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CT Perfusion for Determination of Pharmacologically Mediated Blood Flow Changes in an Animal Tumor Model¹

¹ From the Laboratory for Minimally Invasive Tumor Therapy (A.H., H.P., A.U.H., S.L., S.N.G.), Department of Radiology (A.U.H., C.J.W., J.K., V.D.R., S.N.G.), Beth Israel Deaconess Medical Center, 1 Deaconess Rd, WCC 308B, Boston, MA 02215; and the Department of Interventional Radiology, Gustave Roussy Cancer Institute, Villejuif, France (T.d.B.). Received December 15, 2005; revision requested February 9, 2006; revision received June 1; accepted June 21; final version accepted September 22. Supported by National Cancer Institute Dana Farber/Harvard Cancer Center Renal Cancer SPORE grant 1 P50 CA10194-01. Address correspondence to S.N.G. (e-mail: sgoldber{at}caregroup.harvard.edu).

Purpose: To prospectively compare single- and multisection computed tomographic (CT) perfusion for tumor blood flow determination in an animal model.

Materials and Methods: All animal protocols and experiments were approved by the institutional animal care and use committee before the study was initiated. R3230 mammary adenocarcinoma was implanted in 11 rats. Tumors (18–20 mm) were scanned with dynamic 16-section CT at baseline and after administration of arsenic trioxide, which is known to cause acute reduction in blood flow. The concentration of arsenic was titrated (0–6 mg of arsenic per kilogram of body weight) to achieve a defined blood flow reduction (0%–75%) from baseline levels at 60 minutes, as determined with correlative laser Doppler flowmetry. The mean blood flow was calculated for each of four 5-mm sections that covered the entire tumor, as well as for the entire tumor after multiple sections were processed. Measurements obtained with both methods were correlated with laser Doppler flowmetry measurements. Interobserver agreement was determined for two blinded radiologists, who calculated the percentage of blood flow reduction for the "most representative" single sections at baseline and after arsenic administration. These results were compared with the interobserver variability of the same radiologists obtained by summing blood flow changes for the entire tumor volume.

Results: Overall correlations for acute blood flow reduction were demonstrated between laser Doppler flowmetry and the two CT perfusion approaches (single-section CT, r = 0.85 and r² = 0.73; multisection CT, r = 0.93 and r² = 0.87; pooled data, P = .01). CT perfusion disclosed marked heterogeneity of blood flow, with variations of 36% ± 13 between adjacent 5-mm sections. Given these marked differences, interobserver agreement was much lower for single-section CT (standard deviation, 0.22) than for multisection CT (standard deviation, 0.10; P = .01).

Conclusion: Multisection CT perfusion techniques may provide an accurate and more reproducible method of tumor perfusion surveillance than comparison of single representative tumor sections.

© RSNA, 2007

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