NND: Progress and demonstrations

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1 NND: Progress and demonstrations MD-Paedigree Final Review Marjolein van der Krogt & Frans Steenbrink Brussels, 6/7 July 2017

2 Acknowledgements Jaap Harlaar, Laura Oudenhoven, Eline Flux, Marjolein Piening (VUmc) Kaat Desloovere, Marije Goudriaan (KUL) Maurizio Petrarca, Gessica Vasco, Allessandra Pisano, Enrico Castelli, Enrico Bettine (OPBG) Maria Costa (SHC) Jose Pozo Soler (USFD) Thomas Geijtenbeek, Marcin Burdzy, Hulda Jonasdottir, Frans van der Helm (TUD) Ben van Basten, Johannes Gijsbers, Lars Aarts, Ali Benyahia (Motek) Brussels, 6-7 July, 2017

3 What treatment is best for this patient? Weakness Contracture Spasticity Limited neural control Bone deformities Balance Final review Brussels

4 Patient measurements OVERVIEW MD-Paedigree EU database Biophysical modelling Probabilistic modelling

5 WP6: Harmonized clinical practice MD-Paedigree Final Review Final review Brussels

6 Aim To reach consensus and develop a standardized measurement protocol for gait analysis To enable standardized data collection throughout gait labs in Europe To define a set of clinical relevant outcome parameters (crops) extracted from the data and reach consensus on folder structure and file format Final review Brussels

7 Consensus gait analysis protocol 1. General history 2. Gait-specific information 3. 3D clinical gait analysis 4. Standardized physical exam 5. Energy expenditure (CP) 6. 6-min walk test (DMD+CMT) 7. Lower body MRI Final review Brussels

8 Data collected N=863 Patient Reference Complete Acquired GOAL TOTAL OVERALL PATIENT DATA Total CP prospective extended Total CP prospective clinical Total CP retrospective Total DMD T Total DMD T Total CMT T Total CMT T Final review Brussels

9 Outcome parameters and file format Clinical exam: digitized in standard.xls format Final review Brussels

10 Outcome parameters and file format Gait analysis: crops and curves

11 Scientific studies WP6 Interlaboratory reproducibility Paper under review Final review Brussels, 6-7 July 2017

12 Scientific studies WP6 Interlaboratory reproducibility Paper under review Complexity of motor control in CP versus DMD Paper submitted Final review Brussels, 6-7 July 2017

13 Scientific studies WP6 Interlaboratory reproducibility Paper under review Complexity of motor control in CP versus DMD Paper submitted Automatic classification of gait patterns Joint project with Athena & Siemens Final review Brussels, 6-7 July 2017

14 Scientific studies WP6 Interlaboratory reproducibility Paper under review Complexity of motor control in CP versus DMD Paper submitted Automatic classification of gait patterns Joint project with Athena Studies on effect of functional power training, orthopedic surgery, Final review Brussels, 6-7 July 2017

15 Achievements WP6 Consensus gait analysis protocol 863 data sets for CP, DMD and CMT Standardized outcome measures and formats All data stored in repository Final review Brussels

16 Limitations of current practice 1. Data collection & processing is time consuming More than 4 hours for collection and analysis 2. Little information at muscle level No muscle lengths and forces No information on deeper muscles 3. Only examine comfortable gait Compensations mask underlying impairments

17 What do we need? 1. Data collection & processing is time consuming Faster software? 2. Little information at muscle level Personalized musculoskeletal modeling? 3. Only examine comfortable gait Gait perturbations?

18 WP11: Demo of Modelling Applications MD-Paedigree Final Review

19 What do we need? 1. Data collection & processing is time consuming Faster software? 2. Little information at muscle level Personalized musculoskeletal modeling? 3. Only examine comfortable gait Gait perturbations?

20 Brussels 6-7 May 2014

21 Musculoskeletal modelling for clinical applications MD-PAEDIGREE consensus protocol Less pose dependent Up-to-date with current scientific knowledge Segment definitions match ISB recommendations (Wu et al. 2005) Updated hip joint center regression (Harrington 2007) Functional hip and knee calibration procedures (Halvorsen 2003) Clinical workflow/protocol Feedback to user

22 Functional calibration

The comparison of three models: PiG, CAST & HBM Models (42

Body Model (HBM) PiG CAST HBM Subjects - 18 children with

(GRAIL) - Average over 3 strides per subject Statistics -

23 The comparison of three models: PiG, CAST & HBM Models (42 markers total) - Plug-in-Gait (PiG) - CAST (ISB) - Human Body Model (HBM) PiG CAST HBM Subjects - 18 children with CP - 6 OPBG (overground) - 6 KUL (overground) - 6 VUmc (GRAIL) - Average over 3 strides per subject Statistics - Statistical Parametric Mapping (SPM) with ANOVA & t-tests - RMSE

24 SPM {F} ext (⁰) flex Sagittal plane angles *HBM vs PIG *CAST *PIG/CAST/HBM *PIG/CAST/HBM Final review Brussels

26 Gait Off-line Analysis Tool

27 Achievements WP11 Clinically applicable gait analysis software

28 Added value for clinical practice Much more efficient 3D gait analysis Currently being implemented in clinical practice HBM 2.0 release mail June users, part of total solution for gait analysis & training Real-time gait analysis Dutch charity grant (k 185) obtained for clinical implementation 2 ITN project funded by EC 2 EU proposals under review Brussels 6-7 May 2014

29 What do we need? 1. Data collection & processing is time consuming Faster software? 2. Little information at muscle level Personalized musculoskeletal modeling? 3. Only examine comfortable gait Gait perturbations?

Model Motek Human Body Model Brussels, 6-7 july, 2017

30 WP11 modelling pipeline Siemens USFD TU Delft Motek MRI Segmented 3D Models Complete Anatomical Model OpenSim Model Motek Human Body Model Brussels, 6-7 july, 2017 WP11 - NND Clinic Siemens USFD TU Delft Motek Clinic Next steps

31 Segmentation and parameter extraction SEGMENTATION MORPHING COMPLETE ANATOMICAL TEMPLATE (TLEM) EXTRACTING GEOMETRIC PARAMETERS Brussels, 6-7 july, 2017 WP11 - NND Clinic Siemens USFD TU Delft Motek Clinic Next steps

32 Final Result for CP 4 Brussels, 6-7 July, 2017 WP11 - NND Clinic Siemens USFD TU Delft Motek Clinic Next steps

33 Pipeline summary MD-Paedigree 43 patient cases processed with personalized muscle models Repository: probabilistic modelling/case matching All gait parameters Muscle activation/ lengths Visualization tool Brussels, 6-7 July, 2017 WP11 - NND Clinic Siemens USFD TU Delft Motek Clinic Next steps

Rome, 12 13 May 2017 Inverse dynamics validation Brussels, 6-7 july,

34 Rome, May 2017 Inverse dynamics validation Brussels, 6-7 july, 2017 WP11 - NND Clinic Siemens USFD TU Delft Motek Clinic Next steps

35 Rome, May 2017 Inverse dynamics validation Conclusions Reasonable agreement between EMG and simulation Relatively small inter-model variance Challenges No ground truth No pathological control Future work Cost-benefit of MRI-based models for clinical practice Brussels, 6-7 july, 2017 WP11 - NND Clinic Siemens USFD TU Delft Motek Clinic Next steps

36 Personalized models for clinical practice Brussels, 6-7 july, 2017 WP11 - NND Clinic Siemens USFD TU Delft Motek Clinic Next steps

37 Summary WP11 Clinically applicable gait analysis software 43 personalized models and simulations Brussels, 6-7 july, 2017 WP11 - NND Clinic Siemens USFD TU Delft Motek Clinic Next steps

38 Added value for clinical practice Brussels, 6-7 July, 2017 WP11 - NND Clinic Siemens USFD TU Delft Motek Clinic Next steps

generic purple = MRI-based Important for clinical decision making Brussels,

39 Added value for clinical practice: Muscle-tendon lengths Muscle-tendon length Tibialis posterior right Muscle-tendon length Tibialis posterior left green = generic purple = MRI-based Important for clinical decision making Brussels, 6-7 July, 2017 WP11 - NND Clinic Siemens USFD TU Delft Motek Clinic Next steps

40 Added value for clinical practice: Muscle activations of deeper muscles Muscle activation Tibialis posterior right Muscle activation Tibialis posterior left green = generic purple = MRI-based Important for clinical decision making! Brussels, 6-7 July, 2017 WP11 - NND Clinic Siemens USFD TU Delft Motek Clinic Next steps

41 What do we need? 1. Data collection & processing is time consuming Faster software? 2. Little information at muscle level Personalized musculoskeletal modeling? 3. Only examine comfortable gait Gait perturbations? Brussels, 6-7 july, 2017 WP11 - NND Clinic Siemens USFD TU Delft Motek Clinic Next steps

42 D11.4: Disease-specific muscle model Task 11.3: Disease specific muscle model Muscle model based on clinical asessment Musce model based on joint perturbations Task 11.4: Gait perturbations Mechanical Visual

43 Disease specific muscle model (1) Optimizing hamstrings contracture and spasticity parameters Using instrumented clinical assessment Van der Krogt et al Brussels 6-7 July 2017

44 Disease specific muscle model (2) Separating neural and tissue parameters Using mechanical joint perturbations Sloot et al Brussels 6-7 July 2017

Advanced Clinical Gait Analysis Steady state gait Might not be sensitive enough Patient compensation Not very functional Dynamics of gait perturbations

45 Advanced Clinical Gait Analysis Steady state gait Might not be sensitive enough Patient compensation Not very functional Dynamics of gait perturbations Mechanical gait perturbations Inertial compensation Visual gait perturbations Rome, May, 2017 WP11 - NND Clinic Siemens USFD TU Delft Motek Clinic Next steps

