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Pitt | Swanson Engineering
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Feb

Feb
25
2020

Pitt bioengineer finds support for female pelvic floor research

Bioengineering

PITTSBURGH (Feb. 25, 2020) … A paper published by Steven Abramowitch, associate professor of bioengineering at the University of Pittsburgh, was recently recognized by the editors of the Journal of Biomechanical Engineering (JBME) for exemplifying high quality and significant work (DOI: 10.1115/1.4041743). The article details complications associated with mechanical loads on synthetic mesh used in pelvic organ prolapse and will be listed as an Editors’ Choice paper in JBME’s Annual Special Issue February 2020. William Barone, a bioengineering graduate alumnus, contributed as first author on this paper. Pelvic organ prolapse (POP) is a condition where the organs in the pelvis push against the vagina, creating a “bulge” that can extend outside of the body. It results from a weakening of the muscles and tissues that help support the pelvic organs. Despite the fact that 12.6 percent of women in the U.S. will undergo major surgery for POP by the age of 80,1 most of the studies surrounding these devices were conducted as they are applied to hernias in the abdomen. According to recent research, pelvic floor applications using this technology seem to be more vulnerable to mesh-related complications. Abramowitch’s research in the Swanson School of Engineering and the Center for Interdisciplinary Research in Female Pelvic Health uses experimental and computational methods to examine the mechanical behavior of mesh so that it can be optimized for the female pelvic floor environment. “The textile and structural properties of mesh have proven to be an important factor in its efficacy – particularly the pore size, which has shown to increase complications when less than 1mm in size,” said Abramowitch. “Even though these devices are widely used, the in vivo mechanical behavior of synthetic mesh is largely unknown, as is the impact of its mechanics on surrounding biological tissues.” Though most vaginal mesh is developed with pore sizes large enough to minimize complications, researchers have recently discovered that mechanical loading significantly alters pore dimensions. While previous studies have looked at the effects of uniaxial loading, Abramowitch and his group are broadening research in this area by quantifying multiaxial loading. “Transvaginal meshes, which are most commonly associated with complications and have been recently banned from use in the United States, are fixed at multiple locations in the pelvis. This creates multi-directional forces that cause the mesh to change shape in specific regions,” he explained. “Interestingly, our simulations predict the locations where the most shape change occurs, and they happen to be consistent with the most common sites for complications. This gives us a great possible lead to better understanding the mechanisms that cause mesh complications.” Abramowitch’s group developed an experimental model to quantify pore dimensions in response to clinically relevant mechanical forces and a computational model to simulate the mechanical behavior of transvaginal mesh in response to these forces. By developing these models, they will be able to examine a wide range of mechanical conditions, predict mesh behavior, and eventually optimize devices for the female pelvic floor. This research recently led to a $2,500,000 award from the National Institutes of Health to create a novel repair device designed for the vagina that may improve outcomes in POP surgery. Abramowitch and Pamela Moalli, professor of obstetrics, gynecology, and reproductive sciences at Pitt and pelvic reconstructive surgeon at UPMC Magee-Womens Hospital, will lead this effort. # # # This work was funded by grants from the National Institutes of Health (R01 HD-045590, K12HD-043441) and the National Science Foundation Graduate Research Fellowship (DGE-0753293). 1 Wu JM, Matthews CA, Conover MM, Pate V, Jonsson Funk M. Lifetime risk of stress urinary incontinence or pelvic organ prolapse surgery. Obstet Gynecol. 2014;123(6):1201-6. Epub 2014/05/09. doi: 10.1097/AOG.0000000000000286. PubMed PMID: 24807341; PubMed Central PMCID: PMCPMC4174312.

Feb
20
2020

Kozai Co-Chairs 2020 Gordon Research Conference to Foster Collaborations in Neural Engineering

Bioengineering

PITTSBURGH (Feb. 20, 2020) … Neuroelectronic interfaces are the foundation of technology that connects the human mind to machine and helps to restore motor and sensory function to individuals with neurological diseases and disorders. This technology has been introduced as a successful treatment to the clinical environment, but issues with device stability and longevity remain. The 2020 Gordon Research Conference (GRC) on Neuroelectronic Interfaces will bring together a multidisciplinary group of scientists and engineers to address challenges in this area and collectively discuss how to drive innovation for next-generation devices. Takashi D-Y Kozai, assistant professor of bioengineering at the University of Pittsburgh, will co-chair the event in Ventura, California, March 15-20, 2020. “The challenges with this technology have been long-standing and complex to solve. It requires fundamentally understanding the problem from both biological and engineering perspectives,”  said Kozai, who helms the Bio-Integrating Optoelectric Neural Interface Cybernetics Lab in the Swanson School of Engineering. “Therefore, the goal of this GRC is to bring together fundamental neuroscientists, brain neurophysiologists, brain biocompatibility experts, material scientists, electrical engineers, clinical neural engineers, and clinical scientists to really understand what the fundamental problems and needs are for these neural interface technologies. “The Gordon Research Conference format is conducive to this type of problem solving and innovation as it brings experts together for a week in an intimate setting,” he continued. “This conference has seeded many new collaborations and new directions in neural engineering.” Pitt is no stranger to multidisciplinary research in this area, and this year’s GRC on Neuroelectronic Interfaces will feature presentations from five professors, each representing different departments at the University: Robert Gaunt (Physical Medicine and Rehabilitation Sciences) "Bidirectional Brain Computer Interfaces: Science and Function" Douglas Weber (Bioengineering) "Recording and Stimulating Sensory Neurons in Dorsal Root Ganglia and Spinal Cord" Elizabeth Tyler-Kabara (Neurological Surgery) "Longevity of Intracranial Recordings for BCI" Franca Cambi (Neurology) "The Role of Myelin and Oligodendrocytes in Neural Function and Repair: Implications for Recording Devices" Alberto Vazquez (Radiology) "Optogenetic Assessment of the Contribution of Neuronal Populations to Tissue Metabolic Load and Blood Flow Regulation: Vulnerable Neuronal Populations to Brain Injury" In the past year, Swanson School faculty have received notable awards in this field of research: Kozai received $1,600,000 from the National Institutes of Health (NIH) to develop an innovative wireless neural device for long-term and precise stimulation; and Xinyan Tracy Cui, professor of bioengineering, developed a coating that improves the performance of microelectrode array technology and was awarded a $2,370,218 NIH grant. Douglas Weber, associate professor of bioengineering, and his colleagues in the Rehab Neural Engineering Labs will collaborate on a $20,000,000 Defense Advanced Research Projects Agency (DARPA) grant to develop non-invasive wearable technologies for able-bodied individuals. “We’ve received tremendous support for this conference from the University of Pittsburgh, as well as our industry and foundation partners,” said Kozai. “The level and number of sponsoring partners highlight how important these collaborations are in achieving high-quality work and realizing the full potential of this pioneering and life-changing technology. The leadership at Pitt has cultivated an environment for excellent multidisciplinary research collaborations.” This GRC will be held in conjunction with the "Neuroelectronic Interfaces (GRS): Creating a Roadmap to Translating Neural Technologies" Gordon Research Seminar (GRS). # # #

