Integrated CNS and CV monitoring via telemetry in behavior studies

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1 Measurement Behavior Tutorial - Integrated CNS and CV monitoring via telemetry in behavior studies Thomas Penning European Manager at Data Sciences International The Gold Standard in Physiologic Monitoring

2 Agenda DSI Company Overview New telemetry products for large & small animals Key features for accurate & reliable chronic monitoring New possibilities by the use of customized antennas Examples for combined CNS/CV + behavior monitoring Discussion, Q&A Session

3 Questions?

4 DSI Business Field DSI was founded in 1984 and growed to the global leader in implantable telemetric physiological monitors More than 70 years experience in medical instrumentation and high reputation for signal conditioning & recording Founded in 1986 as spinout of Buxco Company focused in physiological signal analysis Provider of telemetric & hardwired solutions for cardiovascular, CNS and respiratory monitoring & analysis in preclinical research

5 Data Sciences in Figures 28 Years of history (founded 1984) 180+ Employees Systems in 48 Countries 18 Sales offices Brian Brockway DSI founder 500,000+ Subjects monitored Publications 30+ Patents 20% Revenue spending in R&D

6 Implantable Telemetry System

7 DSI Wireless Monitoring Parameters Core Body Temperature Blood Pressure Respiration (breath frequency) ECG electrocardiogram EMG - electromyogram EOG electro-oculogram EEG electroencephalogram LVP, PAP, Intra-Pleural Pressure SNA Bladder Pressure Intracavernosal Pressure Many More

8 Implantable Family Pressure Temperature Biopotential Wide application Reduced stress Minimized variables Increased data accuracy

9 New Telemetry Offerings Physiotel HD Series Physiotel Digital Receiver RSC-1 / RSC-3 DSI Business Services

10 What is HD? HD = Hybrid Digital telemetry New transmitter for small animals Improved reliability & performance More signals & parameter combinations Provide improved reliability & performance. Improved animal welfare Works with existing hardware* * Software update required

11 PhysioTel HD Platform Overview Digital encoded data Device ID & serial number Calibration values Battery status and battery ON time High performance pressure sensing No wrong data due crosstalk Automated Xmitter configuration

12 HD-S21 Dual-pressure Small Animal Telemetry Battery: 2 month Volume: 5.9cc Weight: 8g Signals Measured Two pressures Biopotential Temperature Activity Intended Species Rat Ferret Guinea pig Marmoset Implantable at an animal body weight of 175g

13 Application opportunities with HD-S21 Chronic monitoring applications: Left ventricular pressure + blood pressure (BP) Pulmonary artery pressure + BP Pleural pressure + BP Pulse wave velocity Intra-ocular pressures Uterus pressure + BP Bladder pressure + BP Precise, reliable, high fidelity data is available with an HD-S21. LV P B P EC G

14 LVP, BP & ECG with HD-S21

15 HD-S21 Chronic Parameter Data

16 HD-X11 Transmitter Volume: 1.4cc Weight: 2.2g Battery Life: 30 days Signals Measured Pressure ECG, EMG or EEG Temperature Activity IP implantable from a min. body weight of 30g SC implantable from a min. body weight of 19g Intended Species Mouse Hamster Juvenile rat Plus more!

17 New Capabilities with the HD-X11 Consolidated study of multiple parameters: Reduce in animal use Higher statistical relevance More complete physiologic assessment in CV studies HD-X11 components held together with flexible circuit

18 Simultaneous BP & ECG from a Single Mouse!

19 HD-X11 parameter data

20 PhysioTel Digital Implants Model L21 2 Pressures 1 Biopotential Temperature Activity Battery Life: 12 weeks Technical Data Model L11 1 Pressure 1 Biopotential Temperature Activity Battery Life: 15 weeks

21 Spec Comparison D70 - PCT L11 Weight 47grams 56 grams Volume 32cc 29cc Pressure Drift < 2 mmhg/month max. < 2 mmhg/month max. Battery Life 14 weeks 15 weeks RF - Range 1m 3-5m Bandwidth Biopotential 1 100Hz Hz Biopotential Range Fixed Programmable

22 Implantation in Primates BP catheter with radio opaque marker Antenna inserted in an intramuscular pocket Positive ECG lead loop Intravascular (negative) ECG Leadin superior vena cava

23 System Equipment DSI Telemetry In the animal PhysioTel D70 PhysioTel Digital L21, L11 In the cage RMC-1 TRX-1 In the room DEM CLC

24 Key specs of the system Digital data No cross talk Less disturbances Auto-configuration Longer range (3-5m) Less receivers Multi animals/receiver Group housing (up to 12)

25 Example Canine System

26 Accurate Biopotential Sensing Biopotential Expanded bandwidth Hz Solid Tip electrode for clean ECGs

27 Primate Data

28 Dog Data

29 Minipig Data

30 Example Primate Set-up

31 Surgery Support for DSI Products Training Workshops Quarterly courses at DSI Harlan Courses in EU Labs at AALAS,CALAS, ASR Surgical Support Services: Surgical Videos and manuals Experienced surgeons at DSI Customer reference sites Trained implant services vendors Taconic Charles River Laboratories The Jackson Laboratory DSI Support Trained Technical Sales Representatives, Tech Support Staff

