Pharmacoeconomic evaluation of different doses of Curosurf for treating neonatal acute respiratory distress syndrome.

Neonatal acute respiratory distress syndrome (ARDS) is a serious stage of acute lung injury (ALI) which can be treated by exogenous surfactant. The aim of this study was to explore the clinical efficacy of two different doses of Poractant alfa (Curosurf®) for treating neonatal ARDS and to perform an economic evaluation. Fifty-four patients were divided into Group A (high dose) and Group B (low dose). Pharmacoeconomic evaluation was performed on the two groups regarding the treatment expenses, and the output was the cure rate and complication rate. There were significant differences between Group A and Group B for the duration of receiving oxygen therapy in moderate cases (6.4±3.5d:8.9±2.6d) (P<0.05) and severe cases (10.0±2.6d:14.8±1.3d) (P<0.05). There were significant differences between them for the duration of undergoing mechanical ventilation in severe cases (1.7±2.3d:5.5±2.4d) (P=0.01). There was a significant difference between Group A and Group B for hospitalization expenses in severe cases (P<0.05). There were no significant differences between them in all types of cases for the cure rate (P>0.05). A high dose of Curosurf had an advantage in treating neonatal ARDS, especially in severe cases, with lower final costs and better effects.

Time-of-flight resolved light field fluctuations reveal deep human tissue physiology.

Red blood cells (RBCs) transport oxygen to tissues and remove carbon dioxide. Diffuse optical flowmetry (DOF) assesses deep tissue RBC dynamics by measuring coherent fluctuations of multiply scattered near-infrared light intensity. While classical DOF measurements empirically correlate with blood flow, they remain far-removed from light scattering physics and difficult to interpret in layered media. To advance DOF measurements closer to the physics, here we introduce an interferometric technique, surmounting challenges of bulk motion to apply it in awake humans. We reveal two measurement dimensions: optical phase, and time-of-flight (TOF), the latter with 22 picosecond resolution. With this multidimensional data, we directly confirm the unordered, or Brownian, nature of optically probed RBC dynamics typically assumed in classical DOF. We illustrate how incorrect absorption assumptions, anisotropic RBC scattering, and layered tissues may confound classical DOF. By comparison, our direct method enables accurate and comprehensive assessment of blood flow dynamics in humans.

Use of contrast-enhanced ultrasound for assessment of nodular lymphoid hyperplasia (NLH) in canine spleen.

BACKGROUND: Nodular lymphoid hyperplasia (NLH) is one of the most common non-neoplastic splenic lesions in dogs, especially in old ones, showing a splenic enlargement. More recent studies have been focused on Contrast Enhanced Ultrasonography (CEUS) analysis of the spleen for establishing normal perfusion patterns and blood pool phase peculiarities of focal lesions. The aim of the study was to evaluate the qualitative and quantitative CEUS analysis of the canine splenic NLH, characterizing the CEUS pattern of this pathology on 20 clinical cases. RESULTS: A prospective, observational study was performed using a system equipped with contrast-tuned imaging technology. Mechanical Index was set from 0.08 to 0.11; the contrast medium was a second generation contrast medium composed of sulphur hexafluoride encapsulated of a shell of phospholipids (SonoVue®). Qualitative and quantitative assessment of the enhancement pattern of splenic NLH were performed. Cytology and histology identified 20 splenic NLH. All of the benign hyperplastic lesions assessed were isoechoic with a homogeneous pattern than the surrounding normal spleen, during the wash-in phase (10-20 s) of the CEUS exam. Before finishing the wash-in phase, 20-45 s from the contrast medium inoculation, 19/20 benign nodules became markedly hypoechoic to the adjacent spleen. Sensitivity of hypoechoic pattern for NLH was 95%. CONCLUSIONS: These findings should prove useful in the evaluation of focal splenic masses in dogs. Since enhancement and perfusion patterns of NLH seem to coincide with some neoplastic lesions of the spleen previously reported, in clinical practice attention must be paid to the final diagnosis of canine splenic lesions using only the CEUS exam.

Surfactant Administration in Preterm Infants: Drug Development Opportunities.

