Segurança do Agente de Contraste SF6 (SonoVueⓇ) no Ecocardiograma sob Estresse Farmacológico / Safety of SF6(SonoVue®) Contrast Agent on Pharmacological Stress Echocardiogram

Resumo Fundamento Em 2007, a Food and Drug Administration (FDA) determinou revisões sobre segurança dos agentes de contraste ecocardiográfico (ACE) disponíveis no mercado após relatos de mortes. Ao longo desses anos, diversos estudos comprovaram a segurança dos ACE, porém com poucos estudos relacionados ao SonoVue®. Objetivos Avaliar a segurança do SonoVue® durante o ecocardiograma sob estresse farmacológico (EEF) por meio da análise da incidência de reações alérgicas e da comparação entre os grupos quanto ao surgimento de arritmia, efeitos colaterais menores e eventos adversos. Métodos Estudo observacional, prospectivo, no qual 2.346 pacientes foram submetidos ao EEF e divididos em dois grupos: grupo 1 com ACE (n=1.099) e grupo 2 sem ACE (n=1.247). Os pacientes foram avaliados durante o EEF - 24 horas e 30 dias. Foi definido p significativo quando <0,05. Resultados O grupo 1 apresentou efeitos colaterais mais leves, como cefaleia (5/0,5% vs. 19/1,5%, p=0,012) e hipertensão reativa (3/0,3% vs . 19/1,5%, p=0,002), menos arritmias como extrassístoles ventriculares (180/16,4% vs . 247/19,8%, p=0,032) e taquicardia paroxística supraventricular (2/0,2% vs . 15/1,2%, p=0,003), assim como nenhum evento adverso como infarto agudo do miocárdio (IAM) e óbito. No grupo 2, um paciente apresentou IAM <24h (1/01%) e dois óbitos <30 dias (2/0,1%). Urticária relacionada ao SonoVue® foi observada em 3 (0,3%) pacientes sem reação anafilática. Conclusão SonoVue® demonstrou segurança durante o EEF, não sendo observados morte, IAM ou reação anafilática. Observou-se menor incidência de efeitos colaterais mais leves e arritmias no grupo que utilizou o ACE, assim como baixa incidência de reações alérgicas leves.

Abstract Background In 2007, the United States Food and Drug Administration mandated safety reviews of commercially available echocardiographic contrast agents (ECA), following reports of death. During the past years, different studies have proven the safety of ECA, but there have been few studies on SonoVue®. Objectives To evaluate the safety of SonoVue® during pharmacological stress echocardiography (PSE), by analyzing the incidence of allergic reactions and comparing groups regarding the appearance of arrhythmia, minor side effects and adverse events. Methods In this observational, prospective study, 2346 patients underwent PSE, and they were divided into the following 2 groups: group 1 with ECA (n = 1099) and group 2 without ECA (n = 1247). Patients were evaluated during PSE, at 24 hours, and at 30 days. Statistical significance was defined as p < 0.05. Results Group 1 had fewer minor side effects, such as headache (5/0.5% versus 19/1.5%, p = 0.012) and less reactive hypertension (3/0.3% versus 19/1.5%, p = 0.002); fewer arrhythmias, such as ventricular extrasystoles (180/16.4% versus 247/19.8%, p = 0.032) and paroxysmal supraventricular tachycardia (2/0.2% versus 15/1.2%, p = 0.003); and no adverse events, such as acute myocardial infarction (AMI) or death. In group 2, 1 patient had AMI in < 24 hours (1/01%), and there were 2 deaths in < 30 days (2/0.1%). SonoVue®-related urticaria was seen in 3 (0.3%) patients, without anaphylactic reaction. Conclusion SonoVue® demonstrated safety during PSE. No cases of death, AMI, or anaphylactic reaction were observed. There was a lower incidence of minor side effects and arrhythmias in the group that received ECA, as well as a low incidence of mild allergic reactions.

Flap invertido de membrana limitante interna en agujero macular grande / Inverted internal limiting membrane flap technique in large macular hole

RESUMEN El agujero macular es un desorden de la interface vitreorretinal definido como un defecto de espesor completo desde la membrana limitante interna hasta los segmentos externos de los fotorreceptores, que normalmente involucra a la fóvea. Con el desarrollo de la tomografía de coherencia óptica se han mejorado el diagnóstico, el tratamiento y el seguimiento de las enfermedades de la interface vitreorretinal, entre ellas el agujero macular. La vitrectomía pars plana es la técnica quirúrgica de elección para el agujero macular. Se presenta una paciente de 75 años, pseudofáquica, con mejor agudeza visual corregida en el ojo derecho de 0,1 Snellen. Se diagnostica agujero macular grande (810 µm) según su mínima apertura, con 8 meses de evolución. Se realizó vitrectomía pars plana, el levantamiento de la hialodes posterior, el flap invertido de membrana limitante interna, el uso de hexafluoruro de azufre en mezcla 20 por ciento y el posicionamiento de la paciente 24-72 horas. Se logró el cierre anatómico del agujero macular y la recuperación visual de 0,6 Snellen a los seis meses del tratamiento quirúrgico(AU)

