Development and validation of a novel technique for murine first-pass radionuclide angiography with a fast multiwire...

The use of genetically altered mice as a model system to study cardiovascular disease has created a need for accurate and quantitative assessment of murine ventricular function. To address this very challenging problem, we have developed a technique of murine first-pass radionuclide angiography using pinhole imaging and the short-lived isotope tantalum 178 (Ta-178) with a high-speed multiwire proportional camera (MPC). METHODS AND RESULTS. An MPC was fitted with a pinhole lens of 2-mm-diameter aperture positioned 15 cm from the camera face. The short-lived isotope Ta-178 (half-life 9.3 minutes) was generated from the tungsten 178 (W-178) (half-life 21.7 days)/Ta-178 generator and concentrated on site to an injection volume of 15 to 20 microL. Mice were imaged in the supine position with the chest wall 3 mm from the camera pinhole aperture, and images were acquired at 160 frames per second after a rapid bolus injection of Ta-178. In the absence of a true gold standard, the technology was validated with measurements in control mice and mice with surgically ligated left anterior descending arteries (LADs). In addition, the effects of pharmacologic intervention with verapamil and with dobutamine were observed. Finally, peak aortic velocity measurements obtained with this technology were compared with those obtained with echocardiographic Doppler ultrasonography, the only available quantitative comparator. There was a significant decrease in the mean left ventricular ejection fraction (LVEF) between normal mice (62% +/- 4.6% [mean +/- SEM], n = 12) and mice with experimentally induced myocardial infarction produced by surgical LAD ligation (22% +/- 2.0%, n = 41; P <.01). The LVEF decreased from 51% +/- 5.8% to 37% +/- 3.5% in a group of normal mice receiving verapamil (P <.05, n = 8) and increased from 34% +/- 2.2% to 43% +/- 2.3% in a group of LAD-ligated mice receiving dobutamine (P <.01, n = 48). Peak camera sensitivity during first pass was 25,000 cps/mCi injected. Intraobserver and interobserver variability of LVEF was studied, yielding r = 0.9639 and 0.9529 and SE of the estimate 2.6% and 3.1%, respectively. Reproducibility in serial studies was excellent (r = 0.92, SE of the estimate 5.18).

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.