Bolus Injection Of SonoVue Research Articles

Value of Spleen Dynamic Contrast-enhanced Ultrasound Parameters in Predicting Hepatic Vein Pressure Gradient for Patients With Liver Cirrhosis.

To explore dynamic contrast-enhanced ultrasound (CEUS) parameters in predicting hepatic vein pressure gradient (HVPG) for patients with liver cirrhosis (LC). Noninvasive diagnosis of HVPG remains a challenge. This prospective study included patients with LC undergoing hepatic vein catheterization and pressure measurement at the hospital from May 2021 to January 2023. The CEUS images (Mindray Resona R9, 1-6-MHz probe frequency; mechanical index=0.08; image depth=10cm; focus at the lowest point of the diaphragm; dynamic range=70dB; optimal gain; single SonoVue bolus injection) were taken for 60 seconds after injection and analyzed using VueBox. HVPG (ie, the gold standard for portal hypertension) was measured routinely by catheterization. Fifty patients with LC were included in the study. The rise time (r=0.6, P<0.01), the fall time (r=0.7, P<0.01), the peak time (r=0.6, P<0.01), wash-in area under the curve (AUC) (r=0.5, P<0.01), the wash-out phase AUC (r=0.4, P<0.01) and wash-in and wash-out phase AUC (r=0.4, P<0.01) of the dynamic spleen CEUS were positively correlated with HVPG. The optimal fall time cutoff levels to predict HVPG ≥10mmHg and ≥12mmHg were 27.0 and 36.4 seconds, with the AUC being 0.958 and 0.941, respectively. The optimal area under the wash-in area cutoff level to predict HVPG ≥10mmHg and ≥12mmHg was 1,658,967.38 (a.u) and 4,244,015.90 (a.u), with the AUC being 0.865 and 0.877, respectively. The fall time and wash-in AUC obtained by dynamic CEUS may help diagnose HVPG in patients with LC without requiring invasive hepatic vein catheterization.

Ultrasound Microvascular Imaging Based on Super-Resolution Radial Fluctuations.

Super-resolution ultrasound (SRUS) has become a tool for in vivo microvascular imaging. Most of the SRUS methods are based on microbubble localization: namely, ultrasound localization microscopy (ULM). The aim of this study was to develop a nonlocalization SRUS method and verify its feasibility in microvascular imaging. We introduce a new super-resolution strategy based on the postprocessing of contrast-enhanced ultrasound. The proposed method, which is termed ultrasound diffraction attenuation microscopy (UDAM), uses super-resolution radial fluctuations instead of microbubble localization to overcome acoustic diffraction limits. Biceps of Japanese long-ear white rabbits were adopted to validate its feasibility on muscle vascular imaging, using a clinical accessible ultrasound system at a frame rate of 30 Hz under a single bolus injection of SonoVue (Bracco SpA, Milan, Italy). The super-resolution image was compared with the maximum-intensity projection and ULM. The animal study illustrates that the proposed UDAM can obtain super-resolution microvascular images of rabbits' muscles under a single bolus injection of SonoVue with a 150-second contrast-enhanced ultrasound video. Both ULM and UDAM can achieve a very similar vascular structure with the maximum-intensity projection but much higher spatial resolution. The measurement of 1-dimensional signals shows that UDAM can distinguish the subwavelength structures and substantial reduce the full width at half-maximum of microvessels. We conclude UDAM provides a noninvasive tool for in vivo super-resolution microvascular imaging.

Evaluation of cerebral perfusion by contrast-enhanced ultrasound at low mechanical index in cerebral ischemia rat model.

No data is available for brain low mechanical index (low-MI) contrast-enhanced ultrasound (CEUS). This study aimed to assess low-MI CEUS for cerebral ischemia in rats. Twenty adult Wistar rats were divided to the brain ischemia (N.=12) and sham (N.=8) groups. A Logiq E9 (GE; ML6-15 probe) was used. Bolus injection of SonoVue (Bracco) at 3.6 mL/kg was performed. Cerebral perfusion was evaluated using time to peak (TTP) and area under the curve (AUC) of time-intensity curves (TIC). There was a decrease in peak systolic BFV of anterior cerebral and middle cerebral arteries in ischemic rats and a sharp increase in peak systolic BFV of basilar artery compared with sham rats (all P<0.01). Microbubble enhancement occurred in the Willis circle, followed by diencephalon and telencephalon. The AUC and TTP of the region of interest at telencephalon were significantly different between the two groups; in addition, the differences with the diencephalon were also significant (all P<0.01). There were differences in AUC and TTP between the telencephalon and diencephalon of the same group (all P<0.05). Real-time low-MI CEUS could sensitively demonstrate dynamic microbubble enhancement in brain tissues and allows semi-quantitative assessment of cerebral perfusion after ischemic brain injury using TIC.