OBJECTIVE: To evaluate how frequently surfactant is used off-label in preterm infants. STUDY DESIGN: We conducted a retrospective cohort analysis of prospectively collected administrative data for 2005-2015 from 348 neonatal intensive care units in the US. We quantified off-label administration of poractant alfa, calfactant, or beractant in inborn infants born at <37 weeks of gestational age (GA). Off-label surfactant administration was defined according to the Food and Drug Administration (FDA) label. RESULTS: Of a total of 110 822 preterm infants who received surfactant, 68 226 (62%) received the surfactant off-label. The majority of infants who received surfactant off-label had a higher birth weight than those who received surfactant on-label (40 716 [37%]), had an older GA than those who received surfactant on-label (35 191 [32%]), or were treated with intubation and surfactant administration followed by immediate extubation (INSURE) (32 310 [29%]). Poractant alfa was administered via INSURE more frequently than beractant or calfactant (16 688 [38%], 7137 [20%], and 8485 [27%], respectively). An increasing number of infants received surfactant via INSURE from 2005 to 2015 (from 1697 [19%] to 3368 [36%]). CONCLUSIONS: The majority of surfactant given to preterm infants is administered off-label. The uptrend in administration via INSURE coincides with increased supporting evidence. The gap between FDA labeling and current clinic practice exemplifies an opportunity for label expansion, which may require additional prospective or retrospective safety and/or effectiveness data for infants of older GA and higher birth weight.

Preparation of novel phospholipid-based sonocomplexes for improved intestinal permeability of rosuvastatin: In vitro characterization, dynamic simulation, Caco-2 cell line permeation and in vivo assessment studies.

The study aimed to fabricate innovative drug-phospholipid complexes termed "sonocomplexes" adopting ultrasound irradiation to increase the liposolubility and to enhance the intestinal absorption of rosuvastatin as a model drug for BCS class III active pharmaceutical ingredients (APIs). A 22 full factorial design was fashioned to investigate the influence of phosphatidylcholine content in the phospholipid (∼30 and 60%) and molar ratio of phospholipid to rosuvastatin (1:1 and 2:1) on physicochemical properties of sonocomplexes. In comparison to pure drug, sonocomplexes showed a minimum of about 2 folds and a maximum of about 15 folds increase in lipophilicity (expressed in terms of partition coefficient, P). Results of molecular docking, dynamic simulations, Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) confirmed the strong interactions between rosuvastatin and the phospholipid via hydrogen bonding interaction, van der Waals forces and hydrophobic interaction. The complexation efficiency reached around 99% and transmission electron microscopy (TEM) of the aqueous dispersion of the optimal sonocomplex showed spherical nanosized vesicles. The optimal sonocomplex showed significantly superior Caco-2 cells permeability and markedly better oral bioavailability compared to the pure drug. In summary, sonocomplexes can be considered as effective approach for enhancing the liposolubility and consequently the intestinal permeability of BCS class III drugs.

Contrast-enhanced ultrasound using bolus injections of contrast agent for assessment of postprandial microvascular blood volume in human skeletal muscle.

Methods capable of measuring blood flow in a tissue-specific manner are needed. The purpose of this study was to investigate whether contrast-enhanced ultrasound (CEUS) using bolus injections of SonoVue® is an useful method for assessing postprandial changes in microvascular perfusion in the vastus lateralis muscle. Ten healthy, young subjects were recruited for this study. Six subjects participated in washout and reproducibility protocols to assess washout time of SonoVue® and the reproducibility of the method when measuring microvascular blood volume (MBV). Six subjects (two of which also participated in the washout and reproducibility protocols) participated in exercise and nutrition protocols, to assess the ability of the method to detect changes in MBV in response to these interventions. Intraday variation (coefficients of variation) for MBV indices, as assessed by peak signal intensity (PI) or mean plateau signal intensity (mPI), was high (PI: 19 ± 4·2%; mPI: 23 ± 3·3%). The exercise protocol induced significant increases in MBV indices (PI:+113%, P˂0·0001; mPI:+218%, P˂0·0001) acutely after exercise cessation. There were no changes in MBV indices in response to feeding during the nutrition protocol (PI: P = 0·51; mPI: P = 0·51). We conclude that CEUS using bolus injections of SonoVue® is not capable of detecting changes in MBV of vastus lateralis in response to feeding. This is probably due to the low reproducibility of the method. However, the method is capable of measuring changes in MBV in response to exercise. This method could therefore be used when investigating exercise-induced changes in microvascular perfusion.

Non-Invasive Assessment of Inflammation and Treatment Response in Patients with Crohn's Disease and Ulcerative Colitis using Contrast-Enhanced Ultrasonography Quantification.

