Modelling complex and partially identified engineering problems- Application to the individualised multiscale simulation of the musculoskeletal system

Lead Research Organisation: University of Sheffield
Department Name: Chemical & Biological Engineering

Abstract

Traditionally, engineering design relies on scale separation. Virtually every physical process involves complex interactions across several space-time scales. For most engineering problems it is assumed that processes at different scales can be represented at the larger scale through some averaged property. However, when such assumptions of scale separation cannot be made, as in the modelling of biological systems where scales overlap, the inherent complexity of multi-scale interaction cannot be avoided. This proposal focuses on the establishment of a currently non-existent but essential computational platform for the treatment of musculoskeletal disorders. A multi-scale process in human physiology can be modelled as a collection of single scale models acting on a specific level of biological organisation coupled together across scales using appropriate scale bridging methods. Several unresolved challenges in the biomedical field have inhibited the development of predictive models needed in personalised medicine including (i) How to link mixed multiphysics models across several space-time scales. (ii) How to replace unobservable (possibly invasive and hence expensive) variables and states using proxy measurements (non invasive) reconstructed from the observable variables. (iii) How to use population data across patient classes or animal proxies to accommodate missing data. (iv) How to model uncertainty and the propagation of this across the simulations. (v) How to achieve these objectives within a framework that can be mapped to other engineering problems.
This proposal will tackle each of these challenges with:
- the development of a multi-scale model of the musculoskeletal system that describes the mechanobiological processes from the whole body (neuromuscular control and body dynamics) down to the cellular level (bone remodelling and mechanosensing);
- the creation of a multi-scale model from a partially identified input obtained by fusing a generic atlas of the anatomy, physiology, biology, and biomechanics for each individual.
This framework will be integrated in an efficient hypermodelling approach, numerically optimised at each scale level. Once fully realised, such a multi-scale framework will enable (i) deployment of specialised implementations as decision-support systems for diagnosis, prognosis, and treatment planning and monitoring for specific skeletal diseases such as lower back pain, osteoporosis, bone tumours and secondary metastases and osteoarthritis; (ii) implementation of in silico clinical trials for new orthopaedic and tissue engineering implants, modelling the variability of populations, providing a more accurate pre-clinical assessment for musculoskeletal devices and predicting the clinical outcome of these new devices; (iii) optimised interventions with respect to high socioeconomic impact conditions such as obesity, ageing population, disabilities, and chronic diseases in relation to physical activity, and assistive and rehabilitative technologies for neuromuscular deficits.

Planned Impact

The underlying modelling framework, developed to address multi-scale modelling with unobservable states and uncertainty, is increasingly required for nationally important research disciplines and societal problems such as: healthcare, environmental engineering, energy networks and advanced manufacturing. The focus on the musculoskeletal system addresses the economic burden of musculoskeletal diseases, which according to the WHO is 1%-2.5% of GDP of western nations, i.e. £30 billion p.a. in UK. The need for such a platform is essential considering that total healthcare expenditure in the UK has doubled from 2000-2010 to a staggering 10% of GDP. During this period about half of the annual cost increase has been attributed to the use of new technologies or the intensified use of old ones, such as the increased use of CT scans. To control the spiralling cost, models are required so that patient specific diagnosis and treatment procedures can be pre-assessed to predict the benefits, quality of life, and costs and hence aid decision making in each case. As well as the economic cost, musculoskeletal disorders cause poor quality-of-life, notably pain.
In addition to overcoming the above burden, the UK has industrial strength in the supply of orthopaedic devices, including the world's largest supplier outside the USA, namely Smith & Nephew, and innovative SMEs such as JRI Orthopaedics (each of whom are Partners of Frontier Multi-Scale). The modelling capabilities and the supply of skilled engineers enable their economic growth and anchors their presence in the UK.

Once fully realised, such a multi-scale framework will enable (i) deployment of specialised implementations as decision-support systems for diagnosis, prognosis, and treatment planning and monitoring for specific skeletal diseases such as lower back pain, osteoporosis, bone tumours and secondary metastases and osteoarthritis; (ii) implementation of in silico clinical trials for new orthopaedic and tissue engineerng implants, modelling the variability of populations, providing a more accurate pre-clinical assessment for musculoskeletal devices and predicting the clinical outcome of these new devices; (iii) optimised interventions with respect to high socioeconomic impact conditions such as obesity, ageing population, disabilities, and chronic diseases in relation to physical activity, and assistive and rehabilitative technologies for neuromuscular deficits.

Publications

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Bhattacharya P (2019) A multiscale model to predict current absolute risk of femoral fracture in a postmenopausal population. in Biomechanics and modeling in mechanobiology

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Bhattacharya P (2017) Multiscale modeling methods in biomechanics. in Wiley interdisciplinary reviews. Systems biology and medicine

