ophthalmologyОфтальмологияOphthalmology in Russia1816-50952500-0845Ophthalmology10.18008/1816-5095-2021-2-216-221ophthalmology-1535Research ArticleОБЗОРЫREVIEWSЭхоконтрастирование в диагностике патологии органа зрения: перспективы примененияContrast-Enhanced Ultrasound in the Diagnosis of Ocular Pathology: Application ProspectsКиселеваТ. Н.KiselevaT. N.

доктор медицинских наук, профессор, начальник отдела ультразвуковых исследований,

ул. Садовая-Черногрязская, 14/19, Москва, 105062

MD, Professor, head of Ultrasound diagnostic department,

Sadovaya-Chernogryazskaya str., 14/19, Moscow, 105062

БедретдиновА. Н.BedretdinovA. N.

кандидат медицинских наук, научный сотрудник отдела ультразвуковых исследований,

ул. Садовая-Черногрязская, 14/19, Москва, 105062

PhD, researcher, Ultrasound diagnostic department,

Sadovaya-Chernogryazskaya str., 14/19, Moscow, 105062

anbedretdinov@gmail.comФГБУ «Национальный медицинский исследовательский центр глазных болезней им. Гельмгольца» Министерства здравоохранения Российской ФедерацииРоссияHelmholtz National Medical Research Center of Eye DiseasesRussian Federation202103072021182216221Copyright © Киселева Т.Н., Бедретдинов А.Н., 20212021Киселева Т.Н., Бедретдинов А.Н.Kiseleva T.N., Bedretdinov A.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.ophthalmojournal.com/opht/article/view/1535

Эхография с контрастным усилением — высокоинформативный метод в дифференциальной диагностике очаговых изменений различных органов и тканей, который позволяет визуализировать сосудистые структуры и получать ранее недоступную для стандартного ультразвукового исследования в В-режиме информацию. После разработки в начале XXI века нового поколения контрастных веществ, состоящих из микропузырьков инертного газа, эхоконтрастирование стало широко применяться для улучшения визуальной оценки сосудов мелкого калибра в диагностике патологии органов брюшной полости и забрюшинного пространства: доброкачественных и злокачественных образований печени, патологических изменений селезенки, воспалительных заболеваний и опухолей поджелудочной железы, дефектов почечной перфузии, опухолевых и кистозных поражений почек. В офтальмологии основными направлениями в изучении информативности ультразвукового исследования с контрастным усилением до сих пор остаются оценка микроциркуляции внутриглазных новообразований и диагностика витреоретинальной патологии. В последние годы возрос интерес относительно применения эхоконтрастов в исследовании перфузии различных типов увеальной меланомы в эксперименте на животных. В генной инженерии перспективным направлением является использование локального воздействия ультразвука с контрастным усилением на клетки сетчатки (ганглиозные, пигментный эпителий) для стимуляции процессов трансфекции (введение нуклеиновой кислоты в ДНК клетки невирусным методом), что представляет собой важный элемент клеточной терапии. Несмотря на достигнутые успехи в исследовании эффективности использования эхоконтрастирования в медицине, вопрос повышения информативности этого метода в диагностике офтальмопатологии требует дальнейшего изучения. 

Contrast-enhanced ultrasound is a highly informative method for the differential diagnosis of focal changes in various organs and tissues, which allows to visualize vascular structures and obtain new previously unavailable information when using standard b-scan. At the beginning of the 21st century after the development of a new generation of contrast agents consisting of microbubbles with inert gas contrast-enhanced ultrasound became widely used to improve visual assessment of small-caliber vessels in the diagnosis of the abdominal cavity and retroperitoneal space pathology: benign and malignant liver formations, spleen pathology, inflammatory diseases and tumors of the pancreas, defects in renal perfusion, tumor and cystic lesions of the kidneys. Assessment of intraocular tumors microcirculation and diagnosis of vitreoretinal pathology are still two main directions of using contrast-enhanced ultrasound in ophthalmology. In recent years, there has been a growing interest in the use of contrast-enhanced ultrasound in the study of perfusion of different types of uveal melanoma in an animal experiment. A promising direction in the field of genetic engineering is the use of local contrast-enhanced ultrasound exposure on retinal cells (retinal ganglion cells, retinal pigment epithelium) to promote gene transfection (non-viral nucleic acid delivery into the DNA of a cell), which is an important part of gene therapy. Despite the successes achieved in the study of contrast-enhanced ultrasound effectiveness in medicine, further research is needed to increase the informative value of this method in the diagnosis of ophthalmopathology. 

