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Objective: To investigate the correlation between intravoxel incoherent motion (IVIM) model-derived parameters and histologically determined microvascularity in pancreatic ductal adenocarcinomas (PDACs) and pancreatic neuroendocrine tumors (PNETs)., Materials and Methods: From April 2013 to May 2014, 42 patients with malignant pancreatic tumors were prospectively examined with diffusion-weighted imaging (DWI) magnetic resonance imaging using a breath-hold variant with 9 b values (0-800 seconds/mm). Intravoxel incoherent motion parameters were extracted from 2 types of volumes of interest (VOIs), one VOI encompassing the total tumor volume (TTV) and another VOI corresponding to the histological regional tumor location (RTV). In 36 PDACs and 6 PNETs, microvessel analysis was performed based on representative tissue sections from the resected tumor tissue, and microvessel density (MVD) as well as microvessel area were calculated. We performed a Pearson-correlation test to study the relationship between IVIM-derived and histology-derived parameters., Results: The DWI-IVIM-derived flowing blood volume fraction f was significantly lower in PDACs compared to PNETs (9.9% ± 5.4% vs 15.5% ± 5.2%; P < 0.0001), the diffusion coefficient D was significantly higher (1.2 ± 0.18 × 10 vs 1.03 ± 0.15 × 10 mm/s; P = 0.001). There was no significant difference in the pseudodiffusion coefficient D* (44.9 ± 52.9 ×10 vs 53.8 ± 51.2 × 10 mm/s). Microvessel density was significantly lower in PDACs (36.8 ± 25.9/mm vs 80.0 ± 26.1/mm; P = 0.0005) compared to PNETs. When derived from the RTV, the flowing blood volume fraction f and MVD of PDACs and PNETs showed excellent correlation (r = 0.85). The correlation using the TTV was moderate (0.64). f (RTV and TTV) and microvessel area showed moderate correlation (r = 0.54/0.47)., Conclusions: Intravoxel incoherent motion-derived flowing blood volume fraction f and MVD demonstrate an excellent correlation with histological tumor features in PDAC and PNET. Consequently, IVIM DWI may serve as noninvasive marker of tumor vascularity in different types of pancreatic neoplasms.

Objectives: Study objectives were the quantitative evaluation of whether conventional abdominal computed tomography (CT) perfusion measurements mathematically correlate with quantitative single-acquisition dual-energy CT (DECT) iodine concentration maps, the determination of the optimum time of acquisition for achieving maximum correlation, and the estimation of the potential for radiation exposure reduction when replacing conventional CT perfusion by single-acquisition DECT iodine concentration maps., Materials and Methods: Dual-energy CT perfusion sequences were dynamically acquired over 51 seconds (34 acquisitions every 1.5 seconds) in 24 patients with histologically verified pancreatic carcinoma using dual-source DECT at tube potentials of 80 kVp and 140 kVp. Using software developed in-house, perfusion maps were calculated from 80-kVp image series using the maximum slope model after deformable motion correction. In addition, quantitative iodine maps were calculated for each of the 34 DECT acquisitions per patient. Within a manual segmentation of the pancreas, voxel-by-voxel correlation between the perfusion map and each of the iodine maps was calculated for each patient to determine the optimum time of acquisition topt defined as the acquisition time of the iodine map with the highest correlation coefficient. Subsequently, regions of interest were placed inside the tumor and inside healthy pancreatic tissue, and correlation between mean perfusion values and mean iodine concentrations within these regions of interest at topt was calculated for the patient sample., Results: The mean (SD) topt was 31.7 (5.4) seconds after the start of contrast agent injection. The mean (SD) perfusion values for healthy pancreatic and tumor tissues were 67.8 (26.7) mL per 100 mL/min and 43.7 (32.2) mL per 100 mL/min, respectively. At topt, the mean (SD) iodine concentrations were 2.07 (0.71) mg/mL in healthy pancreatic and 1.69 (0.98) mg/mL in tumor tissue, respectively. Overall, the correlation between perfusion values and iodine concentrations was high (0.77), with correlation of 0.89 in tumor and of 0.56 in healthy pancreatic tissue at topt. Comparing radiation exposure associated with a single DECT acquisition at topt (0.18 mSv) to that of an 80 kVp CT perfusion sequence (2.96 mSv) indicates that an average reduction of Deff by 94% could be achieved by replacing conventional CT perfusion with a single-acquisition DECT iodine concentration map., Conclusions: Quantitative iodine concentration maps obtained with DECT correlate well with conventional abdominal CT perfusion measurements, suggesting that quantitative iodine maps calculated from a single DECT acquisition at an organ-specific and patient-specific optimum time of acquisition might be able to replace conventional abdominal CT perfusion measurements if the time of acquisition is carefully calibrated. This could lead to large reductions of radiation exposure to the patients while offering quantitative perfusion data for diagnosis.

