Grant and Budget Justification

Implantable telemetry solutions allow for in vivo physiologic monitoring of freely moving animals.  Implants are available in a variety of sizes to accommodate species and cage size requirements. The implant transmits information wirelessly, providing the most reliable and efficient method of measuring physiologic parameters such as blood pressure, left ventricular pressure, electrocardiogram (ECG), electroencephalogram (EEG), electromyogram (EMG), core and subcutaneous temperature, and activity. 

Implantable telemetry is superior to tethered physiologic monitoring options in terms of animal welfare and reproducibility.  The handling required with tethered solutions interferes with the animal’s natural habitat or existence, and can elevate stress, influencing physiologic signals.

Implantable telemetry supports the “three R’s” of animal welfare: replacement, reduction, and refinement. Data is more reliable, allowing researchers to use fewer animals per study and reduce pain and stress. 

DSI's PhysioTel, PhysioTel HD, and PhysioTel Digital telemetry allow continuous monitoring, rather than periodically collecting a manual data point.  Continuous data show a more accurate picture as information could be missed if data points are collected periodically. 

Implantable telemetry has been referenced in thousands of publications verifying their performance in vivo in many different animal models. 

To lower the overall cost of ownership, DSI offers an implant exchange program, allowing researchers to trade used implants for new at a lower cost than initial purchase.  Each implant is hand assembled by DSI’s highly skilled technicians and receives 100% inspection to ensure that all components meet our quality standards.  Several steps are taken to ensure the device is biocompatible and guaranteed to perform to specifications in vivo including:

• Installing a new battery to guarantee functionality over the warranty period
• Packaging in a biocompatible housing
• Attachment of biopotential leads and catheters to provide signal fidelity
• Pre-shipment sterilization

 References

1. ALN Magazine. Telemetry 101. https://www.alnmag.com/article/2017/06/telemetry-101. Accessed 22 Aug 2017.
2. Cesarovic N., Jirkof P., Rettich A., Arras M. (2011). Implantation of radiotelemetry transmitters yielding data on ECG, heart rate, core body temperature and activity in free-moving laboratory mice. Journal of Visualized Experiments. 21;(57). pii: 3260. doi: 10.3791/3260
3. Kadam S., White A., Staley K., Dudek F. (2010). Continuous Electroencephalographic Monitoring with Radio-Telemetry in a Rat Model of Perinatal Hypoxia–Ischemia Reveals Progressive Post-Stroke Epilepsy. The Journal of Neuroscience. 30(1):404-415. doi:10.1523/JNEUROSCI.4093-09.2010.
4. NC3Rs. The 3Rs. http://nc3rs.org.uk/the-3rs. Accessed 21 Aug 2017.
5. Wang Y., Thatcher S., Cassis L. (2017). Blood Pressure Monitoring Using Radio Telemetry Method in Mice. Methods in Molecular Biology. 1614:75-85. doi: 10.1007/978-1-4939-7030-8_7.

Digital Large Animal Telemetry

PhysioTel Digital eliminates data contamination from ambient noise or a neighboring animal, where analog technology may have increased variation in results.  Each digital implant has a unique encoded animal ID, ensuring traceability and GLP compliance.

With this technology, a variety of physiologic signals can be collected from a single animal including 2 pressures, multiple biopotential signals, temperature, and activity.  Additional parameters can be derived from the physiologic data such as heart rate and systolic, diastolic, and mean pressure.

PhysioTel Digital includes remote programming capabilities which allow the researcher to start and stop collection without entering the animal lab to activate devices in animals.  This capability minimizes human-animal interaction, resulting in animals that are less stressed and a safer environment for technicians.

References:

1. Andersen NK., Meyer O., Bradley A., Dragsted N., Lassen AB., Sjögren I., Larsen JM., Harvey W., Bator R., Milne A. (2017). Evaluation of the PhysioTel™ Digital M11 cardiovascular telemetry implant in socially housed cynomolgus monkeys up to 16weeks after surgery. J Pharmacol Toxicol Methods. Doi: 10.1016/j.vascn.2017.04.007.
2. Cordes JS., Heyen JR., Volberg ML., Poy N., Kreuser S., Shoieb AM., Steidl-Nichols J. (2016). Validation and utility of the PhysioTel™ Digital M11 telemetry implant for cardiovascular data evaluation in cynomolgus monkeys and Beagle dogs. J Pharmacol Toxicol Methods. 79: 72-9.

