Comparing parametric solid modelling/reconfiguration,global shape modelling and free-form deformation for the generation of 3D digital models of femurs from X-ray images

At present, computer assisted surgery systems help orthopaedic surgeons both plan and perform surgical procedures. To enable these systems to function, it is crucial to have at one's disposal 3D models of anatomical structures, surgical tools and prostheses (if required). This paper analyses and compares three methods for generating 3D digital models of anatomical structures starting from X-ray images: parametric solid modelling/reconfiguration, global shape modelling and free-form deformation. Seven experiences involving the generation of a femur model were conducted by software developers and different skilled users. These experiences are described in detail and compared at different stages and from different points of view.     

Quantitative comparison of freeware software for bone mesh from DICOM files

Musculo-skeletal modelling, 3D printing of bone models and also custom design of relevant prostheses starts from accurate STL files. These are obtained from medical imaging after careful segmentation and 3D reconstruction using specialized software, but most of these are very expensive. The aim of the present study is to assess and compare alternative software available for free. Three freeware software were selected from the most popular, and one standard platform was made available at the institute of the authors. Using each of these four software and starting from available DICOM files obtained previously by a CT scanner, three different bone models were reconstructed from each of five different human anatomical areas for a total of 60 bone model reconstructions. A young radiographer performed the bone reconstruction without specific technical training. 3D spatial matching of corresponding anatomical models was also performed to determine distance-maps for the assessment of final surface quality. In all four software many valuable features were available, with minimum differences, and bone models of good quality were obtained. Large differences in file sizes (mean range over the five anatomical models 66-338) and in the number of triangles (870-1350 thousands) were found, with triangles for MByte ratio ranging from about 4 to 20 thousands. The distance-map analysis revealed that root mean square deviation averaged over the five anatomical models ranged from 0.13 to 2.21 mm for the six spatial matches between the four software. These software are suitable for 3D bone model reconstruction, and do not require special training, and as such these can open up opportunities for biomechanical modelling and medical education.     

Additive Manufacturing of Anatomical Models from Computed Tomography Scan Data

The purpose of the study presented here was to investigate the manufacturability of human anatomical models from Computed Tomography (CT) scan data via a 3D desktop printer which uses fused deposition modelling (FDM) technology. First, Digital Imaging and Communications in Medicine (DICOM) CT scan data were converted to 3D Standard Triangle Language (STL) format by using InVaselius digital imaging program. Once this STL file is obtained, a 3D physical version of the anatomical model can be fabricated by a desktop 3D FDM printer. As a case study, a patient’s skull CT scan data was considered, and a tangible version of the skull was manufactured by a 3D FDM desktop printer. During the 3D printing process, the skull was built using acrylonitrile-butadiene-styrene (ABS) co-polymer plastic. The printed model showed that the 3D FDM printing technology is able to fabricate anatomical models with high accuracy. As a result, the skull model can be used for preoperative surgical planning, medical training activities, implant design and simulation to show the potential of the FDM technology in medical field. It will also improve communication between medical stuff and patients. Current result indicates that a 3D desktop printer which uses FDM technology can be used to obtain accurate anatomical models.     

Conceptual data modelling for bioinformatics

Current research in the biosciences depends heavily on the effective exploitation of huge amounts of data. These are in disparate formats, remotely dispersed, and based on the different vocabularies of various disciplines. Furthermore, data are often stored or distributed using formats that leave implicit many important features relating to the structure and semantics of the data. Conceptual data modelling involves the development of implementation-independent models that capture and make explicit the principal structural properties of data. Entities such as a biopolymer or a reaction, and their relations, eg catalyses, can be formalised using a conceptual data model. Conceptual models are implementation-independent and can be transformed in systematic ways for implementation using different platforms, eg traditional database management systems. This paper describes the basics of the most widely used conceptual modelling notations, the ER (entity-relationship) model and the class diagrams of the UML (unified modelling language), and illustrates their use through several examples from bioinformatics. In particular, models are presented for protein structures and motifs, and for genomic sequences.     

