Bioengineering and Imaging Research Opportunities Workshop V: A Summary

transcript

Bioengineering and Imaging Research Opportunities Workshop V: A whitepaper on imaging and characterizing structure and function in nativeand engineered tissues

William Hendeea�

Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226

Kevin ClearyImaging Science and Information Systems, Georgetown University, 2115 Wisconsin Avenue, NW, Suite 60,Washington, DC 20007

Richard EhmanRadiology Department, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905

Gary FullertonUniversity Texas Health Science Center San Antonio, 7703 Floyd Curl Drive, MSC 7800,San Antonio, Texas 78229

Warren GrundfestUniversity of California Los Angeles, 7523 Boelter Hall, Box 951600, Los Angeles, California 90095

John HallerNational Institutes of Health, NIBIB, 6707 Democracy Boulevard, Suite 200, Bethesda, Maryland 20892

Christine KelleyDivision of Discovery Science and Technology, NIBIB/NIH/DHHS, Democracy Plaza 2,6707 Democracy Boulevard, Suite 200, Bethesda, Maryland 20892

Anne MeyerUniversity of Buffalo, IUCB-110 Parker Hall, Buffalo, New York 14214

Robert F. MurphyBiomedical Engineering, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213

William PhillipsRadiology Department, University of Texas Medical Center San Antonio, Research Division–MSC 7800,7703 Floyd Curl Drive, San Antonio, Texas 78229-3900

Vladimir TorchilinDepartment Pharmacy and Sciences, Northeastern University, 360 Huntington Avenue,Boston, Massachussetts 02115

�Received 3 March 2008; revised 24 May 2008; accepted for publication 27 May 2008;published 8 July 2008�

The fifth Bioengineering and Image Research Opportunities Workshop �BIROW V� was held onJanuary 18–19, 2008. As with previous BIROW meetings, the purpose of BIROW V was to identifyand characterize research and engineering opportunities in biomedical engineering and imaging.The topic of this BIROW meeting was Imaging and Characterizing Structure and Function inNative and Engineered Tissues. Under this topic, four areas were explored in depth: �1� Heteroge-neous single-cell measurements and their integration into tissue and organism models; �2� Func-tional, molecular and structural imaging of engineered tissue in vitro and in vivo; �3� New tech-nologies for characterizing cells and tissues in situ; �4� Imaging for targeted cell, gene and drugdelivery. © 2008 American Association of Physicists in Medicine. �DOI: 10.1118/1.2948317�

Key words: tissue engineering, functional, molecular and structural imaging, imaging of engi-neered tissues, targeted cell, gene and drug delivery, single-cell measurements, emerging imaging

I. OVERVIEW

The fifth Bioengineering and Imaging Research Opportuni-ties Workshop �BIROW V� was held on January 18–19, 2008in North Bethesda, MD. The name of the workshop waschanged slightly from preceding BIROW workshops �whichwere known as Biomedical Imaging Research Opportunities

3428 Med. Phys. 35 „8…, August 2008 0094-2405/2008/35„8

imaging. BIROW V was sponsored by the Academy of Ra-diology Research �ARR�, American Association of Physicistsin Medicine �AAPM�, American Institute for Medical andBiological Engineering �AIMBE�, International Society forAnalytical Cytology �ISAC�, and the National Institute ofBiomedical Imaging and Bioengineering which provided

3429 Hendee et al.: Bioengineering and Imaging Research Opportunities Workshop V 3429

tional societies were included as participating organizations.The purpose of BIROW V �as of BIROWs I–IV which wereheld in 2003, 2004, 2005, and 2006�,1–4 was to identify andcharacterize opportunities for scientific research and engi-neering development in biomedical engineering and imaging.

The topic of BIROW V was imaging and characterizingstructure and function in native and engineered tissues. Themeeting focused on four areas of scientific research that offeropportunities for major developments in biomedical engi-neering and imaging.