BACKGROUND AND AIM: Novel biological therapies in Crohn's disease (CD) or Ulcerative colitis (UC) require a proper follow-up for the assessment of bowel inflammation. While endoscopy is the standard method, the imaging techniques using contrast, particularly contrast enhanced ultrasonography (CEUS), are better tolerated by the patients and can be used more frequently. Our aim was to find the usefulness of dynamic CEUS quantification as compared to endoscopy in the assessment of disease activity and in the follow-up under therapy of the patients suffering from either CD or UC. METHOD: We have prospectively evaluated 67 patients with UC and 46 with CD, diagnosed by ileo-colonoscopy and biopsy, comparing the endoscopic scores with clinical scores, C reactive protein (CRP), intestinal wall thickness, layer scores after CEUS and TIC parameters (using SonoLiver® software - Imax, RT, TTP, mTT and AUC). For 25 patients with UC and 13 with CD we performed comparisons of the parameters before and after 3 months of treatment and correlated them with the changes in the endoscopic scores. RESULTS: For UC, time-intensity curves (TIC) volume parameters (AUC) correlated better with endoscopy (ρ=0.64) than the clinical score (ρ =0.62). Other parameters such as CRP and thickness showed significant but less strong correlation, while TIC flow parameters (RT, TTP and mTT) did not show a significant correlation. Results were similar for CD (ρ=0.64 for Imax vs ρ=0.58 for CDAI). The best predictor for endoscopic improvement in both UC and CD was ln(AUC), with a Wilcoxon Z score of 3.76 and 2.61, respectively. There was also a good correlation between the difference of its values and the difference in endoscopic scores before and after the treatment (rho is 0.68 in UC and 0.73 in CD).

Analysis of the cost-effectiveness of surfactant treatment (Curosurf®) in respiratory distress syndrome therapy in preterm infants: early treatment compared to late treatment.

BACKGROUND: The best criteria for surfactant treatment in the perinatal period are unknown and this makes it of interest to consider the possible economic implications of lessening the use of more restrictive criteria. OBJECTIVE: The objective of this study is the evaluation of the costs of respiratory care for preterm infants with Respiratory Distress Syndrome (RDS) treated with "early rescue" surfactant compared to a "late rescue" strategy. METHODS: The study was carried out applying the costs of materials used, of staff and pharmacological therapy calculated in the Neonatal Intensive Care Unit (NICU) of an Italian hospital to the Verder et al. study (Pediatrics 1999) clinical data. RESULTS: The cost for patients treated with early strategy was slightly lower than for patients treated with late strategy (Euro 4,901.70 vs. Euro 4,960.07). The cost of treatment with surfactant was greater in the early group (Euro 458.49 vs. Euro 311.74), but this was compensated by the greater cost of treatment with Mechanical Ventilation (MV) in the late group (respectively Euro 108.85 vs. Euro 259.25). CONCLUSIONS: The cost-effectiveness analysis performed in this study shows how early treatment with surfactant in preterm infants with RDS, as well as being clinically more effective, is associated with a slightly lower cost.

Quantitative evaluation of contrast-enhanced ultrasound after intravenous administration of a microbubble contrast agent for differentiation of benign and malignant thyroid nodules: assessment of diagnostic accuracy.

OBJECTIVES: To investigate the diagnostic accuracy, through quantitative analysis, of contrast-enhanced ultrasound (CEUS), using a microbubble contrast agent, in the differentiation of thyroid nodules. METHODS: This prospective study enrolled 46 patients with solitary, scintigraphically non-functional thyroid nodules. These patients were scheduled for surgery and underwent preoperative CEUS with pulse-inversion harmonic imaging after intravenous microbubble contrast medium administration. Using histology as a standard of reference, time-intensity curves of benign and malignant nodules were compared by means of peak enhancement and wash-out enhancement relative to the baseline intensity using a mixed model ANOVA. ROC analysis was performed to assess the diagnostic accuracy in the differentiation of benign and malignant nodules on CEUS. RESULTS: The complete CEUS data of 42 patients (31/42 [73.8%] benign and 11/42 [26.2%] malignant nodules) revealed a significant difference (P < 0.001) in enhancement between benign and malignant nodules. Furthermore, based on ROC analysis, CEUS demonstrated sensitivity of 76.9%, specificity of 84.8% and accuracy of 82.6%. CONCLUSIONS: Quantitative analysis of CEUS using a microbubble contrast agent allows the differentiation of benign and malignant thyroid nodules and may potentially serve, in addition to grey-scale and Doppler ultrasound, as an adjunctive tool in the assessment of patients with thyroid nodules. KEY POINTS: • Contrast-enhanced ultrasound (CEUS) helps differentiate between benign and malignant thyroid nodules. • Quantitative CEUS analysis yields sensitivity of 76.9% and specificity of 84.8%. • CEUS may be a potentially useful adjunct in assessing thyroid nodules.

