Recent advances in genetic manipulations affecting the cardiovascular system in mice 1,2 have produced promising new tools for studying cardiac pathophysiology and have in turn created a need for high-quality imaging in very small animals. For example, in assessing adaptations of genetically altered mice to pressure overload 3 or coronary occlusion simulating human heart diseases 4-6 , it is often necessary to quantify ventricular function in vivo several times before and during adaptation. Ultrasound 7-9 , X-rays 10 , and magnetic resonance imaging 11 (MRI) are among the methods that are being adapted for use in mice, but these techniques all have marginal spatial and temporal resolution for use in animals weighing less than 30 g and with heart rates exceeding 600 beats/min.
Radionuclide ventriculographyWe have adapted a form of radionuclide ventriculography used to quantify right ventricular (RV) and left ventricular (LV) ejection fraction (EF) in man for use in mice [12][13][14] . In this method, blood is imaged by detecting the radioactivity of a tracer injected as a bolus into a vein and followed during its passage through the heart. For murine imaging, a multiwire gamma camera 13 optimized for use with Ta-178 was fitted with a pinhole lens 2 mm in diameter positioned 15 cm from the image plane. This was done to project an enlarged image of the mouse heart on the humansized 32 × 32 pixel array at a frame rate of 160/s, compared with 40/s for human imaging (Fig. 1). The Ta-178 (half-life of 9.3 min) is generated and concentrated on site as needed from W-178 (half-life of 21.7 days) 15 using a semi-automated system to maximize consistency. The short half-life allows concentration of human-size doses (20 mCi) in mouse-size volumes (20 µl) to compensate for the 1/2,500 smaller heart volume and 1/4 shorter image acquisition time with acceptable radiation exposure.
Murine imagingTo provide a wide range of ejection fractions, evaluations were done in 18 normal mice, 13 sham-operated mice, and 44 mice with myocardial infarctions produced by left anterior descending (LAD) coronary artery occlusions 6 . We made multiple measurements of LVEF in each animal with either no intervention, a positive inotrope (dobutamine), or a negative inotrope (verapamil) to assess repeatability and the response to agents with known effects on EF in larger animals. Before imaging, mice were anesthetized with 0.2-0.4 ml of pentobarbital sodium solution (4 mg/ml) given intraperitoneally and were taped supine to a small plastic board with ECG electrodes under each limb (Fig. 1a). A jugular line (PE-10 tubing) was placed for injection of 20 mCi of Ta-178 as a bolus in 10 µl of 0.1 molar HCl followed by 10 µl of normal saline. After injection, images were taken for 7.5 s at 160 frames/s and were stored and analyzed by software originally designed and validated 13 for human cardiac imaging and assessment of EF. End-diastolic images from consecutive cardiac cycles after injection are shown in Fig. 2a, along with a scaled photo of a mouse heart. ...
Perfusion abnormalities are demonstrated by means of Cu-62-PTSM PET in 91% of patients with occlusive coronary artery disease seen at the time of cardiac catheterization, and it shows an excellent normalcy rate of 100%.
Cultural training can be a difficult topic to address during the internship year and can be defined or approached in many different ways. This article describes a program designed to provide cultural training focused on increasing cultural awareness for psychology interns. The training program outlined is based in part on anthropological research methods and teaches interns a method for learning about different cultures. Interns focus on one cultural group, and go through a flexible sequence of several steps from gathering general information, meeting with community representatives, meeting specific groups of community members, to finally developing a project using the information learned to serve the group studied. An overview of the program is provided, with a recent project example to highlight the process. Reactions from interns have generally been positive. Examples are discussed of how the project has evolved to reflect intern and staff experiences.
This study demonstrates the development and use of a promising new method that uses the short-lived radioisotope Ta-178 and MPC for noninvasive quantification of murine ventricular function, that produces accurate and highly reproducible results, and that can be applied in multiple serial studies.
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