The four areas are:

�1� heterogeneous single-cell measurements and their inte-gration into tissue and organism models,

�2� functional, molecular, and structural imaging of engi-neered tissue in vitro and in vivo,

�3� new technologies for characterizing cells and tissues insitu, and

�4� imaging for targeted cell, gene and drug delivery.

Each area was addressed in a plenary session in whichseveral speakers presented their analysis of the subject andthe research opportunities and challenges it presents, fol-lowed by audience discussion. Each area was then the focusof discussion at one of four simultaneous breakout sessions.Each breakout session provided a forum for discussion ofresearch opportunities from the perspective of the objectivesof the Roadmap Program of the National Institutes ofHealth.5 These objectives are:

�1� Does it deepen understanding of fundamental biology?�2� Does it promote collaboration of multidisciplinary

teams?�3� Does it reshape clinical research and promote discovery?�4� Does it improve people’s health?

Breakout participants were also asked to identify chal-lenges to the realization of the research opportunities. Thefour questions for this section of the breakout sessions were:

�1� What are the scientific challenges?�2� What are the primary obstacles to development?�3� What are the critical technologies that are lacking?�4� What are the impediments to translating the opportuni-

ties to improved health?

The plenary and breakout sessions yielded a wealth ofinformation that has been synthesized and edited into thefindings and recommendations presented in this article.

II. SESSION I: SINGLE-CELL MEASUREMENTS ANDTHEIR INTEGRATION INTO TISSUE ANDORGANISM MODELS

A number of conventional technologies, including imag-ing methods, are available for assessing the structure andfunction of cells and organisms in vivo. These methods yieldinformation averaged over a volume of tissue in which thecharacteristics of individual cells and small groupings of

Medical Physics, Vol. 35, No. 8, August 2008

gies are emerging that provide an unprecedented ability totarget and analyze the functions of individual cells both invitro and in vivo. This capability presents a differentchallenge—how can information collected at the single-celland cell subpopulation levels be interpreted in terms of thestructural and functional integrity of the organism as awhole. This question must be addressed if the benefits oftissue engineering and regeneration are to be realized �Fig.1�. A particular need and opportunity exists for developmentof methods to automatically integrate information fromsingle-cell measurements into multiscale predictive modes.

II.A. Single-cell measurements: Opportunities

To understand the dynamics of a population of cells, thecharacteristics of individual cells and their interactions withother cells in the population must be known. This necessitydemands that measurements and images must be obtained atthe single-cell level, but with sufficient throughput to ad-equately sample large numbers of cells. Ongoing advancesallow both flow cytometry and fluorescence microscopy tomeet this need, and recent work illustrates how data on sub-cellular and cellular events from these technologies can becombined with machine learning methods to automaticallybuild models.6–8 A major opportunity exists for building ac-tive learning systems that can collect a set of biological data,build a predictive model �or improve an existing model� ofthe biological process from which the data are derived, de-termine what new data would be needed to test the predic-tions of that model, and repeat the cycle of collection andmodel improvement. Such systems are expected to enableboth a greater understanding of fundamental cell biology andhow tissue-level behaviors emerge.

The evolution of single-cell measurements into tissue andorganism models is interdisciplinary by its very nature andrequires expertise from fields as diverse as physics, biology,chemistry, optics, electrical and biomedical engineering, im-aging and computer science, statistics, and mathematics. Asan indication of the interdisciplinary nature of the enterprise,researchers from several different fields self-elected to par-ticipate in the breakout session concerned with single-cellmeasurements. These participants expressed the need for in-terdisciplinary training of persons interested in working onsingle-cell measurements and their integration into systemsmodels.

