2024 | 2023 | 2022 | 2021 | 2020 | 2019
The MU-MCW BME Graduate Seminar Series invites local, regional and national speakers to present current or novel biomedical research and recent innovation to graduate students in the MU-MCW Department of Biomedical Engineering. Below, view this program's recent past speakers.
For a list of upcoming speakers, view the Graduate Seminar Series page. For further information on current or past speakers, please contact Dr. Tanya Onushko.
Dr. Lei Fan is an Assistant Professor in the MU-MCW Joint Department of Biomedical Engineering and Director of the Fan Lab. Broadly, her research interests include computational and experimental biomechanics, blood perfusion, cardiovascular and cerebrovascular mechanics.
Role of interactions between cardiac electromechanics and coronary perfusion in cardiovascular diseases
The heart is a complex multi-physics biological system that functions because of the coordinated interactions between different processes. Coronary perfusion and cardiac electromechanical contraction are two critical processes that are tightly interlinked by a two-way interaction: 1) cardiac electromechanical work affects coronary blood flow via retrograde metabolic signaling mechanisms as well as the generation of extravascular forces and perfusion pressure, and 2) coronary perfusion determines the ability of the heart to perform work. Due to the tight integration and interactions of these processes across multiple levels, factors associated with heart diseases are often confounded. Therefore, it is challenging to quantify their true effects to discern the underlying disease mechanisms solely from experimental/clinical studies. A novel multi-scale cardiac electromechanics-perfusion computational modeling framework is developed that considers coronary flow regulation and myocardial-vessel interactions to address the limitations associated with experimental/clinical studies. This multi-scale computational model is assimilated simultaneously with experimental/clinical measurements of the myocardium and the coronary network. Last, the model is applied to estimate biomarkers under different physiological and pathological conditions, elucidate changes in the myocardial demand-supply feedback system and predict/optimize subject-specific treatment response.
Dr. Guilherme Garcia is an Assistant Professor in the MU-MCW Joint Department of Biomedical Engineering. He specializes in computer modeling of the upper airway for use in surgery planning and drug distribution.
Chris Larkee is the Visual Technology Specialist for the Maquette Visualization Lab (VisLab), a facility that uses visualization technology to be used as an aid in research, teaching, and industrial applications.
Estimation of nasal airway cross-sectional area from endoscopy using depth maps: A proof-of-concept study
In this presentation, we will summarize the results of our project aimed at estimating the cross-sectional area of the human airway based on endoscopy videos. We will discuss the unmet clinical need for this technology, summarize our efforts applying open-source machine-learning algorithms to compute depth maps from clinical endoscopies, and summarize our recent publication that reports a proof-of concept study showing that depth maps provide accurate estimates of the cross-sectional area in 3D models of the nasal cavity based on virtual endoscopy videos. During the seminar, we will watch some illustrative virtual endoscopy videos created in the Marquette Visualization Lab (VisLab).
Dr. Jason Bazil is an Assistant Professor in the Department of Physiology and BioMolecular Science Gateway at Michigan State University. His lab is focused on exploring the dynamics of cardiac energy and its response to heart disease, as well as ischemia/reperfusion injury.
Calcium Effects on Mitochondrial Ultrastructural
Mitochondrial calcium homeostasis has been of great interest to many scientific communities. This is because mitochondria respond to calcium in a manner that can either promote health or cause disease. The orthodox view is that calcium stimulates energy metabolism through a variety of mechanisms if kept below toxic levels. When mitochondrial calcium levels get too high, a phenomenon known as mitochondrial permeability transition occurs which turns mitochondria from ATP producers into ATP consumers. However, before this transition event occurs, mitochondria store excess calcium as calcium phosphate precipitates of heterogeneous composition. In this calcium overloaded state, mitochondria remain intact and functional, albeit with reduced oxidative capacity, and reveal dramatically altered cristae morphologies when imaged with cryo-electron tomography. We show that calcium phosphate precipitates appear to modulate isolated mitochondrial membrane morphology and depress ADP-stimulated respiration which implies a link between structure and function. From these results, a new model of mitochondrial operation is coming into focus, and a testable hypothesis emerges. In this model, cristae junctions play a key role in energy homeostasis, and as a corollary, maintaining cristae junction integrity preserves mitochondrial oxidative capacity. Overall, these findings establish a mechanism of calcium-induced mitochondrial dysfunction which may be causal in many diseases. Thus, new emerging therapeutics that maintain cristae structure and integrity may translate into preserved or enhanced mitochondrial function during stress.
Melissa Thill is a Risk Management Project Manger at Abbott. She has prior experience in transfusion medicine and cell therapies, having worked at Fresenius Kabi. Additionally, she has expertise in bedside cell and gene therapy delivery systems gained from her time at Lupagen. She is a Marquette University BME alum with a background in systems engineering.
Transfusion Medicine—Collection, Processing, Testing, and Administration
Dr. Taosheng Liu is a Professor of Cognition and Cognitive Neuroscience in the Department of Psychology at Michigan State University. Dr. Liu's primary research focuses on visual selective attention and extends to related areas like visual working memory and decision making. He is interested in exploring the interconnected processes from perception to action with a focus on the computational and neural mechanisms of these psychological functions.
Neural mechanisms of attention to visual features and objects
It is well established that visual perception is strongly shaped by selective attention. However, how selection is achieved in the brain remains a major question in cognitive neuroscience and, in particular, the neural mechanisms underlying attention to non-spatial properties remain poorly understood. I will review recent work from our group that investigates the neural mechanisms of feature- and object-based attention, with a focus on the neural instantiation of attentional priority for these properties, how priority signals modulate behavior, and the computational principles underlying these neural representations. I will discuss how neural computations confer the brain with an efficient and robust mechanism to support flexible attentional control.
Dr. Gopal Iyer is an Assistant Professor in the Department of Human Oncology at the University of Wisconsin, Madison. His research seeks to decipher the dynamics of signaling bias regulated by epigenetic and phosphorylation processes.
Unraveling the G-protein gamma subunit GNG2 in Lung Cancer Metastasis to the Brain
Lung cancer metastasis to the brain remains a critical challenge in cancer treatment, with limited therapeutic options and poor patient outcomes. My lab focuses on elucidating the molecular mechanisms driving this devastating process, particularly the role of Netrins in the extracellular matrix (ECM) and their regulation by the heterotrimeric G-protein gamma subunit (GNG2). Preliminary findings have identified GNG2 as a significant regulator of lung-to-brain metastasis, suggesting its involvement in modulating the Netrin-1 and Netrin-4 pathways through focal adhesion kinase (FAK) activation. Our approach combines molecular biology, advanced imaging, and biomechanical techniques to provide a comprehensive understanding of the GNG2-FAK-Netrin axis in lung cancer metastasis. Using both in vitro and in vivo models, we investigate how alterations in GNG2 expression impact cancer cell migration and invasion within Netrin-modified microenvironments. By leveraging human cerebral organoids, we simulate the brain microenvironment to analyze tumor cell behavior under GNG2-FAK signaling and assess the biomechanical aspects of organoid invasion and ECM stiffness modulation. By integrating insights from these diverse approaches, we aim to uncover novel therapeutic targets and develop improved treatment strategies for lung cancer patients, especially those at risk of brain metastasis. This research holds the potential to significantly advance our understanding of the complex mechanisms underlying lung cancer metastasis to the brain, paving the way for more effective and personalized therapies. Our ultimate goal is to translate these findings into clinical practice, improving the lives of lung cancer patients and their families.
Shashanka Rao is currently a Post-doctoral Fellow in Dr. Brandon Tefft's Cardiovascular Regenerative Engineering (CaRE) Laboratory in the Marquette-MCW Joint Department of Biomedical Engineering. He obtained his PhD from LSU Health Science Center in Shreveport, Louisiana. He specializes in redox biology in the context of cardiovascular diseases such as hypertension and atherosclerosis.
