Today’s Presenters:

Harm Knot, PharmD, Ph.D

Chief Technology Officer, TSE Systems

Louis D’Alecy, DMD, Ph.D

Professor of Molecular & Integrative Physiology,

The University of Michigan

Jeffrey Osborn, Ph.D

Professor & Associate Chair, Department of Biology, University of Kentucky

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Telemetry Revisited – The Freedom To Move Anywhere at Anytime and Still Collect Quality Data

Harm Knot, PharmD, Ph.D

Chief Technology Officer,

TSE Systems

Copyright InsideScientific & TSE Systems. All Rights Reserved.

The Hallmark of Next Generation Telemetry is Freedom…

A few continuing challenges facing telemetry:

• reliability: electrical interference (multiple frequencies, high frequency bands, fast)

• smaller devices with longer sending range (battery improvements, latest digital transmitter technology, send on demand

• improved processing & data mining (multiple software partners, open source data)

• complex measurement environments (Phenomaster, Inhalation Toxicology chambers)

The new telemetry toolbox for scientists -- use what you need when you need it!

Stellar Innovations

• on board memory -- freedom to move with no data drop-outs and no required receiver proximity

• solid-state pressure sensor at tip of lead -- variable length, easy handling, virtually drift free

• latest transmitter technology -- extended range with unique digital address… movement, exercise and social interaction in groups is not a problem and animals may leave the room for procedures

• microprocessor -- for protocol execution and scheduling (allows autonomous operation)

The Stellar telemetry solution is enabling

scientists to do more for less… any time

Stellar Telemetry –

Receiver / Antenna

• Place on the wall,

ceiling, in another

room or carry it!

• 5 meter (15ft.)

range with optional

antenna array if

required

• Just (1) one USB

connection required

for data transfer

AND power

Monitor hundreds of animals with a single receiver !

Measurement Parameters

• Pressure(s): blood pressure (aorta, carotid, femoral), intracranial (brain), intrathoracic (chest, respiration)

• Biopotential(s): Electro cardio- (ECG), encephalo- (EEG), myo- (EMG), olfactory- (EOG) gram

• Temperature(s): Core body temperature (implant) and/or external target area such as brown fat an organ(tumor) or the tail

• Heart Rate -- via software from ECG or BP

• Activity -- x,y,z digital activity scoring and tracking

Stellar Telemetry – Receiver Placement complicated housing modalities can be

accomodated

Metabolic Phenotyping Inhalation Toxicology Behavioral Phenotyping

Stellar Telemetry – Software

Stellar Telemetry – Implant Models

Animal Weight (g) > 170 > 240 > 500

Type Model

Pressure Biopotential Temperature Activity

Pressure Biopotential Temperature Activity

Pressure Biopotential Temperature Activity

Leads (length) Variable/Custom Variable/Custom Variable/Custom

Size: Volume (c.c./cm3) Weight (grams)

6 11

8.9 15.5

13.2 26

Battery Life (Months) ~ 12 ~ 24 ~ 36

Summary…

• New generation of telemetry implants using the latest technologies -- A new “toolbox” for physiological monitoring

• All digital single antenna system that can also be used in complex animal (group housing) environments

• Very flexible measurement scheduling, what you need, when you need it, where you need it

• Economical and mobile

Rodent Blood Pressure and ECG Telemetry Using Stellar Implants The D'Alecy Laboratory Experience

Louis D’Alecy, DMD, Ph.D

Professor, Molecular & Integrative

Physiology, University of Michigan

Copyright InsideScientific & TSE Systems. All Rights Reserved.

UNIVERSITY OF

MICHIGAN

What will we review today…

1. How does one ensure proper sensor placement in different sized rodents, especially for protocols where significant growth is a factor?

2. How do we deal with pressure sensor placement and lead (catheter) anchoring

3. How do we deal with anchoring the implant in the abdomen and externalizing leads?

4. How can one ensure reliable long term recording of pressure, ECG, BT, and activity in rodent models (for months)?

How does one ensure proper sensor placement in different sized rodents, especially for protocols where significant

growth is a factor?

• variable lead length

• accommodate growth

• appropriate/stable anchoring of pressure lead

• Independent stabilization of lead tip and implant body

How do we deal with pressure sensor placement and lead

(catheter) anchoring?

• on pressure lead

• Placement of suture for abdominal wall anchor

• Placement of two aortic clamps

• Insertion of pressure lead

• Secure pressure lead to abdominal wall

• Gluing & patch placement

Aortic Pressure Sensor Placement

4-0 ethibond® on tapered needle (or suitable non-absorbable suture with a traumatic needle)

Insertion of Pressure Lead Placement of suture for abdominal wall anchor

Pressure lead Routed

Pressure lead in aorta

Distal clamp

Proximal clamp

Securing Lead with Tissue Adhesive

Placement of Cellulose Fiber Patch

Tissue adhesive applied sparingly with 32 gauge

dispensing tip

Cellulose fiber patch

How do we deal with anchoring the implant in the abdomen so it is stable and safe long term?

