Coulter Funded Projects

(2014-2015) Porous Metal Implants for Osseous Integration for Tendon/Ligament Reattachment

Silvia Blemker, PhD, Biomedical EngineeringJoseph Park, MD, Orthopaedic Surgery

A technology for tendon and ligament ruptures.

(2013-2015) Two Camera Molecular Breast Tomography (2CMBT) For Low Dose Breast Cancer Imaging

Heather R. Peppard, MD, Radiology and Medical Imaging

Mark B. Williams, PhD, Radiology and Medical Imaging, Biomedical Engineering

Zongyi Gong, PhD, Radiology and Medical Imaging

Stan Majewski, PhD, Radiology

The objective of this Coulter project is to develop a new type of molecular imaging scanner for early detection and diagnosis of breast cancer. The availability of this technology would, in addition to improving diagnostic accuracy, clinical throughput and patient convenience while minimizing cost, permit all steps to be accomplished within one radiotracer injection, thereby further minimizing radiation dose.

(2014-2015) Ultrasound Imaging for Surgical Applications

John A. Hossack, PhD, Biomedical Engineering

Gorav Ailawadi, MD, Cardiothoracic Surgery and Biomedical Engineering

Novel technology for Coronary Artery Bypass Graft procedures.

(2013-2015) Proving a wearable, wireless, self powered EKG “A-FIB” Patch

Randall Moorman, MD, Cardiology and Biomedical Engineering

Benton Calhoun, PhD, Electrical Engineering

The objective of this project is to characterize and improve the adhesive EKG patch prototype (developed with a 2013 Coulter grant) and to test it for cardiac monitoring and atrial fibrillation detection in a clinical study. This project is critical for moving the wearable monitoring technology ahead to a point where it can be transitioned to industry for commercialization.

(2013-2015) Rapid detection of E. coli

Kim Kelly, PhD, Biomedical Engineering

Erik Hewlett, MD, Infectious Diseases

John Herr, PhD, Cell Biology

Food safety is of paramount importance worldwide. A major contaminant that causes morbidity and mortality is the Shiga Toxin producing bacterium, E. coli. In the coming year, a phage-flag assay will be optimized and assay conditions will be standardized for both ground beef and cattle fecal samples, by working with farms and food processing manufacturers. This program will develop a point-of-use kit that can be applied at many unserved steps along the food safety chain from farm to fork.

(2013-2014) Refinement, prototyping, and testing of a device to standardize sample processing in fecal microbiota transplant

Will Guilford, PhD, Biomedical Engineering

Laurie Archbald-Pannone, MD, Internal Medicine

Glynis Kolling, PhD, Infectious Diseases

(2013-2014) Profiling antibiotic susceptibility and growth of microbial pathogens with a novel plate reader device

Jason Papin, PhD, Biomedical Engineering

Erik Hewlett, MD, Infectious Diseases

(2013-2011) Development of a Plectin-1-based Blood Test for Detection of Pancreatic Cancer

Kimberly A. Kelly, PhD, Biomedical Engineering

Todd W. Bauer, MD, Surgery

Pancreatic cancer has the shortest survival duration of any solid cancer with an estimated 1-year survival rate of 25% and a 5-year survival rate of only 6%. Early detection and complete surgical resection offers the best hope for longer survival for the 43,000 newly diagnosed patients every year. Unfortunately, there are currently no suitable blood tests or other techniques for early detection. Thus, pancreatic cancer is revealed at an advanced stage in most patients and only 10-15% of patients are eligible for surgery. In previous work, we have identified plectin-1 as a novel biomarker for pancreatic cancer and have discovered a novel peptide that specifically recognized plectin-1 in pancreatic cancers, allowing detection of these tumors with imaging. The objective of our study is to develop a plectin-1-based blood test for pancreatic cancer to aid in early detection.

