The use of preclinical rodent models of disease continues to grow because these models help elucidate pathogenic mechanisms and provide robust test beds for drug development. Among the major anatomic and physiologic indicators of disease progression and genetic or drug modification of responses are measurements of blood vessel caliber and flow. Moreover, cardiopulmonary blood flow is a critical indicator of gas exchange. Current methods of measuring cardiopulmonary blood flow suffer from some or all of the following limitations—they produce relative values, are limited to global measurements, do not provide vasculature visualization, are not able to measure acute changes, are invasive, or require euthanasia.Methods:
In this study, high-spatial and high-temporal resolution x-ray digital subtraction angiography(DSA) was used to obtain vasculature visualization, quantitative blood flow in absolute metrics (ml/min instead of arbitrary units or velocity), and relative blood volume dynamics fromdiscrete regions of interest on a pixel-by-pixel basis .Results:
A series of calibrations linked the DSA flow measurements to standard physiological measurement using thermodilution and Fick’s method for cardiac output (CO), which in eight anesthetized Fischer-344 rats was found to be. Phantom experiments were conducted to calibrate the radiographic density to vessel thickness, allowing a link of DSAcardiac output measurements to cardiopulmonary blood flow measurements in discrete regions of interest. The scaling factor linking relative DSAcardiac output measurements to the Fick’s absolute measurements was found to be .Conclusions:
This calibrated DSA approach allows repeated simultaneous visualization of vasculature and measurement of blood flow dynamics on a regional level in the living rat.
The authors wish to thank David S. Enterline, M.D., and James Waples for the information about the contrast agent, Robert Behringer, Ph.D., for insightful discussion about fluid dynamics, Eric Alford and Aaron Walker for running blood gas and air sample analyses, Owen Doar for scheduling and coordinating the aforementioned analyses, Jim Pollaro, M.S., for the ventilator software control interface and monitoring system, and Laurence Hedlund, Ph.D., for animal support and surgery. All work was performed at the Duke Center for In Vivo Microscopy, an NCRR National Biomedical Technology Research Center (Grant No. P41 RR005959) and NCI Small Animal Imaging Resource Program (Grant No. U24 CA092656), and the Duke Center for Hyperbaric Medicine and Environmental Physiology.
II. MATERIALS AND METHODS
II.A. Radiographic system
II.B. Animal surgical procedures
II.C. Fick’s cardiac output
II.D. Thermodilution-based cardiac output
II.E. SVD flow metric vessel thickness correction and experimental verification
III.A. Fick’s cardiac output
III.B. Thermodilution-based cardiac output
III.C. X-ray DSA-based cardiopulmonary blood flow
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