 
Description We are developing a new healthcare technology that can account for the fact that biological tissues span a number of scales in terms of space and time. For example, the human body will respond to its environment by adapting to it and reducing (e.g. astronauts) or increasing (e.g. athletes) its bone mass. This process involves molecular, cell, tissue response over a time scale that differs for each space scale. In this grant, we are developing a framework that can simulate tissue adaptation for a number of cases. For example, we are now able to predict the risk of femoral bone fracture in osteoporotic patients with more accuracy than conventional clinical practice. We have developed a novel computational and experimental approach to test the effect of a new drug or medical device on bone response in a in vivo mouse pre-clinical testing context.
Exploitation Route We have developed a number of online services available through a web portal to any clinician or researcher. For example, we have developed the CT2S service which enables to predict the risk of bone fracture in a patient-specific manner for osteoporotic patient once the user uploads CT data from the patient.
We are also developing an online service based on High Resolution peripheral Quantitative Computed Tomography (HRpQCT) to calculate the bone stiffness and regions of bone weakening. We have now also completed the definition of a methodology for combining medical images and gait analysis data, which allows us to understand how much force each muscle is producing to allow a person to walk. This has been fully described in a published paper and a step-by-step guide has been shared on FigShare, together with relevant datasets to allow other researchers to replicate our results. We have also launched a new type of event called 'Modelathon' in which PhD students and Research Associates can participate during 3 days to solve a multiscale problem defined by our team. This enables the participants to get acquainted to multiscale modelling and develop further technologies later on for their own challenges.
Sectors Digital/Communication/Information Technologies (including Software),Healthcare,Pharmaceuticals and Medical Biotechnology

URL http://multisim-insigneo.org/
 
Description We have disseminated our gait biomechanics research and multiscale modelling capability to the public through the Sheffield Science Festival in 2017. During 4 sessions of 1 hour each a lay audience mixed of adults and children were able to understand how research in bone biomechanics can improve the diagnostics and treatment of diseases in elderly people.
First Year Of Impact 2017
Sector Digital/Communication/Information Technologies (including Software),Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Societal

 
Description BBSRC Research Grant (Dall Ara)
Amount £261,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2018 
End 12/2019
 
Description Biomedical Research Centre Competition
Amount £4,049,681 (GBP)
Organisation University of Leicester 
Department NIHR Biomedical Research Centre
Sector Hospitals
Country United Kingdom
Start 04/2017 
End 05/2027
 
Description Dassault Systems La Foundation Grant
Amount £85,000 (GBP)
Organisation La Fondation Dassault Systèmes 
Start 10/2016 
End 09/2017
 
Description First Grant Scheme (Dall Ara)
Amount £100,578 (GBP)
Funding ID EP/P015778/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 10/2017 
End 10/2018
 
Description H2020 Research Grant - CompBioMed
Amount € 4,938,215 (EUR)
Funding ID 675451 
Organisation European Commission H2020 
Sector Public
Country Belgium
Start 10/2016 
End 09/2019
 
Description H2020-WIDESPREAD-04-2017-TeamingPhase1
Amount € 399,963 (EUR)
Funding ID 763734 
Organisation European Commission H2020 
Sector Public
Country Belgium
Start 09/2017 
End 08/2018
 
Description Insigneo Bursary for Clinical Translation
Amount £7,720 (GBP)
Organisation Sheffield Hospitals Charity 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2014 
End 12/2014
 
Description MSCA-ITN-EID - European Industrial Doctorates
Amount € 1,588,449 (EUR)
Funding ID 766012 
Organisation European Commission H2020 
Sector Public
Country Belgium
Start 01/2018 
End 12/2021
 
Description NC3Rs Research Grant (Dall Ara)
Amount £357,401 (GBP)
Funding ID NC/R001073/1 
Organisation National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) 
Sector Private
Country United Kingdom
Start 12/2017 
End 08/2020
 
Description Network on Computational Statistics and Machine Learning (NCSML)
Amount £1,000 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 09/2014 
End 09/2016
 
Description Newton Mobility Grants
Amount £3,000 (GBP)
Organisation The Royal Society 
Sector Academic/University
Country United Kingdom
Start 08/2017 
End 11/2017
 
Description Research grants
Amount £16,615 (GBP)
Organisation Sheffield Hospitals Charity 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2016 
End 10/2016
 
Description Research grants
Amount £8,058 (GBP)
Organisation Sheffield Hospitals Charity 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2013 
End 04/2014
 
Description Research grants
Amount £9,896 (GBP)
Organisation White Rose University Consortium 
Sector Academic/University
Country United Kingdom
Start 04/2015 
End 03/2016
 
Description Research grants
Amount £15,000 (GBP)
Organisation The Royal Society 
Sector Academic/University
Country United Kingdom
Start 09/2015 
End 08/2016
 
Title Data for Tagliapietra, L., Modenese, L., Reggiani, M., Ceseracciu, E., Mazzà, C., Validation of a model-based inverse kinematics approach based on wearable inertial sensors Computer Methods in Biomechanics and Biomedical Engineering 
Description Data for Tagliapietra, L., Modenese, L., Reggiani, M., Ceseracciu, E., Mazzà, C., Validation of a model-based inverse kinematics approach based on wearable inertial sensors Computer Methods in Biomechanics and Biomedical Engineering https://doi.org/10.1080/10255842.2018.1522532 This dataset contains all the results presented in the linked paper. Data are organized as follow: - Framework_01 - out_data - ob-ik: contains the joint angles (in degrees) estimated from the orientation based inverse kinematics using the imu's orientations - robot: contains the joint angles recorded from the robot encorders, thus they can be considered the ground of truth - Framework_02 - out_data - ob-ik: contains the joint angles (in degrees) estimated from the orientation based inverse kinematics using the imu's orientations - mb-ik: contains the joint angles (in degrees) estimated from the marker based inverse kinematics, the gold-standard in human motion analysis. Therefore, they are used as reference values. - Framework_03 : same as Framework 02. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact Dataset is available for the research community. 
URL https://doi.org/10.15131/shef.data.7097744.v1
 
Title Data for paper "Free-living and laboratory gait characteristics in patients with multiple sclerosis" 
Description This space has been created to support the paper "Free-living and laboratory gait characteristics in patients with multiple sclerosis", where all the information about the data collection can be recovered. (Paper doi: https://doi.org/10.1371/journal.pone.0196463) The .xlsx file includes information about the participants. The .csv file contains the participant's mean and SD values for each investigated gait parameter. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
Impact This dataset has been made open access (CC BY 4.0) to the research community. 
URL https://doi.org/10.15131/shef.data.5478460
 