Feb
19
2020

Undergrad Innovators Design Wearable Device to Aid People in Posture

Bioengineering, Student Profiles

This story is reprinted from Pittwire Health. Click here to view the original post. In the Classroom to Community Design Lab in the Department of Bioengineering on the fourth floor of Benedum Hall, Jacob Meadows tries on a vest-like device. He bends forward slightly as the device vibrates and a red light on the vest’s shoulder flickers on and off. “This is our first iteration prototype from two years ago, which features a light for demonstration during presentations.” said the bioengineering senior in Pitt’s Swanson School of Engineering. Meadows and fellow bioengineering senior Tyler Bray have been developing this wearable device, Posture Protect, to help people with movement disorders like Parkinson’s disease, as well as their physical therapists. Meadows and Bray are among six teams of student innovators supported by the Classroom to Community program, a new initiative directed by bioengineering assistant professor Joseph Samosky and funded by Pitt’s Office of the Provost. The program helps mentor and bridge potential high-impact student projects from the classroom toward real-world impact. The duo has been working on Posture Protect since 2017 when they first developed their idea and prototype as a capstone project in the course “The Art of Making: A Hands-on Introduction to Systems Design and Engineering”—a human-centered design course taught by Samosky. Bray’s grandmother was diagnosed with a stroke that semester, which spurred the idea to help people with fine motor control problems. In their research, they learned that people with Parkinson’s disease share similar issues and honed their focus. “We sat in on fitness classes at a local boxing gym specifically for people with Parkinson’s disease and we learned that people with that disease struggle daily with posture,” Bray said. “We hadn’t really heard of that before because most people just associate it with hand tremors. We followed up with physical therapists who confirmed that this was true and important because it increases their risk of falls.” The team has been experimenting with different designs, including vests, necklaces and one that rests comfortably on the user’s shoulders. And while people with Parkinson’s disease and stroke may have been the impetus for Posture Protect, the device can also be used by people with other conditions that affect postural control, such as multiple sclerosis. When the user of the device bends over or slouches for a certain period of time, the wearable device will vibrate, informing the user that they are in poor posture. The student innovators say the final product aims to be unobtrusive, preventing unwanted attention. The team’s highly successful capstone project in The Art of Making led to their winning the top award for “Best Overall Design” at the 2017 Swanson School of Engineering Design Expo. The two were then introduced to the Big Idea Center, part of Pitt’s Innovation Institute. The center is a hub for student innovation and entrepreneurship on Pitt’s campus. Posture Protect has made progress in the center’s programs, including the most recent program, the Forge student incubator, which is supported by Pitt Seed funding. "We hadn’t thought about the business side of things before the Innovation Institute’s programs. Being able to get this out of the lab and to the people has been helpful for understanding better who our actual customer might be." - Jacob Meadows “This is an example of a couple of students who really keep going; they haven’t gotten discouraged and have been working steadily with our entrepreneurs-in-residence,” said Babs Carryer, the center’s director. “They’re persistent and it’s been great seeing how far they’ve come in the past two years. I have high hopes for them in future competitions. The persistent student entrepreneurs here usually do best because they take what they learn from previous programs and apply them to their products and business analysis for future competitions.” Meadows and Bray have been working with the center to advance their product development, participating in competitions such as the Randall Family Big Idea Competition, the Startup Blitz and the Michael G. Wells Competition. They are entered into this year’s Randall competition and in April, will take Posture Protect to the ACC InVenture Prize Competition at North Carolina State University. They also plan to start a pilot program with local physical therapists and their patients soon. “We’ve learned a lot about the innovation process as a whole: designing the product, showing it to people to get feedback, understanding business use cases and learning which initial target market may be the best,” said Meadows. “We hadn’t thought about the business side of things before the Innovation Institute’s programs. Being able to get this out of the lab and to the people has been helpful for understanding better who our actual customer might be.” “The Big Idea Center has really helped us round out our experience and our education in terms of product development,” Bray added. “As engineers, we can design and build whatever we want, and we’ve learned some unique ways to do that. But once we graduate, so much of that is driven by business, and to be able to understand how that side of things work is extremely valuable.”

Feb
19
2020

Bryan Brown Featured in the Products of Pittsburgh Podcast

Bioengineering

This story is reposted from the Clinical & Translational Science Institute. Click here to view the original post. The Products of Pittsburgh podcast is about the people in Pittsburgh – innovators, scientists, community leaders – and the remarkable stories behind how they came to be and the work they have produced. In 2001, Bryan Brown came to Pittsburgh to study mechanical engineering at the University of Pittsburgh where he would go on to obtain his PhD in bioengineering and become a faculty member at the university.    From winning multiple awards to co-founding a company, Bryan is well on his way to making an impact on health care innovation. About BrownBryan Brown, PhD is an Associate Professor of Bioengineering with secondary appointments in Obstetrics, Gynecology, and Reproductive Sciences as well as Clinical and Translational Sciences at the University of Pittsburgh.  He’s a core faculty member of the McGowan Institute for Regenerative Medicine where he serves as Director of Educational Outreach. He is a two time Pitt Innovation Challenge awardee and serves as Chief Technology Officer of Renerva, LLC, a Pitt start-up company that he co-founded.  Brown received both his B.S. and PhD from the University of Pittsburgh.

Feb
4
2020

Pitt’s Center for Medical Innovation awards three novel biomedical projects with $47,500 in Round 2 2019 Pilot Funding

Bioengineering

PITTSBURGH (January 31, 2020) … The University of Pittsburgh’s Center for Medical Innovation (CMI) awarded grants totaling $47,500 to three research groups through its 2019 Round-2 Pilot Funding Program for Early Stage Medical Technology Research and Development. The latest funding proposals include a system for preservation of explanted hearts used in transplantation surgery, a new vascular stent with anti-thrombogenic capability, and a rugged, infection resistant material for orthopedic implants. CMI, a University Center housed in Pitt’s Swanson School of Engineering (SSOE), supports applied technology projects in the early stages of development with “kickstart” funding toward the goal of transitioning the research to clinical adoption. Proposals are evaluated on the basis of scientific merit, technical and clinical relevance, potential health care impact and significance, experience of the investigators, and potential in obtaining further financial investment to translate the particular solution to healthcare. “This is our eighth year of pilot funding, and our leadership team could not be more excited with the breadth and depth of this round’s awardees,” said Alan D. Hirschman, PhD, CMI Executive Director. “This early-stage interdisciplinary research helps to develop highly specific biomedical technologies through a proven strategy of linking UPMC’s clinicians and surgeons with the Swanson School’s engineering faculty.” AWARD 1: “A Structurally and Mechanically Tunable Biocarpet for Peripheral Arterial Disease” For the development of a material and method of deployment of specialized materials that coat the inner lumen of synthetic vascular grafts. The coating will greatly improve the viability and anti-thrombogenic properties of long stent grafts which overlap flexible joints. Jonathan P. Vande Geest, PhD, Professor of Bioengineering, Swanson School of Engineering William R. Wagner, PhD, Professor of Surgery and Bioengineering, Surgery, McGowan Institute for Regenerative Medicine Dr. John J. Pacella, MD, Assistant Professor in the School of Medicine, UPMC AWARD 2: “Ex-Vivo Heart Perfusion System for Human Heart Support, Resuscitation, and Physiologic Testing” For the development of a system for preservation of explanted donor hearts suitable for transplantation. Includes means to verify the heart’s mechanical and biological viability to improve recipient response. Christopher Sciortino, MD, PhD; Dept of Cardiothoracic Surgery; UPMC Harvey S. Borovetz, PhD; Dept of Bioengineering; Swanson School of Engineering Rick Shaub, PhD; UPMC Artificial Heart Program; UPMC Garrett Coyan, MD, Dept of Cardiothoracic Surgery; UPMC AWARD 3: “In Vivo Efficacy of an Antibacterial and Biocompatible Polymeric Nanofilm on Titanium Implants” For the development of biocompatible, anti-biofilm coatings for orthopedic use, especially in children. Houssam Bouloussa, MD, MS,  Pediatric Orthopedic Surgery, Children’s Hospital of Pittsburgh Michael McClincy, MD, Assistant Professor, Department of Orthopedic Surgery, UPMC Prashant Kumta, PhD, Professor of Bioengineering, Swanson School of Engineering ### About the University of Pittsburgh Center for Medical Innovation The Center for Medical Innovation is a collaboration among the Swanson School of Engineering, the Clinical and Translational Science Institute (CTSI), the Innovation Institute, and the Coulter Translational Research Partnership II (CTRP). CMI was established in 2012 to promote the application and development of innovative biomedical technologies to clinical problems; to educate the next generation of innovators in cooperation with the schools of Engineering, Health Sciences, Business, and Law; and to facilitate the translation of innovative biomedical technologies into marketable products and services. Over 70 early-stage projects have been supported by CMI with a total investment of over $1.4 million since inception.
Alan Hirschman, PhD, Executive Director, CMI

