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Arteriogenesis: Noninvasive Quantification with Multi–Detector Row CT Angiography and Three-dimensional Volume Rendering in Rodents¹

¹ From the Angiogenesis Research Center (Z.W.Z., L.G., M.M., J.D.P., M.S., E.D.d.M.) and Departments of Radiology (Z.W.Z., J.D.P., T.J.S.), Medicine (Z.W.Z., L.G., M.M., J.D.P., M.S., E.D.d.M.), and Physiology (E.D.d.M.), Dartmouth Medical School, Borwell Research Building HB 7700, 1 Medical Center Dr, Lebanon, NH 03756. Received June 11, 2005; revision requested August 3; revision received September 2; accepted September 22; final version accepted November 23. Z.W.Z. supported by Society of Interventional Radiology Foundation grant. Address correspondence to Z.W.Z. (e-mail: zzw{at}dartmouth.edu).

Purpose: To evaluate two-dimensional (2D) multi–detector row computed tomographic (CT) angiography and three-dimensional (3D) volume rendering for depiction of patterns of arterial growth and quantification of blood vessel density and volume.

Materials and Methods: The institutional animal care and use committee approved this study. The right femoral artery and its branches were ligated and excised in 16 inbred Lewis rats; animals were randomly assigned to receive 70 µL Dulbecco's modified Eagle's medium (DMEM) or 1.5 x 10⁷ bone marrow–derived mononuclear cells (BMC) from isogenic donor rats in 70 µL DMEM. At 2 weeks, CT angiography was performed with injection of 0.45 mL barium sulfate suspension at 0.7 mL/min, followed by silver staining. Number of blood vessels, area, mean area, volume, and blood vessel size distribution derived from digitally subtracted 2D CT angiographic sections were quantified; 3D images were reconstructed. Two-way analysis of variance and paired and unpaired Student t tests were performed.

Results: CT angiography showed two patterns of arterial growth: collateral arterial formation and branching arteriogenesis. Two-way analysis of variance indicated that differences within subjects (ischemic vs nonischemic legs) and between subjects (BMC vs DMEM treatment) were significant for total blood vessel area, total blood vessel volume, and mean of blood vessel area (P < .001). In the BMC group, there were significantly more arteries (mean, 241.6 ± 77.0 [standard deviation] vs 196.4 ± 75.2, P = .028), but mean cross-sectional area of these arteries was smaller in ischemic versus nonischemic legs (5.4 mm² ± 1.2 vs 6.8 mm² ± 1.3, P = .006). Total arterial area and volume did not differ significantly between ischemic and nonischemic legs.

Conclusion: BMC injection had a substantial effect on arteriogenesis, with normalization of total arterial area and volume in the BMC group; this effect was successfully depicted.

© RSNA, 2006