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1 Product Presentation Instruments for Animal Behavioral Research © Metris b.v. 2009.

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Presentation on theme: "1 Product Presentation Instruments for Animal Behavioral Research © Metris b.v. 2009."— Presentation transcript:

1 1 Product Presentation Instruments for Animal Behavioral Research © Metris b.v. 2009

2 2 Content n Company overview n Products n Importance of the energy parameter in Behavioral Pharmacology

3 3 Company overview Goal Provide turnkey solutions / expertise in the area of automatic animal behavior analysis. ProductsMarkets LABORAS Pharmaceutical industry SonoTrack Research institutes/CRO’s Third Party products Universities/ Academic Hospitals Activities Product Development, Product Development, Marketing / Sales, Marketing / Sales, Assembly and Product support. Assembly and Product support.

4 4 History n 5/1999Metris BV start n 9/2001Delivery of first LABORAS for Windows systems n 2/2005Introduction SONOTRACK (Ultrasound recording and analysis) n 7/2005Distributor SleepSign for Animals (EU) n 8/2006Introduction LABORAS 2.0 n 12/2008Introduction SonoTrack USV Playback n 1/2009Introduction SonoTrack 2.0 n Since 2001 ± 400 platforms are delivered and over 50 references on our website support the value of LABORAS as experienced by researchers

5 5 Company Relations Distributors n Neuroscience Inc. (Japan) n Kuo Yang Scientific Corporation (Taiwan) n Mirae Korea Inc. (South Korea) n Medi Analytika Ltd. (India) n AH Medical Supply (China) n Radon Medical (Turkey) Cooperations n DataSciences – Telemetry (USA) n Kissei (Japan) n Porsolt (France) n National Instruments (USA, NL, Armenia)

6 6 LABORAS n LABORAS is a fully automatic system for continuous behavior recognition and tracking of small rodents (mice and rats) n LABORASreplaces, reduces and refines behavioral scoring by human observers n LABORAS replaces, reduces and refines behavioral scoring by human observers n LABORAS sets a new standard in the area of behavioral observation instruments What is LABORAS?

7 7 1980 1990 2000 2010 Infrared beam matrix (8x5) Infrared beam matrix (3D) LABORAS 2.0 Infrared beam matrix (4x3) ANIMEX Video tracking (single point) Video tracking (multi point) LABORAS 1st. generation Low resolution XY track high 0 no. of behaviors >10 Evolution of automatic tracking & behavioral observation systems

8 8 LABORAS technique (1/3) Main components LABORAS n Measurement platform(s) n Electronics (e.g. amplifiers & control & A/D conv.) n LABORAS software for Windows

9 9 LABORAS technique (2/3)

10 10 LABORAS technique (3/3) Locomotion Scratching Example of recognition of behavioral features Fast up and down movement of the hind foot, rubbing the side of the body, neck and face.

11 11 Tracking measurement Tracking information provided by LABORAS  High resolution XY position track  Velocity data (average, max.)  Distance traveled  Position distribution (details like favorite spots)  Circling / turning (Clockwise and counter-clockwise circle count, avg. circle size, avg. circling speed, avg. time in circle)  Sociality Cage (preference to visit specific compartments in cage)  Estimation of energy use (in development)

12 12 Detection of behaviors LABORAS distinguishes more than 16 different rat and mouse behaviours Normal behaviours  Locomotion  Immobility  Rearing  Climbing  Eating  Drinking  Grooming Special behaviours  Scratching (mice)  Seizures - tonic-clonic convulsions, barrel-rolls, Racine P4 and P5 (mice)  Hind limb licking / Formalin test (rat)  Purposeless chewing (rat)  Wet dog shakes (rat)  Headshakes (rat)  Head twitches (rat)

13 13 LABORAS configurations Configuration variables n Up to to 8 measurement platforms connected to one computer n Species: mice, rat or both n Tracking and Behavior software modules: –Tracking –Normal behaviors –Special behaviors n Integration with Telemetry (Behavior & Psychology) n Sociality Cage (special cage that enables sociability test) n User interface specials –GLP –Independent start of the platforms

14 14 Examples of results

15 15 Examples of results

16 16 LABORAS Qualification (1/6) n Operational Validation: –Does LABORAS performs as advertised –Explained in the following sheets n Pharmacological Validation –Does LABORAS assist me with my research –Metris role to assist –E.g. new experiments or new algorithms n Certificates –GLP (Laboratory req.), CE / FCC (electrical req.)