Jan

Jan
31
2020

Got Slime? Using Regenerative Biology to Restore Mucus Production

Bioengineering

PITTSBURGH (Jan. 31, 2020) … Let’s talk about slime. Mucus is a protective, slimy secretion produced by goblet cells and which lines organs of the respiratory, digestive, and reproductive systems. Slime production is essential to health, and an imbalance can be life-threatening. Patients with diseases such as asthma, chronic obstructive pulmonary disease (COPD), and ulcerative colitis produce too much mucus, often after growing too many goblet cells. Loss of goblet cells can be equally devastating - for instance during cancer, after infection, or injury. The balance of slime creation, amount, and transport is critical, so doctors and medical researchers have long sought the origins of goblet cells and have been eager to control processes that regenerate them and maintain balanced populations. Recently, a group of bioengineers at the University of Pittsburgh discovered a case of goblet cell regeneration that is both easily accessible and happens incredibly fast on cells isolated from early developing frog embryos. Their findings were published this week in the journal Nature Communications (DOI: 10.1038/s41467-020-14385-y). Lance Davidson, William Kepler Whiteford Professor of Bioengineering at Pitt, leads the MechMorpho Lab in the Swanson School of Engineering where his researchers study the role of mechanics in human cells as well as the Xenopus embryo - an aquatic frog native to South Africa. “The Xenopus tadpole, like many frogs, has a respiratory skin that can exchange oxygen and perform tasks similar to a human lung,” explained Davidson. “Like the human lung, the surface of the Xenopus respiratory skin is a mucociliated epithelium, which is a tissue formed from goblet cells and ciliated cells that also protects the larva against pathogens. Because of these evolutionary similarities, our group uses frog embryonic organoids to examine how tissue mechanics impact cell growth and tissue formation.” Studying this species is a rapid and cost-effective way to explore the genetic origins of biomechanics and how mechanical cues are sensed, not just in the frog embryo, but universally. When clinicians study cancer in patients, such changes can take weeks, months, or even years, but in a frog embryo, changes happen within hours. “In this project, we took a group of mesenchymal cells out of the early embryo and formed them into a spherical aggregate, and within five hours, they began to change,” Davidson said. “These cells are known to differentiate into a variety of types, but in this scenario, we discovered that they changed very dramatically into a type of cell that they would not have changed into had they been in the embryo.” The lab surprisingly uncovered a case of regeneration that restores a mucociliated epithelium from mesenchymal cells. They performed the experiment multiple times to confirm the unexpected findings and began to look closely at what microenvironmental cues could drive cells into an entirely new type. “We have tools to modulate the mechanical microenvironment that houses the cells, and to our surprise, we found that if we made the environment stiffer, the aggregates changed into these epithelial cells,” explained Davidson. “If we made it softer, we were able to block them from changing. This finding shows that mechanics alone can cause important changes in the cells, and that is a remarkable thing.” Davidson’s group is interested in how cells, influenced by mechanics, may affect disease states. The results detailed in this article may drive new questions in cancer biology, prompting researchers to consider whether certain kinds of invasive cancer cells might revert to a resting cell type based on the stiffness or softness of their surroundings. “When applying these results to cancer biology, one might ask, ‘If tumors are surrounded by soft tissues, would they become dormant and basically non-invasive?’ Or, ‘If you have them in stiff tissues, would they invade and become deadly?’” said Davidson. “These are major questions in the field that biomechanics may be able to help answer. Many researchers focus solely on the chemical pathways, but we are also finding mechanical influencers of disease.” Hye Young Kim, a young scientist fellow at Institute for Basic Science (IBS) and former member of the MechMorpho Lab, will continue this work at the Center for Vascular Research located at Korea Advanced Institute of Science and Technology (KAIST). She will study how cell motility changes during regeneration and how epithelial cells assemble a new epithelium. Davidson and his lab will explore how this novel case of mechanical cues are sensed by mesenchymal cells and how these mechanical induction pathways are integrated with known pathways that control cell fate choices. "Frog embryos and organoids give us unparalleled access to study these processes, far more access than is possible with human organs,” he said. “The old ideas that regeneration is controlled exclusively by diffusing growth factors and hormones is giving way to the recognition that the physical mechanics of the environment – such as how rubbery or fluid the environment -  play just as critical a role." ### This research was supported by a grant from the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health. Image caption: "Green Slime covers the surface of a tadpole (bottom) and a goblet-cell regenerated aggregate (top, not the same scale). The images show the molecule intelectin-1, an important factor in tadpole skin, and one of the slime factors synthesized and secreted by goblet cells (single goblet cells can be seen in the aggregate). In human lung, intelectin-1 binds bacteria and is on the front line of the innate immune system. Images courtesy of Hye Young Kim and Lance Davidson."