(2011-2013) Development of a Serum Diagnostic Test for Uterine and Ovarian Cancer Based on a Cancer-Oocyte Biomarker SAS1R and Elucidation of SAS1R’S Cell Surface Accessible Properties in Cancer Cell Lines

John Herr, PhD, Biomedical Engineering and Cell Biology

David Bruns, MD, Pathology

Over 22,000 women die from ovarian or uterine cancer in the United States every year. Cancer egg cell biomarkers are gene products that are expressed in various tumors (but among healthy tissue are found only in female germ cells) and may present a remarkable opportunity for tumor diagnosis and treatment. There remains lack of definitive diagnostic tests for ovarian and uterine cancers and poor prognosis for patients with these diseases (46% and 71%, respectively). SAS1R, a model cancer egg cell biomarker, offers a potential diagnostic target for earlier diagnosis of these cancers.

(2011-2013) A Hand-carried Ultrasound Device for Spinal Bone Imaging: Technology Development and Pilot Study

John A. Hossack, PhD, Biomedical Engineering

William Mauldin, Jr, PhD, Biomedical Engineering

Mohamed Tiouririne, MD, Department of Anesthesiology

Spinal anesthesia and diagnostic procedures, including epidurals and spinal taps, are common medical practices performed primarily to diagnose disease and alleviate pain. Over 2 million epidurals are performed annually to women giving birth alone. The current standard of care, called the manual or “blind approach,” is associated with failure rates as high as 40% over all cases, and more than 70% in obese patients. It is well known that the prevalence of obesity is increasing significantly within the U.S. and in the developing world. These failures can result in significant health complications and thus, increased non-reimbursable costs to healthcare providers. As a result, fluoroscopy has been increasingly used to replace the blind approach; however, this procedure has become a leading cause of a cumulative radiation dose in the United States. Given the health risks and increased costs associated with current treatment options, there exists a need for advances in medical equipment to increase efficacy and safety and reduce costs for these procedures. In this proposal, we address this clinical need by developing a hand-carried ultrasound device for 3D bone imaging.

(2012-2013)Commercialization of the CAVCAM: A “Point & Shoot” Retinal Camera for Use in Primary Care Diabetic Retinopathy Screening

Paul A. Yates, MD, PhD, Ophthalmology and Biomedical Engineering

Shayn Peirce-Cottler, PhD, Biomedical Engineering

Diabetes and associated diseases are potentially blinding and impair the vision of over 10.7 million diabetic patients in the U.S. It has been increasingly recognized that eye screening within the primary care clinic is critical for early prevention. However, there are significant cost barriers associated with the purchase of an eye camera that has been extremely prohibitive to establishing a nationwide screening network. The proposed end-stage translational research project aims to bring-to-market a novel, lower-cost retinal camera technology that can be used by primary care physicians to screen for eye disease.

(2012-2013) Cerebral Perfusion and Blood-Brain Barrier Permeability Assessed Using Arterial Spin Labeling (ASL)

Craig H. Meyer, PhD, Associate Professor, Biomedical Engineering and Radiology

Max Wintermark, MD, Associate Professor, Radiology, Neurology, Neurological Surgery and Biomedical Engineering

Every year, 795,000 patients suffer from a stroke and 22,340 are diagnosed with brain tumors in the United States. The evaluation of blood flow to the brain has gained significant importance in the modern care of stroke and brain tumor patients. Currently, blood flow is routinely assessed by CT and MRI imaging. In stroke patients, this information is used to characterize brain tissue health, guide blood flow recovery therapies, and predict the onset of hemorrhage. In brain tumor patients, the imaging information is used to characterize cancer growth and used to monitor the response of therapies. However, routine characterization with these techniques involves imaging with the aid of contrast agents, which are detrimental to patients with kidney problems. Arterial spin labeling can measure blood flow without the use of a contrast agent. This proposal will use arterial spin labeling to characterize blood flow to the brain to assess its effectiveness on diagnosing strokes and brain tumors.

(2011-2013) An MRI-Based Muscle-Modeling Tool For Diagnosing Muscle Impairments

Craig H. Meyer, PhD, Associate Professor, Biomedical Engineering and Radiology

Silvia Blemker, Associate Professor, Biomedical Engineering

Mark F. Abel, M.D., Chairman, Orthopedic Surgery

Joe Hart, Ph.D., A.T.C. Orthopedic Surgery

We have developed an image-based modeling suite of tools for imaging muscle and quantifying muscle volumes across the lower extremity. We have demonstrated the utility of this approach in two patient populations: individuals with knee pain and children with cerebral palsy. We now have some initial data demonstrating its potential application to professional athletes. The goal of this phase of the project will be accelerate our progress toward formulation of a startup company.