Hybrid Digital Small Animal Telemetry

PhysioTel HD implants enable collection of various physiologic parameters from mice, rats, hamsters, and other small animals.  Each implant has an animal ID encoded with the telemetry signal to ensure data traceability from the implant to the computer database.

With this technology, two pressures, two biopotentials, blood glucose, temperature, and activity can be monitored in large rodents.  A single implant can also simultaneously measure one pressure, a biopotential, temperature, and activity in mice as small as 19 grams.

Remote battery monitoring capabilities of the system allows for better planning for product end of life.  Automatic loading of device calibrations eliminates the need to keep close track of calibrations and the possibility of human error, maximizing product life and minimizing technician time.

References:

1. Zheng W., McKinney W., Kashon M., Salmen R., Castranova V., Kan H. (2016). The influence of inhaled multi-walled carbon nanotubes on the autonomic nervous system. Particle and Fibre Toxicology. 13:8. DOI: 10.1186/s12989-016-0119-7.

Noise reducing plethysmographs decrease environmental noise in the data collected by ensuring both sensing ports on the differential pressure transducer measure the same pressure from an atmospheric event. 

Restraints which secure animals without compressing the thorax and keep airways completely unobstructed improve animal comfort and data quality as the animal can breathe more naturally. Traditional methods rely on a plunger to restrain, which compresses the animal. Breathing patterns observed using a plunger are unnatural, and frequently exhibit inspiratory holds as the animal struggles to breathe.

Studies have been conducted comparing the DSI Allay™ with traditional plunger style methods to test stress levels in restrained animals.^1,3,4  Animals were instrumented with implantable telemetry to measure cardiovascular and respiratory endpoints such as heart rate, blood pressure, mean arterial pressure, respiratory rate, tidal volume, and minute volume.  Through reduction of these endpoints, the study confirmed less stress with the Allay™ restraint than with other technologies.  As the animal is less stressed, breathing naturally, and positioned properly, studies with the Allay™ restraint are more reproducible and superior for animal welfare than alternative methods.  The more traditional “plunger” method allows for much greater variation in data as the position of the animal depends on the pressure a researcher applies with the plunger.  Positioning of the animal is key to getting good data, especially when used with an inhalation tower.  Inhalation towers feature a “flow past” concentric design, delivering the same exposure to all animals.  If the animals are not positioned in a consistent way, there will be variation in exposure.

Automatic calibration and system diagnostic tests ensure all equipment is functioning and calibrated properly, thus removing the possibility of human error.  Traditionally, calibration was performed manually by injecting air into chambers.  There was significant variability with this calibration, such as how steadily the air was injected, and no verification that calibration was successful.  Without proper calibration, data quality and study reproducibility can suffer.  Within the Buxco systems calibration protocol, all transducers are calibrated, valves are tested for functionality and leaks, reservoirs are tested for leaks, the bias flow is calibrated and tested for accuracy, and the temperature and humidity sensors are tested and calibrated.  Once this process is complete, the system advises the user whether the system is functioning properly or if there are any issues, providing assurance prior to beginning a study.

All of DSI’s Buxco respiratory equipment can be used with a single software platform, FinePointe.  This allows users to perform various types of respiratory experiments without having to maintain multiple software platforms.

