery of a novel adenovirus, HAdV-D80}, journal = {Clinical Infectious Diseases}, year = {2018}, language = {en} } @article{KorkSpiesConradetal.2018, author = {Kork, F. and Spies, Claudia and Conrad, Tim and Weiss, B. and Roenneberg, T. and Wernecke, K.-D. and Balzer, Felix}, title = {Associations of postoperative mortality with the time of day, week and year}, journal = {Anaesthesia}, year = {2018}, language = {en} } @incollection{AmbellanLameckervonTycowiczetal.2019, author = {Ambellan, Felix and Lamecker, Hans and von Tycowicz, Christoph and Zachow, Stefan}, title = {Statistical Shape Models - Understanding and Mastering Variation in Anatomy}, volume = {3}, booktitle = {Biomedical Visualisation}, number = {1156}, editor = {Rea, Paul M.}, edition = {1}, publisher = {Springer Nature Switzerland AG}, isbn = {978-3-030-19384-3}, doi = {10.1007/978-3-030-19385-0_5}, pages = {67 -- 84}, year = {2019}, abstract = {In our chapter we are describing how to reconstruct three-dimensional anatomy from medical image data and how to build Statistical 3D Shape Models out of many such reconstructions yielding a new kind of anatomy that not only allows quantitative analysis of anatomical variation but also a visual exploration and educational visualization. Future digital anatomy atlases will not only show a static (average) anatomy but also its normal or pathological variation in three or even four dimensions, hence, illustrating growth and/or disease progression. Statistical Shape Models (SSMs) are geometric models that describe a collection of semantically similar objects in a very compact way. SSMs represent an average shape of many three-dimensional objects as well as their variation in shape. The creation of SSMs requires a correspondence mapping, which can be achieved e.g. by parameterization with a respective sampling. If a corresponding parameterization over all shapes can be established, variation between individual shape characteristics can be mathematically investigated. We will explain what Statistical Shape Models are and how they are constructed. Extensions of Statistical Shape Models will be motivated for articulated coupled structures. In addition to shape also the appearance of objects will be integrated into the concept. Appearance is a visual feature independent of shape that depends on observers or imaging techniques. Typical appearances are for instance the color and intensity of a visual surface of an object under particular lighting conditions, or measurements of material properties with computed tomography (CT) or magnetic resonance imaging (MRI). A combination of (articulated) statistical shape models with statistical models of appearance lead to articulated Statistical Shape and Appearance Models (a-SSAMs).After giving various examples of SSMs for human organs, skeletal structures, faces, and bodies, we will shortly describe clinical applications where such models have been successfully employed. Statistical Shape Models are the foundation for the analysis of anatomical cohort data, where characteristic shapes are correlated to demographic or epidemiologic data. SSMs consisting of several thousands of objects offer, in combination with statistical methods ormachine learning techniques, the possibility to identify characteristic clusters, thus being the foundation for advanced diagnostic disease scoring.}, language = {en} } @article{HildebrandtBrueningSchmidtetal.2019, author = {Hildebrandt, Thomas and Bruening, Jan Joris and Schmidt, Nora Laura and Lamecker, Hans and Heppt, Werner and Zachow, Stefan and Goubergrits, Leonid}, title = {The Healthy Nasal Cavity - Characteristics of Morphology and Related Airflow Based on a Statistical Shape Model Viewed from a Surgeon's Perspective}, volume = {35}, journal = {Facial Plastic Surgery}, number = {1}, doi = {10.1055/s-0039-1677721}, pages = {9 -- 13}, year = {2019}, abstract = {Functional surgery on the nasal framework requires referential criteria to objectively assess nasal breathing for indication and follow-up. Thismotivated us to generate amean geometry of the nasal cavity based on a statistical shape model. In this study, the authors could demonstrate that the introduced nasal cavity's mean geometry features characteristics of the inner shape and airflow, which are commonly observed in symptom-free subjects. Therefore, the mean geometry might serve as a reference-like model when one considers qualitative aspects. However, to facilitate quantitative considerations and statistical inference, further research is necessary. Additionally, the authorswere able to obtain details about the importance of the isthmus nasi and the inferior turbinate for the intranasal airstream.}, language = {en} } @article{HildebrandtBrueningLameckeretal.2019, author = {Hildebrandt, Thomas and Bruening, Jan Joris and Lamecker, Hans and Zachow, Stefan and Heppt, Werner and Schmidt, Nora and Goubergrits, Leonid}, title = {Digital Analysis of Nasal Airflow Facilitating Decision Support in Rhinosurgery}, volume = {35}, journal = {Facial Plastic Surgery}, number = {1}, doi = {10.1055/s-0039-1677720}, pages = {1 -- 8}, year = {2019}, abstract = {Successful functional surgery on the nasal framework requires reliable and comprehensive diagnosis. In this regard, the authors introduce a new methodology: Digital Analysis of Nasal Airflow (diANA). It is based on computational fluid dynamics, a statistical shape model of the healthy nasal cavity and rhinologic expertise. diANA necessitates an anonymized tomographic dataset of the paranasal sinuses including the complete nasal cavity and, when available, clinical information. The principle of diANA is to compare the morphology and the respective airflow of an individual nose with those of a reference. This enablesmorphometric aberrations and consecutive flow field anomalies to localize and quantify within a patient's nasal cavity. Finally, an elaborated expert opinion with instructive visualizations is provided. Using diANA might support surgeons in decision-making, avoiding unnecessary surgery, gaining more precision, and target-orientation for indicated operations.}, language = {en} } @article{HettichSchierjottSchillingetal.2018, author = {Hettich, G. and Schierjott, R. A. and Schilling, C. and Maas, A. and Ramm, Heiko and Bindernagel, Matthias and Lamecker, Hans and Grupp, T. M.}, title = {Validation of a Statistical Shape Model for Acetabular Bone Defect Analysis}, journal = {ISTA 2018 London Abstract Book}, year = {2018}, abstract = {Acetabular bone defects are still challenging to quantify. Numerous classification schemes have been proposed to categorize the diverse kinds of defects. However, these classification schemes are mainly descriptive and hence it remains difficult to apply them in pre-clinical testing, implant development and pre-operative planning. By reconstructing the native situation of a defect pelvis using a Statistical Shape Model (SSM), a more quantitative analysis of the bone defects could be performed. The aim of this study is to develop such a SSM and to validate its accuracy using relevant clinical scenarios and parameters.}, language = {en} } @article{MirelesConrad2018, author = {Mireles, Victor and Conrad, Tim}, title = {Reusable building blocks in biological systems}, volume = {15}, journal = {Journal of the Royal Society Interface}, number = {149}, doi = {10.1098/rsif.2018.0595}, pages = {1 -- 10}, year = {2018}, abstract = {One of the most widely recognized features of biological systems is their modularity. The modules that constitute biological systems are said to be redeployed and combined across several conditions, thus acting as building blocks. In this work, we analyse to what extent are these building blocks reusable as compared with those found in randomized versions of a system. We develop a notion of decompositions of systems into phenotypic building blocks, which allows them to overlap while maximizing the number of times a building block is reused across several conditions. Different biological systems present building blocks whose reusability ranges from single use (e.g. condition specific) to constitutive, although their average reusability is not always higher than random equivalents of the system. These decompositions reveal a distinct distribution of building block sizes in real biological systems. This distribution stems, in part, from the peculiar usage pattern of the elements of biological systems, and constitutes a new angle to study the evolution of modularity.