Early Changes in Contrast Enhanced Ultrasound Predict for Pathologic Response to Chemotherapy in an Animal Tumor Model

The purpose of this study was to examine CEUS whether could earlier predict pathologic response to chemotherapy than morphologic method in a MCF-7 tumor model. Twenty MCF-7 breast cancer bearing nude mice were included in this study. Animals received either adriamycin or a control substance were imaged before and after treatment with an ultrasound scanner after bolus injection of SonoVue. Dynamic contrast enhanced ultrasound was performed at pretherapy, Day 3, Day 5 and Day 7 after adriamycin administration. Regions of interest within the tumor were analyzed off-line to determine perfusion parameters including peak enhancement (PE), area under the curve of wash-in (WIAUC), wash-in rate (WIR), wash-in perfusion index (WIPI) and quality of fit (QOF). The section equivalent to ultrasound imaging plane was stained with Hematoxylin and Eosin to allow for assessment of tumor cell density and Ki67 for situation of tumor proliferation, CD34 for tumor micro-vascular density. There were no significant differences in tumors perfusion and tumor volumes before treatment. Treatment with adriamycin resulted into a significant decrease in PE, WIAUC, WIR and WIPI in comparison with control group (P < 0.05) at Day 3, when there was no significant difference in tumor volume. The volume of treated tumors was significant smaller than that of control tumors (P < 0.05) at day 7. The tumor cell density estimated by pathology slice was significantly lower in treated tumors than in control tumors at day 7 (P < 0.05). The positive Ki67 cell density and CD34 estimated by pathology slice were also significantly lower in treated tumors than in control tumors at day 7 (P < 0.05). The correlation between micro-vascular and perfusion parameters was obvious (P < 0.05). Changes in tumor micro-vessel functionality as depicted by CEUS early on after starting adriamycin -based chemotherapy can predict final pathologic response. Contrast enhanced ultrasound will be a new way for evaluating tumor response to chemoth.

Dynamic contrast-enhanced ultrasound parametric maps to evaluate intratumoral vascularization.

The purposes of this study were to assess the reliability of parametric maps from dynamic contrast-enhanced ultrasound (DCE-US) to reflect the heterogeneous distribution of intratumoral vascularization and to predict the tissue features linked to vasculature. This study was designed to compare DCE-US parametric maps with histologic vascularity measurements. Dynamic contrast-enhanced ultrasound was performed on 17 melanoma-bearing nude mice after a 0.1-mL bolus injection of SonoVue (Bracco SPA, Milan, Italy). The parametric maps were developed from raw linear data to extract pixelwise 2 semiquantitative parameters related to perfusion and blood volume, namely, area under the curve (AUC) and peak intensity (PI). The mathematical method to fit the time-intensity curve for each pixel was a polynomial model used in clinical routine and patented by the team. Regions of interest (ROIs) were drawn on DCE-US parametric maps for whole tumors and for several local areas of 15 mm within each tumor (iROI), the latter reflecting the heterogeneity of intratumoral blood volume. As the criterion standard correlation, microvessel densities (MVDs) were determined for both ROI categories. In detail, for all iROI of 15 mm, MVD and maturity were divided separately for vessels of 0 to 10 μm, 10 to 40 μm, and greater than 40 μm in diameter, and the results were correlated with the ultrasound findings. Among the 17 studied mice, a total of 64 iROIs were analyzed. For the whole-tumor ROI set, AUC and PI values significantly correlated with MVD (rAUC = 0.52 [P = 0.0408] and rPI = 0.70 [P = 0.0026]). In the case of multiple iROI, a strong linear correlation was observed between the DCE-US parameters and the density of vessels ranging in their diameter from 0 to 10 μm (rAUC = 0.68 [P < 0.0001]; rPI = 0.63 [P < 0.0001]), 10 to 40 μm (rAUC = 0.98 [P = 0.0003]; rPI = 0.98 [P = 0.0004]), and greater than 40 μm (rAUC = 0.86 [P = 0.0120]; rPI = 0.92 [P = 0.0034]), respectively. However, the DCE-US parameter values of perfusion and blood volume were not significantly different according to the diameters (AUC: P = 0.1731; PI: P = 0.2918) and maturity of blood vessels. Parametric maps of DCE-US can be reliably established from raw linear data and reflect the heterogeneous histological measures of vascularization within tumors. In contrast, the values of DCE-US parametric maps (AUC, PI) do not allow deduction of heterogeneous tissue features such as the diameters and maturity of vascular networks.

