TY - JOUR
T1 - DNA-coated microbubbles with biochemically tunable ultrasound contrast activity
AU - Nakatsuka, Matthew A.
AU - Hsu, Mark J.
AU - Esener, Sadik C.
AU - Cha, Jennifer N.
AU - Goodwin, Andrew P.
PY - 2011/11/9
Y1 - 2011/11/9
N2 - Imaging is a vital weapon in the clinician's arsenal with uses at almost every stage of patient care, including routine screening, diagnostic testing, disease staging, surgical assistance, and post-treatment monitoring. Of the many imaging modalities available, ultrasound is one of the most widely employed. The incident sound waves are safe, penetrate deeply into most tissues, and provide millimeter resolution imaging, while multiple tests may be performed relatively cheaply and in real-time with equipment already present in most hospitals and clinics. The main drawback of ultrasound is poor sensitivity to abnormalities in tissue; as most tissues have similar densities and compressibilities only a small fraction of the incident sound is reflected back to the transducer. [1] To address this, colloids and particles with large differences in acoustic impedance, such as microbubbles, [2] emulsions, [3] and air-containing liposomes, [4] have been employed successfully as ultrasound contrast agents owing to their inherent ability to scatter sound more effectively. Gas-filled microbubbles in particular are especially effective for cardiovascular imaging, with success in applications such as determining the presence of thrombosis [5] or malignant prostate carcinomas. [6] Recent advances have included the addition of targeting ligands to the contrast agent to enhance their accumulation in a specific area. [2b,3a,7] However, a contrast agent that activates only in the presence of specific biomarker would relay a positive (bright) signal instead of a void (dark), reducing background and allowing a clinician to distinguish a growing area of inflammation from an imaging artifact or acoustic shadowing. For example, microbubbles that become active only in the presence of thrombin, a biomarker for the clotting cascade, would allow imaging of small but growing clots that are difficult to image by standard methods for early detection of malignant thrombosis. [8].
AB - Imaging is a vital weapon in the clinician's arsenal with uses at almost every stage of patient care, including routine screening, diagnostic testing, disease staging, surgical assistance, and post-treatment monitoring. Of the many imaging modalities available, ultrasound is one of the most widely employed. The incident sound waves are safe, penetrate deeply into most tissues, and provide millimeter resolution imaging, while multiple tests may be performed relatively cheaply and in real-time with equipment already present in most hospitals and clinics. The main drawback of ultrasound is poor sensitivity to abnormalities in tissue; as most tissues have similar densities and compressibilities only a small fraction of the incident sound is reflected back to the transducer. [1] To address this, colloids and particles with large differences in acoustic impedance, such as microbubbles, [2] emulsions, [3] and air-containing liposomes, [4] have been employed successfully as ultrasound contrast agents owing to their inherent ability to scatter sound more effectively. Gas-filled microbubbles in particular are especially effective for cardiovascular imaging, with success in applications such as determining the presence of thrombosis [5] or malignant prostate carcinomas. [6] Recent advances have included the addition of targeting ligands to the contrast agent to enhance their accumulation in a specific area. [2b,3a,7] However, a contrast agent that activates only in the presence of specific biomarker would relay a positive (bright) signal instead of a void (dark), reducing background and allowing a clinician to distinguish a growing area of inflammation from an imaging artifact or acoustic shadowing. For example, microbubbles that become active only in the presence of thrombin, a biomarker for the clotting cascade, would allow imaging of small but growing clots that are difficult to image by standard methods for early detection of malignant thrombosis. [8].
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U2 - 10.1002/adma.201102677
DO - 10.1002/adma.201102677
M3 - Article
C2 - 21956383
AN - SCOPUS:82955246697
SN - 0935-9648
VL - 23
SP - 4908
EP - 4912
JO - Advanced Materials
JF - Advanced Materials
IS - 42
ER -