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Welcome to “Biotelemetry For The Life Sciences”, Session 1:
The Evolution of Wireless Monitoring in The Life Sciences and Review of Industry
Standards in Drug-discovery and Safety Pharmacology and Toxicology
Guest Speakers:
Brian Brockway
President,
VivaQuant, LLC
Robert Hamlin, PhD
DVM, DACVIM, DSPS
QTest Labs and The
Ohio State University
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.
Implantable Telemetry:
Past, Present, and Future
Brian Brockway
President,
VivaQuant, LLC
Copyright InsideScientific & VivaQuant, LLC. All Rights Reserved.
Why Use Implantable Telemetry?
1. Reduce impact of stress as a confounding factor1
2. Percutaneous infections eliminated1
3. Improve safety of lab personnel1
4. Enables longitudinal studies that are otherwise1 impossible
5. Improves animal welfare2
6. Fewer animals3 1. Brian Brockway and Craig Hassler 1993
2. Klaas Kramer 2000
3. Lew Kinter 1994
0
100
200
300
400
500
600
1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010
Discovery
Home-made
Commercialization
Validation
Mainstream
Publication Growth Every 5 Years
Adoption Phases of Implantable Telemetry
… increase in publications follows availability of commercial product
(EST)
*
Significant Events Impacting Development
We’ve Come A Long Way!
Enabling Innovation – Packaging
1. Impervious to
moisture
2. Radio
Frequency
transparent
3. Cost effective,
reliable and
scalable
From: Brockway and Hassler 1993
Enabling Innovation – Sensors
1. Sensor Stability
-- Stanford &
NOVASensor
2. Long-term
pressure sensor
patency
3. Size -- small
sensors for small
spaces
From: Brockway and Hassler 1993
Key Contributors to Mainstream Commercialization
1. Stuart Mackay, UCSF
2. Wen Ko, Case Western
3. Thomas Fryer, NASA
4. James Meindl, Stanford
5. Dave Osgood, MiniMitter
6. Bill Barrows, NASA
Early Data Supporting Implantable Telemetry• Lappe et. al
instrument six rats
and measure MAP
before and after
placing rats in tail-
cuff restraints
• Early BP implant
seeking validation
proves not only
viable, but uncovers
SHR mystery…
• Strain of rats thought
to be hypertensive
proven to be
hypertensive only
when subjected to
stress
From: Brockway and Hassler 1993
• Combined
Pressure and
Blood Flow
• Glucose
• Chemical
Entities
• O2/CO2
Saturation
• Advanced ECG
Continuing Challenges…
• More reliable devices
– Electrical interference
– Failure due to moisture penetration
• Small devices with longer sending range
– Lower infection risk
– Easier/faster surgical procedure
• Improved processing of signals and mining of data
What do we know? What next?...
• Its come a long way since the first implant in 1960
• Now commonly used for EEG, ECG, pressure, temperature
• New suppliers will bring more options & innovation
• However, there’s still a long way to go to reach full potential
References
• Proceedings of the interdisciplinary conference on the use of telemetry in animal behavior and
physiology in relation to ecological problems. Ed. Slater Pergamon Press 1963.
• R. Stuart Mackay, Biomedical Telemetry, 2nd edition. John Wiley 1968
• Thomas Fryer, Implantable Biotelemetry systems. NASA. 1970
• Biotelemetry III, ed. By T. Fryer, H. Miller, and H. Sandler 1976
• Klaas Kramer, Applications and Evaluation of Radio-telemetry in Small Laboratory Animals. PhD
Thesis Vrije University 1990
• Brian Brockway and Craig Hassler, Application of radiotelemetry to cardiovascular measurements in
pharmacology and toxicology. In New Technologies and concepts for reducing drug toxicity.
Pp 109-132. CRC Press 1993.
Predicting the Liability and
Safety of Test Articles By
Implantable Telemetry
Robert Hamlin, PhD
DVM, DACVIM, DSPS
QTest Labs and The
Ohio State University
Copyright InsideScientific & QTest Labs. All Rights Reserved.
Presumptive Knowledge…
1. What are the parameters to be investigated?
2. What difference in them translates to benefit or risk?
3. How can they be measured with the precision
required and safety assured, without distorting them?
