1. M24 meeting MP-Paedigree Amsterdam, 23 February, 2015 Neurological and Neuromuscular Diseases WP6 – WP11

2. MD Paedigree for NND NND M24 meeting / February 2015 MODEL DRIVEN, 2 tracks 1. Individualized musculoskeletal models to enhance gait analysis as an etiological focused diagnostic tool 2. To employ pattern recognition statistical tools, on large datasets, to enable prediction of treatment outcome

3. Main tasks after 1 st year review by EU NND M24 meeting / February 2015 1.WP6 : speed up data collection 2.WP 11: clarify role of DXA 3.Suggest adaptation of DOW 4.Update self assessment After M12 self-evalution: 5.Intensify contact infrastructure group

4. T6.1 – QA on data collection and clinical protocols D6.1 : CGA clinical protocols at M18 Status at M18: Task T6.1.1 Technical Quality Assurance (TQA) on clinical protocols and on data collection TQA and data collection protocols agreed TQ assessed accordingly in all 3 centres (processing finalized by M24 > D6.2) Task T6.1.2 Definition of standard clinical protocol for CGA Standard and extended protocols agreed D6.1 Delivered @ M18

5. T6.1 – QA on data collection and clinical protocols D6.2 : sharing CGA clinical protocols at M24 Status at M18: Ready for sharing at ESMAC 2014 in Rome Status at M24 : to be reported today

6. T6.2 – Gait analysis collection CP D6.3 : report on collected data at M36 Status at M18: Task T6.2.1 Retrospective data for CP OPBG : 200/200 identified 50 ready for upload Leuven: 100*/400 identified 25* ready for upload (20 / month to go) *) mixed pre & post treatment DOW changes: minor Status at M24 : to be reported today

7. T6.2 – Gait analysis collection CP D6.3 : report on collected data at M36 Status at M18: Task T6.2.1 Retrospective data for CP OPBG : 200/200 identified 50 ready for upload Leuven: 100*/400 identified 25* ready for upload (20 / month to go) *) mixed pre & post treatment DOW changes: minor Status at M24 : to be reported today

8. T6.2 – Gait analysis collection - CP D6.3 : report on collected data at M36 Status at M18: Task T6.2.2 Prospective data for CP Protocols agreed Ethical approval reached Age range extended First patients measured (OPBG) KUL and Vumc to start (1 per 1,5 month) DOW changes none Status at M24 : to be reported today

9. T6.3 – Gait analysis collection – DMD/CMT D6.3 : report on collected data at M36 Status at M18: Task T6.3 Prospective data for DMD & CMT Protocols agreed Ethical approval pending or reached Age range extended, first DMD patients measured DOW changes: 10 DMD, 10 CMT, 2 times CGA per centre (KUL OPBG) 1 time an MRI Status at M24 : to be reported today

10. T6.4 – Image acquisition D6.4 : report on collected data at M44 Status at M18: Protocols agreed Ethical approval reached in all centres Age range extended, CMT1 replaces SMA OPBG : 14 MRI sets healthy children, 11 patients: 7 DMD, 1 CMT1A, 3 CP VUmc : 1 healthy adult (test scan) KULeuven : starting DOW adjustments: no DXA scans (abandoned, see WP11) Status at M24: to be reported today

11. NND - WP11 DOW adjustments and next steps MD-P M24meeting - Amsterdam

12. Developments in WP11 Analysis after meeting July 2014 No more DXA scans and analysis  Too little evidence for added value DXA  Problems with ethical approval Less emphasis on mass distribution model  Not sensitive to model output  Mass and inertia tensor still calculated using subject-specific bone/muscle/fat volumes; but no bone mass distribution (as could be based on DXA) Steps from MRI to model more complex than expected (see red circles scheme next slide)

14. Main changes needed in WP11 More emphasis on sensitive parameters  Based on sensitivity study  I.e. joint centers and axes; muscle attachments; muscle/tendon lengths  more effort is needed to make this happen USFD can play a role in this instead of DXA image processing

15. Details of WP11 changes needed (see next sheet) Wr.t. Joint centers / axes  Comparison:  Based on bone meshes and MRI markers (USFD)  Based on gait data (MM)  Based on combination of both (USFD)  Advanced methods explored to create subject- specific joint models (not necessarily hinge/ball) using bone surface meshes (USFD)

17. W.r.t. muscle attachments  Not easily identifyable from MRI  New methods explored to follow muscle belly midline to bone mesh (USFD)  + Can possibly be morphed using atlas data? (Siemens) Details of WP11 changes needed (2) (see previous sheet)

18. W.r.t. muscle fiber / tendon slack lengths  Idea to use ultrasound measurements for this, but seems not a (realistic) option within this project anymore Details of WP11 changes needed (3)

19. Next steps Siemens  Try out Leuven annotated MRI images as atlas  Use this to create annotated MRIs of our own data (incl bony landmarks and attachment points) Sheffield  Create accurate joint models based on meshes  Create methods for muscle attachment site (using mesh morphing or extrapolation of muscles)  Conversion from annotated-MRI to model parameters

20. Next steps TU Delft  Create patient-specific OpenSim models with USFD input  Sensitivity / effect studies of model changes  Validation against measured data  Explore predictive models Motek  Create workflow for personalization without imaging  Using functional joint centers; accurate length scaling; bone deformities; …  Apply TUD image-based models in HBM

21. MRI data OPBG (30) MRI data KUL (30) MRI data VUMC (10) GAIT+PE data OPBG GAIT+PE data KUL GAIT+PE data VUMC SIEMENSUSFD TUD MOTEK 1A 1B 1C 2 SYSTEM INTEGRATION OVERVIEW MD-PAEDIGREE WP11 3 4A 4B 4C 5A 5B 5C 6 Brief description of output – input data 1.MRI images (Dicom format; stacks combined to one image) 2.Segmented MRI images (… format; bones and muscles segmented; anatomical landmarks & attachment sites indicated) 3.Model parameters from MRI (… format; muscle volumes; segment mass & inertia; femur and tibia torsion; joint centers/models; attachment sitesl; in segment reference frames) 4.Gait and calibration trials (C3D/MOX format – same as 5) + (instrumented) physical exam; dynamometry; O2; anamnesis (txt/pdf format) 5.Gait and calibration trials (C3D/MOX format – same as 4) 6.Personalized OpenSim models (.osim format) 7.HBM output to repository 7