17 17 LABORAS Qualification (2/6) Camera Platform Electronics

18 18 LABORAS Qualification (3/6)

19 19 LABORAS Qualification (4/6)

20 20 LABORAS Qualification (5/6) Validation Results ● Correlation with human observers (according to validation criterion) – Locomotion, Climbing > 95% – Immobility, Grooming > 90% – Eating, Drinking, Rearing> 80% – Special behaviors> 80-90% ● Since 2001 ± 400 platforms are delivered and over 50 references on our website support the value of LABORAS as experienced by researchers

21 21 LABORAS Qualification (6/6) Development of new algorithms Good animal behavior definitionGood animal behavior definition Proper definition of the experiment protocolProper definition of the experiment protocol - and use of the LABORAS experiment administration Choice of pharmacological relevant behaviorsChoice of pharmacological relevant behaviors Good correlation with the real behavior (acceptation criterion) - Not always human observer referenceGood correlation with the real behavior (acceptation criterion) - Not always human observer reference Results presentation - Recording and Presentation of result data - Use of previous raw data/ result summariesResults presentation - Recording and Presentation of result data - Use of previous raw data/ result summaries Enabling the full benefit of LABORAS

22 22 Examples of performance Normal Behaviour (rat)

23 23 Examples of performance Wet Dog Shakes (rat)

24 24 Examples of performance Head Twitches (rat)

25 25 Examples of performance Circling (rat)

26 26 Examples of performance Sociality Cage (mice)

27 27 Applications LABORAS n LABORAS application areas are: (behavioral assessment in) –Drug Development– Phenotyping –Safety Pharmacology– Lab. animal science –Toxicology n Typical customers are: –Pharmaceutical Corp– CRO’s (Contract Research Org.) –Academic institutes– Lab. animal suppliers –Hospitals– Governmental Organizations

28 28 Applications LABORAS Monitoring of behavioral changes and effects in: n Drug Development Drug Discovery research –Efficacy studies of new compounds –Long term observation tests (e.g. circadian rhytm,eat-drink patterns) –Experimentally induced behaviors (e.g. grooming, drinking, movement patterns, hindlimb-licking / formalin-test, scratching, WDS, Head Shakes) n Safety Pharmacology n Toxicology n Phenotyping research –High Capacity Phenotyping with transgenic mice

29 29 Applications LABORAS n Animal models based on behavioral assessment in home cage environment –Normal behaviors –Drug induced behaviors n Pain studies –Automated Formalin Test n Social Interaction –Preference studies (with stranger and familiar mouse – Sociality cage) n Animal welfare studies –Cage enrichment studies –Behavioral effects of manipulation of animal

30 30 Applications LABORAS Examples of LABORAS applications in drug discovery TESTRESULT Behavioral phenotyping transgenic mice Target discovery for future drug development Primary observation test Adverse drug effects Open field test E.g. sedative, stimulant, anxiolytic, anxiogenic properties Pain test (formaline induced hindlimb licking) Analgesic properties Dermatology test (scratching) Skin protective effects Telemetry & Behavior Integrated cardiovascular, CNS and behavioral data Sociability Test Analysis of social behavior (for amongst other Autism research)

31 31 Applications LABORAS TESTRESULTS Effect on Pharmacologically induced effects, such as m-CPP hypolocomotion and hypophagia m-CPP hypolocomotion and hypophagia 8-OH-DPAT hyperlocomotion 8-OH-DPAT hyperlocomotion d-Amphetamine hyperactivity d-Amphetamine hyperactivity Angiotensin II polydypsia Angiotensin II polydypsia Orexin-A induced grooming Orexin-A induced grooming Excessive climbing Excessive climbing Turning/circling behavior Turning/circling behavior Wet Dog Shakes (WDS) Wet Dog Shakes (WDS) Head Shake & Head Twitch Head Shake & Head Twitch Seizure Seizure Pharmacological efficacy of (potential) leads Pharmacological antagonist efficacy, eg. anticonvulsant activity Examples of LABORAS applications in drug discovery

32 32 Applications LABORAS NEAR FUTURE APPLICATIONS Antagonism of pharmacologically induced effects, such as  Dyskinesia  Startle response FUTURE APPLICATIONS Respiration Adverse effects Heart beat Efficacy and safety issues Sniffing, Digging, Jumping Detailed Exploration/Anxiety measure Energy spend Metabolic effects Disturbed feeding / drinking patterns (Eating / Drinking) Hypo- or hyperphagia; Hypo- or polydipsia Examples of LABORAS applications in drug discovery

33 33 Overall benefits LABORAS General benefits for customer ●Standard and objective method −Eliminates inter- and intra observer deviation −Does not require trained or experienced raters ●Reduces time & costs (>75% reduction) ●Results are almost immediately available ●Many independent parameters can be measured with just one system (Tracking & behavior recognition combined in single system) ●Growth potential to determine several new behavioral and tracking parameters

34 34 Overall benefits LABORAS Important benefits for experiment ●Independent of light conditions ●Home cage environment and non-invasive method (stress minimized) ●Large scale observational experiments possible ●Long test periods possible ●More consistent results

35 35 SONOTRACK

36 36 What is SONOTRACK? ● SONOTRACK records, visualizes and plays back Ultrasound Calls ● SONOTRACK records the full spectrum from 15kHz up to 100kHz ● SONOTRACK records 4 independent ultrasound channels ● SONOTRACK can easily be adjusted to experimental environment and is easy to use