Objective: Dynamic contrast-enhanced computed tomography (CT) is a sensitive method to evaluate functional changes of the tumor microvasculature after antitumor therapy by monitoring the kinetics of the contrast agent (CA) passage. Therefore, the pharmacokinetic properties of the CA possess a central role: iodinated x-ray CAs are small molecules that distribute rapidly within the extravascular extracellular space, whereas larger macromolecular compounds have a prolonged vascular phase and a restricted volume of distribution. The aim of this animal study was to compare the x-ray CA iopromide and the experimental gadolinium-based dendrimeric Gadomer in the assessment of early therapy response after a single dose of the novel multikinase inhibitor regorafenib., Materials and Methods: For the study, an experimental GS9L rat glioma model was used. For each CA, the animals were divided randomly into a therapy (n = 8) and a placebo group (n = 4). All animals underwent a baseline CT and a second examination 24 hours after therapy with regorafenib (10 mg/kg body weight, oral) and placebo, respectively. The CAs were administered intravenously at a dosage of 0.5 g I or Gd per kg body weight and dynamic CT scans (80 kV, 160 mAseff, no table feed) of the tumor region were performed up to 404 seconds post injection (p.i.). Image evaluation was done by analyzing tumor time-density curves, the area under the curve (AUC), and the results of the 2-compartment Patlak modeling., Results: Significant differences in the time-density curves, the AUC, and the Patlak transfer constant (Ktrans) were observed 24 hours after the regorafenib therapy but not after the placebo treatment. The treatment effects visualized with iopromide were most pronounced at early time points (<100 seconds p.i.), whereas imaging with Gadomer was most effective at a later time window (300-404 seconds p.i.). Comparable reductions of the AUC to 0.69 ± 0.12 (iopromide) and 0.76 ± 0.11 (Gadomer) were found 24 hours after the therapy. A significant higher Ktrans was detected with iopromide (14.3 ± 2.7 mL per 100 mL/min) compared with Gadomer (1.8 ± 0.2 mL per 100 mL/min). However, the relative reduction in Ktrans to 67% ± 11% (iopromide) and to 68% ± 7% (Gadomer) 24 hours after the therapy was similar., Conclusions: Dynamic contrast-enhanced CT detects early treatment effects on tumor microvasculature after a single dose of regorafenib, independently of the used CA. Gadomer showed a later optimal imaging window than iopromide did. However, the efficacy of Gadomer- and iopromide-enhanced imaging is equivalent. The results demonstrate the potential of dynamic contrast-enhanced CT using clinically available x-ray CA in the assessment of early treatment response after administration of novel antitumor therapeutic agents.

Introduction: Stroma reaction leading to fibrosis is the most characteristic histopathological feature of both pancreatic carcinoma and chronic pancreatitis with increased fibrosis compared with healthy pancreatic tissue and further increased fibrosis during radiochemotherapy. Recent studies using intravoxel incoherent motion-derived parameters did not show differences for structural diffusion constant D between these 2 diseases. The aim of this study was to verify the hypothesis that D correlates with the histopathological grade of fibrosis in pancreatic lesions., Materials and Methods: We included 15 patients with histopathologically proven pancreatic carcinoma and 9 patients with histopathologically proven focal chronic pancreatitis. Diffusion-weighted magnetic resonance imaging was performed using 10 b values between 25 and 800 s/mm² before surgery. We calculated the apparent diffusion coefficient and the intravoxel incoherent motion-derived parameters D and f within tumors and focal chronic pancreatitis. The resected tissue was evaluated with regard to the grade of fibrosis., Results: Fourteen patients were found to have moderate fibrosis and 10 patients had severe fibrosis. The difference between the D values for the moderate and severe fibrosis was significant with mean (SD) D value of 1.02 × 10⁻³ (0.48 × 10⁻³ mm/s) and mean (SD) D of 1.22 × 10⁻³ (0.76 × 10⁻³) mm²/s. There were no significant differences for the f and ADC values., Conclusions: Contrary to our hypothesis, D rises from moderate to severe fibrosis. It seems that cellular complexes surrounded by fibrosis provide more structural limitations than does fibrosis alone. Our data suggest that D is not intuitively related to the degree of fibrosis. Compared with healthy tissue, D is reduced in moderate fibrosis but increases when severe fibrosis is present.

