• Journal of Veterinary Clinics
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• v.32 no.6
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• pp.486-490
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• 2015

Two-demensional echocardiography is routinely used for evaluation of cardiac function. Visualization of the endocardial border is essential for the assessment of global and regional left ventricular with cardiac disease. SonoVue$^{TM}$ is a microbubble contrast agent that consists of sulfur hexafluoride-filled microbubbles in a phospholipid shell. There were many studies about contrast echocardiographic examination using SonoVue$^{TM}$ contrast agent, and various doses of SonoVue$^{TM}$ were used. To our knowledge, in published veterinary medicine, there was not reported for diagnostic efficient dose of SonoVue$^{TM}$ to evaluate contrast enhanced left ventricular endocardial border delineation (LVEBD). The purpose of this study is to compare the visualization time of LVEBD and find efficient dose of SonoVue$^{TM}$ for using various doses in dogs. Ten healthy Beagles were recruited to the study. Three different doses (0.03 ml/kg, 0.05 ml/kg and 0.1 ml/kg) of SonoVue$^{TM}$ were injected. Endocardial segments were assigned based on previously established methodology, where by the four-chamber views of the LV were divided into 6 segments. In this study, Contrast enhancement of the LVEBD after each injection was evaluated visually at the time point of overall contrast enhancement (Segmental scoring 5+) in the LV by three investigators in a blind manner. Statistical analysis was performed with SPSS version 14.0. All data were analyzed using one-way ANOVA, the multiple comparison Scheffe test. When data for the three offsite readers were combined, mean durations of useful contrast were $3.54({\pm}2.14)$, $6.15({\pm}2.61)$, and $24.39({\pm}11.10)$ seconds for the 0.03 ml/kg, 0.05 ml/kg, and 0.1 ml/kg SonoVue$^{TM}$ doses, respectively. After injection of contrast agent, there were no significant change in side effects such as urticaria, angioedema, hypersensitivity reactions, and digestive system disorders. This study suggests that efficient dose of SonoVue$^{TM}$ contrast agent for improvement of the left ventricle visualization is 0.1 ml/kg. The duration of useful enhancement of LVEBD and the reproducibility were also the highest at the 0.1 ml/kg dosage.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.493-497
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• 2012

This study was conducted to retrospectively evaluate the pattern of contrast enhancement with SonoVue on gray-scale ultrasonography of hepatic angiomyolipoma (HAML). Imaging features of 33 pathologically proven HAML lesions in 33 patients who underwent baseline ultrasound and contrast-enhanced ultrasonography (CEUS) were assessed retrospectively. All lesions were enhanced in the arterial phase and showed whole-tumor filling in. Thirty-two of 33 (97%) lesions showed early positive enhancement in the arterial phase. Twenty-three of these exhibited isoechoic or hyperechoic features in the portal phase. HAML demonstrate characteristic manifestations with SonoVue-enhanced real-time gray-scale ultrasonography.

• Journal of the Korean Society of Radiology
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• v.13 no.1
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• pp.21-29
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• 2019

The purpose of this study was to compare the MI using SonoVue along with different machines output and to infer the meaning of the signal difference under the same condition. All of the comparative instruments showed strong signal values at early stage as MI value increased. Over time, the inter-instrumental signal values showed signal attenuation under all conditions except for 10 min of the condition of MI 0.1 of RS85A. E9 and EPIQ7 showed signal degradation due to microbubble collapse over time at all MI values. In the comparison of equipment, the signal strengths of MI 0.1, 0.2, and 0.4 were high in order of EPIQ7, RS85A and E9. In the quantitative analysis, there were statistically significant from the SNR and CNR that were obtained from RS85A and E9 (P-value<0.05). In the quantitative analysis, Epiq7 was statistically significant except for CNR as the MI value was changed In the contrast-enhanced ultrasound, even though MI value was low (MI <0.05), it will be helpful for diagnosis, controlling the MI and scan time because a difference in signal intensity was shown between the three machines.

• Korean Journal of Radiology
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• v.23 no.11
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• pp.1067-1077
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• 2022