Whole Body Plethysmography

Whole Body Plethysmography is a technique where respiratory endpoints are collected from unanesthetized and unrestrained animal models, by means of a pneumotach, differential pressure transducer, and specialized software with calculations that generate physiologically relevant data.  This technique is ideal for studies that are longitudinal in nature, need to be noninvasive, and can collect from many subjects in a highly efficiency manner.  Parameters such as Tidal Volume, Breathing Frequency, Minute Volume, Inspiration Time, Expiration Time, Peak Inspiratory Flow, Peak Expiratory Flow, EF50, Rpef, PenH, and more, are all possible with this system. The FinePointe© solution from DSI/Buxco is the gold standard Whole Body Plethysmography system, with an integrated digital controller that runs complex diagnostics and calibrations with a single click, provides fresh air via clean low-noise pumps to enhance signal fidelity, can administer automated aerosol or gas challenges, and generates automated reports that can include additional parameters such as respiratory metabolism, video recording, and apnea scoring.

Non-Invasive Airway Mechanics (Double Chamber)

Double-chamber plethysmography is a technique where respiratory endpoints are collected from unanesthetized and restrained animal models, by means of a pair of pneumotachs and differential pressure transducers per chamber, and specialized software with calculations that generate physiologically relevant data.  This technique is ideal for studies that are longitudinal in nature, need to be noninvasive, and can collect from subjects in an efficient manner with no surgery or anesthesia.  Parameters such as Tidal Volume, Breathing Frequency, Minute Volume, Inspiration Time, Expiration Time, Peak Inspiratory Flow, Peak Expiratory Flow, EF50, Rpef, , and more, are all possible with this system.  The ‘double-chamber’ aspect allows for the assessment of airway resistance by measuring the phase shift between nasal and thoracic flows, and calculating a parameter called Specific Airway Resistance (sRaw).  This is different than the Enhanced Pause (PenH) parameter calculated from Whole Body Plethysmography, which is an indirect indicator of bronchoconstriction rather than a direct measure of thoracic-to-nasal phase shift.  Asthma research in particular normally utilizes a Methacholine Dose Response challenge to compare increasing levels of airway resistance in awake subjects.  The FinePointe© Noninvasive Airway Mechanics (NAM) solution from DSI/Buxco is the gold standard double-chamber system, with an integrated digital controller that runs complex diagnostics and calibrations with a single click, calculates Time Constants automatically during calibration to enhance accuracy of resistance measurements, provides fresh air via clean low-noise pumps to enhance signal fidelity, can administer automated aerosol challenges, and generates automated reports that quickly allow examination of key parameters from a large number of subjects over any length of time. The FinePointe system also utilizes a unique and patented method of restraining rodents called the ‘Allay’ which uses a collar and latex seal rather than a plunger from behind, allowing the subjects to reach a more natural breathing position and better isolate the nasal and thoracic chambers, ultimately leading to more accurate measurements and better data integrity overall.

References:

1. Chapman R., (2013) Use of the Allay Restraint Collar to Facilitate the Measurement of Ventilation in Conscious Rats.
2. da Silva A., Magalhães R., Branco V., Silva J., Cruz F., Marques P., Ferreira T., Morales M., Martins M., Olsen P., and Rocco P. (2016) The tyrosine kinase inhibitor dasatinib reduces lung inflammation and remodelling in experimental allergic asthma. British Journal of Pharmacology, 173: 1236–1247. doi: 10.1111/bph.13430.
3. Fischer KD., Hall SC., Agrawal DK. (2016) Vitamin D Supplementation Reduces Induction of Epithelial-Mesenchymal Transition in Allergen Sensitized and Challenged Mice. PLoS ONE 11(2): e0149180. https://doi.org/10.1371/journal.pone.0149180
4. House A., Girand M. Inhalation Exposure Systems for Aerosol Delivery Advancements: Perspective from a Bench Scientist [webinar]. April 30, 2015. http://xtalks.com/Inhalation-Exposure-Systems-for-Aerosol-Delivery.ashx.
5. Kearney, K., Pittman, R., Appleby, C., Roche, B. (2017) Are All Respiratory Chambers Created Equal? A Comparative Assessment Between Allay Restraint and Standard Head Out Plethysmography. Journal of Pharmacological and Toxicological Methods. 88 part 2: 234. https://doi.org/10.1016/j.vascn.2017.09.215
6. Roche B., Payseur J. Combining Cardiovascular, Respiratory and Neurobehavioral Endpoints for Efficient Study Design [webinar]. October 20, 2016. http://insidescientific.com/webinar/combining-cardiovascular-respiratory-and-neurobehavioral-endpoints-datasci/. 

Ponemah is a robust, GLP validated, software platform for data acquisition and analysis.  It can be used with implantable and external telemetry, traditional hardwired monitoring, and to collect endpoints such as cardiovascular/hemodynamic and respiratory.  Ponemah is a multi-application platform, used in physiology, pharmacology, and toxicology laboratories.  The software is modular, consisting of multiple acquisition interfaces, as well as a library of pre-programmed, validated analysis modules, providing flexible configurations and easy expansion options for evolving research emphases.

Analysis Modules

Ponemah analysis modules are trusted by researchers worldwide for consistent, reliable, and robust results.  A variety of analysis modules are available to calculate physiologic parameters from many animal models, using validated algorithms developed from scientific and peer reviewed journals.  Analysis modules are applied during acquisition to provide real-time results.

Ponemah Review allows researchers to view, sort, and sync calculated data with multiple graphic presentations to quickly locate outliers and confirm accurate creation of waveforms. 

Electrocardiogram Analysis

This module integrates ECG cycle detection method to provide robust, accurate results.  Over 30 derived parameters can be calculated for every complex on a beat-to-beat basis and presented in real-time or during subsequent analysis sessions.

ECGPro

Ponemah offers a template-based ECG analysis module which allows selection of a templated cardiac cycle to be used for precise comparison to other cycles in the dataset for more accurate analysis.    Researchers can build a library of cardiac cycles to mix and match regions of interest with multiple templates.  Once libraries are built, the Batch Template Analysis function can be used to analyze multiple subject ECG channels without any user interaction.

Left Ventricular Pressure

This module specifically analyzes the left ventricular pressure from the heart.  Some of the on-line derived parameters include LVEDP, HR, +/-dP/dt, Q-A interval and Tau.

Blood Pressure

This module can analyze pressure from the circulatory system and can derive, on a beat-to-beat basis, values for the cardiac cycle such as systolic and diastolic pressures, heart rate, and +/-dP/dt.

Glucose

This module analyzes the blood glucose signal obtained from the HD-XG implant.  The analysis calculates the common parameters that are associated with glucose after the signal has been calibrated.

Blood Pressure Respiration

This module can analyze any pressure from the circulatory system and can derive, on a beat-to-beat basis, respiration values from the cardiac cycle.

Cardiac Volume

This module analyzes any volume from the circulatory system and derives real-time values relative to the cardiac cycle, such as filling and emptying rates, stroke work, and cardiac output.

Pressure-Volume Loop

This module operates in conjunction with the LVP and Cardiac Volume analysis modules to calculate a wide host of derived parameters including PRSW, ESPVR, and EDPVR.

Coronary Blood Flow

This module derives typical flow information such as Maximum and Minimum Flow, Mean, Stroke Volume and Cardiac Output. When coupled with the Left Ventricular Pressure Module, the addition of timing information from this module allows for flows and volumes to be calculated specific to the Systolic and Diastolic portions of the cardiac cycle.

Systemic Blood Flow

This module analyzes both coronary and systemic blood flow. Common derived parameters generated from the Systemic Blood Flow analysis include, but are not limited to, Max and Min Flow, Stroke Volume, and Cardiac Output. 

Pulmonary Volume

This module calculates, on a breath-to-breath basis, values for respiratory volume, flow and a host of other calculated parameters.

Pulmonary Airflow & Airway Resistance

This module calculates, on a breath-to-breath basis, values for the respiratory cycle obtained from plethysmograph boxes or pneumotachs. Tidal volume, peak flows and PEnh are examples of the derived output that are available.

Unrestrained Plethysmography

This module analyzes signals obtained from free-roaming chambers. Derived values for flow and volume measurements, as well as PEnh, are examples of measurements performed by this module. 

Electromyogram

The purpose of this module is to compute physiologically meaningful parameters from digitized EMG data.