Single-cell cell subpopulation measurements have the po-tential to greatly impact human health. Measurements in thelymphoid subpopulations of cells are critical to improvedunderstanding of immune-mediated diseases and have al-ready revolutionized the treatment of acquired immune-deficiency syndrome �AIDS�. Because they are simpler andless invasive, single-cell tests have the potential to improvepatient compliance with screening tests and may lead tochanges in clinical practice through earlier and improved in-tervention in disease and disability. Automated creation ofmodels from single-cell measurements may be a key to indi-vidualized medicine by enabling personalized diagnosis and

II.B. Single-cell measurements: Challenges

A major challenge to single-cell measurements is the needfor improved methods for single-cell segmentation and vali-dation, and for automated pattern characterization acrosscells and cell-types. Also needed are improved methods forimaging live cells at high resolution �especially in vivo�, andcompiling atlases of protein and RNA localization across tis-sues and disease states. A number of limitations were notedby breakout participants that are impeding the developmentof single-cell and cell subpopulation measurement tech-niques and their integration into clinical medicine. Amongthese limitations are �1� insufficient resources and mecha-nisms for sharing and annotating images and for compilingthem into image collections for the purpose of training sys-tems for machine learning; �2� omission of image analysisdetails in scientific publications so that reproduction of re-sults is often difficult and sometimes impossible; �3� limitedavailability of state-of-the-art instrumentation, computationalpower, and interdisciplinary scientists needed to bridge theknowledge gap between single-cell measurements, their ex-trapolation to higher-order scales, and their integration into

FIG. 1. Clinical applicati

tissue and organism models. Also needed are improved la-

beling and sampling methods, better label-free imagingmethods and in vivo sensors, more exacting standards forsingle-cell measurement technologies, enhanced techniquesfor tracking cells in the in vivo environment, and develop-ment of methods for active learning in hierarchical systems.

III. SESSION II: FUNCTIONAL MOLECULAR ANDSTRUCTURAL IMAGING OF ENGINEEREDTISSUES IN VITRO AND IN VIVO

Imaging methods have the potential to offer fast, nonin-vasive, and accurate assessments of cell growth, cell differ-entiation, and tissue development, including matrix develop-ment, in native and engineered tissues �Fig. 2�. Talks in thissession covered two major topics: �1� Molecular imaging invivo, including noninvasive tracking and evaluation of im-planted cells and the fate of three-dimensional �3D� engi-neered constructs; and �2� structural and functional imagingof 3D engineered tissue constructs in vitro. These topics en-compassed a plethora of imaging techniques including mag-netic resonance imaging, micropositron emission tomogra-phy �PET�, optical coherence tomography, multiphoton

eas for diseased tissues.

microscopy, and several multimodality imaging methods.

The talks and discussion emphasized the importance of com-munication and interaction between tissue-engineering re-searchers and biomedical imagers in order to realize the po-tential benefits of imaging in tissue engineering andregenerative medicine.

III.A. Imaging of engineered tissues: Opportunities

Imaging is a critical element of tissue engineering andregenerative medicine. It has the potential to monitor tissuefunction and host response in vivo and to detect implant fail-ure early enough to permit corrective action. Further, imag-ing could make the processes of tissue replacement and re-generation more effective and less invasive compared withconventional implants. Increased imaging characterization ofboth natural and engineered tissues would lead to improveddesign of tissue engineering therapies.9

It is widely recognized that two-dimensional cell-culturesystems are artificial and that cells raised in these systems arephenotypically different from those grown in a three-dimensional environment. The latter cells offer a rich re-source for studying cell function and cell-cell, cell-matrix,and cell-medium interactions.10 Three-dimensional engi-neered tissue systems open new possibilities for studyingcomplex physiological and pathophysiological processes in acontrolled environment, including cell and tissue growth pat-terns and the reasons for success and failure of engineeredtissues implanted in the body.11

Tissue engineering is distinctly an interdisciplinary re-search effort that requires biological, engineering, and medi-cal knowledge tempered with input from experts in bioinfor-matics, computational biology, embryology, and sensortechnologies. Also needed are individuals who are highlyknowledgeable about the technology-transfer process, trans-lational research, and the protection and commercializationof intellectual property. Shortfalls were acknowledged in theability of technology-transfer offices of many academic in-stitutions to capitalize on promising new technologies, inpart because these offices are often under considerable pres-

FIG. 2. Biological principles and design of engineered tissues �courtesy ofGordana Vunjak-Novakovic, Columbia University, New York, NY�.

sure to realize short-term profits by early sell-off of promis-

ing new technologies at prices well below their ultimate mar-ket value. Also recognized was the need for closerinvolvement of clinicians with biomedical engineers and oth-ers engaged in tissue engineering.