Modularity and homology: modelling of the titin type I modules and their interfaces

Titin is a giant muscle protein with a highly modular architecture consisting of multiple repeats of two sequence motifs, named type I and type II. Type I motifs are homologous to members of the fibronectin type 3 (Fn3) superfamily, one of the motifs most widespread in modular proteins. Fn3 domains are thought to mediate protein-protein interactions and to act as spacers. In titin, Fn3 modules are present in two different super-repeated patterns, likely to be involved in sarcomere assembly through interactions with A-band proteins. Here, we discuss results from homology modelling the whole family of Fn3 domains in titin. Homology modelling is a powerful tool that will play an increasingly important role in the post-genomic era. It is particularly useful for extending experimental structure determinations of parts of multidomain proteins that contain multiple copies of the same motif. The 3D structures of a representative titin type I domain and of other extracellular Fn3 modules were used as a template to model the structures of the 132 copies in titin. The resulting models suggest residues that contribute to the fold stability and allow us to distinguish these from residues likely to have functional importance. In particular, analysis of the models and mapping of the consensus sequence onto the 3D structure suggest putative surfaces of interaction with other proteins. From the structures of isolated modules and the pattern of conservation in the multiple alignment of the whole titin Ig and Fn3 families, it is possible to address the question of how tandem modules are assembled. Our predictions can be validated experimentally.     

The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling

MOTIVATION: Homology models of proteins are of great interest for planning and analysing biological experiments when no experimental three-dimensional structures are available. Building homology models requires specialized programs and up-to-date sequence and structural databases. Integrating all required tools, programs and databases into a single web-based workspace facilitates access to homology modelling from a computer with web connection without the need of downloading and installing large program packages and databases. RESULTS: SWISS-MODEL workspace is a web-based integrated service dedicated to protein structure homology modelling. It assists and guides the user in building protein homology models at different levels of complexity. A personal working environment is provided for each user where several modelling projects can be carried out in parallel. Protein sequence and structure databases necessary for modelling are accessible from the workspace and are updated in regular intervals. Tools for template selection, model building and structure quality evaluation can be invoked from within the workspace. Workflow and usage of the workspace are illustrated by modelling human Cyclin A1 and human Transmembrane Protease 3. AVAILABILITY: The SWISS-MODEL workspace can be accessed freely at http://swissmodel.expasy.org/workspace/     

Integrating intracellular dynamics using CompuCell3D and Bionetsolver: applications to multiscale modelling of cancer cell growth and invasion

In this paper we present a multiscale, individual-based simulation environment that integrates CompuCell3D for lattice-based modelling on the cellular level and Bionetsolver for intracellular modelling. CompuCell3D or CC3D provides an implementation of the lattice-based Cellular Potts Model or CPM (also known as the Glazier-Graner-Hogeweg or GGH model) and a Monte Carlo method based on the metropolis algorithm for system evolution. The integration of CC3D for cellular systems with Bionetsolver for subcellular systems enables us to develop a multiscale mathematical model and to study the evolution of cell behaviour due to the dynamics inside of the cells, capturing aspects of cell behaviour and interaction that is not possible using continuum approaches. We then apply this multiscale modelling technique to a model of cancer growth and invasion, based on a previously published model of Ramis-Conde et al. (2008) where individual cell behaviour is driven by a molecular network describing the dynamics of E-cadherin and β-catenin. In this model, which we refer to as the centre-based model, an alternative individual-based modelling technique was used, namely, a lattice-free approach. In many respects, the GGH or CPM methodology and the approach of the centre-based model have the same overall goal, that is to mimic behaviours and interactions of biological cells. Although the mathematical foundations and computational implementations of the two approaches are very different, the results of the presented simulations are compatible with each other, suggesting that by using individual-based approaches we can formulate a natural way of describing complex multi-cell, multiscale models. The ability to easily reproduce results of one modelling approach using an alternative approach is also essential from a model cross-validation standpoint and also helps to identify any modelling artefacts specific to a given computational approach.     