Using ex-vivo siRNA approach to endothelialize commercially available vascular grafts
Myocardial infraction is a leading cause of death, and surgical intervention is often required to treat severe coronary artery disease. Synthetic vascular grafts less than 6 mm diameter fail due to unacceptable patency rates (approximately 60% at 1 year of implantation). The loss of patency is accredited to platelet activation, thrombosis, and neointimal hyperplasia. A promising strategy to improve patency is to endothelialize synthetic vascular grafts ex vivo, but previous attempts have met with modest success due to detachment of cells upon exposure to fluid shear stress. Using RNA seq approach for adherent endothelial cells (ECs), we found that fibronectin leucine-rich transmembrane protein 2 (FLRT2) was significantly downregulated in adherent ECs subpopulation. We used silencing RNA (siRNA) approach to seed FLRT2 silenced ECs onto a commercially available Goretex graft material ex vivo and subjected them to fluid shear stress of 30 dyn/cm2 for 20 minutes. We observed an increase in retention of FLRT2 silenced ECs on Goretex graft material in comparison to non-specifically targeted scramble siRNA containing ECs under shear stress. In conclusion, we here for the first time show that siRNA approach may be a great strategy to reendothelialize commercially available vascular grafts ex vivo and that loss of FLRT2 plays an important role in EC adhesion. We would like to further investigate the molecular mechanisms underlying the role of FLRT2 in EC adhesion and use this strategy to reendothelialize commercially available synthetic grafts ex vivo and test it in our porcine models for patency.
Don Anderson is the Richard and Jan Johnson Chair in Orthopedic Biomechanics, Professor, and Vice-Chair of Research in the Department of Orthopedics & Rehabilitation at the University of Iowa. He holds a BSE in Biomedical Engineering, as well as an MS and PhD in Mechanical Engineering, all earned at the University of Iowa. Dr. Anderson has 30+ years of experience with image analysis, computer modeling, and computational stress analysis in musculoskeletal applications. Dr. Anderson's primary research focus throughout his career has been on articular joint biomechanics, specifically studying the mechanical relationship between joint injury and the subsequent development of post-traumatic osteoarthritis. All of his post-graduate career has been spent working in a clinical orthopedic setting, which has guided his work toward informing and influencing patient care.
Post-Traumatic Osteoarthritis Risk from Pathomechanics: Supporting Studies and New Intervention Strategies
The long-term goal of our research is to forestall post-traumatic osteoarthritis (PTOA), the disabling condition that often develops after joint injuries like an intra-articular fracture (IAF) of the tibial plafond. PTOA is one of the leading causes of mobility-related disability, affecting approximately 5.6 million individuals in the U.S. alone. PTOA leads to permanent disability in nearly 30% of individuals having sustained an IAF, with those of the foot and ankle being the most disabling. The impairment associated with ankle OA is comparable to that caused by end-stage kidney disease or congestive heart failure. The vast majority of ankle OA is post-traumatic, with tibial plafond IAFs often leading to disabling PTOA within two to five years. As a result, patients with ankle injuries provide an ideal population in which to study this degenerative pathway so that we can optimize treatment. We have developed patient-specific precision medicine approaches to predict PTOA risk in the ankle using CT-based measures of pathomechanical factors associated with IAFs (fracture severity and elevated contact stress post-treatment) of the tibial plafond. A primary objective of the group’s present work is to enable the use of these innovative methods for assessing IAFs to better inform patient care and to guide future clinical trials of new therapies directed at mitigating or arresting the environment that triggers progressive joint degeneration.
Dr. Christian Kastrup is a Professor in the Department of Surgery at MCW, a Senior Investigator with Versiti Blood Research Institute, and a Secondary Faculty member in the MU-MCW Joint Department of Biomedical Engineering.
RNA and Lipid Nanomedicines to Control Bleeding and Thrombosis
Bleeding and thrombotic disorders are common, affecting hundreds of thousands of North Americans, often due to an imbalance between the formation (coagulation) and destruction (fibrinolysis) of blood clots. Modulating fibrinolysis instead of coagulation is an alternate clinical approach for patients with bleeding and thrombotic disorders. However, only a small number of medications can influence pro- and anti-fibrinolytic proteins and enzymes, and they are short-acting. We developed a library of RNA and lipid nanoparticle (LNP) agents targeting the synthesis of pro- and anti-fibrinolytic proteins in vivo to modulate fibrinolysis long-term. Encapsulating mRNA and siRNA agents in LNP enabled delivery to the liver and bone marrow, where many pro- and anti-fibrinolytic proteins are synthesized. siRNA mediates gene silencing by degrading the target mRNA, resulting in long-term depletion of the corresponding protein in blood plasma for weeks to months. These mRNA-LNP can also be delivered to platelets, which allows further control of blood proteins. Administering pro- and anti-fibrinolytic RNA-LNP modulated fibrinolysis in vivo for weeks to months in small and large animal models of bleeding and thrombosis, the appropriate siRNA-LNPs corrected bleeding or thrombosis, showing promising therapeutic potential for humans.
Dr. Amy Lenz is a Research Assistant Professor in the Department of Orthopaedics at the University of Utah School of Medicine.
Learn more about Lenz Research Group
Foot and Ankle Biomechanics: Empowering Clinical Interventions with Advanced Technology to Study 3D Morphology and Kinematics
The foot and ankle is a complex structure of numerous articular relationships which operate to provide a stable base of support through active and passive tissue interactions. Altered morphology can lead to injury, instability, pathological deformity, and osteoarthritis. My lab’s goal is to characterize healthy, diseased, and post-surgical foot and ankle morphology and in-vivo function to improve clinical treatment of ankle pathologies leading to end-stage ankle osteoarthritis. Our recent studies have investigated the relationship between morphology and in-vivo function of the subtalar joint in patients that received a tibiotalar arthrodesis or total ankle replacement (TAR) surgery. Dynamic joint articulation measurements, such as joint space distance, coverage, and congruence can be investigated in combination with morphology analyses using statistical shape modeling and biplane fluoroscopy kinematics to investigate the form and function relationship occurring at the subtalar joint following surgical intervention. Our ongoing studies highlight the complexity of the foot and ankle, the value of a robust 3D analyses, the utility of in-vitro robotic experiments, and the necessity to further investigate interactions of function and morphology to clinically evaluate flatfoot deformity, osteoarthritis, and injury mechanisms.
Dr. Joseph T. Barbieri is a Professor in the Department of Microbiology and Immunology and is the Associate Director of the Medical Scientist Training Program at MCW.
Dr. Bo Wang is an Assistant Professor in the MU-MCW Joint Department of Biomedical Engineering and the Director of the Tissue Regenerative Engineering (TRE) Lab.
Application of Human Amniotic Membrane in Tissue Engineering
Human amniotic membrane (HAM) is the innermost layer of the placenta, which is a thin and semi-transparent membrane and contains various collagenous, non-collagenous proteins, and growth factors. HAM has many unique biological properties, including anti-inflammation, low immunogenicity, anti-fibrosis, and promotion of epithelialization, that make it an ideal biomaterial for such clinical applications as ophthalmic, abdominal, dental, plastic surgeries, and wound healing.
In our laboratory, we've successfully developed a method for decellularizing HAM, effectively removing cellular components while preserving crucial extracellular matrix (ECM) constituents, resulting a decellularized amniotic membrane (DAM). We have investigated the use of DAM as a wound dressing material for repairing several types of tissue injuries, including wounds in oral cavity, bone, liver, and muscle. Furthermore, we've explored the use of DAM in the fabrication of small vascular grafts, and these DAM-based grafts have demonstrated exceptional material stability, biocompatibility, and long-term patency when employed in vascular transplantation surgery.
Dr. Monica Rosenberg is an Assistant Professor in the Department of Psychology at the University of Chicago.
