title: Influence of temperature, needle gauge and injection rate on the size distribution, concentration and acoustic responses of ultrasound contrast agents at high frequency.
abstract: This paper investigated the influence of needle gauge (19G and 27G), injection rate (0.85ml·min(-1), 3ml·min(-1)) and temperature (room temperature (RT) and body temperature (BT)) on the mean diameter, concentration, acoustic attenuation, contrast to tissue ratio (CTR) and normalised subharmonic intensity (NSI) of three ultrasound contrast agents (UCAs): Definity, SonoVue and MicroMarker (untargeted). A broadband substitution technique was used to acquire the acoustic properties over the frequency range 17-31MHz with a preclinical ultrasound scanner Vevo770 (Visualsonics, Canada). Significant differences (P<0.001-P<0.05) between typical in vitro setting (19G needle, 3ml·min(-1) at RT) and typical in vivo setting (27G needle, 0.85ml·min(-1) at BT) were found for SonoVue and MicroMarker. Moreover we found that the mean volume-based diameter and concentration of both SonoVue and Definity reduced significantly when changing from typical in vitro to in vivo experimental set-ups, while those for MicroMarker did not significantly change. From our limited measurements of Definity, we found no significant change in attenuation, CTR and NSI with needle gauge. For SonoVue, all the measured acoustic properties (attenuation, CTR and NSI) reduced significantly when changing from typical in vitro to in vivo experimental conditions, while for MicroMarker, only the NSI reduced, with attenuation and CTR increasing significantly. These differences suggest that changes in physical compression and temperature are likely to alter the shell structure of the UCAs resulting in measureable and significant changes in the physical and high frequency acoustical properties of the contrast agents under typical in vitro and preclinical in vivo experimental conditions.
authors.affiliation: Medical Physics, Centre for Cardiovascular Research, University of Edinburgh, Edinburgh, UK; Ultrasound Department, Xijing Hospital, Xi'an, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.affiliation: Medical Physics, Centre for Cardiovascular Research, University of Edinburgh, Edinburgh, UK.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Panagakou
authors.affiliation: Medical Physics, Centre for Cardiovascular Research, University of Edinburgh, Edinburgh, UK; Institute of Biochemistry, Biophysics and Bioengineering, Heriot-Watt University, Edinburgh, UK.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Sboros
authors.affiliation: Medical Physics, Centre for Cardiovascular Research, University of Edinburgh, Edinburgh, UK; Institute of Biochemistry, Biophysics and Bioengineering, Heriot-Watt University, Edinburgh, UK.
authors.forename: Mairead B
authors.initials: MB
authors.lastname: Butler
authors.affiliation: Medical Physics, Centre for Cardiovascular Research, University of Edinburgh, Edinburgh, UK.
authors.forename: David
authors.initials: D
authors.lastname: Kenwright
authors.affiliation: Medical Physics, Centre for Cardiovascular Research, University of Edinburgh, Edinburgh, UK.
authors.forename: Adrian J W
authors.initials: AJ
authors.lastname: Thomson
authors.affiliation: Medical Physics, Centre for Cardiovascular Research, University of Edinburgh, Edinburgh, UK. Electronic address: carmel.moran@ed.ac.uk.
authors.forename: Carmel M
authors.initials: CM
authors.lastname: Moran
mesh_terms: D003287:Contrast Media / Q000008:administration & dosage* / Q000737:chemistry* / Q000528:radiation effects; D004867:Equipment Design; D019544:Equipment Failure Analysis; D007267:Injections / Q000295:instrumentation*; D008422:Materials Testing; D009339:Needles; D010316:Particle Size; D015203:Reproducibility of Results; D012542:Scattering, Radiation; D012680:Sensitivity and Specificity; D013696:Temperature; D000069453:Ultrasonic Waves; D014463:Ultrasonography / Q000295:instrumentation / Q000379:methods*
chemical_list: D003287:Contrast Media
keywords: Acoustic characterisation; High frequency ultrasound; Injection rate; Microbubble; Needle gauge; Temperature