ABSTRACT Macular hole is a disorder of the vitreous-retina interface defined as a full-thickness defect from the internal limiting membrane to the external segments of photoreceptors which typically involves the fovea. The development of optical coherence tomography has improved the diagnosis, treatment and follow-up of vitreous-retina interface diseases, among them macular hole. Pars plana vitrectomy is the surgical technique of choice for macular hole. A case is presented of a female 75-year-old pseudophakic patient with best corrected right eye visual acuity of 0.1 on the Snellen chart. Large macular hole is diagnosed (810 µm) according to its minimum opening, of 8 month's evolution. The following procedures were performed: pars plana vitrectomy, posterior hyalode lifting, inverted internal limiting membrane flap, use of sulfur hexafluoride in a 20% mixture, and positioning of the patient for 24-72 hours. Anatomical closure of the macular hole and a visual recovery of 0.6 Snellen were achieved six months after surgery(AU)

Resultado a corto plazo de la trabeculectomía asociada al hexafluoruro de azufre / Short-term outcomes of trabeculectomy associated to sulfur hexafluoride

Objetivo: describir los resultados a corto plazo de la trabeculectomía asociada al hexafluoruro de azufre. Métodos: se realizó un estudio analítico de caso-control en 30 ojos (30 pacientes) donde 15 ojos (15 pacientes) recibieron trabeculectomía con mitomicina C y hexafluoruro de azufre (grupo caso) y 15 ojos (15 pacientes) recibieron trabeculectomía con mitomicina C (grupo control). Se evaluaron la agudeza visual mejor corregida y la presión intraocular preoperatorias y posoperatorias, así como las complicaciones quirúrgicas. Se realizó seguimiento hasta los 3 meses posoperatorios. Resultados: en el preoperatorio la agudeza visual mejor corregida media fue 88 VAR (±16; 79-97) para el grupo caso y 86 VAR (± 16; 77-95) para el grupo control (p= 0,628) y la presión intraocular media 28,8 mmHg (± 6,3; 25,2-32,3) y 30 mmHg (± 9,5; 24,8-35,3) respectivamente (p= 0,868). A los 3 meses la agudeza visual mejor corregida media fue similar en ambos grupos: 88 VAR (± 13; 80-95) y 84 VAR (± 17; 74-93) respectivamente; (p= 0,659); mientras la presión intraocular fue 14,6 mmHg (± 2,8; 13,0-16,3) y 15,7 mmHg (± 5,4; 12,7-18,8) respectivamente (p= 0,707). Las complicaciones más frecuentes para el grupo caso fueron catarata (6,7 por ciento) y uveítis (6,7 por ciento), y para el grupo control fueron atalamia (19,9 por ciento), hipema (13,3 por ciento) y quiste de Tenon (13,3 por ciento). La densidad celular descendió a 2 004 cél/mm2 (± 87) en el grupo caso y 1 886 cél/mm2 (± 66) en el grupo control (p= 0,494). Conclusiones: el resultado visual, el poder hipotensor y las complicaciones quirúrgicas, a corto plazo, son similares en la trabeculectomía con mitomcina C con/sin hexafluoruro de azufre asociado. Se requieren estudios a mediano-largo plazo para evaluar el beneficio hipotensor del hexafluoruro de azufre(AU)

Objective: describe the short-term results of trabeculectomy associated to sulfur hexafluoride. Methods: an analytical case-control study was conducted of 30 eyes (30 patients) of which 15 eyes (15 patients) underwent trabeculectomy with mitomycin C and sulfur hexafluoride (case group) and 15 eyes (15 patients) underwent trabeculectomy with mitomycin C (control group). An evaluation was performed of the best corrected visual acuity, preoperative and postoperative intraocular pressure and surgical complications. Follow-up extended for up to three months after surgery. Results: mean preoperative best corrected visual acuity was 88 VAR (± 16; 79-97) for the case group and 86 VAR (± 16; 77-95) for the control group (p= 0,628). Mean intraocular pressure was 28.8 mmHg (± 6.3; 25.2-32.3) and 30 mmHg (± 9.5; 24.8-35.3) respectively (p= 0.868). At three months, mean best corrected visual acuity was similar in the two groups: 88 VAR (± 13; 80-95) and 84 VAR (± 17; 74-93) respectively; (p= 0.659); whereas intraocular pressure was 14.6 mmHg (± 2.8; 13.0-16.3) and 15.7 mmHg (± 5.4; 12.7-18.8) respectively (p= 0.707). The most common complications were cataract (6.7 percent) and uveitis (6,7 percent) in the case group, and athalamia (19.9 percent), hyphema (13.3 percent) and Tenon's cyst (13.3 percent) in the control group. Cellular density dropped to 2 004 cell/mm2 (± 87) in the case group and 1 886 cell/mm2 (± 66) in the control group (p= 0.494). Conclusions: short-term visual outcomes, hypotensive effects and surgical complications were similar in trabeculectomy with mitomycin C with or without associated sulfur hexafluoride. Medium-term studies are required to evaluate the hypotensive effect of sulfur hexafluoride(AU)

