Biomedical Engineering
2013 Xerox Research Opportunities
Prof. Regine Choe
Department of Biomedical Engineering
Regine_Choe@urmc.rochester.edu
Research Project:
The overall goals of Professor Choe's laboratory are to assess and improve the capabilities of diffuse optical technology in breast cancer therapy monitoring and detection. In clinical measurements of human breasts with tumor, we focus on identifying functional parameters measurable with diffuse optics, which can serve as early indicators of therapy efficacy. Using a preclinical animal model, we study the metabolic mechanism of varied responses to therapy seen in the clinic, and investigate new therapeutic drugs and interventions. Also, we explore new functional and metabolic parameters (e.g. glucose metabolism) accessible through near-infrared fluorescent optical agents. The students will have opportunities to participate in various aspects of research: instrumentation construction and characterization, data analysis algorithm development, preclinical experiments, and/or clinical experiments.
Prof. Stephen McAleavey
Department of Biomedical Engineering
stephen.mcaleavey@rochester.edu
Research Project:
The ultimate goal of this project is to develop and test a combined quasi-static compression and shear wave elastography system to characterize the linear and nonlinear mechanical properties of breast tissues. Breast cancer is the most common non-cutaneous cancer in American women with over 220,000 cases expected to be diagnosed in 2012. Most (~75%) biopsies are negative and represent a significant economic and psychological cost that could be reduced with improved imaging methods. Ultrasound elastography of the breast as well as other tissues has shown success in improving the sensitivity and specificity of breast lesion classification.
Our laboratory uses acoustic radiation force impulse (ARFI) methods to generate small (order of microns) displacements in tissue that act as controllable shear wave sources. The velocity of the resulting shear wave can be measured by ultrasound tracking methods to characterize shear wave velocity and, through a tissue model, mechanical properties. ARFI methods induce very small strain (<1%) within the tissue under investigation; therefore it cannot measure the nonlinear behavior of soft tissues. To overcome this limitation, we propose to apply a larger static strain to the tissue during ARFI-based shear wave imaging. When ARFI displacements are then applied, the incremental strain allows estimation of the mechanical properties at the static strain operating point. The strain dependence of shear wave velocity may thus be acquired over a wide range of strain values.
In the near term this project will develop a combined radiation-force-based and quasi-static elastography system to measure shear wave velocity in the linear and nonlinear regime. This system will use linear positioning stages to apply strains to tissues and compliant materials under computer control while simultaneously allowing imaging with an ultrasound transducer array. This array will generate shear waves via acoustic radiation force impulses, and track the resulting tissue motion to estimate shear wave velocity. The performance of the system will be evaluated with tissue mimicking phantom materials.
Prof. Amy Lerner
Department of Biomedical Engineering
amy.lerner@rochester.edu
Research Project:
The overall goal of our research program is to understand the risks for musculoskeletal joint disorders. For example, we are particularly interested in the effects of gender, ethnicity, obesity, knee injuries and gait patterns in the risks for knee osteoarthritis. We use a combined approach involving gait analysis, medical imaging and computational modeling to study these effects and try to predict the clinical risk factors associated with each factor, and combinations of these factors. Students may help with image analysis to better understand the role of the meniscus in distributing loads during knee flexion, or help to develop subject-specific finite element models with meniscal injuries or partial meniscectomy. These models may be modified to consider a variety of loading conditions representing different types of activities. Our long term goal is to assist clinicians in advising their patients about appropriate exercise, activity and treatments to prevent the onset or progression of disease.
Prof. Diane Dalecki
Department of Electrical and Computer Engineering, and Biomedical Engineering
dalecki@bme.rochester.edu
Research Project: Biomedical Ultrasound
The primary goals of Professor Dalecki’s laboratory are to advance novel diagnostic ultrasound techniques, and to discover new therapeutic applications of ultrasound in medicine and biology. For this project, students will work towards developing new ultrasound technologies for the field of tissue engineering and regenerative medicine. Specifically, students will investigate the effects of ultrasound on extracellular matrix proteins and cell functions that are key for engineering artificial 3D tissues and enhancing wound repair. Students will develop skills in acoustic field calibration, signal processing, cellular and tissue preparation procedures, cell and extracellular matrix biology, and ultrasound physics. The research is highly multidisciplinary and spans the fields of biomedical ultrasound, acoustics, medical imaging, cell and tissue engineering, and biomechanics.