Parameters, which if affected, are known to
translate to morbidity or mortality…
1. Chronotrope
2. Inotrope
3. Lusitrope
4. Energetic balance
5. Opposition to Ejection:
impedance and
resistance
6. Venous Capacity
7. Baroreceptor function:
high and low pressure
8. Cardiac output and
fractionation
9. Dromotrope
10. Irritability
SA Node
How Can They Be Measured?
1. ECG (PQ, QRS, QT)
2. Pressure (AoP, LVP, dP/dt)
3. Blood Flow (CO, SV, Vp)
4. PV Loops (inotrope, lusitropy, SV, Ea, ESPVR, PRSW, VO2)
5. Imaging (Echo, MRI, CT)
6. ???
Aortic
Pressure
Left Ventricular
Pressure
Left Atrial
Pressure
Left Ventricular
Wall Thickness
Left
Ventricular
Volume
Left Ventricular
Wall Tension
Coronary
Blood Flow
1 2 3 4 5 6 7 8
ventricular diastolic
suction
EDV
ESV
EDWT
Peak=AL
ESWT
ventricular diastolic
suction
ventricular systolic
suction
After Wiggers
Left Ventricular
Pressure
Coronary
Blood Flow
Left Ventricular
Pressure
Left Ventricular
Volume
Left Ventricular
Wall Thickness
Left Ventricular
Wall Tension
3 2 1 6 5 4 3
curve
s
EDV EDV ESV
mitral
valve
aortic
valve
A-V
ring is
“pulled”
down
ESV
Phonocardiogram S4 S1 S2 S3
Electrocardiogram
P Ta QRS
T
QT
J-Point
ST-T
SV = stroke volume (EDV-ESV)
time = time between heart beats=1/heart rate
w = wave
r = reflected
i = initial
t = total
f = function of
svr = systemic vascular resistance
f(SV,εAo)
f(svr, εAo, time)
atrial “kick”
Isovolumetric
contraction
mean pressure=DP+(PS-DP)/3
Peak Systolic Pressure (PS)
“Diastolic” Pressure (DP)
Late systolic augmentation
Pulsepressure
• Pulse Pressure is
a predictor of
morbidity and
mortality
• Peak Systolic
Pressure is a
predictor of stroke
• Diastolic Pressure
is a predictor of
heart failure
-3000
-1000
1000
3000
5000
7000
9000
11000
13000
0
20
40
60
80
100
120
140
ECG
PAo
dLVP/dt
LVP
Pulse
Systolic
LV
Mean
Diastolic
EDV = (EDP - PPL) / LV
ESV
1
2
1
2
V
ADH/VP
AII
ANF
NO
ET1
Adenosine
Rx’s
SAP
CO
Ao,svr arterial smooth muscle
SV
HR SAN
Ao, svr
vmax
BV = (waterin - urineout)
Cv
“a kick”
●
●
-
lung Affectors
After Rushmer
SV
HR SAN
EDV = (EDP - PPL) / LV
ESV
1
2
1
2
V
ADH/VP
AII
ANF
NO
ET1
Adenosine
Rx’s
SAP
CO
Ao,svr arterial smooth muscle
Ao, svr
vmax
BV = (waterin - urineout)
Cv
“a kick”
●
●
-
lung Affectors
After Rushmer
EDV = (EDP - PPL) / LV
ESV
1
2
1
2
V
ADH/VP
AII
ANF
NO
ET1
Adenosine
Rx’s
SAP
CO
Ao,svr arterial smooth muscle
SV
HR SAN
Ao, svr
vmax
BV = (waterin - urineout)
Cv
“a kick”
●
●
-
lung Affectors
After Rushmer
So, we know what to measure,
and how to measure it precisely and safely.
Unfortunately nobody will tell us — for anything
but QTc — what difference makes a difference!
Therefore, how do we know with what precision a
measurement should be made, or even if it should
be made?
Thank You!
SESSION 2: Freedom: The Promise of Telemetry
Revisited - “The Freedom To Move Anywhere At
Anytime And Still Collect Quality Data”
REGISTER FOR OUR SERIES @ WWW.INSIDESCIENTIFIC.COM
ACCESS THE RECORDING AND SUPPLIMENTARY MATERIALS
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JOIN OUR GROUP ON LINKEDIN FOR INFORMATION
ON UPCOMING EVENTS, ON-DEMAND WEBINARS,
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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.