Learn more about Dr. Rosenberg
Characterizing attention dynamics with functional brain dynamics
Although maintaining attention to a task at hand is crucial to navigating daily life, our attentional state waxes and wanes. Despite our best efforts, fluctuations in focus are ubiquitous during psychological tasks and everyday activities, such as watching movies and listening to lectures. What brain systems predict these attentional state changes? Do similar neural dynamics underlie attentional dynamics regardless of what we attend to, or do associations between neural and attentional dynamics vary by context? To address these questions, I will first provide evidence that a common functional brain network predicts changes in attention task performance on time scales from minutes to months in independent datasets. I will then show evidence from a deep imaging study measuring attention fluctuations in controlled and naturalistic tasks. Latent state analysis revealed that a common brain state consistently predicted periods of inattention, but different brain states occurred when participants were attentive to the tasks and movies. Thus, associations between brain-state dynamics and attention dynamics are both context-general and context-specific: whereas a brain state associated with suboptimal attention is shared across contexts, the brain state optimal for focus varies with cognitive and attentional demands.
Dr. Kenneth Tichauer is an Associate Professor and the Associate Chair of Graduate Affairs in the Department of Biomedical Engineering at Illinois Institute of Technology.
Quantitative methods in fluorescence guided surgery and retinal imaging
The focus of this presentation will be on highlighting methods for extracting quantitative physiological and biomolecular parameters from contrast enhanced imaging approaches. Parameters of interest will include blood flow, vascular permeability, cell-surface receptor concentrations, and other drug targets. Several preclinical and clinical applications will be covered, including surgical margin assessment in head and neck cancer tumor resection, rapid and noninvasive lymph node biopsy, early prediction of diabetic retinopathy, and in vivo monitoring of drug binding.
Dr. Colin Burnett is a graduate of the University of Iowa Roy J. and Lucille A. Carver College of Medicine and a current Electrophysiology Fellow at the Medical College of Wisconsin.
Putting the Heat Back into Calorimetry
Obesity continues to worsen along with its comorbid conditions, and the limited efficacy of current pharmacotherapies necessitates reevaluation of the most common method of metabolic rate measurement: gas respirometry. Direct calorimetry overcomes the limitations of gas respirometry to reveal unappreciated changes in metabolism. Designing better calorimeters will become necessary to advance the understanding of the pathophysiology of obesity and to create more effective treatments of obesity.
Austin is a doctoral candidate and research assistant in Dr. Bo Wang's Tissue Regenerative Engineering Laboratory (TRE Lab).
Development of a New Generation of Nanoparticles with Acellular Porcine Bone for Regenerative Engineering and Orthopedic Therapy
The increasing prevalence of bone-related diseases and physiological conditions has posed a significant health challenge, particularly to an aging society and those with bone-disease-related conditions. As an important tool of nanomedicine, Nanoparticles (NPs) have been extensively studied in areas including disease diagnosis and therapy, biomedical imaging, and drug and gene delivery, in large part due to their low toxicity, controllable physical stability, and tailorable characteristics for surface binding and encapsulation of drugs or molecules of interest. Although there are currently no FDA approved NP options for clinical orthopedic treatment, scientists are developing new NPs for improving the safety, diagnostic, and therapeutic efficiency that will address potential risks associated with NP use including elevated risks of low biocompatibility and drug delivery efficiency, unwanted accumulation in non-targeted organs, and a high chance for toxic side effects. Our lab has developed a novel type of multifunctional bone-based nanoparticle (BPs) using the decellularized extracellular matrix (dECM) of porcine bone tissue designed for orthopedic use. In this talk, I will discuss our current research using the BPs including 1) Local application of BPs for In vivo bone regeneration and healing, 2) Encapsulation of Indocyanine Green (ICG) for use with Near-Infrared Spectroscopy Imaging (NIR) in both local and systemic applications, and 3) Modification for bone-targeting systemic delivery with in situ, real time monitoring capability.
Dr. Rey is an assistant professor in the Department of Neurosurgery at the Medical College of Wisconsin and the Marquette-MCW Joint Department of Biomedical Engineering. He graduated in Electronic Engineering from the University of Buenos Aires, where he also obtained his PhD. He joined the University of Leicester (UK) in 2010 to perform his postdoctoral studies, and in 2012 he was awarded a Special Training Fellowship in Biomedical Informatics from the Medical Research Council (UK).
Recording Neural Activity 24/7 at Different Scales in the Human Brain: A Unique Opportunity to Study Mechanisms Underlying Memory and Epilepsy
Epilepsy affects about 1% of the population worldwide, causing mortality, morbidity and reducing quality of life. When epilepsy becomes refractory (i.e., pharmacologically resistant), it is common to implant (macro) electrodes to record intracranial electroencephalogram (iEEG) in candidates identified for a surgical solution. In this talk, I will show you how we can apply modern technologies to simultaneously record from the human brain at different scales: from iEEG with clinical electrodes, to field potentials and single neuron activity from microwires protruding from the clinical probe. In fact, we are now able to record 24/7 for about a week, while the patient undergoes long-term monitoring to identify the epileptogenic zone (EZ), the area of the brain that is necessary for the appearance of seizures. During this time, the patient can engage in behavioral tasks while the neural signals are being recorded. In my lab, we are developing a research program that would allow to use this setup to answer important questions in clinical and cognitive neuroscience. The cognitive studies will allow us to unravel the building blocks of episodic memory and the associated neural mechanism, but will also provide us a platform to study other brain processes like perception, attention, language, and decision making. On the clinical research, we will search for new biomarkers to improve diagnosis and treatment in epilepsy. To achieve this, we rely on developing and applying methods to improve acquisition and analysis of neurophysiological data, based on concepts from signal processing and machine learning.
Dr. Vaicik is an assistant professor of Biomedical Engineering within the Armour College of Engineering at the Illinois Institute of Technology. She earned her BS in Chemical Engineering from Purdue, and earned her MS in Bioengineering from the University of Illinois at Chicago. She completed her PhD at the Illinois Institute of Technology and her postdoctoral research at the Department of Veterans Affairs, Edward Hines Jr. VA Hospital, in Illinois.
Novel Therapeutic Targets and Development of Drug Delivery Systems for Use in Adipose Tissues Abstract
Adipose tissue (fat), the largest endocrine organ in the body, is comprised of adipocytes as the main cell type surrounded by specialized extracellular matrix (ECM). The ECM is a network of proteins that regulate adhesion, migration, proliferation, apoptosis, or differentiation in adipose tissue. Recent research from our group and others has emerged with new therapeutic targets in the ECM to instruct cell behavior in adipose tissue. Additional drug delivery systems are needed to realize the potential of these novel therapeutic targets. A major challenge in adipose tissue is that Adipocyte cells are difficult to transfect cells making drug delivery challenging. Novel polymeric hydrogel nanoparticles in inverse mini-emulsion are in development to achieve long-term drug delivery into hard to transfect cells. Engineering strategies to successfully identify and target adipocytes and ECM in adipose tissue has the potential to deliver drugs to treat metabolic disorders, type II diabetes and obesity.
Song Hu’s research focuses on the development of cutting-edge optical and photoacoustic technologies for high-resolution structural, functional, metabolic and molecular imaging in vivo and their applications in neurovascular disorders, cardiovascular diseases, regenerative medicine, and cancer.
Light + Sound: Peering into Brain Function and Metabolism
Exploiting the optical absorption contrast of blood hemoglobin, photoacoustic microscopy (PAM) is an emerging technology for label-free imaging of the microvasculature, which plays an essential role in supplying oxygen to the biological tissue and maintain the metabolic activity in vivo. The multi-parametric PAM developed in Dr. Hu's lab enables, for the first time, comprehensive and quantitative characterization of the microvascular structure, function, and associated tissue oxygen metabolism at the microscopic level. In this seminar, Dr. Hu will present their latest progress on the development of PAM and the integration of PAM with other intravital light microscopy techniques for studying brain function and energy metabolism.
Dr. Yubing Tong is a Senior Research Investigator at the University of Pennsylvania Center for Undergraduate Research and Fellowships.