37 37 Ultrasonic Vocalizations

38 38 What is SONOTRACK ● SONOTRACK can be used for long term experiments ● SONOTRACK recognizes and counts Ultrasonic Vocalizations in user definable frequency bands ● SONOTRACK offers a new approach for characterization of animal behavior

39 39 SONOTRACK Applications ● SONOTRACK can be used to monitor animal welfare and interaction between animals based on the ultrasonic vocalizations of the animals ● Typical research areas: – Pain – Anxiety – Stress – Depression – Social interaction – Animal Welfare

40 40 SONOTRACK Applications ● Playback of Ultrasounds to the animal (stimulus) - playing back parts or complete recordings - playing back specific (artificial) frequency patterns

41 41 Examples of results

42 42 Examples of results

43 43 Examples of results

44 44 Examples of Results

45 45 Examples of results Marmoset Rats, Mother & Pup Ultrasound Vocalizations

46 46 Example of results

47 47 What is SleepSign? n Software for scoring of sleep stages n Based on EMG and EEG signals n Sleep stages can be scored in a manual mode as well as well as automatically n Scores pre-assigned sleep stages (such as REM, WAKE, SWS) and up to 3 user defined vigilance stages

48 48 Special features n Works with wireless or wired EMG and EEG signals n In depth analysis using Hypnograms and Trend Graphs n Various analysis functions, incl. Stage Graphs, Vigilance State Parameter Display, FFT analysis n Integrated with Video

49 49 Application areas n Pharmaceutical Research n Sleep Disorder Studies and Sleep pattern Analysis

50 50 Integration of Systems Integration of systems such as LABORAS, Video, DSI Telemetry, SonoTrack & Sleepsign  Less Experiments & Experimental lead time  Less Resources (animals, researchers & money)  Integrated analysis of parameters from different domains collected from the same experiment - Behavioral data and Tracking data - Psychological data - Sounds - Sleep stages

51 51 Integration of Systems With Sonotrack LABORAS With SleepSign Example of integration in Laboras

52 52 ENERGY & PHARMACOLOGY Behavior and external / internal conditions Environment - External condition Process in the Body – Internal condition

53 53 ENERGY & PHARMACOLOGY Basic structure BEHAVIOR = Function { Internal stimulus, external stimulus}

54 54 ENERGY & PHARMACOLOGY Animal behavior and environment BEHAVIOR= Function { Process in the Body nervous system structure, nervous function, hormonal effects, biological clocks, perceptual mechanisms, Genes, stimulus filtering} BEHAVIOR= Function { Process in the Body, nervous system structure, nervous function, hormonal effects, biological clocks, perceptual mechanisms, Genes, stimulus filtering}

55 55 ENERGY & PHARMACOLOGY External factor and environmental variables Temperature = function { temperature control Unit, CV } Airflow = function air-conditioning} Barometric pressure = function { place, time } Humidity = function { office level or place } Visual effect = function { walking researchers in the laboratory} Light = function { lights control unit} Sounds = function { sounds generating equipment, voices } Vibration = function { refrigerators, ventilators, PCs, specific equipment } Elektromagnetic waves = function{ transmitting equipment, magnets} Smell = function {specific gases, parfums, etc,}

56 56 ENERGY & PHARMACOLOGY Rule of energy preservation of the body E = K + P = constant(Formula of energetic balance) n Potential Energy of the Body P = ∆U+ δ(ε − Tη + Pν) -∆U is the change in biochemical energy - Ε is the internal energy - Tη is the entropy energy - Pv is the thermodynamic energy

57 57 THE IMPORTANCE OF THE ENERGY PARAMETER IN BEHAVIORAL PHARMACOLOGY Kinetical energy of body Kinetical energy of body E (Locomotion) = Mv²/2 V = velocity, M = total mass of body E (Oscillation) = δm ω²R²/2 ω = radial frequency, R = radius of oscillation, δm = mass of oscillating body part Mv²/2 δm  ²R²/2 +  E k =

58 58 THE IMPORTANCE OF THE ENERGY PARAMETER IN BEHAVIORAL PHARMACOLOGY Kinetical energy of body Kinetical energy of body E (Locomotion) is the kinetic energy resulting from: Locomotion, Walking, Rearing, Climbing Locomotion, Walking, Rearing, Climbing E (Oscillation) is the kinetic energy resulting from different repetitive movements: Scratching, Grooming, Chewing, Sniffing, Wet Dog Shakes, Head Shakes, Head Twitches, Tremors Scratching, Grooming, Chewing, Sniffing, Wet Dog Shakes, Head Shakes, Head Twitches, Tremors

59 59 Detection, recognition and registration of behavior Locomotion Scratching Fast up and down movement of the hind foot, rubbing the side of the body, neck and face. Detection of behavioral features

60 60 LABORAS HS Signal Analog Digital Analog Digital

61 61 E ( Oscillation ) / E ( Locomotion ) spectrogram

62 62 More information mail: info@metris.nl Metris BV Kruisweg 825 2132 NG Hoofddorp Phone:+31 23 5623400 Fax:+31 23 5623425 www.metris.nl Questions? For Fast, Efficient & Quality Pre-clinical Research


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