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Temperature, oncology, cancer

Monitoring Temperature in Tumors

 

Continuously monitoring temperature in oncology studies gives researchers a better understanding of tumor burden, therapeutic response, immunity status, and stress response. 


Temperature in Oncology Research
Temperature is a valuable biomarker in understanding physiological responses in acute and chronic studies. Researchers monitor temperature as an early indicator of disease and response in animals and humans. Temperature is considered highly translatable to the clinical setting and cancer researchers use data collected to assess tumor burden, therapeutic response, immunity status, and stress.1

In addition to using temperature as a biomarker to tumor and health progression, researchers are using temperature to help increase uptake of cancer therapies.  Hyperthermia is being used as an adjunct cancer treatment in the clinical setting to promote tumor-treatment response.  Temperatures of between 38.5 and 42 degrees Celsius have been shown to decrease hypoxia within the tumor microenvironment, improve efficacy of immunotherapies, and increase production of pro-inflammatory cytokines.2  


3,380
temperature publications citing DSI in 
Google Scholar


Animal models

Monitoring core body temperature continuously with implantable telemetry is the gold standard of thermoregulatory measurements and helps researchers understand how a drug, therapy or disease state impact's the animal's ability to regulate temperature,Temperature continues to be an important biomarker in almost every study, because it impacts endpoints like heart rate, blood pressure, neurological function, metabolism immune response and behavior as the body generates and dissipates heat. 

Looking at thermoregulation is done in a variety of species, from mouse to non-human primate.  With temperature being one of the first signs of disease, it is also being used in a variety of disease models.  To understand which temperature has the greatest impact on tumor response, researchers are monitoring core body temperature, subcutaneous temperature, and local temperature.  Heart rate and physical motor activity are additional endpoints that are observed to assess for overall health of the animal. 

In order to understand if a drug or therapy impacts the chosen animal model's ability to regulate temperature, it is important to understand its thermal regulatory characteristics including its thermoneutral zone.  The thermoneutral zone is defined as the range of ambient temperatures where core temperature is controlled without significant changes in metabolic heat production.  Ambient temperature, age, species and gender all play a role in affecting the animal’s thermoneutral zone.




Methods
Below are thermoregulator indicators and parameters researchers are using in animal studies. 
Core Body Temperature

This can be measured via telemetry by implanting a temperature telemetry device in the intraperitoneal space.  Rectal probes have been used for this measurement in the past and are best used in acute monitoring of anesthetized animals.  Core temperature may be averaged over time in most cases, but before averaging, ensure you understand the particular animal's circadian rhythm whether it be daily, weekly, or monthly so you can accurately subtract the normal rhythm to detect a true fever.

Subcutaneous Temperature

Infrared cameras can capture skin temperature gradients in some cases.  Fur from the animal may impede the measurement.  Peripheral temperature measurements can also be taken by placing a temperature telemetry device subcutaneously or via a hardwired thermistor probe in anesthetized models.

Local Temperatures

In some animal models, specific localized temperatures may be recorded such as Brown Adipose Tissue (BAT), brain, tail, or other specific tissue and organ temperatures.  A thermistor at the end of a temperature probe may be required to enable this measurement.  DSI offers telemetry products which have external thermistor probes for use in small animals.  These are commonly used in neonatal, target organ and metabolic studies looking at quick temperature changes.

 









Temp 

DSI Temperature Sensing Technology

DSI telemetry is completely implantable and designed for acquiring physiologic data from conscious, freely moving laboratory animals, reducing animal stress and ensuring the most reliable data. Our temperature monitoring technology offers researchers the ability to observe real-time core, subcutaneous, and/or local temperatures. Almost telemetry implants from DSI have the ability to monitor core body temperature, heart rate and activity with other endpoints. Below you will find devices that are strictly used to monitor temperature, heart rate and activity. 



Temperature Only Telemetry Implants for Mouse (Miniature), Small Animal, and Large Animal Models
PhystioTel temperature only implants are designed for use in a range of research models, from mice to non-human primates. For more information about DSI telemetry implants that measure temperature along with additional endpoints, visit our implantable telemetry site.


TA F10

TA F40

     F40 TT

M00

 




The Power of Ponemah Software
Data collection and analysis for preclinical studies

High resolution image (139 KB)


Easy Experiment Management
  • Save time with intuitive user interface and automated subject setup 
  • Simplify data management with automated file handling
  • Review previous days’ results during acquisition to observe mid-experiment data
  • Visualize sampling configuration and protocols with tabbed sampling layout
  • Use scheduled sampling function to collect periodic data from more subjects at user-defined intervals

Robust Connectivity with 3rd Party Solutions
  • Acquire high quality video recordings in Ponemah's integrated solution with Noldus Media Recorder and synchronize with physiologic signals for better interpretation of your data
  • Import and analyze CNS data - EEG and EMG data with video recordings - in NeuroScore Data Analysis Software 
  • Allow 3rd party applications to view Ponemah derived parameter data with Remote Connection