Effect of RNA Interference Targeting Gene Combined with Ultrasonic Irradiation and SonoVue Microbubbles on Proliferation and Apoptosis in Keratinocytes of Psoriatic Lesions / 中华医学杂志(英文版)

Background@#Signal transducer and activator of transcription 3 (STAT3) was strongly expressed and activated in psoriatic keratinocytes (KCs) and correlated with the severity of psoriasis. The study aimed to investigate the effects of STAT3 small interfering RNA (siRNA) combined with ultrasonic irradiation and SonoVue microbubbles on the proliferation and apoptosis in KCs of psoriatic lesions and the relative mechanisms.@*Methods@#Psoriatic KCs were transfected under four experimental conditions: (1) STAT3 siRNA carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles (LUS group); (2) STAT3 siRNA only carried by Lipofectamine 3000 (L group); (3) the negative control of siRNA carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles (siRNA-NC); (4) not treated as Blank. Cell Counting Kit-8 assay was used to evaluate the cell proliferation. Cell cycle analysis was detected with cycle test Plus DNA reagent kit associated with flow cytometer. FITC Annexin V apoptosis detection kit associated with flow cytometer was applied for apoptosis analysis. Fluo calcium indicator associated with flow cytometer was used to analyze intracellular free calcium concentration ([Ca]). The expressions of cyclin D1 and Bcl-xL were detected both at the mRNA level by real-time reverse transcription-polymerase chain reaction (RT-PCR) and at the protein level by Western blotting. The obtained data were statistically evaluated by two-way analysis of variance.@*Results@#STAT3 siRNA inhibited the growth of KCs in a time-dependent manner showing the highest proliferation inhibition in LUS group with proliferation ratio of 45.38% ± 5.85% at 72h (P < 0.05 vs. L group, siRNA-NC, or Blank). STAT3 siRNA induced an altered cell cycle distribution of KCs showing the highest increases in G2/M-phase population up to 18.06% ± 0.36% in LUS group (P < 0.05 vs. L group, siRNA-NC, or Blank). STAT3 siRNA induced late apoptosis of KCs with the highest late apoptosis percentage of 22.87% ± 1.28% in LUS group (P < 0.05 vs. L group, siRNA-NC, or Blank). STAT3 siRNA induced the elevation of [Ca]of KCs with the highest calcium fluorescence intensity mean of 1213.67 ± 60.51 in LUS group (P < 0.05 vs. L group, siRNA-NC, or Blank). STAT3 siRNA induced the downregulation of cyclin D1 and Bcl-xL expressions of KCs at mRNA and protein levels with the lowest expressions in LUS group with cyclin D1 expression of 51.81% ± 9.58% and 70.17% ± 4.22% at mRNA level and at protein level, respectively, and with Bcl-xL expression of 37.58% ± 4.92% and 64.06% ± 7.78% at mRNA level and at protein level, respectively (P < 0.05 vs. L group, siRNA-NC, or Blank).@*Conclusions@#STAT3 siRNA inhibited the growth and induced the apoptosis in psoriatic KCs likely partly through altering cell cycle distribution, elevating [Ca], and downregulating cyclin D1 and Bcl-xL expressions. Silencing the target gene STAT3 in psoriatic KCs with siRNA combined with ultrasonic irradiation and microbubbles would contribute to a significant innovation as a new clinical therapy for psoriasis.

