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Description of Services


 

Acute Experiments (PPC-A)

When anesthesia is required, isoflurane inhalation is used to minimize inhibition of the autonomic function (compared to injectable anesthetics). Thermal support and continuous monitoring of core temperature and ECG, and if necessary, mechanical ventilation and fluid administration are provided. Data are collected and stored digitally via multi-channel physiological systems, with or without physiological and pharmacological intervention. We currently measure the following variables:

  • Catheter-based Hemodynamics: high-fidelity Mikro-tip catheters (Millar Instruments) for the measurement of blood pressure, right or left ventricular pressure, and cardiac output via thermodilution techniques (Columbus Instruments or Edwards Lifesciences)
  • Regional blood flow: flow probes (Transonic system) placed on the aorta and other large arteries (renal, pulmonary, coronary, or femoral) or veins (hepatic, portal, vena cava)
  • Pulmonary function: respiratory mechanics by measuring airway and esophageal pressure, and lung volume; diffusion capacity of the lung measured by rebreathing methods of He/CO mixed gases
  • Biopotentials: ECG, EEG, EMG
  • Autonomic function: recordings of renal sympathetic nerve activity; heart rate variability (FFT analysis of ECG recordings) for vagal or sympathetic activity

At the end of an experiment, the animal is euthanized and, if requested, blood and tissue samples are collected.

Biomicroscopy (PPC-B)

Ultrasound is versatile and provides a high throughput imaging modality for various organs and tissues. Clinical ultrasound units have low ultrasound frequencies (8-12 MHz) for long penetration distance, but provide low spatial resolution that is inadequate for small animals like mice.

Visualsonics Vevo 2100 (13-75 MHz) is a high frequency ultrasound system that offers a near-microscopic spatial resolution at ~30 microns (so-called biomicroscopy), and high temporal resolution up to 1000 frame per sec at M-mode unmatchable by MRI and CT. It also enables contrast imaging and 3D-Mode Imaging & Volume Analysis. The imaging can be performed with light sedation, or even in conscious (unsedated) animals when necessary.

  • Cardiac ultrasound imaging: the heart can be visualized in multiple imaging modes, such as B-Mode and M-Mode, Pulsed-Wave Doppler, Color Flow and Power Doppler, and Tissue Doppler. Measurements include chamber geometry (size and wall thickness), valve movement and flow, myocardial perfusion, and diastolic and systolic ventricular function.

    Figure 1. 2D and M-Mode images of mouse left and right ventricles
    Figure 1. 2D and M-Mode images of mouse left and right ventricles.
     
  • Ultrasound imaging of blood vessels and blood flow: Diameter and wall thickness are measured with M-Mode imaging, velocity profiles in the large veins and arteries by Pulsed-Wave Doppler, flow in the smaller vessels down to 100 μm via Color Flow and Power Doppler, and tissue perfusion (i.e. flow near capillary level) by contrast imaging. Expression of biomarkers, such as VEGFR2 and P-Selectin on the endothelial cell surface of the vessels can be quantified by molecular imaging.

    Figure 2. Biomicroscopic studies of a mouse femoral artery branch
    Figure 2. Biomicroscopic studies of a mouse femoral artery branch.
     
  • Imaging-guided injection, extraction, and gene transfer 

  • Cancer applications include the quantification of: 1) tumor size and shape in 2- and 3-dimensional images; 2) blood flow in and around tumors via Power and Color Flow Doppler, and relative tumor perfusion in untargeted contrast imaging; and 3) vascularity and angiogenesis via targeted contrast imaging.

  • Neurobiology applications include visualizing: 1) embryonic and neonatal brain and spinal cord; 2) adult brain with craniotomy; 3) cerebral blood flow via Doppler; 4) nerves; and 5) guided needle injections and tissue biopsies. For example, nerve damage and healing can change nerve texture and brightness; this can be quantified by measuring pixel intensity with histograms.

  • Nephrology applications include visualizing the renal and renal-related structures such as medulla, cortex, renal vein and artery, ureter, and bladder. Renal blood flow in large and small vessels can be measured by various modes of Doppler.

  • Hepatology applications include visualizing the liver, pancreas, and gall bladder. Doppler can be used for blood flow of the distributing arteries and veins, and tissue perfusion of the liver and pancreas.

  • Musculoskeletal applications include visualizing joints, muscles, tendons, cartilage and ligaments in various anatomical regions. Bone and articular cartilage surface smoothness can be visualized for estimates of inflammatory responses. Blood flow in joint areas can be quantified.

Chronic Experiments and Models (PPC-C)

Implant Surgery

Implant surgery usually requires in vivo measurements in conscious and free moving animals that obtain the most relevant physiological data (without acute anesthesia and surgery). We implant the following devices in mice with 15 g body weight or larger animals.

