Center of Biomedical Engineering and Physics Medical University of Vienna, AustriaWinfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 1 Technological Ressources Plastics Lab. Microelectronics Computer / Microcomputer Mechanics CAD/CAM Electronics Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 2 OUR TEAM – Permanent Staff, Biomedical Engineering Temporary Staff University Education: FES-Walking + PCs, Network, µ-Computer FES-Implants + Electronics FES-DDM + Co-operations Mechanics Sensor-/Actuator- Digital Signal applications Processing + + Sensors/ PC-Measurement, Measurement CAD Ph.D. Modeling/Simulation Sub-University Education: Ph.D. EMG-Feedback-FES Industry collaboration Mechanical Engineer CAD/CAM Precision Mechanics Software Engineer Mechanic Electrical Engineer Microelectronics CAD/CAM Winfried Mayr, MedUni Wien 1 Co-operation partners Industriekooperationen: Clinics & Departments, Vienna Medical Univ. Otto Bock TU Biomed Med-El Medexternal Clinics, Clinics, Insight Instruments Departments & Rehab Seibersdorf Centers: Präzisionsteile GmbH Wilhelminenspital Plansee Vienna, University of Vienna, Graz, Weißer Hof A, Schott Bad Häring A, Bad ..... Murnau D, Bad Wildungen D, Hamburg, Tübingen, Heidelberg, Padova, Ljubljana, Padova, Moscow, Liverpool, . . . Moscow, . Winfried Mayr . . . . Vienna Medical University - Center of Biomedical Engineering & Physics 4 Examples for co-operations projects: EOG for remote control Heater for local hyperdermia Pruritometer Tool for gaining brain samples diagnostic ERG Winfried Mayr Force distribution measurement knee joint endo-prostheses Vienna Medical University - Center of Biomedical Engineering & Physics 5 ISEK 2006 - Torino “From Research to Clinical Practice” Functional Electrical Stimulation Basic Research: - indispensable for clinical application - explanation of clinical observations Clinical Research: - part of Clinical Practice Clinical Practice -> “Clinical Routine” - routine component in rehabilitation Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 6 Winfried Mayr, MedUni Wien 2 Cardiac Pacemaker: First Prototyp 1958 – the most successful FES-Product today Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 7 Auditory prostheses: Cochlea implants Visual prostheses: • epiretinal • subretinal • optic nerve • cortical Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 8 Practically all FES-applications are based on NERVE- and NOT on MUSCLE stimulation ! Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 9 Winfried Mayr, MedUni Wien 3 FES is a rather coarse tool for activation of very small and complex nerve structures Frank Rattay “Electrical Nerve Stimulation” Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 10 Stimulations parameters M-wave Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 11 Electrodes for nerve stimulation Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 12 Winfried Mayr, MedUni Wien 4 Vienna epineural elektrode Mechanical stability Biocompatibility Electrochemical stability Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 13 Electrode technology Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 14 Rules for constructing active implants All surfaces biomaterials, smoothly biomaterials, structured, no edges structured, Robust but lightweight Components and DC-conducting leads in DChermetic case (metal oder ceramics) ceramics) Pure metals, no alloys Preferably welding, if unavoidable acidwelding, acidfree soldering, never conductive bonding soldering, Antenna coils inside the case Long isolation distances Polymer sealing in Nitrogen atmosphere, atmosphere, avoiding bubbles and fast temperature changes during curing ..... Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 15 Winfried Mayr, MedUni Wien 5 3 Generations of Vienna FES-Implants Rf-powered 8-channel implant Rf-powered 20-channel implant battery powered 8-channel implant Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 16 Rf-powered 8-channel External supply and control unit Display Rechargable battery Control switches Implant µ-controller board Hysol Antenna coil State-of-the-art 27 MHz Carrier Covar case Amplitude-limiter Antenna coil Power supply Decoder low,5ms high,40ms Carrier Suppression,5ms Impulse generator RF-link Current source Output switch array Antenna coil DC decoupling capacitors 24 bit Data Phase Change Electrode connector RF-link to a SECOND IMPLANT Stimulus Duration 8 stimulation electrodes Battery powered 8-channel Implant Titanium case Interface box RS 232 Antenna coil WG 8602 battery Charge pumpe Current source Output switch array DC decoupling capacitors Amplifier µ-controller Hysol Antenna coil Telemetry circuit Next generation RF data link Electrode connector Electrode connector 8 stimulation electrodes Recording electrodes Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 17 Locomotion pacemaker Vienna, 1983 Wien, 1983 Montpellier, 2000 Montpellier, 2000 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 18 Winfried Mayr, MedUni Wien 6 Wien, 1983 Montpellier, 2000 Montpellier, 2000 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 19 Phrenic pacemaker - enormous improvement in quality of life Vienna / Bad Wildungen, 1984 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 20 Phrenic pacemaker - enormous improvement in quality of life Avery / US Atrotech / Finnland Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 21 Winfried Mayr, MedUni Wien 7 Brindley‘s sacral anterior root stimulator – bladder control more than 2000 implantations more than 25 years lifetime Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 22 What decides about the survival of an FES implant ? There should be a need a smart solution technology, application, handling sufficient legal requirements fulfilled fast reacting support in application and in case of failure justification of costs “unlimited” financial room to move ..... Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 23 POTENTIAL APPLICATIONS: a b Continence (Graciloplasty) Phrenic pacing Cardiac support (latissimus) Hand-/ arm-neuroprosthesis e c Peroneus-stimulator Walking aid Spinal cord stimulation - Chronic pain therapy f - Treatment of spasticity - Locomotion ..... Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 24 Winfried Mayr, MedUni Wien 8 What is new and promising ? 2 examples of novel implant applications: Activation of movement generators in the SCI (Milan Dimitrijevic) Dimitrijevic) Release of insulin via stimulation of the autonomic nervous system (Janez Rozman) Rozman) Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 25 FES of Spinal Cord Movement pattern generators CPG, LLPG 26 Mimicking brain stem control of the lumbar network tonic suprasegmental drive spinal cord injury spinal cord stimulation (SCS) intermittent phasic afferent input Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 27 Winfried Mayr, MedUni Wien 9 Methods: Epidural spinal cord stimulation Cross-section at T12 vertebral level Vertebral bone Vertebral canal Spinal cord Spine Electrode Anterior roots Spinal cord Posterior roots Dura mater Epidural space Pulse generator Epidural electrode site Continuous stimulation 210 µs pulse width 1 – 10 V 2.2 – 100 Hz Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 28 Non-patterned spinal cord stimulation induces stepping movements NonElectromyographic recording Descending input Spinal cord Spine Electrode Complete spinal cord injury Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 29 A Q H TA TS KJA 10 V, 6 Hz 1 mV 1.5 mV 10 V, 31 Hz 0.5 mV 0.5 mV 1 mV 1.5 mV 0.5 mV 45° 2s 1.5 mV 45° 2s B Q H TA TS KM 9 V, 30 Hz 2 mV 1 mV 1 mV 1 mV 90° 2s Q 2 mV Stimulus artifacts 0.05 s Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 30 Winfried Mayr, MedUni Wien 10 Can the LLPG process sensory feedback input to generate functional EMG patterns? Methods patterns? Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 31 Can the LLPG process sensory feedback input to generate functional EMG patterns? Results patterns? Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 32 FES of Autonomic Nervous System Insulin delivery 33 Winfried Mayr, MedUni Wien 11 Experiments in dogs: 39-electrode cuff around left vagus biphasic rectangular: 200µs, 1mA, 20Hz Winfried Mayr increase of insulin release in both intact and partly dysfunctioned (alloxan) pancreas Vienna Medical University - Center of Biomedical Engineering & Physics 34 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 35 surface electrodes surface electrodes stimulation module 1 stimulation module 2 stimulation modul 3 stimulation module 4 stimulation module 1 stimulation module 2 stimulation modul 3 stimulation module 4 APPLICATIONS: Leg neural prosthesis Peroneus stimulator Remobilisation I2C bus EMG- signals EMG- signals I2C bus 4 channel surface stimulator I2C bus I2C bus Continence therapy Pain therapy COM-Port I2C Interface AD-board PC µP-system (HC16) Therapy of spasticity Muscle training in space Long-term bed rest Chronic heart insufficiency Sports ….. Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 36 Winfried Mayr, MedUni Wien 12 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 37 Technical WP 3 stimulation module 1 stimulation module 2 stimulation modul 3 stimulation module 4 stimulation module 1 stimulation module 2 stimulation modul 3 stimulation module 4 I2C Control Unit RS232 RS232 433MHz FM Wireless LAN RS232 I2C Interface Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 38 EMG-triggerte FES-training Relearning of lost movement functions after partial lesions University Clinic for Physical Medicine and Rehabilitation, MUW University Clinic for Neurology, AKH Rehabilitationscenters Weißer Hof and Stiwell / Medel / Otto Bock Winfried Mayr Werner Wicker-Klinik, Bad Wildungen Vienna Medical University - Center of Biomedical Engineering & Physics 39 Winfried Mayr, MedUni Wien 13 Long-term space flights are associated with degenerative changes in the neuromuscular system. Conventional exercising (treadmill, bicycle, expander...) at least 3-4 h per day required to be efficient. Problems: loss of working time, motivation Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 40 Alternative FES training: MYOSTIM isometric muscle training with low intensity, 6h per day, during routine work easy to handle equipment: - electrode trousers (Patent D. Rafolt) - automized 8 c - hannel stimulator First time in history application of FES for muscle training in space Dec.98 – Feb.99 und Feb.99 – Aug.99 in co o - peration with IBMP Moscow Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 41 Very positive judgement by both cosmonauts Clear improvements in the functional tests: · Test 108, Ergometric locomotion · Equitest, sensomotoric coordination Indications of positive effects of FES training in the neuromuscular tests: · Tendometry · Dynamometry · Reflex test Histological results, to interprete with reservation: · Biopsy vom Vastus Lateralis No in relation to FES interpretable results: · Bone density measurements Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 42 Winfried Mayr, MedUni Wien 14 Preparation of potential application onboard ISS Participation in the international terrestrial isolation study in Moscow(4 subjects) 23. March 2001 Terrestrial application: successful application of the method in chronic heart insufficiency patients Co o - peration: University clinic für Physical Medicine and Rehabilitation, Vienna ISS French russian crew an onboard of MIR - Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 43 NMES-Group (n=17) Age: 59 ± 6 BMI: 22,7 ± 3,2 LVEF: 15,1 ± 3,1 NHYA: » II: 4 » III: 10 » IV: 3 Control group (n=16) Age: 57 ± 8 BMI: 25,7 ± 3,9 LVEF: 18,1 ± 5,2 NHYA: » II: 4 » III: 9 » IV: 3 since, weeks: 24 ± 6 since, weeks: 26 ± 5 • all on a waiting list for HTX • stable medication • voluntary training not possible Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 44 FES training parameters • biphasic rectangular impulses CV / 0,7ms / 50Hz • 2 s on / 6 s off • Intensity: 25 - 30% MVC • initially 30 min / day • after 2 weeks increased to 60 min / day • entire FES training period: 8 weeks Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 45 Winfried Mayr, MedUni Wien 15 Force-Endurance-Test Stimulation group Control group 310 290 E x tens ion force (N) Extension force (N) * * * * * 310 290 270 250 230 210 190 270 250 230 210 190 170 150 0 5 10 Minutes 15 20 before after 170 150 0 5 10 Minutes 15 before after 20 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 46 NYHA NMES-group • 8 patients + 1 class – 3: IV auf III – 5: III auf II • 9 patients unchanged Control group • 1 patient + 1 class – 1: IV auf III • 15 patients unchanged ADL SCORE 22 pre post P<0,0001 P=0,3 20 18 16 14 12 10 NMES Control Maximum: 21 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 47 Summary: clearly positive effect of the FES training – not only in the stimulated muscles – but also on the general condition of the patient no side effects ! Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 48 Winfried Mayr, MedUni Wien 16 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 49 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 50 Population pyramids 1950/2000/2050 male female 85 year Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 0 85 year 0 85 year 0 51 Winfried Mayr, MedUni Wien 17 FES of Denervated Muscles Direct muscle stimulation 52 Upper motor neuron lesion Lower motor neuron lesion Nerve stimulation Winfried Mayr Muscle stimulation Vienna Medical University - Center of Biomedical Engineering & Physics 53 Stimulation parameter – surface electrodes Nerve stimulation: Amplitude range ±100V / ±300mA Pulse width (biphasic) typ. 0.5ms per phase typ. 0.5ms Frequency (fused contr.) contr.) 25 Hz Muscle stimulation: Amplitude range ±100V / ±300mA Pulse width (biphasic) typ. 20ms ( 100ms) per phase typ. Frequency (fused contr.) contr.) 25 Hz Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 54 Winfried Mayr, MedUni Wien 18 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 55 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 56 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 57 Winfried Mayr, MedUni Wien 19 Lomo 1985 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 58 Valencic et. al. 1985 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 59 FES of the denervated posterior cricoarytenoid muscle for glottis opening in synchrony with inspiration External supply and control unit Display Rechargable battery RS 232 Antenna coil Power supply µ-controller Control switches µ-controller board Hysol Titanium case Implant Modulation/demodulation Current source Amplifier Output endstage, channel selector RF power link RF data link DC decoupling capacitors Antenna connector Electrode connector Electrode connector Dual-channel stimulation electrodes EMG recording electrodes Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 60 Winfried Mayr, MedUni Wien 20 Clinical program for FES of subjects with lower motor neuron lesion Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 61 5th Framework programme „Quality of Life and Management of Living Resources“ „Research relating to persons with disabilities“ „RISE“ „Use of electrical stimulation to restore standing in paraplegics with long-term denervated degenerated muscles (DDM)“ Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 62 3 cm Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 63 Winfried Mayr, MedUni Wien 21 per million EU citizens yearly: • 100 new spinal cord injuries • 250 rehospitalisations • 500 outpatient treatments • 63 % paraplegics • about 1/3 flaccid paraplegia Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 64 no adequate rehabilitation method available • fast degeneration of muscles, skeleton, joints, skin, ... • frequent secondary diseases • problems with social and professional integration Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 65 Objectives of RISE • New rehabilitation methode - transfer to clinical practice • Technical equipment - new product family for biomedical industry • Adaptation of EU-regulations for FES-devices - scientific basis Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 66 Winfried Mayr, MedUni Wien 22 Consortium: Mayr, Vienna (Co-ordinator) Kern, Vienna Salmons, Liverpool Girsch, Vienna Carraro, Padova Gruber, Vienna Dimitrijevic, Ljubljana Gerner, Heidelberg Exner, Hamburg Kaps, Tübingen additional: [Cerrel-Bazo, Vicenca] [Helgason, Iceland] [Protasi, Chieti] Biomedical Engineering Clinical Study Rabbit Study Pig Study Muscle Regeneration Muscle Histology Neurology Rehabilitation Clinic Rehabilitation Clinic Rehabilitation Clinic Rehabilitation Clinic Rehabilitation Clinic Muscle Fibre Structure Rehabilitation Centre Rehabilitation Centre Rehabilitation Centre Dermatology Animal Department Muscle Function 67 Subcontract: Schrei, Klosterneuburg Jonas, Bad Häring Potulski, Murnau Schmidt, Vienna Losert, Vienna Gallasch, Graz Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 68 RISE Project Start Nov. 1, 2001 Kick Off Meeting Jan. 2002 in Vienna Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 69 Winfried Mayr, MedUni Wien 23 Pilot Study on Rabbits I x t = const. 