Purpose: To determine which of the quantitative parameters obtained from intravoxel incoherent motion diffusion weighted imaging (DWI) is the most significant for the differentiation between pancreatic carcinoma and mass-forming chronic pancreatitis., Materials and Methods: Twenty-nine patients with pancreatic masses were included, 9 proved to have a mass-forming pancreatitis and 20 had a pancreatic carcinoma. The patients were studied using intravoxel incoherent motion DWI with 11 b-values and the apparent diffusion coefficient (ADC), the true diffusion constant (D) and the perfusion fraction (f) were calculated. The diagnostic strength of the parameters was evaluated using receiver operating characteristic analysis., Results: The ADC in chronic pancreatitis was higher than in pancreatic carcinoma with significant differences at b = 50, 75, 100, 150, 200, 300 s/mm (ADC50 = 3.17 ± 0.67 vs. 2.55 ± 1.09, ADC75 = 2.46 ± 0.4 vs. 1.93 ± 0.52, ADC100 = 2.28 ± 0.48 vs. 1.73 ± 0.45, ADC150 = 1.97 ± 0.26 vs. 1.63 ± 0.40, ADC200 = 1.98 ± 0.24 vs. 1.53 ± 0.28, and ADC300 = 1.76 ± 0.19 vs. 1.46 ± 0.31 × 10(-3) mm2/s). No significant differences were found at b = 25, 400, 600, and 800 s/mm (ADC25 = 4.69 ± 0.65 vs. 4.04 ± 1.35, ADC400 = 1.57 ± 0.21 vs. 1.37 ± 0.30, ADC600 = 1.38 ± 0.18 vs. 1.24 ± 0.25, and ADC800 = 1.27 ± 0.10 vs. 1.18 ± 0.19 × 10(-3) mm2/s) nor using ADCtot (1.42 ± 0.23 vs. 1.28 ± 0.12 × 10(-3) mm2/s). The perfusion fraction f was significantly higher in pancreatitis compared with pancreatic carcinoma (16.3% ± 5.30% vs. 8.2% ± 4.00%, P = 0.0001). There was no significant difference between groups for D (1.07 ± 0.224 × 10(-3) mm2/s for chronic pancreatitis and 1.09 ± 0.3 × 10(-3) mm2/s for pancreatic carcinoma, P = 0.66). For f, the highest area under the curve (0.894) and combined sensitivity (80%) and specificity (89.9%) were found., Conclusions: There were significant differences in ADC50-300 between chronic pancreatitis and pancreatic carcinoma. Because D is not significantly different between groups, differences in ADC can be attributed mainly to differences in perfusion. The perfusion fraction f proved to be the superior DWI-derived parameter for differentiation of mass-forming pancreatitis and pancreatic carcinoma.

