Development and validation of a novel technique for murine first-pass radionuclide angiography with a fast multiwire camera and tantalum 178

Background. The use of genetically altered mice as a model system to study cardiovascular disease has created a need for accurate and quantitative ass essment of murine ventricular function, To address this very challenging pr oblem, we have developed a technique of murine first-pass radionuclide angi ography 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) (h alf-life 21.7 days)/Ta-178 generator and concentrated on site to an injecti on volume of 15 to 20 muL. 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 a bsence of a true gold standard, the technology was validated with measureme nts in control mice and mice with surgically ligated left anterior descendi ng arteries (LADs), In addition, the effects of pharmacologic intervention with verapamil and with dobutamine were observed. Finally, peak aortic velo city measurements obtained with this technology were compared with those ob tained with echocardiographic Doppler ultrasonography, the only available q uantitative comparator, There was a significant decrease in the mean left v entricular ejection fraction (LVEF) between normal mice (62% +/- 4.6% [mean +/- SEM], n = 12) and mice with experimentally induced myocardial infarcti on produced by surgical LAD Ligation (22% +/- 2.0 %, n = 41; P < .01). The LVEF decreased from 51% <plus/minus> 5.8% to 37% +/- 3.5% in a group of nor mal mice receiving verapamil (P < ,05, n = 8) and increased from 34% <plus/ minus> 2.2% to 43% +/- 2.3% in a group of LAD-ligated mice receiving dobuta mine (P < .01, n = 48), Peak camera sensitivity during first pass was 25,00 0 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), Conclusions, This study demonstrates the development and use of a promising new method that uses the short-lived radioisotope Ta-178 and MPC for nonin vasive quantification of murine ventricular function, that produces accurat e and highly reproducible results, and that can be applied in multiple seri al studies.