(2010-2012) Commercialization of the CAVCAM: A “Point & Shoot” Retinal Camera for Use in Primary Care Diabetic Retinopathy Screening

Paul A. Yates, MD, PhD, Department of Ophthalmology

Shayn Peirce-Cottler, PhD, Department of Biomedical Engineering

(2010-2012) Cerebral Perfusion and Blood-Brain Barrier Permeability Assessed Using Arterial Spin Labeling (ASL)

Craig H. Meyer, PhD, Associate Professor, Departments of Biomedical Engineering and Radiology

Max Wintermark, MD, Associate Professor, Departments of Radiology, Neurology, Neurological Surgery and Biomedical Engineering

(2011-2012) S1P Inhibition of Umbilical Cord Blood Stem Cells to Enhance Engraftment

Edward Botchwey, PhD, Biomedical Engineering

Mary J. Laughlin, MD, School of Medicine

Kevin R. Lynch, PhD, Pharmacology

An estimated 128 million individuals, or one in three Americans, could benefit from regenerative medicine involving stem cells. These stem cells may be donated from one patient and transplanted into another to assist in the treatment of brain injury, Type 1diabetes, and cardiovascular damage. In the past 10 years, over 20,000 stem cell transplantations have been made from umbilical cord blood. However, donor engraftment remains an impediment to successful outcomes, particularly among adult patients. The overall objective of this proposal is to manipulate the cell receptors of bone marrow to increase the attachment of umbilical cord-derived stem cells. An increased adhesion of these stem cells to marrow may result in a more successful engraftment. These pre-clinical laboratory studies will be conducted to set the basis for a subsequent FDA investigational new drug application beyond this grant.

(2010-2011) Phage Based Molecular Diagnostics for Tuberculosis

Eric Houpt, MD, Internal Medicine

Kimberly Kelly, PhD, Biomedical Engineering

James Landers, PhD, Biomedical Engineering

Bacteriophage are commonly used as biosensors for human health organisms due to their high specificity, long shelf life, and prevalence. More recently, engineers began altering phage with luminescent or chromogenic substrates for easy detection. However it is often difficult to simultaneously detect for multiple bacteria without manipulating each phage to render a distinct signal. The goal of this project is to use two bacteria specific phage to develop three unique detection assays to for two bacterial pathogens: mycobacterium tuberculosis and E.coli. Mycobacterium tuberculosis is the world’s most deadly bacterial pathogen and accounts for about 2.7% of all deaths. E.coli has been involved in millions of food-borne illnesses, hundreds of thousands of hospitalizations, and thousands of deaths.

(2008-2010) Cytokines as Diagnostic Markers for Prediction of Neonatal Sepsis

Jeff Saucerman, PhD, Biomedical Engineering

Karen Fairchild, MD, Neonatology

Randal Moorman, MD, Cardiology

Late-onset neonatal sepsis affects 20 to 25% of very low birth weight (VLBW) infants, accounting for 45% of late deaths and longer durations of hospitalizations, mechanical ventilation, and antibiotic use. The NICHD Neonatal Network has concluded that “strategies to reduce late infections in VLBW neonates and their medical, social, and economic toll are needed urgently.” Dr. Moorman’s group at UVa has pioneered the development and clinical validation of monitoring heart rate characteristics (HRC) for early detection of neonatal sepsis. This project will incorporate aspects of HRC with cytokines, an important marker during early stage sepsis.

(2008-2010) Determination of the Need for Blood Platelet Transfusion During Cardiopulmonary Bypass Surgery with an Ultrasound-Based Technique for Real-time Blood Viscosity Estimation

Michael Lawrence, PhD, Biomedical Engineering

Gorav Ailawadi, MD, Surgery

A critical need exists for rapid, point of care determination of blood coagulation status during cardiopulmonary bypass procedures. We will use a sensitive blood viscoelastic measure based on ultrasound radiation force to determine the reasons why a patient’s blood does not clot after surgery. This device would be valuable because there are no function-based assays suitable for use in the operating room that have the capability to inform the surgeon as to what the patient needs to return to normal clotting times.