Title Data for paper: A multiscale model to predict current absolute risk of femoral fracture in a postmenopausal population 
Description Complete results set of the study reported in "A multiscale model to predict current absolute risk of femoral fracture in a postmenopausal population" by Pinaki Bhattacharya, Zainab Altai, Muhammad Qasim, and Marco Viceconti (preprint: https://doi.org/10.17605/OSF.IO/549UM) 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
Impact Recently published, too soon to say. 
URL https://doi.org/10.15131/shef.data.5882554
 
Title Data for paper: An objective functional characterisation of head movement impairment in individuals with neck muscle weakness due to Amyotrophic lateral sclerosis 
Description Please refer to the Readme.docx file for information about the dataset. These data were collected for a research project entitled "An objective functional characterisation of head movement impairment in individuals with neck muscle weakness due to Amyotrophic lateral sclerosis" published in PLOS ONE https://doi.org/10.1371/journal.pone.0169019. Methods involved in generating the data are described in the paper. Data are also included in the PhD thesis entitled "Assessing residual neck mobility when wearing a cervical orthosis: an application in patients with Motor Neurone Disease" which is available online through WREO http://etheses.whiterose.ac.uk/id/eprint/16179. REFERENCES https://doi.org/10.1371/journal.pone.0169019 http://eprints.whiterose.ac.uk/109783/ http://etheses.whiterose.ac.uk/id/eprint/16179 FUNDING EPSRC Frontier Engineering Awards, Grant Reference No. EP/K03877X/1 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact See: "An objective functional characterisation of head movement impairment in individuals with neck muscle weakness due to Amyotrophic lateral sclerosis" published in PLOS ONE https://doi.org/10.1371/journal.pone.0169019. 
URL https://doi.org/10.15131/shef.data.4476734
 
Title Data for paper: Extended discrete element method can evaluate the effect of time dependency and translation of the talus on the estimation of cartilage pressure at the ankle joint 
Description Data for paper "Extended discrete element method can evaluate the effect of time dependency and translation of the talus on the estimation of cartilage pressure at the ankle joint" 15.02.2018, 11:49 by Ivan Benemerito Luca Modenese Erica Montefiori Claudia Mazza Marco Viceconti Damien Lacroix Lingzhong Guo Input kinematics and ankle forces are included as MATLAB file. The Extended Discrete Element Method has been used to compute the ankle joint contact pressure distribution. For details email ibenemerito1@sheffield.ac.uk 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
Impact Recently published, too soon to report. 
URL https://doi.org/10.15131/shef.data.5829120
 
Title Data for paper: Sensitivity of a juvenile subject -specific musculoskeletal model of the ankle joint to the variability of operator dependent input 
Description MultiSim (Grant No. EP/K03877X/1) Data for paper 'Sensitivity of a juvenile subject -specific musculoskeletal model of the ankle joint to the variability of operator dependent input' 25.07.2017, 15:52 by Iain Hannah Erica Montefiori Luca Modenese Marco Viceconti Claudia Mazza These files represent the data used for the study reported in the paper: Hannah, I. et al. (2017) Sensitivity of a juvenile subject-specific musculoskeletal model of the ankle joint to the variability of operator dependent input. Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine. ISSN 0954-4119. https://doi.org/10.1177/0954411917701167 The Statistics folder contains the raw data for the inter- and intra-operator analysis, for each subject, for the three considered procedures: muscles attachments adjustment; virtual palpation, reference systesms definition. Three folders represent the subjects' data used for the simulations: Subject A, Subject B, Subject C. Inside each subject's folder there is a folder with the input data (static motion data), and the musculoskeletal simulations for each operator (i.e. Mod A.1 contains the simulations for subject A done by operator 1 ). Inside these folders there are the results for each simulated walking trial and the final OpenSim model of the subject, done by the respective operator. REFERENCES https://doi.org/10.1177/0954411917701167 http://multisim-insigneo.org/ FUNDING EPSRC: EP/K03877X/1 and EUROPEAN COMMISSION - FP6/FP7: MDPAEDIGREE - 600932 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact See: Hannah, I. et al. (2017) Sensitivity of a juvenile subject-specific musculoskeletal model of the ankle joint to the variability of operator dependent input. Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine. ISSN 0954-4119. https://doi.org/10.1177/0954411917701167 
URL https://doi.org/10.15131/shef.data.4286519
 
Title Data for the assessment of the effect of repositioning in in vivo loading studies with Digital Volume Correlation 
Description Data for the assessment of the effect of repositioning in in vivo loading studies with Digital Volume Correlation Fileset modified on 10.09.2018, 10:59 by Enrico Dall'Ara Mario Giorgi Link to the data used in: Giorgi, M., Dall'Ara, E. (2018) Variability in strain distribution in the mice tibia loading model: preliminary study using digital volume correlation. Medical Engineering and Physics 2018 The images and data are too large to be uploaded in ORDA, so please contact e.dallara@sheffield.ac.uk or the Project Management Office at: pmo@insigneo.org if you are interested in working on the files. Only an example of a dataset has been uploaded. In the B-03-a folder the preloaded image (Scan1_crop.dcm) has been registered with three different files "Scan2_cop.dcm" that represent: 01_Scan2_preload_REGwith_Scan1_load: registration between the second preloaded image and the first loaded image 01_Scan2_preload_REGwith_Scan2: registration between the second preloaded image and the repeated image in the loaded configuration 01_Scan2_preload_REGwith_Repositioning: registration between the second preloaded image and the image of the loaded specimen taken after repositioning In the folder C-03-a-02-Nodes the results from the deformable registration are reported for each registration for Node Spacing of 50. Registrations have been done with ShIRT followed by the voxel detection algorithms as described in the paper. "output_map.txt" reports the coordinates of the nodes of the grid and the computed displacements "results.txt" reports the principal strains in each node The whole dataset is stored in the University of Sheffield file-store at the link: https://web-unidrive.sheffield.ac.uk/shared/multisim2/WP7/Mario_Giorgi/DVC_Tibia_Precision_Study/ 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
Impact This data has been made available to the research community (CC BY 4.0) 
URL https://doi.org/10.15131/shef.data.7058078
 