Synthesis of ultrasound contrast agents: characteristics and size distribution analysis (secondary publication)

PURPOSE: The purpose of this study was to establish a method for ultrasound (US) contrast agent synthesis and to evaluate the characteristics of the synthesized US contrast agent. METHODS: A US contrast agent, composed of liposome and sulfur hexafluoride (SF₆), was synthesized by dissolving 21 μmol 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine (DPPC, C₄₀H₈₀NO₈P), 9 μmol cholesterol, and 1.9 μmol of dihexadecylphosphate (DCP, [CH₃(CH₂)15O]₂P(O)OH) in chloroform. After evaporation in a warm water bath and drying for 12-24 hours, the contrast agent was synthesized using the sonication process by the addition of a buffer and SF₆ gas. The size distribution of the bubbles was analyzed using dynamic light scattering measurement methods. The degradation curve was evaluated by assessing the change in the number of contrast agent bubbles using light microscopy immediately, 12, 24, 36, 48, 60, 72, and 84 hours after synthesis. The echogenicity of the synthesized microbubbles was compared with commercially available microbubbles (SonoVue, Bracco). RESULTS: contrast agent was synthesized successfully using an evaporation-drying-sonication method. Most bubbles had a mean diameter of 154.2 nm and showed marked degradation 24 hours after synthesis. Although no statistically significant differences were observed between SonoVue and the synthesized contrast agent, a difference in echogenicity was observed between the synthesized contrast agent and saline (P<0.01). CONCLUSION: We successfully synthesized a US contrast agent using an evaporation-dryingsonication method. These results may help future research in the fields of anticancer drug delivery, gene delivery, targeted molecular imaging, and targeted therapy.

Comparison of 20% sulfur hexafluoride with air for intraocular tamponade in Descemet membrane endothelial keratoplasty (DMEK) / Comparação de hexafluoreto de enxofre a 20% com ar para tamponamento intraocular na ceratoplastia endotelial de membrana Descemet (DMEK)

ABSTRACT Purpose: To compare the effect of 20% sulfur hexafluoride (SF6) with that of air on graft detachment rates for intraocular tamponade in Descemet membrane endothelial keratoplasty (DMEK). Methods: Forty-two eyes of patients who underwent DMEK by a single surgeon (A.S.J.) at Wilmer Eye Institute between January 2012 and 2014 were identified; 21 received air for intraocular tamponade and the next consecutive 21 received SF6. The main outcome measure was the graft detachment rate; univariate and multivariate analyses were performed. Results: The graft detachment rate was 67% in the air group and 19% in the SF6 group (p<0.05). No complete graft detachments occurred, and all partial detachments underwent intervention with injection of intraocular air. The percentages of eyes with 20/25 or better vision were not different between the groups (67% vs. 71%). Univariate analysis showed significantly higher detachment rates with air tamponade (OR, 8.50; p<0.005) and larger donor graft size (OR, 14.96; p<0.05). Multivariate analysis with gas but not graft size included showed that gas was an independent statistically significant predictor of outcome (OR, 6.65; p<0.05). When graft size was included as a covariate, gas was no longer a statistically significant predictor of detachment but maintained OR of 7.81 (p=0.063) similar to the results of univariate and multivariate analyses without graft size. Conclusion: In comparison with air, graft detachment rates for intraocular tamponade in DMEK were significantly reduced by 20% SF6.

RESUMO Objetivo: Comparar as taxas de descolamento do botão endotelial com o uso de gás hexafluoreto de enxofre a 20% (SF6) em relação ao ar para o tamponamento intraocular na ceratoplastia endotelial da membrana de Descemet (DMEK). Métodos: Quarenta e dois olhos foram operados com a técnica de DMEK por um único cirurgião (A.S.J.) no Wilmer Eye Institute entre janeiro de 2012 a 2014. Os primeiros 21 olhos receberam ar para o tamponamento intraocular após o enxerto do botão endotelial e os 21 olhos seguintes receberam SF6. O desfecho primário medido foi a taxa de descolamento do botão endotelial por análise univariada e multivariada. Resultados: A taxa de descolamento do botão endotelial foi de 67% no grupo que recebeu ar vs 19% no grupo que recebeu SF6 (p<0,05). Não houve nenhum descolamento total de botão e todos os parciais foram tratados com injeção de ar intraocular. Não houve diferença estatística significativa entre os grupos em relação a AV de 20/25 ou melhor (67% vs 71%). A análise univariada demonstrou maior taxa de descolamento com o tamponamento por ar intraocular (OR 8,50, p<0,005) e com botões doadores maiores (OR 14,96, p<0,05). Na análise multivariada, incluindo gás, mas não o tamanho do botão doador, o tipo de gás usado permaneceu sendo um fator preditivo independente e estatisticamente significativo para o desfecho primário, com OR de 6,65 (p<0,05). Porém, quando o tamanho do botão doador foi incluso como covariável, o gás perdeu a sua significância como preditor de descolamento, mantendo o OR de 7,81 (p=0,063), semelhante as análises univariada e multivariada excluindo o tamanho do botão doador. Conclusão: O uso de gás hexafluoreto de enxofre a 20% (SF6) para o tamponamento intraocular reduz a taxa de descolamento do botão endotelial quando comparado ao uso de ar no DMEK.