Contrast-enhanced US quantitatively detects changes of tumor perfusion in a murine breast cancer model during adriamycin chemotherapy

Currently used morphologic criteria have limitations in assessing tumor response to chemotherapy because of the relatively slow tumor shrinkage as measured by conventional morphologic imaging. Functional imaging techniques show promising results in early assessment of tumor response to treatment. To quantitatively detect changes in tumor perfusion during chemotherapy with contrast-enhanced ultrasound. Twenty-three MCF-7 breast cancer bearing nude mice treated by either adriamycin (n = 11) or sterile saline (n = 12) were imaged before and after treatment with an ultrasound scanner after bolus injection of SonoVue. Regions of interest within the tumor were analyzed offline to determine perfusion parameters including peak enhancement (PE), area under the curve of wash-in (WiAUC), rise time (RT), wash-in rate (WiR), wash-in perfusion index (WiPI), and quality of fit (QOF). Hematoxylin and eosin was used to assess tumor cell density and immunohistochemical analysis was performed for evaluation of microvascular density (MVD). Treatment with adriamycin significantly reduced tumor growth in comparison to the control group (P < 0.001). There was no significant difference in perfusion parameters before treatment. Treatment with adriamycin resulted in a significant decrease in PE, WiAUC, WiR, and WiPI in comparison with control group (P < 0.01). The tumor cell density estimated by pathology slice was significantly lower in treated tumors than in control tumors after treatment (P < 0.001). Immunohistochemistry showed significant decreases of MVD in treated tumors as compared with control tumors (P < 0.001) after treatment. Quantitative contrast-enhanced ultrasound can detect the change of tumor perfusion after chemotherapy, which may enable early assess tumor response to chemotherapy.

Prolonged Heterogeneous Liver Enhancement on Contrast-Enhanced Ultrasound

Prolonged heterogeneous liver enhancement (PHLE) is a rare phenomenon that is similar to the ultrasound findings of portal venous gas. The purpose of this report is to describe the phenomenon of PHLE after the injection of the ultrasound contrast agent SonoVue(®). From 2000 to 2013, 13 patients with PHLE ("cloudy", "wool-like") after bolus injection of SonoVue(®) were observed. The height, weight, and body mass index (BMI) of the patients, and the number of injections were analyzed. In addition, the literature was reviewed. The phenomenon occurred as early as 2 minutes after bolus contrast administration and lasted up to 5 hours on both B-mode and contrast-specific ultrasound. 8/13 (62 %) patients received two or more boluses. None of the patients experienced SonoVue(®)-related side effects or health problems. The phenomenon was not reproducible in 3 patients who received a second SonoVue(®) injection 24 hours after receiving the first. This phenomenon is more likely to occur in patients who receive high-dose (or multiple) injections of UCA. It may occur as early as 2 minutes after contrast administration, and therefore, may affect the evaluation of focal liver lesions in the late phase. This phenomenon should not be misdiagnosed as a pathological finding of the liver.

Quantitative low mechanical index contrast-enhanced endoscopic ultrasound for the differential diagnosis of chronic pseudotumoral pancreatitis and pancreatic cancer