[Assessment of protein synthesizing function of the liver in experimental hepatitis].

Liver protein synthesis was estimated comparing the levels of prothrombin and its inactive form PIVKA-prothrombin. The latter indicates liver dysfunction. These diagnostic tests allow monitoring the effectiveness of the commonly applied preparation "Essentiale Forte" and that of the liposomal form of the biologically active additive (BAA) FLP-MD based on phospholipids of various origin.

Intrahepatic transit time predicts liver fibrosis in patients with chronic hepatitis B: quantitative assessment with contrast-enhanced ultrasonography.

We investigated the use of contrast-enhanced ultrasonography (CEUS) with quantitative measurements to assess the stages of liver fibrosis in patients with chronic hepatitis B. One-hundred twenty-two patients with chronic hepatitis B were divided into three groups according to the Scheuer scoring system pathologically and according to clinical evidence: mild fibrosis (S0 and S1, n = 36); moderate fibrosis (S2 and S3, n = 24); and cirrhosis (S4 and clinically typical cirrhosis, n = 62). CEUS of hepatic vessels and parenchyma was performed using the Cadence contrast pulse sequencing technique, with an intravenous bolus injection of a contrast agent (SonoVue). Real-time CEUS imaging of the liver was recorded and analyzed offline. Contrast arrival time, baseline, and peak intensity in the hepatic artery, portal vein, right hepatic vein, and liver parenchyma were used to calculate intrahepatic transit times, hepatic artery to hepatic vein transit time (HA-HVTT) and portal vein to hepatic vein transit time (PV-HVTT), as well as increased signal intensity (ISI). The correlations between these quantitative parameters and the stages of fibrosis were analyzed using Spearman rank correlation coefficients. HA-HVTT and PV-HVTT were shortened gradually with the progression of liver fibrosis. PV-HVTT was statistically significant differences existed between the two paired groups (mild vs. moderate vs. cirrhosis groups, p < 0.001), whereas HA-HVTT was changed significantly between mild and moderate or cirrhosis groups (p < 0.001). HA-HVTT and PV-HVTT changes were significantly correlated with liver fibrosis severity (r = -0.5930, p < 0.001; r = -0.8215, p < 0.001). Area under receiver operating characteristic curves for HA-HVTT and PV-HVTT were 0.891 +/- 0.034 and 0.955 +/- 0.020 at fibrosis scores >or=S2, and 0.785 +/- 0.040 and 0.946 +/- 0.018 at fibrosis score >or=S4, respectively. ISI values in the portal vein and liver parenchyma decreased with the severity of fibrosis. This study demonstrated that hepatic CEUS with quantitative measurements of intrahepatic transit time reflected the severity of liver fibrosis. The real-time CEUS imaging with use of software-based quantitative analysis could provide reliable information of hepatic hemodynamic changes to noninvasively assess the severity of liver fibrosis in patients with chronic hepatitis B.

Inflammation within carotid atherosclerotic plaque: assessment with late-phase contrast-enhanced US.