}, language = {en} } @article{MaConradAlchikhetal.2018, author = {Ma, Xiaolin and Conrad, Tim and Alchikh, Maren and Reiche, J. and Schweiger, Brunhilde and Rath, Barbara}, title = {Can we distinguish respiratory viral infections based on clinical features? A prospective pediatric cohort compared to systematic literature review}, volume = {28}, journal = {Medical Virology}, number = {5}, doi = {10.1002/rmv.1997}, pages = {1 -- 12}, year = {2018}, abstract = {Studies have shown that the predictive value of "clinical diagnoses" of influenza and other respiratory viral infections is low, especially in children. In routine care, pediatricians often resort to clinical diagnoses, even in the absence of robust evidence-based criteria. We used a dual approach to identify clinical characteristics that may help to differentiate infections with common pathogens including influenza, respiratory syncytial virus, adenovirus, metapneumovirus, rhinovirus, bocavirus-1, coronaviruses, or parainfluenza virus: (a) systematic review and meta-analysis of 47 clinical studies published in Medline (June 1996 to March 2017, PROSPERO registration number: CRD42017059557) comprising 49 858 individuals and (b) data-driven analysis of an inception cohort of 6073 children with ILI (aged 0-18 years, 56\% male, December 2009 to March 2015) examined at the point of care in addition to blinded PCR testing. We determined pooled odds ratios for the literature analysis and compared these to odds ratios based on the clinical cohort dataset. This combined analysis suggested significant associations between influenza and fever or headache, as well as between respiratory syncytial virus infection and cough, dyspnea, and wheezing. Similarly, literature and cohort data agreed on significant associations between HMPV infection and cough, as well as adenovirus infection and fever. Importantly, none of the abovementioned features were unique to any particular pathogen but were also observed in association with other respiratory viruses. In summary, our "real-world" dataset confirmed published literature trends, but no individual feature allows any particular type of viral infection to be ruled in or ruled out. For the time being, laboratory confirmation remains essential. More research is needed to develop scientifically validated decision models to inform best practice guidelines and targeted diagnostic algorithms.}, language = {en} } @article{AlchikhConradHoppeetal.2018, author = {Alchikh, Maren and Conrad, Tim and Hoppe, Christian and Ma, Xiaolin and Broberg, Eeva K. and Penttinen, P. and Reiche, J. and Biere, Barbara and Schweiger, Brunhilde and Rath, Barbara}, title = {Are we missing respiratory viral infections in infants and children? Comparison of a hospital-based quality management system with standard of care. Clinical Microbiology and Infection}, journal = {Clinical Microbiology and Infection}, number = {06/18}, doi = {10.1016/j.cmi.2018.05.023}, pages = {1 -- 1}, year = {2018}, language = {en} } @inproceedings{JayrannejadConrad2017, author = {Jayrannejad, Fahrnaz and Conrad, Tim}, title = {Better Interpretable Models for Proteomics Data Analysis Using rule-based Mining}, booktitle = {Springer Lecture Notes in Artificial Intelligence}, pages = {studi}, year = {2017}, abstract = {Recent advances in -omics technology has yielded in large data-sets in many areas of biology, such as mass spectrometry based proteomics. However, analyzing this data is still a challenging task mainly due to the very high dimensionality and high noise content of the data. One of the main objectives of the analysis is the identification of relevant patterns (or features) which can be used for classification of new samples to healthy or diseased. So, a method is required to find easily interpretable models from this data. To gain the above mentioned goal, we have adapted the disjunctive association rule mining algorithm, TitanicOR, to identify emerging patterns from our mass spectrometry proteomics data-sets. Comparison to five state-of-the-art methods shows that our method is advantageous them in terms of identifying the inter-dependency between the features and the TP-rate and precision of the features selected. We further demonstrate the applicability of our algorithm to one previously published clinical data-set.}, language = {en} } @inproceedings{TackZachow2019, author = {Tack, Alexander and Zachow, Stefan}, title = {Accurate Automated Volumetry of Cartilage of the Knee using Convolutional Neural Networks: Data from the Osteoarthritis Initiative}, booktitle = {IEEE 16th International Symposium on Biomedical Imaging (ISBI 2019)}, doi = {10.1109/ISBI.2019.8759201}, pages = {40 -- 43}, year = {2019}, abstract = {Volumetry of cartilage of the knee is needed for knee osteoarthritis (KOA) assessment. It is typically performed manually in a tedious and subjective process. We developed a method for an automated, segmentation-based quantification of cartilage volume by employing 3D Convolutional Neural Networks (CNNs). CNNs were trained in a supervised manner using magnetic resonance imaging data and cartilage volumetry readings performed by clinical experts for 1378 subjects provided by the Osteoarthritis Initiative. It was shown that 3D CNNs are able to achieve volume measures comparable to the magnitude of variation between expert readings and the real in vivo situation. In the future, accurate automated cartilage volumetry might support both, diagnosis of KOA as well as longitudinal analysis of KOA progression.}, language = {en} } @misc{AmbellanTackEhlkeetal.2019, author = {Ambellan, Felix and Tack, Alexander and Ehlke, Moritz and Zachow, Stefan}, title = {Automated Segmentation of Knee Bone and Cartilage combining Statistical Shape Knowledge and Convolutional Neural Networks: Data from the Osteoarthritis Initiative (Supplementary Material)}, volume = {52}, journal = {Medical Image Analysis}, number = {2}, doi = {10.12752/4.ATEZ.1.0}, pages = {109 -- 118}, year = {2019}, abstract = {We present a method for the automated segmentation of knee bones and cartilage from magnetic resonance imaging that combines a priori knowledge of anatomical shape with Convolutional Neural Networks (CNNs). The proposed approach incorporates 3D Statistical Shape Models (SSMs) as well as 2D and 3D CNNs to achieve a robust and accurate segmentation of even highly pathological knee structures. The shape models and neural networks employed are trained using data of the Osteoarthritis Initiative (OAI) and the MICCAI grand challenge "Segmentation of Knee Images 2010" (SKI10), respectively. We evaluate our method on 40 validation and 50 submission datasets of the SKI10 challenge. For the first time, an accuracy equivalent to the inter-observer variability of human readers has been achieved in this challenge. Moreover, the quality of the proposed method is thoroughly assessed using various measures for data from the OAI, i.e. 507 manual segmentations of bone and cartilage, and 88 additional manual segmentations of cartilage. Our method yields sub-voxel accuracy for both OAI datasets. We made the 507 manual segmentations as well as our experimental setup publicly available to further aid research in the field of medical image segmentation. In conclusion, combining statistical anatomical knowledge via SSMs with the localized classification via CNNs results in a state-of-the-art segmentation method for knee bones and cartilage from MRI data.}, language = {en} } @article{AmbellanTackEhlkeetal.2019, author = {Ambellan, Felix and Tack, Alexander and Ehlke, Moritz and Zachow, Stefan}, title = {Automated Segmentation of Knee Bone and Cartilage combining Statistical Shape Knowledge and Convolutional Neural Networks: Data from the Osteoarthritis Initiative}, volume = {52}, journal = {Medical Image Analysis}, number = {2}, doi = {10.1016/j.media.2018.11.009}, pages = {109 -- 118}, year = {2019}, abstract = {We present a method for the automated segmentation of knee bones and cartilage from magnetic resonance imaging that combines a priori knowledge of anatomical shape with Convolutional Neural Networks (CNNs). The proposed approach incorporates 3D Statistical Shape Models (SSMs) as well as 2D and 3D CNNs to achieve a robust and accurate segmentation of even highly pathological knee structures. The shape models and neural networks employed are trained using data of the Osteoarthritis Initiative (OAI) and the MICCAI grand challenge "Segmentation of Knee Images 2010" (SKI10), respectively. We evaluate our method on 40 validation and 50 submission datasets of the SKI10 challenge. For the first time, an accuracy equivalent to the inter-observer variability of human readers has been achieved in this challenge. Moreover, the quality of the proposed method is thoroughly assessed using various measures for data from the OAI, i.e. 507 manual segmentations of bone and cartilage, and 88 additional manual segmentations of cartilage. Our method yields sub-voxel accuracy for both OAI datasets. We made the 507 manual segmentations as well as our experimental setup publicly available to further aid research in the field of medical image segmentation. In conclusion, combining statistical anatomical knowledge via SSMs with the localized classification via CNNs results in a state-of-the-art segmentation method for knee bones and cartilage from MRI data.