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The Evolution of Wireless Monitoring in The Life Sciences and Review of Industry Standards in Drug-discovery and Safety Pharmacology and Toxicology

  • 1.
  • 2. Welcome to “Biotelemetry For The Life Sciences”, Session 1: The Evolution of Wireless Monitoring in The Life Sciences and Review of Industry Standards in Drug-discovery and Safety Pharmacology and Toxicology Guest Speakers: Brian Brockway President, VivaQuant, LLC Robert Hamlin, PhD DVM, DACVIM, DSPS QTest Labs and The Ohio State University
  • 3. 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.
  • 4. Implantable Telemetry: Past, Present, and Future Brian Brockway President, VivaQuant, LLC Copyright InsideScientific & VivaQuant, LLC. All Rights Reserved.
  • 5. Why Use Implantable Telemetry? 1. Reduce impact of stress as a confounding factor1 2. Percutaneous infections eliminated1 3. Improve safety of lab personnel1 4. Enables longitudinal studies that are otherwise1 impossible 5. Improves animal welfare2 6. Fewer animals3 1. Brian Brockway and Craig Hassler 1993 2. Klaas Kramer 2000 3. Lew Kinter 1994
  • 6. 0 100 200 300 400 500 600 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 Discovery Home-made Commercialization Validation Mainstream Publication Growth Every 5 Years Adoption Phases of Implantable Telemetry … increase in publications follows availability of commercial product (EST) *
  • 8. We’ve Come A Long Way!
  • 9. Enabling Innovation – Packaging 1. Impervious to moisture 2. Radio Frequency transparent 3. Cost effective, reliable and scalable From: Brockway and Hassler 1993
  • 10. Enabling Innovation – Sensors 1. Sensor Stability -- Stanford & NOVASensor 2. Long-term pressure sensor patency 3. Size -- small sensors for small spaces From: Brockway and Hassler 1993
  • 11. Key Contributors to Mainstream Commercialization 1. Stuart Mackay, UCSF 2. Wen Ko, Case Western 3. Thomas Fryer, NASA 4. James Meindl, Stanford 5. Dave Osgood, MiniMitter 6. Bill Barrows, NASA
  • 12. Early Data Supporting Implantable Telemetry• Lappe et. al instrument six rats and measure MAP before and after placing rats in tail- cuff restraints • Early BP implant seeking validation proves not only viable, but uncovers SHR mystery… • Strain of rats thought to be hypertensive proven to be hypertensive only when subjected to stress From: Brockway and Hassler 1993
  • 13. • Combined Pressure and Blood Flow • Glucose • Chemical Entities • O2/CO2 Saturation • Advanced ECG
  • 14. Continuing Challenges… • More reliable devices – Electrical interference – Failure due to moisture penetration • Small devices with longer sending range – Lower infection risk – Easier/faster surgical procedure • Improved processing of signals and mining of data
  • 15. What do we know? What next?... • Its come a long way since the first implant in 1960 • Now commonly used for EEG, ECG, pressure, temperature • New suppliers will bring more options & innovation • However, there’s still a long way to go to reach full potential
  • 16. References • Proceedings of the interdisciplinary conference on the use of telemetry in animal behavior and physiology in relation to ecological problems. Ed. Slater Pergamon Press 1963. • R. Stuart Mackay, Biomedical Telemetry, 2nd edition. John Wiley 1968 • Thomas Fryer, Implantable Biotelemetry systems. NASA. 1970 • Biotelemetry III, ed. By T. Fryer, H. Miller, and H. Sandler 1976 • Klaas Kramer, Applications and Evaluation of Radio-telemetry in Small Laboratory Animals. PhD Thesis Vrije University 1990 • Brian Brockway and Craig Hassler, Application of radiotelemetry to cardiovascular measurements in pharmacology and toxicology. In New Technologies and concepts for reducing drug toxicity. Pp 109-132. CRC Press 1993.
  • 17. Predicting the Liability and Safety of Test Articles By Implantable Telemetry Robert Hamlin, PhD DVM, DACVIM, DSPS QTest Labs and The Ohio State University Copyright InsideScientific & QTest Labs. All Rights Reserved.