Diagnostic Efficacy of Contrast-Enhanced Ultrasound for Small Renal Masses

PURPOSE: Ultrasound (US) is highly sensitive in the detection of renal masses. However, it may not be able to differentiate benign and malignant lesions in smaller masses. The purpose of this study was to determine the diagnostic efficacy of contrast-enhanced ultrasound (CEUS) for small renal masses. MATERIALS AND METHODS: From January 2011 to December 2013, a total of 85 patients underwent CEUS for evaluation of renal masses. Of these patients, CEUS findings were retrospectively analyzed for small renal cell carcinoma (RCC) cases (n=38) and angiomyolipoma (AML) cases (n=11). The tumor echogenicity and enhancement patterns and degrees were evaluated. The diagnostic efficacy of CEUS in differentiating the two diseases was compared. RESULTS: On CEUS, the findings of diffuse heterogeneous enhancement (observed in 78.9% of RCCs and 27.3% of AMLs, p=0.003), washout from hyperenhancement or iso-enhancement to hypoenhancement in late phase (73.7% of RCCs and 18.2% of AMLs, p=0.001), and perilesional rim-like enhancement (57.9% of RCCs and 9.1% of AMLs, p=0.006) were significantly different between AML and RCC cases. The corresponding sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 86.8% (33/38), 63.6% (7/11), 89.2% (33/37), 58.3% (7/12), and 81.6% (40/49), respectively. CONCLUSIONS: Our results suggest that the characteristic CEUS features could have diagnostic value in the evaluation of small renal mass. CEUS showed a higher diagnostic efficacy than conventional US for differentiating RCC and AML.

Diagnostic Efficacy of Contrast-Enhanced Ultrasound for Small Renal Masses

PURPOSE: Ultrasound (US) is highly sensitive in the detection of renal masses. However, it may not be able to differentiate benign and malignant lesions in smaller masses. The purpose of this study was to determine the diagnostic efficacy of contrast-enhanced ultrasound (CEUS) for small renal masses. MATERIALS AND METHODS: From January 2011 to December 2013, a total of 85 patients underwent CEUS for evaluation of renal masses. Of these patients, CEUS findings were retrospectively analyzed for small renal cell carcinoma (RCC) cases (n=38) and angiomyolipoma (AML) cases (n=11). The tumor echogenicity and enhancement patterns and degrees were evaluated. The diagnostic efficacy of CEUS in differentiating the two diseases was compared. RESULTS: On CEUS, the findings of diffuse heterogeneous enhancement (observed in 78.9% of RCCs and 27.3% of AMLs, p=0.003), washout from hyperenhancement or iso-enhancement to hypoenhancement in late phase (73.7% of RCCs and 18.2% of AMLs, p=0.001), and perilesional rim-like enhancement (57.9% of RCCs and 9.1% of AMLs, p=0.006) were significantly different between AML and RCC cases. The corresponding sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 86.8% (33/38), 63.6% (7/11), 89.2% (33/37), 58.3% (7/12), and 81.6% (40/49), respectively. CONCLUSIONS: Our results suggest that the characteristic CEUS features could have diagnostic value in the evaluation of small renal mass. CEUS showed a higher diagnostic efficacy than conventional US for differentiating RCC and AML.

Synthesis of Ultrasound Contrast Agent: Characteristics and Size Distribution Analysis

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 micromol DPPC (1, 2-Dihexadecanoyl-sn-glycero-3-phosphocholine, C40H80NO8P), 9 micromol cholesterol, 1.9 micromol of DCP(Dihexadecylphosphate, [CH3(CH2)15O]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.

Current consensus and guidelines of contrast enhanced ultrasound for the characterization of focal liver lesions

The application of ultrasound contrast agents (UCAs) is considered essential when evaluating focal liver lesions (FLLs) using ultrasonography (US). Microbubble UCAs are easy to use and robust; their use poses no risk of nephrotoxicity and requires no ionizing radiation. The unique features of contrast enhanced US (CEUS) are not only noninvasiveness but also real-time assessing of liver perfusion throughout the vascular phases. The later feature has led to dramatic improvement in the diagnostic accuracy of US for detection and characterization of FLLs as well as the guidance to therapeutic procedures and evaluation of response to treatment. This article describes the current consensus and guidelines for the use of UCAs for the FLLs that are commonly encountered in US. After a brief description of the bases of different CEUS techniques, contrast-enhancement patterns of different types of benign and malignant FLLs and other clinical applications are described and discussed on the basis of our experience and the literature data.