}, language = {en} } @article{ShaoBjaanaesHellandetal.2019, author = {Shao, Borong and Bjaanaes, Maria and Helland, Aslaug and Sch{\"u}tte, Christof and Conrad, Tim}, title = {EMT network-based feature selection improves prognosis prediction in lung adenocarcinoma}, volume = {14}, journal = {PLOS ONE}, number = {1}, doi = {10.1371/journal.pone.0204186}, year = {2019}, abstract = {Various feature selection algorithms have been proposed to identify cancer prognostic biomarkers. In recent years, however, their reproducibility is criticized. The performance of feature selection algorithms is shown to be affected by the datasets, underlying networks and evaluation metrics. One of the causes is the curse of dimensionality, which makes it hard to select the features that generalize well on independent data. Even the integration of biological networks does not mitigate this issue because the networks are large and many of their components are not relevant for the phenotype of interest. With the availability of multi-omics data, integrative approaches are being developed to build more robust predictive models. In this scenario, the higher data dimensions create greater challenges. We proposed a phenotype relevant network-based feature selection (PRNFS) framework and demonstrated its advantages in lung cancer prognosis prediction. We constructed cancer prognosis relevant networks based on epithelial mesenchymal transition (EMT) and integrated them with different types of omics data for feature selection. With less than 2.5\% of the total dimensionality, we obtained EMT prognostic signatures that achieved remarkable prediction performance (average AUC values above 0.8), very significant sample stratifications, and meaningful biological interpretations. In addition to finding EMT signatures from different omics data levels, we combined these single-omics signatures into multi-omics signatures, which improved sample stratifications significantly. Both single- and multi-omics EMT signatures were tested on independent multi-omics lung cancer datasets and significant sample stratifications were obtained.}, language = {en} } @article{BernardSalamancaThunbergetal.2017, author = {Bernard, Florian and Salamanca, Luis and Thunberg, Johan and Tack, Alexander and Jentsch, Dennis and Lamecker, Hans and Zachow, Stefan and Hertel, Frank and Goncalves, Jorge and Gemmar, Peter}, title = {Shape-aware Surface Reconstruction from Sparse 3D Point-Clouds}, volume = {38}, journal = {Medical Image Analysis}, doi = {10.1016/j.media.2017.02.005}, pages = {77 -- 89}, year = {2017}, abstract = {The reconstruction of an object's shape or surface from a set of 3D points plays an important role in medical image analysis, e.g. in anatomy reconstruction from tomographic measurements or in the process of aligning intra-operative navigation and preoperative planning data. In such scenarios, one usually has to deal with sparse data, which significantly aggravates the problem of reconstruction. However, medical applications often provide contextual information about the 3D point data that allow to incorporate prior knowledge about the shape that is to be reconstructed. To this end, we propose the use of a statistical shape model (SSM) as a prior for surface reconstruction. The SSM is represented by a point distribution model (PDM), which is associated with a surface mesh. Using the shape distribution that is modelled by the PDM, we formulate the problem of surface reconstruction from a probabilistic perspective based on a Gaussian Mixture Model (GMM). In order to do so, the given points are interpreted as samples of the GMM. By using mixture components with anisotropic covariances that are "oriented" according to the surface normals at the PDM points, a surface-based fitting is accomplished. Estimating the parameters of the GMM in a maximum a posteriori manner yields the reconstruction of the surface from the given data points. We compare our method to the extensively used Iterative Closest Points method on several different anatomical datasets/SSMs (brain, femur, tibia, hip, liver) and demonstrate superior accuracy and robustness on sparse data.}, language = {en} } @article{SarichDjurdjevacConradBruckneretal.2014, author = {Sarich, Marco and Djurdjevac Conrad, Natasa and Bruckner, Sharon and Conrad, Tim and Sch{\"u}tte, Christof}, title = {Modularity revisited: A novel dynamics-based concept for decomposing complex networks}, volume = {1}, journal = {Journal of Computational Dynamics}, number = {1}, doi = {10.3934/jcd.2014.1.191}, pages = {191 -- 212}, year = {2014}, language = {en} } @article{AkbariShandizBoulosSavarssonetal.2018, author = {Akbari Shandiz, Mohsen and Boulos, Paul and S{\ae}varsson, Stefan and Ramm, Heiko and Fu, Chun Kit and Miller, Stephen and Zachow, Stefan and Anglin, Carolyn}, title = {Changes in Knee Shape and Geometry Resulting from Total Knee Arthroplasty}, volume = {232}, journal = {Journal of Engineering in Medicine}, number = {1}, doi = {10.1177/0954411917743274}, pages = {67 -- 79}, year = {2018}, abstract = {Changes in knee shape and geometry resulting from total knee arthroplasty can affect patients in numerous important ways: pain, function, stability, range of motion, and kinematics. Quantitative data concerning these changes have not been previously available, to our knowledge, yet are essential to understand individual experiences of total knee arthroplasty and thereby improve outcomes for all patients. The limiting factor has been the challenge of accurately measuring these changes. Our study objective was to develop a conceptual framework and analysis method to investigate changes in knee shape and geometry, and prospectively apply it to a sample total knee arthroplasty population. Using clinically available computed tomography and radiography imaging systems, the three-dimensional knee shape and geometry of nine patients (eight varus and one valgus) were compared before and after total knee arthroplasty. All patients had largely good outcomes after their total knee arthroplasty. Knee shape changed both visually and numerically. On average, the distal condyles were slightly higher medially and lower laterally (range: +4.5 mm to -4.4 mm), the posterior condyles extended farther out medially but not laterally (range: +1.8 to -6.4 mm), patellofemoral distance increased throughout flexion by 1.8-3.5 mm, and patellar thickness alone increased by 2.9 mm (range: 0.7-5.2 mm). External femoral rotation differed preop and postop. Joint line distance, taking cartilage into account, changed by +0.7 to -1.5 mm on average throughout flexion. Important differences in shape and geometry were seen between pre-total knee arthroplasty and post-total knee arthroplasty knees. While this is qualitatively known, this is the first study to report it quantitatively, an important precursor to identifying the reasons for the poor outcome of some patients. Using the developed protocol and visualization techniques to compare patients with good versus poor clinical outcomes could lead to changes in implant design, implant selection, component positioning, and surgical technique. Recommendations based on this sample population are provided. Intraoperative and postoperative feedback could ultimately improve patient satisfaction.}, language = {en} } @article{TackMukhopadhyayZachow2018, author = {Tack, Alexander and Mukhopadhyay, Anirban and Zachow, Stefan}, title = {Knee Menisci Segmentation using Convolutional Neural Networks: Data from the Osteoarthritis Initiative}, volume = {26}, journal = {Osteoarthritis and Cartilage}, number = {5}, doi = {10.1016/j.joca.2018.02.907}, pages = {680 -- 688}, year = {2018}, abstract = {Abstract: Objective: To present a novel method for automated segmentation of knee menisci from MRIs. To evaluate quantitative meniscal biomarkers for osteoarthritis (OA) estimated thereof. Method: A segmentation method employing convolutional neural networks in combination with statistical shape models was developed. Accuracy was evaluated on 88 manual segmentations. Meniscal volume, tibial coverage, and meniscal extrusion were computed and tested for differences between groups of OA, joint space narrowing (JSN), and WOMAC pain. Correlation between computed meniscal extrusion and MOAKS experts' readings was evaluated for 600 subjects. Suitability of biomarkers for predicting incident radiographic OA from baseline to 24 months was tested on a group of 552 patients (184 incident OA, 386 controls) by performing conditional logistic regression. Results: Segmentation accuracy measured as Dice Similarity Coefficient was 83.8\% for medial menisci (MM) and 88.9\% for lateral menisci (LM) at baseline, and 83.1\% and 88.3\% at 12-month follow-up. Medial tibial coverage was significantly lower for arthritic cases compared to non-arthritic ones. Medial meniscal extrusion was significantly higher for arthritic knees. A moderate correlation between automatically computed medial meniscal extrusion and experts' readings was found (ρ=0.44). Mean medial meniscal extrusion was significantly greater for incident OA cases compared to controls (1.16±0.93 mm vs. 0.83±0.92 mm; p<0.05). Conclusion: Especially for medial menisci an excellent segmentation accuracy was achieved. Our meniscal biomarkers were validated by comparison to experts' readings as well as analysis of differences w.r.t groups of OA, JSN, and WOMAC pain. It was confirmed that medial meniscal extrusion is a predictor for incident OA.