  • Telemetry indices (DSI transmitters) for measurements of blood pressure, locomotor activity, core temperature, ECG, EEG, EMG, or renal sympathetic nerve activity
  • Tethered devices, including flow probe (Transonics) for aortic, arterial, venous, or duct flow; catheters for pressure measurements, blood sampling, or drug injection; electrodes for biopotential measurements (ECG, EEG, and EMG). The Dragonfly swivel system is used to interface to the data acquisition system.
  • Osmotic pump, programmable Micro infusion pump, vascular access port for drug delivery or blood sampling

Chronic Experiments

The PPC has the expertise and equipment for long-term recordings of telemetry or non-telemetry (tethered) data in implanted animals, with or without physiological manipulations including hypoxia, hyperoxia, dietary treatment, and drug infusion. Multiple data systems are available, including DSI telemetry system, BioPac system, dragonfly swivels, Transonic flowmeters, Triton system, and Omega-24 sleep system. The core has a specific “quiet facility” that provides an environment with minimal interruption to enable the study of circadian rhythm in rodents.

Figure 3. Long-term recordings of blood pressure and cardiac output in an implanted mouse
Figure 3. Long-term recordings of blood pressure and cardiac output in an implanted mouse.
 

Animal Models

The PPC has substantial expertise in microsurgery for acute and chronic animal models. The following are examples of various procedures.

Cardiac models:
  • Coronary ligation: myocardial ischemia/reperfusion, infarction, post-infarct hypertrophy, or heart failure
  • Pressure or volume overload: transverse aortic constriction; neonatal aortic banding; ascending aortic banding; aortic banding; aortico-caval fistula; aortic insufficiency
  • Toxic cardiomyopathy: administration of monocrotaline, angiotensin II, adriamycin, epinephrine, and aldosterone
Vascular models:
  • Carotid ligation
  • Arterio-venous fistula
Other models:
  • Chronic sustained or intermittent hypoxia or hyperoxia
  • Adrenalectomy
  • Carotid arc denervation
  • Thymectomy
  • Unilateral nephrectomy

Non-invasive Measurements (PPC-N)

A two-channel Hatteras computerized system is available for the measurement of blood pressure and heart rate of mice and rats in a restrained, but unsedated condition. The tailcuff technique is adequate for the serial screening of blood pressure in a large sample size. Pre-acclimatization of animals helps to reduce standard deviation.

Equipment Rental (PPC-R)

The following major equipment is available through the PPC:

Vevo 2100 System: The most updated biomicroscopy system from VisualSonics, Inc. It is the first high-frequency, high-resolution digital imaging platform with linear array technology and Color Doppler Mode for a wide range of applications and animal models.

BioPac MP System: the modular interface system is equipped with various amplifiers and accessories for measurement of pressures, volumes, biopotentials (e.g. ECG, EEG, EMG, and sympathetic nerve activity), flows, and temperatures. Amplifiers snap together and pull apart for simple customization up to 16 channels. Biopac System, Inc.  

Telemetry System: for simultaneous long-term and telemetry recordings of pressure, temperature, biopotentials (ECG, EEG, EMG), and locomotor activity up to 8 animals. For investigators who prefer a pilot study, transmitters (TAC-10 and F-10) are available for rental. Data Sciences International, Inc.  

Transonic Flowmeter: a dual channel Perivascular module and 4 nano flowprobes for fluid flow in the aorta, large arteries and veins, and ducts in mice or larger animals. The meter can be interfaced to Biopac MP System, DSI Telemetry System, or other digital data systems. Transonic System, Inc.  

Cardiac output computers: two systems, one from Edwards and one from Columbus Instruments, Inc. are available, respectively for cardiac output measurement via thermodilution technique, respectively in mice and in larger animals.

Tailcuff Blood Pressure System: a SC1000 dual channel system is available for non-invasive measurement of blood pressure in mice and rats. Hatteras System, Inc.  

Environment System: computerized system that enables sustain or intermittent exposure of hypoxia or hyperoxia in long-term. The system supports simultaneous exposure of up to 30 mice or 10 rats.

Surgical Suite: a suite with equipment for sterile or non-sterile microsurgery is available, including a dissecting microscopy, small animal ventilator, surgical lights, isoflurane vaporizers, and an Indus thermoregulated platform for rats or mice with thermal and ECG monitoring;, and etc.

Other equipment that is available includes: Triton multi-channel data system, Omega-24 sleep data system, Mouse or Rat Heart Perfusion System.

Technical Support (PPC-T)

We provide consultation on study design, IACUC protocols, etc. Moreover, we provide training on surgeries and procedures performed in the PPC.