Title Data for the paper: "Uncertainties of Synchrotron microCT-based Digital Volume Correlation bone strain measurements under simulated deformation" 
Description Link to the data used in: Comini F, Palanca M, Cristofolini L, Dall'Ara E. (2019) Uncertainties of Synchrotron microCT-based Digital Volume Correlation bone strain measurements under simulated deformation. Journal of Biomechanics 2019. The images and data are too large to be uploaded in ORDA, so please contact the corresponding author at: e.dallara@sheffield.ac.uk or the Project Management Office at: pmo@insigneo.org if you are interested in working on the files. In this repository we have uploaded only the result file obtained from the Digital Volume Correlation analyses post-processed with Matlab. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact This data has been made available to the research community (CC BY 4.0) 
URL https://doi.org/10.15131/shef.data.7624958.v1
 
Title Data for the paper: A new proxy measurement algorithm with applications to estimation of vertical ground reaction forces using wearable sensors 
Description Data for the paper "A new proxy measurement algorithm with applications to estimation of vertical ground reaction forces using wearable sensors" 06.12.2017, 12:49 by Yuzhu Guo Fabio Storm Yifan Zhao Stephen Billings Alex Pavic Claudia Mazza Lingzhong Guo Guo, Y., Storm, F., Zhao, Y. et al. (2017) A new proxy measurement algorithm with application to the estimation of vertical ground reaction forces using wearable sensors. Sensors, 17 (10). 2181. ISSN 1424-8220. DOI:10.3390/s17102181 Measurement of the ground reaction forces (GRF) during walking is typically limited to laboratory settings and only short observations using wearable pressure insoles have been reported so far. In this study, a new proxy measurement method is proposed to estimate the vertical component of the GRF (vGRF) from wearable accelerometer signals. The accelerations are used as the proxy variable. An orthogonal forward regression algorithm (OFR) is employed to identify the dynamic relationships between the proxy variables and the measured vGRF using pressure-sensing insoles. The obtained model, which represents the connection between the proxy variable and the vGRF, is then used to predict the latter. The results have been validated using pressure insoles data collected from nine healthy individuals under two outdoor walking tasks in non-laboratory settings. Results show that the vGRFs can be reconstructed with high accuracy (with an average prediction error of less than 6%) using only one wearable sensor mounted at forehead level. Proxy measures with different sensor positions are also discussed. Results show that the forehead accelerations based proxy measurement is more stable with less inter-task and inter-subject variability than the proxy measures using cervical and low back level accelerations. The proposed proxy measure provides a promising low-cost method for monitoring ground reaction forces in real life settings and introduces a novel generic approach for replacing the direct determination of difficult to measure variables in many applications. REFERENCES https://doi.org/10.3390/s17102181 http://eprints.whiterose.ac.uk/121805/ FUNDING The research was funded by the UK Engineering and Physical Sciences Research Council (EP/K03877X/1). 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact See: Guo, Y., Storm, F., Zhao, Y. et al. (2017) A new proxy measurement algorithm with application to the estimation of vertical ground reaction forces using wearable sensors. Sensors, 17 (10). 2181. ISSN 1424-8220. DOI:10.3390/s17102181 
URL https://doi.org/10.15131/shef.data.5341309
 
Title Data for the paper: Gait event detection in laboratory and real life settings: accuracy of ankle and waist sensor based methods 
Description Data for the paper 'Gait event detection in laboratory and real life settings: accuracy of ankle and waist sensor based methods' 28.09.2017, 17:13 by Fabio Storm Chris Buckley Claudia Mazza The aim of this study was to evaluate the accuracy of two algorithms for the detection of gait events and temporal parameters during free-living walking, one based on two shank-worn inertial sensors, and the other based on one waist-worn sensor. The algorithms were applied to gait data of ten healthy subjects walking both indoor and outdoor, and completing protocols that entailed both straight supervised and free walking in an urban environment. REFERENCES http://dx.doi.org/10.1016/j.gaitpost.2016.08.012 http://eprints.whiterose.ac.uk/103798/ FUNDING This study was supported by the EPSRC Frontier Engineering Awards, Grant Reference No. EP/K03877X/1 and by the MRC and Arthritis Research UK as part of the MRC - Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA). 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact See: Gait event detection in laboratory and real life settings: Accuracy of ankle and waist sensor based methods Storm, Fabio A. et al. Gait & Posture , Volume 50 , 42 - 46 http://dx.doi.org/10.1016/j.gaitpost.2016.08.012 
URL https://doi.org/10.15131/shef.data.3503180
 