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0 0 [N] Amplitude Fmax Amplitude Fmax 20 40 60 Pulse width [ms] Twitch reaction 150 [ms] 100 50 0 0 Duration at 50% Fmax 100 ms Time to peak 20 40 60 Pulse width [ms] Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 70 Rabbit Study NOTEBOOK TRANSMITTER UNIT STIMULATOR ELECTRODES Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 71 Rabbit model of denervation Denervated ankle dorsiflexors Physiological properties • Excitability • Force generation and kinetics • Fatigue resistance • 10 - 51 weeks (≅ 3 – 14 years in humans) (≅ Morphological properties • • • • • Weight and CSA Morphology Fibre areas Fibre types Electron microscopy Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 72 Winfried Mayr, MedUni Wien 24 Conclusions: rabbit model Denervation up to 1 year produced: – – – – Profound muscle and individual fibre atrophy Little degeneration / regeneration Loss in tetanic force generation Poor morphological structure No evidence of progressive changes; stable between 10 and 51 weeks denervation. denervation. Atrophy, NOT degeneration, in denervated rabbit ankle dorsiflexor muscles. Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 73 What was achieved Long-term rabbit model of denervation established LongSelective motor denervation avoided problems of self-harm selfInitial plan was to denervate 10, 25 or 40 days By the end we had denervated up to 357 days! Safe envelope for stimulation established Temperature rise under electrodes less than 1 deg C No damage under electrodes (other than thickened connective tissue) tissue) No damage in muscle, even with the most intensive long-term stimulation regimes long- Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 74 What was achieved (contd) Excitability Did not change after 4 d Was not improved by stimulation Size and morphology Stimulation restored original weight and CSA (~40% normal without) (~40% Histological appearance substantially restored Electron microscopy (not yet liaised on stimulated-denervated) stimulated- denervated) Conclusions Any changes in excitability are not at cellular level, or are dependent on more atrophy dependent or degeneration than we saw Changes in SR and T-system suggest loss of E-C coupling TEWinfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 75 Winfried Mayr, MedUni Wien 25 What was achieved (contd) Tension-generating capacity TensionStimulation increased tetanic tension from ~27% to ~49% of normal Force recovery not commensurate with recovery in weight and CSA Contractile speed Time to peak twitch, half-relaxation and speed of shortening all much slower (like halfsoleus!) soleus!) Stimulation did not alter this Conclusions Slowness and loss of tetanic tension could be due to loss of E-C coupling EDisadvantage: reduction in power available from muscle Advantage: fusion achievable at a lower frequency Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 76 What was achieved (contd) Endurance Denervation increases mitochondria (NADH-TR, EM) (NADHBut muscles, if anything, MORE susceptible to fatigue Fatigue resistance NOT improved by stimulation—worse with 40 Hz patterns! stimulation— Lack of degeneration Major difference between rabbit (motor branches) and rat (whole sciatic) Could be species or procedural difference Intact muscles maintain vascular pumping, may avoid damage due to venous to congestion Conclusions Stimulation does not improve endurance; may make it worse Rabbit is a GOOD model of human muscle at 1-2 years post-injury 1postRat may be a good model of degenerative changes at longer periods periods Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 77 Pig Study Transformation of results from the rabbit study