}, language = {en} } @inproceedings{AmbellanTackEhlkeetal.2018, author = {Ambellan, Felix and Tack, Alexander and Ehlke, Moritz and Zachow, Stefan}, title = {Automated Segmentation of Knee Bone and Cartilage combining Statistical Shape Knowledge and Convolutional Neural Networks: Data from the Osteoarthritis Initiative}, booktitle = {Medical Imaging with Deep Learning}, year = {2018}, abstract = {We present a method for the automated segmentation of knee bones and cartilage from magnetic resonance imaging, that combines a priori knowledge of anatomical shape with Convolutional Neural Networks (CNNs). The proposed approach incorporates 3D Statistical Shape Models (SSMs) as well as 2D and 3D CNNs to achieve a robust and accurate segmentation of even highly pathological knee structures. The method is evaluated on data of the MICCAI grand challenge "Segmentation of Knee Images 2010". For the first time an accuracy equivalent to the inter-observer variability of human readers has been achieved in this challenge. Moreover, the quality of the proposed method is thoroughly assessed using various measures for 507 manual segmentations of bone and cartilage, and 88 additional manual segmentations of cartilage. Our method yields sub-voxel accuracy. In conclusion, combining of anatomical knowledge using SSMs with localized classification via CNNs results in a state-of-the-art segmentation method.}, language = {en} } @article{ChaumelSchotteBizzarroetal.2020, author = {Chaumel, J{\´u}lia and Schotte, Merlind and Bizzarro, Joseph J. and Zaslansky, Paul and Fratzl, Peter and Baum, Daniel and Dean, Mason N.}, title = {Co-aligned chondrocytes: Zonal morphological variation and structured arrangement of cell lacunae in tessellated cartilage}, volume = {134}, journal = {Bone}, doi = {10.1016/j.bone.2020.115264}, pages = {115264}, year = {2020}, abstract = {In most vertebrates the embryonic cartilaginous skeleton is replaced by bone during development. During this process, cartilage cells (chondrocytes) mineralize the extracellular matrix and undergo apoptosis, giving way to bone cells (osteocytes). In contrast, sharks and rays (elasmobranchs) have cartilaginous skeletons throughout life, where only the surface mineralizes, forming a layer of tiles (tesserae). Elasmobranch chondrocytes, unlike those of other vertebrates, survive cartilage mineralization and are maintained alive in spaces (lacunae) within tesserae. However, the function(s) of the chondrocytes in the mineralized tissue remain unknown. Applying a custom analysis workflow to high-resolution synchrotron microCT scans of tesserae, we characterize the morphologies and arrangements of stingray chondrocyte lacunae, using lacunar morphology as a proxy for chondrocyte morphology. We show that the cell density is comparable in unmineralized and mineralized tissue from our study species and that cells maintain the similar volume even when they have been incorporated into tesserae. This discovery supports previous hypotheses that elasmobranch chondrocytes, unlike those of other taxa, do not proliferate, hypertrophy or undergo apoptosis during mineralization. Tessera lacunae show zonal variation in their shapes—being flatter further from and more spherical closer to the unmineralized cartilage matrix and larger in the center of tesserae— and show pronounced organization into parallel layers and strong orientation toward neighboring tesserae. Tesserae also exhibit local variation in lacunar density, with the density considerably higher near pores passing through the tesseral layer, suggesting pores and cells interact (e.g. that pores contain a nutrient source). We hypothesize that the different lacunar types reflect the stages of the tesserae formation process, while also representing local variation in tissue architecture and cell function. Lacunae are linked by small passages (canaliculi) in the matrix to form elongate series at the tesseral periphery and tight clusters in the center of tesserae, creating a rich connectivity among cells. The network arrangement and the shape variation of chondrocytes in tesserae indicate that cells may interact within and between tesserae and manage mineralization differently from chondrocytes in other vertebrates, perhaps performing analogous roles to osteocytes in bone.}, language = {en} } @article{SchotteChaumelDeanetal.2020, author = {Schotte, Merlind and Chaumel, J{\´u}lia and Dean, Mason N. and Baum, Daniel}, title = {Image analysis pipeline for segmentation of a biological porosity network, the lacuno-canalicular system in stingray tesserae}, volume = {7}, journal = {MethodsX}, doi = {10.1016/j.mex.2020.100905}, pages = {100905}, year = {2020}, abstract = {A prerequisite for many analysis tasks in modern comparative biology is the segmentation of 3-dimensional (3D) images of the specimens being investigated (e.g. from microCT data). Depending on the specific imaging technique that was used to acquire the images and on the image resolution, different segmentation tools will be required. While some standard tools exist that can often be applied for specific subtasks, building whole processing pipelines solely from standard tools is often difficult. Some tasks may even necessitate the implementation of manual interaction tools to achieve a quality that is sufficient for the subsequent analysis. In this work, we present a pipeline of segmentation tools that can be used for the semi-automatic segmentation and quantitative analysis of voids in tissue (i.e. internal structural porosity). We use this pipeline to analyze lacuno-canalicular networks in stingray tesserae from 3D images acquired with synchrotron microCT. * The first step of this processing pipeline, the segmentation of the tesserae, was performed using standard marker-based watershed segmentation. The efficient processing of the next two steps, that is, the segmentation of all lacunae spaces belonging to a specific tessera and the separation of these spaces into individual lacunae required modern, recently developed tools. * For proofreading, we developed a graph-based interactive method that allowed us to quickly split lacunae that were accidentally merged, and to merge lacunae that were wrongly split. * Finally, the tesserae and their corresponding lacunae were subdivided into anatomical regions of interest (structural wedges) using a semi- manual approach.}, language = {en} } @article{AlchikhConradMaetal.2019, author = {Alchikh, Maren and Conrad, Tim and Ma, Xiaolin and Broberg, Eeva K. and Penttinen, P. and Reiche, J. and Biere, Barbara and Schweiger, Brunhilde and Rath, Barbara and Hoppe, Christian}, title = {Are we missing respiratory viral infections in infants and children? Comparison of a hospital-based quality management system with standard of care}, volume = {25}, journal = {Clinical Microbiology and Infection}, number = {3}, issn = {1469-0691}, doi = {10.1016/j.cmi.2018.05.023}, pages = {380.e9 -- 380.e16}, year = {2019}, language = {en} } @article{RamsConrad2020, author = {Rams, Mona and Conrad, Tim}, title = {Dictionary Learning for transcriptomics data reveals type-specific gene modules in a multi-class setting}, volume = {62}, journal = {it - Information Technology}, number = {3-4}, publisher = {De Gruyter}, address = {Oldenbourg}, issn = {2196-7032}, doi = {https://doi.org/10.1515/itit-2019-0048}, year = {2020}, language = {en} } @article{LindowBruenigDercksenetal.2020, author = {Lindow, Norbert and Br{\"u}nig, Florian and Dercksen, Vincent J. and Fabig, Gunar and Kiewisz, Robert and Redemann, Stefanie and M{\"u}ller-Reichert, Thomas and Prohaska, Steffen and Baum, Daniel}, title = {Semi-automatic stitching of filamentous structures in image stacks from serial-section electron tomography}, journal = {bioRxiv}, doi = {10.1101/2020.05.28.120899}, year = {2020}, abstract = {We present a software-assisted workflow for the alignment and matching of filamentous structures across a 3D stack of serial images. This is achieved by combining automatic methods, visual validation, and interactive correction. After an initial alignment, the user can continuously improve the result by interactively correcting landmarks or matches of filaments. Supported by a visual quality assessment of regions that have been already inspected, this allows a trade-off between quality and manual labor. The software tool was developed to investigate cell division by quantitative 3D analysis of microtubules (MTs) in both mitotic and meiotic spindles. For this, each spindle is cut into a series of semi-thick physical sections, of which electron tomograms are acquired. The serial tomograms are then stitched and non-rigidly aligned to allow tracing and connecting of MTs across tomogram boundaries. In practice, automatic stitching alone provides only an incomplete solution, because large physical distortions and a low signal-to-noise ratio often cause experimental difficulties. To derive 3D models of spindles despite the problems related to sample preparation and subsequent data collection, semi-automatic validation and correction is required to remove stitching mistakes. However, due to the large number of MTs in spindles (up to 30k) and their resulting dense spatial arrangement, a naive inspection of each MT is too time consuming. Furthermore, an interactive visualization of the full image stack is hampered by the size of the data (up to 100 GB). Here, we present a specialized, interactive, semi-automatic solution that considers all requirements for large-scale stitching of filamentous structures in serial-section image stacks. The key to our solution is a careful design of the visualization and interaction tools for each processing step to guarantee real-time response, and an optimized workflow that efficiently guides the user through datasets.}, language = {en} } @article{PimentelSzengelEhlkeetal.2020, author = {Pimentel, Pedro and Szengel, Angelika and Ehlke, Moritz and Lamecker, Hans and Zachow, Stefan and Estacio, Laura and Doenitz, Christian and Ramm, Heiko}, title = {Automated Virtual Reconstruction of Large Skull Defects using Statistical Shape Models and Generative Adversarial Networks}, volume = {12439}, journal = {Towards the Automatization of Cranial Implant Design in Cranioplasty}, editor = {Li, Jianning and Egger, Jan}, edition = {1}, publisher = {Springer International Publishing}, doi = {10.1007/978-3-030-64327-0_3}, pages = {16 -- 27}, year = {2020}, abstract = {We present an automated method for extrapolating missing regions in label data of the skull in an anatomically plausible manner. The ultimate goal is to design patient-speci� c cranial implants for correcting large, arbitrarily shaped defects of the skull that can, for example, result from trauma of the head. Our approach utilizes a 3D statistical shape model (SSM) of the skull and a 2D generative adversarial network (GAN) that is trained in an unsupervised fashion from samples of healthy patients alone. By � tting the SSM to given input labels containing the skull defect, a First approximation of the healthy state of the patient is obtained. The GAN is then applied to further correct and smooth the output of the SSM in an anatomically plausible manner. Finally, the defect region is extracted using morphological operations and subtraction between the extrapolated healthy state of the patient and the defective input labels. The method is trained and evaluated based on data from the MICCAI 2020 AutoImplant challenge. It produces state-of-the art results on regularly shaped cut-outs that were present in the training and testing data of the challenge. Furthermore, due to unsupervised nature of the approach, the method generalizes well to previously unseen defects of varying shapes that were only present in the hidden test dataset.}, language = {en} } @article{OeltzeJaffraMeuschkeNeugebaueretal.2019, author = {Oeltze-Jaffra, Steffen and Meuschke, Monique and Neugebauer, Mathias and Saalfeld, Sylvia and Lawonn, Kai and Janiga, Gabor and Hege, Hans-Christian and Zachow, Stefan and Preim, Bernhard}, title = {Generation and Visual Exploration of Medical Flow Data: Survey, Research Trends, and Future Challenges}, volume = {38}, journal = {Computer Graphics Forum}, number = {1}, publisher = {Wiley}, doi = {10.1111/cgf.13394}, pages = {87 -- 125}, year = {2019}, abstract = {Simulations and measurements of blood and air flow inside the human circulatory and respiratory system play an increasingly important role in personalized medicine for prevention, diagnosis, and treatment of diseases. This survey focuses on three main application areas. (1) Computational Fluid Dynamics (CFD) simulations of blood flow in cerebral aneurysms assist in predicting the outcome of this pathologic process and of therapeutic interventions. (2) CFD simulations of nasal airflow allow for investigating the effects of obstructions and deformities and provide therapy decision support. (3) 4D Phase-Contrast (4D PC) Magnetic Resonance Imaging (MRI) of aortic hemodynamics supports the diagnosis of various vascular and valve pathologies as well as their treatment. An investigation of the complex and often dynamic simulation and measurement data requires the coupling of sophisticated visualization, interaction, and data analysis techniques. In this paper, we survey the large body of work that has been conducted within this realm. We extend previous surveys by incorporating nasal airflow, addressing the joint investigation of blood flow and vessel wall properties, and providing a more fine-granular taxonomy of the existing techniques. From the survey, we extract major research trends and identify open problems and future challenges. The survey is intended for researchers interested in medical flow but also more general, in the combined visualization of physiology and anatomy, the extraction of features from flow field data and feature-based visualization, the visual comparison of different simulation results, and the interactive visual analysis of the flow field and derived characteristics.}, language = {en} } @article{RathConradMylesetal.2017, author = {Rath, Barbara and Conrad, Tim and Myles, Puja and Alchikh, Maren and Ma, Xiaolin and Hoppe, Christian and Tief, Franziska and Chen, Xi and Obermeier, Patrick and Kisler, Bron and Schweiger, Brunhilde}, title = {Influenza and other respiratory viruses: standardizing disease severity in surveillance and clinical trials}, volume = {15}, journal = {Expert Review of Anti-infective Therapy}, number = {6}, doi = {10.1080/14787210.2017.1295847}, pages = {545 -- 568}, year = {2017}, abstract = {Introduction: Influenza-Like Illness is a leading cause of hospitalization in children. Disease burden due to influenza and other respiratory viral infections is reported on a population level, but clinical scores measuring individual changes in disease severity are urgently needed. Areas covered: We present a composite clinical score allowing individual patient data analyses of disease severity based on systematic literature review and WHO-criteria for uncomplicated and complicated disease. The 22-item ViVI Disease Severity Score showed a normal distribution in a pediatric cohort of 6073 children aged 0-18 years (mean age 3.13; S.D. 3.89; range: 0 to 18.79). Expert commentary: The ViVI Score was correlated with risk of antibiotic use as well as need for hospitalization and intensive care. The ViVI Score was used to track children with influenza, respiratory syncytial virus, human metapneumovirus, human rhinovirus, and adenovirus infections and is fully compliant with regulatory data standards. The ViVI Disease Severity Score mobile application allows physicians to measure disease severity at the point-of care thereby taking clinical trials to the next level.