BackgroundSecond-generation intravenous blood-pool ultrasound contrast agents are increasingly used in endoscopic ultrasound (EUS) for characterization of microvascularization, differential diagnosis of benign and malignant focal lesions, as well as improved staging and guidance of therapeutic procedures.MethodsThe aim of our study was to prospectively compare the vascularisation patterns in chronic pseudotumoral pancreatitis and pancreatic cancer using quantitative low mechanical index (MI) contrast-enhanced EUS. We included 51 patients with chronic pseudotumoral pancreatitis (n = 19) and pancreatic cancer (n = 32). Perfusion imaging started with a bolus injection of Sonovue (2.4 ml), followed by analysis in the early arterial (wash-in) and late venous (wash-out) phase. Perfusion analysis was performed by post-processing of the raw data (time intensity curve [TIC] analysis). TIC analysis was performed inside the tumor and the pancreatic parenchyma, with depiction of the dynamic vascular pattern generated by specific software. Statistical analysis was performed on raw data extracted from the TIC analysis. Final diagnosis was based on a combination of EUS-FNA, surgery and follow-up of minimum 6 months in negative cases.ResultsThe sensitivity and specificity of low MI contrast enhanced EUS using TIC were sensitivity and specificity of low MI contrast enhanced EUS using TIC analysis were 93.75% (95% CI = 77.77 - 98.91%) and 89.47% (95% CI = 65.46 - 98.15%), respectively. Pseudotumoral chronic pancreatitis showed in the majority of cases a hypervascular appearance in the early arterial phase of contrast-enhancement, with a dynamic enhancement pattern similar with the rest of the parenchyma. Statistical analysis of the resulting series of individual intensities revealed no statistically relevant differences (p = .78). Pancreatic adenocarcinoma was usually a hypovascular lesion, showing low contrast-enhancement during the early arterial and also during the late venous phase of contrast-enhancement, also lower than the normal surrounding parenchyma. We found statistically significant differences in values during TIC analysis (p < .001).ConclusionsLow MI contrast enhanced EUS technique is expected to improve the differential diagnosis of focal pancreatic lesions. However, further multicentric randomized studies will confirm the exact role of the technique and its place in imaging assessment of focal pancreatic lesions.

Evaluation with DCE-US of antiangiogenic treatments in 539 patients allowing the selection of one surrogate marker correlated to overall survival.

4618 Background: A prospective study of dynamic contrast-enhanced ultrasound (DCE-US) with quantification for the evaluation of antiangiogenic treatments was launched (19 centers), supported by the French National Cancer Institute. The objectives were the diffusion of the standardized method, a cost evaluation and the identification of perfusion parameters predicting tumor response. Methods: All patients had DCE-US at baseline, D7, D14, D30, D60 and every two months. Each examination included a bolus injection of sonovue (Bracco) and 3 minutes of raw linear data with an Aplio (Toshiba). Raw data were analyzed with a mathematical model (patent PCT/IB2006/003742) to evaluate 7 parameters characterizing the tumor perfusion curve. Response to treatment was evaluated every 2 months with RECIST criteria. In order to have sufficient follow-up data, the statistical analysis has to be performed more than 6 months after the inclusion of the last analyzed patient. Inclusions were closed in March 2010. Results: A total of 539 patients have been included (mainly RCC (157) and HCC (107)); more than 2 000 DCE-US and 1700 CT-scan were performed. A follow-up more than 12 months showed that 3 parameters have a strong significant difference (p&lt;0.0003) according to the response at 6 months. The decrease of more than 40% of AUC at one month is correlated to the TTP (p&lt; 001) and OS (p&lt; 0.04). Conclusions: Final results confirm the usefulness of this tool to monitor anti-angiogenic treatments. The criteria: the decrease of more than 40% of AUC at one month is predictive of response.

Value of contrast-enhanced ultrasound in analysing testicular and epididymal mass lesions

Objective To investigate the differential value of contrast-enhanced ultrasonography (CEUS) and time-intensity curves(TIC) in diagnosing testicular and epididymal mass lesions.Methods CEUS via intravenous bolus injection of SonoVue and TIC were performed for quantitative analysis of testicular and epididymal mass lesions.Forty-one patients with 42 testicular and epididymal mass lesions and 26 normal testicles were examined with CUES,the perfusion progress were recorded dynamically,which findings were compared with surgery.Results Twenty-three (54.76％) malignant masses displayed enhanced pattern as evenly enhanced,fast-in and fast-out (8.7％),evenly enhanced,fast-in and slow-out (65.2 ％ ),unevenly enhanced,fast-in and slow-out (26.1％ ).Ninteen (45.24 ％ ) benign masses revealed enhanced pattern as unevenly enhanced,fast-in and slow-out ( 10.5 ％),evenly enhanced,slow-in and slowout ( 10.5 ％ ),unevenly enhanced,slow-in and slow-out ( 36.9 ％ ),without enhancement ( 42.1％ ).There was statistical difference of peak intensity,time to peak and areas among malignant group,benign group and normal group ( P ＜ 0.05).Conclusions CEUS combined with TIC could provide differential diagnostic value for testicular and epididymal mass lesions. Key words: Ultrasonography; Microbubbles; Testicular neoplasms; Epididymal diseases

Comparison of consecutive bolus tracking and flash replenishment measurements for the assessment of tissue hemodynamics using contrast-enhanced ultrasound (CEUS) in an experimental human squamous cell carcinoma model