Objective: To determine whether Sonazoid-enhanced ultrasound (SZUS) was noninferior to SonoVue-enhanced ultrasound (SVUS) in diagnosing hepatocellular carcinoma (HCC) using the same diagnostic criteria. Materials and Methods: This prospective, single-center, noninferiority study (NCT04847726) enrolled 105 at-risk participants (71 male; mean age ± standard deviation, 63 ± 11 years; range, 26-86 years) with treatment-naïve solid hepatic nodules (≥ 1 cm). All participants underwent same-day SZUS (experimental method) and SVUS (control method) for one representative nodule per participant. Images were interpreted by three readers (the operator and two independent readers). All malignancies were diagnosed histopathologically, while the benignity of other lesions was confirmed by follow-up stability or pathology. The primary endpoint was per-lesion diagnostic accuracy for HCC pooled across three readers using the conventional contrast-enhanced ultrasound diagnostic criteria, including arterial phase hyperenhancement followed by mild (assessed within 2 minutes after contrast injection) and late (≥ 60 seconds with a delay of 5 minutes) washout. The noninferiority delta was -10%p. Furthermore, different time delays were compared as washout criteria in SZUS, including delays of 2, 5, and > 10 minutes. Results: A total of 105 lesions (HCCs [n = 61], non-HCC malignancies [n = 19], and benign [n = 25]) were evaluated. Using the 5-minutes washout criterion, per-lesion accuracy of SZUS pooled across the three readers (72.4%; 95% confidence interval [CI], 64.1%-79.3%) was noninferior to that of SVUS (71.4%; 95% CI, 63.1%-78.6%), meeting the statistical criterion for non-inferiority (difference of 0.95%p; 95% CI, -3.8%p-5.7%p). The arterial phase hyperenhancement combined with the 5-minutes washout criterion showed the same sensitivity as that of the > 10-minutes criterion (59.0% vs. 59.0%, p = 0.989), and the specificities were not significantly different (90.9% vs. 86.4%, p = 0.072). Conclusion: SZUS was noninferior to SVUS for diagnosing HCC in at-risk patients using the same diagnostic criteria. No significant improvement in HCC diagnosis was observed by extending the washout time delay from 5 to 10 minutes.

• Ultrasonography
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• v.32 no.1
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• pp.59-65
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• 2013

Purpose: The purpose of this study is to establish the methodology regarding synthesis of ultrasound contrast agent imaging, and to evaluate the characteristics of the synthesized ultrasound contrast agents, including size or degradation interval and image quality. Materials and Methods: The ultrasound contrast agent, composed of liposome and SF6, was synthesized from the mixture solution of $21{\mu}mol$ DPPC (1, 2-Dihexadecanoyl-sn-glycero-3-phosphocholine, $C_{40}H_{80}NO_8P$), $9{\mu}mol$ cholesterol, $1.9{\mu}mol$ of DCP (Dihexadecylphosphate, $[CH_3(CH_2)_{15}O]_2P(O)OH$), and chloroform. After evaporation in a warm water bath and drying during a period of 12-24 hours, the contrast agent was synthesized by the sonication process by addition of buffer and SF6 gas. The size of the contrast agent was controlled by use of either extruder or sonication methods. After synthesis of contrast agents, analysis of the size distribution of the bubbles was performed using dynamic light scattering measurement methods. The degradation curve was also evaluated by changes in the number of contrast agents via light microscopy immediate, 12 hours, 24 hours, 36 hours, 48 hours, 60 hours, 72 hours, and 84 hours after synthesis. For evaluation of the role as an US contrast agent, the echogenicity of the synthesized microbubble was compared with commercially available microbubbles (SonoVue, Bracco, Milan, Italy) using a clinical ultrasound machine and phantom. Results: The contrast agents were synthesized successfully using an evaporation-drying-sonication method. The majority of bubbles showed a mean size of 154.2 nanometers, and they showed marked degradation 24 hours after synthesis. ANOVA test revealed a significant difference among SonoVue, synthesized contrast agent, and saline (p < 0.001). Although no significant difference was observed between SonoVue and the synthesized contrast agent, difference in echogenicity was observed between synthesized contrast agent and saline (p < 0.01). Conclusion: We could synthesize ultrasound contrast agents using an evaporation-drying-sonication method. On the basis of these results, many prospective types of research, such as anticancer drug delivery, gene delivery, including siRNA or microRNA, targeted molecular imaging, and targeted therapy can be performed.

• Korean Journal of Radiology
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• v.22 no.5
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• pp.801-810
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• 2021

Objective: To investigate imaging biomarkers of microperfusion in contrast-induced nephropathy (CIN) using contrast-enhanced ultrasound (CEUS). Materials and Methods: The CIN model was fabricated by administering indomethacin (10 mg/kg), L-NAME (15 mg/kg), and iopamidol (10 mL/kg) to Sprague-Dawley rats. After 24 hours, CEUS was performed on CIN (n = 6) and control (n = 6) rats with sulphur hexafluoride microbubbles (SonoVue). From time-intensity curves obtained from the kidney arriving time (AT), acceleration time (AC), time to peak (TTP), and peak enhancement (PE) were measured and compared between the groups. After CEUS, the rats were sacrificed, and cell apoptosis markers were evaluated to confirm the development of CIN. Results: Among CEUS parameters, AT (7.8 ± 1.6 vs. 4.2 ± 0.5 s, p = 0.002), AC (4.7 ± 1.4 vs. 2.0 ± 0.4 s, p = 0.002), and TTP (12.5 ± 2.9 vs. 6.2 ± 0.6 s, p = 0.002) were significantly prolonged in the CIN group compared to controls. PE was significantly higher in the control group than in the CIN group (17.1 ± 1.9 vs. 12.2 ± 2.0 dB, p = 0.004). In kidney tissue, mRNA and protein levels of the apoptotic makers were significantly higher in the CIN group than in the control group (p = 0.003 and p = 0.002). Conclusion: CEUS parameters can be used as imaging biomarkers for microperfusion in CIN. In rats with CIN, AT, AC, and TTP were significantly prolonged, while PE was significantly lower compared to controls.

