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Tumor Vascularity: Evaluation in a Murine Model with Contrast-enhanced Color Doppler US—Effect of Angiogenesis Inhibitors¹

¹ From the Departments of Radiology (I.I., P.D., G.A.T.) and Surgery (C.B., B.Z.), Children’s Hospital and Harvard Medical School, 300 Longwood Ave, Boston, MA 02115. Received March 26, 2001; revision requested April 23; revision received June 8; accepted July 5. Address correspondence to G.A.T. (e-mail: george.taylor@tch.harvard.edu).

View larger version (25K): [in a new window]   Figure 1A. A, Graph shows estimates at US of prostatic tumor volume over time. * = significant difference in tumor volume between treated () and control () animals (P < .016, repeated-measures analysis of variance). No control animals survived beyond week 6. B-E, Composite gray-scale sagittal US images of prostate tumor in a control animal show increasing tumor volume. F-I, Composite gray-scale sagittal US images of a tumor in a treated animal show no significant change in tumor volume during 6 weeks. Cursors and numbers denote measurements with electronic calipers.

View larger version (109K): [in a new window]   Figure 1B-E. A, Graph shows estimates at US of prostatic tumor volume over time. * = significant difference in tumor volume between treated () and control () animals (P < .016, repeated-measures analysis of variance). No control animals survived beyond week 6. B-E, Composite gray-scale sagittal US images of prostate tumor in a control animal show increasing tumor volume. F-I, Composite gray-scale sagittal US images of a tumor in a treated animal show no significant change in tumor volume during 6 weeks. Cursors and numbers denote measurements with electronic calipers.

View larger version (138K): [in a new window]   Figure 1F-I. A, Graph shows estimates at US of prostatic tumor volume over time. * = significant difference in tumor volume between treated () and control () animals (P < .016, repeated-measures analysis of variance). No control animals survived beyond week 6. B-E, Composite gray-scale sagittal US images of prostate tumor in a control animal show increasing tumor volume. F-I, Composite gray-scale sagittal US images of a tumor in a treated animal show no significant change in tumor volume during 6 weeks. Cursors and numbers denote measurements with electronic calipers.

View larger version (23K): [in a new window]   Figure 2. Graph shows correlation between estimates of tumor volume at US and measurements at autopsy (n = 30; r = .89, P < .001, linear regression).

View larger version (142K): [in a new window]   Figure 3a. (a) Unenhanced sagittal color Doppler US image of tumor in a control animal shows peripheral pattern of vascularity (arrows). (b) Contrast-enhanced color Doppler US image of the same tumor shows flow in central portions of the tumor (arrows) in a mixed pattern of vascularity.

View larger version (125K): [in a new window]   Figure 3b. (a) Unenhanced sagittal color Doppler US image of tumor in a control animal shows peripheral pattern of vascularity (arrows). (b) Contrast-enhanced color Doppler US image of the same tumor shows flow in central portions of the tumor (arrows) in a mixed pattern of vascularity.

View larger version (28K): [in a new window]   Figure 4A. A, Graph of pixel density versus tumor size at unenhanced color Doppler US shows a strong negative correlation between tumor volume and color pixel density (r = -.71, P < .001, power regression analysis). There were no significant differences between treated and control tumors. B, Graph of pixel density versus tumor size at contrast-enhanced color Doppler US shows a strong negative correlation between tumor volume and color pixel density (r = -.64, P < .001, power regression analysis). There were no significant differences between treated and control tumors. C-H, Composite of sagittal contrast-enhanced color Doppler US images in a treated tumor shows decreasing pixel density over 57 days.

View larger version (28K): [in a new window]   Figure 4B. A, Graph of pixel density versus tumor size at unenhanced color Doppler US shows a strong negative correlation between tumor volume and color pixel density (r = -.71, P < .001, power regression analysis). There were no significant differences between treated and control tumors. B, Graph of pixel density versus tumor size at contrast-enhanced color Doppler US shows a strong negative correlation between tumor volume and color pixel density (r = -.64, P < .001, power regression analysis). There were no significant differences between treated and control tumors. C-H, Composite of sagittal contrast-enhanced color Doppler US images in a treated tumor shows decreasing pixel density over 57 days.

View larger version (110K): [in a new window]   Figure 4C-H. A, Graph of pixel density versus tumor size at unenhanced color Doppler US shows a strong negative correlation between tumor volume and color pixel density (r = -.71, P < .001, power regression analysis). There were no significant differences between treated and control tumors. B, Graph of pixel density versus tumor size at contrast-enhanced color Doppler US shows a strong negative correlation between tumor volume and color pixel density (r = -.64, P < .001, power regression analysis). There were no significant differences between treated and control tumors. C-H, Composite of sagittal contrast-enhanced color Doppler US images in a treated tumor shows decreasing pixel density over 57 days.

View larger version (153K): [in a new window]   Figure 5a. (a) Transverse contrast-enhanced color Doppler US image in a treated tumor shows a mixed pattern of vascularity. (b) Photomicrograph of the same tumor as in a shows low vascular density. (Anti-CD1 antibody stain; original magnification, x100). (c) Transverse contrast-enhanced color Doppler US image in a control tumor shows a pattern of mixed vascularity. (d) Photomicrograph of the same tumor as in c shows high vascular density in a control tumor. Vascular endothelium is shown in red. (Anti-CD1 antibody stain; original magnification, x100).

View larger version (189K): [in a new window]   Figure 5b. (a) Transverse contrast-enhanced color Doppler US image in a treated tumor shows a mixed pattern of vascularity. (b) Photomicrograph of the same tumor as in a shows low vascular density. (Anti-CD1 antibody stain; original magnification, x100). (c) Transverse contrast-enhanced color Doppler US image in a control tumor shows a pattern of mixed vascularity. (d) Photomicrograph of the same tumor as in c shows high vascular density in a control tumor. Vascular endothelium is shown in red. (Anti-CD1 antibody stain; original magnification, x100).

View larger version (148K): [in a new window]   Figure 5c. (a) Transverse contrast-enhanced color Doppler US image in a treated tumor shows a mixed pattern of vascularity. (b) Photomicrograph of the same tumor as in a shows low vascular density. (Anti-CD1 antibody stain; original magnification, x100). (c) Transverse contrast-enhanced color Doppler US image in a control tumor shows a pattern of mixed vascularity. (d) Photomicrograph of the same tumor as in c shows high vascular density in a control tumor. Vascular endothelium is shown in red. (Anti-CD1 antibody stain; original magnification, x100).

View larger version (189K): [in a new window]   Figure 5d. (a) Transverse contrast-enhanced color Doppler US image in a treated tumor shows a mixed pattern of vascularity. (b) Photomicrograph of the same tumor as in a shows low vascular density. (Anti-CD1 antibody stain; original magnification, x100). (c) Transverse contrast-enhanced color Doppler US image in a control tumor shows a pattern of mixed vascularity. (d) Photomicrograph of the same tumor as in c shows high vascular density in a control tumor. Vascular endothelium is shown in red. (Anti-CD1 antibody stain; original magnification, x100).