эхоконтрастированиеультразвуковое исследование глазамикроциркуляциямикропузырькиувеальная меланомаcontrast-enhanced ultrasoundultrasound of the eyemicrocirculationmicrobubblesuveal melanomaReferencesGramiak R., Shah P.M. Echocardiography of the aortic root. Invest Radiol. 1968;3:356–366. DOI: 10.1097/00004424-196809000-00011Gramiak R., Shah P.M. Echocardiography of the aortic root. Invest Radiol. 1968;3:356–366. DOI: 10.1097/00004424-196809000-00011Gramiak R., Nanda N.C. New techniques in cardiac imaging with ultrasound: state of the art. Radiology. 1979 Dec;133(3 Pt 1):669–675. DOI: 10.1148/133.3.669Gramiak R., Nanda N.C. New techniques in cardiac imaging with ultrasound: state of the art. Radiology. 1979 Dec;133(3 Pt 1):669–675. DOI: 10.1148/133.3.669Serruys P.W., Hagemeijer F., Ligtoet C., Roelandt J. Contrast echocardiology in two dimensions and in real time. 1. Ultrasonic techniques. Arch Mal Coeur Vaiss. 1978 Jun;71(6):600–610.Serruys P.W., Hagemeijer F., Ligtoet C., Roelandt J. Contrast echocardiology in two dimensions and in real time. 1. Ultrasonic techniques. Arch Mal Coeur Vaiss. 1978 Jun;71(6):600–610.Goldberg B.B., Liu J.B., Burns P.N., Merton D.A., Forsberg F. Galactosebased intravenous sonographic contrast agent: experimental studies. J Ultrasound Med. 1993;12(8):463–470. DOI: 10.7863/jum.1993.12.8.463Goldberg B.B., Liu J.B., Burns P.N., Merton D.A., Forsberg F. Galactosebased intravenous sonographic contrast agent: experimental studies. J Ultrasound Med. 1993;12(8):463–470. DOI: 10.7863/jum.1993.12.8.463Albrecht T., Hoffmann C.W., Schettler S., Overberg A., Ilg M., von Behren P.L., Bauer A., Wolf K.J. B-mode enhancement at phase-inversion US with air-based microbubble contrast agent: initial experience in humans. Radiology. 2000;216(1):273– 278. DOI: 10.1148/radiology.216.1.r00jl27273Albrecht T., Hoffmann C.W., Schettler S., Overberg A., Ilg M., von Behren P.L., Bauer A., Wolf K.J. B-mode enhancement at phase-inversion US with air-based microbubble contrast agent: initial experience in humans. Radiology. 2000;216(1):273– 278. DOI: 10.1148/radiology.216.1.r00jl27273Harvey C.J., Blomley M.J., Eckersley R.J., Cosgrove D.O. Developments in ultrasound contrast media. Eur Radiol. 2001;11(4):675–689. DOI: 10.1007/s003300000624Harvey C.J., Blomley M.J., Eckersley R.J., Cosgrove D.O. Developments in ultrasound contrast media. Eur Radiol. 2001;11(4):675–689. DOI: 10.1007/s003300000624Lencioni R., Cioni D., Bartolozzi C. Tissue harmonic and contrast-specific imaging: back to gray scale in ultrasound. Eur Radiol. 2002;12(1):151–165. DOI: 10.1007/s003300101022Lencioni R., Cioni D., Bartolozzi C. Tissue harmonic and contrast-specific imaging: back to gray scale in ultrasound. Eur Radiol. 2002;12(1):151–165. DOI: 10.1007/s003300101022Morel D.R., Schwieger I., Hohn L., Terrettaz J., Llull J.B., Cornioley Y.A., Schneider M. Human pharmacokinetics and safety evaluation of SonoVue, a new contrast agent for ultrasound imaging. Invest Radiol. 2000;35(1):80–85. DOI: 10.1097/00004424-200001000-00009Morel D.R., Schwieger I., Hohn L., Terrettaz J., Llull J.B., Cornioley Y.A., Schneider M. Human pharmacokinetics and safety evaluation of SonoVue, a new contrast agent for ultrasound imaging. Invest Radiol. 