The Small Animal Echocardiography Core provides an imaging resource to support cardiovascular phenotyping efforts. The Core staff offers expertise, materials, training, consultation, access to equipment and performs scanning and analysis on a fee for service basis.
The Core serves Investigators affiliated with the Medical College of Wisconsin on a first come, first served basis. Time lines for projects vary according to the nature of the project and current workload of the Core. Information about fees is available from the Core Medical Director. Successful and timely animal scanning and data analysis requires a concerted, collaborative effort of the Investigator and the Core staff in all stages of the experiment. Investigators planning on utilizing Core services are therefore encouraged to contact the staff early in the planning stages of the experiment.
Echocardiography is the cornerstone of the phenotyping process. Its highly versatile nature makes it the non-invasive tool of choice. This form of non-invasive assessment is ideal for performing serial evaluations of cardiac function or real-time monitoring during and after pharmacological or therapeutic intervention.
Echocardiography has the versatility that allows for rapid and comprehensive evaluation of myocardial function, valvular and vascular structure in animal models. Protocols are adaptable to the needs of the investigator.
A comprehensive small animal echocardiogram includes:
Non-invasive single transthoracic cardiac ultrasound exam performed under anesthesia that includes 2D and M-mode images of the left ventricle and Doppler recordings of trans-valvular flow indices.
Echocardiograms that must occur on specific days and must be repeated on the same animal at a specific later date. Includes all the analysis of a screening echocardiogram at each echo date.
When regional wall motion abnormalities are expected, then the echocardiographic study requires more than M-mode and 2D images. For these echocardiograms, we will include segmental wall motion analysis with 2D speckle tracking and strain analysis.
Full echocardiograms to document the outcome of a specific surgery other than myocardial infarction (such as TAC, AAB or NAB). This echo may include 2D and M-mode images and analysis of the left ventricle, or Doppler recordings of trans-valvular flow indices (gradients), Doppler recordings (gradients) across the aortic constriction. Analysis of diastolic function may be included for an additional cost.
Previously unscheduled echoes that are necessary to do immediately because the animal is in newly discovered end-stage heart failure and may expire, or other emergent conditions. This also includes non-emergent studies that need to be performed with less than 2 business days notice.
Ultrasound scanning is used to delineate structural and functional abnormalities of the aorta or other vessels. Includes an analysis of these parameters and data reporting.
Includes ultrasound imaging of other organs and vasculature including renal, vascular and embryo ultrasounds.
Includes studies that the core staff and the PI have discussed in detail and that are not offered on a routine basis. Analysis and data reporting will be included.
2D speckle tracking echocardiography is a novel technique that enables the assessment of myocardial strain through the analysis of speckle motion inherently present in a standard, 2D echocardiographic image. This technique is angle independent, preload independent, not affected by tethering between segments and less operator dependent. This technique has been validated in experimental and human studies and found to correspond well to established “gold standard” techniques.
Why use strain imaging for your study?
Why analyze strain rate for your study?
Diastolic strain rate may be used as an additional surrogate of ventricular fibrosis and segmental relaxation abnormalities.
By providing insight into regional diastolic function, segmental diastolic strain rate can readily uncover the presence and extent of regional ischemia and viability.
We routinely assess LV diastolic function in small animals based on three Doppler-derived parameters: E/E’, Vp, and IVRT/RR. Another index is E/A; however, distinct E and A peaks are generally not discernible in anesthetized rodents. Doppler is also used to assess transvalvular velocities and regurgitant lesions.
Note: Mitral inflow indexes (E, A, and E/A) are complex and subject to misinterpretation because these parameters are dependent on not only intrinsic relaxation properties of the LV but also on other factors such as HR, the volume loading conditions, left atrial–LV pressure gradients, and LV compliance. Although the ratio of peak early transmitral flow velocity (E) to the peak early myocardial tissue velocity (E’) is a more robust indicator of LV diastolic dysfunction, it too has its shortcomings. E’ measures the velocity of myocardial displacement as the LV expands during diastole and can, therefore, be considered a surrogate marker for tau (the time constant of relaxation). Likewise, Vp is relatively independent of changes in preload and heart rate and also closely reflects tau.
