@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{KoltaiSchuette2018, author = {Koltai, P{\´e}ter and Sch{\"u}tte, Christof}, title = {A multiscale perturbation expansion approach for Markov state modeling of non-stationary molecular dynamics}, volume = {16}, journal = {SIAM J. Multiscale Model. Simul.}, number = {4}, publisher = {SIAM}, doi = {10.1137/17M1146403}, pages = {1455 -- 1485}, year = {2018}, abstract = {We investigate metastable dynamical systems subject to non-stationary forcing as they appear in molecular dynamics for systems driven by external fields. We show, that if the strength of the forcing is inversely proportional to the length of the slow metastable time scales of the unforced system, then the effective behavior of the forced system on slow time scales can be described by a low-dimensional reduced master equation. Our construction is explicit and uses the multiscale perturbation expansion method called two-timing, or method of multiple scales. The reduced master equation—a Markov state model—can be assembled by constructing two equilibrium Markov state models; one for the unforced system, and one for a slightly perturbed one.}, 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} }