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Experimental Studies |
1 From the Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, 1 Deaconess Rd, West Campus 302B, Boston, MA 02215 (J.B.K., R.A.K., S.N.G.); and Laboratory of Surgical Biology, Boston University School of Medicine, Mass (P.T.). Received February 4, 2003; revision requested April 14; final revision received September 15; accepted October 8. Supported by National Cancer Institute grant R21-CA8963402. J.B.K. supported by the RSNA R & E Foundation through the RSNA Scholar Award. Address correspondence to J.B.K. (e-mail: jkruskal@bidmc.harvard.edu).
PURPOSE: To evaluate whether intrahepatic flow alterations occur during formation of hepatic colorectal cancer metastases and to identify possible causes of these alterations.
MATERIALS AND METHODS: Intravital imaging of exteriorized livers was performed in 72 live mice. Three groups of mice were studied: a sham-operated control group (n = 24), a group with nonmetastasizing subcutaneous gliomas (n = 24), and a group with developing hepatic CX-1 colon cancer metastases (n = 24). Microvascular flow parameters, leukocyte-endothelial interactions, and wall shear stress were directly measured in hepatic sinusoids and postsinusoidal venules at 2-day intervals prior to and during the development of metastases. The Kruskal-Wallis test was used initially to test for overall equality of medians in each data group. Single posttest comparisons of independent samples were performed with the Mann-Whitney test, with an overall statistical significance of .05.
RESULTS: Prior to the development of visible colorectal cancer metastases, significant (P < .05) reductions occurred in sinusoidal and postsinusoidal flow and wall shear rates, coupled with increased leukocyte rolling and adherence. With tumor growth, flow was further compromised in 92% of tumors larger than 0.5 mm in diameter by extrinsic compression of sinusoids and portal venules and narrowing caused by adherent leukocytes.
CONCLUSION: Significant intrahepatic flow alterations occur in mouse livers prior to growth of visible metastases and provide a rational explanation for elevation in the Doppler perfusion index that occurs prior to tumor formation.
© RSNA, 2004
Index terms: Animals Colon neoplasms, 75.321 Liver neoplasms, metastases, 761.332 Ultrasound (US), Doppler studies, 76.12984
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