The influence of data shape acquisition process and geometric accuracy of the mandible for numerical simulation

Computer-aided technologies have allowed new 3D modelling capabilities and engineering analyses based on experimental and numerical simulation. It has enormous potential for product development, such as biomedical instrumentation and implants. However, due to the complex shapes of anatomical structures, the accuracy of these technologies plays an important key role for adequate and accurate finite element analysis (FEA). The objective of this study was to determine the influence of the geometry variability between two digital models of a human model of the mandible. Two different shape acquisition techniques, CT scan and 3D laser scan, were assessed. A total of 130 points were controlled and the deviations between the measured points of the physical and 3D virtual models were assessed. The results of the FEA study showed a relative difference of 20% for the maximum displacement and 10% for the maximum strain between the two geometries.     

The influence of data shape acquisition process and geometric accuracy of the mandible for numerical simulation

Computer-aided technologies have allowed new 3D modelling capabilities and engineering analyses based on experimental and numerical simulation. It has enormous potential for product development, such as biomedical instrumentation and implants. However, due to the complex shapes of anatomical structures, the accuracy of these technologies plays an important key role for adequate and accurate finite element analysis (FEA).

The objective of this study was to determine the influence of the geometry variability between two digital models of a human model of the mandible. Two different shape acquisition techniques, CT scan and 3D laser scan, were assessed. A total of 130 points were controlled and the deviations between the measured points of the physical and 3D virtual models were assessed.

The results of the FEA study showed a relative difference of 20% for the maximum displacement and 10% for the maximum strain between the two geometries.     

Petri net modelling of biological networks

Mathematical modelling is increasingly used to get insights into the functioning of complex biological networks. In this context, Petri nets (PNs) have recently emerged as a promising tool among the various methods employed for the modelling and analysis of molecular networks. PNs come with a series of extensions, which allow different abstraction levels, from purely qualitative to more complex quantitative models. Noteworthily, each of these models preserves the underlying graph, which depicts the interactions between the biological components. This article intends to present the basics of the approach and to foster the potential role PNs could play in the development of the computational systems biology.     

Comparative modelling by restraint-based conformational sampling

Background  

Although comparative modelling is routinely used to produce three-dimensional models of proteins, very few automated approaches are formulated in a way that allows inclusion of restraints derived from experimental data as well as those from the structures of homologues. Furthermore, proteins are usually described as a single conformer, rather than an ensemble that represents the heterogeneity and inaccuracy of experimentally determined protein structures. Here we address these issues by exploring the application of the restraint-based conformational space search engine, RAPPER, which has previously been developed for rebuilding experimentally defined protein structures and for fitting models to electron density derived from X-ray diffraction analyses.     

An approach to multiscale modelling with graph grammars

Background and Aims

Functional–structural plant models (FSPMs) simulate biological processes at different spatial scales. Methods exist for multiscale data representation and modification, but the advantages of using multiple scales in the dynamic aspects of FSPMs remain unclear. Results from multiscale models in various other areas of science that share fundamental modelling issues with FSPMs suggest that potential advantages do exist, and this study therefore aims to introduce an approach to multiscale modelling in FSPMs.

Methods

A three-part graph data structure and grammar is revisited, and presented with a conceptual framework for multiscale modelling. The framework is used for identifying roles, categorizing and describing scale-to-scale interactions, thus allowing alternative approaches to model development as opposed to correlation-based modelling at a single scale. Reverse information flow (from macro- to micro-scale) is catered for in the framework. The methods are implemented within the programming language XL.

Key Results

Three example models are implemented using the proposed multiscale graph model and framework. The first illustrates the fundamental usage of the graph data structure and grammar, the second uses probabilistic modelling for organs at the fine scale in order to derive crown growth, and the third combines multiscale plant topology with ozone trends and metabolic network simulations in order to model juvenile beech stands under exposure to a toxic trace gas.