2000;35(1):80–85. DOI: 10.1097/00004424-200001000-00009Schneider M., Arditi M., Barrau M.B., Brochot J., Broillet A., Ventrone R., Yan F. BR1: a new ultrasonographic contrast agent based on sulfur hexafluoride-filled microbubbles. Invest Radiol. 1995;30(8):451–471. DOI: 10.1097/00004424199508000-00001Schneider M., Arditi M., Barrau M.B., Brochot J., Broillet A., Ventrone R., Yan F. BR1: a new ultrasonographic contrast agent based on sulfur hexafluoride-filled microbubbles. Invest Radiol. 1995;30(8):451–471. DOI: 10.1097/00004424199508000-00001Bauer A., Solbiati L., Weissman N. Ultrasound imaging with SonoVue: low mechanical index real-time imaging. Acad Radiol. 2002;9(Suppl 2):S282–284. DOI: 10.1016/s1076-6332(03)80204-0Bauer A., Solbiati L., Weissman N. Ultrasound imaging with SonoVue: low mechanical index real-time imaging. Acad Radiol. 2002;9(Suppl 2):S282–284. DOI: 10.1016/s1076-6332(03)80204-0Burns P.N., Wilson S.R. Microbubble contrast for radiological imaging: 1. Principles. Ultrasound Q. 2006;22(1):5–13.Burns P.N., Wilson S.R. Microbubble contrast for radiological imaging: 1. Principles. Ultrasound Q. 2006;22(1):5–13.Quaia E. Microbubble ultrasound contrast agents: an update. Eur Radiol. 2007;17(8):1995–2008. DOI: 10.1007/s00330-007-0623-0Quaia E. Microbubble ultrasound contrast agents: an update. Eur Radiol. 2007;17(8):1995–2008. DOI: 10.1007/s00330-007-0623-0Piscaglia F., Bolondi L. The safety of Sonovue in abdominal applications: retrospective analysis of 23188 investigations. Ultrasound Med Biol. 2006; 32(9):1369–1375. DOI: 10.1016/j.ultrasmedbio.2006.05.031Piscaglia F., Bolondi L. The safety of Sonovue in abdominal applications: retrospective analysis of 23188 investigations. Ultrasound Med Biol. 2006; 32(9):1369–1375. DOI: 10.1016/j.ultrasmedbio.2006.05.031Bartolotta T.V., Midiri M., Quaia E., Bertolotto M., Galia M., Cademartiri F., Lagalla R. Liver haemangiomas undetermined at grey-scale ultrasound: contrast-enhancement patterns with SonoVue and pulse-inversion US. Eur Radiol. 2005;15(4):685–693. DOI: 10.1007/s00330-004-2569-9Bartolotta T.V., Midiri M., Quaia E., Bertolotto M., Galia M., Cademartiri F., Lagalla R. Liver haemangiomas undetermined at grey-scale ultrasound: contrast-enhancement patterns with SonoVue and pulse-inversion US. Eur Radiol. 2005;15(4):685–693. DOI: 10.1007/s00330-004-2569-9Wang L.Y., Wang J.H., Lin Z.Y., Yu M.L., Lu S.N., Chuang W.L., Chen S.C., Hseih M.Y., Tsai J.F., Chang W.Y. Hepatic focal nodular hyperplasia: findings on color Doppler ultrasound. Abdom Imaging. 1997;22(2):178–181. DOI: 10.1007/s002619900167Wang L.Y., Wang J.H., Lin Z.Y., Yu M.L., Lu S.N., Chuang W.L., Chen S.C., Hseih M.Y., Tsai J.F., Chang W.Y. Hepatic focal nodular hyperplasia: findings on color Doppler ultrasound. Abdom Imaging. 