Hepatocyte Injury Induced by Contrast‐Enhanced Diagnostic Ultrasound

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149493/1/jum14883_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149493/2/jum14883.pd

Do Anesthetic Techniques Influence the Threshold for Glomerular Capillary Hemorrhage Induced in Rats by Contrast‐Enhanced Diagnostic Ultrasound?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135638/1/jum2016352373.pd

Effects of Emulsion Composition on Pulmonary Tobramycin Delivery During Antibacterial Perfluorocarbon Ventilation

Background: The effectiveness of inhaled aerosolized antibiotics is limited by poor ventilation of infected airways. Pulmonary delivery of antibiotics emulsified within liquid perfluorocarbon [antibacterial perfluorocarbon ventilation (APV)] may solve this problem through better airway penetration and improved spatial uniformity. However, little work has been done to explore emulsion formulation and the corresponding effects on drug delivery during APV. This study investigated the effects of emulsion formulation on emulsion stability and the pharmacokinetics of antibiotic delivery via APV. Methods: Gravity-driven phase separation was examined in vitro by measuring emulsion tobramycin concentrations at varying heights within a column of emulsion over 4 hours for varying values of fluorosurfactant concentration (Cfs?=?5?48?mg/mL H2O). Serum and pulmonary tobramycin concentrations in rats were then evaluated following pulmonary tobramycin delivery via aerosol or APV utilizing sufficiently stable emulsions of varying aqueous volume percentage (Vaq?=?1%?5%), aqueous tobramycin concentration (Ct?=?20?100?mg/mL), and Cfs (15 and 48?mg/mL H2O). Results: In vitro assessment showed sufficient spatial and temporal uniformity of tobramycin dispersion within emulsion for Cfs?≥15?mg/mL H2O, while lower Cfs values showed insufficient emulsification even immediately following preparation. APV with stable emulsion formulations resulted in 5?22 times greater pulmonary tobramycin concentrations at 4 hours post-delivery relative to aerosolized delivery. Concentrations increased with emulsion formulations utilizing increased Vaq (with decreased Ct) and, to a lesser extent, increased Cfs. Conclusions: The emulsion stability necessary for effective delivery is retained at Cfs values as low as 15?mg/mL H2O. Additionally, the pulmonary retention of antibiotic delivered via APV is significantly greater than that of aerosolized delivery and can be most effectively increased by increasing Vaq and decreasing Ct. APV has been further proven as an effective means of pulmonary drug delivery with the potential to significantly improve antibiotic therapy for lung disease patients.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140106/1/jamp.2015.1235.pd

Assessment of the biodistribution of an [ 18 F]FDG‐loaded perfluorocarbon double emulsion using dynamic micro‐PET in rats

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97497/1/cmmi1532.pd

Characterization of a Reverse-Phase Perfluorocarbon Emulsion for the Pulmonary Delivery of Tobramycin

Background: Aerosolized delivery of antibiotics is hindered by poor penetration within distal and plugged airways. Antibacterial perfluorocarbon ventilation (APV) is a proposed solution in which the lungs are partially or totally filled with perfluorocarbon (PFC) containing emulsified antibiotics. The purpose of this study was to evaluate emulsion stability and rheological, antibacterial, and pharmacokinetic characteristics. Methods: This study examined emulsion aqueous droplet diameter and number density over 24?hr and emulsion and neat PFC viscosity and surface tension. Additionally, Pseudomonas aeruginosa biofilm growth was measured after 2-hr exposure to emulsion with variable aqueous volume percentages (0.25, 1, and 2.5%) and aqueous tobramycin concentrations (Ca=0.4, 4, and 40?mg/mL). Lastly, the time course of serum and pulmonary tobramycin concentrations was evaluated following APV and conventional aerosolized delivery of tobramycin in rats. Results: The initial aqueous droplet diameter averaged 1.9±0.2??m with little change over time. Initial aqueous droplet number density averaged 3.5±1.7?109 droplets/mL with a significant (p<0.01) decrease over time. Emulsion and PFC viscosity were not significantly different, averaging 1.22±0.03?10?3 Pa·sec. The surface tensions of PFC and emulsion were 15.0±0.1?10?3 and 14.6±0.6?10?3 N/m, respectively, and the aqueous interfacial tensions were 46.7±0.3?10?3 and 26.9±11.0?10?3 N/m (p<0.01), respectively. Biofilm growth decreased markedly with increasing Ca and, to a lesser extent, aqueous volume percentage. Tobramycin delivered via APV yielded 2.5 and 10 times larger pulmonary concentrations at 1 and 4?hr post delivery, respectively, and significantly (p<0.05) lower serum concentrations compared with aerosolized delivery. Conclusions: The emulsion is bactericidal, retains the rheology necessary for pulmonary delivery, is sufficiently stable for this application, and results in increased pulmonary retention of the antibiotic.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140105/1/jamp.2013.1058.pd