Diaphragmatic EMG

This module is used to calculate respiratory parameters from EMG data acquired from the diaphragm. Tidal Volume, Minute Ventilation, and Respiration Rate are examples of derived outputs available in breath-to-breath or time averaged presentations.

Action Potential

This module identifies common parameters such as Maximum, Minimum and Plateau voltages. User defined Recovery Points as well as rates of change are also generated by this module.

Pulsatile Tissue & Gut Motility

This module calculates, on a contraction-to-contraction basis, derived values such as Maximum and Minimum values, Average (AUC) and Rate. Numerous other parameters can be generated in real time such as first and second derivatives.

Automatic Arrhythmia Detection Using Data Insights™

Data Insights™ optimizes data analysis using interactive tools which give the user multi-faceted views of data so they can remain engaged in the decision-making process and save time.  As researchers can quickly locate data sections with morphology variations, they are able to adjust settings and reanalyze as needed.  In addition, they can visualize signal noise to confidently eliminate artifact.  When this is done manually, without considering inter-animal variability, the algorithm may exclude good, physiological data and/or mismark reported data.  Data Insights can apply quality assessment-based searches to ensure the data are reported accurately and minimize the exclusion of data.  By reducing the amount of manual data analysis, Data Insights™ reduces variability and increases reproducibility.

Researchers can identify complexes to use with ECG template libraries.  Data Insights™ correlates physiologic interactions between waveform types allowing efficient performance of waveform marking validation.

Data Insights™ can help researchers select the most appropriate subjects by screening prior to study, developing and characterizing disease models, and creating individual subject arrhythmia signatures to discern treatment effects.

Alarms for monitoring system and animal health

With Remote Notification, researchers can set alarms in Ponemah to notify appropriate personnel, based on alarm conditions, via email or text message. 

Remote Notification can also be used as an animal welfare refinement method to monitor for signals of pain, stress, and infection.  Alerts can be set to notify veterinary staff when vital signs go outside specified ranges (e.g. when temperature exceeds a certain threshold).

Advanced GLP Compliance

Data Security

Ponemah’s Data Security Option (DSO) allows the system to operate within FDA 21 CFR Part 11 regulations.  DSO uses a Smart Card technology and electronic signatures to provide a high level of system security and data control.  DSO also provides secure program login, electronic signatures, controlled user privileges, multiple user profiles, file integrity validation, and audit trail.

Data File Management

Ponemah manages all data files collected throughout the study in an underlying SQL Database Express Engine.  The SQL database provides structure and control, allowing users to run studies consistently across workstations locally or world-wide. 

Reporting

Reporting is a customizable data organization, analysis, visualization, and reporting tool seamlessly integrated with Ponemah.  Reporting generates individual derived data listings, group mean summary tables, and graphs directly into MS Word.  The GLP feature locks tables and graphs so no changes can be made to the final report.

References:

1. Boulay E., Pugsley MK., Jacquemet V., Vinet A., Accardi MV., Soloviev M., Troncy E., Doyle JM., Pierson JB., Authier S. (2017). Cardiac contractility: Correction strategies applied to telemetry data from a HESI-sponsored consortium. J Pharmacol Toxicol Methods. Doi: 10.1016/j.vascn.2017.04.009.
2. Lagrange J., Kossmann S., Wenzel P. (2017). Assessment of Vascular Dysfunction and Inflammation Induced by Angiotensin II in Mice. Inflammation. 1559: 439-453.

FinePointe software collects, analyzes, and reports life science data.  Data is stored using Microsoft SQL Server®, and the software can operate on a single computer or, if enabled, across a network. 

FinePointe offers researchers the flexibility to employ additional applications as they expand and move into adjacent respiratory approaches (e.g. head out, whole body plethysmography, non-invasive airway mechanics, resistance and compliance, pulmonary function testing, and inhalation).  The platform incorporates acquisition, analysis, and reporting capabilities as well as nebulization and bias flow control, and other application specific features.