To evaluate "bolus-tracking" (BT) and "flash-replenishment" (FR) for the assessment of tissue hemodynamics by contrast-enhanced ultrasound (CEUS) in an experimental small-animal-squamous-cell-carcinoma-model. Since the underlying tissue is the same, strong correlations between parameter outcomes of both techniques are expected. Human hypopharynx-carcinoma-cells were subcutaneously injected into the left flank of 18 female athymic-nude-rats. After 10 days of subcutaneous tumour growth, bolus tracking and flash-replenishment measurements were performed consecutively in the same imaging plane in each rat after bolus-injection of SonoVue via the lateral tail vein using a high-end ultrasound system with a 15 MHz probe. Video-sequences were analysed with dedicated software (VueBox®, Bracco-Suisse®). From BT measurements, the parameters peak enhancement (PEBT), wash-in area-under-the-curve (Wi-AUCBT), mean transit time (MTTBT), wash-in-rate (WiRBT) and perfusion-index (Wi-PIBT) were derived; FR yielded estimates of relative-blood-volume (rBVFR), mean transit time MTTFR, relative blood flow rBFFR and wash-in rate Wi-RFR. In all rats, BT and FR measurements could be completed successfully. Highly significant correlations were observed between rBVFR and PEBT, rBVFR and Wi-AUCBT, rBVFR and MTTBT, rBVFR and WiPIBT, MTTFR and MTTBT, rBFFR and PEBT, rBFFR and Wi-AUCBT, rBFFR and WiRBT, rBFFR and WiPIBT, WiRFR and PEBT, WiRFR and Wi-AUCBT, WiRFR and WiRBT and WiRFR and WiPIBT. Whereas bolus tracking can be used in a wide range of modalities including CEUS, CT and MR, FR as a technique for the assessment of tissue hemodynamics is unique to CEUS. Although BT and FR yield different parameters, the underlying tissue hemodynamics are equal. In this work, we were able to demonstrate strong correlations between different parameters of both modalities in a small-animal-tumor-model, indicating that flash-replenishment is a valid alternative to the more established bolus-tracking technique. Although the lack of absolute, quantitative parameters hinders a direct comparison of both modalities, FR and BT should both be suitable for a relative comparison, e.g. between baseline and follow-up examinations.

Final results of a French multicentric prospective study of dynamic contrast-enhanced ultrasound (DCE-US) for the evaluation of antiangiogenic treatments in 537 patients.

e13500 Background: A prospective evaluation of dynamic contrast-enhanced ultrasound (DCE-US) with quantification to evaluate antiangiogenic treatments was launched in 2007 in 19 French comprehensive anticancer centers with 65 radiologists, and was supported by the French National Cancer Institute. The objectives were to disseminate the standardized method and to identify the perfusion parameters predicting tumor response to different antiangiogenic treatments. Methods: All patients had an examination just before the start of the antiangiogenic treatment (D-1) and at D7, D14, D30 and D60. Each examination included a bolus injection of Sonovue (Bracco) and raw linear data were recorded over 3 minutes with an Aplio (Toshiba). The raw linear data were analyzed with a mathematical model (patent PCT/IB2006/003742) to evaluate 7 parameters characterizing the tumor perfusion curve. The quantification of DCE-US raw data was done blinded to clinical data. Response to treatment was evaluated every 2 months with RECIST criteria with scanographic evaluations and blind double reading Complete or partial responses and stabilization were classified as successes and progression as treatment failure. Results: Since October 2007, 537 patients have been included (mainly with renal cell carcinomas [157] and hepatocellular carcinoma [107]). 1823 DCE-US examinations and 1296 scanographic evaluations have been performed. After a median follow-up of 12 months, we confirm that 5 parameters exhibit a significant difference (P<0.05) in their variation between D-1 and D30 according to DFS. Conclusions: Our results confirm the validity of this tool for monitoring antiangiogenic treatments. Decision rules will be proposed to classify patients according to their risk of relapse.