(2008-2010)CardioSolutions: Technologies for Treating In-Stent Restenosis

John Hossack, PhD, Biomedical Engineering

Brian Wamhoff, PhD, Cardiology

Alexander Klibanov, PhD, Internal Medicine

Michael Ragosta, MD, Cardiology

This group intends to develop novel technologies to treat the challenges associated with drug eluting stents. Percutaneous revascularization of diseased blood vessels is currently performed by balloon angioplasty followed by deployment of a metal stent. Maintenance of vessel patency following stent deployment represents a major clinical challenge. Following stent deployment, smooth muscle cells rapidly proliferate and may result in vessel re-narrowing; a clinical process known as in-stent restenosis. To address this, several major medical device companies have developed drug-eluting stents that release anti-proliferative agents. These devices been shown to effectively prevent restenosis and are currently on the US market and have been widely embraced by the interventional cardiology community. Recently, however, it has been observed that drug-eluting stents may be associated with a rare, but increased risk of stent thrombosis (i.e. a blood clot in the stent), a potentially fatal event.

(2009-2010) Self illuminated handheld fundus lens for examination of the retina

Shayn Peirce-Cottler, PhD, Biomedical Engineering

Paul Yates, MD, Ophthalmology

In the United States, there are over 26.8 million diagnosed cases of diabetes, with 1.5 million new cases annually. Close to 40% of these diabetics will develop Diabetic Retinopathy (DR) in their lifetime, the leading cause of adult onset blindness. The only way to promptly detect DR is by routine eye screening, which can help up to 90% of diabetics with DR avoid vision loss. However, cost and interpretation barriers have prohibited establishing a nationwide screening network. The goal of this project is to bring-to-market and clinically implement a novel, low-cost retinal camera technology that can be used within the primary care setting.

(2009-2010) The development of a new cancer bioassay system using the Soft-Plate 96 Technology

Brett Blackman, PhD, Biomedical Engineering

Thomas Parsons, PhD. Department of Microbiology

Todd Bauer, MD, Department of Surgery

There is a need in both the basic research and drug development laboratories for new in vitro approaches to model the microenvironment of cancer cells and assess how that microenvironment impacts response to therapeutic drugs. Thus far, evidence points to the mechanical properties of the tumor microenvironment as a driver of carcinogenesis and metastasis. The goal of this project is to develop a novel throughput assay system for cancer research to uniquely assess the functional characteristics (e.g., growth and death) of tumor cells on substrates with different elastic properties.

(2008-2010)Therapeutic Modification of Myocardial Infarct Anisotropy

Jeff Holmes, MD, Ph.D, Biomedical Engineering

Gorav Ailawadi, MD, Surgery

Currently over 80,000,000 American adults suffer some form of cardiovascular disease. Of these, 10% have myocardial infarction, a severe form of heart attack. This project uses computational modeling to understand the physical stresses on the heart as a result of myocardial infarction. Following the computational modeling, the group will design and optimize novel technologies that are aimed to improve heart mechanics and function.

(2008-2009) Enhanced Targeting of Adipose Stem Cells to Ischemic Injury

Shayn Peirce-Cottler, Ph.D, Biomedical Engineering  

Ellen Keeley, M.D.

This transformative research project will lead to the development and testing of a new commercializable adult stem cell therapy for the treatment of cardiovascular diseases including peripheral vascular disease (PVD), acute myocardial infarction (AMI), and ischemic stroke. Experimental data in animals has long indicated intravenous infusion of stem cells as a viable therapeutic approach for the treatment of ischemic injury. Recently, this has led to the initiation of human clinical trials to treat AMI using both bone marrow stem cells, as well as human adipose stem cells (hASCs). Preliminary data from these trials suggest that stem cell infusion is safe and feasible, although only marginally effective. This limited efficacy is likely a result of the low number of stem cells that incorporate into the injured tissue, representing a potential opportunity for our technology. To address this problem, our team has identified a sub-population of adipose stem cells that are able to target to ischemic blood vessels more effectively than other stem cell populations.