Engineered tissues hold great promise to supplement andeven replace donor tissues and biological fluids that are per-petually in short supply.12 Three-dimensional engineered tis-sues may become highly useful tools for development ofdrugs and major incentives for better imaging methods, es-pecially when compared with animal models currently usedfor evaluation of drugs and imaging techniques.

III.B. Imaging of engineered tissues: Challenges

Imaging of engineered tissues faces many challenges, sev-eral of which are due to incomplete knowledge of cell physi-ology and dynamics, especially with regard to the interactionand integration of engineered and host tissues. Progress intissue engineering requires a number of technological inno-vations, including: �1� noninvasive, real-time imaging meth-ods to continuously monitor cell differentiation �e.g., mo-lecular imaging of gene expression�; �2� techniques for label-free imaging that are as sensitive as imaging using labels atmolecular and cellular levels; �3� ways to identify and trackindividual cells and cell subpopulations in vivo; �4� proce-dures to enhance the likelihood that stem cells will seek the“proper” location when they are injected in vivo;13 and im-aging techniques to verify that the desired location has beenreached; and �5� processes to image cells at deeper levelswithin tissues and organs.14

Other imaging advances that would accelerate the trans-lation of tissue engineering from the laboratory to clinicaluse include: �1� better exogenous markers and identificationof additional endogenous biomarkers; �2� improved three-dimensional image analysis and quantification; �3� methodsto evaluate the evolution of scaffold degradation and tissuereplacement over time; �4� improved imaging procedures forautomated edge detection, deeper penetration into tissueswithout excessive loss of spatial resolution, and use inside oroutside a bioreactor; �5� multimodality imaging facilities andcustomized imaging methods, including imaging laboratoriesfor larger animals; and �6� better ways to compile, store andmine imaging data. Additional concerns include the cost andnonportability of many imaging methods, and the need forphysician awareness and acceptance of the potential of engi-neered tissues to address a variety of human disorders.

IV. SESSION III: NEW TECHNOLOGIES FORCHARACTERIZING CELLS AND TISSUES IN SITU

Emerging technologies are offering new approaches toquantitative assessment of tissue properties that heretoforecould not be measured in situ. Many of these technologiesutilize imaging methods that exploit interactions of energywith tissues, and some employ the conversion of energy fromone form to another �energy transduction�. Examples includemagnetic resonance elastography15,16 �Fig. 3�, photoacoustictomography,17 thermoacoustic tomography and ultrasound-

elastographic19 and acoustic radiation force based methods.20

Other approaches bring sensors and microscopic imagingtechniques into contact with tissues of interest by minimallyinvasive, image-guided methods. Many of the emergingtechnologies are as adaptable to imaging tissue constructs asthey are to imaging cells and cell subpopulations in vivo.

IV.A. Characterizing cells and tissues:Opportunities

Emerging technologies improve biological understandingby offering new methods to characterize the properties oftissues at the multicell level. They also help reveal the inter-play between a target tissue and its surroundings, leading to

FIG. 4. Optical microprobes have the potential to distinguish normal tissuefrom multicellular aggregates of cancer cells. The challenge is to developthis potential into technologies capable of delineating the margins of tumorsfor surgical extraction and radiation treatment �courtesy of Dr. Alexander

FIG. 3. Magnetic resonance elastography. �Left� A conventional magnetic remagnetic resonance imaging technique is used to image propagating sheaprocessed to generate a quantitative image of tissue stiffness. �Right� This emuch higher than the normal value of 2 kPa, indicating the presence of sediagnosis �from Richard L. Ehman�.

