title: Acoustic characterization of echogenic liposomes: frequency-dependent attenuation and backscatter.
abstract: Ultrasound contrast agents (UCAs) are used clinically to aid detection and diagnosis of abnormal blood flow or perfusion. Characterization of UCAs can aid in the optimization of ultrasound parameters for enhanced image contrast. In this study echogenic liposomes (ELIPs) were characterized acoustically by measuring the frequency-dependent attenuation and backscatter coefficients at frequencies between 3 and 30 MHz using a broadband pulse-echo technique. The experimental methods were initially validated by comparing the attenuation and backscatter coefficients measured from 50-μm and 100-μm polystyrene microspheres with theoretical values. The size distribution of the ELIPs was measured and found to be polydisperse, ranging in size from 40 nm to 6 μm in diameter, with the highest number observed at 65 nm. The ELIP attenuation coefficients ranged from 3.7  ±  1.0 to 8.0  ±  3.3 dB/cm between 3 and 25 MHz. The backscatter coefficients were 0.011  ±  0.006 (cm str)(-1) between 6 and 9 MHz and 0.023 ± 0.006 (cm str)(-1) between 13 and 30 MHz. The measured scattering-to-attenuation ratio ranged from 8% to 22% between 6 and 25 MHz. Thus ELIPs can provide enhanced contrast over a broad range of frequencies and the scattering properties are suitable for various ultrasound imaging applications including diagnostic and intravascular ultrasound.
authors.affiliation: Department of Biomedical Engineering, University of Cincinnati, 2901 Campus Drive, Cincinnati, Ohio 45221, USA. jonathan.kopechek@gmail.com
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Kopechek
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Haworth
authors.forename: Jason L
authors.initials: JL
authors.lastname: Raymond
authors.forename: T
authors.initials: T
authors.lastname: Douglas Mast
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Perrin
authors.forename: Melvin E
authors.initials: ME
authors.lastname: Klegerman
authors.forename: Shaoling
authors.initials: S
authors.lastname: Huang
authors.forename: Tyrone M
authors.initials: TM
authors.lastname: Porter
authors.forename: David D
authors.initials: DD
authors.lastname: McPherson
authors.forename: Christy K
authors.initials: CK
authors.lastname: Holland
mesh_terms: D003287:Contrast Media; D004548:Elasticity; D008081:Liposomes; D008863:Microspheres; D008962:Models, Theoretical; D010316:Particle Size; D011137:Polystyrenes; D011312:Pressure; D015203:Reproducibility of Results; D012542:Scattering, Radiation; D012815:Signal Processing, Computer-Assisted; D014160:Transducers, Pressure; D014465:Ultrasonics / Q000295:instrumentation; D018084:Ultrasonography, Interventional
chemical_list: D003287:Contrast Media; D008081:Liposomes; D011137:Polystyrenes
references.citation: J Acoust Soc Am. 2005 Jul;118(1):539-50
references.pmid: 16119373
references.citation: J Am Coll Cardiol. 2009 Aug 11;54(7):652-9
references.pmid: 19660697
references.citation: Radiology. 1992 Nov;185(2):453-6
references.pmid: 1410353
references.citation: IEEE Trans Ultrason Ferroelectr Freq Control. 2001 Jan;48(1):232-48
references.pmid: 11367791
references.citation: Ultrasound Med Biol. 2004 Feb;30(2):181-90
references.pmid: 14998670
references.citation: J Acoust Soc Am. 1998 Jun;103(6):3169-79
references.pmid: 9637027
references.citation: Biochim Biophys Acta. 2004 Oct 11;1665(1-2):134-41
references.pmid: 15471579
references.citation: Ultrasound Med Biol. 2002 Mar;28(3):277-86
references.pmid: 11978407
references.citation: J Pharm Sci. 1996 May;85(5):486-90
references.pmid: 8742939
references.citation: J Acoust Soc Am. 2000 Apr;107(4):2272-80
references.pmid: 10790053
references.citation: Ultrasound Med Biol. 2005 Mar;31(3):391-9
references.pmid: 15749563
references.citation: Ultrasonics. 1993;31(3):175-81
references.pmid: 8484195
references.citation: Circulation. 2002 Jun 11;105(23):2772-8