1997;22(2):178–181. DOI: 10.1007/s002619900167Ricci P., Cantisani V., D’Onofrio M., Sahani D., Pagliara E., Calliada F., Mehmet E., Sanjeva K., Faccioli N., Pozzi-Mucelli R., D’Ambrosio U., Passariello R. Behavior of hepatocellular adenoma on real-time low-mechanical index contrast-enhanced ultrasonography with a second-generation contrast agent. J Ultrasound Med. 2008;27(12):1719–1726. DOI: 10.7863/jum.2008.27.12.1719Ricci P., Cantisani V., D’Onofrio M., Sahani D., Pagliara E., Calliada F., Mehmet E., Sanjeva K., Faccioli N., Pozzi-Mucelli R., D’Ambrosio U., Passariello R. Behavior of hepatocellular adenoma on real-time low-mechanical index contrast-enhanced ultrasonography with a second-generation contrast agent. J Ultrasound Med. 2008;27(12):1719–1726. DOI: 10.7863/jum.2008.27.12.1719Xu H.X., Lu M.D., Liu G.J., Xie X.Y., Xu Z.F., Zheng Y.L., Liang J.Y. Imaging of peripheral cholangiocarcinoma with low-mechanical index contrast-enhanced sonography and SonoVue: initial experience. J Ultrasound Med. 2006;25(1):23–33. DOI: 10.7863/jum.2006.25.1.23Xu H.X., Lu M.D., Liu G.J., Xie X.Y., Xu Z.F., Zheng Y.L., Liang J.Y. Imaging of peripheral cholangiocarcinoma with low-mechanical index contrast-enhanced sonography and SonoVue: initial experience. J Ultrasound Med. 2006;25(1):23–33. DOI: 10.7863/jum.2006.25.1.23Bolondi L., Gaiani S., Celli N., Golfieri R., Grigioni W.F., Leoni S., Venturi A.M., Piscaglia F. Characterization of small nodules in cirrhosis by assessment of vascularity: the problem of hypovascular hepatocellular carcinoma. Hepatology. 2005;42(1):27–34. DOI: 10.1002/hep.20728Bolondi L., Gaiani S., Celli N., Golfieri R., Grigioni W.F., Leoni S., Venturi A.M., Piscaglia F. Characterization of small nodules in cirrhosis by assessment of vascularity: the problem of hypovascular hepatocellular carcinoma. Hepatology. 2005;42(1):27–34. DOI: 10.1002/hep.20728Tarantino L., Francica G., Sordelli I., Esposito F., Giorgio A., Sorrentino P., de Stefano G., Di Sarno A., Ferraioli G., Sperlongano P. Diagnosis of benign and malignant portal vein thrombosis in cirrhotic patients with hepatocellular carcinoma: color Doppler US, contrast-enhanced US, and fine-needle biopsy. Abdom Imaging. 2006;31(5):537–544. DOI: 10.1007/s00261-005-0150-xTarantino L., Francica G., Sordelli I., Esposito F., Giorgio A., Sorrentino P., de Stefano G., Di Sarno A., Ferraioli G., Sperlongano P. Diagnosis of benign and malignant portal vein thrombosis in cirrhotic patients with hepatocellular carcinoma: color Doppler US, contrast-enhanced US, and fine-needle biopsy. Abdom Imaging. 2006;31(5):537–544. DOI: 10.1007/s00261-005-0150-xPark B.K., Kim S.H., Moon M.H., Jung S.I. Imaging features of gray-scale and contrast-enhanced color Doppler US for the differentiation of transient renal arterial ischemia and arterial infarction. Korean J Radiol. 2005;6(3):179–184. DOI: 10.3348/kjr.2005.6.3.179Park B.K., Kim S.H., Moon M.H., Jung S.I. Imaging features of gray-scale and contrast-enhanced color Doppler US for the differentiation of transient renal arterial ischemia and arterial infarction. Korean J Radiol. 2005;6(3):179–184. DOI: 10.3348/kjr.2005.6.3.179Kim J.H., Eun H.W., Lee H.K., Park S.J., Shin J.H., Hwang J.H., Goo D.E., Choi D.L. Renal perfusion abnormality. Coded harmonic angio US with contrast agent. Acta Radiol. 2003;44(2):166–171.Kim J.H., Eun H.W., Lee H.K., Park S.J., Shin J.H., Hwang J.H., Goo D.E., Choi D.L. Renal perfusion abnormality. Coded harmonic angio US with contrast agent. Acta Radiol. 