Contrast-enhanced ultrasonic parametric perfusion imaging in the evaluation of antiangiogenic tumor treatment

To assess the validity of contrast-enhanced ultrasonic parametric perfusion imaging in the evaluation of antiangiogenic tumor treatment by using histology as the reference standard. H22 hepatoma-bearing mice were treated with thalidomide or placebo by intraperitoneal injection. Contrast-enhanced ultrasound was performed on day 8 after bolus injection of SonoVue. Three different parametric perfusion images were calculated based on the following parameters: area under the curve (AUC), maximum intensity (IMAX) and perfusion index (PI). A score from 1 to 5 (1 = low, 5 = excellent) was used for analysis of parametric perfusion images by two independent readers. Immunohistochemical analysis was performed for evaluation of microvascular density (MVD). Treatment with thalidomide resulted in a significant decrease in perfusion scores assigned to AUC, IMAX and PI parametric images as compared with control tumors (P < 0.001). Immunohistochemistry showed significant decreases of MVD in treated tumors as compared with control tumors (P = 0.002). MVD was positively correlated with the perfusion scores assigned to AUC parametric images (r = 0.568, P = 0.009), IMAX parametric images (r = 0.614, P = 0.004) and PI parametric images (r = 0.636, P = 0.003). Contrast-enhanced ultrasonic parametric perfusion imaging provides a noninvasive tool to directly visualize tumor perfusion changes after antiangiogenic tumor treatment.

Value of quantitatively analyzing tissue perfusion parameters of contrast enhanced ultrasound in the evaluation of antiangiogenic therapeutics effect in a mouse hepatoma model

Objective To evaluate the value of quantitatively analyzing tissue perfusion parameters of contrast-enhanced ultrasound in the evaluation of antiangiogenic therapeutics effect. Methods Kun-min mouse were subcutaneously implanted with H22 cells. Ten mouse were treated with thalidomide (200 mg/kg once daily) by intraperitoneal injection over 7 days,starting at day 2 post-implantation. Ten control mouse were treated with an equivalent volume of 0.5 CMC. Contrast-enhanced gray-scale ultrasound was performed on day 8 after bolus injection of SonoVue (0.1 ml) and the imaging was recorded on cine.Regions of interest within tumour were analyzed off-line with the software of SonoLiver to determine the area under the curve (AUC), maximum intensity (Imax), perfusion index (PI), mean transit time (mTT),time to peak (TTP) and quality of fit (QOF). Immediately after imaging, minces were euthanized and tumour tissue removed for fixation in a 10% formalin solution. Microvascular density (MVD) was measured after anti-CD34 staining. Results The body weight and the tumor volume of treated tumors were significant different (lower) than that of control tumors (P ＜0.05). Treatment with thalidomide resulted into a significant decrease in AUC,PI and Imax in comparison with control tumors ( P ＜0.05). There were no significant difference in mTT and TTP between control and treated tumours ( P ＞0.05). Treated tumours were associated with a significantly lower MVD as compared with control tumours( P ＜0.05). ConclusionsQuantitatively analyzing tissue perfusion parameters of contrast enhanced ultrasound shows promise for monitoring tumor response to antiangiogenic therapy. Key words: Ultrasonography; Microbubbles; Liver neoplasms; Angiogenesis inhibitors

Quantitative Evaluation of the Peripheral Nerve Blood Perfusion with High Frequency Contrast-Enhanced Ultrasound

The blood perfusion of peripheral nerves plays an important role in regeneration after nerve injury. Previous studies have shown that it is possible to quantitatively assess the blood perfusion of the tissue using contrast-enhanced ultrasound (CEUS). The aim of this study was to evaluate the feasibility of CEUS for quantitative assessment of the blood perfusion of the sciatic nerve in normal New Zealand white rabbits and to compare these parameters to those of surrounding skeletal muscle and the main artery in the thigh. CEUS of the bilateral sciatic nerves was performed in 12 normal New Zealand white rabbits after a bolus injection of SonoVue (0.13 mL/kg). Pulse-inversion harmonic imaging was used for real-time CEUS. The blood perfusion of the left sciatic nerve was compared to that of its surrounding muscle, the arterial branch in the thigh, and the contralateral side. The supplying arteries in the sciatic nerve could be demonstrated during the early phase of CEUS, followed by the homogeneous enhancement of the whole nerve. The area under the curve and the perfusion index of the sciatic nerve were higher than those of the surrounding muscle and lower than those of the arterial branch in the thigh (both P values = .000). The maximum intensity of the sciatic nerve was similar to that of skeletal muscle and lower than that of the arterial branch. The time to peak was not significantly different among the sciatic nerve, skeletal muscle, and arterial branch (P = .551). There were no differences in area under the curve, mean transit time, perfusion index, maximum intensity, and time to peak between the left and right sciatic nerves (P > .05). CEUS may be a feasible method for the quantitative assessment of blood perfusion of the peripheral nerves.

