U-M research center spurs new approach to musculoskeletal health

ANN ARBOR – A promising new approach to musculoskeletal disease that focuses on the interactions between body systems like bone and muscle is a top priority at the newly established Michigan Integrative Musculoskeletal Health Core Center.

Led by Karl Jepsen, the Henry Ruppenthal Family Professor for Orthopaedic Surgery and Bioengineering and a biomedical engineering professor at the University of Michigan, the center is spearheading a research model that looks at bone, muscle and connective tissue as a single system instead of individual components. It’s funded by a $3.9 million grant from the National Institutes of Health and brings together 60 faculty members from seven schools across the University of Michigan to accelerate new cross-disciplinary research between engineers, doctors and others throughout the university.

Jepsen believes that their efforts could help doctors take action early, enabling more patients to avoid musculoskeletal disease rather than waiting until after disease and injury risk develop. It could also help people avoid maladies like bone fractures and stay more active, improving overall quality of life.

U-M schools involved with center include the School of Medicine, School of Dentistry, Michigan Engineering, School of Kinesiology, Life Sciences Institute, School of Public Health and College of Literature, Science and the Arts.

Jepsen says the new center will provide researchers with access to equipment and other resources, as well as opportunities to collaborate as they study the interactions among the body’s systems. They aim to develop treatments that help patients maintain bone, muscle, tendon, ligament and cartilage health over a lifetime rather than reacting to individual health problems as they occur.

“The field is moving toward a more integrative approach, and we have a diverse group of people at U-M who are doing the world’s best bone and muscle research. Our work with osteoporosis is just one example” Jepsen said. “Our goal is to make sure those departments are talking to each other so that collectively, we can make the maximum impact in these areas.”

The center will help enable interdisciplinary studies across U-M. In Jepsen’s own work with collaborators at the School of Public Health, the team is scouring a database with anonymized medical records dating back decades for thousands of women. Researchers are looking at patients’ entire musculoskeletal systems to identify red flags that lead to osteoarthritis and osteoporosis and bone fractures later in life.

“Ideally, we want to move the diagnostic process for diseases like osteoporosis into people’s 40s, instead of waiting until they’re in their 60s and have already lost much of their muscle mass,” Jepsen said. “We want to change the focus from a reactive to a proactive approach, helping people maintain their bone-muscle system so that it’s prepared to age well.”

Other examples of cross-disciplinary work at the center include research into new three-dimensional imaging techniques for cartilage that could lead to more effective arthritis treatments. Today, cartilage imaging is mostly limited to two-dimensional visual slices; Jepsen believes that improved techniques could help doctors get a better look at how arthritis affects the body.

“Cartilage is mostly water, so it’s very difficult to get good imaging,” Jepsen said. “Three-dimensional imaging would give us a much better picture of how arthritis progresses in a patient; how big the damage is, how deep it is and how it changes the overall bone surface.”

The center will focus on three main goals:

  • Enabling center investigators to conduct vertically-oriented science from the molecular level to the organ/functional level
  • Creating new opportunities for collaboration, training and mentorship
  • Promoting opportunities for novel and emerging science by focusing on research between basic scientists and clinicians, studies on sex-specific differences and interactions among tissues

Three main research cores within the center will focus on histological assessment, structural and compositional assessment and functional assessment. The cores move from molecular mechanisms through functional outcomes.

“This is an exciting time for those of us in musculoskeletal research,” Jepsen says. “Greater interactions between basic scientists and clinicians are important to the future of medicine and the care we will be able to provide to patients in the years to come.”

Source:

  • By: Gabe Cherry, Michigan Engineering
  • Original Publication: http://www.engin.umich.edu/college/about/news/stories/2016/october/u-m-research-center-spurs-new-approach-to-musculoskeletal-health

Turning blood into a laser emitter for drug testing, cancer treatment

University of Michigan researchers have successfully demonstrated a new technique that combines laser light with an FDA-approved fluorescent dye to monitor cell structure and activity at the molecular level. This could lead to improved clinical imaging and better monitoring of tumors and other cell structures. It could also be used during drug testing to monitor the changes that cells undergo when exposed to prospective new drugs.

The team, led by Biomedical Engineering professor Xudong (Sherman) Fan, shined laser light into a small laser cavity containing whole human blood infused with Indocyanine green, an FDA-approved fluorescent dye. By analyzing the light that was reflected back out, researchers observed cell structures and changes within the blood on the molecular level.

A key advantage of the new technique over current methods is the ability to process laser light—it can be amplified to make small changes easier to see or filtered to remove unwanted background noise. Current methods use similar dyes with infrared or visible light, relying on visible fluorescence to observe cell activity and making small changes can be difficult to see.

Currently, the researchers have only demonstrated the technique on whole blood outside the body. But they predict that in the future, they may be able to use it on tissue inside the body. This could enable better monitoring of cell activity and tissue properties inside the body, or enable a surgeon to precisely identify the edge of a tumor during guided surgery.

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$3.46M to Combine Supercomputer Simulations with Big Data

A new way of computing could lead to immediate advances in aerodynamics, climate science, cosmology, materials science and cardiovascular research. The National Science Foundation is providing $2.42 million to develop a unique facility for refining complex, physics-based computer models with big data techniques at the University of Michigan, with the university providing an additional $1.04 million.

The focal point of the project will be a new computing resource, called ConFlux, which is designed to enable supercomputer simulations to interface with large datasets while running. This capability will close a gap in the U.S. research computing infrastructure and place U-M at the forefront of the emerging field of data-driven physics. The new Center for Data-Driven Computational Physics will build and manage ConFlux.