Title Dataset SRACC: Synchrotron microCT for testing accuracy of Digital Volume Correlation (DVC) methods 
Description Database of the results obtained in: Palanca et al. Local Displacement and Strain Uncertainties in different Bone Types by Digital Volume Correlation of Synchrotron Microtomograms JBiomech 2017 http://doi.org/10.1016/j.jbiomech.2017.04.007 The images are too large to be uploaded in figshare so please contact the corresponding author at: e.dallara@sheffield.ac.uk or the Project Management Office at: pmo@insigneo.org if interested in working on the files. REFERENCES http://doi.org/10.1016/j.jbiomech.2017.04.007 FUNDING EPSRC Frontier Grant (MultiSim project code EP/K03877X/1), FP7 European program MAMBO (PIEF-GA-2012-327357), Diamond Light Source (MT10315), 'Marco Polo' travel grant awarded by University of Bologna 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact See: Palanca et al. Local Displacement and Strain Uncertainties in different Bone Types by Digital Volume Correlation of Synchrotron Microtomograms JBiomech 2017 http://doi.org/10.1016/j.jbiomech.2017.04.007 
URL https://doi.org/10.15131/shef.data.4865300
 
Title FE-based Femoral strength of 100 osteoporotic women 
Description FE-based Femoral strength of 100 osteoporotic women 11.10.2017, 15:39 by Marco Viceconti Complete results set of the study reported in "Patient-Specific Finite Element Estimated Femur Strength as a Predictor of the Risk of Hip Fracture: The Effect of Methodological Determinants" by Muhammad Qasim, Giovanna Farinella, Ju Zhang, Xinshan Li, Lang Yang, Richard Eastell, and Marco Viceconti, Osteoporosis International, 2016. DOI: 10.1007/s00198-016-3597-4. Open access full text: http://link.springer.com/article/10.1007/s00198-016-3597-4 REFERENCES http://dx.doi.org/10.1007/s00198-016-3597-4 FUNDING EP/K03877X/1 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact See: "Patient-Specific Finite Element Estimated Femur Strength as a Predictor of the Risk of Hip Fracture: The Effect of Methodological Determinants" by Muhammad Qasim, Giovanna Farinella, Ju Zhang, Xinshan Li, Lang Yang, Richard Eastell, and Marco Viceconti, Osteoporosis International, 2016. DOI: 10.1007/s00198-016-3597-4. 
URL https://doi.org/10.15131/shef.data.3124108
 
Title Failure strength of infant femurs under 4 point bending of 15 cases 
Description Failure strength of infant femurs under 4 point bending of 15 cases 28.10.2016, 13:52 by Xinshan Li Complete results set of the study reported in " X. Li, M. Viceconti, M. C. Cohen, G. C. Reilly, M. J. Carre, A. C. Offiah 2015. "Developing CT Based Computational Models of Pediatric Femurs", in Journal of Biomechanics, 48, 2034-40" REFERENCES http://dx.doi.org/10.1016/j.jbiomech.2015.03.027 FUNDING EP/K03877X/1 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact See: Complete results set of the study reported in " X. Li, M. Viceconti, M. C. Cohen, G. C. Reilly, M. J. Carre, A. C. Offiah 2015. "Developing CT Based Computational Models of Pediatric Femurs", in Journal of Biomechanics, 48, 2034-40" http://dx.doi.org/10.1016/j.jbiomech.2015.03.027 
URL https://doi.org/10.15131/shef.data.3969285
 
Title Figures for the review article: In Vitro Bone Cell Models: Impact of Fluid Shear Stress on Bone formation 
Description Figures for the review article: 'In Vitro Bone Cell Models: Impact of Fluid Shear Stress on Bone formation' 28.09.2017, 17:16 by Claudia Wittkowske Cecile Perrault Damien Lacroix Gwendolen Reilly This folder contains the figures which were included in the review article "In Vitro Bone Cell Models: Impact of Fluid Shear Stress on Bone formation" (Frontiers in Bioengineering and Biotechnology 4:87. doi: 10.3389/fbioe.2016.00087). This review describes the role of bone cells and their surrounding matrix in maintaining bone strength through the process of bone remodeling. Subsequently, this work focusses on how bone formation is guided by mechanical forces and fluid shear stress in particular. In vitro, it has been reported that bone cells respond to fluid shear stress by releasing osteogenic signaling factors, such as nitric oxide, and prostaglandins. This work focusses on the application of in vitro models to study the effects of fluid flow on bone cell signaling, collagen deposition, and matrix mineralization. REFERENCES http://dx.doi.org/10.3389/fbioe.2016.00087 http://eprints.whiterose.ac.uk/109118/ FUNDING MultiSim, an EPSRC Frontier Engineering Award, Grant Reference No. EP/K03877X/1 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact See: 'In Vitro Bone Cell Models: Impact of Fluid Shear Stress on Bone formation' 28.09.2017, 17:16 by Claudia Wittkowske Cecile Perrault Damien Lacroix Gwendolen Reilly http://dx.doi.org/10.3389/fbioe.2016.00087 http://eprints.whiterose.ac.uk/109118/ 
URL https://doi.org/10.15131/shef.data.4203153
 