For example, visualization of the heart during direct myocardial injection.
All echocardiograms are performed by a trained sonographer who has over 8 years experience scanning animals including mice, rats, rabbits, pigs and primates. Consultation services are provided by Jennifer Strande, MD, PhD a board-certified cardiologist and Medical Director of the lab. Dr. Strande’s background in cell and molecular biology facilitates interpretation of the findings and correlation with changes at the cellular level. Core staff has a strong background in both clinical medicine and the evaluation of animal models and can help design protocols to answer research questions.
The Vivid 7 or EchoPAC software is available without a sonographer for a reduced fee.
There is a minimum 3 hour instruction period to teach basic machine function. This will also include minimal ultrasound scanning techniques. This assumes that the investigator has a basic understanding of cardiac anatomy and echocardiographic views and is familiar with the specific echocardiographic equipment being used.
Researchers may also do their own analysis after completing 2 hours of EchoPAC software training.
Users must demonstrate proficient use and cleaning of equipment prior to independent use.
Ultrasound is well suited for the examination and delineation of soft tissue structures; however, echocardiography requires extensive knowledge of cardiac and vascular anatomy, physiology, hemodynamics, ultrasound physics, the Doppler principle and the underlying acoustic physics of color and pulsed wave Doppler. Knowledge of scanning protocols and proficient use of the equipment is also required for the production of quantifiable data.
Rodents need to be shaved and anesthetized immediately before the scanning. The type and route of anesthesia should be determined by the investigator prior to initiating the study. Contact the Core Medical Director for recommendations.Standard Small Animal Cardiac Imaging Protocol
Images are first acquired in the indicated sequence from the various modes within each of the four echo views. The images are subsequently analyzed offline, and the appropriate parameters derived from these measurements. For consistency and to minimize variability, it is essential to maintain the predetermined order and timing of these acquisitions between subjects and for longitudinal measurements within a subject. 2D, two-dimensional; LV, left ventricular; SV, stroke volume; CO, cardiac output; endo, endocardial; epi, epicardial; V, velocity; S, strain; SR, strain rate; WT, wall thickness; FS, fractional shortening; EF, ejection fraction; E, early; A, atrial; Vp, mitral inflow propagation velocity; IVRT, isovolumic relaxation time.
Flow chart adapted from: Cardiovascular Genomics, Methods in Molecular Biology, 2009, Humana Press; 573.
Sonin, D, Wakatsuki, T, Routhu, K, Harmann, L, Peterson M, Meyer, J, Strande, J. Protease-Activated Receptor I Inhibition by SCH79797 Attenuates Left Ventricular Remodeling and Profibrotic Activities of Cardiac Fibroblasts. Journal of Cardiovascular Pharmacology and Therapeutics, 2013; 18(5): 460-475.
Lenarczyk, M, Lam V, Jensen, E, Fish, B, Su, J, Koporowski, S, Komorowski, R, Harmann, L, Migrino, R, Li, X, Hopewell, J, Moulder, J, Baker, J. Cardiac Injury After 10 Gy Total Body Irradiation: Indirect Role of Effects on Abdominal Organs. Radiation Research, on-line 8/2013.
Sethumadhavan,S, Vasquez-Vivar, J, Migrino, R, Harmann, L, Jacob, H, Lazar, J. Mitochondrial DNA Variant for Complex Reveals a Role in Diabetic Cardiac Remodeling. Journal of Biologic Chemistry, 2012, 287(26):22174-82.
Migrino, R, Bowers, M, Harmann, L, Prost, R, LaDisa, J. Carotid Plaque Regression Following 6-Month Statin Therapy Assessed By 3T MRI: comparison with Ultrasound Intima Media Thickness. Journal of Cardiovascular Magnetic Resonance, 2011, 13:37.29:1039-46.
