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© 2006 by the American Institute of Ultrasound in Medicine
J Ultrasound Med 25:15-21 • 0278-4297

In Vivo Perfusion Estimation Using Subharmonic Contrast Microbubble Signals

Flemming Forsberg, PhD, Ji-Bin Liu, MD, William T. Shi, PhD, Raymond Ro, BS, Kathryn J. Lipcan, MBA, RDMS, Xuedong Deng, MD and Anne L. Hall, PhD

Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania USA (F.F., J.-B.L., R.R., K.J.L., X.D.); and GE Healthcare, Milwaukee, Wisconsin USA (W.T.S., A.L.H.). Dr Shi is now with Philips Research USA, Briarcliff Manor, New York USA; Dr Deng is now with the Department of Ultrasound, Nanjing Medical University, Suzhou Hospital, Suzhou, China.

Address correspondence to Flemming Forsberg, PhD, Department of Radiology, Thomas Jefferson University Hospital, Suite 763J, Main Building, 132 S 10th St, Philadelphia, PA 19107 USA. E-mail: flemming.forsberg{at}jefferson.edu

Objective. The purpose of this study was to quantify perfusion in vivo using contrast-enhanced subharmonic imaging (SHI). Methods. A modified LOGIQ 9 scanner (GE Healthcare, Milwaukee, WI) operating in gray scale SHI mode was used to measure SHI time-intensity curves in vivo. Four dogs received intravenous contrast bolus injections (dose, 0.1 mL/kg), and renal SHI was performed. After 3 contrast agent injections, a microvascular staining technique based on stable (nonradioactive) isotope-labeled microspheres (BioPhysics Assay Laboratory Inc, Worcester, MA) was used to quantify the degree of perfusion in 8 sections of each kidney. Low perfusion states were induced by ligating surgically exposed segmental renal arteries followed by contrast agent injections and microvascular staining. Digital clips were transferred to a personal computer, and SHI time-intensity curves were acquired in each section using Image-Pro Plus software (Media Cybernetics, Silver Spring, MD). Subharmonic fractional blood volumes were calculated, and the perfusion was estimated from the initial slope of the fractional blood volume uptake averaged over 3 injections. Subharmonic perfusion data were compared with the gold standard (ie, the microspheres) using linear regression analysis. Results. In vivo gray scale SHI clearly showed flow and, thus, perfusion in the kidneys with almost complete suppression of tissue signals. In total, 270 SHI time-intensity curves were acquired, which reduced to 94 perfusion estimates after averaging. Subharmonic perfusion estimates correlated significantly with microsphere results (r = 0.57; P < .0001). The best SHI perfusion estimates occurred for high perfusion states in the anterior of the kidneys (r = 0.73; P = .0001). The corresponding root mean square error was 2.4%. Conclusions. Subharmonic perfusion estimates have been obtained in vivo. The perfusion estimates were in reasonable to good agreement with a microvascular staining technique.

Key Words: in vivo flow measurements • perfusion estimation • subharmonic imaging • ultrasound contrast agent

Abbreviations: FBV, fractional blood volume • RMSE, root mean square error • ROI, region of interest • SHI, subharmonic imaging




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