In Situ Transfection by Controlled Release of Lipoplexes Using Acoustic Droplet Vaporization

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/133565/1/adhm201600008_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/133565/2/adhm201600008.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/133565/3/adhm201600008-sup-0001-S1.pd

Multiple ultrasound cavitation-enabled treatments for myocardial reduction

Abstract Background Ultrasound myocardial cavitation enabled treatment (MCET) is an image-guided method for tissue reduction. In this study, a strategy of fractionated (multiple) treatments was tested for efficacy. Methods Dahl SS rats were anesthetized and prepared for treatment with a focused ultrasound transducer in a warm water bath. Aiming at the anterior left ventricular wall was facilitated by imaging with a 10 MHz phased array (10S, GE Vivid 7, GE Vingmed Ultrasound, Horten, Norway). MCET was accomplished at 1.5 MHz by pulse bursts of 4 MPa peak rarefactional pressure amplitude, which were intermittently triggered 1:8 from the ECG during infusion of a microbubble suspension for cavitation nucleation. Test groups were sham, a 200 s treatment, three 200 s treatments a week apart, and a 600 s treatment. Treatment outcome was observed by plasma troponin after 4 h, echocardiographic monitoring and histology at 6 wk. Results The impacts of the fractionated treatments summed to approximately the same as the long treatment; e. g. the troponin result was 10.5 ± 3.2 for 200 s, 22.7 ± 5.4 (p < 0.001) for the summed fractionated treatments and 29.9 ± 6.4 for 600 s (p = 0.06 relative to the summed fractionated). While wall thickness was not reduced for the fractionated treatment, tissue strain was reduced by 35% in the target area relative sham (p < 0.001). Conclusion The ability to fractionate treatment may be advantageous for optimizing patient outcome relative to all-or nothing therapy by surgical myectomy or alcohol ablation.https://deepblue.lib.umich.edu/bitstream/2027.42/139057/1/40349_2017_Article_107.pd

Ultra-high-speed dynamics of acoustic droplet vaporization in soft biomaterials: Effects of viscoelasticity, frequency, and bulk boiling point

Phase-shift droplets are a highly adaptable platform for biomedical applications of ultrasound. The spatiotemporal response of phase-shift droplets to focused ultrasound above a certain pressure threshold, termed acoustic droplet vaporization (ADV), is influenced by intrinsic features (e.g., bulk boiling point) and extrinsic factors (e.g., driving frequency and surrounding media). A deep understanding of ADV dynamics is critical to ensure the robustness and repeatability of an ADV-assisted application. Here, we integrated ultra-high-speed imaging, at 10 million frames per second, and confocal microscopy for a full-scale (i.e., from nanoseconds to seconds) characterization of ADV. Experiments were conducted in fibrin-based hydrogels to mimic soft tissue environments. Effects of fibrin concentration (0.2 to 8 % (w/v)), excitation frequency (1, 2.5, and 9.4 MHz), and perfluorocarbon core (perfluoropentane, perfluorohexane, and perfluorooctane) on ADV dynamics were studied. Several fundamental parameters related to ADV dynamics, such as expansion ratio, expansion velocity, collapse radius, collapse time, radius of secondary rebound, resting radius, and equilibrium radius of the generated bubbles were extracted from the radius vs time curves. Diffusion-driven ADV-bubble growth was fit to a modified Epstein-Plesset equation, adding a material stress term, to estimate the growth rate. Our results indicated that ADV dynamics were significantly impacted by fibrin concentration, frequency, and perfluorocarbon liquid core. This is the first study to combine ultra-high-speed and confocal microscopy techniques to provide insights into ADV bubble dynamics in tissue-mimicking hydrogels