Flexible Data Analysis
  • Analyze data using time-based averages or on a beat-by-beat basis
  • Immediate results with real-time parameter calculations and trend graph generation
  • Complete control of data analysis with adjustable settings to analyze signals from various species and unique morphologies
  • Automatic export of calculated data to MS Excel® to view and analyze results across multiple days of acquisition
Smart, Powerful Tools
  • Refine data analysis post-acquisition to change how parameters are measured or eliminate signal noise from results
  • Use multiple graph and reporting presentations to view, sort and sync calculated parameters
  • Select data sections to view and report using Data Reduction and Data Parser rules.
  • Receive automated email or text alerts for subject- and system-level conditions

ScheduledSampling

Flexible Licensing Options
  • 3, 6, and 12 month subscription or full purchase options
  • Available for acquisition and post-analysis systems, plus analysis modules
  • Ideal for trials and short-term studies


Learn More About the Power of Ponemah Software


Ponemah Full System Package

Temperature system set up

Receivers and Transceivers
Telemetry implants broadcast telemetry data via radio frequency signals to the receiver or transceiver located under or near the cage. Multiple options exist and selection depends on study design. 

Communication Manager
The MX2 for small animals or the CLC for large animals manage communication between your chosen implant and Ponemah software. Fully calibrated telemetry data acquisition, optimized to maintain data integrity throughout the system. 

Network Hardware
DSI recommends using a dedicated network to permit the hardware to communicate to the computer. A router is used to assign IP addresses and a switch with PoE (Power over Ethernet) is used to power the hardware and allow multiple connections to the network. 




