Hybrid Completion of Aortic Repair after Type A Aortic Dissection in a Patient with Marfan's Syndrome.

Medicine and engineering are in collaboration to assist in the tackling of daunting surgical techniques which are associated with high rates of morbidity and mortality, in exchange for minimally invasive approaches with lower procedural risk. Endovascular procedures in general have already reduced the risk of surgery by limiting the extent of open surgery and often replacing it with purely percutaneous or hybrid procedures. Here, we describe a patient who had complex staged surgery with open repair of a proximal portion of a type A aortic dissection followed by a staged endovascular reconstruction of the arch and descending aorta by means of a fenestrated stent-graft to secure the left subclavian artery and the posterior cerebral circulation.

A Targeting Microbubble for Ultrasound Molecular Imaging.

RATIONALE: Microbubbles conjugated with targeting ligands are used as contrast agents for ultrasound molecular imaging. However, they often contain immunogenic (strept)avidin, which impedes application in humans. Although targeting bubbles not employing the biotin-(strept)avidin conjugation chemistry have been explored, only a few reached the stage of ultrasound imaging in vivo, none were reported/evaluated to show all three of the following properties desired for clinical applications: (i) low degree of non-specific bubble retention in more than one non-reticuloendothelial tissue; (ii) effective for real-time imaging; and (iii) effective for acoustic quantification of molecular targets to a high degree of quantification. Furthermore, disclosures of the compositions and methodologies enabling reproduction of the bubbles are often withheld. OBJECTIVE: To develop and evaluate a targeting microbubble based on maleimide-thiol conjugation chemistry for ultrasound molecular imaging. METHODS AND RESULTS: Microbubbles with a previously unreported generic (non-targeting components) composition were grafted with anti-E-selectin F(ab')2 using maleimide-thiol conjugation, to produce E-selectin targeting microbubbles. The resulting targeting bubbles showed high specificity to E-selectin in vitro and in vivo. Non-specific bubble retention was minimal in at least three non-reticuloendothelial tissues with inflammation (mouse heart, kidneys, cremaster). The bubbles were effective for real-time ultrasound imaging of E-selectin expression in the inflamed mouse heart and kidneys, using a clinical ultrasound scanner. The acoustic signal intensity of the targeted bubbles retained in the heart correlated strongly with the level of E-selectin expression (|r|≥0.8), demonstrating a high degree of non-invasive molecular quantification. CONCLUSIONS: Targeting microbubbles for ultrasound molecular imaging, based on maleimide-thiol conjugation chemistry and the generic composition described, may possess properties (i)-(iii) desired for clinical applications.

Quantitative ultrasound molecular imaging.

Ultrasound molecular imaging using targeting microbubbles is predominantly a semi-quantitative tool, thus limiting its potential diagnostic power and clinical applications. In the work described here, we developed a novel method for acoustic quantification of molecular expression. E-Selectin expression in the mouse heart was induced by lipopolysaccharide. Real-time ultrasound imaging of E-selectin expression in the heart was performed using E-selectin-targeting microbubbles and a clinical ultrasound scanner in contrast pulse sequencing mode at 14 MHz, with a mechanical index of 0.22-0.26. The level of E-selectin expression was quantified using a novel time-signal intensity curve analytical method based on bubble elimination, which consisted of curve-fitting the bi-exponential equation [Formula: see text] to the elimination phase of the myocardial time-signal intensity curve. Ar and Af represent the maximum signal intensities of the retained and freely circulating bubbles in the myocardium, respectively; λr and λf represent the elimination rate constants of the retained and freely circulating bubbles in the myocardium, respectively. Ar correlated strongly with the level of E-selectin expression (|r|>0.8), determined using reverse transcriptase real-time quantitative polymerase chain reaction, and the duration of post-lipopolysaccharide treatment-both linearly related to cell surface E-selectin protein (actual bubble target) concentration in the expression range imaged. Compared with a conventional acoustic quantification method (which used retained bubble signal intensity at 20 min post-bubble injection), this new approach exhibited greater dynamic range and sensitivity and was able to simultaneously quantify other useful characteristics (e.g., the microbubble half-life). In conclusion, quantitative determination of the level of molecular expression is feasible acoustically using a time-signal intensity curve analytical method based on bubble elimination.