MR Image Segmentation & Analytics to Characterize the Upper Airway Structure in Obese Children with Obstructive Sleep Apnea Syndrome (OSAS)
This aims to introduce Dr. Tong's work on Obstructive Sleep Apnea Syndrome (OSAS) within recent years. It will include upper airway segmentation and image analysis to characterize the upper airway's structure in patients with OSAS. The approaches of upper airway and surrounding object segmentation from static MRI and dynamic MRI will also be introduced. Previous approaches of non-Deep Learning (DL) using automatic anatomy recognition (AAR) for upper segmentation, and the recently developed hybrid intelligence-based segmentation, combining natural intelligence and artificial intelligence, will be introduced. The upper airway segmentation from dynamic MRI includes work using both non-DL and DL techniques. The image analysis part will briefly introduce our approach of extracting useful features/biomarker to distinguish patients with Obese OASAS versus those who are obese but non-OSAS. In general, this talk will include an anatomy introduction, technical perspectives of deep learning and non-deep learning approaches, as well as feature extraction and prediction.
Dr. Morelli (Welch) completed her BS and MS degrees at the University of Tennessee, Knoxville, and earned her PhD in Exercise Physiology at the University of Wisconsin—Milwaukee. She completed her postdoctoral fellowship at Northwestern University Feinberg School of Medicine in the NCI-funded T32 training program in cancer prevention and survivorship. In 2019, she was appointed to a faculty position at Northwestern University Feinberg School of Medicine prior to joining the MCW faculty in 2022.
Development of Patient-Centered, Personalized Physical Activity Interventions Using Digital Health Technology
Dr. Morelli (Welch) is an exercise physiologist whose overall research goal is to increase physical activity in populations at high risk for being inactive, with an emphasis on preventing or managing chronic disease. Her research interests and expertise include creatively using digital health technology, such as wearable devices, to develop and test innovative physical activity interventions to manage or prevent chronic disease or physical function decline among high-risk populations (cancer survivors, older adults). Dr. Morelli is particularly interested in moving beyond the "one size fits all" physical activity prescription and developing tailored, personalized physical activity prescriptions for individuals based on their personal, social, emotional, and physical circumstances. This talk will explore the opportunities to collaboratively work at the intersection of behavioral medicine and biomedical engineering to improve the health and quality of life for those with chronic conditions.
Dr. Alexandra Walsh is an Assistant Professor of Biomedical Engineering at Texas A&M University. Her research interests include biophotonics, image analysis, and laser-tissue interactions.
Label-free Quantitative Imaging of Cellular Metabolism via Fluorescence Microscopy
Cellular metabolism, the process by which cells generate energy, is dysregulated in many diseases and pathologies including cancer, neurodegeneration, and diabetes. Current biochemical assays for metabolism are limited to either cell-destructive protocols, such as mRNA analysis, and/or measure readouts from collective cell populations, such as oxygen consumption assays. Yet single-cell measurements of metabolism are important since cellular heterogeneity is known to drive disease progression, cancer metastasis, and resistance to therapies. Fluorescence lifetime imaging of the metabolic coenzymes, reduced nicotinamide adenine (phosphate) dinucleotide (NAD(P)H) and oxidized flavin adenine dinucleotide (FAD), provides a label-free method to interrogate cellular metabolism. Both coenzymes, NAD(P)H and FAD, exist in either a free or protein-bound configuration, each of which has a distinct fluorescence lifetime. Single-cell segmentation and analysis of fluorescence lifetime images allows metabolic measurements at the cellular level. To facilitate cell-level analysis of fluorescence images, we are developing automated segmentation algorithms. Additionally, we are creating and testing models for predicting metabolic phenotypes from fluorescence lifetime metrics. Our applications of single-cell metabolic phenotyping include evaluating temporal responses of cancer cells to chemotherapy and characterizing macrophage phenotypes.
Dr. Justin Grobe moved to the Medical College of Wisconsin’s Department of Physiology in June 2019. He holds a secondary appointment in the Department of Biomedical Engineering, and serves as the founding director of the Comprehensive Rodent Metabolic Phenotyping Core facility. Before joining the faculty at MCW, Dr. Grobe was a tenured associate professor in the Department of Pharmacology at the University of Iowa.
The Brain Renin-Angiotensin System in Metabolic Control and Obesity & Introduction to the MCW Comprehensive Rodent Metabolic Phenotyping Core (CRMPC)
Roughly 71% of adult Americans are overweight or obese, and although people can lose weight with diet, exercise, drugs, and surgeries, the majority regain that weight within a few years. Increasing evidence indicates that this weight regain is due to adaptation (suppression) of resting metabolic rate (RMR). This seminar will describe both ongoing research in our laboratory to understand RMR adaptation, and related rodent metabolic phenotyping capabilities provided by the new MCW Comprehensive Rodent Metabolic Phenotyping Core (CRMPC).
Part 1: Our research has identified a key role for the angiotensin II type 1 receptor (AT1), localized to a specific subtype of neuron within the hypothalamus that also expresses Agouti-related peptide (AgRP), in the normal, physiological, integrative control of RMR. Specifically, we have determined that in the lean state, AT1 in AgRP neurons couples through a Gi-mediated pathway to inhibit the cell and thereby ultimately disinhibit (stimulate) RMR. We have also discovered that obesity and RMR adaptation are associated with a disruption of this second-messenger signaling cascade, as AT1 receptors stop signaling through the Gi pathway and instead exhibit a “G protein switch” in which these receptors begin to signal via a Gq-mediated, stimulatory pathway. Finally, our work suggests that reactivation of the normal Gi signaling cascade within this neuron can restore RMR control even during obesity. We propose that this G protein switch within the AgRP neuron represents a molecular basis for the clinical manifestation of RMR adaptation during or following obesity.
Part 2: The new MCW CRMPC offers guided and fee-for-service access to advanced cardiometabolic phenotyping capabilities for rodents of various sizes (including mice and rats). Examples of major equipment offerings include a 16-chamber multiplexed home-cage phenotyping system (Promethion, Sable Systems International), a time-domain nuclear magnetic resonance body composition analyzer (LF110, Bruker), semi-micro bomb calorimeters (Parr), metabolic caging (Tecniplast), bioimpedance spectroscopy (ImpediVet), respirometry/indirect and direct calorimetry systems, an ashing oven, flame atomic absorption spectrophotometry, freezing point depression osmometry, and more (please see PMC8914175 for more details). The core additionally provides training, experimental design, best practice, data analysis, and statistical support.
Dr. Agrahara Bharatkumar is an associate professor of diagnostic radiology at the Froedtert and the Medical College of Wisconsin.
Learn more about Dr. Bharatkumar
Artificial Intelligence in Radiology
Artificial intelligence (AI) is the computer science term used for methods that enable computers to perform tasks that normally require human intelligence. “Machine learning” is a subset of AI, and refers to the process by which computer algorithms “learn” from datasets in order to develop predictive models. The application of machine learning techniques to medical images has become a topic of great interest to researchers and practitioners alike. While traditional machine learning methods require hand-engineered feature extraction from inputs in order to point out the relevant features of the data on which predictive models are based, “deep learning” refers to a class of machine learning methods that learn what relevant features to extract directly from raw input data in order to use that data to develop predictive models. Deep learning models are multilayer artificial neural networks, loosely inspired by biologic neural systems, and they are gaining success and attracting interest in many domains, including computer vision, speech recognition, and natural language processing. With the advent of large datasets and increased computing power, deep learning methods can produce models with exceptional performance – that is, exceptional predictive capability – but without the need for feature engineering or data labeling. For computer vision tasks – or tasks by which computers derive information and understanding from images, convolutional neural networks (CNNs) have proven to be effective. Recently, several clinical applications of CNNs have been proposed and studied in radiology for classification, detection, and segmentation tasks. This seminar will review key fundamental concepts of AI, briefly describe emerging applications of AI in clinical radiology, and outline limitations and future directions in this field.
Dr. LaViolette is an Associate Professor in the Department of Radiology at the Medical College of Wisconsin. His research focuses on creating and validating imaging techniques that improve patient outcome and treatment efficacy.
Learn more about Dr. LaViolette
Radio-pathomic Mapping of Brain Cancer
The computational extraction of features from radiographic imaging of cancer is termed radiomics, and combining this data with tumor genetics is termed radio-genomics. Our research is taking this idea further by training predictive models with machine learning applied to pathology samples aligned to MRI. The results can be applied to imaging data from patients prior to intervention to produce quantitative ‘radio-pathomic’ maps of cancer characteristics. In this talk I will be discussing our ongoing efforts in brain cancer research where we are combining tissue from our brain bank with clinical imaging to detect tumor invasion beyond conventional margins defined by gadolinium contrast based methods.