32 Keys for accurate chronic monitoring Pressure Sensing Techniques Battery challenges Sampling frequency and bandwidth Housing and environment

33 Sensing Technology Considerations

34 Summary Sensing Technology Good adoption of frequency to phys. signals High temperature stability (less drift) Proven reliability in chronic applications Easy to remove without damage Inexpensive replacement (refurbishment) Antithrombotic & proven biocompatibility

35 Maintenance cost Self maintenance with re-gel procedure Transmitter exchange program 3,000 2,500 2,000 1,500 1, HD-X11 new Refurbishment Durablity solid tip Cost fluid filled

36 Exchange Program Factory site renewal of: Catheter Lead electrodes Housing Battery Calibration Sterilization Sterile Package Last approx. 3 weeks Returned transmitter As New Warranty of up to 18 month* * MWP = Maximum Warranty Period (Type depended)

37 Signal Frequency Characteristic The frequency characteristic of a catheter is the ability to follow pressure changes over time. The higher the HR the higher needs to be the bandwidth of the catheter. smaller higher Hz Bandwidth Bandwidth khz Drop in amplitude Slow rise time Inaccurate contractility Increase of noise More disturbances Same physiol. info

38 LVP signal in the frequency domain HR = 320bpm = 5.3 Hz This amplitude spectrum shows which catheter frequency would be necessary for a accurate reproduction of a ventricular pressure signal. Higher frequency portions then the heart frequency are seen due the nonsinusoidal shape of the LVP signal

39 Catheter Frequency Characteristics The frequency characteristic of a catheter depends on material and length. The shorter the catheter the higher the bandwidth Empirically the bandwidth for BP monitoring should be 5 times higher than the heart frequency.

40 Rat LVP two catheter types Time rel. Time abs. Date Num Sys LVEDP DP HR dp/dt Time rel. Time abs. Date Num Sys LVEDP DP HR dp/dt 0000:29:53 11:18:15 1/27/ :29:53 11:18:15 1/27/ :29:53 11:18:15 1/27/ :29:53 11:18:15 1/27/ :29:53 11:18:15 1/27/ :29:53 11:18:15 1/27/ :29:54 11:18:16 1/27/ :29:54 11:18:16 1/27/ Hz 2 khz

41 Catheter Bandwidth for BP Monitoring Depends on the HR of the animal smaller higher Hz Bandwidth Bandwidth khz BP Rat: 300bpm (5Hz) * 5 = 25Hz Mouse 900bpm (15Hz) * 5 = 75Hz Drop in amplitude Slow rise time Inaccurate contractility Increase of noise More disturbances Same physiol. info

42 Drift Compensation Sensing technology of HD devices have a small temperature drift and long term offset drift due advanced compensation technology Electronic housing Cath. Tip Bridge in DSI transmitter housing Bridge in solid tipped catheters

43 Reliability / Patency DSI Pressure Sensing Catheter Non-Compressible Gel Bloodstream around pressure sensing tip and antithrombotic treatment prevents clothing Solid Tip Catheter Fragile latex membrane Long term reliability of the gel-tip tested and proved in chronic studies.

44 Charging Challenges No defined distance between charger & implant. Energy transmission creates heat Impact on temperature monitoring Impact on animal behavior Impact on animal welfare Electrical field can create disturbances More artifacts in signal recording Makes refurbishment not obsolete Necessary exchanges of catheter & lead material Recommended annual factory re-calibration

45 Battery Operation Lifetime specified for continuous operation Battery can be turn ON/OFF by a magnet, Exchange by refurbishment procedure, Advantages of Battery Devices: Longer operation times without maintenance, Known battery status, Vendor warranted operation time, No recharging required (impact on behavior and temperature) No tissue irritations Accurate temperature monitoring Typical Battery Lifetime: PA-C10 = 1.5month; CTA-F40 = 6 month; TA-F40 = 11month

46 What s the max. sampling rate? Limited by Carrier Frequency Typically 5x transmitter bandwidth Sampling rate can be increased by interpolation Example: TF50-W-F2 for Sympathetic Nerve Analysis (SNA) Bandwidth: 1kHz Sampling rate: 5kHz

47 Use of customized antennas Transmission range restricted by energy consumption Other influences on transmission ranges: Interferences Metal shielding Environmental noise Transmission range / m Large animal implant PT Digital Large animal implant D70-EEE Small animal implant HD-X Small animal implant HD-X11 Large animal implant D70-EEE Large animal implant PT Digital Series

48 Telemetry + Environmental + Behavioral data Behavioral data: running wheels, drinking and feeding activity, stimulus, etc. Combine with video based Behavior Analysis. DSI data into Observer XT/Noldus Combine with other Behavioral analysis systems: Laboras/Metris Direct and Dynamic data exchange with Excel: scoring, develop homemade systems, Control output

49 Telemetry + Environmental data

50 Telemetry + Behavioral data

51 Food intake behavior and CV monitoring

52 CNS and Behavior Monitoring

53 FAQ s How can I interface between Noldus behavior systems and DSI telemetry?

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