Effect of High-Intensity Ultrasound–Targeted Microbubble Destruction on Perfusion and Function of the Rat Heart Assessed by Pinhole-Gated SPECT

• Published in: Ultrasound in medicine & biology Vol. 36; no. 1; pp. 158 - 165
• Main Authors: Hernot, Sophie, Cosyns, Bernard, Droogmans, Steven, Garbar, Christian, Couck, Pedro, Vanhove, Christian, Caveliers, Vicky, Van Camp, Guy, Bossuyt, Axel, Lahoutte, Tony
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 2010
• Subjects: Animals; Bioeffects; Biomarkers - metabolism; Blood Volume; Echocardiography; Heart - diagnostic imaging; Heart - physiopathology; Male; Microbubble; Microbubbles; Pinhole-gated SPECT; Radiology; Rats; Rats, Wistar; Regional Blood Flow; Technetium Tc 99m Sestamibi; Tomography, Emission-Computed, Single-Photon - methods; Troponin; Troponin - metabolism; Ultrasonic Therapy - adverse effects; Ultrasound-targeted microbubble destruction; Ventricular Dysfunction, Left - diagnostic imaging; Ventricular Dysfunction, Left - metabolism; Ventricular Dysfunction, Left - pathology; Bioeffects; Troponin; Microbubble; Ultrasound-targeted microbubble destruction; Pinhole-gated SPECT
• ISSN: 0301-5629; 1879-291X
• DOI: 10.1016/j.ultrasmedbio.2009.08.011

Abstract Although ultrasound-targeted microbubble destruction (UTMD) has been shown to induce bioeffects, UTMD is still desirable for therapeutic applications. Therefore, we studied the effects of UTMD on perfusion and function of the rat heart, assessed by99m Tc-MIBI pinhole-gated SPECT (Ph-gSPECT) compared with biomarker release and histopathology. Fifty-two male Wistar rats were studied. UTMD was performed using SonoVue, with a mechanical index of 1.0 or 1.6. Controls were treated without microbubbles or without ultrasound application. At baseline, day 1, day 7 and day 30, 35 rats were imaged with99m Tc-MIBI Ph-gSPECT to quantify left ventricular perfusion and function. In addition, troponin release and histopathology were investigated. No significant differences were observed for left ventricular ejection fractions, end-systolic and end-diastolic volumes, regional perfusion and functional scores up to 30 days after UTMD compared with controls. UTMD induced mild troponin release and early erythrocyte extravasation without necrosis, inflammation or fibrosis. Although UTMD has the potential to induce microlesions of the heart in small animals, these effects were transient without histological evidence of irreversible damage. Furthermore, UTMD does not induce abnormalities on perfusion or function of the heart, as assessed by Ph-gSPECT, which is reassuring concerning the use of SonoVue for potential therapeutic applications. (E-mail: sophie.hernot@gmail.com )