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NND: Progress and demonstrations
MD-Paedigree Final Review
Marjolein van der Krogt & Frans Steenbrink
Brussels, 6/7 July 2017
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AcknowledgementsJaap 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
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What treatment is best for this patient?
Final review Brussels
SpasticityContracture
BalanceLimited neural
control Bone deformities
Weakness
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Pat
ien
t m
eas
ure
me
nts
OVERVIEW
MD-Paedigree EU database
Probabilistic modelling
Biophysical modelling
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WP6: Harmonized clinical practice
MD-Paedigree Final Review
Final review Brussels
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Aim
• To reach consensus and develop a standardizedmeasurement 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
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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
http://www.md-paedigree.eu/clinical-scenario-nnd/gait-analysis-protocol/
Final review Brussels
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Data collected
N=863Patient Reference Complete Acquired GOAL
TOTAL OVERALL PATIENT DATA 863 830
Total CP prospective extended 28 30
Total CP prospective clinical 136 120
Total CP retrospective 626 600
Total DMD T0 26 20
Total DMD T1 16 20
Total CMT T0 18 20
Total CMT T1 13 20
Final review Brussels
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Outcome parameters and file format
• Clinical exam: digitized in standard .xls format
Final review Brussels
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Outcome parameters and file format
• Gait analysis: crops and curves
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Scientific studies WP6
• Interlaboratory reproducibilityPaper under review
Final review Brussels, 6-7 July 2017
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Scientific studies WP6
• Interlaboratory reproducibilityPaper under review
• Complexity of motor control in CP versus DMDPaper submitted
Final review Brussels, 6-7 July 2017
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Scientific studies WP6
• Interlaboratory reproducibilityPaper under review
• Complexity of motor control in CP versus DMDPaper submitted
• Automatic classification of gait patternsJoint project with Athena& Siemens
Final review Brussels, 6-7 July 2017
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Scientific studies WP6
• Interlaboratory reproducibilityPaper under review
• Complexity of motor control in CP versus DMDPaper submitted
• Automatic classification of gait patternsJoint project with Athena
• Studies on effect of functional power training, orthopedic surgery, …
Final review Brussels, 6-7 July 2017
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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
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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
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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?
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WP11: Demo of Modelling Applications
MD-Paedigree Final Review
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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?
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Brussels – 6-7 May 2014
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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 (Halvorsen2003)
• Clinical workflow/protocol– Feedback to user
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Functional calibration
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The comparison of three models: PiG, CAST & HBM
Models (42 markers total)
- Plug-in-Gait (PiG)
- CAST (ISB)
- Human Body Model (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
PiG CAST HBM
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Sagittal plane angles
Final review Brussels
*HBM vs PIG *CAST *PIG/CAST/HBM *PIG/CAST/HBM
SPM
{F}
ext
(⁰)
fle
x
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Gait Off-line Analysis Tool
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Achievements WP11
• Clinically applicable gait analysis software
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Added value for clinical practice
• Much more efficient 3D gait analysis– Currently being implemented in clinical practice
• HBM 2.0 release mail June 26
• 51 users, part of total solution for gaitanalysis & 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
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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?
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Clinic Siemens USFD TU Delft Motek ClinicNext stepsBrussels, 6-7 july, 2017 WP11 - NND
WP11 – modelling pipeline
Siemens USFD MotekTU Delft
MRI Segmented3D Models
OpenSim Model Motek HumanBody Model
Complete Anatomical Model
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Clinic Siemens USFD TU Delft Motek ClinicNext stepsBrussels, 6-7 july, 2017 WP11 - NND
Segmentation and parameter extractionMORPHING COMPLETE
ANATOMICAL TEMPLATE (TLEM) EXTRACTING GEOMETRIC PARAMETERSSEGMENTATION
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Clinic Siemens USFD TU Delft Motek ClinicNext stepsBrussels, 6-7 July, 2017 WP11 - NND
Final Result for CP 4
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Clinic Siemens USFD TU Delft Motek ClinicNext stepsBrussels, 6-7 July, 2017 WP11 - NND
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
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Clinic Siemens USFD TU Delft Motek ClinicNext stepsBrussels, 6-7 july, 2017 WP11 - NND
Inverse dynamics validation
Rome, 12 – 13 May 2017
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Clinic Siemens USFD TU Delft Motek ClinicNext stepsBrussels, 6-7 july, 2017 WP11 - NND
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
Rome, 12 – 13 May 2017
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Clinic Siemens USFD TU Delft Motek ClinicNext stepsBrussels, 6-7 july, 2017 WP11 - NND
Personalized models for clinical practice
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Clinic Siemens USFD TU Delft Motek ClinicNext stepsBrussels, 6-7 july, 2017 WP11 - NND
Summary WP11
• Clinically applicable gait analysis software
• 43 personalized models and simulations
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Clinic Siemens USFD TU Delft Motek ClinicNext stepsBrussels, 6-7 July, 2017 WP11 - NND
Added value for clinical practice
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Clinic Siemens USFD TU Delft Motek ClinicNext stepsBrussels, 6-7 July, 2017 WP11 - NND
Added value for clinical practice: Muscle-tendon lengths
Muscle-tendon lengthTibialis posterior right
Muscle-tendon lengthTibialis posterior left
green = genericpurple = MRI-based
Important for clinical decision making
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Clinic Siemens USFD TU Delft Motek ClinicNext stepsBrussels, 6-7 July, 2017 WP11 - NND
Added value for clinical practice: Muscle activations of deeper muscles
Muscle activationTibialis posterior right
Muscle activationTibialis posterior left
green = genericpurple = MRI-based
Important for clinical decision making!
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Clinic Siemens USFD TU Delft Motek ClinicNext stepsBrussels, 6-7 july, 2017 WP11 - NND
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?
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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
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Disease specific muscle model (1)
Brussels – 6-7 July 2017
• Optimizing hamstrings contracture andspasticity parameters
• Using instrumented clinical assessment
Van der Krogt et al. 2016
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Disease specific muscle model (2)
Brussels – 6-7 July 2017
• Separating neural and tissue parameters
• Using mechanical joint perturbations
Sloot et al. 2015
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Clinic Siemens USFD TU Delft Motek ClinicNext stepsRome, 22-23 May, 2017 WP11 - NND
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
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Clinic Siemens USFD TU Delft Motek ClinicNext stepsRome, 22-23 May, 2017 WP11 - NND
Mechanical perturbations
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Clinic Siemens USFD TU Delft Motek ClinicNext stepsRome, 22-23 May, 2017 WP11 - NND
Inertial compensation
* Patent pending
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Clinic Siemens USFD TU Delft Motek ClinicNext stepsBrussels, 6-7 July, 2017 WP11 - NND
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): e0144815.
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Clinic Siemens USFD TU Delft Motek ClinicNext stepsBrussels, 6-7 July, 2017 WP11 - NND
Visual gait perturbations
Van Gelder et al. 2016Booth et al. 2017
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Clinic Siemens USFD TU Delft Motek ClinicNext stepsBrussels, 6-7 July, 2017 WP11 - NND
Visual gait perturbations
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Clinic Siemens USFD TU Delft Motek ClinicNext stepsBrussels, 6-7 July, 2017 WP11 - NND
Achievements WP11
• Clinically applicable gait analysis software
• 43 personalized models and simulations
• Dynamics of gait perturbations
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Clinic Siemens USFD TU Delft Motek ClinicNext stepsBrussels, 6-7 July, 2017 WP11 - NND
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
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WP 12 – NNDValidating Musculoskeletal Models
Brussels, 6-7 July 2017
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Inverse vs Forward Simulation
Brussels, 6-7 July, 2017
Neuro-logical signals
Muscle Activation
Muscle Force
Joint Moments
External Forces
Motion
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Musculoskeletal model
Inverse vs Forward Simulation
Brussels, 6-7 July, 2017
Inverse simulation
Advantages Disadvantages
Established method Limited validation options
Efficient processing No prediction (“what-if?”)
Neuro-logical signals
Muscle Activation
Muscle Force
Joint Moments
External Forces
Motion
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Musculoskeletal modelControl model
Contactmodel
Inverse vs Forward Simulation
Brussels, 6-7 July, 2017
Advantages Disadvantages
Strong model validation potential Open research
Predict interventions (“what-if?”) Longer processing time
Forward simulation
Neuro-logical signals
Muscle Activation
Muscle Force
Joint Moments
External Forces
Motion
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Forward dynamics validation
Brussels, 6-7 July, 2017
Generation 1 Generation ~5 Generation ~20 Generation ~1000
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Healthy model
Brussels, 6-7 July, 2017
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Shortened hamstrings
Brussels, 6-7 July, 2017
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Shortened hamstrings + surgery
Brussels, 6-7 July, 2017
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Weak quadriceps
Brussels, 6-7 July, 2017
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Spastic gastrocnemius
Brussels, 6-7 July, 2017
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Spastic gastrocnemius + BOTOX
Brussels, 6-7 July, 2017
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Predictive simulations: Face validity
• 10 clinical experts asked to score validity of simulation outcome:
Brussels, 6-7 July, 2017
Simulation Validity score
Healthy gait 4.1 (/5) > quite realistic
Shortened Hamstrings 4.2 (/5) > quite realistic
Weakened Vastii 3,0 (/5) > fair
General muscle weakness 3,2 (/5) > fair
Spastic Gastrocnemius 4,4 (/5) > very realistic
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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
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AcknowledgementsJaap 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