Mechanical perturbations Rome, 22-23 May, 2017 WP11 -

46 Mechanical perturbations Rome, May, 2017 WP11 - NND Clinic Siemens USFD TU Delft Motek Clinic Next steps

47 Inertial compensation * Patent pending Rome, May, 2017 WP11 - NND Clinic Siemens USFD TU Delft Motek Clinic Next steps

48 Mechanical gait perturbations Sloot, L.H., van den Noort, J.C., van der Krogt, M.M., Bruijn, S.M., Harlaar, J. (2015) Can treadmill perturbations evoke stretch reflexes in the calf muscles? PLoS ONE 10(12): e Brussels, 6-7 July, 2017 WP11 - NND Clinic Siemens USFD TU Delft Motek Clinic Next steps

49 Visual gait perturbations Van Gelder et al Booth et al Brussels, 6-7 July, 2017 WP11 - NND Clinic Siemens USFD TU Delft Motek Clinic Next steps

50 Visual gait perturbations Brussels, 6-7 July, 2017 WP11 - NND Clinic Siemens USFD TU Delft Motek Clinic Next steps

51 Achievements WP11 Clinically applicable gait analysis software 43 personalized models and simulations Dynamics of gait perturbations Brussels, 6-7 July, 2017 WP11 - NND Clinic Siemens USFD TU Delft Motek Clinic Next steps

52 Added value for clinical practice Mechanical perturbations for diagnostics Nominated best paper ESMAC 2015&2017 Visual gait perturbations for gait training Nominated for best poster award RehabWeek 2017 Implemented in rehabilitation practice Grant application pending for training evaluation Brussels, 6-7 July, 2017 WP11 - NND Clinic Siemens USFD TU Delft Motek Clinic Next steps

53 WP 12 NND Validating Musculoskeletal Models Brussels, 6-7 July 2017

54 Inverse vs Forward Simulation Neurological signals Muscle Activation Muscle Force Joint Moments External Forces Motion Brussels, 6-7 July, 2017

Inverse vs Forward Simulation Inverse simulation Musculoskeletal model Neurological signals Muscle Activation Muscle Force Joint Moments External

55 Inverse vs Forward Simulation Inverse simulation Musculoskeletal model Neurological signals Muscle Activation Muscle Force Joint Moments External Forces Motion Advantages Established method Efficient processing Disadvantages Limited validation options No prediction ( what-if? ) Brussels, 6-7 July, 2017

56 Inverse vs Forward Simulation Forward simulation Control model Musculoskeletal model Contact model Neurological signals Muscle Activation Muscle Force Joint Moments External Forces Motion Advantages Strong model validation potential Predict interventions ( what-if? ) Disadvantages Open research Longer processing time Brussels, 6-7 July, 2017

57 Forward dynamics validation Generation 1 Generation ~5 Generation ~20 Generation ~1000 Brussels, 6-7 July, 2017

58 Healthy model Brussels, 6-7 July, 2017

59 Shortened hamstrings Brussels, 6-7 July, 2017

60 Shortened hamstrings + surgery Brussels, 6-7 July, 2017

61 Weak quadriceps Brussels, 6-7 July, 2017

62 Spastic gastrocnemius Brussels, 6-7 July, 2017

63 Spastic gastrocnemius + BOTOX Brussels, 6-7 July, 2017

64 Predictive simulations: Face validity 10 clinical experts asked to score validity of simulation outcome: Simulation Healthy gait Shortened Hamstrings Weakened Vastii General muscle weakness Spastic Gastrocnemius Validity score 4.1 (/5) > quite realistic 4.2 (/5) > quite realistic 3,0 (/5) > fair 3,2 (/5) > fair 4,4 (/5) > very realistic Brussels, 6-7 July, 2017

65 Major achievements Consensus protocol for clinical gait analysis Consistent data-set (n=863) in the repository Standardized outcome measures and formats Personalized modelling pipe-line Clinically commercial available state-of-the-art musculoskeletal model and off-line analysis tool Medical certification 2 protocols for advance perturbation-based CGA Forward dynamic model for predictive modelling 1 international patent 20 international (conference) publications Brussels, 6-7 July, 2017

66 Acknowledgements Jaap Harlaar, Laura Oudenhoven, Eline Flux, Marjolein Piening (VUmc) Kaat Desloovere, Marije Goudriaan (KUL) Maurizio Petrarca, Gessica Vasco, Allessandra Pisano, Enrico Castelli, Enrico Bettine (OPBG) Maria Costa (SHC) Jose Pozo Soler (USFD) Thomas Geijtenbeek, Marcin Burdzy, Hulda Jonasdottir, Frans van der Helm (TUD) Ben van Basten, Johannes Gijsbers, Lars Aarts, Ali Benyahia (Motek) Brussels, 6-7 July, 2017

Toe walking gives rise to parental concern. Therefore, toe-walkers are often referred at the 3 years of age.

Toe walking gives rise to parental concern. Therefore, toe-walkers are often referred at the 3 years of age. IDIOPATHIC TOE WALKING Toe walking is a common feature in immature gait and is considered normal up to 3 years of age. As walking ability improves, initial contact is made with the heel. Toe walking gives