Microbubbles enhanced HIFU ablation on rabbit hepatic VX2 tumors: detecting residual tumor with contrast-enhanced ultrasound and spiral CT / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To assess the application of gray-scale contrast-enhanced ultrasound (CEUS) and contrast-enhanced spiral computed tomography (CECT) in detection of residual tumor after high intensity focused ultrasound (HIFU) ablation with microbubbles on rabbit hepatic VX2 tumors.</p><p><b>METHODS</b>Forty rabbits with hepatic VX2 tumors were randomly divided into three groups before ablation. Group I (n=10) served as sham ablation controls, rabbits in group II (n=15) and group III (n=15) were ablated using HIFU under the manipulation of computer. A bolus of 0.2 ml SonoVue solution was injected via ear marginal vein of rabbits in group III before ablation. Tumors were examined with CEUS and CECT before and within 3h after HIFU ablation. Necropsy and histopathological assessment were performed immediately after the completion of images evaluation.</p><p><b>RESULTS</b>Before ablation, intense arterial feeding vessels was detected in the tumors (77.5%,31/40 Compared with 52.5%,21/40) or the periphery of the tumors (22.5%,9/40 Compared with 47.5%,19/40) by CEUS and CECT, respectively. The tumors were characterized by quick wash-in and wash-out (high and rapid peak of enhancement in the arterial phase,followed by a fast decrease in enhancement level). The dose parameters used to achieve therapeutic effect in group III were significantly lower than those in group II(P<0.01). There were local residual viable tumor tissues due to incomplete ablation in 60.0% (9/15) of group II and 13.3% (2/15) of group III revealed by histopathology(P<0.05). The concordance rate of CECT and CEUS with histopathology on residual tumor detection was 27.3% and 81.8% (P<0.05), respectively.</p><p><b>CONCLUSION</b>The administration of microbubble agent enhances the efficacy of HIFU on rabbit hepatic VX2 tumors. CEUS is more sensitive than CECT in detection of residual viable rabbit VX2 tumor after HIFU.</p>

Correlation between enhanced intensity of atherosclerotic plaque at contrast-enhanced ultrasonography and density of histological neovascularization / 华中科技大学学报（医学）（英德文版）

The feasibility of contrast-enhanced ultrasonography in the assessment of atherosclerotic plaque neovascularization and its relation to histological findings were investigated. Abdominal aortic atherosclerotic plaque model was induced in 25 New Zealand white rabbits by a combination of high cholesterol-rich diet and balloon aortic denudation. Standard and contrast-enhanced ultrasonography was performed at the 16th week of the model induction period. The plaques were classified as echogenic plaques or echolucent plaques according to their echogenicity at standard ultrasonography. The maximum thickness of plaque was measured in the longitudinal section. Time intensity curve was used to quantify the enhanced intensity of the plaque. Animals were euthanized and abdominal aortas were harvested for histological staining of CD31 to evaluate the neovascularization density of atherosclerotic plaque. The results showed that the echolucent plaques had higher enhanced intensity during contrastenhanced ultrasonography and higher neovascularization density at CD31 staining than the echogenic plaques. The enhanced intensity of atherosclerotic plaque and its ratio to lumen were well correlated with histological neovascularization density (r=0.75, P<0.001; r=0.68, P<0.001, respectively). However, the maximum thickness of plaque was not correlated with neovascularization density (r=0.235, P=0.081). These findings demonstrated that the enhanced intensity in the plaque and ratio of enhanced intensity to that in the lumen of abdominal aorta may be more accurate in the evaluation of plaque neovascularization than maximum thickness. Our study indicates that contrast-enhanced ultrasonography provides us a reliable method for the evaluation of plaque neovascularization.

Voiding urosonography with SonoVue and fluoroscopic voiding cystourethrography in evaluation of vesicoureteral reflux: a comparative study / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the value of voiding urosonography (VUS) with SonoVue in evaluation of vesicoureteral reflux.</p><p><b>METHODS</b>Thirty-six pediatric patients (72 pyeloureter units [PUUs]) suspected of vesicoureteral reflux underwent both VUS and fluoroscopic voiding cystourethrography (VCUG). The sensitivity of VUS and VCUG and their consistency in detecting vesicoureteral reflux as well as in grading vesicoureteral reflux were compared.</p><p><b>RESULTS</b>Vesicoureteral reflux was detected in 26 of the 72 PUUs (36.1%) by VUS while in 21 PUUs (29.2%) by VCUG (P=0.347). The two modalities yielded the same results for 65 PUUs (κ=0.843), showing a very good consistency between them. VUS also detected post-urethral valve in 2 patients via transperineal scans.</p><p><b>CONCLUSION</b>VUS with Sonovue has at least comparable, if not better, sensitivity in detecting vesicoureteral reflux with VCUG, and therefore should serve as the primary screening and follow-up modality for vesicoureteral reflux. In addition, transperineal VUS can be helpful in evaluation of post-urethral lesions.</p>