Dr. Kevin Dibbern is a postdoctoral fellow working with the labs at the Marquette University and Medical College of Wisconsin Orthopaedic & Rehabilitation Engineering Center (OREC). He has done previous work with foot and ankle weightbearing CT imaging, and is a recent doctoral graduate of the University of Iowa.
Automatable 3D Assessment of Weightbearing CT Data: Improving Diagnosis and Treatment in the Foot and Ankle
Until recently, standard diagnosis and treatment of foot and ankle pathologies were dependent on 2D X-ray measurements or non-weightbearing 3D imaging modalities like MRI and conventional CT. Over the past decade, weightbearing conebeam CT (WBCT) has become available to perform rapid weightbearing assessment of the foot and ankle. It affords low-radiation-dose 3D imaging of the lower extremity in functional positions. Combined with recent research efforts, it has taken over as the gold standard for identifying flat foot and other foot and ankle pathologies. However, new clinical measurements have still relied upon planar 2D interpretation of these complex 3D data.
Recently, machine learning has enabled automated 3D model creation from these scans. This has led to a unique opportunity to quantitatively examine the lower limbs in their functionally loaded positions without losing relevant features to planar interpretation. Such advancements are enabling early detection of subtle changes related to injury and deformity and optimizing patient specific care though improved understanding of the type and timing surgical intervention needed.
Dr. Brian Hoffmann is the Study Director of Mass Spectrometry and Protein Chemistry at The Jackson Laboratory and former faculty of the Marquette-Medical College of Wisconsin Joint Department of Biomedical Engineering.
Advances and Applications in Mass Spectrometry Imaging
In recent years there have been significant advances in high-resolution mass spectrometry imaging of tissues to measure the spatial distribution of lipids, small molecules, and peptides. Using matrix-assisted laser desorption/ionization technology coupled with ion mobility, spectral images representing the distribution of analytes at high-resolution (5–10 um) across the entirety of a tissue section can be acquired. These analyses also benefit from trapped ion mobility spectrometry (TIMS) to separate isobaric or isomeric analytes, allowing you to differentiate analytes when high mass resolution is not sufficient alone. In this talk, I will be discussing advances in mass spectrometry imaging, sample preparation considerations, and provide examples of data acquired from multiple tissue systems (brain, kidney, lung and tumor) using our facilities’ Bruker timsTOF FLEX. In addition, the post-processing data analysis required and the associated challenges will be discussed. Lastly, the talk will explore data collected with our collaborator, Dr. Alison Kriegel (MCW), focused on the progression of changes in the lipid profile of mouse kidneys during polycystic disease.
Dr. Daniel Sem is Vice Provost of Research and Innovation at Concordia University. He has terminal degrees in intellectual property law and biochemistry. He has special interest in pharmaceutical design and biochemistry.
Resources for Healthcare and HealthTech Startups in Southeast Wisconsin
Healthcare and HealthTech startups, coming largely from regional universities, have many needs. This talk will review resources connected to CTSI, as well as resources that assist startups in the areas of drafting business models, plans and investor pitches, corporate and legal assistant with forming a company and closing investor rounds, raising investor capital, types of investment instruments (e.g., SAFE, Convertible notes, value rounds), identifying talent for a startup, regulatory advice for drugs, devices and diagnostics, and networking to connect with other startups to identify synergies and partnerships. Resources discussed will include CTSI-AMPDNR (Accelerating Medical Products through Networked Resources), BioForward and HealthTech MKE, Catalyst Bioconsulting, NSF and NIH I-Corps, Bridge to Cures, WEDC, CTC, and the various angel investor groups, including Brightstar, MVP, Golden Angels and CU Ventures. Examples of startups that have navigated these steps will also be discussed.
Dr. Derek Kamper is an associate professor of Biomedical Engineering within the Joint Department of Biomedical Engineering at NC State and the University of North Carolina. His research focuses on improvement of upper extremity function, especially for the hand, in cases of injury or disease.
Addressing Functional Hand Limitations After Stroke
In the Hand Rehabilitation Lab, Dr. Kamper and his team seek to improve outcomes for individuals with neuromuscular impairments, especially those affecting control of the hand. The lab's strategy has been to increase understanding of sensorimotor control, to identify mechanisms of impairment, and to use this knowledge to develop new interventions. As an example, Dr. Kamper will present a completed clinical trial involving stroke survivors with chronic upper extremity deficits. After stroke, functional limitations often arise due to a seemingly paradoxical combination of involuntary motor unit hyperexcitability and diminished motor unit excitation during voluntary activation. The lab has attempted to address both phenomena through a multimodal intervention by administering cyproheptadine hydrochloride to reduce involuntary muscle activation and by instituting active training of muscle activation patterns with an electromyographically (EMG) driven hand exoskeleton and EMG-controlled “serious” computer games.
Dr. Celin is an experienced pediatrician with a demonstrated history of working with children with motor disabilities, skeletal dysplasias and growth problems in pediatric hospitals.
A Multicenter Study to Evaluate Pain Characteristics in Osteogenesis Imperfecta
The goals of this study were to investigate the characteristics of chronic pain in various osteogenesis imperfecta (OI) types, analyze association of pain with different clinical co-variates, and evaluate pain interference in activities. Cross-sectional analysis of data on adults and children enrolled in the Brittle Bone Disorders Consortium. Characteristics of chronic pain, demographic, clinical, and surgical co-variates were collected. Mobility outcomes were analyzed using Gillette Functional Assessment Questionnaire (GFAQ), Functional Mobility Scale (FMS), Brief Assessment Motor Function (BAMF), and 6-minute walk test (6MWT). Pain intensity, pain interference and limitation to participation were analyzed from PODCI and SF-12v2.
Alkis Hadjiosif is a Postdoctoral Fellow at Johns Hopkins University. He received his Diploma in Electrical and Computer Engineering from the National Technical University of Athens, Greece in 2008 and his PhD in Bioengineering from Harvard University in 2015 studying the influence of environmental variability in motor adaptation. His research aims to understand mechanisms of motor learning and motor control, in both healthy individuals and ones afflicted by motor disorders, and leverage this understanding to improve the assessment and rehabilitation of neurological impairment in the motor system.
Learn more about Dr. Hadjiosif
Post-stroke Postural Abnormalities in the Arm and Their Relationship to Loss of Motor Control
Abnormal resting postures are one of the most common and widely recognizable motor symptoms after stroke. For example, the typical hemiparetic arm posture consists of flexion at the fingers, wrist, and elbow. This pattern appears to parallel the abnormal muscle synergies during active movement, such as the abnormal coupling of muscles that move the shoulder vs. the elbow joint. Whether these synergies are generated by the same mechanism as abnormal resting postures remains an open question; it might instead be that resting abnormalities are inactive during movement. Also unknown is the degree to which resting postural abnormalities influence active moving and holding.
Here we systematically assessed resting postural abnormalities in stroke patients. We found that patients exhibited abnormal postural forces at rest, which mirrored characteristics of abnormal synergies: for example, postural abnormalities were markedly lower when the arm was supported against gravity, and, critically, strongly related to the Fugl-Meyer scale, a measure based on abnormal synergies. These findings suggest a shared mechanism between resting abnormalities and abnormal synergies after stroke.
We then examined whether these resting postural abnormalities affected the motor control of active reaching in the same workspace. We did not find any systematic effects of resting postural forces either across patients with different resting posture magnitudes, nor between high- vs. low-resting postural force regions for the same patient. However, we found evidence suggesting that resting postural abnormalities might influence active holding control. We conclude that post-stroke deficits in posture and movement may be driven by separate mechanisms. Moreover, our findings identify arm support as a way to alleviate these resting postural abnormalities.
Dr. Williams is an assistant professor within the Marquette-MCW Joint Department of Biomedical Engineering, and Director and Principal Investigator of the NEIMO Lab, which employs a combination of neurophysiology, optogenetics, viral gene therapy, and optical imaging techniques to develop novel neuroprosthetic and gene therapy approaches to alleviate motor deficits caused by conditions such as spinal cord injury or ALS.