Jan
22
2020

Researchers Regrow Damaged Nerves with Polymer and Protein

Bioengineering

Reposted with permission from UPMC. Click here to view the original press release. PITTSBURGH, Jan. 22, 2020 –University of Pittsburgh School of Medicine researchers have created a biodegradable nerve guide — a polymer tube — filled with growth-promoting protein that can regenerate long sections of damaged nerves, without the need for transplanting stem cells or a donor nerve. So far, the technology has been tested in monkeys, and the results of those experiments appeared today in Science Translational Medicine. “We’re the first to show a nerve guide without any cells was able to bridge a large, 2-inch gap between the nerve stump and its target muscle,” said senior author Kacey Marra, Ph.D., professor of plastic surgery at Pitt and core faculty at the McGowan Institute for Regenerative Medicine. “Our guide was comparable to, and in some ways better than, a nerve graft.” Half of wounded American soldiers return home with injuries to their arms and legs, which aren’t well protected by body armor, often resulting in damaged nerves and disability. Among civilians, car crashes, machinery accidents, cancer treatment, diabetes and even birth trauma can cause significant nerve damage, affecting more than 20 million Americans. Peripheral nerves can regrow up to a third of an inch on their own, but if the damaged section is longer than that, the nerve can’t find its target. Often, the disoriented nerve gets knotted into a painful ball called a neuroma. The most common treatment for longer segments of nerve damage is to remove a skinny sensory nerve at the back of the leg — which causes numbness in the leg and other complications, but has the least chance of being missed — chop it into thirds, bundle the pieces together and then sew them to the end of the damaged motor nerve, usually in the arm. But only about 40 to 60% of the motor function typically returns. “It’s like you’re replacing a piece of linguini with a bundle of angel hair pasta,” Marra said. “It just doesn’t work as well.” Marra’s nerve guide returned about 80% of fine motor control in the thumbs of four monkeys, each with a 2-inch nerve gap in the forearm. The guide is made of the same material as dissolvable sutures and peppered with a growth-promoting protein — the same one delivered to the brain in a recent Parkinson’s trial — which releases slowly over the course of months. The experiment had two controls: an empty polymer tube and a nerve graft. Since monkeys’ legs are relatively short, the usual clinical procedure of removing and dicing a leg nerve wouldn’t work. So, the scientists removed a 2-inch segment of nerve from the forearm, flipped it around and sewed it into place, replacing linguini with linguini, and setting a high bar for the nerve guide to match. Functional recovery was just as good with Marra’s guide as it was with this best-case-scenario graft, and the guide outperformed the graft when it came to restoring nerve conduction and replenishing Schwann cells — the insulating layer around nerves that boosts electrical signals and supports regeneration. In both scenarios, it took a year for the nerve to regrow. The empty guide performed significantly worse all around. With these promising results in monkeys, Marra wants to bring her nerve guide to human patients. She’s working with the Food and Drug Administration (FDA) on a first-in-human clinical trial and spinning out a startup company, AxoMax Technologies Inc. “There are no hollow tubes on the market that are approved by the FDA for nerve gaps greater than an inch. Once you get past that, no off-the-shelf tube has been shown to work,” Marra said. “That’s what’s amazing here.” Additional authors on the study include Neil Fadia, Jacqueline Bliley, Gabriella DiBernardo, Donald Crammond, Ph.D., Benjamin Schilling, Wesley Sivak, M.D., Ph.D., Alexander Spiess, M.D., Kia Washington, M.D., Matthias Waldner, M.D., Liao Han Tsung, Ph.D., Isaac James, M.D., Danielle Minteer, Ph.D., Casey Tompkins-Rhoades, Deok-Yeol Kim, Riccardo Schweizer, M.D., Debra Bourne, M.D., Adam Cottrill, George Panagis, Asher Schusterman, M.D., Francesco Egro, M.D., Insiyah Campwala, Tyler Simpson, M.S., Douglas Weber, Ph.D., Trent Gause, M.D., Jack Brooker, Tvisha Josyula, Astrid Guevara, Alexander Repko and Christopher Mahoney, all of Pitt. This study was funded by the Armed Forces Institute of Regenerative Medicine (award number W81XWH-14-2-0003). MedGenesis Therapeutix Inc. supplied the growth-promoting protein. Axomax Technologies was formed after the experiments were completed. For additional multimedia, contact Erin Hare at HareE@upmc.edu or 412-738-1097. #  #  # Video credit: UPMC.