PURPOSE: To determine if the number of nontargeted microbubbles retained in human carotid plaque is sufficient to be detected with ultrasonography (US). MATERIALS AND METHODS: The study protocol was approved by the local research ethics committee. Informed consent was obtained. A total of 37 subjects with carotid atherosclerosis (mean age, 69.9 years; age range, 49-86 years), of whom 27 (73%) were men (mean age, 69.7 years; age range, 58-86 years) and 10 (27%) were women (mean age, 70.3 years; age range, 49-86 years), were studied between December 2008 and May 2009 with late-phase (LP) contrast material-enhanced US by using flash imaging with a nonlinear mode at an intermediate mechanical index of 0.34 6 minutes after bolus contrast agent injection. Plaques were defined as symptomatic if symptoms consistent with stroke, transient ischemic attack, or amaurosis fugax had occurred in the neurovascular territory of the plaque studied within 12 months prior to entry into the study. Plaques were defined as asymptomatic if no such events had ever occurred within the neurovascular territory. Raw linear data were used to quantify echogenicity of the plaque, which was normalized to lumen echogenicity. Gray-scale median score was also calculated. RESULTS: Of the 37 subjects, 16 (43%) had symptomatic plaques and 21 (57%) had asymptomatic plaques. All examinations yielded evaluable LP contrast-enhanced US data. Normalized LP plaque echogenicity was greater in the symptomatic group (0.39; 95% confidence interval: -0.11, 0.89) than in the asymptomatic group (0.69; 95% confidence interval: -1.04, -0.34) (P = .0005). There was a moderate (rho = -0.44, P = .016) inverse correlation between normalized LP plaque echogenicity and gray-scale median score. CONCLUSION: By quantifying microbubble retention within the carotid plaque, LP contrast-enhanced US depicts clear differences between groups of subjects with plaque ipsilateral to symptoms and asymptomatic plaques. This technique has promise as a tissue-specific marker of inflammation and a potential role in the risk stratification of atherosclerotic carotid stenosis.

Contrast-enhanced ultrasound assessment of arterial vascularization of small nodules arising in the cirrhotic liver.

BACKGROUND AND AIM: Aim of this study was to compare contrast-enhanced ultrasound and multi-detector row computed tomography in detecting arterial hypervascularity in small cirrhotic nodules. PATIENTS AND METHODS: Sixty-two nodules (41 measuring 1.0-2.0 cm, 21 measuring 2.1-3.0 cm) found in 55 cirrhotic patients were examined with both methods. Lesions displaying arterial hypervascularity with washout in the portal/venous phase on both studies were considered hepatocellular carcinomas and treated; all other nodules were subjected to ultrasound-guided fine-needle biopsy. RESULTS: The larger nodules (2.1-3.0 cm) included 19 hepatocellular carcinomas (90%), 1 macroregenerative nodule type I and 1 macroregenerative nodule type II; 35 (87%) of the smaller nodules were hepatocellular carcinomas, 2 were macroregenerative nodules type I, 2 macroregenerative nodules type II and 2 hemangiomas. The two studies yielded concordant findings for 54 nodules (87%), including 46 hypervascular on both examinations and 8 that were consistently hypovascular. Two of the latter nodules were hepatocellular carcinomas. The other eight nodules displayed arterial hypervascularity on only one of the studies. Six of these (75%) were hepatocellular carcinomas, including five that were negative in the contrast-enhanced ultrasound study. CONCLUSION: Computed tomography and contrast-enhanced ultrasound show high agreement in the vascular classification of small nodules detected by ultrasound in cirrhotic livers, although the former technique was slightly more sensitive in the detection of arterial hypervascularization.

Is microbubble-enhanced ultrasonography sufficient for assessment of response to percutaneous treatment in patients with early hepatocellular carcinoma?

The objective of this study was to assess the efficacy of contrast-enhanced ultrasonography (CEUS) with SonoVue to evaluate the response to percutaneous treatment (ethanol injection/radiofrequency) of hepatocellular carcinoma in comparison with spiral computed tomography (CT) immediately and 1 month after treatment. Forty-one consecutive cirrhotic patients with early stage tumor (not suitable for resection) were included. Spiral CT and CEUS were performed in all patients before treatment, in the following 24 h, and 1 month later. The results of each examination were compared with the 1-month spiral CT, considered the gold standard technique. The 24-h CEUS and the 24-h spiral CT sensitivity to detect residual disease were 27% and 20%, respectively. The 24-h CEUS and the 24-h spiral CT positive predictive value of persistent vascularization detection were 75% and 66%, respectively. The 1-month CEUS detected partial responses in ten out of 11 cases (91% sensitivity, 97% specificity, 95% accuracy). Spiral CT and CEUS performed in the 24 h following treatment are slightly useful to evaluate therapeutic efficacy. The 1-month CEUS has a high diagnostic accuracy compared with spiral-CT in the usual assessment of percutaneous treatment response.

Diagnostic efficacy of SonoVue, a second generation contrast agent, in the assessment of extracranial carotid or peripheral arteries using colour and spectral Doppler ultrasound: a multicentre study.