Contrast-enhanced ultrasound imaging features of diabetic foot ulcers / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate contrast-enhanced ultrasound imaging features of diabetic foot ulcers.</p><p><b>METHODS</b>Sixteen patients with diabetic foot ulcers underwent conventional and contrast-enhanced ultrasound examinations, and the features of contrast-enhanced ultrasound imaging were analyzed. Pathological examination was also carried out in some cases.</p><p><b>RESULTS</b>Contrast-enhanced ultrasound showed slow enhancement in the artery phase in the 16 ulcers after administration of SonoVue. The mean time of initial enhancement was 30.02 ± 2.35 s, and the mean time for the occurrence of peak enhancement was 37.54 ± 4.13 s. In 5 cases a homogeneous enhancement pattern was clearly displayed, and in the other 11 cases, a pattern of homogenous peripheral enhancement with non-enhanced patches within the ulcers was found. Contrast-enhanced ultrasound showed a greater ulcerous area than conventional ultrasound.</p><p><b>CONCLUSION</b>Contrast-enhanced ultrasound is a valuable means for evaluating the ulcerous area and the treatment efficacy for diabetic foot ulcers.</p>

Cyclocryotherapy and Intravitreal Gas Tamponade of a Chronic Cyclodialysis Cleft: Case Report

PURPOSE: To report a case of chronic hypotony maculopathy caused by traumatic cyclodialysis cleft and treated with 20% sulfur hexafluoride (SF6) gas tamponade with cyclocryotherapy. CASE SUMMARY: A 39-year-old woman with a history of blunt trauma developed a unilateral chronic ocular hypotony in her left eye. She was treated with topical atropine sulphate 1% for 2 months. Three years later, she was referred to our clinic for evaluation and treatment of persistent hypotony. The intraocular pressure (IOP) was 4 mm Hg and the best corrected visual acuity was 0.4. B-scan echography revealed a choroidal effusion and fundus examination showed choroidal detachment and macular folds. Gonioscopy examination revealed cyclodialysis cleft from the direction of 7 o'clock to 11 o'clock. A single bubble of SF6 20% (0.4 cc) was injected into the vitreous cavity and transconjunctival cyclocryotherapy was performed under retrobulbar anesthesia. Six months later, the IOP was 12 mm Hg and the best corrected visual acuity was 1.0. B-scan echograpy and fundus examination showed the disappearance of the choroidal effusion. CONCLUSIONS: Gas tamponade with cyclocryotherapy may be useful in cases of cyclodialysis cleft that failed to respond to medical therapy.

Contrast-enhanced ultrasound analysis of renal perfusion in normal micropigs

Contrast-enhanced ultrasound is one of method for evaluating renal perfusion. The purpose of this project was to assess perfusion patterns and dynamics in normal micropig kidney using ultrasonographic contrast media. Eight young healthy micropigs were included in this study. Micropigs were anesthetized with propofol and received an intravenous bolus of microbubble contrast media through an ear vein. Time/mean pixel value (MPV) curves were generated for selected regions in the right renal cortex and medulla. The parenchyma was enhanced in two phases. The cortex was first enhanced followed by a more gradual enhancement of the medulla. A significant difference in perfusion was detected between the cortex and medulla. Following the bolus injection, the average upslope was 0.68 +/- 0.27 MPV/sec, downslope was -0.27 +/- 0.13 MPV/sec, baseline was 73.9 +/- 16.5 MPV, peak was 84.6 +/- 17.2 MPV, and time-to-peak (from injection) was 17.5 +/- 6.6 sec for the cortex. For the medulla, the average upslope was 0.50 +/- 0.24 MPV/sec, downslope was -0.12 +/- 0.06 MPV/sec, baseline was 52.7 +/- 7.0 MPV, peak was 65.2 +/- 9.3 MPV, and time-to-peak (from injection) was 27.5 +/- 5.0 sec. These data can be used as normal reference values for studying young micropigs.

