title: Frequency Dependence of Petechial Hemorrhage and Cardiomyocyte Injury Induced during Myocardial Contrast Echocardiography.
abstract: Myocardial contrast echocardiography (MCE) for perfusion imaging can induce microscale bio-effects during intermittent high-Mechanical Index scans. The dependence of MCE-induced bio-effects on the ultrasonic frequency was examined in rats at 1.6, 2.5 and 3.5 MHz. Premature complexes were counted in the electrocardiogram, petechial hemorrhages with microvascular leakage on the heart surface were observed at the time of exposure, plasma troponin elevation was measured after 4 h and cardiomyocyte injury was detected at 24 h. Increasing response to exposure above an apparent threshold was observed for all endpoints at each frequency. The effects decreased with increasing ultrasonic frequency, and the thresholds increased. Linear regressions for frequency-dependent thresholds indicated coefficients and exponents of 0.6 and 1.07 for petechial hemorrhages, respectively, and 1.02 and 0.8 for cardiomyocyte death, compared with 1.9 and 0.5 (square root) for the guideline limit of the mechanical index. The results clarify the dependence of cardiac bio-effects on frequency, and should allow development of theoretical descriptions of the phenomena and improved safety guidance for MCE.
authors.affiliation: Department of Radiology, University of Michigan Health System, Ann Arbor, Michigan, USA. Electronic address: douglm@umich.edu.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Miller
authors.affiliation: Department of Radiology, University of Michigan Health System, Ann Arbor, Michigan, USA.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Radiology, University of Michigan Health System, Ann Arbor, Michigan, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Fabiilli
authors.affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor, Michigan, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Fields
authors.affiliation: Department of Radiology, University of Michigan Health System, Ann Arbor, Michigan, USA.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Dou
mesh_terms: D000818:Animals; D016923:Cell Death; D003287:Contrast Media; D004195:Disease Models, Animal; D004452:Echocardiography / Q000009:adverse effects*; D006470:Hemorrhage / Q000209:etiology*; D008297:Male; D032383:Myocytes, Cardiac / Q000473:pathology*; D011693:Purpura / Q000209:etiology; D051381:Rats; D054772:Rats, Hairless; D014336:Troponin / Q000097:blood
chemical_list: D003287:Contrast Media; D014336:Troponin
keywords: Cardiomyocyte injury; Diagnostic ultrasound adverse effects; Myocardial contrast echocardiography; Ultrasonic cavitation biology