  • 18. Presumptive Knowledge… 1. What are the parameters to be investigated? 2. What difference in them translates to benefit or risk? 3. How can they be measured with the precision required and safety assured, without distorting them?
  • 19. Parameters, which if affected, are known to translate to morbidity or mortality… 1. Chronotrope 2. Inotrope 3. Lusitrope 4. Energetic balance 5. Opposition to Ejection: impedance and resistance 6. Venous Capacity 7. Baroreceptor function: high and low pressure 8. Cardiac output and fractionation 9. Dromotrope 10. Irritability SA Node
  • 20. How Can They Be Measured? 1. ECG (PQ, QRS, QT) 2. Pressure (AoP, LVP, dP/dt) 3. Blood Flow (CO, SV, Vp) 4. PV Loops (inotrope, lusitropy, SV, Ea, ESPVR, PRSW, VO2) 5. Imaging (Echo, MRI, CT) 6. ???
  • 21. Aortic Pressure Left Ventricular Pressure Left Atrial Pressure Left Ventricular Wall Thickness Left Ventricular Volume Left Ventricular Wall Tension Coronary Blood Flow 1 2 3 4 5 6 7 8 ventricular diastolic suction EDV ESV EDWT Peak=AL ESWT ventricular diastolic suction ventricular systolic suction After Wiggers
  • 23. Left Ventricular Pressure Left Ventricular Volume Left Ventricular Wall Thickness Left Ventricular Wall Tension
  • 24. 3 2 1 6 5 4 3 curve s EDV EDV ESV mitral valve aortic valve A-V ring is “pulled” down ESV Phonocardiogram S4 S1 S2 S3 Electrocardiogram P Ta QRS T QT J-Point ST-T
  • 25. SV = stroke volume (EDV-ESV) time = time between heart beats=1/heart rate w = wave r = reflected i = initial t = total f = function of svr = systemic vascular resistance f(SV,εAo) f(svr, εAo, time) atrial “kick” Isovolumetric contraction mean pressure=DP+(PS-DP)/3 Peak Systolic Pressure (PS) “Diastolic” Pressure (DP) Late systolic augmentation Pulsepressure
  • 26. • Pulse Pressure is a predictor of morbidity and mortality • Peak Systolic Pressure is a predictor of stroke • Diastolic Pressure is a predictor of heart failure
  • 28. EDV = (EDP - PPL) / LV ESV 1 2 1 2 V ADH/VP AII ANF NO ET1 Adenosine Rx’s SAP CO Ao,svr arterial smooth muscle SV HR SAN Ao, svr vmax BV = (waterin - urineout) Cv “a kick” ● ● - lung Affectors After Rushmer
  • 29. SV HR SAN EDV = (EDP - PPL) / LV ESV 1 2 1 2 V ADH/VP AII ANF NO ET1 Adenosine Rx’s SAP CO Ao,svr arterial smooth muscle Ao, svr vmax BV = (waterin - urineout) Cv “a kick” ● ● - lung Affectors After Rushmer
  • 30. EDV = (EDP - PPL) / LV ESV 1 2 1 2 V ADH/VP AII ANF NO ET1 Adenosine Rx’s SAP CO Ao,svr arterial smooth muscle SV HR SAN Ao, svr vmax BV = (waterin - urineout) Cv “a kick” ● ● - lung Affectors After Rushmer
  • 31. So, we know what to measure, and how to measure it precisely and safely. Unfortunately nobody will tell us — for anything but QTc — what difference makes a difference! Therefore, how do we know with what precision a measurement should be made, or even if it should be made?
  • 32. Thank You! SESSION 2: Freedom: The Promise of Telemetry Revisited - “The Freedom To Move Anywhere At Anytime And Still Collect Quality Data” REGISTER FOR OUR SERIES @ WWW.INSIDESCIENTIFIC.COM
  • 33. ACCESS THE RECORDING AND SUPPLIMENTARY MATERIALS FOR THIS EVENT AND OTHERS AT INSIDESCIENTIFIC.COM/PAST-EVENTS JOIN OUR GROUP ON LINKEDIN FOR INFORMATION ON UPCOMING EVENTS, ON-DEMAND WEBINARS, AND ADDITIONAL LAB RESOURCES
  • 34. 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.