Comparison of EGF with VEGF Non-Viral Gene Therapy for Cutaneous Wound Healing of Streptozotocin Diabetic Mice

BACKGROUND: To accelerate the healing of diabetic wounds, various kinds of growth factors have been employed. It is the short half-life of administered growth factors in hostile wound beds that have limited wide-spread clinical usage. To overcome this limitation, growth factor gene therapy could be an attractive alternative rather than direct application of factors onto the wound beds. We administered two growth factor DNAs, epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) into a cutaneous wound on diabetic mice. We compared the different characteristics of the healing wounds. METHODS: Streptozotocin was injected intraperitoneally to induce diabetes into C57BL/6J mice. The ultrasound micro-bubble destruction method with SonoVue as a bubbling agent was used for non-viral gene delivery of EGF828 and VEGF165 DNAs. Each gene was modified for increasing efficacy as FRM-EGF828 or minicircle VEGF165. The degree of neoangiogenesis was assessed using qualitative laser Doppler flowmetry. We compared wound size and histological findings of the skin wounds in each group. RESULTS: In both groups, accelerated wound closure was observed in the mice receiving gene therapy compared with non treated diabetic control mice. Blood flow detected by laser doppler flowmetry was better in the VEGF group than in the EGF group. Wound healing rates and histological findings were more accelerated in the EGF gene therapy group than the VEGF group, but were not statistically significant. CONCLUSION: Both non-viral EGF and VEGF gene therapy administrations could improve the speed and quality of skin wound healing. However, the detailed histological characteristics of the healing wounds were different.

Sulfur hexafluoride 20% versus lactated ringer's solution for prevention of early postoperative vitreous hemorrhage after diabetic vitrectomy

To compare the hemostatic effect of sulfur hexafluoride 20% [SF6 20%] with lactated Ringer's solution for prevention of early postoperative vitreous hemorrhage following diabetic vitrectomy. In a prospective randomized clinical trial, 50 eyes undergoing diabetic vitrectomy were divided into two groups. At the conclusion of surgery, in one group the vitreous cavity was filled with SF6 20% while in the other group lactated Ringer's solution was retained in the vitreous cavity. The two groups were compared for the rate of early postoperative vitreous hemorrhage. The incidence of vitreous hemorrhage was lower in the SF6 group than the Ringer's group 4 days [20% vs. 68%, P=0.001], 7 days [24% vs. 60%, O=0.01] and 4 weeks [16% vs. 40%, P=0.059] after vitrectomy. In comparison with lactated ringer's solution, SF6 20% had a significant hemostatic effect especially in the early postoperative period after diabetic vitrectomy and reduced the incidence of vitreous hemorrhage

Effects of high intensity focused ultrasound with SonoVue on blood vessels pathological examinations / 生物医学工程学杂志

The injury of tumor blood vessels will break up the nutrition supply for the tumor. In this paper, we investigated the effects exerted by high intensity focused ultrasound (HIFU) combined with ultrasound microbubble agent on blood vessels. Ultrasound diagnosis was used to find the goat hepatic blood vessels each being approximately 3mm in diameter. HIFU was focused on the blood vessels. The acoustic power was 250W; HIFU irradiating Mode was line scan (the length of the line: 10 mm; speed: 3 mm/s; irradiating time: 30s). In the experimental group, 0.03 ml/kg SonoVue was injected into the goat before HIFU irradiation,while normal saline was given to the control group. The goats were killed at 24h after HIFU irradiation, then goat liver tissues and blood vessels of target area were taken out. HE staining and Victoria's blue and Ponceau's staining of tissue section showed that the endothelial cells of blood vessels dropped off and became necrosed, and the continuity of blood vessels was interrupted. HIFU combined with SonoVue will damage large blood vessels on HIFU focus, but there is no evident discrepancy between the group with SonoVue and the group without SonoVue.

Diagnostic value of contrast-enhanced ultrasonography in preoperative T-staging of gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the diagnostic value of contrast-enhanced ultrasonography (CEUS) in preoperative T-staging of gastric cancer.</p><p><b>METHODS</b>A sulfur hexafluoride-filled microbubble ultrasound contrast agent and a continuous real-time imaging technique of contrast pulse sequencing were used. Normal gastric wall was examined by CEUS in 8 healthy volunteers and the results were compared with the findings on multislice computed tomography. Sixty-two patients with gastric cancer proved by biopsies who received preoperative CEUS examination were involved in this study, and the CEUS result was compared with postoperative pathological findings.</p><p><b>RESULTS</b>The normal gastric wall presented a one-layer structure in the portal venous phase and a three-layer structure in the arterial and equilibrium phase including a slightly hyper-enhanced inner layer, a hypo-enhanced intermediate layer, and a markedly hyper-enhanced outer layer, which corresponded histologically to the mucosal, submucosal, and muscular-serosal layer, respectively. The accuracy of transabdominal ultrasonography and CEUS in determining the T stage of gastric cancer was 72.9% and 88.1% respectively, and the difference was statistically significant (chi(2)=4.37, P=0.036).</p><p><b>CONCLUSIONS</b>CEUS shows the normal gastric wall as a one- or a three-layer structure, which provides a theory base for CEUS in preoperative T-staging of gastric cancer. CEUS is a useful diagnostic method for preoperative T-staging of gastric cancer.</p>