The purpose of this study was to demonstrate the improvement in diagnostic quality and diagnostic accuracy of SonoVue microbubble contrast-enhanced ultrasound (CE-US) versus unenhanced ultrasound imaging during the investigation of extracranial carotid or peripheral arteries. 82 patients with suspected extracranial carotid or peripheral arterial disease received four SonoVue doses (0.3 ml, 0.6 ml, 1.2 ml and 2.4 ml) with Doppler ultrasound performed before and following each dose. Diagnostic quality of the CE-US examinations was evaluated off-site for duration of clinically useful contrast enhancement, artefact effects and percentage of examinations converted from non-diagnostic to diagnostic. Accuracy, sensitivity and specificity were assessed as agreement of CE-US diagnosis evaluated by an independent panel of experts with reference standard modality. The median duration of clinically useful signal enhancement significantly increased with increasing SonoVue doses (p< or =0.002). At the dose of 2.4 ml of SonoVue, diagnostic quality evaluated as number of inconclusive examinations significantly improved, falling from 40.7% at baseline down to 5.1%. Furthermore, SonoVue significantly (p<0.01) increased the accuracy, sensitivity and specificity of assessment of disease compared with baseline ultrasound. SonoVue increases the diagnostic quality of Doppler images and improves the accuracy of both spectral and colour Doppler examinations of extracranial carotid or peripheral arterial disease.

Phospholipid nanosomes.

Phospholipid nanosomes are small, uniform liposomes manufactured utilizing supercritical fluid technologies. Supercritical fluids are first used to solvate phospholipid raw materials, and then decompressed to form phospholipid nanosomes that can encapsulate hydrophilic molecules such as proteins and nucleic acids. Hydrophobic therapeutics are co-solvated with phospholipid raw materials in supercritical fluids that, when decompressed, form phospholipid nanosomes encapsulating these drugs in their lipid bilayers. Mathematical modeling and semi-empirical experiments indicate that the size and character of phospholipid nanosomes depend on the several process parameters and material properties including the size and design of decompression nozzle, bubble size, pressure and the rate of decompression, interfacial forces, charge distribution and the nature of compound being encapsulated. Examples are presented for the encapsulation of a protein and hydrophobic drugs. In vitro and in vivo data on breast cancer cells and xenografts in nude mice indicate that paclitaxel nanosomes are less toxic and much more effective than paclitaxel in Cremophor EL (Taxol). Camptothecin nanosomes demonstrate that the normally very water-insoluble camptothecin can be formulated in a biocompatible aqueous medium while retaining in vivo efficacy against lymphoma xenografts in nude mice. In vitro data for betulinic acid nanosomes demonstrate enhanced efficacy against HIV-1 (EC50 of 1.01 microg/ml versus 6.72 microg/ml for neat betulinic acid). Phospholipid nanosomes may find utility in the enhanced delivery of hydrophilic drugs such as recombinant proteins and nucleic acid as well as hydrophobic anticancer and anti-HIV drugs.

Feasibility of continuous venous infusion of SonoVue for qualitative assessment of reversible coronary perfusion defects in stress myocardial contrast echocardiography.

OBJECTIVE: To study the feasibility of continuous intravenous SonoVue contrast echocardiography for qualitative assessment of reversible myocardial perfusion in dipyridamole stress tests. METHODS: Eleven patients (10 male and 1 female, mean age 66 years) with a history of chest pain and a clinical indication for stress sestamibi single photon emission computed tomography (SPECT) underwent concurrent SonoVue 99mTc myocardial contrast echocardiography (MCE). RESULTS: Of the total 176 segments obtained, 53 (30%) were regarded as indeterminate, 39 (22%) as discordant, and 84 (48%) as concordant between MCE and SPECT imaging. Two patients had abnormal SPECT results. The overall feasibility and specificity of MCE were 70 and 74%, respectively. The concordant (p = 0.59) and discordant (p = 0.55) segments were comparable with either MCE technique. However, continuous low-mechanical-index imaging produced fewer indeterminate segments (17 segments, 32%) than intermittent harmonic B-mode imaging (36 segments, 68%) (p = 0.04). Significantly more indeterminate segments were found in the left anterior descending artery territory. However, the overall concordance was similar (p = 0.5) in all three coronary artery territories. The concordance and discordance rates at different left ventricular levels (i.e., basal, mid, and apical) were similar (p = 0.50 and 0.08, respectively). CONCLUSION: Continuous-infusion SonoVue contrast echocardiography is feasible, with high specificity, for detecting myocardial perfusion defects as assessed by dipyridamole SPECT.