Title MAMBO_IND sub-project: Indentation data for cortical bone (Depth-sensing Micro-Indentation and RPI), database and statistics 
Description MultiSim (Grant No. EP/K03877X/1) MAMBO_IND sub-project: Indentation data for cortical bone (Depth-sensing Micro-Indentation and RPI), database and statistics 11.10.2017, 14:54 by Enrico Dall'Ara The data are reported in a spreadsheet. Each sheet reports the data from microindentation tests (along the three directions axial A, circumferential C and radial R) and reference point indentation (RPI) tests. Details are reported in the manuscript: Estimation of local anisotropy of plexiform bone: Comparison between depth sensing micro-indentation and Reference Point Indentation. Dall'Ara E, Grabowski P, Zioupos P, Viceconti M. J Biomech. 2015 Nov 26;48(15):4073-80. doi: 10.1016/j.jbiomech.2015.10.001. Epub 2015 Oct 9. For any questions the reader can contact Dr Enrico Dall'Ara e.dallara@sheffield.ac.uk REFERENCES http://www.sciencedirect.com/science/article/pii/S0021929015005473 FUNDING EPSRC (MultiSim project EP/K03877X/1 and Point-of-Care High Accuracy Fracture Risk Prediction EP/K020196) and FP7 European Program (PIEF-GA-2012-327357) 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact See: Estimation of local anisotropy of plexiform bone: Comparison between depth sensing micro-indentation and Reference Point Indentation. Dall'Ara E, Grabowski P, Zioupos P, Viceconti M. J Biomech. 2015 Nov 26;48(15):4073-80. doi: 10.1016/j.jbiomech.2015.10.001. Epub 2015 Oct 9. 
URL https://doi.org/10.15131/shef.data.3827046
 
Title METVERT_Validation_Results: Micro Finite Element models of the vertebral body: Validation of local displacement predictions 
Description This file contains the results collected in the study: "Micro Finite Element models of the vertebral body: Validation of local displacement predictions" by "Costa, Tozzi, Cristofolini, Danesi, Viceconti, Dall'Ara" published in PLoS ONE 12(7): e0180151. https://doi.org/10.1371/journal.pone.0180151. In order to access the original raw files the reader can contact the the corresponding author (Dr Enrico Dall'Ara, e.dallara@sheffield.ac.uk). The files are stored in the University of Sheffield file-store at the link: https://web-unidrive.sheffield.ac.uk/shared/multisim2/WP7/METVERT_Validation/ REFERENCES https://doi.org/10.1371/journal.pone.0180151 FUNDING The project was partially funded by the Sheffield Hospitals Charity (141515-1), the Engineering and Physical Sciences Research Council (EP/K03877X/1) and the Royal Society (RG130831 and RG150012) 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact See: "Micro Finite Element models of the vertebral body: Validation of local displacement predictions" by "Costa, Tozzi, Cristofolini, Danesi, Viceconti, Dall'Ara" published in PLoS ONE 12(7): e0180151. https://doi.org/10.1371/journal.pone.0180151. 
URL https://doi.org/10.15131/shef.data.5121871
 
Title Mechanoregulation of bone remodelling in mice under physiological loading 
Description Mechanoregulation of bone remodelling in mice under physiological loading 11.10.2017, 15:39 by Marco Viceconti Enrico Dall'Ara Maya Boudiffa These are the raw data analysed and reported in the manuscript entitled "EVALUATION OF DIFFERENT BONE REMODELLING THEORIES ON THE CHANGES IN BONE MINERAL DENSITY OF MICE TIBIAE UNDER PHYSIOLOGICAL LOADING" by Yongtao Lu, Enrico Dall'Ara, Maya Boudiffa, and Marco Viceconti, submitted for publication to the Journal of the Royal Society Interface. FUNDING This work was funded by the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), grant number:NC/K000780/1, the Engineering and Physical Sciences Research Council - MultiSim project, grant number: EP/K03877X/1 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact See: "EVALUATION OF DIFFERENT BONE REMODELLING THEORIES ON THE CHANGES IN BONE MINERAL DENSITY OF MICE TIBIAE UNDER PHYSIOLOGICAL LOADING" by Yongtao Lu, Enrico Dall'Ara, Maya Boudiffa, and Marco Viceconti, submitted for publication to the Journal of the Royal Society Interface. 
URL https://doi.org/10.15131/shef.data.3814701
 
Title MicroCT Dataset of mouse tibiae for DVC precision analyses (repeated scans ex vivo and in vivo) 
Description Database of the images (repeated scans of mouse tibiae obtained in vivo and ex vivo) used in: Precision of DVC approaches for strain analysis in bone imaged with µCT at different dimensional levels. by: Enrico Dall'ara, Marta Peña-Fernández, Marco Palanca, Mario Giorgi, Luca Cristofolini, Gianluca Tozzi Original Research, Front. Mater. - Mechanics of Materials, 2017 The images related to the precision of DVC applied to the mouse tibiae are too large to be uploaded in figshare so please contact the corresponding author at: e.dallara@sheffield.ac.uk or the Project Management Office at: pmo@insigneo.org if interested in working on the files. The files are stored in the University of Sheffield file-store at the link: https://web-unidrive.sheffield.ac.uk/shared/multisim2/WP7/Mario_Giorgi/DVC_Tibia_Precision_Study 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact See: Dall'Ara Enrico, Peña-Fernández Marta, Palanca Marco, Giorgi Mario, Cristofolini Luca, Tozzi Gianluca Precision of Digital Volume Correlation Approaches for Strain Analysis in Bone Imaged with Micro-Computed Tomography at Different Dimensional Levels Frontiers in Materials (2017) 4, 31 https://www.frontiersin.org/articles/10.3389/fmats.2017.00031/abstract https://doi.org/10.3389/fmats.2017.00031 
URL https://doi.org/10.15131/shef.data.5528104
 