}, language = {en} } @article{MarzbanConradMarbanetal.2018, author = {Marzban, Forough and Conrad, Tim and Marban, Pouria and Sodoudi, Sahar}, title = {Estimation of the Near-Surface Air Temperature during the Day and Nighttime from MODIS in Berlin, Germany}, volume = {7}, journal = {International Journal of Advanced Remote Sensing and GIS}, number = {1}, doi = {10.23953/cloud.ijarsg.337}, pages = {2478 -- 2517}, year = {2018}, abstract = {Air temperature (Tair or T2m) is an important climatological variable for forest biosphere processes and climate change research. Due to the low density and the uneven distribution of weather stations, traditional ground-based observations cannot accurately capture the spatial distribution of Tair. In this study, Tair in Berlin is estimated during the day and night time over six land cover/land use (LC/LU) types by satellite remote sensing data over a large domain and a relatively long period (7 years). Aqua and Terra MODIS (Moderate Resolution Imaging Spectroradiometer) data and meteorological data for the period from 2007 to 2013 were collected to estimate Tair. Twelve environmental variables (land surface temperature (LST), normalized difference vegetation index (NDVI), Julian day, latitude, longitude, Emissivity31, Emissivity32, altitude, albedo, wind speed, wind direction and air pressure) were selected as predictors. Moreover, a comparison between LST from MODIS Terra and Aqua with daytime and night time air temperatures (Tday, Tnight) was done respectively and in addition, the spatial variability of LST and Tair relationship by applying a varying window size on the MODIS LST grid was examined. An analysis of the relationship between the observed Tair and the spatially averaged remotely sensed LST, indicated that 3 × 3 and 1 × 1 pixel size was the optimal window size for the statistical model estimating Tair from MODIS data during the day and night time, respectively. Three supervised learning methods (Adaptive Neuro Fuzzy Inference system (ANFIS), Artificial Neural Network (ANN) and Support vector machine (SVR)) were used to estimate Tair during the day and night time, and their performances were validated by cross-validation for each LC/LU. Moreover, tuning the hyper parameters of some models like SVR and ANN were investigated. For tuning the hyper parameters of SVR, Simulated Annealing (SA) was applied (SA-SVR model) and a multiple-layer feed-forward (MLF) neural networks with three layers and different nodes in hidden layers are used with Levenber-Marquardt back-propagation (LM-BP), in order to achieve higher accuracy in the estimation of Tair. Results indicated that the ANN model achieved better accuracy (RMSE= 2.16°C, MAE = 1.69°C, R2 = 0.95) than SA_SVR model (RMSE= 2.50°C, MAE = 1.92°C, R2 = 0.91) and ANFIS model (RMSE= 2.88°C, MAE= 2.2°C, R2 = 0.89) over six LC/LU during the day and night time. The Q-Q diagram of SA-SVR, ANFIS and NN show that all three models slightly tended to underestimate and overestimate the extreme and low temperatures for all LC/LU classes during the day and night time. The weak performance in the extreme and low temperatures are a consequence of the small number of data in these temperatures. These satisfactory results indicate that this approach is proper for estimating air temperature and spatial window size is an important factor that should be considered in the estimation of air temperature.}, language = {en} } @inproceedings{EstacioEhlkeTacketal.2021, author = {Estacio, Laura and Ehlke, Moritz and Tack, Alexander and Castro-Gutierrez, Eveling and Lamecker, Hans and Mora, Rensso and Zachow, Stefan}, title = {Unsupervised Detection of Disturbances in 2D Radiographs}, booktitle = {2021 IEEE 18th International Symposium on Biomedical Imaging (ISBI)}, doi = {10.1109/ISBI48211.2021.9434091}, pages = {367 -- 370}, year = {2021}, abstract = {We present a method based on a generative model for detection of disturbances such as prosthesis, screws, zippers, and metals in 2D radiographs. The generative model is trained in an unsupervised fashion using clinical radiographs as well as simulated data, none of which contain disturbances. Our approach employs a latent space consistency loss which has the benefit of identifying similarities, and is enforced to reconstruct X-rays without disturbances. In order to detect images with disturbances, an anomaly score is computed also employing the Frechet distance between the input X-ray and the reconstructed one using our generative model. Validation was performed using clinical pelvis radiographs. We achieved an AUC of 0.77 and 0.83 with clinical and synthetic data, respectively. The results demonstrated a good accuracy of our method for detecting outliers as well as the advantage of utilizing synthetic data.}, language = {en} } @article{SekuboyinaBayatHusseinietal.2020, author = {Sekuboyina, Anjany and Bayat, Amirhossein and Husseini, Malek E. and L{\"o}ffler, Maximilian and Li, Hongwei and Tetteh, Giles and Kukačka, Jan and Payer, Christian and Štern, Darko and Urschler, Martin and Chen, Maodong and Cheng, Dalong and Lessmann, Nikolas and Hu, Yujin and Wang, Tianfu and Yang, Dong and Xu, Daguang and Ambellan, Felix and Amiranashvili, Tamaz and Ehlke, Moritz and Lamecker, Hans and Lehnert, Sebastian and Lirio, Marilia and de Olaguer, Nicol{\´a}s P{\´e}rez and Ramm, Heiko and Sahu, Manish and Tack, Alexander and Zachow, Stefan and Jiang, Tao and Ma, Xinjun and Angerman, Christoph and Wang, Xin and Wei, Qingyue and Brown, Kevin and Wolf, Matthias and Kirszenberg, Alexandre and Puybareau, {\´E}lodie and Valentinitsch, Alexander and Rempfler, Markus and Menze, Bj{\"o}rn H. and Kirschke, Jan S.}, title = {VerSe: A Vertebrae Labelling and Segmentation Benchmark for Multi-detector CT Images}, journal = {arXiv}, arxiv = {http://arxiv.org/abs/2001.09193}, year = {2020}, language = {en} } @article{WulkowConradDjurdjevacConradetal.2021, author = {Wulkow, Hanna and Conrad, Tim and Djurdjevac Conrad, Natasa and M{\"u}ller, Sebastian A. and Nagel, Kai and Sch{\"u}tte, Christof}, title = {Prediction of Covid-19 spreading and optimal coordination of counter-measures: From microscopic to macroscopic models to Pareto fronts}, volume = {16}, journal = {PLOS One}, number = {4}, publisher = {Public Library of Science}, doi = {10.1371/journal.pone.0249676}, year = {2021}, language = {en} } @inproceedings{Mukhopadhyay2016, author = {Mukhopadhyay, Anirban}, title = {Total Variation Random Forest: Fully automatic MRI segmentation in congenital heart disease}, volume = {LNCS 10129}, booktitle = {RAMBO 2016, HVSMR 2016: Reconstruction, Segmentation, and Analysis of Medical Images}, doi = {10.1007/978-3-319-52280-7_17}, pages = {165 -- 171}, year = {2016}, language = {en} } @inproceedings{MukhopadhyayMorilloZachowetal.2016, author = {Mukhopadhyay, Anirban and Morillo, Oscar and Zachow, Stefan and Lamecker, Hans}, title = {Robust and Accurate Appearance Models Based on Joint Dictionary Learning Data from the Osteoarthritis Initiative}, volume = {9993}, booktitle = {Lecture Notes in Computer Science, Patch-Based Techniques in Medical Imaging. Patch-MI 2016}, doi = {10.1007/978-3-319-47118-1_4}, pages = {25 -- 33}, year = {2016}, abstract = {Deformable model-based approaches to 3D image segmentation have been shown to be highly successful. Such methodology requires an appearance model that drives the deformation of a geometric model to the image data. Appearance models are usually either created heuristically or through supervised learning. Heuristic methods have been shown to work effectively in many applications but are hard to transfer from one application (imaging modality/anatomical structure) to another. On the contrary, supervised learning approaches can learn patterns from a collection of annotated training data. In this work, we show that the supervised joint dictionary learning technique is capable of overcoming the traditional drawbacks of the heuristic approaches. Our evaluation based on two different applications (liver/CT and knee/MR) reveals that our approach generates appearance models, which can be used effectively and efficiently in a deformable model-based segmentation framework.}, language = {en} } @article{SahuMukhopadhyaySzengeletal.2017, author = {Sahu, Manish and Mukhopadhyay, Anirban and Szengel, Angelika and Zachow, Stefan}, title = {Addressing multi-label imbalance problem of Surgical Tool Detection using CNN}, volume = {12}, journal = {International Journal of Computer Assisted Radiology and Surgery}, number = {6}, publisher = {Springer}, doi = {10.1007/s11548-017-1565-x}, pages = {1013 -- 1020}, year = {2017}, abstract = {Purpose: A fully automated surgical tool detection framework is proposed for endoscopic video streams. State-of-the-art surgical tool detection methods rely on supervised one-vs-all or multi-class classification techniques, completely ignoring the co-occurrence relationship of the tools and the associated class imbalance. Methods: In this paper, we formulate tool detection as a multi-label classification task where tool co-occurrences are treated as separate classes. In addition, imbalance on tool co-occurrences is analyzed and stratification techniques are employed to address the imbalance during Convolutional Neural Network (CNN) training. Moreover, temporal smoothing is introduced as an online post-processing step to enhance run time prediction. Results: Quantitative analysis is performed on the M2CAI16 tool detection dataset to highlight the importance of stratification, temporal smoothing and the overall framework for tool detection. Conclusion: The analysis on tool imbalance, backed by the empirical results indicates the need and superiority of the proposed framework over state-of-the-art techniques.