Many factors affect the sensitivity and reliability of
tumor vasculature assessment at the small doses of
contrast agent necessary for imaging mice. In this study we investigate the dose-response relationship of ultrasound
contrast agent for a minimal exposure power Doppler technique (minexPD) in a murine
melanoma model. K1735 murine
melanomas grown in 25 C3H/HeN mice were imaged by power Doppler ultrasound using different doses of
contrast agents,
Optison(R) and
Definity(R). Six mice were treated with an antivascular agent,
combretastatin A4-phosphate (CA4P), and imaged before and
after treatment. The color-weighted fractional area (CWFA) of the peak-enhanced image was measured to assess
tumor perfusion on a relative scale of 0 to 100. CWFA increased logarithmically with dose (R(2)=0.97). Treatment with CA4P resulted in pronounced reduction in
tumor perfusion 2 h after contrast injection, but perfusion recovered in the
tumor periphery after 2 days. CWFA was significantly different between pre- and post-treatment for all doses at 2 h and 2 days (p < 0.05, respectively). There was no significant difference detectable between the two
contrast agents,
Optison(R) and
Definity(R) (p = 0.46). In vivo
tumor enhancement in mice increases as logarithmic function with dose. Although the extent of enhancement is dose dependent, the difference between pre- and post-
therapy enhancement is relatively unchanged and uniform at varying doses. The two
contrast agents tested in this study performed equally well. These results suggest that quantitative contrast-enhanced power Doppler imaging is an effective method for monitoring
therapy response of
tumors in mice.