Conclusions

The graph data structure supports data representation and grammar operations at multiple scales. The results demonstrate that multiscale modelling is a viable method in FSPM and an alternative to correlation-based modelling. Advantages and disadvantages of multiscale modelling are illustrated by comparisons with single-scale implementations, leading to motivations for further research in sensitivity analysis and run-time efficiency for these models.     

Online homology modelling as a means of bridging the sequence-structure gap

For even the best-studied species, there is a large gap in their representation in the protein databank (PDB) compared to within sequence databases. Typically, less than 2% of sequences are represented in the PDB. This is partly due to the considerable experimental challenge and manual inputs required to solve three dimensional structures by methods such as X-ray diffraction and multi-dimensional nuclear magnetic resonance (NMR) spectroscopy in comparison to high-throughput sequencing. This gap is made even wider by the high level of redundancy within the PDB and under-representation of some protein categories such as membrane-associated proteins which comprise approximately 25% of proteins encoded in genomes. A traditional route to closing the sequence-structure gap is offered by homology modelling whereby the sequence of a target protein is modelled on a template represented in the PDB using in silico energy minimisation approaches. More recently, online homology servers have become available which automatically generate models from proffered sequences. However, many online servers give little indication of the structural plausibility of the generated model. In this paper, the online homology server Geno3D will be described. This server uses similar software to that used in modelling structures during structure determination and thus generates data allowing determination of the structural plausibility of models. For illustration, modelling of a chemotaxis protein (CheY) from Pseudomononas entomophila L48 (accession YP_609298) on a template (PDB id. 1mvo), the phosphorylation domain of an outer membrane protein PhoP from Bacillus subtilis, will be described.     

Soft tissue modelling for applications in virtual surgery and surgical robotics

Soft tissue modelling has gained a great deal of importance, for a large part due to its application in surgical training simulators for minimally invasive surgery (MIS). This article provides a structured overview of different continuum-mechanical models that have been developed over the years. It aims at facilitating model choice for specific soft tissue modelling applications. According to the complexity of the model, different features of soft biological tissue will be incorporated, i.e. nonlinearity, viscoelasticity, anisotropy, heterogeneity and finally, tissue damage during deformation. A brief summary of experimental methods for material characterisation and an introduction to methods for geometric modelling are also provided. The overview is non-exhaustive, focusing on the most important general models and models with specific biological applications. A trade-off in complexity must be made for enabling real-time simulation, but still maintaining realistic representation of the organ deformation. Depending on the organ and tissue types, different models with emphasis on certain features will prove to be more appropriate, meaning the optimal model choice is organ and tissue-dependent.     

Soft tissue modelling for applications in virtual surgery and surgical robotics

Soft tissue modelling has gained a great deal of importance, for a large part due to its application in surgical training simulators for minimally invasive surgery (MIS). This article provides a structured overview of different continuum-mechanical models that have been developed over the years. It aims at facilitating model choice for specific soft tissue modelling applications. According to the complexity of the model, different features of soft biological tissue will be incorporated, i.e. nonlinearity, viscoelasticity, anisotropy, heterogeneity and finally, tissue damage during deformation. A brief summary of experimental methods for material characterisation and an introduction to methods for geometric modelling are also provided.

The overview is non-exhaustive, focusing on the most important general models and models with specific biological applications. A trade-off in complexity must be made for enabling real-time simulation, but still maintaining realistic representation of the organ deformation. Depending on the organ and tissue types, different models with emphasis on certain features will prove to be more appropriate, meaning the optimal model choice is organ and tissue-dependent.     