Title MicroCT Dataset of mouse tibiae for evaluating the effect of the integration time on output parameters 
Description Database of the results obtained from the images (repeated scans of mouse tibiae obtained ex vivo with different scanning parameters) used in: Oliviero, S., Lu, Y., Viceconti, M. et al. (2017) Effect of integration time on the morphometric, densitometric and mechanical properties of the mouse tibia. Journal of Biomechanics , 65. https://doi.org/10.1016/j.jbiomech.2017.10.026 The images are too large to be uploaded in figshare so please contact the corresponding author at: e.dallara@sheffield.ac.uk or the Project Management Office at: pmo@insigneo.org if interested in working on the files. The files are stored in the University of Sheffield file-store at the link: https://web-unidrive.sheffield.ac.uk/shared/multisim2/WP7/In_vivo_imaging_procedure/ REFERENCES https://doi.org/10.1016/j.jbiomech.2017.10.026 FUNDING UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs, Grant number: NC/K000780/1) and by the Engineering and Physical Sciences Research Council (EPSRC, MultiSim project, Grant number: EP/K03877X/1) 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact See: Oliviero, S., Lu, Y., Viceconti, M. et al. (2017) Effect of integration time on the morphometric, densitometric and mechanical properties of the mouse tibia. Journal of Biomechanics , 65. https://doi.org/10.1016/j.jbiomech.2017.10.026 
URL https://doi.org/10.15131/shef.data.5562529
 
Title MicroCT, DVC and MicroFE datasets for the validation for finite element models of the Mouse Tibia 
Description Link to the data used in: Oliviero, S., Giorgi, M., Dall'Ara, E. (2018) Validation of Finite Element models of the Mouse Tibia using Digital Volume Correlation. Journal of Mechanical Behaviour of Biomedical Materials 2018. https://doi.org/10.1016/j.jmbbm.2018.06.022 The images and data are too large to be uploaded in ORDA, so please contact the corresponding author at: e.dallara@sheffield.ac.uk or the Project Management Office at: pmo@insigneo.org if you are interested in working on the files. The files are stored in the University of Sheffield file-store at the link: https://web-unidrive.sheffield.ac.uk/shared/multisim2/WP7/Validation/Oliviero_JMBBM_2018/ 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
Impact This data has been made available to the research community (CC BY 4.0) 
URL https://doi.org/10.15131/shef.data.6635561
 
Title Models and data for the paper: To what extent is joint and muscle mechanics predicted by musculoskeletal models sensitive to soft tissue artefacts? 
Description MultiSim (Grant No. EP/K03877X/1) Models and data for the paper "To what extent is joint and muscle mechanics predicted by musculoskeletal models sensitive to soft tissue artefacts?" 28.09.2017, 15:55 by Giuliano Lamberto Saulo Martelli Aurelio Cappozzo Claudia Mazzà Model and data used in the study "To what extent is joint and muscle mechanics predicted by musculoskeletal models sensitive to soft tissue artefacts?" by Giuliano Lamberto, Saulo Martelli, Aurelio Cappozzo, and Claudia Mazzà, Journal of Biomechanics. Please, consider the READ ME document to understand the structure and names of the dataset included in this repository. REFERENCES http://dx.doi.org/10.1016/j.jbiomech.2016.07.042 http://eprints.whiterose.ac.uk/103365/ FUNDING EP/K03877X/1; European Commission, 7th FP, "MD- Paedigree", ICT Programme (Contract Number 600932); the Australian Research Council (DE140101530) 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact See: "To what extent is joint and muscle mechanics predicted by musculoskeletal models sensitive to soft tissue artefacts?" by Giuliano Lamberto, Saulo Martelli, Aurelio Cappozzo, and Claudia Mazzà, Journal of Biomechanics. http://dx.doi.org/10.1016/j.jbiomech.2016.07.042 
URL https://doi.org/10.15131/shef.data.3502652
 
Title Moving from laboratory to real life conditions: Influence on the assessment of variability and stability of gait 
Description Data for the paper: Tamburini, Paola; Storm, Fabio; Buckley, Christopher; Cristina Bisi, Maria; Stagni, Rita; Mazza, Claudia (2017): Moving from laboratory to real life conditions: Influence on the assessment of variability and stability of gait. Gait & Posture, 2018, 59, 248-252 REFERENCES http://www.sciencedirect.com/science/article/pii/S0966636217309815 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact See: Tamburini, Paola; Storm, Fabio; Buckley, Christopher; Cristina Bisi, Maria; Stagni, Rita; Mazza, Claudia (2017): Moving from laboratory to real life conditions: Influence on the assessment of variability and stability of gait. Gait & Posture, 2018, 59, 248-252 REFERENCES http://www.sciencedirect.com/science/article/pii/S0966636217309815 
URL https://doi.org/10.15131/shef.data.5519680
 
Description FP7 PIPER (Xinshan Li) 
Organisation European Commission
Country European Union (EU) 
Sector Public 
PI Contribution We are currently investigating the difference in mechanical response by comparing the 3-yr-old PIPER model and our personalised model. The PIPER model is generated by scaling down from an adult femur. This research will shine some light on the validity of scaling adult models for paediatric applications, and could be a game changer if the adult model is proven to be inaccurate.
Collaborator Contribution There has been 2 teleconference. And we have received some help from the consortia regarding the running of 3-yr-old PIPER model. The PIPER consortia provided some additional material in terms of the validation of their organ-scale model for the 3-yr-old femur, which was not previously made public, as part of the open source code released by the consortia.
Impact Not yet. The final year project student is wrapping up the work. There could be a potential publication.
Start Year 2017
 