Turbulence simulations for a vortex such as a tornado, a galaxy, or the swirls that form at the tips of airplane wings. Courtesy of Karthik Duraisamy, Aerospace Engineering.

Turbulence simulations for a vortex such as a tornado, a galaxy, or the swirls that form at the tips of airplane wings. Courtesy of Karthik Duraisamy, Aerospace Engineering.

Turbulence simulations for a vortex such as a tornado, a galaxy, or the swirls that form at the tips of airplane wings. Courtesy of Karthik Duraisamy, Aerospace Engineering.

Turbulence simulations for a vortex such as a tornado, a galaxy, or the swirls that form at the tips of airplane wings. Courtesy of Karthik Duraisamy, Aerospace Engineering.

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The project will add supercomputing nodes designed specifically to enable data-intensive operations. The nodes will be equipped with next-generation central and graphics processing units, large memories and ultra-fast interconnects.

A three petabyte hard drive will seamlessly handle both traditional and big data storage. Advanced Research Computing – Technology Services at University of Michigan provided critical support in defining the technical requirements of ConFlux. The project exemplifies the objectives of President Obama’s new National Strategic Computing Initiative, which has called for the use of vast data sets in addition to increasing brute force computing power.

The common challenge among the five main studies in the grant is a matter of scale. The processes of interest can be traced back to the behaviors of atoms and molecules, billions of times smaller than the human-scale or larger questions that researchers want to answer.

Even the most powerful computer in the world cannot handle these calculations without resorting to approximations, said Karthik Duraisamy, an assistant professor of aerospace engineering and director of the new center. “Such a disparity of scales exists in many problems of interest to scientists and engineers,” he said.

But approximate models often aren’t accurate enough to answer many important questions in science, engineering and medicine. “We need to leverage the availability of past and present data to refine and improve existing models,” Duraisamy explained.

Turbulence simulations for a vortex such as a tornado, a galaxy, or the swirls that form at the tips of airplane wings. Courtesy of Karthik Duraisamy, Aerospace Engineering.

Data from hospital scans, when fed into a computer model of blood flow, can become a powerful predictor of cardiovascular disease. Courtesy of Alberto Figueroa, Biomedical Engineering.

Turbulence simulations for a vortex such as a tornado, a galaxy, or the swirls that form at the tips of airplane wings. Courtesy of Karthik Duraisamy, Aerospace Engineering.

Data from hospital scans, when fed into a computer model of blood flow, can become a powerful predictor of cardiovascular disease. Courtesy of Alberto Figueroa, Biomedical Engineering.

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This data could come from accurate simulations with a limited scope, small enough to be practical on existing supercomputers, as well as from experiments and measurements. The new computing nodes will be optimized for operations such as feeding data from the hard drive into algorithms that use the data to make predictions, a technique known as machine learning.

“Big data is typically associated with web analytics, social networks and online advertising. ConFlux will be a unique facility specifically designed for physical modeling using massive volumes of data,” said Barzan Mozafari, an assistant professor of computer science and engineering, who will oversee the implementation of the new computing technology.

The faculty members spearheading this project come from departments across the University, but all are members of the Michigan Institute for Computational Discovery and Engineering (MICDE), which was launched in 2013.

“MICDE is the home at U-M of the so-called third pillar of scientific discovery, computational science, which has taken its place alongside theory and experiment,” said Krishna Garikipati, MICDE’s associate director for research.

The following projects will be the first to utilize the new computing capabilities:

  • Cardiovascular disease. Noninvasive imaging such as MRI and CT scans could enable doctors to deduce the stiffness of a patient’s arteries, a strong predictor of diseases such as hypertension. By combining the scan results with a physical model of blood flow, doctors could have an estimate for arterial stiffness within an hour of the scan. The study is led by Alberto Figueroa, the Edward B. Diethrich M.D. Research Professor of Biomedical Engineering and Vascular Surgery.
  • Turbulence. When a flow of air or water breaks up into swirls and eddies, the pure physics equations become too complex to solve. But more accurate turbulence simulation would speed up the development of more efficient airplane designs. It will also improve weather forecasting, climate science and other fields that involve the flow of liquids or gases. Duraisamy leads this project.
  • Clouds, rainfall and climate. Clouds play a central role in whether the atmosphere retains or releases heat. Wind, temperature, land use and particulates such as smoke, pollen and air pollution all affect cloud formation and precipitation. Derek Posselt, an associate professor of atmospheric, oceanic and space sciences, and his team plan to use computer models to determine how clouds and precipitation respond to changes in the climate in particular regions and seasons.
  • Dark matter and dark energy. Dark matter and dark energy are estimated to make up about 96 percent of the universe. Galaxies should trace the invisible structure of dark matter that stretches across the universe, but the formation of galaxies plays by additional rules – it’s not as simple as connecting the dots. Simulations of galaxy formation, informed by data from large galaxy-mapping studies, should better represent the roles of dark matter and dark energy in the history of the universe. August Evrard and Christopher Miller, professors of physics and astronomy, lead this study.
  • Material property prediction. Material scientists would like to be able to predict a material’s properties based on its chemical composition and structure, but supercomputers aren’t powerful enough to scale atom-level interactions up to bulk qualities such as strength, brittleness or chemical stability. An effort led by Garikipati and Vikram Gavini, a professor and an associate professor of mechanical engineering, respectively, will combine existing theories with the help of data on material structure and properties.

“It will enable a fundamentally new description of material behavior—guided by theory, but respectful of the cold facts of the data. Wholly new materials that transcend metals, polymers or ceramics can then be designed with applications ranging from tissue replacement to space travel,” said Garikipati, who is also a professor of mathematics.