Acquisition with FinePointe Station

FinePointe Station allows control of acquisition from the FinePointe site hardware or the computer.  Others on the network, with proper security, can view acquisition live and archive data remotely in real time.  FinePointe also provides the ability to pause live scrolls of data allowing users to scroll back to review data already acquired while acquisition continues.

Automated Analysis with FinePointe Review

FinePointe Review stores data completely, including signals, analyzed results, measurement intervals, event marks, and tick information.  FinePointe automatically analyzes data and prepares it for a variety of reporting options.

Site Types (Analysis Modules)

Several FinePointe site types are offered, allowing for proper analysis of a variety of respiratory signals and applications.

Flow Derived Parameters (FDP)

This analyzer derives common pulmonary parameters from a respiratory flow signal. It can be used for any direct pulmonary flow method, including a flow signal from a pneumotach or a head out chamber. Conscious or anesthetized animals can be used with the analyzer.

Non-Invasive Airway Mechanics (NAM)

This analyzer monitors the animals’ thoracic and nasal flow signals simultaneously from within a double chamber plethysmograph.  Ventilatory parameters are derived from the thoracic signal.

Pulmonary Function Testing (PFT)

This analyzer monitors a respiratory flow signal and any airway pressure signal during a succession of forced pulmonary tests from an anesthetized test subject.  These tests offer a unique and comprehensive look at the function of the lung.

Resistance and Compliance (RC)

This analyzer monitors a respiratory flow signal and any airway pressure signal from a test subject and computes ventilatory resistance and compliance.

Whole Body Plethysmography (WBP)

This analyzer derives common pulmonary parameters from a respiratory flow signal, and is used with whole body plethysmographs. Cough analysis can also be done for specific species.

Apnea Analysis

This module provides the ability to score each breath and categorize it (e.g. apnea type 0, 1, or 2, sigh, sniff, erratic, normal, etc.) removing the need to manually over-read respiratory waveforms.

Gas Automation

Automated, software-driven gas challenge eliminates the need to manually control gas tanks saving time and increasing reproducibility. 

Reporting

While all data can be exported to Excel, text, Open Office®, and a variety of other statistical packages for report processing, FinePointe software comes with a complete built-in reporting capability.  Within a single study, the researcher can set up as many reports as needed.    Multiple reports can be created and updated at any time, allowing for unique study customization. 

Subjects can be added and removed from groups at any time. When groups are changed, finalized reports are updated instantly.

FinePointe software provides common statistics, and if the statistics provided are not sufficient, the report can be exported directly into Excel®, GraphPad Prism™, or SPSS™.   The report can also be exported to text files, which can be read by any other statistical software program.

References:

1. Chen L., Lai K., Lomask JM., Jiang B., Zhong N. (2013) Detection of Mouse Cough Based on Sound Monitoring and Respiratory Airflow Waveforms. PLoS ONE 8(3): e59263. https://doi.org/10.1371/journal.pone.0059263

NeuroScore is an analysis software used to analyze neurophysiologic data collected in Ponemah, Dataquest ART, EDF/EDF+, and other file formats.  NeuroScore increases CNS analysis throughput by quickly delivering summarized results and analyzing large, continuous data sets common to EEG, sleep and seizure studies. 

NeuroScore’s modular design allows it to be tailored to a specific research application.  The core software is the foundation of the analysis platform and contains most the program features and functions.  Optional modules can be added to enhance the core software.

Optional Modules

Batch Processing Module

This module increases data throughput by automating analysis processes on multiple recordings at once.  Researchers can build custom workflows to automatically score multiple recordings, export signal or parameter data, and generate/export reports.

Once complete, the recording can be opened to view and augment automated scorings performed during the Batch workflow.

Sleep Scoring Modules

Automated Rodent Sleep Scoring

This module automatically assigns a vigilance stage to each epoch based on EEG, EMG, and activity data.  Stages scored include paradoxical sleep, slow wave sleep (with option to distinguish between SWS-1 and SWS-2), wake, and active wake.  NeuroScore uses the EEG signal frequency content (delta vs. theta), electromyogram (EMG) activity, and locomotor activity acquired with telemetry to compute a complex probabilistic matrix used to automatically score sleep stages.  Rather than manually analyzing the data, results are available automatically within seconds.  In addition, researchers can synchronize video with data acquisition for accurate sleep stage evaluation.