Meining, Klinikum rechts der Isar, Munich, Germany�.

greater knowledge of differences between normal and dis-eased tissue. At the microscopic scale now achievable fortissue characterization, variations in normal tissues can bemeasured to yield a range of normal tissue characteristicsrather than just an average. Participants in the breakout ses-sion emphasized that in situ characterization of tissues couldradically improve the process of clinical trials of new thera-pies by early monitoring of changes at cellular and tissuelevels as they occur. They also recognized that emerging im-aging technologies could lead to new low-cost screeningmethods that would be accessible to all, including popula-tions that are currently underserved or deprived of adequatehealth care. Examples of such technologies include elastog-raphy for liver fibrosis16 and endomicroscopy �Fig. 4� for invivo cancer diagnosis.21 Realization of the potential ofemerging technologies requires a multidisciplinary effort thatincludes physicians from the clinical arena as well as scien-tists and engineers from the laboratory.

IV.B. Characterizing cells and tissues: Challenges

Tissue characterization with emerging technologies en-counters many challenges, including: �1� distinguishing tran-sient from chronic phenomena; �2� applying the technologiesacross multiple scales, from cells to the whole organism; �3�characterizing the interactions between focal lesions and sur-rounding tissues; �4� recognizing early signs of evolvinghealth problems such as precancerous states in cells and tis-sues, gene modulation by the cellular environment, and ini-tial stages of mental illness; and �5� determining the impor-tance of cell and tissue variables that are currentlyinaccessible �e.g., hydrostatic pressure�. In addressing thesechallenges, it is essential to put preconceptions aside and tothink in novel ways to arrive at solutions—a rule that appliesto problem solving in general and not just to tissue charac-terization.

Developing breakthrough technologies requires an invest-ment of money and time beyond that awarded through thetraditional funding mechanisms of federal agencies. This is-sue has been a perpetual problem in research funding that is

ce image of the upper abdomen reveals no abnormality. �Center� A speciales that are generated in the upper abdomen. The shear wave images areram reveals that the stiffness of the liver is approximately 8 kPa, which is

hepatic fibrosis, a condition that has traditionally required liver biopsy for

sonanr wavlastogvere

slowly being addressed by federal agencies. Technological

innovation is an extremely valuable characteristic in researchthat should be nurtured and supported in funding and regu-latory agencies and in academic institutions.

To realize the benefits of new approaches to characteriz-ing cells and tissues, better tools are needed such as physicaland chemical sensors that offer higher sensitivity, improvedspatial and temporal resolution, and greater penetration oftissues. Multimodality and multiparametric probes would behelpful in measuring complementary cell and tissue charac-teristics, many of which currently are immeasurable. Physi-cians should be brought into this effort so that the potentialof these approaches can be exploited in the clinic. Finally,the cost effectiveness of early detection and treatment of dis-ease through methods such as cell and tissue characterizationby imaging technologies should be emphasized as an avenueto reduction of health care costs.

V. SESSION IV: IMAGING FOR TARGETED CELL,GENE, AND DRUG DELIVERY

A major challenge in the delivery of cells, genes, anddrugs to tissues is the present uncertainty about where the

FIG. 5. In vivo distribution of 186Re-labeled chemotherapeutic nanoliposomimaging. MicroSPECT imaging is useful for monitoring whole body distrGarcia-Rojas, A. Bao, G. D. Dodd III, C. Santoyo, R. Perez, B. Goins, and WFollowing Intratumoral Delivery of Radiolabeled Liposomes in a Human Soof Molecular Imaging and the Society for Molecular Imaging. Providence,

substances localize within cells and tissues after administra-

tion. These substances may prove to be ineffective becausethey do not reach the intended target in adequate amounts, orbecause they are not retained in the target long enough todeliver the hoped-for impact. The development of new thera-peutic approaches using cells, genes, and drugs, and the im-provement of existing moieties, depends heavily on bettermethods to identify and track the migration, deposition,function, and elimination of these substances in cells andtissues in the body. New imaging technologies that offerthese capabilities would be a major contribution to develop-ment and application of new diagnostic and therapeutic mo-dalities �Fig. 5�.

