Quantitative contrast enhanced ultrasound and CT assessment of tumor response to antiangiogenic therapy in rats.

Contrast-enhanced computed tomography (CECT) and contrast-enhanced destruction-replenishment subharmonic ultrasound (CEDRSU) were used to quantify blood flow and tumor viability during antiangiogenic therapy. SU11657 or placebo was administered to R3230AC tumor-baring rats over a two-week period. CEDRSU vascular volume (ASI) and volume flow (VF) and CECT perfusion (PR) and permeability (PM) measurements were made on day 0, 7 and 14. The percent change in imaging parameters was calculated between day 0 and 7 and 14. Serum drug level (SDL) was compared with imaging parameters. Imaging estimates of tumor viability were compared with histology images on day 14. The percent change in imaging measures for control and treated groups were significantly different on day 7(ASI, p = 0.02; VF, p = 0.008, PR, p = 0.0007; PM, p = 0.003) and 14 (ASI, p = 0.0004; VF, p = 0.002, PR, p = 0.003; PM, p = 0.005). Imaging identified animals with lower SDLs as having higher tumor vascularity and flow. Spatial estimates of tumor viability correlated with histology (CEDRSU, r(2) = 0.92, p << 0.001; CT, r(2) = 0.86, p << 0.001). CEDRSU and CECT provide measures of blood flow and viability in tumors during antiangiogenic therapy. Tumors with higher flow were identified in animals with lower SDL. SU11657 treatment results in decreased tumor flow and viability.

Contrast-enhanced computed tomography and ultrasound for the evaluation of tumor blood flow.

OBJECTIVE: We evaluated implanted rat mammary adenocarcinoma tumors during a 5-week period using ultrasound, computed tomography (CT), and histology. MATERIALS AND METHODS: Contrast-enhanced ultrasound with a destruction-replenishment imaging scheme was used to derive estimates of blood volume and flow. These ultrasound-derived measures of microvascular physiology were compared with contrast-enhanced CT-derived measures of perfusion and vascular volume made by the Mullani-Gould formula and Patlak analysis, respectively. RESULTS: The tumor cross-sectional area and necrotic core cross-sectional area determined by the 3 methods were correlated (r>0.8, P<0.001, n=15). The spatial integral of perfusion estimated by CT correlated with the spatial integral of flow from ultrasound (P<0.05). The contrast-enhanced tumor area calculated from the ultrasound analysis was highly correlated with the contrast-enhanced area estimated by CT images (r=0.89, P<0.001, n=15). However, the fraction of the tumor area enhanced by the CT contrast agent was significantly larger than either the fraction enhanced by ultrasound contrast agent or than the viable area as estimated from histology slides. CONCLUSION: Destruction-replenishment ultrasound provides valuable information about the spatial distribution of blood flow and vascular volume in tumors and ultrasound analysis compares favorably with a validated contrast-enhanced CT method.