Testing of patient equipment Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 78 Winfried Mayr, MedUni Wien 26 PIG MODEL surgical model for chronic denervation: denervation: isolated transsection and resection of TA and EDL motor branch 79 0 0 1 2 3 pigs 4 5 6 7 8 9 10 20 30 40 weeks 50 60 70 80 90 100 110 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 80 PIG EXPERIMENTS Technical setup for invasive investigation: investigation: Surgical exposure of TA and EDL Direct needle EMG Intramuscular stimulation to evaluate ELECTROPHYSIOLOGICAL PARAMETERS BIOPSIES for histochemical investigation 81 Winfried Mayr, MedUni Wien 27 Weight & Handling Problems Bodyweight: time of denervation mean 29 kg now R 1 - 5 mean age 103 weeks 105kg R 6 - 9 mean age 76 weeks 98kg 82 PIG EXPERIMENTS FES R2 since 29.08.05 R5 since 05.12.05 83 R1 44 weeks denervated EDL muscle 73% fat, connective tissue 27% 84 Winfried Mayr, MedUni Wien 28 R1 67 weeks denervated EDL muscle 25% fat, connective tissue 75% 85 Electrode arrangement C B A A... monopolar stimulation needle B... stimulation reference C... concentric EMG-needle Measurement setup: Benchstimulator DAQ – PC-Card with preamplifier oszilloscope Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 86 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 87 Winfried Mayr, MedUni Wien 29 R1 EDL den li EDL 151204_44w 100 90 80 70 60 50 40 30 20 li EDL 230205_51w li EDL 200405_67w li EDL 080805_83w Amplitude/V 83w 10 0 0 10 20 Pulsbreite/ms 30 67w 51w 49w 40 50 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 88 49w 51w 89w EMG-signa not found 3V/0.1ms; D:22mm Latency: 3,6ms speed:6,1m/s 3V/0.1ms; D:22mm Latency: 3.7ms speed:5,9m/s R1_EDL li Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 1-2ms 1-2ms 89 Technical WPs WP 3: Equipment for home-based training homeWP 4: Test- and measurement equipment Test- Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 90 Winfried Mayr, MedUni Wien 30 Patient Study / Technical WP3 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 91 Required pulse width initially 120 - 150 ms after appr. 1 year 30 - 40 ms shortest pulse width 25 - 35 ms (Nerve stimulation: 0.2 – 2ms) t Peak amplitude +/- 80 V +/- 250 mA Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 92 Technical WP 3 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 93 Winfried Mayr, MedUni Wien 31 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 94 Patient Study / Technical Workpackage 4 Force Kon trac tion FES Transversal muscle stiffness Force Agonist 4 3.5 3 2.5 2 Displacement 1.5 1 0.5 0 0 2 4 6 8 10 12 14 16 Displacement Antagonist 0.2 Tendometry Problem of Co-contraction Oscillation Tonometry no stimulatin 0.15 F 0.1 0.05 0 -0.05 50 100 150 200 250 300 t 350 400 With stimulation Mucle Stiffness & Viscosity t Oscillation Tonometry a mobile and a stationary system 96 Winfried Mayr, MedUni Wien 32 no stimulation Oscillation Tonometry Piendl weak stimulation 2,0 1,8 1,6 1,4 1,2 1,0 0,8 0,6 0,4 0,2 0,0 0 50 60 70 80 90 99 Stimulation in % of 80V Frequenz Daempfung 97 Leg responses while FES amplitude was increased Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 98 Pendulum test Modeling and estimated parameters pendulum test data T... joint torque limb geometrical data model for pendular leg motion C...joint stiffness D...viscous moment J...moment of inertia CG... gravity spring &+ & J ϕ& D ⋅ ϕ + mgL ⋅ sin(ϕ ) + C ⋅ ϕ = 0 with mgL sin(ϕ ) = CG Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 99 Winfried Mayr, MedUni Wien 33 Oscillation Tonometry FES-induced elastic moment [%] 700 109-7.7y 105-7.5y 600 116 Ness 301-6.5 y 112-6.2y 117-6.2y 500 FES-induced elastic moment [%] 206-5.5y 110 Skul 400 104-4.1y 106-3.5y 108-3.3y 111 Pien 300 119-3.3y 111-1.8y 117 Lan 200 113-1.7y 207-15m 118-13m 205 Bär 206 Böt 110-11m 116-10m 114-10m 100 119 Thö 0 0 -100 stimulation [V] 8 16 24 32 40 48 56 64 72 80 120-10m 115-10m 205-9m 201-9m mean 100 Vergleich: Änderung des Parameters D Beispiel: Patient 7,3 Jahre denerviert 0,14 Beispiel: Patient 1,5 Jahre denerviert 2,50 vor dem Training nach 1 Jahr Training Änderung von D in Nms 0,12 0,10 0,08 0,06 0,04 0,02 0,00 0 Änderung von D in Nms 40 48 56 64 72 80 vor dem Training nach 1 Jahr Training 2,00 1,50 1,00 0,50 0,00 8 16 24 32 0 8 16 24 32 40 48 56 64 72 80 Stimulationsamplitude in V Stimulationsam plitude in V Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 101 0.2 0.15 F 0.1 0.05 0 t 50 100 150 200 250 300 350 400 -0.05 Time to peak (TTP) Half relaxation time (HRT) El.mech. delay Rot: pre FES Blau: 1 Jahr FES TTP, HRT und El.Mech.Delay bei verschiedenen Pulsbreiten (1, 5, 10, 20, 40, 80, 120, 160ms) Kein Balken bedeutet: kein Twitch detektierbar Mit FES ist die Detektionsschwelle von 40ms auf 20ms gesunken. Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 102 Winfried Mayr, MedUni Wien 34 Single fiber recordings / measurement setup Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 103 Analysis of muscle fibre conduction velocity (MFCV) first pos. spike > 50µV (5.76 ms) last pos. spike (8.22 ms) mean latency of all recorded spikes > 50µV (7.10 ms) distance betw. electrodes betw. 32 mm max. MFCV = 5.6 ms-1 min. MFCV = 3.9 ms-1 mean MFCV = 4.5 ms-1 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 104 Double pulse stimulation of denervated muscle Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 105 Winfried Mayr, MedUni Wien 35 RISE Pat. 108 after 1st and 2nd year of FES ISI = 6 ms; MFCV = 1.85 m/s Winfried Mayr ISI = 3 ms; MFCV = 4.12 m/s 106 Vienna Medical University - Center of Biomedical Engineering & Physics RISE Pat. 119 before and after 1 year of FES MFCV = 0.98 m/s; ISI = 8 ms MFCV = 1.83 m/s; ISI = 3 ms Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 107 CT scans every 10 cm trochanter 0 cm 10 cm 20 cm 30 cm 40 cm Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 108 Winfried Mayr, MedUni Wien 36 Planimetry Cross Sectional Area (cm²) and Density (HU) 8.7a denervated cross sectional area = ??? 1.7a dendervated cross sectional area = 50.17 cm² mean density = 30 HU Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 109 A.B. # 18 ( 205 ) 0.8y denervated Cross section right thigh at 20 & 30cm 1y 2.5y stimulation 0y 20cm 30cm Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 110 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 111 Winfried Mayr, MedUni Wien 37 H.T. # 36 ( 119 ) 3.2y denervated 0y Cross section right thigh at 20 & 30cm 1.1y 1.6y stimulation 20cm 30cm Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 112 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 113 K.L. # 24 ( 109 ) 7.7y denervated 0y Cross section right thigh at 20 & 30cm 1.3y 2.5y stimulation 20cm 30cm Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 114 Winfried Mayr, MedUni Wien 38 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 115 Biopsies Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 116 Long-term Denervated Human Muscle Lower Motor Neuron Lesion Prof. Ugo Carraro - Applied Myology Lab - Padova –
[email protected] 0.9-y [110 (26-5)] 4.0-y [104 (20-5)] 1.9-y [111 (28-5)] Winfried Mayr 8.7-y [103 (14-1)] 117 Vienna Medical University - Center of Biomedical Engineering & Physics Winfried Mayr, MedUni Wien 39 Long-term Lower Motor Neuron Lesion FES Training of Denervated Human Muscle From: Kern H et al J Rehabil Res Dev 2005 Prof. Ugo Carraro - Applied Myology Lab - Padova –
[email protected] Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 118 Myofiber Regeneration in Long-term Denervated Human Muscle MHC-emb+ Regenerating Myofibers Lower Motor Neuron Lesion From: Kern H et al J. Neuropathl Exp Neurol 2004; 63: 919-931. Prof. Ugo Carraro - Applied Myology Lab Padova –
[email protected] FES Training 119 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics Effect of FES Training on Myofiber Size of Long-term Denervated Human Muscle FES Trained 70 60 Normal Peripheral Denervation Central Lesion Minimum Diameter (µm) 50 40 30 20 10 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 De ne rvation (ye ar) 14th ECPRM - Wien, May 15, 2004 Prof. Ugo Carraro - Applied Myology Lab - Padova –