Pieper, G, Shah, A, Harmann, L, Cooley, B, Ionova, I, Migrino, R. Speckle Tracking 2-Dimensional Strain Echocardiography: A New Noninvasive Imaging Tool to Evaluate Acute Rejection in Cardiac Transplantation. Journal of Heart and Lung Transplantation, 2010; 29:1039-46
Baker, J, Fish, B, Su, J, Haworth, S, Strande, J, Komorowski, R, Migrino, R, Doppalapudi, A, Harmann, L, Li, A, Hopewell, J, Moulder, J. 10gy Total Body Irradiation Increases Risk of Coronary Sclerosis, Degeneration of Heart Structure and Function in a Rat Model. International Journal of Radiation Biology, 2009, 85: 12, 1089-1100.
Migrino R, Harmann L, Brahmbhatt T, Mohyuddin T, Prost R, Christenson R, Jurva J, Woods T. 2-dimensional strain echocardiography for regional assessment of myocardial viability in ischemic heart disease. Abstract and poster presentation at American Society of Echocardiography Scientific Sessions, Seattle, WA. June 2007.
Swarajit, G, Zhang, R, Mader, M, Migrino, R, Harmann, L, Zhao, M, Moulder, J, Jacobs, E, Medhora, M. Radiation-induced injury to the rat lung and right heart: preferential mitigation by captopril over losartan. Abstract presentation Radiation Research Society, Boston, MA. 2008
Strande, J, Routhu, K, Harmann, L, Migrino, R, Baker, J. Improvement of Left Ventricular Remodeling and Function by Protease-Activated Receptor 1 Inhibition in Rats with Heart Failure and Myocardial Ischemia and Reperfusion. Abstract presentation American College of Cardiology Scientific Sessions, Orlando FL. 2009
Gundert, T, Aggarwal D, Kalyanaraman, B, Harmann, L, Migrino, R. Use of Statistical Parametric Mapping (Radial Strain Heat Map Derived from 2D Strain Echo) to Characterize Doxorubicin Cardiomyopathy in Rats. Poster presentation at American Society of Echocardiography Scientific Session, Washington, DC. 2009
Shah, A, Pieper, G, Harmann, L, Cooley, B, Ionova, I, Migrino, R. Strain of the Rejected Heart: Novel Assessment Using 2-dimensional Strain Echocardiography. Abstract presentation American College of Cardiology Scientific Sessions, Atlanta, GA. 2010
Harmann, L, Pieper, G, Shah, A, Cooley, B, Ionova, I, Migrino, R. Speckle-Tracking 2-Dimensional Strain Echocardiography: A New Noninvasive Imaging Tool to Evaluate Rejection in Cardiac Transplantation. American Society of Echocardiography Scientific Sessions, San Diego, CA. June 2010
Feng, G, Narayanan, J, Jacobs, E, Strande, J, Harmann, L, Moulder, J, Down, J, Fish, B, Medhora, M. Pleural effusion and edema by lethal doses of radiation to the whole lungs of WAG/RijCmcr rats. Radiation Research Society, New Orleans, LA. September 2013.
Baker, J, Marek, L, Lam, V, Komorowski, R, Migrino R, Jensen, E, Li, W, Su, J, Harmann, L, Fish, B, Hopewell, J, Moulder, J. Cardiac Injury Following 10 GY Total Body Irradiation: Indirect Role of Effects on Abdominal Organs and Mitigation with Simvastatin. American Heart Association Scientific Sessions, New Orleans, LA. November 2013
Animal Echo Core to provide services for a pre-clinical trial for the treatment of myotubular myopathy (MTM)
University of Washington investigators are studying myotubularin gene transfer in dogs that have an MTM-like disease. Jennifer Strande, MD, PhD and Leanne Harmann, BA, RDCS, RDMS, RVT will provide echocardiography services and expertise during the trial.
Read more about MTM Research
Hourly rates are invoiced in 15 minute increments, and mileage @ the current IRS limit is added to the invoice, when applicable.
Hourly rates are invoiced in 15 minute increments, and mileage @ the current IRS limit is added to the invoice, when applicable.
Contact the Core Medical Director to establish a project outline, timeline, and to review the experimental design. After review of the project with Core staff, you will need to provide the following documentation to initiate the experiment:
Please complete the following form to request use of the Vivid 7 ultrasound system or the EchoPac analysis system. Reservations are made on a first-come first-serve basis.