Official Proceedings - AIUM

American Institute of Ultrasound in Medicine Proceedings J Ultrasound Med 32(suppl):S1–S134, 2013SPECIAL INTEREST SESSIONSMONDAY, APRIL 8, 2013, 1:30 PM–3:30 PMCellular Bioeffects and ApplicationsModerator: Diane Dalecki, PhDApplications of Ultrasound Standing Wave Fields in Tissue EngineeringDiane Dalecki University of Rochester, Rochester, New YorkUSAThe field of tissue engineering aims to develop technologiesthat enable the repair or replacement of diseased or injured tissues and organs.The spatial organization of cells within native and engineered tissuesis essential for proper tissue assembly and organ function. Thus, successfulengineering of complex tissues and organs requires methods to controlcell organization in 3 dimensions. Acoustic radiation forces associatedwith ultrasound standing wave fields provide a rapid, noninvasive approachto spatially pattern cells in 3 dimensions without affecting cell viability.Results of several investigations will be presented that demonstratethe use of ultrasound standing wave fields to pattern cells or protein-boundmicroparticles in 3D hydrogels. Furthermore, patterning of endothelialcells with ultrasound standing wave fields leads to rapid and extensivevessel network formation in 3D collagen-based constructs. Thus, ultrasoundstanding wave fields provide new strategies to pattern cells and directvascular network formation and morphology within engineered tissueconstructs.Interactions of Microbubbles With Cells and Their Applications forDrug and Gene DeliveryCheri Deng University of Michigan, Ann Arbor, MichiganUSASonoporation uses ultrasound application to generate microbubbleactivities to transiently disrupt the cell membrane for enhancingintracellular transport of exogenous agents for drug and gene deliveryapplications. However, success of sonoporation is hindered by low deliveryefficiencies and variable outcomes. These difficulties are due to thelack of understanding of the detailed processes supporting ultrasound-inducedtransport into and within the cytoplasm of living cells. The dynamicmicrobubble activities driven by ultrasound application induce cellularbioeffects that can determine the delivery outcome, including delivery efficiencyand cell viability. In this presentation, we provide an examinationof these biophysical and biochemical effects resulting from interactionof ultrasound-driven microbubbles with cells and whether they play importantroles in the sonoporation outcome. We developed novel techniquesto control and investigate ultrasound-driven microbubble cavitation in referenceto single cells and the resulting membrane disruptions. We used simultaneouswhole-cell patch clamp recording and fluorescence microscopyto characterize the formation and resealing of ultrasound-induced membranepores. We demonstrated spatiotemporally controlled subcellular deliveryand calcium signaling in targeted cells. In addition, based on theultrasound-driven microbubble activities, we implemented an ultrasoundexposure strategy to improve gene transfection. These results may providerelevant information for further development of sonoporation.Directing Extracellular Matrix Protein Microstructure With UltrasoundDenise Hocking Pharmacology and Physiology, Universityof Rochester, Rochester, New York USAThe extracellular matrix is a complex network of interconnectedproteins and polysaccharides that provides structure to tissues and instructscell behaviors. The microstructure and molecular conformation of extracellularmatrix proteins provide signals that direct cell functions critical totissue formation and regeneration, including proliferation, migration, andmatrix remodeling. Thus, controlling extracellular matrix protein structureprovides a means to regulate the mechanical properties of biomaterialsand control cellular responses. Moreover, biomaterials with regionallydefined extracellular matrix structure could provide local cues to instructcell behavior and drive proper tissue function in 3 dimensions. Collagenis the primary fibrous component of the extracellular matrix. The tremendousdiversity of the functional properties of type I collagen arises fromvariations in the micromolecular and macromolecular structure of polymerizedcollagen fibers. Results of our studies demonstrate the capabilityof ultrasound to spatially pattern various collagen microstructures withinan engineered tissue noninvasively, thus enhancing the level of complexityof extracellular matrix microenvironments and cellular functionsachievable within 3D engineered tissues.Elastography 2013Moderator: Richard Barr, MD, PhDElastography of Diffuse Liver DiseaseGiovanna Ferraioli,* Carlo Filice Infectious Diseases, FondazioneIstituto di Ricovero e Cura a Carattere Scientifico,Policlinico San Matteo, Medical School, University of Pavia,Pavia, ItalyThe prognosis and management of patients with chronic liverdiseases largely depend on the extent and progression of liver fibrosis.Liver biopsy is still considered the reference standard for assessing liverfibrosis. It is an invasive procedure that carries a risk of complications.Moreover, it is not an ideal method for repeated evaluation of disease progression.For these reasons, techniques that noninvasively assess liver fibrosishave been developed. Elastography is a technique that analyzes themechanical and elastic properties of soft tissue that could be modified bypathologic conditions. Real-time elastography, which allows measurementof tissue’s stiffness while guided by the B-mode image, is either strainbased or shear wave based. With strain-based elastography, the displacementof tissues due to an applied stress is detected. With all the shear wavebasedtechniques, there is a generation of shear waves determined bytissue’s displacement induced by the force of a focused ultrasound beam.Real-time elastographic methods are included in standard ultrasound systems.Based on our experience and that of other groups, we believe thatshear wave–based methods are ready to be used in patients with chronichepatitis C to assess liver fibrosis before therapy at a safe level of predictability.S31