(2008-2009)Targeted Molecular Imaging of Vulnerable Atherosclerotic Plaque

Craig Meyer, PhD, Biomedical Engineering  

David Glover, PhD, Cardiology  

George Beller, MD, Cardiology

The goal of the project is to translate a noninvasive molecular imaging technique to clinical application in the assessment of plaque complication risk and the assessment of myocardial ischemia. To achieve this, the group will develop novel non-invasive imaging methods targeted at a specific marker of vulnerable and advanced atherosclerotic plaque. They will demonstrate targeted molecular imaging of a specific marker in vivo for the first time in a mouse model of atherosclerosis using four different imaging modalities to determine the best one for determining plaque vulnerability. The group will then correlate the marker with other known characteristics of plaque vulnerability.

(2006-2009) Adipose stem cells for the healing of chronic wounds

Shayn Peirce Cottler, PhD, Biomedical Engineering  

Adam Katz, MD, Plastic and Reconstructive Surgery

Cell-based therapies for the treatment of chronic wounds offer a novel, multifaceted approach to complex, multi-factor problem. Adipose stem cells from human fat share many of the same characteristics and behaviors as bone marrow-derived cells, with the added advantages of abundance, ease of harvest, expendability, and appeal. In this early-stage project, Shayn Peirce-Cottler (BME) and Adam Katz (Plastic Surgery) are developing a novel cell-based wound dressing that uses a patient’s own adipose stem cells to re-boot the body’s healing mechanism.

(2008-2009) Subxyphoid Access System for Use With the Epicardial Tool Kit

George Gillies, PhD, Mechanical and Aerospace Engineering with a secondary appointment in BME  

Srijoy Mahapatra, MD, Cardiology

There are currently no minimally invasive tools designed for epicardial electrophysiology via subxiphoid approach, despite its proven utility in treating problems such as heart failure and epicardial ventricular tachycardia. At least 100,000 people in the U.S. could benefit from this procedure if it were more easily available so to address this need we are developing the Epicardial Tool Kit (ETK).

(2008-2009) Comparison of Molecular Imaging Using a Double-Sided Gamma Camera and Contrast Enhanced MRI for Breast Cancer Detection and Characterization

Mark Williams, PhD, Radiology with a secondary appointment in BME  

Brandi Nicholson, MD, Surgery

In recent years, gadolinium-contrast-enhanced MRI (CE-MRI) has been evaluated as a screening tool for women at high risk (at least 20% lifetime risk) of developing breast cancer, and is also being investigated as a problem-solving tool for cases in which mammography and ultrasound are inconclusive. At this time, the primary obstacles to routine use of CE-MRI for breast cancer screening and diagnosis are a) its moderate specificity and poor positive predictive value, b) its high cost, and c) the established linkage between gadolium-based contrast agents and renal failure. Therefore, imaging modalities are being sought with higher specificity and lower cost that could act as an alternate to CE-MRI to improve the specificity of mammography. The purpose of this proposed study is to compare the performance of a unique scanner for molecular breast imaging to that of CE-MRI in the task of breast lesion detection and characterization.

(2006-2008)Real-time cardiac stress testing using MRI

Craig Meyer, PhD, Department of Biomedical Engineering  

Chris Kramer, MD, Radiology/Non-Invasive Cardiology

Magnetic resonance imaging (MRI) is a powerful tool. However, when it comes to ischemic heart disease, existing imaging techniques are limited. Craig Meyer (BME) and Chris Kramer (Radiology) are developing an MRI stress test of the heart using real-time imaging at 30 frames per second – a demanding goal that will be met by combining highly-parallel MRI with spiral kspace techniques. A reliable MRI stress test – capable of providing real-time, consistent, high-quality, and highly detailed images of contraction during ischemic stress – will significantly improve the noninvasive evaluation of ischemic heart disease, the #1 cause of death in the US.

(2007-2008) Novel treatment regimens for the prevention and reversal of heart failure

Brent French, PhD, Department of Biomedical Engineering 

Chris Kramer, MD, Radiology

Drs. French and Kramer have developed a mouse model of heart attack that simulates a patient’s progression to heart failure. They use cardiac MRI to monitor disease progression in this model, and to measure the efficacy of novel drugs against heart failure. Using this system, Drs. French and Kramer have identified a drug that is highly effective in preventing heart failure in mice. Their Coulter project seeks to make this drug available to heart attack patients. Shown at left is a cardiac MRI movie of a normal mouse heart in long-axis orientation.