references.pmid: 12057993
references.citation: J Mol Biol. 1965 Aug;13(1):238-52
references.pmid: 5859039
references.citation: Am J Cardiol. 1998 Jun 18;81(12A):58G-61G
references.pmid: 9662229
references.citation: Acta Biomater. 2010 Sep;6(9):3542-9
references.pmid: 20226284
references.citation: Eur Radiol. 2004 Oct;14 Suppl 8:P11-5
references.pmid: 15700328
references.citation: Ultrasound Med Biol. 2008 Aug;34(8):1272-80
references.pmid: 18407399
references.citation: Ultrasound Med Biol. 2002 Mar;28(3):339-48
references.pmid: 11978414
references.citation: Ultrasound Med Biol. 2006 Aug;32(8):1257-67
references.pmid: 16875959
references.citation: Ultrasound Med Biol. 1999 Oct;25(8):1321-4
references.pmid: 10576274
references.citation: J Ultrasound Med. 2008 Nov;27(11):1597-606
references.pmid: 18946099
references.citation: J Acoust Soc Am. 2010 Feb;127(2):1156-64
references.pmid: 20136236
references.citation: Med Biol Eng Comput. 2009 Aug;47(8):861-73
references.pmid: 19468770
references.citation: Biochim Biophys Acta. 2005 Dec 30;1720(1-2):22-7
references.pmid: 16375851
references.citation: Ultrasound Med Biol. 1998 Mar;24(3):469-72
references.pmid: 9588001
references.citation: Ultrasound Med Biol. 2000 Jul;26(6):1009-19
references.pmid: 10996701
references.citation: Gene Ther. 2005 Sep;12(17):1305-12
references.pmid: 15829992
references.citation: Ultrasound Med Biol. 2007 May;33(5):797-809
references.pmid: 17412486
references.citation: Ultrasound Med Biol. 2008 Sep;34(9):1421-33
references.pmid: 18378380
references.citation: Circulation. 2010 Oct 19;122(16):1578-87
references.pmid: 20921443
references.citation: J Control Release. 2003 Jan 17;86(2-3):235-42
references.pmid: 12526820
references.citation: Ultrasound Med Biol. 1998 May;24(4):523-33
references.pmid: 9651962
references.citation: J Pharm Sci. 2008 Jun;97(6):2242-9
references.pmid: 17894368
references.citation: Proc Natl Acad Sci U S A. 1990 Apr;87(7):2448-51
references.pmid: 2157200
references.citation: J Exp Biol. 2006 Mar;209(Pt 5):801-9
references.pmid: 16481569
references.citation: Thromb Res. 2009 Jul;124(3):306-10
references.pmid: 19217651
references.citation: Int J Cardiovasc Intervent. 2005;7(2):75-87
references.pmid: 16093216
references.citation: Proc IEEE Int Symp Biomed Imaging. 2009 Jun 28;2009:755-758
references.pmid: 20383294
references.citation: J Control Release. 2005 Oct 3;107(2):253-61
references.pmid: 16046023
references.citation: Phys Med Biol. 2006 Feb 21;51(4):793-807
references.pmid: 16467579
references.citation: Ultrasound Med Biol. 2007 Sep;33(9):1376-88
references.pmid: 17521801
references.citation: J Am Soc Echocardiogr. 2000 Jun;13(6):608-14
references.pmid: 10849515
references.citation: Circulation. 1996 Dec 15;94(12):3334-40
references.pmid: 8989148
references.citation: IEEE Trans Ultrason Ferroelectr Freq Control. 1997;44(2):515-25
references.pmid: 18244149
references.citation: J Acoust Soc Am. 2004 Nov;116(5):2832-42
references.pmid: 15603131
references.citation: Circulation. 2008 Jul 15;118(3):291-308
references.pmid: 18625905
references.citation: Biophys J. 2008 Apr 1;94(7):L51-3
references.pmid: 18212008
references.citation: J Control Release. 2010 Jun 15;144(3):288-95
references.pmid: 20202474
references.citation: Ultrasound Med Biol. 2010 Jan;36(1):145-57
references.pmid: 19900755
references.citation: J Am Coll Cardiol. 2004 Feb 4;43(3):453-60
references.pmid: 15013130
references.citation: Stroke. 2010 Oct;41(10 Suppl):S50-3
references.pmid: 20876505
references.citation: Adv Drug Deliv Rev. 2008 Jun 30;60(10):1167-76
references.pmid: 18479776
references.citation: J Liposome Res. 2008;18(2):95-112
references.pmid: 18569446
references.citation: J Control Release. 2010 Mar 19;142(3):326-31
references.pmid: 19903503
references.citation: J Pharm Sci. 2001 Dec;90(12):1917-26
references.pmid: 11745750
references.citation: J Am Coll Cardiol. 1999 Mar;33(3):867-75
references.pmid: 10080492