Jan
22
2020

Impacting human life now

Bioengineering, Student Profiles

Reposted with permission from the University of Pittsburgh Center for Research Computing. Click here to read the original story. Two images of MRI brain scans are displayed side-by-side on a poster in the Radiofrequency Research Facility in the basement of BST 3, one image marked 3T and one 7T. On the 7T image the hippocampus region of the brain displays a tracing of vessels not visible on the 3T image. “You can clearly see a microstructure in the 7T scan that doesn’t appear in the 3T scan,”  post-doc Tales Santini points out. “That kind of detail is what our scanner system offers.” That scanner is one of the most powerful MRI devices in the world – designated 7T  for 7 Tesla, a measure of the strength of an electromagnetic field (by comparison, Earth’s magnetic field is about 0.00065 T and a refrigerator magnet 0.01 T). MRI scanners in use are primarily 1.5 and 3 Tesla. The increased power of the 7 Tesla scanner reveals details not visible in typical MRI machines. With a resolution up to 180 microns – a micron is a millionth of a meter – the 7 Tesla can identify problems much earlier than existing scanners. 7 Tesla is particularly effective in early detection of brain issues implicated in diseases associated with aging, such as Alzheimer’s and late life depression, diseases which are a focus of the Radiofrequency Research Facility and the 7 Tesla Bioengineering Research program, directed by Tamer Ibrahim, professor of bioengineering, radiology, and psychiatry. The increased frequency of the 7 Tesla represents challenges. If the electromagnetic waves do not enter the skull evenly in a uniform pattern, heat concentrates in individual areas of the brain, considerably raising their temperatures. The maximum possible heating allowed by the U.S.. Food and Drug Administration is one degree centigrade. The lab is currently developing technology to smooth those electromagnetic waves using an array of 70 intricate radiofrequency antennas surrounding the head and neck, dubbed the Tic-Tac-Toe antenna owing to a nine-square grid marked with X’s and O’s displayed on the array’s housing. The team uses the Center for Research Computing to simulate hundreds of thousands of possible configurations of the antennas to create the most uniform possible waves. “The wavelength of tissue is short, about 12 centimeters at 7 Tesla, while the human head is electrically large, about 20 cm front to back,” explains Ibrahim. “We must create a relatively homogenous magnetic field to image a head that is about twice the wavelength of the 7 Tesla in tissue. This is extremely challenging. Without a uniform field, the image quality and usefulness will significantly degrade, and the electrical field can localize and heat the tissue.” Engineer Anthony Defranco, Tamer Ibrahim, and post-doc Tales Santini. Santini is holding the housing of the Tic-Tac-Toe antenna. Now the computational problem. Hundreds of thousands of configurations of the Tic-Tac-Toe antennas must be modeled to optimize that balance of uniform imaging while minimizing the danger of heating before any testing. Each of the 70 antennas is simulated in the presence of the other 69 antennas, the electromagnetic fields from these simulations are combined – potentially in hundreds of millions of different ways - to form the most even, yet safe, magnetic field distribution.  “We use CRC to do the simulation and optimization of the coils, but also in processing human imaging data,” Santini explained. The 7 Tesla scanner and Tic-Tac-Toe antennas are being heavily used in clinical studies. Ibrahim estimates that his team of 12 PhD students, several MS and BS students, two engineering staff, and two post-docs has performed 4,000 human head and neck scans between 2017 and 2024 looking at blood flow, cerebral spinal fluid, small vessels and microstructures in the hippocampus and other brain regions, all of which correlate with diseases like Alzheimer’s. The research is not limited to conditions associated with aging but includes major depressive disorder, schizophrenia, sickle cell, mild cognitive impairment, normal aging, late-life depression, dementia, psychosis, neurocognitive disparities, and linking personality to health, among others. The Tic-Tac-Toe radiofrequency coil system has achieved breakthrough results in terms of image quality and consistency at 7 Tesla. The new capabilities are stimulating significant translational and collaborative research.  Through extensive collaborations with the Alzheimer Disease Research Center and the  Pitt departments of Psychiatry, Medicine, Epidemiology, Neurology, Psychology, and Anesthesiology, Ibrahim’s lab has attracted close to $40 million in grant funding over the last four years, including 17 National Institutes of Health grants. A recent NIH award of over $3.75 million funds research by Ibrahim and collaborators in the Department of Psychiatry into developing new 7 Tesla technology to investigate relationships between preclinical Alzheimer’s disease and small vessel and cerebrospinal fluid conditions. Ibrahim is also central to an initiative of the departments of Bioengineering and Psychiatry to create a multidisciplinary training program for pre-doc bioengineering students to participate in mental health research, an initiative that recently received $1.1 million from the NIH. “This is an exciting time,” says Ibrahim. “Our engineering innovations are being used on real patient studies. We’re not making something that just could be used some time in the future. We are impacting human life now.”

Jan
9
2020

Advancing Neural Stimulation: Kozai Designs a Wireless, Light-Activated Electrode

Bioengineering

PITTSBURGH (Jan. 9, 2020) … Neural stimulation is a pioneering technology that can be used to recover function and improve the quality of life for individuals who suffer from brain injury or disease. It serves an integral role in modern neuroscience research and human neuroprosthetics, including advancements in prosthetic limbs and brain-computer interfaces. A challenge that remains with this technology is achieving long-term and precise stimulation of a specific group of neurons. Takashi D-Y Kozai, assistant professor of bioengineering at the University of Pittsburgh, recently received a $1,652,844 award from the National Institutes of Health (1R01NS105691-01A1) to develop an innovative solution to address these limitations. “Implantation of these devices causes a reactive tissue response which degrades the functional performance over time, thus limiting device capabilities,” Kozai explained. “Current electrical stimulation implants are tethered to the skull, which leads to mechanical strain in the tissue, and in turn, causes chronic inflammation and increases the possibility of an infection.” Kozai, who leads the Bio-Integrating Optoelectric Neural Interface Cybernetics Lab in the Swanson School of Engineering, will use the NIH award to develop a wireless in vivo stimulation technology that will enable precise neural circuit probing while minimizing tissue damage. In this design, the electrode will be implanted in the brain and activated by light - via the photoelectric effect - with a far-red or infrared laser source, which can sit outside of the brain. “This use of photostimulation removes the mechanical requirements necessary in traditional microstimulation technology and improves spatial selectivity of activated neurons for stable, long-term electrical stimulation,” Kozai said. His group found that photostimulation drives a more localized population of neurons when compared to electrical stimulation under similar conditions. When used, the activated cells were closer to the electrode, which indicates increased spatial precision. The proposed technology will be smaller than traditional photovoltaic devices but larger than nanoparticles to improve device longevity. “With this project, we hope to develop advanced neural probes that are capable of activating specific neurons for long periods of time and with great precision,” Kozai said. “This technology could significantly impact neuroscience research and ultimately the treatment of neurological injury and disease in humans.” ###