Peripheral Optogenetic Stimulation of Motor Activity for Spinal Cord Injury Rehabilitation
Electrical stimulation of muscle activity has been the mainstay approach to reanimating paralyzed muscle function in conditions such as spinal cord injury for decades. However, this approach has traditionally been plagued by several drawbacks including an unnatural recruitment order of muscle fibers and early muscle fatigue that have limited its therapeutic ceiling for patients. Conversely, peripheral optogenetic stimulation of muscle activity is a recently emerging approach that has shown promise in alleviating these drawbacks in addition to other unique advantages. In this gene therapy technology, nerves are labelled with light-sensitive ion channels via virus injection that allow them to be stimulated with light. However, modifying the biology of the peripheral nervous system in this manner (as opposed to only electrically interfacing with it) raises its own set of challenges including exposure to the immune system and long paths of retrograde virus travel after muscle injection in order to reach targeted motor neurons in the spinal cord. In this talk, I will discuss some of my lab’s recent approaches in rodent and non-human primate models to characterize and overcome these hurdles to clinical translation. In addition, I will describe our efforts to exploit previously underutilized advantages of peripheral optogenetic neuromodulation as well as to extend these viral transduction techniques to spinal cord injury models.
Roger Guillory II is an assistant professor of Biomedical Engineering at Michigan Tech with research interests including cellular and molecular interactions of biomaterials, metallic biocorrosion, biomaterial histopathology, biocompatibility, and degradable metals for cardiovascular implants.
The interplay of Biodegradable Metal Performance and Physiological Microenvironments: Informing the Material Design of Advanced Cardiovascular Implants
Non-degradable metal stents are the current gold standard in treating patients with coronary artery disease. However, there is an interest in pursuing metal stents made from biodegradable metals such as magnesium or zinc, in an effort to minimize long term complications in patients. Metallic magnesium and zinc are prominent metal candidates for stenting applications, although both require advanced metallurgical and surface engineering in order to reach the appropriate biomechanical and biodegradation benchmarks. These engineering modifications while necessary, can cause shifts in the clinical performance of the materials. The link between biocompatibility, elemental additions, microstructural evolution, and biodegradation profiles remains elusive for biodegradable metals. We have identified key metallurgical and biodegradation factors that influence the tissue response of advanced biodegradable metals in-vivo using a large-scale statistical histological approach. However, understanding the tissue response towards any implanted degrading vascular material is confounded by the complicated material and biological variables which contribute towards the final outcome. Presently, it is unclear how material biodegradation rate, implant derived metal cations, cellular injury, or cellular activity contribute to negative biologic reactions to the materials. To fill this knowledge gap, we have been investigating the bioactivity of biodegradable metal materials in-vitro in order to relate cellular events such as cell death, intracellular metal regulation, reactive species generation, with alloy composition and biodegradation characteristics. Our work demonstrates the need for a critical understanding of the biometal-biocorrosion-cellular/tissue response axis, in order to rationally design future degradable metal materials for cardiovascular applications.
Dr. Garcia is an assistant professor of Biomedical Engineering within the Marquette University - Medical College of Wisconsin Joint Department of Biomedical Engineering.
Modeling Drug Delivery to the Nasal Passages with Nasal Sprays
Nasal sprays are widely used over-the-counter medications to treat sinusitis, allergic rhinitis, and nasal obstruction. The Food and Drug Administration (FDA) is interested in understanding how the intranasal distribution, absorption, and bioavailability of the aerosolized medication is influenced by factors such as interindividual variability in nasal anatomy, spray nozzle position in the nostril, and spray pump characteristics that vary among commercial products (e.g., initial droplet velocity, droplet size distribution, spray cone angle, etc.). In this presentation, I will summarize an ongoing project in the Airway Lab that is funded by the FDA to develop and validate computer models of intranasal distribution of nasal sprays. We will discuss how the computer models are validated with in vitro experiments in anatomically accurate, 3D printed nasal replicas. To illustrate a practical application of the model, we will discuss how the nozzle position within the nostril affects the dose delivered to relevant target sites.
Janelle Cross received her doctorate degree in Biomedical Engineering from Marquette University with a Rehabilitation Biomechanics specialization. Her dissertation work focused on developing a biplanar fluoroscopic system for analyzing in vivo and ankle kinematics during gait.
Adolescent Baseball Pitching Biomechanics: Implications on Injury Risk and Performance
Joint forces and moments are important factors in determining the risk of injury to baseball pitchers. Due to the repetitive nature of pitching, adolescent baseball pitchers are at a high risk for sustaining injuries to the upper extremity (UE) joints. Two critical periods of high risk of injury have been identified in current literature: 1) shortly before the point where the arm reaches maximum external rotation, when shoulder internal rotation torque and elbow valgus torque are generated and 2) shortly after ball release, when shoulder compression force, posterior force and horizontal abduction torque are generated. A series of studies investigating adolescent baseball pitchers was conducted to assess relationships among injury history, hip clinical measures, spin rate and pitching biomechanics. Several associations were found that have indications for injury prevention and performance enhancement.
Josh Roth is an Assistant Professor in the Departments of Orthopedics and Rehabilitation, and Mechanical Engineering at the University of Wisconsin-Madison. He earned a B.S. in Mechanical Engineering from California Polytechnic State University, and an M.S. and Ph.D. in Biomedical Engineering from the University of California, Davis. The mission of his research group, the Biomechanical Advances in Medicine (BAM) Lab, is to enhance personalized treatments of musculoskeletal injuries and disease. To fulfill this mission, he develops and applies translational technologies to measure joint and tissue biomechanics to enhance planning, execution, and evaluation in the clinical environment.
Development and Pre-Clinical Testing of Our Handheld Ligament Tensiometer
Ligaments are important tissues that act like stiff springs connecting our bones at most joints. One key role of ligaments is to act as mechanical restraints to stabilize the joint and guide its motion. Injury, disease, and surgical intervention can disrupt a ligament’s tension-length relationship, which consequently disrupts its ability to stabilize the joint and guide its motion. Although clinicians attempt to account for these disruptions, there are currently no devices available to directly and non-invasively measure these changes in vivo. In this talk, I will describe the underlying theory and development progress of our ligament tensiometer, which is a hand-held sensor to directly and non-invasively measure ligament tension based on the shear wave propagation speed in the structure. I will also show two clinically relevant examples to demonstrate the promise of this sensor to enhance clinical decision making in total knee replacement.
Dr. Jeong is a NIDILRR ARRT postdoctoral fellow at Marquette University. She received her Bachelor’s and Master’s degree in Physical Therapy at Yonsei University, South Korea. She has completed her Ph.D. training at Washington University in St. Louis, MO, in the Movement Science program, investigating foot and ankle biomechanics in people with diabetes. Her postdoctoral work investigates biomechanics of upper and lower extremities in children with hypermobile Ehlers-Danlos syndrome. She is particularly interested in understanding the rehabilitation of movement patterns over a lifespan.
Biomechanical Phenotyping of Children with Hypermobile Ehlers-Danlos Syndrome
Ehlers-Danlos syndrome (EDS) is a rare genetic connective tissue disorder that impacts 1/5000 people worldwide. Hypermobile EDS (hEDS) is the most common EDS subtype and the only subtype with an unknown genetic origin. Current diagnosis of hEDS often relies on clinical findings, which leads to delayed or misdiagnosis in hEDS and ultimately burdens the quality of life across the lifespan in children with hEDS. Therefore, characterizing a biomedical phenotype is necessary to understand the clinical features better and improve rehabilitation strategies for children with hEDS. The main goal of this talk is to share characteristics of movement phenotypes in children with and without hEDS.
Dr. Choe's research is focused on the development of diffuse optical methods for the clinical application of breast cancer diagnosis and therapy monitoring.