Objectives: To report our initial experience with dual-energy computed-tomography (CT) cholangiography in potential donors for living-related liver transplantation., Materials and Methods: Seventeen potential donors for living-related liver transplantation (6 women and 11 men; average age 37.8 +/- 10.4 years) underwent contrast-enhanced dual-energy CT cholangiography. A dual-energy CT scan of the liver was carried out with acquisition of 2 raw datasets at tube currents of 140 and 80 kV, respectively. A third weighted average dataset were obtained (weighting ratio: 70% 140 kV, 30% 80 kV). Pure iodine images (fourth dataset) and contrast-optimized images (fifth dataset) were reconstructed. Analysis of all datasets comprised determination of bile duct visualization scores (on a scale of 1 to 4: 1, not visualized; 2, faintly seen; 3, identified but the origin or portions of the duct are not visualized; and 4, excellent visualization from origin to branches), maximum bile duct diameters, bile duct attenuation, and liver parenchyma attenuation as well as image noise, signal-to-noise ratio, and contrast-to-noise ratio., Results: Highest maximum bile duct diameters were detected for optimized-contrast images and the 80 kV dataset, intermediate for pure iodine images and the weighted average dataset and lowest for the 140 kV dataset with significant differences. Highest bile duct attenuation was detected for optimized-contrast images (535.7 +/- 148.3 HU) and the 80 kV dataset (533.7 +/- 145.9 HU) with significant differences compared with pure iodine images (344.9 +/- 106.5 HU) and the weighted average dataset (355.5 +/- 87.6 HU) (P < 0.001). Highest image noise was detected for the 80 kV dataset (39.3 +/- 5.4 HU) with significant differences compared with the optimized-contrast images (31.5 +/- 4.0) (P < 0.001). Highest signal-to-noise ratio and contrast-to-noise ratio were detected for pure iodine images (18.3 +/- 7.1 and 17.6 +/- 7.0) and optimized-contrast images (17.3 +/- 5.8 and 14.8 +/- 5.5) with significant differences compared with the 80 kV dataset (14.0 +/- 5.2 and 11.8 +/- 4.8) and the weighted average dataset (15.1 +/- 4.4 and 12.1 +/- 4.1) (P < 0.001 and P < 0.01)., Conclusions: Dual-energy CT cholangiography in potential donors for living-related liver transplantation is remarkable. Pure iodine images and contrast-optimized images allow precise analysis of the biliary system with increased image quality compared with conventional images. Contrast-optimized images should be used for detection and localization of the bile ducts and pure iodine images for quantitative description of the anatomic dimensions of the biliary segments.

Objectives: To assess the pharmacodynamic behavior of cyanoacrylate, streptavidin-coated microbubbles (MBs) and to investigate their suitability for molecular ultrasound imaging., Materials and Methods: Biodistribution of MBs was analyzed in tumor-bearing mice using gamma-counting, immunohistochemistry, flow cytometry, and ultrasound. Further, vascular endothelial growth factor receptor 2-antibody coupled MBs were used to image tumor neovasculature., Results: After 1 minute >90% of MBs were cleared from the blood and pooled in the lungs, liver, and spleen. Subsequently, within 1 hour a decent reincrease of MB-concentration was observed in the blood. The remaining MBs were removed by liver and spleen macrophages. About 30% of the phagocytosed MBs were intact after 48 hours. Shell fragments were found in the kidneys only. No relevant MB-accumulation was observed in tumors. In contrast, vascular endothelial growth factor receptor 2-specific MBs accumulated significantly within the tumor vasculature (P < 0.05)., Conclusions: The pharmacokinetic behavior of streptavidin-coated cyanoacrylate MBs has been studied. In this context, the low amount of MBs in tumors after >5 minutes is beneficial for specific targeting of angiogenesis.

Rationale and Objectives: To develop a new model for a more realistic evaluation of radial strength and elastic recoil of balloon expandable stents using a new ex vivo model in human cadaver bifurcations of the aorta., Materials and Methods: Four different stents (each group n = 10) were implanted in cadaver common iliac arteries. Randomization was performed either to right or left iliac artery. The specimens were cast filled with silicone caoutchouc and after 24 hours the vascular walls including the stents were removed from the hardened casts. The weight of the cast cylinders of the stents was measured in air and in purified water: the difference of the two values resulted in the buoyancy force and because of that the volume of the bodies as a relative degree for the radial strength could be calculated. The findings were correlated with the workbench tests of the manufacturers., Results: Manufacturer's workbench tests were incomparable because of wide spread specifications. There was a significant difference between the theoretical maximal volume (0.866 mL) and the real cast volumes ( P< 0.025) that corresponds directly to the elastic recoil of the stents. The following mean real cast volumes were measured (corrected for 1 cm): Sinus-Stent 0.677 mL, Palmaz-Stent 0.708 mL, Jostent 0.715 mL, Saxx-Stent 0.732 mL, thus reflecting the various degree of radial strength; therefore, the ranking in radial strength resistance was Saxx, Jostent, Palmaz, and Sinus., Conclusion: High radial strength and low elastic recoil are important requirements of any stent design. Ex vivo tests unlike in vitro physical testing facilitate a realistic evaluation of the inherent stent characteristics. The model used in this study proved to be uniformly valid for physical stent design testing.