Integrating modelling of biodiversity composition and ecosystem function

There is increasing reliance on ecological models to improve our understanding of how ecological systems work, to project likely outcomes under alternative global change scenarios and to help develop robust management strategies. Two common types of spatiotemporally explicit ecological models are those focussed on biodiversity composition and those focussed on ecosystem function. These modelling disciplines are largely practiced separately, with separate literature, despite growing evidence that natural systems are shaped by the interaction of composition and function. Here we call for the development of new modelling approaches that integrate composition and function, accounting for the important interactions between these two dimensions, particularly under rapid global change. We examine existing modelling approaches that have begun to combine elements of composition and function, identifying their potential contribution to fully integrated modelling approaches. The development and application of integrated models of composition and function face a number of important challenges, including biological data limitations, system knowledge and computational constraints. We suggest a range of promising avenues that could help researchers overcome these challenges, including the use of virtual species, macroecological relationships and hybrid correlative‐mechanistic modelling. Explicitly accounting for the interactions between composition and function within integrated modelling approaches has the potential to improve our understanding of ecological systems, provide more accurate predictions of their future states and transform their management. Synthesis There is increasing attention from researchers and policy makers around the world on both assessing and projecting the state of the planet's biodiversity, its ecosystems and the essential services they provide to society. However, existing modelling approaches largely ignore the interactions between biodiversity composition and ecosystem function. We highlight the key challenges and potential solutions to developing integrated models of composition and function. Such models will require a new effort and focus from ecologists, yet the benefits are likely to be substantial, including better informing the management of natural systems at regional, national and international scales.     

Kinematic models of lower limb joints for musculo-skeletal modelling and optimization in gait analysis

Kinematic models of lower limb joints have several potential applications in musculoskeletal modelling of the locomotion apparatus, including the reproduction of the natural joint motion. These models have recently revealed their value also for in vivo motion analysis experiments, where the soft-tissue artefact is a critical known problem. This arises at the interface between the skin markers and the underlying bone, and can be reduced by defining multibody kinematic models of the lower limb and by running optimization processes aimed at obtaining estimates of position and orientation of relevant bones. With respect to standard methods based on the separate optimization of each single body segment, this technique makes it also possible to respect joint kinematic constraints. Whereas the hip joint is traditionally assumed as a 3 degrees of freedom ball and socket articulation, many previous studies have proposed a number of different kinematic models for the knee and ankle joints. Some of these are rigid, while others have compliant elements. Some models have clear anatomical correspondences and include real joint constraints; other models are more kinematically oriented, these being mainly aimed at reproducing joint kinematics. This paper provides a critical review of the kinematic models reported in literature for the major lower limb joints and used for the reduction of soft-tissue artefact. Advantages and disadvantages of these models are discussed, considering their anatomical significance, accuracy of predictions, computational costs, feasibility of personalization, and other features. Their use in the optimization process is also addressed, both in normal and pathological subjects.     

ElePhant: an anatomic-electronic simulation system for the evaluation of computer assisted interventions and surgical education]

BACKGROUND: Suitable simulation systems providing realistic conditions are required for preclinical evaluation of computer assisted interventions and surgical training. Techniques are necessary for an objective detection of injuries to the structures at risk. The aim of this study was the technical realization of a simulation system for the ENT intervention, mastoidectomy.MATERIALS AND METHODS: The basis of the simulation system was a CT scan of a cadaver skull. Using 3D printing, an anatomical phantom with realistic bone-like properties was created. Electronic detection systems were integrated into the structures at risk. A study with 16 ENT surgeons was conducted to prove the system's suitability for surgical training.RESULTS: The creation of simulation systems for the objective evaluation of surgical intervention qualities is feasible. A modular structure enables economic and simple replacement of the simulation area. The modules are cost effective and reproducible with high accuracy. The present study shows that the simulation system can be applied in surgical education and evaluation as an alternative to cadavers.CONCLUSION: Objective evaluation of injured structures at risk can be realized in real time. The simulation system permits preclinical evaluation studies of computer assisted instruments and surgical education. Reproducibility of the results makes multi-center studies possible.