[email protected] Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 120 Winfried Mayr, MedUni Wien 40 Muscle excitability Ca++ release - t – tubulus (1) - sarcoplasmatic reticulum (2) - triad (3) 3 1 2 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 121 15-month Denervated Human Quadriceps Muscle 15- N N A, Severe atrophic fiber. B, a triad in normally innervated muscle. C-D, following long-term denervation the frequency of ECC units decreases and the morphology changes dramatically: Many junctions appear to be dyspedic (i.e. they lack RyRs). Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics Ugo Carraro, Applied Myology Lab, University of Padova 122 Long-term Denervated Human Muscle Lower Motor Neuron Lesion 1. Conclusions Human skeletal muscle undergoes three phases during long-term denervation: i) Atrophy; ii) Lipodystrophy; iii) Fibrosis, Myofibers survive denervation much longer than generally accepted (years) After permanent lower-motoneuron lesion repeated cycles of myofiber death/regeneration contribute to long-term skeletal muscle tissue persistence Regenerated myofibers have higher excitability and strength than longterm denervated myofibers Long-term FES training reverts severe denervation atrophy and maintains trophism of regenerated myofibers Prof. Ugo Carraro - Applied Myology Lab - Padova –
[email protected] 2. 3. 4. 5. Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 123 Winfried Mayr, MedUni Wien 41 Patient Study Preselection Begin of Clinical study Evaluation September 03 May 04 End of study Wilhelminenspital Weißer Hof Bad Häring Murnau Heidelberg Hamburg Tübingen Vicenza Island Piacenza/Lotta Patienten gesamt 93 60 38 15 13 13 13 13 13 13 12 8 8 8 8 8 8 8 5 5 5 5 5 5 2 1 1 2 3 0 1 1 2 1 14 3 2 2 5 4 2 1 2 3 1 25 22 4 3 3 3 3 3 3 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 124 Patient Study 28 Patients with traumatic fracture between Th5 und L1 (9 Th11, 13 Th12) 11 10 9 8 num b er of p atien ts 23 men ∅ 36 a ∅ 4.9 a denervated 7 6 5 4 3 2 5 women ∅ 43 a ∅ 5.8 a denervated Winfried Mayr 1 0 up to 1,5 2 to 5 6 to 10 years of denervation 11 to 20 20 + Vienna Medical University - Center of Biomedical Engineering & Physics 125 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 126 Winfried Mayr, MedUni Wien 42 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 127 additional Rat Study x 40 A B x 4500 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 128 Simulation of FES field distribution in the thigh muscle fiber tubular openings extra cellular intra cellular myofibrills sarkolem m a transversal tubulus longitudinal tubulus sarcomere AP-Excitation and Propagation Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 129 Winfried Mayr, MedUni Wien 43 Colour-coded T2-maps of human ColourT2skeletal muscle before (left) and after (right) short-term FES. short- Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 130 RISE Plenary Meeting - Iceland June 2005 End of RISE - May 31, 2006 Winfried Mayr Vienna Medical University - Center of Biomedical Engineering & Physics 131 9th VIENNA INTERNATIONAL WORKSHOP on FUNCTIONAL ELECTRICAL STIMULATION Basics, Technology, Application 19.Sept. - 22. Sept. 2007 http://2007.fesworkshop.org/ The conference location is in one the most lovely regions of Austria named "Wachau", in the city of Krems/Danube 132 Winfried Mayr, MedUni Wien 44 9th VIENNA INTERNATIONAL WORKSHOP on FUNCTIONAL ELECTRICAL STIMULATION 19.Sept. - 22. Sept. 2007 Special Topics 1. FES of denervated muscles 2. Spinal cord stimulation (CPG, LLPG) 3. Stimulation of autonomic nervous system •Insulin delivery •Blood Pressure 4. Battery powered FES implants Further Main Topics 5. Neuromuscular physiology •Nerve and muscle: metabolism, fatigue, plasticity •Histology •Impulse pattern, management •Biomechanics •Simulation, modeling 6. Technology of external devices and implants •Electronics, microelectronics •Microprocessor control •Software •Sensors, closed loop control •Biomaterials, encapsulation •Connectors, cables, electrodes 7. Application •Diaphragm •Bladder, pelvic floor, graciloplasty •Skeletal muscles for cardiac assist, cardiomyoplasty, heart •Upper and lower extremities (hemi-, para-, tetraplegia) •Cochlear prosthesis, eye, vocal cord •Pain, spasticity •Rehabilitation strategies •Other methods 8. Product transfer to the clinic •Safety •Regulatory affairs, quality assurance 133 Winfried Mayr, MedUni Wien 45