2003;44(2):166–171.Catalano O., Sandomenico F., Matarazzo I., Siani A. Contrast-enhanced sonography of the spleen. AJR Am J Roentgenol. 2005;184(4):1150–1156. DOI: 10.2214/ajr.184.4.01841150Catalano O., Sandomenico F., Matarazzo I., Siani A. Contrast-enhanced sonography of the spleen. AJR Am J Roentgenol. 2005;184(4):1150–1156. DOI: 10.2214/ajr.184.4.01841150D’Onofrio M., Zamboni G., Faccioli N., Capelli P., Pozzi Mucelli R. Ultrasonography of the pancreas. 4. Contrast-enhanced imaging. Abdom Imaging. 2007;32(2):171– 181. DOI: 10.1007/s00261-006-9010-6D’Onofrio M., Zamboni G., Faccioli N., Capelli P., Pozzi Mucelli R. Ultrasonography of the pancreas. 4. Contrast-enhanced imaging. Abdom Imaging. 2007;32(2):171– 181. DOI: 10.1007/s00261-006-9010-6Miszalok V., Fritzsch T., Wollensak J. Contrast echography of the eye and orbit. Ophthalmologica. 1986;193(4):231-235. DOI: 10.1159/000309715Miszalok V., Fritzsch T., Wollensak J. Contrast echography of the eye and orbit. Ophthalmologica. 1986;193(4):231-235. DOI: 10.1159/000309715Brabrand K., Kerty E., Jakobsen J.A. Contrast-enhanced ultrasound Doppler examination of the retrobulbar arteries. Acta Radiol. 2001 Mar;42(2):135–139.Brabrand K., Kerty E., Jakobsen J.A. Contrast-enhanced ultrasound Doppler examination of the retrobulbar arteries. Acta Radiol. 2001 Mar;42(2):135–139.Fowlkes J.B. American Institute of Ultrasound in Medicine consensus report on potential bioeffects of diagnostic ultrasound: executive summary. J Ultrasound Med. 2008 Apr;27(4):503–515. DOI: 10.7863/jum.2008.27.4.503Fowlkes J.B. American Institute of Ultrasound in Medicine consensus report on potential bioeffects of diagnostic ultrasound: executive summary. J Ultrasound Med. 2008 Apr;27(4):503–515. DOI: 10.7863/jum.2008.27.4.503Киселева Т.Н., Луговкина К.В., Зайцев М.С. Вопросы безопасности диагностического ультразвука в офтальмологии. Офтальмология. 2018; 15(4):447–454. DOI: 10.18008/1816-5095-2018-4-447-454Kiseleva T.N., Zaitsev M.S., Lugovkina K.V. The Safety of Diagnostic Ultrasound in Ophthalmology. Ophthalmology in Russia = Oftal’mologiya. 2018;15(4):447–454 (In Russ.). DOI: 10.18008/1816-5095-2018-4-447-454Hirokawa T., Nishikage T., Moroe T., Kajima M., Hayashi M., Naito T., Yamane S., Shiota H. Visualization of uveal perfusion by contrast-enhanced harmonic ultrasonography at a low mechanical index: a pilot animal study. J Ultrasound Med. 2002 Mar;21(3):299–307. DOI: 10.7863/jum.2002.21.3.299Hirokawa T., Nishikage T., Moroe T., Kajima M., Hayashi M., Naito T., Yamane S., Shiota H. Visualization of uveal perfusion by contrast-enhanced harmonic ultrasonography at a low mechanical index: a pilot animal study. J Ultrasound Med. 2002 Mar;21(3):299–307. DOI: 10.7863/jum.2002.21.3.299Han S.S., Chang S.K., Yoon J.H., Lee Y.J. The use of contrast-enhanced color Doppler ultrasound in the differentiation of retinal detachment from vitreous membrane. Korean J Radiol. 2001 Oct-Dec;2(4):197–203. DOI: 10.3348/kjr.2001.2.4.197Han S.S., Chang S.K., Yoon J.H., Lee Y.J. The use of contrast-enhanced color Doppler ultrasound in the differentiation of retinal detachment from vitreous membrane. Korean J Radiol. 