Jan
6
2020

Take heart: Pitt study reveals how relaxin targets cardiovascular disease

Bioengineering, Student Profiles

PITTSBURGH (Jan. 6, 2020) … As a healthy heart ages, it becomes more susceptible to cardiovascular diseases. Though researchers have discovered that relaxin, an insulin-like hormone, suppresses atrial fibrillation (AF), inflammation, and fibrosis in aged rats, the underlying mechanisms of these benefits are still unknown. In a recent Scientific Reports paper, University of Pittsburgh graduate student Brian Martin discusses how relaxin interacts with the body’s signaling processes to produce a fundamental mechanism that may have great therapeutic potential. The study, “Relaxin reverses maladaptive remodeling of the aged heart through Wnt-signaling” (DOI: 10.1038/s41598-019-53867-y) was led by Guy Salama, professor of medicine at Pitt, and Brian Martin, a graduate student researcher from the Swanson School of Engineering’s Department of Bioengineering. “Relaxin is a reproductive hormone discovered in the early 20th century that has been shown to suppress cardiovascular disease symptoms,” said Martin. “In this paper, we show that relaxin treatment reverses electrical remodeling in animal models by activating canonical Wnt signaling - a discovery that reveals a fundamental underlying mechanism behind relaxin’s benefits.” A better understanding of how relaxin interacts with the body may improve its efficacy as a therapy to treat cardiovascular disease in humans. As the U.S. population ages, the rates of these age-associated diseases are expected to rise, requiring better treatment for this leading cause of death. According to a report from the American Heart Association, the total direct medical costs of cardiovascular disease are projected to increase to $749 billion in 2035. “A common problem in age-associated cardiovascular disease is altered electrical signaling required for proper heart contraction,” Martin explained. “When ions in the heart and their associated channels to enter or exit the heart are disrupted, complications occur.” “Natural, healthy aging has been shown to be accompanied by changes in structure and function,” Salama added. “For example, aged cardiomyocytes start to express embryonic contractile proteins and fewer voltage-gated Na+ channels by unknown mechanisms. The reversal of some aspects of the aging process by relaxin is mediated by the reactivation of Wnt canonical signaling which may partly explain mechanisms of the aging process.” The group’s study found that relaxin upregulated the prominent sodium channel, Nav1.5, in cells of heart tissue via a mechanism inhibited by the Wnt pathway inhibitor Dickkopf-1. “Wnt signaling is thought to be active primarily in the developing heart and inactive later in life,” Martin said. “However, we show that relaxin can reactivate Wnt signaling in a beneficial way to increase Nav1.5.” Increased Nav1.5 is associated with better electrical signaling in the heart may reduce susceptibility to cardiac rhythm disorders. “Further, we show that relaxin can also reverse the age-associated reduction in cell adhesion molecules and cell-cell communication proteins,” he continued. “In summary, relaxin appears to reverse problematic reductions or pathological reorganization of vital cardiac signaling proteins.” While these data provide new insight into relaxin’s mechanisms of action, further work is needed to understand the precise steps required for relaxin to alter Wnt signaling and if steps can be taken to directly alter Wnt signaling to provide its beneficial effects. ### Image caption: “Left ventricular tissue sections (7-µm thick) from aged rat hearts (24 months old) were labeled with the nuclear stain (DAPI-blue) and an antibody against β-catenin (green). Rats were treated with Relaxin (0.4 mg/kg/day for 2-weeks) (left panel) or with the control vehicle (sodium acetate) (right panel) and the tissue sections were imaged by confocal microscopy (600X magnification). Relaxin treatment (left) produced a marked positive remodeling of aged ventricles with a reduction of cell hypertrophy, improved organization of myofibrils and cell membrane compared to untreated, control aged hearts (right).” Credit: Dr. Guillermo Romero.