Temperature References Citing DSI Technology
General Best Practices
  • Gordon, C. J. "Thermal physiology of laboratory mice: Defining thermoneutrality." Journal of Thermal Biology (2012).
  • Swoap, Steven J., J. Michael Overton, and Graham Garber. "Effect of ambient temperature on cardiovascular parameters in rats and mice: a comparative approach." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 287.2 (2004): R391-R396. 
  • POSTER: Setser, J. J. 2009. "Comparison of rectal, transponder, and telemetry thermometry for collection of body temperatures in rats, dogs and monkeys."
Rodent References
  • Colbourne, Frederick, Garnette R. Sutherland, and Roland N. Auer. "An automated system for regulating brain temperature in awake and freely moving rodents." Journal of neuroscience methods 67.2 (1996): 185-190.
  • DeBow, Suzanne, and Frederick Colbourne. "Brain temperature measurement and regulation in awake and freely moving rodents." Methods 30.2 (2003): 167-171.
  • Leon, Lisa R., et al. "Biotelemetry transmitter implantation in rodents: impact on growth and circadian rhythms." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 286.5 (2004): R967-R974.
  • Hasegawa, Hiroshi, et al. "Alteration in dopamine metabolism in the thermoregulatory center of exercising rats." Neuroscience letters 289.3 (2000): 161-164.
  • Sakurada, Sotaro, et al. "Autonomic and behavioural thermoregulation in starved rats." The Journal of Physiology 526.2 (2000): 417-424.
  • Eliason, Heather L., and James E. Fewell. "Thermoregulatory control during pregnancy and lactation in rats." Journal of Applied Physiology 83.3 (1997): 837-844.
  • POSTER: Grippo, AJ. Allen, SM. Chandler, DL. Dave, P. McDaniel, V. McNeal, N. 2010. "A Comparison of two radiotelemetry transmitters for the recording of behavioral and electrocardiographic data in prairie voles (Microtus Ochrogaster)"
  • POSTER: Bracq. E, Maurin. A, Champeroux. P, Richard. S. "Measurement of tail skin temperature in ovariectomised rats: A model of hot flushes."
Mouse References
  • Duffy, P. H., R. J. Feuers, and R. W. Hart. "Effect of age and torpor on the circadian rhythms of body temperature, activity, and body weight in the mouse (Peromyscus leucopus)." Progress in clinical and biological research 227 (1987): 111.
  • Kramer, Klaas, et al. "Effect of conditioning on the increase of heart rate and body temperature provoked by handling in the mouse." ATLA. Alternatives to laboratory animals 32 (2004): 177-181.
  • Mitchell, Gary F., Andreas Jeron, and Gideon Koren. "Measurement of heart rate and QT interval in the conscious mouse." American Journal of Physiology-Heart and Circulatory Physiology 274.3 (1998): H747-H751.
  • Slade, R. A. L. P. H., WILLIAM P. Watkinson, and GARY E. Hatch. "Mouse strain differences in ozone dosimetry and body temperature changes."American Journal of Physiology-Lung Cellular and Molecular Physiology 272.1 (1997): L73-L77.
  • POSTER: Meijer. 2000.  "Implantation of a radio-telemetry transmitter in the mouse: some practical considerations."
Guinea Pig References
  • Provan, Gayle, et al. "Development of a surgical approach for telemetering guinea pigs as a model for screening QT interval effects." Journal of pharmacological and toxicological methods 52.2 (2005): 223-228.
  • Stemkens-Sevens, Sylvia, et al. "The use of radiotelemetry to assess the time needed to acclimatize guineapigs following several hours of ground transport." Laboratory animals 43.1 (2009): 78-84.
  • POSTER: Betat, A. M. 2004. "Influence of hypokalemia on drug induced qt prolongation in the conscious telemetered guinea pig."
  • Crisanti, K. C. 1999. "Aminophylline alters the core temperature response to acute hypoxemia in newborn and order guinea pigs." Journal of Physiology 46 (1999)
  • POSTER: Mumford. "The impact of anesthetic, surgery and saline administration on guinea pig spontaneous cage activity."
Ferret References
  • POSTER: Main, Brad.  2011.  "Ferrets-A Small Alternative to Dogs in Cardiovascular Pharmacology Studies."
Rabbit References
  • Lawrence, William S., et al. "The physiologic responses of Dutch belted rabbits infected with inhalational anthrax." Comparative medicine 59.3 (2009): 257.
  • POSTER: Bynum, K.S. 2008. "Validation of the Rabbit Telemetry Model for Cardiovascular Safety Pharmacology studies.
Dog References
  • Gauvin, David V., et al. "Electrocardiogram, hemodynamics, and core body temperatures of the normal freely moving laboratory beagle dog by remote radiotelemetry." Journal of pharmacological and toxicological methods 53.2 (2006): 128-139.
  • Kearney, Kenneth, et al. "Evaluation of respiratory function in freely moving Beagle dogs using implanted impedance technology." Journal of pharmacological and toxicological methods 62.2 (2010): 119-126.
  • POSTER: Kishimoto, T. "Inter-facility differences in electrocardiographic and hemodynamic parameters in anesthetized dogs."
  • POSTER: Stewart, L. A. 2000. "Comparison of telemetric thermometry and manual rectal temperature recordings in the beagle dog."
Non-Human Primate References
  • Speece, Ty, et al. "Validation of the jacketed, external telemetry JET™ system for monitoring ECGs in non-human primates." Journal of Pharmacological and Toxicological Methods 58.2 (2008): 154.
  • Baird, T. J., et al. "Simultaneous assessment of ECGs using intracardiac and subcutaneous leads under various environmental conditions in non-human primates." Journal of Pharmacological and Toxicological Methods 56.2 (2007): e33.
  • Perret, M., and F. Aujard. "Daily hypothermia and torpor in a tropical primate: synchronization by 24-h light-dark cycle." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 281.6 (2001): R1925-R1933.
  • POSTER: Crosby, N. 2008. "Identification of Behavior and Position-related artifacts in nonhuman primate telemetry using a time-synchronized video telemetry system."  *if interested in this article see ILF!
  • POSTER: Willens, S. 2009.  "Body temperature analysis in three species of nonhuman primates after exposure to aerosolized bacillus anthracis."
Pig References
  • Jørgensen, Henry, and Peter Kappel Theil. "Use of telemetry technique in research with pigs." Use of telemetry technique in research with pigs: 6-6.
  • de Jong12, Ingrid C., et al. "Mixing induces long-term hyperthermia in growing pigs." CHRONIC STRESS PARAMETERS IN PIGS 69 (1999): 109.
  • Theil, Peter Kappel, et al. "Relation between oxygen consumption and heart rate in four breeds of pigs measured in short-and long-term changes of environmental temperature." Energy metabolism in animals. Proceedings of the 15th symposium on energy metabolism in animals, Snekkersten, Denmark, 11-16 September 2000.. Wageningen Pers, 2001.
  • Jørgensen, Henry, et al. "Surgical techniques for quantitative nutrient digestion and absorption studies in the pig." Livestock Science 133.1 (2010): 57-60.
  • Skytte, Christina, and A. Makin. "Measurement of cardiovascular effects in minipigs using telemetry." Journal of Pharmacological and Toxicological Methods 58.2 (2008): 172.
  • Mesangeau. "Six month telemetric study shows development of cardiovascular autonomic neuropathy in diabetic miniature pigs." Cardiovascular Research 45 (2000).
  • Dauncey. "Radiotelemetry of deep body temperature from one piglet within a group." Journal of Physiology 371 (1986)


References

1 J E Hunter, J Butterworth, N D Perkins, M Bateson, & C A Richardson. (2014). Using body temperature, food and water consumption as biomarkers of disease progression in mice with Eμ-myc lymphoma. British Journal of Cancer, 110(4), 928-34.

2 Repasky, E. A., Evans, S. S., & Dewhirst, M. W. (2013). Temperature Matters! And Why it Should Matter to Tumor Immunologists. Cancer Immunology Research, 1(4), 210–216. http://doi.org/10.1158/2326-6066.CIR-13-0118

3 Fischer, A. W., Cannon, B., & Nedergaard, J. (2018). Optimal housing temperatures for mice to mimic the thermal environment of humans: An experimental study. Molecular Metabolism, 7, 161–170. http://doi.org/10.1016/j.molmet.2017.10.009