}, language = {en} } @article{ConradKarschObermeieretal.2015, author = {Conrad, Tim and Karsch, K. and Obermeier, Patrick and Seeber, L. and Chen, X. and Tief, Franziska and Muehlhans, S. and Hoppe, Christian and Boettcher, Sindy and Diedrich, S. and Rath, Barbara}, title = {Human Parechovirus Infections Associated with Seizures and Rash: A Syndromic Surveillance Study in Children}, volume = {34}, journal = {The Pediatric Infectious Disease Journal}, number = {10}, year = {2015}, language = {en} } @article{ConradMireles2015, author = {Conrad, Tim and Mireles, Victor}, title = {Minimum-overlap clusterings and the sparsity of overcomplete decompositions of binary matrics}, volume = {51}, journal = {Procedia Computer Science}, doi = {10.1016/j.procs.2015.05.500}, pages = {2967 -- 2971}, year = {2015}, abstract = {Given a set of n binary data points, a widely used technique is to group its features into k clusters. In the case where n {\ensuremath{<}} k, the question of how overlapping are the clusters becomes of interest. In this paper we approach the question through matrix decomposition, and relate the degree of overlap with the sparsity of one of the resulting matrices. We present analytical results regarding bounds on this sparsity, and a heuristic to estimate the minimum amount of overlap that an exact grouping of features into k clusters must have. As shown below, adding new data will not alter this minimum amount of overlap.}, language = {en} } @article{ConradShao2015, author = {Conrad, Tim and Shao, Borong}, title = {Are NoSQL data stores useful for bioinformatics researchers?}, volume = {3}, journal = {International Journal on Recent and Innovation Trends in Computing and Communication (IJRITCC)}, number = {3}, doi = {10.17762/ijritcc2321-8169.1503176}, pages = {1704 -- 1708}, year = {2015}, language = {en} } @article{ConradLeichtleCeglareketal.2013, author = {Conrad, Tim and Leichtle, Alexander Benedikt and Ceglarek, Uta and Weinert, P. and Nakas, C.T. and Nuoffer, Jean-Marc and Kase, Julia and Witzigmann, Helmut and Thiery, Joachim and Fiedler, Georg Martin}, title = {Pancreatic carcinoma, pancreatitis, and healthy controls - metabolite models in a three-class diagnostic dilemma}, volume = {9}, journal = {Metabolomics}, number = {3}, doi = {10.1007/s11306-012-0476-7}, pages = {677 -- 687}, year = {2013}, abstract = {Background: Metabolomics as one of the most rapidly growing technologies in the ?-omics?field denotes the comprehensive analysis of low molecular-weight compounds and their pathways. Cancer-specific alterations of the metabolome can be detected by high-throughput massspectrometric metabolite profiling and serve as a considerable source of new markers for the early differentiation of malignant diseases as well as their distinction from benign states. However, a comprehensive framework for the statistical evaluation of marker panels in a multi-class setting has not yet been established. Methods: We collected serum samples of 40 pancreatic carcinoma patients, 40 controls, and 23 pancreatitis patients according to standard protocols and generated amino acid profiles by routine mass-spectrometry. In an intrinsic three-class bioinformatic approach we compared these profiles, evaluated their selectivity and computed multi-marker panels combined with the conventional tumor marker CA 19-9. Additionally, we tested for non-inferiority and superiority to determine the diagnostic surplus value of our multi-metabolite marker panels.  Results: Compared to CA 19-9 alone, the combined amino acid-based metabolite panel had a superior selectivity for the discrimination of healthy controls, pancreatitis, and pancreatic carcinoma patients [Volume under ROC surface (VUS) = 0.891 (95\\% CI 0.794 - 0.968)]. Conclusions: We combined highly standardized samples, a three-class study design, a highthroughput mass-spectrometric technique, and a comprehensive bioinformatic framework to identify metabolite panels selective for all three groups in a single approach. Our results suggest that metabolomic profiling necessitates appropriate evaluation strategies and ?despite all its current limitations? can deliver marker panels with high selectivity even in multi-class settings.}, language = {en} } @article{GuptaReinschSpoetteretal.2013, author = {Gupta, Pooja and Reinsch, Norbert and Sp{\"o}tter, Andreas and Conrad, Tim and Bienefeld, Kaspar}, title = {Accuracy of the unified approach in maternally influenced traits - illustrated by a simulation study in the honey bee (Apis mellifera)}, volume = {14}, journal = {BMC Genetics}, number = {36}, doi = {10.1186/1471-2156-14-36}, year = {2013}, language = {en} } @article{ConradYou2016, author = {Conrad, Tim and You, Xintian}, title = {Acfs: accurate circRNA identification and quantification from NGS data}, volume = {6}, journal = {Nature Scientific Reports}, doi = {10.1038/srep38820}, year = {2016}, abstract = {Circular RNAs (circRNAs) are a group of single-stranded RNAs in closed circular form. They are splicing-generated, widely expressed in various tissues and have functional implications in development and diseases. To facilitate genome-wide characterization of circRNAs using RNA-Seq data, we present a freely available software package named acfs. Acfs allows de novo, accurate and fast identification and abundance quantification of circRNAs from single- and paired-ended RNA-Seq data. On simulated datasets, acfs achieved the highest F1 accuracy and lowest false discovery rate among current state-of-the-art tools. On real-world datasets, acfs efficiently identified more bona fide circRNAs. Furthermore, we demonstrated the power of circRNA analysis on two leukemia datasets. We identified a set of circRNAs that are differentially expressed between AML and APL samples, which might shed light on the potential molecular classification of complex diseases using circRNA profiles. Moreover, chromosomal translocation, as manifested in numerous diseases, could produce not only fusion transcripts but also fusion circRNAs of clinical relevance. Featured with high accuracy, low FDR and the ability to identify fusion circRNAs, we believe that acfs is well suited for a wide spectrum of applications in characterizing the landscape of circRNAs from non-model organisms to cancer biology.}, language = {en} } @article{HoppeObermeierMehlhansetal.2016, author = {Hoppe, Christian and Obermeier, Patrick and Mehlhans, S. and Alchikh, Maren and Seeber, L. and Tief, Franziska and Karsch, K. and Chen, X. and Boettcher, Sindy and Diedrich, S. and Conrad, Tim}, title = {Innovative Digital Tools and Surveillance Systems for the Timely Detection of Adverse Events at the Point of Care: A Proof-of-Concept Study}, volume = {39}, journal = {Drug Safety}, number = {10}, doi = {10.1007/s40264-016-0437-6}, pages = {977 -- 988}, year = {2016}, abstract = {Regulatory authorities often receive poorly structured safety reports requiring considerable effort to investigate potential adverse events post hoc. Automated question-and-answer systems may help to improve the overall quality of safety information transmitted to pharmacovigilance agencies. This paper explores the use of the VACC-Tool (ViVI Automated Case Classification Tool) 2.0, a mobile application enabling physicians to classify clinical cases according to 14 pre-defined case definitions for neuroinflammatory adverse events (NIAE) and in full compliance with data standards issued by the Clinical Data Interchange Standards Consortium. METHODS: The validation of the VACC-Tool 2.0 (beta-version) was conducted in the context of a unique quality management program for children with suspected NIAE in collaboration with the Robert Koch Institute in Berlin, Germany. The VACC-Tool was used for instant case classification and for longitudinal follow-up throughout the course of hospitalization. Results were compared to International Classification of Diseases , Tenth Revision (ICD-10) codes assigned in the emergency department (ED). RESULTS: From 07/2013 to 10/2014, a total of 34,368 patients were seen in the ED, and 5243 patients were hospitalized; 243 of these were admitted for suspected NIAE (mean age: 8.5 years), thus participating in the quality management program. Using the VACC-Tool in the ED, 209 cases were classified successfully, 69 \\% of which had been missed or miscoded in the ED reports. Longitudinal follow-up with the VACC-Tool identified additional NIAE. CONCLUSION: Mobile applications are taking data standards to the point of care, enabling clinicians to ascertain potential adverse events in the ED setting and during inpatient follow-up. Compliance with Clinical Data Interchange Standards Consortium (CDISC) data standards facilitates data interoperability according to regulatory requirements.