TY - GEN A1 - Ambellan, Felix A1 - Lamecker, Hans A1 - von Tycowicz, Christoph A1 - Zachow, Stefan T1 - Statistical Shape Models - Understanding and Mastering Variation in Anatomy N2 - 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. T3 - ZIB-Report - 19-13 Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-72699 SN - 1438-0064 ER - TY - GEN A1 - Ambellan, Felix A1 - Tack, Alexander A1 - Ehlke, Moritz A1 - Zachow, Stefan T1 - Automated Segmentation of Knee Bone and Cartilage combining Statistical Shape Knowledge and Convolutional Neural Networks: Data from the Osteoarthritis Initiative N2 - 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. T3 - ZIB-Report - 19-06 Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-72704 SN - 1438-0064 N1 - Innovation Excellence Award 2020 ER - TY - GEN A1 - Banisch, Ralf A1 - Djurdjevac Conrad, Natasa A1 - Schütte, Christof T1 - Reactive flows and unproductive cycles for random walks on complex networks N2 - We present a comprehensive theory for analysis and understanding of transition events between an initial set A and a target set B for general ergodic finite-state space Markov chains or jump processes, including random walks on networks as they occur, e.g., in Markov State Modelling in molecular dynamics. The theory allows us to decompose the probability flow generated by transition events between the sets A and B into the productive part that directly flows from A to B through reaction pathways and the unproductive part that runs in loops and is supported on cycles of the underlying network. It applies to random walks on directed networks and nonreversible Markov processes and can be seen as an extension of Transition Path Theory. Information on reaction pathways and unproductive cycles results from the stochastic cycle decomposition of the underlying network which also allows to compute their corresponding weight, thus characterizing completely which structure is used how often in transition events. The new theory is illustrated by an application to a Markov State Model resulting from weakly damped Langevin dynamics where the unproductive cycles are associated with periodic orbits of the underlying Hamiltonian dynamics. T3 - ZIB-Report - 15-19 KW - Complex networks KW - molecular transition networks KW - transition path theory KW - cycle decomposition KW - reactive trajectories KW - Markow State Methods Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-54239 SN - 1438-0064 ER - TY - GEN A1 - Wang, Han A1 - Schütte, Christof T1 - Building Markov State Models for Periodically Driven Non-Equilibrium Systems N2 - Recent years have seen an increased interest in non-equilibrium molecular dynamics (NEMD) simulations, especially for molecular systems with periodic forcing by external fields, e.g., in the context of studying effects of electromagnetic radiation on the human body tissue. Lately, an NEMD methods with local thermostating has been proposed that allows for studying non-equilibrium processes in a statistically reliable and thermodynamically consistent way. In this article, we demonstrate how to construct Markov State Models (MSMs) for such NEMD simulations. MSM building has been well-established for systems in equilibrium where MSMs with just a few (macro-)states allow for accurate reproduction of the essential kinetics of the molecular system under consideration. Non-equilibrium MSMs have been lacking so far. The article presents how to construct such MSMs and illustrates their validity and usefulness for the case of conformation dynamics of alanine dipeptide in an external electric field. T3 - ZIB-Report - 14-46 KW - Non-equilibrium KW - Markov states model KW - Alanine dipeptide KW - Electric field KW - Floquet theory Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-53167 SN - 1438-0064 N1 - To appear in: Journal of Chemical Theory and Computation ER - TY - GEN A1 - Gul, Raheem A1 - Schütte, Christof A1 - Bernhard, Stefan T1 - Mathematical modeling and sensitivity analysis of arterial anastomosis in arm arteries N2 - Cardiovascular diseases are one of the major problems in medicine today and the number of patients increases worldwide. To find the most efficient treatment, prior knowledge about function and dysfunction of the cardiovas- cular system is required and methods need to be developed that identify the disease