V.A. Imaging for targeted delivery: Opportunities

Imaging methods to track the delivery of cells, genes anddrugs in situ may contribute to a heightened understanding ofbasic cellular processes such as transporter and receptor ki-netics, cell-membrane structure, biochemical and signalpathways, endocytosis, apoptosis, etc. These methods mayalso reveal new information about disease biology, specificbiomarkers for disease processes, and the reasons why a

n be imaged and quantified via microSPECT/CT and planar scintigraphicn as well as the intratumoral distribution of lipid nanoparticles �from X.illips. MicroSPECT/CT Imaging of Intratumoral Distribution and Retentionumor Xenograft. Abstract—Joint Molecular Imaging Conference; Academyeptember 2007�.

es caibutio

. Phlid T

treatment may succeed or fail based on the delivery of the

therapeutic agent to the target. Imaging studies are importantto the development of new therapeutic entities and have thepotential to greatly reduce the time and cost of bringing newtherapies to the market and to patients.

Ultimately, imaging may help match the characteristics ofindividual patients with the properties of specific therapeuticregimens, leading to realization of the vision of “personal-ized medicine” through better patient characterization andimproved therapeutic products.22 To realize this potential, amultidisciplinary effort is required that includes broadly edu-cated physicians working with scientists and engineers in theresearch and development of new therapies, delivery systemsfor them, and methods to monitor the responses of patientsafter the therapies are administered.

V.B. Imaging for targeted delivery: Challenges

A major shortcoming of current therapeutic regimens in-volving drugs and other internally administered therapies isthe lack of knowledge of exactly where the therapies localizeafter administration, how much of the therapies are concen-trated and retained in the target tissues, the uniformity ofdistribution of the therapies within the targeted tissues at thelocal level,23 and what happens to the remainder of the prod-uct from the standpoint of toxicity in normal tissues. Inad-equate delivery of a particular therapeutic agent to its tar-geted site may frequently be the cause of ineffective therapy.To solve this problem, new drug delivery systems are neededto improve uptake and distribution of a therapeutic agentwithin the targeted disease process.24 Imaging of the distri-bution of the drug can be a key tool for development of newdrug delivery systems.25,26 A major challenge in the develop-ment of gene therapies is the need to track the presence,migration, and replication of viruses in the body. This chal-lenge must be met if virus-mediated gene therapy is ever tosucceed.

Several specific challenges impede the development ofmaterials for targeted delivery in cells and tissues. Thesechallenges include: �1� inadequate standards for image guid-ance of therapeutic intervention in animal studies, causingdifficulties in replication of results and their ultimate appli-cation in the clinic; �2� absence of quantitative imagingmethods for stem cell tracking, which are required for suc-cessful development of stem-cell therapies; �3� high cost ofsome commercially available imaging agents and othermarkers that are useful in animal and clinical studies; �4�regulatory challenges in gaining approval for labeling a spe-cific therapy to permit imaging during initial clinical evalu-ation.

There are technologies that are essential to the evolutionof more effective drugs and other therapies. Among thesetechnologies are: �1� combined imaging systems �e.g., PET/CT, SPECT/PET, PET/MRI, US/CT� for evaluation of drugdelivery, localization, and monitoring and for image-guidedtherapy; �2� small and large animal imaging facilities that areaccessible to researchers exploring new cell, gene, and drugtherapies; �3� optical and other new imaging modalities that

and that can be translated into imaging techniques for usewith patients; and �4� automation technologies for quantita-tive labeling and for image analysis.

The development of new therapies delivered by cells,genes, and drugs is expensive, and additional research fund-ing is needed to realize their potential to alleviate humandisease and suffering. In addition to core imaging facilitiesfor small and large animals, more funding is needed to sup-port phase 1 studies of new therapies, and for translationalresearch in general. Finally, a major effort should be directedto the interdisciplinary education and training of scientistsand clinicians so that they have the integrated knowledgenecessary to work productively in this new arena ofmedicine.