(2007-2008) Heart rate monitoring enabling closed-loop control in people with type 1 diabetes

Milton Adams, PhD, Department of Biomedical Engineering

Boris Kovatchev, PhD, Psychiatric Medicine 

Eugene Barrett, MD, PhD, Diabetes Center

Increasing scientific and industrial effort is focused on the development of closed-loop systems (artificial pancreas) to control glucose metabolism of people with diabetes, particularly Diabetes Type 1. Experiments are being conducted with continuous glucose monitors (CGM) coupled with insulin pumps and a control algorithm. While such systems have proven feasible in steady metabolic states, they fail during changing metabolic demands, such as meals and physical activity. This innovative team is researching methods to capture physical activity and integrate the data with meals into a CGM.

(2007-2008) Primary evaluation of cardiovascular biomarkers in patients with abdominal aortic aneurysm

Klaus Ley, MD, Department of Biomedical Engineering 

Nancy Harthun, MD, Surgery

Death from ruptured abdominal aortic aneurysm (AAA) is the fifteenth leading killer of men and the twentieth leading killer of women in the United States. Safe treatment is available if the AAA is discovered prior to rupture, however, screening for AAA is in its infancy. The only screening tools currently employed are various types of cross-sectional imaging which is costly and is not likely to be cost-effective for large populations. The goal of the proposed research is to identify one or more proteins that will serve as biomarkers for those with previously undiagnosed aneurysms. The ultimate goal will be to formulate new clinical diagnostic tests that can be performed at low cost in many venues.

(2007-2008) Enhanced radiation therapy using quantum dot photosensitizer conjugates

Brian Helmke, PhD, Department of Biomedical Engineering 

Paul Read, MD, PhD, Radiation Oncology

The leading cause of cancer-related deaths is lung tumors. Although some tumors remain resistant to standard radiation therapy, increasing the dose would cause radiation-related side effects in patients. Additional cell killing by a different mechanism could be achieved by photodynamic therapy (PDT). Drs Helmke and Reed are investigating a method to achieve increased cell death in tumors using quantum dots.

(2007-2008) Bioengineering a novel delivery method for dry eye

Ed Botchwey, PhD, Department of Biomedical Engineering 

Gordon Laurie, PhD, Cell Biology 

Roy Ogle, PhD, Medicine 

Brian Conway, MD, Ophthalmology

Dry eye is the most common eye disease affecting up to 10% of the population. Current treatment comprises saline-based ophthalmic solutions of different viscosity as ‘artificial tears’ but patients are unhappy with the brevity of relief and are vocal for more advanced approaches. Drs. Botchwey, Laurie and Conway are researching a delivery method that slowly releases bioactive ‘lacritin’ will offer relief of dry eye.

(2006-2007) Quantitative unbiased immunohistochemical signaling pathway analysis (QUISPA): Development and application of therapy-directed classification of malignant gliomas

Jason Papin, PhD, Biomedical Engineering 

James Mandell, MD, PhD, Pathology 

David Schiff, MD, Neurology

This early stage project tackles the complex web of signaling in cancer. Jason Papin (BME), James Mandell (Pathology), and David Schiff (Neurology) are working to develop computational tools to make better, unbiased diagnoses and better predictions of ideal drug targets. The initial focus is on a particularly aggressive form of brain cancer, but research will expand to other types of cancer within the framework.

(2006-2007) Ear tube insertion device

Shayn Peirce-Cottler, PhD, Biomedical Engineering 

Bradley Kesser, MD, Otolaryngology

This late stage to very-late stage project will lead to a new device for inserting ventilation tubes in the ears of patients, usually children, suffering from chronic OME, or chronic fluid in the middle ear. Shayn Peirce-Cottler (BME) and Brad Kesser (Otolaryngology) are building a better mousetrap: They are replacing a tray full of instruments and a technically challenging procedure with a one-handed device to perform two key tasks (tube insertion and fluid suction) in a single pass. A 1st-generation device was developed in 2006 as a BME undergraduate design project.