Description Great Ormond Street Hospital (Xinshan Li) 
Organisation Great Ormond Street Hospital (GOSH)
Country United Kingdom 
Sector Hospitals 
PI Contribution The Sheffield team developed a new pipeline to create personalised paediatric long bone models from paired MRI-CT scans. This is the first in the field as the combination of mineralising bone and mineralised bone in infant bone modelling has never been attempted before.
Collaborator Contribution We received 4 sets of paired MRI-CT scans from GOSH. We have also visited the GOSH team in the past for 4 face to face meetings. The GOSH team has also provided valuable clinical opinion on the topic of personalised modelling for children.
Impact There is a publication being submitted to CMBBE. No specific agreements, as it only involved a small number of dataset which has already got research ethics approval on the GOSH side.
Start Year 2016
 
Description Making things through movement, Leeds, Mazza 
Organisation University of Leeds
Country United Kingdom 
Sector Academic/University 
PI Contribution Access and expert support in the use of motion capture technology, provided by the Insigneo Gait Laboratory, associated with MultiSim WP2.
Collaborator Contribution Dancers and choreography to create a performance and video of performance.
Impact This is a collaboration between Mechanical Engineering - Biomechanics, providing motion capture technology and the creative arts providing creative dance and choreography. A collaborative performance 'Making things through movement' working across disabled and able communities, recorded under engagement. Further funding and opportunities are being explored to extend this collaboration and produce further performances.
Start Year 2017
 
Description Making things through movement, Leeds, Mazza 
Organisation University of Sheffield
Department Department of Infection, Immunity and Cardiovascular Disease
Country United Kingdom 
Sector Academic/University 
PI Contribution Access and expert support in the use of motion capture technology, provided by the Insigneo Gait Laboratory, associated with MultiSim WP2.
Collaborator Contribution Dancers and choreography to create a performance and video of performance.
Impact This is a collaboration between Mechanical Engineering - Biomechanics, providing motion capture technology and the creative arts providing creative dance and choreography. A collaborative performance 'Making things through movement' working across disabled and able communities, recorded under engagement. Further funding and opportunities are being explored to extend this collaboration and produce further performances.
Start Year 2017
 
Description Dem Bones are Gonna Walk About, Sheffield Festival of Science 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Dem Bones Gonna Walk Around: An overview of our session
This session briefly explains how the musculoskeletal system is made up of bones, muscles and joints that help us take part in everyday physical activities such as sitting, standing and walking. It then demonstrates how these movements can be captured and used to predict the forces created in our joints between the muscles and bones. Find out how computer models of physical activities can be developed to predict the risk of bone fracture!
Members of the public were invited to the Insigneo Gait Laboratory, for an hour long workshop, including presentations and interactive demonstrations of motion capture and computer simulations. This workshop was ran four times over Sheffield Festival of Science to groups of 20 people, across a wide range of ages.
Year(s) Of Engagement Activity 2017
URL http://multisim-insigneo.org/events/fun-inspiring-free-events-sheffield-festival-science-engineering...
 
Description Making things through movement, Leeds, Mazza 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Making things through movement explored the creative, socially beneficial and therapeutic benefits of working with and through movement across disabled and abled communities. On this project, supported, by the Faculty of Engineering as part of their outreach events, we worked with cultural theorist and choreographer, Nicolas Salazar Sutil (University of Leeds). The project brought together disabled participants with different levels of paralysis and previous exposure to dance, collaborating with a dancer and choreographer to explore and extend the experience of embodiment, through movement, narration and music. Motion capture technology was used to produce a visualisation of the processes through which movement was collaboratively explored. The topic that organically emerged from the participants' interactions is pain, and this video shows a performance that developed from the collaboration. It was, however, the process of working across arts and humanities and engineering, with active input from our participants, that made this project particularly rewarding for everyone involved. We aim to extend it further to explore how motion capture technology can augment the experience of movement for people who have limited movement.
Year(s) Of Engagement Activity 2017
URL http://mhs.group.shef.ac.uk/moving-bodies-humanitiesengingeering-pilot-projects/
 
Description Modelathon 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Aim of Modelathon: To engage researchers in the field of musculoskeletal and cardiovascular research with the principles and practice of multiscale modelling through addressing an authentic research challenge using both industrial and open source research tools and frameworks. To raise the profile of the project amongst the academic community and industry.

The MultiSim Modelathon brings together PhD and PostDoc researchers in the field of Multi-Scale Modelling and Biomechanical Engineering, from around the world, to compete in teams against one another to solve a complex multi-scale modelling problem. This three-day event is based on the concept of a hackathon event where different teams work on a challenging problem to 'hack' a computer code. Here there is no 'hacking' but 'modelling'. The teams competed to solve a challenging multi-scale biomechanical problem within the musculoskeletal system using state-of-the-art techniques and software.

Industry members and multi-scale experts supported the event, including software providers and Ansys, Simpleware, Materialise and Simulia. They supported the Modelathon by providing licences for the academic developers preparing and testing the challenges before the event, and the Modelathon participants during the event. They provided expertise and technical support during the event to encourage participants to make the most of the software available and sponsored the events to subsidise the costs to the participants.

In 2017, a scene-setting one-day symposium was added to the Modelathon.

Each year the Modelathon attracts approximately 25 researchers.
Year(s) Of Engagement Activity 2015,2016,2017,2018,2019
URL http://multisim-insigneo.org/modelathon/
 
Description SoleLincs 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Three researchers from MultiSim WP2, Body Model, were invited to a CPD (Career and Professional Development) day workshop by Sole Lincs, a practice network in for Foot Health professionals based in Lincolnshire. The researchers presented their work on the biomechanics of the gait cycle in the morning, with demonstrations of the sensors and motion capture equipment. In the afternoon, participants then reflected on how this knowledge may influenced their practice in the context of case studies that they brought to the session.
Year(s) Of Engagement Activity 2018