in an early stage. Mathematical modeling is a powerful tool for prediction and investigation of cardiovascular diseases. It has been shown that the Windkessel model, being based on an analogy between electrical circuits and fluid flow, is a simple but effective method to model the human cardiovascular system. In this paper, we have applied parametric local sensitivity analysis (LSA) to a linear elastic model of the arm arteries, to find and rank sensitive param- eters that may be helpful in clinical diagnosis. A computational model for end-to-side anastomosis (superior ulnar collateral anastomosis with posterior ulnar recurrent, SUC-PUR) is carried out to study the effects of some clinically relevant haemodynamic parameters like blood flow resistance and terminal re- sistance on pressure and flow at different locations of the arm artery. In this context, we also discuss the spatio-temporal dependency of local sensitivities. The sensitivities with respect to cardiovascular parameters reveal the flow resistance and diameter of the vessels as most sensitive parameters. These parameters play a key role in diagnosis of severe stenosis and aneurysms. In contrast, wall thickness and elastic modulus are found to be less sensitive. T3 - ZIB-Report - 15-22 KW - computational cardiovascular model KW - cardiovascular parameters KW - sensitivity analysis KW - anastomosis KW - Windkessel model Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-54339 SN - 1438-0064 ER - TY - GEN A1 - Gupta, Pooja A1 - Gramatke, Annika A1 - Einspanier, Ralf A1 - Schütte, Christof A1 - von Kleist, Max A1 - Sharbati, Jutta T1 - In silicio cytotoxicity assessment on cultured rat intestinal cells deduced from cellular impedance measurements N2 - Early and reliable identification of chemical toxicity is of utmost importance. At the same time, reduction of animal testing is paramount. Therefore, methods that improve the interpretability and usability of in vitro assays are essential. xCELLigence’s real-time cell analyzer (RTCA) provides a novel, fast and cost effective in vitro method to probe compound toxicity. We developed a simple mathematical framework for the qualitative and quantitative assessment of toxicity for RTCA measurements. Compound toxicity, in terms of its 50% inhibitory concentration IC_{50} on cell growth, and parameters related to cell turnover were estimated on cultured IEC-6 cells exposed to 10 chemicals at varying concentrations. Our method estimated IC50 values of 113.05, 7.16, 28.69 and 725.15 μM for the apparently toxic compounds 2-acetylamino-fluorene, aflatoxin B1, benzo-[a]-pyrene and chloramphenicol in the tested cell line, in agreement with literature knowledge. IC_{50} values of all apparent in vivo non-toxic compounds were estimated to be non-toxic by our method. Corresponding estimates from RTCA’s in-built model gave false positive (toxicity) predictions in 5/10 cases. Taken together, our proposed method reduces false positive predictions and reliably identifies chemical toxicity based on impedance measurements. The source code for the developed method including instructions is available at https://git.zib.de/bzfgupta/toxfit/tree/master. T3 - ZIB-Report - 17-08 KW - Real-time cell analyzer KW - Toxicity KW - Mathematical modeling KW - IC_{50} Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-62666 SN - 1438-0064 ER - TY - GEN A1 - Koltai, Peter A1 - Ciccotti, Giovanni A1 - Schütte, Christof T1 - On metastability and Markov state models for non-stationary molecular dynamics BT - 2016 Editor's Choice of The Journal of Chemical Physics T2 - The Journal of Chemical Physics N2 - We utilize the theory of coherent sets to build Markov state models for non- equilibrium molecular dynamical systems. Unlike for systems in equilibrium, “meta- stable” sets in the non-equilibrium case may move as time evolves. We formalize this concept by relying on the theory of coherent sets, based on this we derive finite-time non-stationary Markov state models, and illustrate the concept and its main differences to equilibrium Markov state modeling on simple, one-dimensional examples. T3 - ZIB-Report - 16-11 KW - coherent set, KW - Markov state model KW - non-equilibrium molecular dynamics KW - metastability Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-57869 SN - 1438-0064 VL - 174103 ET - 145 ER -