Aortic Pressure Sensor Closure

1. Linea alba

2. Interrupted suture, each eyelet & each space

3. Incorporate eyelets

4. Tissue adhesive

5. Finish passing RA and securing LL & Ground

6. Staple and adhesive

7. Secure RA

Interrupted Sutures

Incorporating Eyelets

After this photo, we decided that 4-0 ethibond® on tapered needle is more

manageable than 2-0 prolene

How can one ensure reliable long term recording of pressure,

ECG, BT, and activity in rodent models (for months)?

Final Answer & Summary:

• wire vs. fluid-filled lead maximizes flexibility and selection of pressure sensor location – solid-state technology permits measurement at the source

• use of extra lead length allows for growth and motion without signal loss

• independent stabilizing sensor and implant body enhances long-term recording stability

• flexibility of data collection & power management

Non-Human Primate Models of Human Hypertension: Telemetric monitoring of Blood Pressure in Free Ranging Vervet Monkeys

Jeffrey Osborn, Ph.D

Professor & Associate Chair,

Department of Biology,

University of Kentucky

Copyright InsideScientific & TSE Systems. All Rights Reserved.

Summary of Research Application:

• Large Animal and Non-Human Primate Research are critical to studying cardiovascular pathophysiology

• Challenge 1: Studying Non-Human Primates within a natural environment.

• Challenge 2: Assuring full behavioral assimilations with non-human primates is essential for cardiovascular data integrity.

• Challenge 3: Acquiring reproducible non-human primate measurements of cardiovascular function over extended time periods using direct telemetry recording.

• The African Green or Vervet Monkey provides a translational model of human essential hypertension.

Descending Aorta (3-4 cm isolation)

Purse String Suture (Catheter Entry Point)

• Abdominal Aorta isolated 3-4 cm caudad to the left renal artery/vein.

• Purse string suture embedded into aorta adventitia (5-O TevdekR)

• Umbilical tape reduces aortic flow. 16 g needle provides insertion site.

• Catheter insertion 3-5 cm.

• Purse string suture closure holds implanted catheter.

• Dacron patch 1 cm x 1 cm glues catheter to aorta (VetbondR).

• Postoperative recovery at 2 weeks.

• Current procedure does not expose transmitter unit.

Aortic Walls

Catheter in Vessel Lumen

Longitudinal Section Ultrasound Images: John Dascanio, DVM Ross University School of Veterinary Medicine Bassaterre, St. Kitts-Nevis

Catheter Tip

Cross Section of Aorta Ultrasound Images: John Dascanio, DVM Ross University School of Veterinary Medicine Bassaterre, St. Kitts-Nevis

• Cross Sectional view of catheter sensor tip within abdominal aorta.

• Note how catheter tip remains intact within the laminar flow region (lumen) of the large vessel.

• Ketamine sedation (12 mg/kg i.m.)

• Longitudinal view of catheter within abdominal aorta.

• Note how catheter tip remains intact within the laminar flow region (lumen) of the large vessel.

• Ketamine sedation (12 mg/kg i.m.)

Example Data – Vervet Monkey #8224:

• Recording conducted approximately 10 days post-surgical implantation.

• Recording Parameters: 200 Hz; 10 seconds every 10 minutes.

• Standard errors represent variability within each hour of recording.

Blood Pressure Variability in Hypertensive Monkey #8224

Day 1 Day 2 Day 3

• Hourly variability relatively stable over daytime to nighttime cycle.

• Note: Systemic essential hypertension.

Day 1 Day 2 Day 3

Three Consecutive Day Recording: MAP & HR

(HT Monkey #8224)

Day 1 Day 2 Day 3

• Heart Rate (HR; bpm) and mean arterial pressure (MAP; mmHg) measured 3 consecutive days in essential hypertensive, male vervet monkey.

• Note synchronous, 24 hour relationship between HR and core body temperature.

Three Consecutive Day Recording: BT & HR (HT Monkey #8224)

• Heart Rate (HR; bpm) and core body temperature (oC) measured 3 consecutive days in essential hypertensive, male, vervet monkey.

Day 1 Day 2 Day 3

Current & Ongoing Recordings (#8085 and #8201)

• March 21, 2014 Start Date

• Recording 12:00a.m. & 12:00 p.m. 15 sec every 12 hours.

• Recording Continuously Through July 15, 2014

• Collected data, microchip stored for end of experiment download

Translating Non-Human Primate Models to Human Hypertension The Genetic Basis of Essential Hypertension

Summary…

• Telemetry of freely moving, behavioral acclimatized non-human primates requires unique data collection and transmission properties

• The STELLAR system provides the necessary technology to overcome these challenges

• Implantation of the STELLAR catheter in the freely moving, vervet monkey records consistent blood pressure, heart rate and core body temperature with 24 hour precision and accuracy

• The vervet monkey animal model plus STELLAR technology provides a unique translational species for the long-term study of the pathophysiology of cardiovascular function and hypertension

Thank You!

For additional information on Stellar Telemetry and other related products from TSE Systems visit: http://www.tse-systems.com/products/implantable-telemetry/animal-telemetry-system.htm

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InsideScientific is an online educational environment designed

for life science researchers. Our goal is to aid in the sharing and

distribution of scientific information regarding innovative

technologies, protocols, research tools and laboratory services.