Non-invasive contrast enhanced ultrasound for quantitative assessment of tumor microcirculation. Contrast mixed mode examination vs. only contrast enhanced ultrasound examination

To evaluate the different ultrasound techniques for quantification of contrast enhanced ultrasound (CEUS) in an experimental rat prostate carcinoma model. Prostate carcinoma (MLLB-2) cells were subcutaneously injected into the right flank of male rat (Charles River, Sulzfeld, Germany, 180 to 220 g body weight). Following 18 days of subcutaneous tumor growth 9 rats underwent CEUS examination. Real time CEUS was performed after a bolus injection of SonoVue (0.2 ml, Bracco, Italy) via the lateral tail vein using a high end ultrasound system (Siemens Sequoia 512®/Acuson, Mountain View) with an 15 Mhz probe. Two different CEUS techniques, pure contrast (pc) and contrast with background (cbg) examination, were analyzed (CPS-software). Exported signal intensity (SI)-time curves and the normalized area under the curve (AUC) for the active tumor tissue, whole tumor and necrosis were compared. The mean normalized AUC for the active tumor tissue and the whole tumor was 0.84 and 0.5 in the pure contrast examination group and 0.49 and 0.3 for the contrast examination with background signal. Therefore the signal intensity of the pc group was in every examination significant higher than of the cbg group (p < 0.02). The advantage of using the additional background information is to detect the anatomic landmarks in the solid tumor model in comparison to the pure contrast enhanced ultrasound examination. The complete extension of the tumor is much easier to detect with the cbg technique due to orientation of the anatomic landmarks. As the signal intensity of the pc group is always significant higher we recommend this technique for quantification of contrast enhanced ultrasound, especially for the follow up of tumor microcirculation.

Diagnostic Features of Real-Time Contrast-Enhanced Ultrasound in Focal Nodular Hyperplasia of the Liver

The typical appearance of focal nodular hyperplasia (FNH) in radiological contrast techniques (helical CT or MRI) includes homogeneous enhancement in the arterial phase, but the exact timing for the best visualization of this pattern is unknown. The aim of the present study was to assess the ultrasound pattern of FNH with special attention to real-time contrast-enhanced ultrasonography (CEUS) appearance and specifically to the timing of perfusion patterns. 72 patients (60 females, 12 males) with a total of 90 FNH nodules with a diameter ranging from 8 to 100 mm (mean +/- SD, 40.6 +/- 21.5 mm) were examined continuously for at least 4 minutes using CnTI and CPS methods (ESAOTE, Genoa, Italy and Acuson-Siemens) after bolus injection of SonoVue (BRACCO, Milan, Italy). 87 of 90 nodules showed the typical coin-like hyperechogenicity in the arterial phase. The remaining three nodules were all in the same patient and were diagnosed as FNH after resection. Contrast started to appear within the lesions after a mean of 15.7 +/- 4.6 seconds (range 7 - 27 s) and reached peak signal intensity, with the greatest differentiation between the lesion and the surrounding parenchyma, at around 22.6 +/- 7.0 seconds (range 14 - 72 s). In the late phase, 65 lesions (72.2 %) became isoechoic (after a mean of 80.8 +/- 85.7 s, range 20 - 300 s), 22 (24.4 %) slightly hyperechoic and 3 (3.3 %) faintly hypoechoic. FNH shows a typical homogeneous hyperechoic pattern during the arterial phase in real-time CEUS which disappears slowly on average but occasionally even as soon as 20 seconds after contrast injection. If the first scans are taken later than 20 seconds after injection (which is still considered to be a full arterial phase), the ultrasound hyperechogenicity may be missed in some cases. Real-time study of these lesions is therefore strongly recommended to avoid possible false-negative results.

Effect of Tadalafil on prostate haemodynamics: preliminary evaluation with contrast-enhanced US

Phosphodiesterase-5 (PDE-5) inhibitors have an established role in the treatment of erectile dysfunction, but there is increasing evidence that these drugs are effective also for the treatment of lower urinary tract symptoms and benign prostatic hyperplasia (BPH). The mechanism of action of PDE-5 inhibitors in the prostate, however, is poorly understood. It is conceivable that these drugs act by reducing the smooth muscle tone of the organ, but this effect could produce vascular changes as well. The aim of this study was to investigate whether administration of Tadalafil, a PDE-5 inhibitor, in patients with BPH produces haemodynamic changes in the prostate that can be assessed using contrast-enhanced US (CEUS). Twelve consecutive patients with BPH underwent transrectal CEUS before and 90 min after administration of 20 mg Tadalafil. CEUS was performed during bolus injection of SonoVue (4.8 ml) using a nondestructive US mode. The same scan plane, imaging parameters and technique were used before and after Tadalafil administration. Digital clips were recorded and processed using dedicated software (QontraXt v.3.60. Signal intensity (SI) changes in a region of interest (ROI) encompassing the entire prostate were fitted to a gammavariate curve. Changes in enhancement peak, time to peak (TTP), sharpness of the bolus transit and area under the curve (AUC) were considered for further analysis. After Tadalafil administration, the enhancement peak and AUC increased significantly (p<0.01), reflecting changes in prostate vascularity. TTP and sharpness did not change significantly. In patients with BPH, vascular changes are observed in the prostate after Tadalafil administration, which can be detected with CEUS.

Interest of DCE-US with quantification to demonstrate the VDA effect on vascularization in patients with advanced solid tumors treated with AVE8062

e14522 Background: To determine the optimal time for the assessment of the perfusion in patients receiving AVE8062 (Vascular Disrupting Agent) at different doses combined with a fixed dose of cisplatin and then to correlate these results with the tumor response. Methods: Patients (pts) with advanced solid tumors, treated with AVE8062 (from 11.5 to 30 mg/m2) in combination with 75 mg/m2 cisplatin given every 3 weeks, were prospectively followed by DCE-US. DCE-US was performed before treatment, at 3 time points (0, 6 and 24 hours (h)) on Day 1 of the first (C1) and second cycle (C2), then every 2 cycles thereafter. Contrast uptake was acquired using VRI perfusion software after SonoVue bolus injection. Time-Intensity Curves (TIC) were determined using linear raw- data from CHI-Q (Toshiba) software. Peak Intensity (PI) representing the blood volume was calculated from automatic modeling of TIC. CT-scans performed before treatment and every 2 cycles were reviewed and tumor response assessed (RECIST). Results: A total of 96 DCE-US were performed in 13 pts, 11 of whom had data for both cycle 1 and cycle 2. Among these 11 patients, 8 presented with a dramatic decrease of PI and 3 with an increase of PI. At cycle 1, mean change from baseline in PI was -36% at 6h and -47% at 24h after AVE8062 infusion. Greater decreases were observed at cycle 2, -70% at 6 h and 78% at 24 h. No pt had a clinical response, but by cycle 2, the 8 pts with a decrease in PI at 24h went on to have stable disease as best response; 3 pts with increased PI 24h after their second treatment all had disease progression as best response. Conclusions: The best timing to observe the effect of AVE8062 on the PI seems to be 24 hours after drug administration at cycle 2. These preliminary results suggest that 24 hr PI at cycle 2 could be useful for determining pts who are more likely to have disease progression as best response to AVE8062. If confirmed, the assessment of PI variation may predict the clinical response to AVE8062. Further studies are needed to assess the possible predictive value of DCE-US on duration of progression-free survival. No significant financial relationships to disclose.

Contrast-Enhanced Sonography in Early Kidney Graft Dysfunction

Objectives The aim of this study was a comparison of contrast-enhanced sonography (CEUS) and power Doppler ultrasound (US) findings in renal grafts within 30 days posttransplantation. Methods A total of 39 kidney recipients underwent CEUS (SonoVue bolus injection) and US examinations at 5 (T0), 15 (T1), and 30 (T2) days after grafting. The results were correlated with clinical findings and functional evolution. Fourteen patients displayed early acute kidney dysfunction: 10 had acute tubular necrosis (acute tubular necrosis [ATN] group); four acute rejection episodes (ARE group); 25 with normal evolution (as control, C group). Renal biopsies were performed to obtain a diagnosis in the four ATN cases and in all ARE patients. Creatinine and estimated glomerular filtration rate were used as kidney function parameters. CEUS analysis was performed both on cortical and medullary regions while US resistivity indexes (RI) were obtained on main, infrarenal, and arcuate arteries. From an analysis of CEUS time-intensity curves, we computed peak enhancement (PEAK), time to peak (TTP), mean transit time (MTT), regional blood flow (RBF) and volume (RBV), and cortical to medullary ratio of these indies (RATIO). Results An increased RI was present in the ATN and ARE groups as well as a reduced PEAK and RBF. RATIO-RBV and RATIO-MTT were lower than C among ATN cases, while TTP was higher compared to C in ARE. No statistical difference was evidence for RI between ATN and ARE groups. MTT (T0) was significantly related to creatinine at follow-up (T2). Conclusions US and CEUS identified grafts with early dysfunction, but only some CEUS-derived parameters distinguished ATN from ARE, adding prognostic information.