Prof. Danielle Benoit
Department of Biomedical Engineering and Chemical Engineering
benoit@bme.rochester.edu
Research Project: Hydrogel culture environments for regenerative medicine applications
We can interrogate and take advantage of the critical interactions between cells and extracellular matrix (ECM) to create bioactive materials capable of controlling cell function and tissue evolution (described in Figure 1). To determine the requirements of the microenvironment, we utilize hydrogels easily modified with respect to mechanical integrity, adhesive peptides, ECM molecules, degradability, and incorporation of drugs, to direct cellular differentiation through a variety of mechanisms.
In particular, we are interested in utilizing hydrogel microenvironments to direct encapsulated mesenchymal stem cell (adult stem cell) function for applications in musculoskeletal tissue engineering. A thorough understanding of how material properties effect cell differentiation and tissue evolution is essential to tailor ‘instructive materials’ to direct cell function.
Prof. Richard Waugh
Department of Biomedical Engineering
waugh@bme.rochester.edu
Research Project: Blood Cell Bioreactor
We are working on designs of micro-scale chambers where we can control the physical environment of red blood cell precursors as the mature into enucleated red blood cells. Previous study has shown that red cells go through a period of mechanical instability as they mature, and our hypothesis is that by controlling the mechanical environment of the cell, we will be able to improve the properties of cells produced from pre-cursors in culture. The project will involve modification of reactor design, cell culture in the reactor and characterization of the physical properties of the cells that are produced. The goal is to develop a system capable of producing red blood cells that would be suitable for transfusion or as vehicles for drug delivery.
Prof. Mark Buckley
Department of Biomedical Engineering
mark.buckley@rochester.edu
Research Project
Tendon, ligament, cartilage and many other soft biological tissues serve predominantly mechanical functions. However, unlike steel, concrete and other elastic solids, these structurally complex materials exhibit a history- and time-dependent response to loading (i.e., viscoelasticity) that must be characterized in order to predict in vivo deformations and understand loss of mechanical function in the pathological state. Our lab is interested in evaluating changes in soft tissue viscoelastic properties across multiple length scales during processes including exercise, aging, injury and disease and identifying the specific biological and structural factors responsible for these alterations. To characterize viscoelasticity at the tissue, matrix- and cellular-levels, we combine simultaneous high-speed microscopy, force measurement and control of deformation on live tissue explants. Using our findings, we seek to devise strategies for assessing the efficacy of treatments or diagnosing damage based on viscoelastic measurements.
Prof. Jong-Hoon Nam
Department of Biomedical Engineering and Mechanical Engineering
jong-hoon.nam@rochester.edu
Research Project: Measurement of Mechanical Properties of the Cochlear Partition
We are working on designs of micro-scale chambers where we can control the physical environment of red blood cell precursors as the mature into enucleated red blood cells. Previous study has shown that red cells go through a period of mechanical instability as they mature, and our hypothesis is that by controlling the mechanical environment of the cell, we will be able to improve the properties of cells produced from pre-cursors in culture. The project will involve modification of reactor design, cell culture in the reactor and characterization of the physical properties of the cells that are produced. The goal is to develop a system capable of producing red blood cells that would be suitable for transfusion or as vehicles for drug delivery.
Prof. Lisa DeLouise
Department of Biomedical Engineering
lisa_delouise@urmc.rochester.edu
Research Project
Skin cancer is the most common form of cancer in the US. More than 2 million skin cancers are diagnosed annually. Approximately 20% are SCCs which are directly associated with UVR skin exposure. Metastases from SCCs account for the majority of non-melanoma skin cancer deaths, ~3000 per year in the US. Tumor size and morphology are considered to be prognostic factors for recurrence, but there are no genetic mutations or molecular markers that can be reliably used by clinicians to predict tumor metastatic potential or to guide therapeutic strategies. The discovery, quantification, and characterization of cells with tumor initiating capacity in SCC are essential for developing prognostic and predictive biomarkers of metastasis. The traditional approach to identify tumor initiating cells (TICs) replies on sorting cells using flow cytometry based on the presence of cell surface proteins suspected to be expressed only on or at higher levels on TICs. Successfully sorted cells are then tested in functional assays that include measuring the in vitro clonogenic potential (CP, the ability to self-replicate), invasiveness (ability of cells to migrate through gels), and the in vivo tumorigenicity (tumor generation in mice). Unfortunately, the positive correlation between the expression of suspected cell surface markers with tumorigenicity, invasiveness, and/or CP value have proven inconsistent suggesting that new approaches are needed. The DeLouise Lab is currently developing new assays based on Polydimethylsiloxane (PDMS) microbubble arrays that can enrich, sort, and characterize TICs. MB arrays are produced by gas expansion molding. The unique architecture of the MB well is highly advantaged for single cell culture and cell sorting applications. Our approach is to exploit phenotypic differences that exist between malignant and normal cells; principally anchorage independent proliferation and a privileged capacity to condition their microenvironment in an autocrine fashion. We developed the Polydimethylsiloxane Assay for Non-adherent Tumor cell Sub-population (PANTS) to enrich for sphere-forming cells (anchorage independent proliferation) that expressed higher levels of stem cell surface markers. The nonadherent cells exhibited a higher CP value than the adherent cells which we measured using MB well array technology. On-going studies seek to optimize the application the PANTS and MB array assays to identify TIC in SCCs using established cell lines and primary cell samples derived from human tumors. The TICs that we isolate will be characterized by determining their CP value, their invasive characteristics, and their gene expression patterns. Ultimately these studies will enable us to identify and validate candidate SCC TIC biomarkers that can be used by clinicians to diagnosis aggressive tumors early.