APPENDIX: BIROW V SESSIONS AND SPEAKERS

Presenters at BIROW V are listed as follows.

I. Plenary session 1: Heterogeneous single cellmeasurements and their integration into tissue andorganism models

Polychromatic and Hyperspectral Flow Cytometry forModeling Relationships in Heterogeneous Cell Populations:Paul Robinson, Purdue University

Automated Learning of Protein Subcellular Locations forModeling of Cell Behavior: Robert Murphy, Carnegie-Mellon University

Optical Measurements and Light Distribution for the De-tection of Cancer: Eva Sevick Muraca, Baylor College ofMedicine

Cellular and Tissue Optical Measurements for the Detec-tion of Colo-Rectal Cancer—Does the Field Effect Exist?:Vadim Backman, Northwestern University

II. Plenary session II: Functional, molecularand structural imaging of engineered tissue in vitroand in vivo

The Needs for Functional Imaging of Engineered Tissues,in vitro and in vivo: Gordan Vunjak-Novakovic, ColumbiaUniversity

Multi-modality Imaging of Engineered Tissues in vivo:Charles Lin, Massachusetts General Hospital

Imaging for Design and Evaluation of Tissue EngineeredConstructs: Scott Hollister, University of Michigan

Optical Imaging of Engineered Tissues: Mark Brezinski,Brigham and Women’s Hospital

III. Plenary session III: New technologiesfor characterizing cells and tissues in situ

Energy Transduction Imaging: PAT, TAT, UOT: LihongWang, Washington University

New Technologies in Acoustical Tissue Characterization:Kathryn Nightingale, Duke University

Magnetic Resonance Elastography: Richard Ehman,

Minimally Invasive Contact Tissue Characterization: Sen-sors and Optical Imaging: Kevin Cleary, Georgetown Medi-cal Center

IV. Plenary session IV: Imaging for targeted cell,gene, and drug delivery

Dynamic Imaging of Targeted and Activatable Vehicles:Katherine Ferrara, University of California Davis

Imaging of siRNA Delivery and Silencing: Anna Moore,Harvard Medical School

Liposomal Carriers for Drug Delivery Imaging: WilliamPhillips, University of Texas Medical Center San Antonio

Imaging Component of Multifunctional PharmaceuticalNanocarriers: Vladimir Torchilin, Northeastern University

V. BIROW V sponsoring organizations

The organizers and authors of the BIROW V white papersincerely thank the 25 scientific and educational societiesthat participated by sending representatives, ideas and otherresources to make this project possible: �1� Sponsors: Acad-emy of Radiology Research, American Institute of Medicaland Biological Engineering, American Association of Physi-cists in Medicine, International Society for Analytical Cytol-ogy, and National Institute of Biomedical Imaging andBioengineering and �2� Participating Societies: AmericanBrachytherapy Society, American Institute of Ultrasound inMedicine, Academy of Molecular Imaging, American Medi-cal Informatics Association, American Roentgen Ray Soci-ety, Acoustical Society of America, Association of UniversityRadiologists, Fleischner Society for Chest Diagnosis, Insti-tute of Electronic and Electrical Engineers, International So-ciety for Magnetic Resonance in Medicine, Medical ImagePerception Society, North American Society for Cardiac Im-aging, Radiological Society of North America, Society forImaging Informatics in Medicine, Society of Chairmen ofAcademic Radiology Departments, Society of InterventionalRadiology, Society for Molecular Imaging, Society ofNuclear Medicine, SPIE—The International Society for Op-tical Engineering, Society of Radiopharmaceutical Sciences,and the IEEE Ultrasonics Ferroelectrics Frequency ControlSociety.

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Bioengineering and Imaging Research Opportunities Workshop V: A Summary

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