Non-invasive Hemodynamic Monitoring of Bone, Brain and Breast Using Diffuse Optics
Diffuse optical tomography (DOT) and diffuse correlation tomography (DCT) are non-invasive three-dimensional hemodynamic imaging techniques that can probe deep tissue using light sources in the near-infrared spectral window (650–950 nm). By modeling the photon propagation in tissue, one can quantify oxygenated hemoglobin, deoxygenated hemoglobin, water and lipid concentrations with DOT, and blood flow with DCT. These intrinsic physiological parameters have great potential to assess therapeutic efficacy of various treatments. In addition, the use of non-ionizing radiation and technologically simple, fast, inexpensive instrumentation makes diffuse optical and correlation tomography attractive for translational research.
Dr. Hokanson's research interests include urologic function/dysfunction, electrical stimulation/neuromodulation therapies, signal processing and machine learning, clinical diagnostics, autonomic nervous system and organ physiology, and neural engineering.
Improving Incontinence Therapy Outcomes with Electrical Stimulation and Improved Diagnostics
Urinary incontinence is prevalent (estimated to impact over 40% of women over 40), has a high cost-burden, and negatively impacts quality of life. Most therapies for treating urgency urinary incontinence fail to make patients dry. One study demonstrated that upwards of 90% of patients fail to respond to drug therapy and another demonstrated that less than 20% of drug-refractory patients become completely dry after Botox or sacral neuromodulation therapies. In my talk I’ll highlight experimental work aimed at improving incontinence therapy using electrical stimulation, as well as statistical modeling aimed at improving diagnosis and therapy selection. With both sets of examples I’ll demonstrate how important science often happens along the journey rather than, or in addition to, getting to the destination. Implications for translating electrical stimulation studies from animals to people will also be discussed.
Dr. Pierce's lab develops novel optical imaging systems for applications ranging from basic biomedical research studies to clinical patient care. His lab also collaborates extensively with clinical partners in surgery, radiation oncology, pathology, and image analysis.
Short-wave Infrared Optical Imaging in Small Animal Models of Cancer
Short-wave infrared (SWIR) light has several advantages for biomedical optical imaging applications. SWIR light (900–1700 nm wavelengths) scatters less within tissue than near-infrared or visible light, resulting in sharper images. Tissue autofluorescence is negligible in the SWIR region, minimizing background light and improving contrast. Our lab is developing rare-earth doped nanocomposites as imaging contrast agents which generate light at SWIR wavelengths. Encapsulation within an albumin shell renders these nanocomposites biocompatible, while also providing binding sites for molecular targeting ligands. We have used these nanocomposites to label tumors in small animal models of breast and ovarian cancer, toward potential applications in pre-clinical drug screening, tracking of micrometastatic lesions, and image guided surgery. This presentation will discuss challenges and opportunities in imaging these SWIR-emitting nanocomposites across macro and microscopic spatial scales.
Dr. Jiang is an assistant professor of biomedical engineering and surgery. Their research interests include vascular regeneration, stem cells, biomaterials, and tissue engineering.
Autologous Vascular Regeneration for Peripheral Artery Disease with Induced Pluripotent Stem Cells
The clinical translation of stem cell-based therapies for the treatment of peripheral artery disease (PAD) is currently hindered by the lack of a defined cell source, sub-optimal delivery strategies, and unknown fate of administered cells. The advent of induced pluripotent stem cells (iPSCs) offers an exceptional opportunity for regenerating functional tissues for various diseases, including PAD. Nuclear imaging techniques together with reporter gene transgenic expression provide a highly sensitive, non-invasive tool to monitor the fate of viable transplanted cells in vivo. Furthermore, advanced functional biomaterial scaffolds that can deliver stem cells to the targeted tissues/organs and promote stem cell survival, differentiation and integration to host tissues may potentially transform the clinical outcome of stem-cell based regenerative therapies. In this seminar, I will cover our recent efforts in (1) generating autologous iPSC derived vascular endothelial cells (iPSC-ECs) as an autologous cell source for PAD patient vascular regeneration, (2) demonstrating non-invasive cell tracking in vivo using a clinical applicable non-invasive imaging technique, and (3) promoting long-term cell survival with advanced biomaterial design. The hypotheses are: (1) the survival and biodistribution of iPSC-ECs expressing human sodium iodide symporter (hNIS) can be tracked non-invasively in vivo via Single Photon Emission Computed Tomography /Computed Tomography (SPECT/CT) without affecting EC functions; and (2) an antioxidant cell engraftment niche that promotes cell adhesion and spreading of iPSC-ECs, and supports vascular regeneration will reduce oxidative cell damage, improve cell engraftment and survival rate, and support limb revascularization. This study is essential to help establish optimized cell manufacturing protocols, develop cell preservation agents for limb revascularization, and develop cell tracking procedures to offer additional treatment options for PAD patients.
Dr. Bates' research focuses on human airways and how they change with various disease conditions, specifically airway behavior in children with obstructive sleep apnea (OSA) and premature babies born with tracheomalacia (TM) and congenital abnormalities.
Understanding Airway Movement Through CFD Simulations of Respiratory Airflow Based on Cine MRI
Several respiratory diseases are caused by collapse and obstruction of the airway. In obstructive sleep apnea (OSA), this collapse occurs behind the tongue or soft palate, or in the larynx. In tracheomalacia, the trachea collapses. This talk will focus on both conditions; OSA in pediatric patients and tracheomalacia in neonates who are born prematurely. CFD simulations of respiratory airflow calculate many metrics that are clinically useful in understanding these conditions such as localized resistance, work of breathing, and pressure differences. However, to calculate these parameters in a moving airway, the airway motion must be realistically included in the simulation’s boundary conditions. One way to do this is to image airway motion using cine MRI, which provides a 3D airway image several times per second. The motion between each image can then be calculated via image registration and applied as a moving boundary condition.
In OSA, CFD simulations with prescribed wall motion can be used to assess airway muscle tone and function by comparing how the airway wall moves with the aerodynamic pressures acting on the wall. Where the wall moves in a manner that cannot be explained by the pressure acting on it, muscular activity is the most likely cause of that motion. Given that the upper airway is made of highly dynamic structures such as the tongue, soft palate, and epiglottis, mapping muscular activity is an important consideration in understanding airway collapse in OSA.
In neonates who are born prematurely, patients suffer abnormalities of both the lung parenchyma and the airway, in the form of tracheomalacia. Moving wall respiratory CFD simulations, allow the effect of the tracheomalacia to be calculated separately from the lung parenchymal issues which leads to individualized treatment plans to be designed for each baby.
Dr. Beard is a Professor in the Department of Molecular and Integrative Physiology and holds affiliate appointments in Biomedical Engineering and Emergency Medicine. His laboratory is focused on systems engineering approaches to understanding the biophysical and biochemical operation of physiological systems.
Metabolic and Mechanical Determinants of Reserve Cardiac Power Output (What Determines Exercise Capacity?)
Changes in the myocardial energetics associated with aging and heart failure—reductions in creatine phosphate/ATP ratio, total creatine, and ATP—mirror changes observed in failing hearts compared to healthy controls. Similarly, both aging and heart failure are associated with significant reductions in cardiac performance and maximal left ventricular cardiac power output compared with young healthy individuals. Based on these observations, we hypothesize that reductions in the concentrations of cytoplasmic adenine nucleotide, creatine, and phosphate pools that occur with aging and age-associated disease impair the myocardial capacity to synthesize ATP at physiological free energy levels and that the resulting changes to myocardial energetic status impair the mechanical pumping ability of the heart. To test these hypotheses, to determine the potential impact of reductions in key myocardial metabolite pools in causing metabolic/energetic and cardiac mechanical dysfunction, we analyzed data on myocardial mechanics and energetics during voluntary exercise using a multiscale model of cardiac metabolism and mechanics. Model simulations support the hypotheses and provide a novel theoretical/computational framework for further probing complex relationships between the energetics and performance of the heart with aging.
Dr. Cormode's research focuses on the development of novel and multifunctional nanoparticle contrast agents for medical imaging applications. A current major focus is the development of gold and bismuth nanoparticles as contrast agents for computed tomography (CT).