2001 Oct-Dec;2(4):197–203. DOI: 10.3348/kjr.2001.2.4.197Labruyere J.J., Hartley C., Holloway A. Contrast-enhanced ultrasonography in the differentiation of retinal detachment and vitreous membrane in dogs and cats. J Small Anim Pract. 2011 Oct;52(10):522–530. DOI: 10.1111/j.17485827.2011.01099.xLabruyere J.J., Hartley C., Holloway A. Contrast-enhanced ultrasonography in the differentiation of retinal detachment and vitreous membrane in dogs and cats. J Small Anim Pract. 2011 Oct;52(10):522–530. DOI: 10.1111/j.17485827.2011.01099.xBertolotto M., Serafini G., Sconfienza L.M., Lacelli F., Cavallaro M., Coslovich A., Tognetto D., Cova M.A. The use of CEUS in the diagnosis of retinal/choroidal detachment and associated intraocular masses — preliminary investigation in patients with equivocal findings at conventional ultrasound. Ultraschall Med. 2014 Apr;35(2):173–180. DOI: 10.1055/s-0032-1330321Bertolotto M., Serafini G., Sconfienza L.M., Lacelli F., Cavallaro M., Coslovich A., Tognetto D., Cova M.A. The use of CEUS in the diagnosis of retinal/choroidal detachment and associated intraocular masses — preliminary investigation in patients with equivocal findings at conventional ultrasound. Ultraschall Med. 2014 Apr;35(2):173–180. DOI: 10.1055/s-0032-1330321Forte R., Cennamo G., Staibano S., De Rosa G. Echographic examination with new generation contrast agent of choroidal malignant melanomas. Acta Ophthalmol Scand. 2005 Jun;83(3):347–354. DOI: 10.1111/j.1600-0420.2005.00428.xForte R., Cennamo G., Staibano S., De Rosa G. Echographic examination with new generation contrast agent of choroidal malignant melanomas. Acta Ophthalmol Scand. 2005 Jun;83(3):347–354. DOI: 10.1111/j.1600-0420.2005.00428.xVenturini M., Colantoni C., Modorati G., Di Nicola M., Colucci A., Agostini G., Picozzi P., De Cobelli F., Parmiani G., Mortini P., Bandello F., Del Maschio A. Preliminary results of contrast-enhanced sonography in the evaluation of the response of uveal melanoma to gamma-knife radiosurgery. J Clin Ultrasound. 2015 Sep;43(7):421–430. DOI: 10.1002/jcu.22262Venturini M., Colantoni C., Modorati G., Di Nicola M., Colucci A., Agostini G., Picozzi P., De Cobelli F., Parmiani G., Mortini P., Bandello F., Del Maschio A. Preliminary results of contrast-enhanced sonography in the evaluation of the response of uveal melanoma to gamma-knife radiosurgery. J Clin Ultrasound. 2015 Sep;43(7):421–430. DOI: 10.1002/jcu.22262Ветшева Н.Н., Фисенко Е.П., Степанова Ю.А., Камалов Ю.Р., Тимина И.Е., Киселева Т.Н., Жестовская С.И. Ультразвуковое исследование с контрастным усилением: терминология, технические и методологические аспекты. Медицинская визуализация. 2016;(4):132–140.Vetsheva N.N., Fisenko E.P., Stepanova Y.A., Kamalov J.R., Timina I.E., Kiseleva T.N., Zhestovskaya S.I. Contrast Enhanced Ultrasound: Terminology, Technical and Methodological Aspects. Medical Visualization = Medicinskaya vizualizaciya. 