• Korean Journal of Radiology
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• v.20 no.5
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• pp.781-790
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• 2019

Objective: To assess the relationship between contrast-enhanced ultrasound (CEUS) parameters and perfusion CT (PCT) parameters of gastric cancers and their correlation with histologic features. Materials and Methods: This prospective study was approved by our Institutional Review Board. We included 43 patients with pathologically-proven gastric cancers undergoing CEUS using SonoVue^® (Bracco) and PCT on the same day. Correlation between the CEUS parameters (peak intensity [PI], area under the curve [AUC], rise time [RT] from 10% to 90% of PI, time to peak [TTP_US], and mean transit time [MTT_US]) and PCT parameters (blood flow, blood volume, TTP_CT, MTT_CT, and permeability surface product) of gastric cancers were analyzed using Spearman's rank correlation test. In cases of surgical resection, the CEUS and PCT parameters were compared according to histologic features using Mann-Whitney test. Results: CEUS studies were of diagnostic quality in 88.4% (38/43) of patients. Among the CEUS parameters of gastric cancers, RT and TTP_US showed significant positive correlations with TTP_CT (rho = 0.327 and 0.374, p = 0.045 and 0.021, respectively); PI and AUC were significantly higher in well-differentiated or moderately-differentiated tumors (n = 4) than poorly-differentiated tumors (n = 18) (p = 0.026 and 0.033, respectively), whereas MTT_CT showed significant differences according to histologic types (poorly cohesive carcinoma [PCC] vs. non-PCC), T-staging (≤ T2 vs. ≥ T3), N-staging (N0 vs. N-positive), and epidermal growth factor receptor expression (≤ faint vs. ≥ moderate staining) (p values < 0.05). Conclusion: In patients with gastric cancers, CEUS is technically feasible for the quantification of tumor perfusion and may provide correlative and complementary information to that of PCT, which may allow prediction of histologic features.

• Ultrasonography
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• v.32 no.2
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• pp.132-142
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• 2013

Purpose: The purpose of this study is to investigate the correlations of various kinetic parameters derived from the time intensity curve in a xenograft mouse model injected with a prostate cancer model (PC-3 and LNCaP) using an ultrasound contrast agent with histopathologic parameters. Materials and Methods: Twenty nude mice were injected with human prostate cancer cells (15 PC-3 and five LNCaP) on their hind limbs. A bolus of $500{\mu}L$ ($1{\times}10^8$ microbubbles) of second-generation US contrast agent (SonoVue) was injected into the retroorbital vein. The region of interest was drawn over the entire tumor. The time intensity curve was acquired and then fitted to a gamma variate function. The maximal intensity (A), time to peak (Tp), maximal wash-in rate (washin), washout rate (washout), area under the curve up to 50 sec ($AUC_{50}$), area under the ascending slope ($AUC_{in}$), and area under the descending slope ($AUC_{out}$) were derived from the parameters of the gamma variate fit. Immunohistochemical staining for VEGF and CD31 was performed. Tumor volume, the area percentage of VEGF stained in a field, and the count of CD31 (microvessel density, MVD) positive vessels showed correlation with the parameters from the time intensity curve. Results: No significant differences were observed between the kinetic and histopathological parameters from each group. MVD showed positive correlation with A (r=0.625, p=0.003), washin (r=0.462, p=0.040), $AUC_{50}$ (r=0.604, p=0.005), and $AUC_{out}$ (r=0.587, p=0.007). Positive correlations were also observed between tumor volume and $AUC_{50}$ (r=0.481, p=0.032), washin (r=0.662, p=0.001), and $AUC_{out}$ (r=0.547, p=0.012). Washout showed negative correlations with MVD (r=-0.454, p=0.044) and tumor volume (r=-0.464, p=0.039). The area percentage of VEGF did not show any correlation with calculated data from the curve. Conclusion: MVD showed correlations with several of the kinetic parameters. CEUS has the potential for prediction of tumor vascularity in a prostate cancer animal model.