"Micro-CT" Scans of Mice Zoom in on Heart Defects
Mysteries of Heart Disease
By imaging the beating hearts of mice using a unique cardiac CT scanner developed by engineers at Duke University Medical Center, the researchers believe they can unlock many mysteries of heart disease.
To image the tiny mouse hearts, about 3,000 times smaller than a human heart, the scanner achieves nearly 500 times the resolution of clinically available CT scanners. What's more, the mouse heart beats ten times faster, making the challenge of capturing clear images of the pumping heart even more difficult. Such problems led many radiologists to believe such high-resolution images of living mouse hearts were technically impossible.
"Transgenic manipulations in mice and rats are increasingly used to study genetic and physiological aspects of human cardiovascular disease: the leading cause of death in the United States and major cause of death worldwide," said assistant professor of radiology Cristian Badea, Ph.D., of the Duke Center for In Vivo Microscopy. "However, cardiac studies in small animals are not easy to do because of the animals' small size and increased rate of biological functions."
The new scanner, however, will enable studies of the small abnormalities in "transgenic" mice induced by mutating genes involved in heart function, they said.
Despite their apparent differences, mice and humans share many of the same genes. Therefore, mutant mice, or mouse "models of disease," have become increasingly common to unravel the underlying basis for diseases -- including cancer, Parkinson's and heart disease -- and for advancing toward possible new therapies.
Mouse models include "knockout" mice, which lack critical genes, and those altered to overproduce proteins encoded by particular disease-related genes. Such genetically-modified animals typically display symptoms that mimic those observed in patients affected with the disease.
However, characterizing those disease symptoms in mice presents major challenges, Badea said. The high-resolution images made possible by the newly developed micro-CT scanner should help to overcome some of those hurdles, he said.
While clinical scanners rotate an X-ray tube and detector around the patient, the newly developed system instead rotates animals between a fixed tube and detector. The researchers also place the mice on a mechanical ventilator, such that each iteration of a scan can be synchronized with both the heart and breathing motion, thereby reducing blurring of the image. The researchers described the new system in the April-June 2005 Molecular Imaging.
"The cardiac CT images we are now getting are nearly 500 times higher resolution than the state-of-the-art in clinical CT imaging," said G. Allan Johnson, director of the Duke center. "The temporal resolution is also ten times greater than that of the clinical arena."
The new scanner is the very first to take advantage of a new class of molecular imaging agents designed to render blood visible by X-ray scans, Johnson said. Unlike conventional agents, which are rapidly cleared by the kidneys, the new chemical, called Fenestra VC (Alerion Biomedical, San Diego, CA) remains in the bloodstream for more than three hours.
The four-dimensional images produced by the micro-CT scanner will not only allow researchers to capture "pretty images," but also allow them to assess cardiac function in a manner comparable to that used in clinical settings, Badea said. Using computer software, developed by Pittsburgh Supercomputing Center, for visualization and analysis, the researchers can "slice" and analyze the images, he added.
"Recent reports have suggested that cardiac micro-CT in mice would be impossible, even with state-of-the-art technology," Badea said. "With the development of our four-dimensional scanner, we've proved this to be incorrect."
The Duke Center for In Vivo Microscopy provides imaging resources to other Duke researchers, as well as researchers nationally and internationally. The center is a National Institutes of Health/National Center for Research Resources National Resource. Additional support was provided by the National Cancer Institute and the Department of Defense. - Durham, N.C.