2016;(4):132–140 (In Russ.).Gao M., Tang J., Liu K., Yang M., Liu H. Quantitative Evaluation of Vascular Microcirculation Using Contrast-Enhanced Ultrasound Imaging In Rabbit Models of Choroidal Melanoma. Invest Ophthalmol Vis Sci. 2018 Mar 1;59(3):1251–1262. DOI: 10.1167/iovs.17-22197Gao M., Tang J., Liu K., Yang M., Liu H. Quantitative Evaluation of Vascular Microcirculation Using Contrast-Enhanced Ultrasound Imaging In Rabbit Models of Choroidal Melanoma. Invest Ophthalmol Vis Sci. 2018 Mar 1;59(3):1251–1262. DOI: 10.1167/iovs.17-22197Kang S.J., Zhang Q., Patel S.R., Berezovsky D., Yang H., Wang Y., Grossniklaus H.E. In vivo high-frequency contrast-enhanced ultrasonography of choroidal melanoma in rabbits: imaging features and histopathologic correlations. Br J Ophthalmol. 2013 Jul;97(7):929–933. DOI: 10.1136/bjophthalmol-2013-303343Kang S.J., Zhang Q., Patel S.R., Berezovsky D., Yang H., Wang Y., Grossniklaus H.E. In vivo high-frequency contrast-enhanced ultrasonography of choroidal melanoma in rabbits: imaging features and histopathologic correlations. Br J Ophthalmol. 2013 Jul;97(7):929–933. DOI: 10.1136/bjophthalmol-2013-303343Zhang Q., Yang H., Kang S.J., Wang Y., Wang G.D., Coulthard T., Grossniklaus H.E. In vivo high-frequency, contrast-enhanced ultrasonography of uveal melanoma in mice: imaging features and histopathologic correlations. Invest Ophthalmol Vis Sci. 2011 Apr 1;52(5):2662–2268. DOI: 10.1167/iovs.10-6794Zhang Q., Yang H., Kang S.J., Wang Y., Wang G.D., Coulthard T., Grossniklaus H.E. In vivo high-frequency, contrast-enhanced ultrasonography of uveal melanoma in mice: imaging features and histopathologic correlations. Invest Ophthalmol Vis Sci. 2011 Apr 1;52(5):2662–2268. DOI: 10.1167/iovs.10-6794Sonoda S., Tachibana K., Yamashita T., Shirasawa M., Terasaki H., Uchino E., Suzuki R., Maruyama K. and Sakamoto T. Selective gene transfer to the retina using intravitreal ultrasound irradiation. J Ophthalmol. 2012:412752. DOI: 10.1155/2012/412752Sonoda S., Tachibana K., Yamashita T., Shirasawa M., Terasaki H., Uchino E., Suzuki R., Maruyama K. and Sakamoto T. Selective gene transfer to the retina using intravitreal ultrasound irradiation. J Ophthalmol. 2012:412752. DOI: 10.1155/2012/412752Xie W., Liu S., Su H., Wang Z., Zheng Y. and Fu Y. Ultrasound microbubbles enhance recombinant adeno associated virus vector delivery to retinal ganglion cells in vivo. Acad Radiol. 2010;17:1242–1248. DOI: 10.1016/j.acra.2010.05.008Xie W., Liu S., Su H., Wang Z., Zheng Y. and Fu Y. Ultrasound microbubbles enhance recombinant adeno associated virus vector delivery to retinal ganglion cells in vivo. Acad Radiol. 2010;17:1242–1248. DOI: 10.1016/j.acra.2010.05.008Li H., Wan C., Li F. Recombinant adeno-associated virus-, polyethylenimine/plasmidand lipofectamine/carboxyfluorescein-labeled small interfering RNA-based transfection in retinal pigment epithelial cells with ultrasound and/or SonoVue. Mol. Med. Rep. 11 (5) (2015) 3609–3614. DOI: 10.3892/mmr.2015.3219Li H., Wan C., Li F. Recombinant adeno-associated virus-, polyethylenimine/plasmidand lipofectamine/carboxyfluorescein-labeled small interfering RNA-based transfection in retinal pigment epithelial cells with ultrasound and/or SonoVue. Mol. Med. Rep. 11 (5) (2015) 3609–3614. DOI: 10.3892/mmr.2015.3219

The authors declare that there are no conflicts of interest present.