Prof. Geunyoung Yoon
Department of Biomedical Engineering, Institute of Optics, and Center for Visual Science
yoon@cvs.rochester.edu
Research Project #1: Overcoming Presbyopia: Extending Depth of Focus using Wavefront Interaction
Accommodation refers to the ability of the crystalline lens of the human eye to dynamically change focus in order to visualize objects at various distances clearly at the retina. The accommodative ability steadily decreases with aging and this age-related loss of accommodation known as presbyopia becomes noticeable as a lack of unassisted near vision in middle age. Many strategies exist for overcoming presbyopia, however none truly return the eye to its youthful, accommodating state of dynamic power change. From simple solutions, like reading glasses and bifocal spectacles, presbyopic solutions have greatly evolved in the last few decades. Our approach is to develop multifocal designs to extend depth of focus. Specifically, we use optical interactions between different wavefront aberrations and these designs can be adapted to ophthalmic lenses such as contact lens and intraocular lens. The project involves both theoretical and experimental investigations using wavefront/aberration theory, Fourier optics, advanced optical metrology systems to assess image quality through the multifocal designs. Visual performance of human subjects will also be made.
Research Project #2: Overcoming Presbyopia: Extending Depth of Focus using Wavefront Interaction
Dry eye is a multifactorial disease of the ocular surface and tears, resulting in symptoms of discomfort, visual disturbance, and instability of the tear film with the potential for ocular surface damage. It is recognized as one of the most common ocular disorders affecting many patients aged 50 years and older. Current clinical measurement techniques used for dry eye evaluation is a critical barrier to effectively diagnosing and treating the disease because they are often invasive and ineffective to comprehend the complex interplay between tear film, ocular surface and environmental variations. We use the state-of-art multimodal tear imaging technology developed in the laboratory for the accurate and objective assessment of the tear parameters and their response to controlled environmental changes. The multimodal tear imaging technology such as tear surface topography/wavefront sensor, ocular surface optical coherence tomography, imaging ellipsometer and thermal imaging will be used to characterize the tear. The project also involves development of various computer algorithms to analyze tear images automatically.
Prof. Jean-Philippe Couderc
Department of Biomedical Engineering
Jean-Philippe.Couderc@heart.rochester.edu
Research Project: Developing the Next Generation of Non-Contact Physiological Monitoring Devices
Atrial fibrillation (AF) is the most common cardiac rhythm disturbance encountered in clinical practice. It is estimated that greater than 2.2 million people in the United States are affected by AF with a prevalence reaching 0.4 – 1% of the general population. Hospitalizations for AF have also significantly increased due to the increased prevalence of chronic heart disease, aging population, and increased detection by ambulatory monitoring. The clinical consequences range from diminished quality of life and increase in congestive heart failure, to devastating thromboembolic events and increased mortality. The ECG and ambulatory monitoring systems are considered efficient tools to detect the presence of AF, yet they remain cumbersome to monitor patients continuously and difficult to access and to use by patients when needed. First, they must be prescribed by a health care professional, secondarily they are often limited to short monitoring time periods (a couple of days), or they are based on implanted technologies for long-term cardiac rhythm trending data (loop recorders) that represent expensive investigational tools. Therefore, there is great interest in any novel technologies that could detect the presence of AF while minimally disturbing the patients’ quality of life and decreasing the cost of periodic monitoring of patients inside and outside clinical settings. The proposed project is to improve and validate software algorithm to extract physiological measurements from video of patients face and hand. Using data from non-contact monitoring apparatus evaluated in patients from the Strong Medical Center, the proposed project includes the following activities: 1) learning about human physiology, 2) assisting human experimentations in clinical settings, and 3) analyzing image and electrocardiographic digital signals using basic signal processing techniques.
