TY - JOUR
T1 - Temperature dependence of ultrasonic enhancement with a site-targeted contrast agent
AU - Hall, Christopher S.
AU - Marsh, Jon N.
AU - Scott, Michael J.
AU - Gaffney, Patrick J.
AU - Wickline, Samuel A.
AU - Lanza, Gregory M.
PY - 2001
Y1 - 2001
N2 - Molecular imaging contrast agents specifically detect the biochemical "signatures" of disease before anatomical manifestations are apparent. Sensitive and specific localization of fibrin both in vivo and in vitro has been demonstrated with the use of a ligand-directed liquid perfluorocarbon nanoparticle. Since the acoustic properties of perfluorocarbons are known to vary with temperature, it was hypothesized that temperature could be used to augment the magnitude of enhancement imparted by targeted nanoparticles. Accordingly, the acoustic backscatter of two different substrates, nitrocellulose membrane and human plasma clot, targeted by the nanoparticles was measured at temperatures ranging from 27° to 47°C in 5°C increments. Classic avidin-biotin interactions were utilized to couple biotinylated nanoparticles to avidin-conjugated nitrocellulose membranes. Ultrasonic contrast enhancement of the nitrocellulose membrane at 25 MHz, measured by acoustic microscopy, increased from 2.0±0.3 dB at 27°C to 3.7±0.4 at 47°C. In a similar experiment, antifibrin nanoparticles bound to human plasma clots also exhibited temperature-dependent ultrasonic signal enhancement ranging from 13.9±1.5 dB at 27°C to 18.1±1.5 dB at 47°C. The increase in ultrasonic contrast enhancement measured was well described by a simple, acoustic transmission line model with temperature-dependent impedance. These results suggest that temperature-dependent changes in acoustic backscatter may be used to further differentiate tissues targeted with site-specific nanoparticles from surrounding normal soft tissues.
AB - Molecular imaging contrast agents specifically detect the biochemical "signatures" of disease before anatomical manifestations are apparent. Sensitive and specific localization of fibrin both in vivo and in vitro has been demonstrated with the use of a ligand-directed liquid perfluorocarbon nanoparticle. Since the acoustic properties of perfluorocarbons are known to vary with temperature, it was hypothesized that temperature could be used to augment the magnitude of enhancement imparted by targeted nanoparticles. Accordingly, the acoustic backscatter of two different substrates, nitrocellulose membrane and human plasma clot, targeted by the nanoparticles was measured at temperatures ranging from 27° to 47°C in 5°C increments. Classic avidin-biotin interactions were utilized to couple biotinylated nanoparticles to avidin-conjugated nitrocellulose membranes. Ultrasonic contrast enhancement of the nitrocellulose membrane at 25 MHz, measured by acoustic microscopy, increased from 2.0±0.3 dB at 27°C to 3.7±0.4 at 47°C. In a similar experiment, antifibrin nanoparticles bound to human plasma clots also exhibited temperature-dependent ultrasonic signal enhancement ranging from 13.9±1.5 dB at 27°C to 18.1±1.5 dB at 47°C. The increase in ultrasonic contrast enhancement measured was well described by a simple, acoustic transmission line model with temperature-dependent impedance. These results suggest that temperature-dependent changes in acoustic backscatter may be used to further differentiate tissues targeted with site-specific nanoparticles from surrounding normal soft tissues.
UR - http://www.scopus.com/inward/record.url?scp=0034838890&partnerID=8YFLogxK
U2 - 10.1121/1.1395584
DO - 10.1121/1.1395584
M3 - Article
C2 - 11572376
AN - SCOPUS:0034838890
SN - 0001-4966
VL - 110
SP - 1677
EP - 1684
JO - Journal of the Acoustical Society of America
JF - Journal of the Acoustical Society of America
IS - 3 I
ER -