A High-Precision Contrast Injector for Small Animal X-Ray Digital Subtraction Angiography

Abstract

The availability of genetically altered animal models of human disease for basic research has generated great interest in new imaging methodologies. Digital subtraction angiography (DSA) offers an appealing approach to functional imaging in small animals because of the high spatial and temporal resolution, and the ability to visualize and measure blood flow. The micro-injector described here meets crucial performance parameters to ensure optimal vessel enhancement without significantly increasing the total blood volume or producing overlap of enhanced structures. The micro-injector can inject small, reproducible volumes of contrast agent at high flow rates with computer-controlled timing synchronized to cardio-pulmonary activity. Iterative bench-top and live animal experiments with both rat and mouse have been conducted to evaluate the performance of this computer-controlled micro-injector, a first demonstration of a new device designed explicitly for the unique requirements of DSA in small animals. Injection protocols were optimized and screened for potential physiological impact. For the optimized protocols, we found that changes in the time-density curves for representative regions of interest in the thorax were due primarily to physiological changes, independent of micro-injector parameters.

Synchrotron Radiation Imaging for Advancing Our Understanding of Cardiovascular Function

“…Higher resolution in vivo angiography became established in the mid 1980s for studying the function of small pulmonary vessels. 15,16 Coronary arteries were visualized in rats using a large focal spot X-ray tube to deliver sufficient flux with exposure times of <10 ms. 17 However, these angiographic methods have a limited spatial resolution of >100 μm. Although it is possible to improve spatial resolution down to ≈10 μm in the rat brain and mouse hindlimb by using direct magnification radiography combined with a microfocus X-ray tube, the imaging speed varies from 1 image per second 18 to 30 images per second (33-ms exposure per frame), 19 so that temporal resolution is compromised.…”

In Vivo X-Ray Digital Subtraction and CT Angiography of the Murine Cerebrovasculature Using an Intra-Arterial Route of Contrast Injection

“…While other groups performed in vivo x-ray DSA of liver, 19 thoracic, and cerebral vessels in rats, 11,17,18,21 and of the renal vasculature in mice, 17 no studies described x-ray DSA for imaging of the cerebrovasculature in live mice. Our findings, however, demonstrate that this is highly achievable.…”

“…11,15,17 Because most institutions do not have easy access to a synchrotron, smaller, less expensive, and more accessible methods are preferred. For example, some researchers have implemented x-ray-based DSA of the thoracic and liver vasculature in mice.…”

“…For example, some researchers have implemented x-ray-based DSA of the thoracic and liver vasculature in mice. [17][18][19][20][21] Focusing on neurovascular imaging, we found no publications describing x-ray-based DSA of the murine cerebrovasculature.…”

In vivo small animal imaging: Current status and future prospects

“…9 Computer-controlled microinjectors are necessary for small animal applications to optimize reproducibility of injection dose, pressure, and rate of contrast boluses. 77 Small animal DSA has been applied for lung perfusion imaging or coronary artery angiography with gating techniques to avoid motion artifacts, or for visualization of tumor or liver or kidney microvessels down to 46 m resolution. 78 Combined micro-CT and micro-DSA with iodinated blood pool and conventional contrast media, respectively, has been applied in animal models of fibrosarcoma to provide coregistered information that combine the exquisite threedimensional angioarchitecture of micro-CT with the functional hemodynamics of digital subtraction angiography in order to analyze tumor angiogenesis and monitor antiangiogenic therapies.…”