}, language = {en} } @inproceedings{ShaoConrad2016, author = {Shao, Borong and Conrad, Tim}, title = {Epithelial Mesenchymal Transition Regulatory Network-based Feature Selection in Lung Cancer Prognosis Prediction}, volume = {9656}, booktitle = {Lecture Notes in Computer Science (LNCS)}, doi = {10.1007/978-3-319-31744-1_13}, pages = {1235 -- 146}, year = {2016}, abstract = {Feature selection technique is often applied in identifying cancer prognosis biomarkers. However, many feature selection methods are prone to over-fitting or poor biological interpretation when applied on biological high-dimensional data. Network-based feature selection and data integration approaches are proposed to identify more robust biomarkers. We conducted experiments to investigate the advantages of the two approaches using epithelial mesenchymal transition regulatory network, which is demonstrated as highly relevant to cancer prognosis. We obtained data from The Cancer Genome Atlas. Prognosis prediction was made using Support Vector Machine. Under our experimental settings, the results showed that network-based features gave significantly more accurate predictions than individual molecular features, and features selected from integrated data (RNA-Seq and micro-RNA data) gave significantly more accurate predictions than features selected from single source data (RNA-Seq data). Our study indicated that biological network-based feature transformation and data integration are two useful approaches to identify robust cancer biomarkers.}, language = {en} } @article{TiefHoppeSeeberetal.2016, author = {Tief, Franziska and Hoppe, Christian and Seeber, L. and Obermeier, Patrick and Chen, X. and Karsch, K. and Muehlhans, S. and Adamou, E. and Conrad, Tim and Schweiger, Brunhilde and Adam, T. and Rath, Barbara}, title = {An inception cohort study assessing the role of bacterial co-infections in children with influenza and ILI and a clinical decision model for stringent antibiotic use}, volume = {21}, journal = {Antiviral Therapy}, doi = {10.3851/IMP3034}, pages = {413 -- 424}, year = {2016}, abstract = {BACKGROUND: Influenza-like illness (ILI) is a common reason for paediatric consultations. Viral causes predominate, but antibiotics are used frequently. With regard to influenza, pneumococcal coinfections are considered major contributors to morbidity/mortality. METHODS: In the context of a perennial quality management (QM) programme at the Charit{\'e} Departments of Paediatrics and Microbiology in collaboration with the Robert Koch Institute, children aged 0-18 years presenting with signs and symptoms of ILI were followed from the time of initial presentation until hospital discharge (Charit{\'e} Influenza-Like Disease = ChILD Cohort). An independent QM team performed highly standardized clinical assessments using a disease severity score based on World Health Organization criteria for uncomplicated and complicated/progressive disease. Nasopharyngeal and pharyngeal samples were collected for viral reverse transcription polymerase chain reaction and bacterial culture/sensitivity and MaldiTOF analyses. The term 'detection' was used to denote any evidence of viral or bacterial pathogens in the (naso)pharyngeal cavity. With the ChILD Cohort data collected, a standard operating procedure (SOP) was created as a model system to reduce the inappropriate use of antibiotics in children with ILI. Monte Carlo simulations were performed to assess cost-effectiveness. RESULTS: Among 2,569 ChILD Cohort patients enrolled from 12/2010 to 04/2013 (55\\% male, mean age 3.2 years, range 0-18, 19\\% {\ensuremath{>}}5 years), 411 patients showed laboratory-confirmed influenza, with bacterial co-detection in 35\\%. Influenza and pneumococcus were detected simultaneously in 12/2,569 patients, with disease severity clearly below average. Pneumococcal vaccination rates were close to 90\\%. Nonetheless, every fifth patient was already on antibiotics upon presentation; new antibiotic prescriptions were issued in an additional 20\\%. Simulation of the model SOP in the same dataset revealed that the proposed decision model could have reduced the inappropriate use of antibiotics significantly (P{\ensuremath{<}}0.01) with an incremental cost-effectiveness ratio of -99.55?. CONCLUSIONS: Physicians should be made aware that in times of pneumococcal vaccination the prevalence and severity of influenza infections complicated by pneumococci may decline. Microbiological testing in combination with standardized disease severity assessments and review of vaccination records could be cost-effective, as well as promoting stringent use of antibiotics and a personalized approach to managing children with ILI.}, language = {en} } @article{ObermeierMuehlhansHoppeetal.2016, author = {Obermeier, Patrick and Muehlhans, S. and Hoppe, Christian and Karsch, K. and Tief, Franziska and Seeber, L. and Chen, X. and Conrad, Tim and Boettcher, Sindy and Diedrich, S. and Rath, Barbara}, title = {Enabling Precision Medicine With Digital Case Classification at the Point-of-Care}, volume = {4}, journal = {EBioMedicine}, doi = {10.1016/j.ebiom.2016.01.008}, pages = {191 -- 196}, year = {2016}, abstract = {Infectious and inflammatory diseases of the central nervous system are difficult to identify early. Case definitions for aseptic meningitis, encephalitis, myelitis, and acute disseminated encephalomyelitis (ADEM) are available, but rarely put to use. The VACC-Tool (Vienna Vaccine Safety Initiative Automated Case Classification-Tool) is a mobile application enabling immediate case ascertainment based on consensus criteria at the point-of-care. The VACC-Tool was validated in a quality management program in collaboration with the Robert-Koch-Institute. Results were compared to ICD-10 coding and retrospective analysis of electronic health records using the same case criteria. Of 68,921 patients attending the emergency room in 10/2010-06/2013, 11,575 were hospitalized, with 521 eligible patients (mean age: 7.6 years) entering the quality management program. Using the VACC-Tool at the point-of-care, 180/521 cases were classified successfully and 194/521 ruled out with certainty. Of the 180 confirmed cases, 116 had been missed by ICD-10 coding, 38 misclassified. By retrospective application of the same case criteria, 33 cases were missed. Encephalitis and ADEM cases were most likely missed or misclassified. The VACC-Tool enables physicians to ask the right questions at the right time, thereby classifying cases consistently and accurately, facilitating translational research. Future applications will alert physicians when additional diagnostic procedures are required.}, language = {en} } @article{ConradBrucknerKayser2013, author = {Conrad, Tim and Bruckner, Sharon and Kayser, Bastian}, title = {Finding Modules in Networks with Non-modular Regions}, volume = {7933}, journal = {Lecture Notes in Computer Science (Proceedings of SEA 2013)}, doi = {10.1007/978-3-642-38527-8_18}, pages = {188 -- 199}, year = {2013}, abstract = {Most network clustering methods share the assumption that the network can be completely decomposed into modules, that is, every node belongs to (usually exactly one) module. Forcing this constraint can lead to misidentification of modules where none exist, while the true modules are drowned out in the noise, as has been observed e.g. for protein interaction networks. We thus propose a clustering model where networks contain both a modular region consisting of nodes that can be partitioned into modules, and a transition region containing nodes that lie between or outside modules. We propose two scores based on spectral properties to determine how well a network fits this model. We then evaluate three (partially adapted) clustering algorithms from the literature on random networks that fit our model, based on the scores and comparison to the ground truth. This allows to pinpoint the types of networks for which the different algorithms perform well.}, language = {en} } @article{ConradRathTiefetal.2013, author = {Conrad, Tim and Rath, Barbara and Tief, Franziska and Karsch, K. and Muehlhans, S. and Obermeier, Patrick and Adamou, E. and Chen, X. and Seeber, L. and Peiser, Ch. and Hoppe, Christian and von Kleist, Max and Schweiger, Brunhilde}, title = {Towards a personalized approach to managing of influenza infections in infants and children - food for thought and a note on oseltamivir}, volume = {13}, journal = {Infectious Disorders - Drug Targets}, number = {1}, pages = {25 -- 33}, year = {2013}, language = {en} }