Automated Large Animal Sleep Scoring

This module automatically assigns a vigilance stage to each epoch within a large animal dataset.  The algorithm is based upon the American Academy of Sleep Medicine standards for human sleep scoring and relies on EEG, EMG, EOG, and activity data from each subject.  Stages assigned include REM, Non-REM (N1, N2, and N3), Wake, and Active Wake.  Automated scoring can reduce analysis time and variability in comparison to manual scoring.

Seizure Detection

The spike train detector is designed primarily for seizure detection from EEG waveforms.  The detector scans the waveform for repeating spike activity using amplitude-based criteria.  Several parameters, including the spike train duration and number of spikes, can be displayed per event or summarized over longer time intervals.

Video Synchronization

This module imports video data acquired with either Dataquest A.R.T. or Ponemah and synchronizes it with the physiologic waveforms, allowing playback in real-time or fast speed.  Subjects’ behavior is visible to validate or further classify detected events or scored vigilance stages.  Incorporating video data can improve the confidence level of results. 

References:

• Caulder E., Huitt T., Stapleton-Kotloski J., Godwin D. Validation of NeuroScore 2.0 Seizure Detection Module.
• Dittrich L., Morairty SR., Warrier DR., Kilduff TS. (2015). Homeostatic sleep pressure is the primary factor for activation of cortical nNOS/NK1 neurons. Neuropsychopharmacology 40: 632–639.
• Cho K-O., Lybrand ZR., Ito N., et al. (2015) Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline. Nature Communications 6:6606. doi:10.1038/ncomms7606.
• Saevarsson G., Keating G., Arnarsson H., Hilmarsson O., Karlsson K., Decker M. Validation of a Commercially Available Rodent Polysomnographic Scoring Algorithm.

Surgical Services

Surgical proficiency is critical to successful physiologic monitoring with telemetry. Experience higher surgical success rates with surgical and training programs available to drive procedural efficiencies.  Participating in surgical training shortens the learning curve for implantation techniques.  Contracting surgeons to perform surgeries at the researcher’s site ensures reliable outcomes with consistent device placement.  Ordering animals pre-implanted alleviates preparation efforts by delivering animals that are ready for study acclimation as everything from pre-surgical preparation through complete post-operative care has already been completed.  DSI surgeons use techniques and best practices developed specifically for DSI implants, and are led by a Diplomate of the American College of Veterinary Surgery.  The group is comprised of experienced surgeons including Surgical Research Specialists certified by the Academy of Surgical Research with additional qualifications including a Certified Veterinary Technician (CVT), and Registered Laboratory Animal Technologist (RLATG).

Data Services

Contracting complete data analysis and reporting ensures data are accurately analyzed, evaluated and reported following quality procedures, for non-GLP and GLP studies (including OECD).  Anonymity of data is protected with secure measures including blinding data sets and adhering to the client’s security requirements.  High-quality, comprehensive reports are created and delivered for evaluation of: hemodynamics, heart rate variability, ECG interval quantification, arrhythmia detection, seizure detection, sleep scoring, blood pressure, respiration, inhalation, temperature and activity that change from study to study and subject to subject.  The delivery format includes is a short summary of the experimental design and results, graphs and tables representing the results and a summary report of the study with graphs and observations.  DSI has credentialed full-time staff including physiologists and biomedical engineers offering experience in animal model and drug development, data analysis and interpretation of physiologic experimental results.

Validation Services

Software validation services are provided to achieve full system GLP compliance through establishment and execution of a commercial off the shelf (COTS) validation plan which controls costs and minimizes the burden of developing compliance and change control programs.  DSI’s experienced team works closely with Quality Assurance departments to reduce regulatory risks and drive consistent documentation across systems.  The service and documentation includes: validation master plan, installation and qualification plan, test scripts and reports, audit resolution, summary report, supporting electronic test files, back up electronic files storage on a secure server and dedicated on-site support.