Body tumor CT perfusion protocols: optimization of acquisition scan parameters in a rat tumor model.

PURPOSE: To evaluate the effects of total scanning time (TST), interscan delay (ISD), inclusion of image at peak vascular enhancement (IPVE), and selection of the input function vessel on the accuracy of tumor blood flow (BF) calculation with computed tomography (CT) in an animal model. MATERIALS AND METHODS: All animal protocols and experiments were approved by the institutional animal care and use committee prior to study initiation. After injection of 0.2 or 0.4 mL of iodinated contrast material, six rats with mammary adenocarcinoma (three tumors each) were scanned in the axial mode for 5 minutes with 1-second ISD (reference scan), 2.5-mm section thickness, 2.5-mm interval, pitch of 1.3, 120 kV, 240 mA, and 0.5-second rotation time. A total of 126 dynamic data sets were created with commercial software by varying TST and ISD, including or excluding the IPVE, and using the aorta or inferior vena cava (IVC) as the input function. Comparative analyses were used to test for significant differences (t test, Wilcoxon signed rank test). Regression analysis was performed to assess the relationship between attenuation of the input function vessel and BF. RESULTS: No significant difference was observed (P > .05) when TST was as short as 30 seconds (range, 20-23 mL/100 g). In sequences performed with an ISD longer than 8 seconds, BF was significantly elevated (P < .01). Inclusion of the IPVE eliminated this difference (P > .10). Use of the IVC as the input function resulted in significantly higher BF (P < .02), with a correlation between peak attenuation and BF (R(2) = 0.43). CONCLUSION: To reduce radiation dose in tumor perfusion with CT, TST can be reduced without causing significant changes in BF calculation in an animal model. Scanning the aortic reference with peak contrast enhancement reduces variability sufficiently to allow for longer ISDs.

Perfusion MDCT enables early detection of therapeutic response to antiangiogenic therapy.

OBJECTIVE: The objective of our study was to determine whether perfusion CT can be used to detect early changes in therapeutic response to antiangiogenic therapy in an animal tumor model. MATERIALS AND METHODS: Twenty-five rats implanted with R3230 mammary adenocarcinoma (diameter, 1.2-2.0 cm) randomly received 7.5 or 30 mg/kg of an antiangiogenic agent, sorafenib, by daily gavage for 4 (n = 4), 9 (n = 9), or 14 (n = 5) days. Seven untreated animals served as a control group. Perfusion MDCT was performed at days 0, 4, 9, and 14 with 0.4 mL of ioversol (350 mg/mL) and included four 5-mm slices covering the entire tumor volume. Changes in tumor growth were determined by volumetric analysis of CT data. Serial changes in tumor volume and blood flow were assessed and correlated with pathology findings. RESULTS: All control tumors grew larger (from 2.0 +/- 0.7 cm(3) at day 0 to 5.9 +/- 1.0 cm(3) at day 14), whereas all treated tumors shrank (from 2.5 +/- 1.1 to 2.1 +/- 1.0 cm(3)), with a statistically significant rate of growth or shrinkage in both groups (p < 0.05). Although perfusion in the control tumors changed little from day 0 to day 14 (day 0, 18.1 +/- 9.2 mL/min/100 g; day 4, 15.8 +/- 5.6; day 9, 21.7 +/- 12.2; day 14, 27.7 +/- 34), in the sorafenib group, the mean blood flow was significantly lower at day 4 (5.2 +/- 3.2 mL/min/100 g, 77% decrease), day 9 (6.4 +/- 4.0 mL/min/100 g, 66% decrease), and day 14 (6.3 +/- 5.2 mL/min/100 g, 83% decrease) compared with day 0 (23.8 +/- 11.6 mL/min/100 g) (p < 0.05). Poor correlation was seen between changes in blood flow and tumor volume for days 0-9 (r(2) = 0.34), 4-9 (r(2) = 0.0004), and 9-14 (r(2) = 0.16). However, when comparing day 4 images with days 9 and 14 images, seven of 14 (50%) sorafenib-treated tumors had focal areas of new perfusion that correlated with areas of histopathologic viability despite the fact that these tumors were shrinking in size from day 4 onward (day 4, 2.18 +/- 0.8 cm(3); day 9, 1.98 +/- 0.8 cm(3)). CONCLUSION: Perfusion MDCT can detect focal blood flow changes even when the tumor is shrinking, possibly indicating early reversal of tumor responsiveness to antiangiogenic therapy. Given that changes in tumor volume after antiangiogenic therapy do not necessarily correlate with true treatment response, physiologic imaging of tumor perfusion may be necessary.

CT perfusion for determination of pharmacologically mediated blood flow changes in an animal tumor model.

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 r(2)=0.73; multisection CT, r=0.93 and r(2)=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.