title: Effect of shell type on the in vivo backscatter from polymer-encapsulated microbubbles.
abstract: This study compared in vivo enhancement from four different polymer-encapsulated ultrasound (US) contrast agents. The agents were produced with a rigid shell composed of the biodegradable block copolymer poly[D,L-lactide-co-glycolide] (PLGA) with the lactic and glycolic acid ratios 50:50, 75:25, 85:15 and 100:0 (i.e., increasingly hydrophobic shell compositions). Approximately the same bubble diameter (1.2 microm) and concentration (0.4 g/mL) were obtained for each agent. In four rabbits, audio Doppler signals were acquired from a 10 MHz cuff transducer placed around a surgically exposed vessel (contrast dose: 0.0125 to 0.15 mL/kg). In vivo dose responses were calculated off-line (in dB). Nine rabbit kidneys were imaged during contrast administration (0.1 mL/kg) in power Doppler and grey-scale pulse inversion harmonic (PIHI) modes using an HDI 5000 scanner (Philips Medical Systems, Bothell, WA). Time-intensity curves were produced and the time-to-peak, peak intensity, slope, area under the curve (AUC) and total duration of enhancement for each agent were compared. All agents produced marked Doppler enhancement with increasing duration from the 50:50 agent (48 +/- 10 s) to the 75:25 agent (166 +/- 46 s), the 85:15 agent (403 +/- 83 s) and with the 100:0 agent (603 +/- 93 s) lasting longest (p < 0.02). No other parameters changed significantly, except the AUC of the 85:15 agent, which was greater than that of the 50:50 agent (190.75 vs. 61.58; p = 0.02). The in vivo dose-response curves were similar for all agents, with mean enhancement up to 20.6 +/- 1.11 dB (p = 0.17). In conclusion, contrast duration increases by an order of magnitude as the lactic acid component in the polymer-encapsulated bubbles increases and the shell, thus, becomes increasingly hydrophobic.
authors.affiliation: Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USA. flemming.forsberg@jefferson.edu
authors.forename: Flemming
authors.initials: F
authors.lastname: Forsberg
authors.forename: Justin D
authors.initials: JD
authors.lastname: Lathia
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Merton
authors.forename: Ji-Bin
authors.initials: JB
authors.lastname: Liu
authors.forename: Ngocyen T
authors.initials: NT
authors.lastname: Le
authors.forename: Barry B
authors.initials: BB
authors.lastname: Goldberg
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Wheatley
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D001673:Biodegradation, Environmental; D003287:Contrast Media / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding; D006016:Glycolates / Q000032:analysis; D007668:Kidney / Q000000981:diagnostic imaging*; D019344:Lactic Acid / Q000032:analysis; D045423:Microbubbles; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011817:Rabbits; D013997:Time Factors; D014463:Ultrasonography
chemical_list: D001672:Biocompatible Materials; D003287:Contrast Media; D006016:Glycolates; D011108:Polymers; C031149:glycolic acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid