The Department of Biomedical EngineeringModel of the total artificial heartfrom the laboratory of WilliamSmith, D. Eng., P.E., Section ofBiomedical Devices14Continued from Page 13Fukamachi, M.D., Ph.D., supports the researchefforts of CCF’s Kaufman Center for HeartFailure, co-directed by Patrick M. McCarthy,M.D. (Department of Thoracic and CardiovascularSurgery) and James B. Young, M.D. (Departmentof Cardiovascular Medicine). The majorfocus is on cardiovascular dynamics of cardiacdevices and animal and bench testing of surgicalinterventions to treat heart failure. This groupfocuses on testing various devices, including oneto treat dilated cardiomyopathy by changing theshape of the left ventricle (Myosplint tm ) andcatheter-type ventricular assist devices (enabler tmand Impella tm ). Based on years of research intononpulsatile blood flow, the Cardiac Assist andReplacement Laboratory, headed by William A.Smith, D.Eng., P.E., is (a) developing a family ofblood pump devices (total artificial heart withinternal battery, ventricular assist devices rangingfrom long-term adult to miniature pediatricapplications—all based on MagScrew TM technology),(b) defining test methods to accurately/repeatably characterize them, (c) developing arational design philosophy for rotary bloodpumps’ performance, efficiency, size, lowhemolysis level and minimal deposition, (d) usingacoustic methods for diagnostic monitoring ofblood pumps, and (e) refining external supportpump systems, including an emergency cardiopulmonarybypass/extracorporeal membraneoxygenation system, funded by the Departmentof Defense, a catheter pump for minimallyinvasive surgery, and an external-use version ofone internal system. These efforts also involvework funded through the NIH’s Small BusinessInnovation <strong>Research</strong> mechanism.The rapidly evolving field of BioMEMSand Nanotechnology provides several diverselines of investigation. Aaron J. Fleischman, Ph.D.,and Shuvo Roy, Ph.D., use microelectronics,microfabrication and micromachining technologiesas enabling technology to improve medicaldiagnostics and therapies by reducing device sizeand cost. Their collaborative studies involveengineering micro-/nanometer-sized features fortissue engineering, protein analyses, assays, andcell interrogation; among the applications beingdeveloped are miniaturized versions of drugdelivery systems, transducers for ultrasoundimages, and in situ telemetrically monitoredpressure/temperature sensors for minimallyinvasive surgery/follow-up. Maciej Zborowski,Ph.D., investigates magnetic flow cell sorting forvarious diagnostic and therapeutic applications,such as rapid screening for cancer cells in blood orblood-forming stem-cell transplantation (withCCF’s Taussig Cancer Center) and in model cellsystems of human peripheral lymphocytes,cultured cell lines, and samples donated bypatients, such as bone marrow. Continuousmagnetic flow sorting is a high-speed, gentleprocess, with high specificity and high recoveryof sorted fractions via cell tagging (e.g., via aniron-doped polymeric nanoparticle developedwith Bar-Ilan University in Israel). Cell TrackingVelocimetry, developed with the Ohio StateUniversity, can analyze individual cell velocitiesof hundreds of cells at a time, yielding data aboutthe population average and dispersion, based onquadrupole and dipole magnetic fields, which cansort some 10 million cells/second with 70%recovery of target cells and be optimized forincreased fractionation resolution and speed. P.Stephen Williams, Ph.D., builds mathematicalmodels of field-flow fractionation usingquadrupole magnets. His work informs the designof devices for cell separation.Several BME investigators work in the areaof Cardiovascular Bioengineering in studiesof blood vessels and heart valves, especially ininteraction with implanted prostheses. Linda M.Graham, M.D., seeks to design longer-lived tissueengineeredvascular grafts. Her group investigates,at the molecular level, how smooth-muscle cells(SMCs) and collagen affect cell proliferation andingrowth into prosthetic grafts, including: 1) themolecular mechanisms involved in the posttranscriptionalregulation of collagen secretion bygraft SMCs, 2) the mechanism by which oxidizedLDL inhibits endothelial cell migration, and 3)the effect of hypercholesterolemia on endothelialcell ingrowth onto prosthetic grafts in vivo. ScottColles, Ph.D., focuses on the role of glutathioneperoxidase and lipid oxidation products in thedevelopment of vascular disease. Lipid oxidationproducts are thought to be major factors in theContinued on Page 15
The Department of Biomedical EngineeringContinued on Page 14development of various vascular diseases includingatherosclerosis. Roy Greenberg, M.D., joint staffwith the Department of Vascular Surgery, focuseson the development of novel techniques andendovascular devices (e.g., stents and stent grafts)to treat aortic aneurysms and dissections, asignificant threat to the aging population. His aimis to ward off the main complication ofendovascular repair, the development of early orlate endoleak, which remains undetected byconventional clinical methods. The Heart ValveLaboratory team led by Ivan Vesely, Ph.D., studiesthe structure/function relationship of heart valvetissues to determine failure mechanisms ofmanufactured replacement heart valves, with theaim of developing a bioprosthetic valve thatcompletely mimics the natural valve’s function. Thegroup uses materials testing, mathematicalmodeling, microscopy, biochemical analysis, andcell culture, along with micromechanical testing,video image processing, and extensions to Fung’soriginal Quasi-Linear Viscoelastic theory. Incollaboration with NASA researchers, they aredeveloping advanced soft-tissue models forsimulating robotic surgery in a virtual-realitytraining system. The group also addresses geneticand biomechanical characteristics of aorticvalves affected by myxomatous mitral valvedisease, a condition characterized by thickeningof valve tissues and stretching of leaflets andchordae, causing the valve to leak. The group isalso creating tissue-engineering implants ofelastin, collagen and glycosaminoglycanssynthesized by cells in culture or purified fromtissues, then manipulated to mimic the aorticvalve’s normal structural framework. Dr.Geoffrey Vince’s work also contributes to thisarea of emphasis.<strong>Research</strong>ers in the Whitaker ImagingLaboratory specialize in micro-CT, magneticresonance imaging (MRI), and ultrasound.Kimerly Powell, Ph.D., uses high-resolutionmicro-CT, a 3D x-ray imaging technology, toevaluate bone microarchitecture in early bone lossand bone formation in small-animal models ofosteoporosis, as well as to monitor the effects ofvarious treatments longitudinally. with a goal ofhelping the aging population at risk for bone loss.Future goals include modes that can be usedinteractively in reviewing, localizing, andquantifying information obtained from variousimaging modalities at different spatial resolutions.Elizabeth Fisher, Ph.D., uses MRI to quantifybrain atrophy in patients with multiple sclerosisand predict the course of disease. The Fishergroup is (a) participating in a 5-year longitudinalstudy of clinical, MRI, immunologic, andpathologic correlates of brain atrophy in MSpatients and a 10-year follow-up image-analysisstudy to relate images of pathology to specificdomains of cognitive impairment, (b) exploringthe relationships between clinical and MRIvariables and time course of changes in the MRImeasurements via a novel postmortemimaging protocol indonated brains, and (c)developing and refiningsoftware (now in clinicaltrials) to incorporate brainatrophy measures into clinicalpractice. Raj Shekhar, Ph.D.,works on real-time 3D(RT3D) image acquisition, anew trend in ultrasoundimaging that eliminates motion artifacts and enablesrapid, more accurate imaging of dynamic anatomy(e.g., heart) in the operating room or at remotelocations. Improved visualization and imageprocessing software will allow tracking of an organ’sshape over time and alignment of 3D images withimproved speed and accuracy for serial comparisonof various image modalities. The goal of D.Geoffrey Vince, Ph.D., is to improve intravascularultrasound (IVUS) imaging to achieve a precisetomographic assessment of the coronary arteryanatomy in vivo in real time. His group seeks toeliminate three major limitations (time consumption,reduced resolution, and variability in the data setcaused by the operator) by taking into accountultrasound radiofrequency signals (backscatter). Thegroup has custom-developed software that usesspectral analysis methods to determine plaquecomposition from IVUS images and to display a“Virtual Histology” map, which has been licensedto Volcano Therapeutics (Laguna Hills, CA) and isundergoing trials in Europe. In collaboration withthe BioMEMS technology of Drs. Shuvo Roy andAaron Fleischman, the group will design and buildhigh-frequency IVUS transducers comprisingtraditional ceramic and novel polymeric materialsand assess how well these transducers perform forhigh-frequency harmonic imaging.The topic of Neural Control is addressed inContinued on Page 16Image at left: Human femurdepicted through the use of highresolutionmicro-CT, a 3D x-rayimaging technology, to evaluatebone microarchitecture in earlybone loss in osteoporosis. ByKimerly Powell, Ph.D., theWhitaker Imaging Laboratory.Below: 3-Dimensional tomographicassessment of the humancoronary artery anatomy in vivo inreal time. By Geoffrey Vince,Ph.D., the Whitaker ImagingLaboratory.15
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