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.

Radiofrequency ablation: effect of surrounding tissue composition on coagulation necrosis in a canine tumor model.

PURPOSE: To determine the effect of surrounding tissue type on coagulation necrosis from radiofrequency (RF) ablation in a homogeneous animal tumor model. MATERIALS AND METHODS: Thirty canine venereal sarcomas were implanted in three tissue sites (subcutaneous, kidney, and lung) in 13 mildly immunosuppressed dogs. Five of 25 tumors, which were 19 mm +/- 3 (mean +/- SD) in diameter, were allocated to each of five groups: (a) subcutaneous tumors, (b) kidney tumors, (c) lung tumors with blood flow, and (d) subcutaneous and (e) renal tumors without blood flow, which was achieved by sacrificing the animal to eliminate tumor perfusion. A sixth group comprised larger subcutaneous tumors (mean diameter, 46 mm +/- 4) that were also treated. RF ablation was performed with a 1-cm tip and 5 minutes of ablation at 90 degrees C +/- 1. Impedance, temperature, and resultant coagulation diameter were recorded and compared. Data were analyzed statistically, including one-way analysis of variance to determine the effect of tissue conductivity (ie, systemic impedance) on necrosis size and tissue temperatures. Linear regression analysis was used to compare changes in impedance between the control and experimental groups. RESULTS: Increasing linear correlation was observed between tumor coagulation diameter and overall baseline system impedance (R(2) = 0.65). RF ablation of lung tumors resulted in the greatest coagulation diameter (13.0 mm +/- 3.5) compared with that in the other groups (P <.01). The smallest coagulation diameter was observed in kidney tumors in the presence of blood flow (7.3 mm +/- 0.6) compared with that in the other groups (P <.01). Elimination of blood flow in kidney tumors increased coagulation diameter to 10.3 mm +/- 0.6 (P <.01). After RF ablation, coagulation diameter in the subcutaneous tumor groups was the same (mean, 9.8 mm +/- 1.0) (difference not significant), regardless of tumor size or presence of blood flow. CONCLUSION: The characteristics of tissue that surrounds tumor, including vascularity and electric conductivity, affect ablation outcome. Predominance of tissue-specific characteristics will likely result in site-specific differences in RF-induced coagulation necrosis.

Beneficial effects of CD39/ecto-nucleoside triphosphate diphosphohydrolase-1 in murine intestinal ischemia-reperfusion injury.

CD39 (ecto-nucleoside triphosphate diphosphohydrolase-1; E-NTPDase-1), is highly expressed on quiescent vascular endothelial cells and efficiently hydrolyzes extracellular ATP and ADP to AMP and ultimately adenosine. This action blocks extracellular nucleotide-dependent platelet aggregation and abrogates endothelial cell activation. However, CD39 enzymatic activity is rapidly lost following exposure to oxidant stress. Modulation of extracellular nucleotide levels may therefore play an important role in the pathogenesis of vascular injury. Acute ischemic injury of the bowel is a serious medical condition characterized by high mortality rates with limited therapeutic options. Here we evaluate the effects of cd39-deletion in mutant mice and the use of supplemental NTPDase or adenosine in influencing the outcomes of intestinal ischemia-reperfusion. Wild-type, cd39-null, or hemizygous cd39-deficient mice were subjected to intestinal ischemia. In selected animals, 0.2 U/g apyrase (soluble NTPDase) was administered prior to re-establishment of blood-flow. In parallel experiments adenosine/amrinone was infused over 60 min during reperfusion periods. Survival rates were determined, serum and tissue samples were taken. Intravital videomicroscopy and studies of vascular permeability were used to study platelet-endothelial cell interactions and determine capillary leakage. In wild-type animals, ischemia reperfusion injury resulted in 60% mortality within 48 hours. In mutant mice null or deficient for cd39, ischemia reperfusion-related death occurred in 80% of animals. Apyrase supplementation protected all wild-type animals from death due to intestinal ischemia but did not fully protect cd39-null and cd39-hemizygote mice. Adenosine/amrinone treatment failed to improve survival figures. In wild type mice, platelet adherence to postcapillary venules was significantly decreased and vascular integrity was well preserved following apyrase administration. In cd39-null mice, ischemia-reperfusion induced marked albumin leakage indicative of heightened vascular permaeability when compared to wild-type animals (p=0.04). Treatment with NTPDase or adenosine supplementation abrogated the increased vascular permeability in ischemic jejunal specimens of both wild-type mice and cd39-null. CD39 activity modulates platelet activation and vascular leak during intestinal ischemia reperfusion injury in vivo. The potential of NTPDases to maintain vascular integrity suggests potential pharmacological benefit of these agents in mesenteric ischemic injury.

Computed tomography colonography (virtual colonoscopy): update on technique, applications, and future developments.

Computed topography colonography (CTC) was first described in 1994 as a rapid, non-invasive imaging method to investigate the colon and rectum. Since the advent of CTC, it has been regarded as a potential alternative technique to conventional colonoscopy for detection of colorectal polyps and cancers. Patients undergo standard bowel preparation 24 to 48 hours before the procedure, using either a standard barium enema preparation or balanced polyethylene glycol (PEG) solution. This rapid examination, without the use of sedation or intervention, is well-tolerated by patients. The potential for limited bowel preparation can reduce discomfort associated with traditional purging techniques significantly, and result in an improved perception of the screening study. CTC is performed using a single or multislice CT scanner, with acquisition of volumetric data from the entire colon. Multislice technology enables fast scanning with high resolution. To minimize the radiation dose, efforts have been made to adapt the tube current to the minimum accepted dose while not diminishing study performance. Acquired CT data are transferred onto a dedicated workstation equipped with navigator software, which permits the radiologist to obtain multiplanar reformations as well as construct an endoluminal model of the air-distended colon. Currently, the most widely accepted application for CTC is following incomplete colonoscopy. Other indications that await further clinical validation include colorectal screening. The collective experience of published studies shows CTC to be an accurate tool for detection of clinically significant colorectal polyps. Specificity and sensitivity of CTC are excellent for polyps larger than 10 mm.