Inorganic Nanoparticles for Multi-energy X-ray Imaging and Therapeutics
X-ray based imaging has been used in medicine for the past 120 years. Despite the age of this technology, we are in an era of rapid innovation in x-ray imaging methods. In particular, multi-energy x-ray imaging (such as dual energy mammography) is becoming widely available to patients, and is providing benefits such as more accurate cancer detection. These new imaging technologies require novel contrast agents that are specifically aligned to them, to allow high contrast generation. The development of such novel contrast agents will be described. For example, silver-based nanoparticles that provide improved contrast in dual energy mammography and are highly biocompatible will be discussed. Specific and multiplexed detection of contrast agents such as gold nanoparticles with spectral photon-counting computed tomography will be presented. These agents are designed for clinical translation and so their biodegradation and excretion will be discussed. Applications of these agents/systems for tumor detection, vascular imaging and cell tracking will be described. Moreover, the use of these nanoparticles as anti-cancer and anti-biofilm agents will be reported.
Dr. Pawela was awarded a Ph.D. in Biophysics from the Medical College of Wisconsin in 2008. He joined the MCW faculty immediately upon graduation with research interests that include brain connectivity and neural plasticity.
Neuroaugmentation in the Context of Peripheral Nerve Injury and Repair
Extremity injuries involving peripheral nerve damage are a significant medical risk for the modern warfighter. Nerve damage can result from blunt, penetrating, or compression injuries caused by explosions, projectiles, vehicular accidents, or other duty related events. Current treatment of peripheral nerve injuries by direct end-to-end microsurgical repair and nerve grafts/conduits is typically followed by incomplete recovery of sensorimotor function, abnormal phantom sensations, neuropathic pain, and muscle atrophy that often lead to permanent disability in veterans. Minimal advancement of treatment has been achieved in the last 30 years. To address this need, our novel treatment approach provides continuous electrical stimulation to the injured peripheral nerve immediately after nerve repair surgery through a bipolar nerve cuff electrode placed proximal to the repair site. This is based on our central hypothesis that the loss of normal sensory input to the central nervous system (CNS) leads to disordered neuroplasticity, and that surrogate activity provided by electrical stimulation of the injured nerve proximal to the injury can prevent the loss of connectivity between the CNS and the peripheral nervous system that otherwise leads to dysfunction. Our methodology is technologically similar to spinal cord stimulators (1968) and cardiac pacemakers (1958) which have been used clinically for over 50 years. In this seminar, data will be presented from pilot studies performed in an animal model that replicates many key features of clinical injury and rehabilitation. We have successfully applied our treatment approach in a rodent model following complete median nerve transection and repair. Our pilot studies, which were funded by a completed VA SPiRE grant, demonstrate a significant improvement in functional magnetic resonance (fMRI) measured brain response to median nerve stimulation, as well as skilled limb reaching performance as quantified by an automated behavioral device. Early pilot data also points to improvement in peripheral nerve regeneration after our treatment is applied, as measured by nerve conduction studies. Finally, we will discuss the optimization of treatment effectiveness of our novel methodology and future studies introducing impediments to regeneration that reflect clinical circumstances, such as interposed nerve grafts or conduits. The impact of various electrical stimulation patterns in neuroaugmentation will be discussed. Our goal is to first develop foundational work in animal models and proceed to eventual clinical translation for enhancing rehabilitation of injured veterans.
Dr. Kandail is interested in Computer-Aided (Biomedical) Engineering with particular emphasis on the amalgamation of clinical imaging techniques such as computed tomography and magnetic resonance imaging with computational cardiovascular biomechanics. He works to elucidate the role structural deformations and haemodynamics play in cardiovascular disease development and progression, along with designing novel biomedical devices to treat such diseases. Current approaches include computational fluid and solid mechanics along with fluid-structure interactions.
Fluid-Structure Interaction Simulations for Paediatric Heart Valves: Challenges, Solutions and Applications
Fluid-Structure Interaction (FSI) simulations are becoming increasingly popular with biomedical engineers to design bioprosthetic paediatric heart valves and with doctors to non-invasively assess the hemodynamic efficiency of the heart valves. However, given the dynamic nature of valve kinematics, many numerical challenges still hinder the complete and adequate translation of these FSI simulations from the lab to the clinic. The first aim of this talk is to summarize key numerical difficulties faced by researchers when developing FSI models for paediatric heart valves, such as extreme mesh deformation of the fluid domain that is associated with sudden opening and closing of the heart valves, resolving contact between the valve leaflets, and ensuring that the FSI simulations are physiologically and clinically realistic. The second aim of this talk is to share some novel and practical solutions to the challenges mentioned above. The third and final aim of this talk is to share a real-life application of this methodology to showcase how FSI simulations can be used to design radical monocusp valves for kids with the Tetralogy of Fallot.
Dr. Sergio uses behavioral and brain imaging techniques to examine the effects of age, sex, neurological disease, head injury, and experience (elite versus non-elite athletes) on the brain’s control of complex movement. Dr. Sergio works with a wide range of adult populations, including elite-level athletes and individuals affected by dementia.
The Wounded Brain: Assessing Function Pre-dementia and Post-concussion
Two prominent health issues facing individuals today are 1) the impact of dementing illness on the elderly and 2) the impact of concussion on young athletes and workers. Whether caused by trauma or degenerative disease, the effect of mild brain insult on one’s functional abilities is not well understood. I will review my group's research to date which shows that "cognitive-motor integration", or tasks which rely on rules to plan a movement (such as "push the computer mouse forward to move the cursor up"), is impaired both in the early stages of dementia (and even those with no symptoms but simply at risk for dementia), and after sustaining a concussion. I will also discuss the development of a clinical cognitive-motor assessment tool to detect dementia in its early stages, and to assess brain function following concussion. Finally, I will discuss my research into preserving brain health using cognitive-motor integration.
Dr. Valdez-Jasso is an assistant professor of Bioengineering at the University of California, San Diego. Her research interests include soft-tissue biomechanics, cardiovascular physiology, pulmonary hypertension, vascular biology, and mathematical modeling.
Learn more about Dr. Valdez-Jasso
From the Right Heart to the Pulmonary Arteries: a Multi-scale Approach to Understanding Pulmonary Arterial Hypertension
Pulmonary arterial hypertension (PAH) is a rapidly progressive vasculopathy that commonly results in intractable right-heart failure and premature death. Transplantation of the lung remains the only cure, suggesting our limited understanding of the pathophysiology. Here I present recent results from my research laboratory using a rat animal model of PAH. A multiscale approach is used to elucidate the organ- (hemodynamic), tissue- (structural and mechanical), and cellular (molecular) response of the pressure-overloaded right ventricle, the dynamic vascular remodeling process in PAH and their ventriculo-vascular interaction. Experimental findings are incorporated into mechanistic mathematical models for testable quantitative formulations of organ and tissue function. We will discuss how our experimental data measured at different scales are implemented in the computational models to determine underlying mechanisms governing PAH, and how the models are interrogated to determine their prediction capabilities and infer on data and model uncertainty.
Dr. Witzenburg is an assistant professor of Biomedical Engineering at the University of Wisconsin. Her research interests include cardiovascular biomechanics and physiology, computational modeling, tissue growth, remodeling and failure.
Learn more about Dr. Witzenburg
Predicting Growth and Failure of Cardiovascular Soft Tissues
Cardiovascular soft tissues serve critical mechanical functions within the body, but pathologic changes to these tissues alter their material properties causing disruption or reduction in function. This loss can be sudden, such as the rupture of an aortic aneurysm, or it can be gradual, such as ventricular hypertrophy and heart failure or aneurysm dilation. In this talk, I will share strategies for predicting the temporal and spatial characteristics of cardiovascular soft tissues. First, I will discuss developing and employing a computational model to predict cardiac growth and remodeling under overload conditions such as mitral regurgitation, aortic stenosis and myocardial infarction. Second, I will expand on experimental testing and analysis techniques for determining the heterogeneous properties of soft tissues. I will close by discussing future applications of these modeling and analysis techniques for predicting growth, remodeling, and failure.
Dr. Kainerstorfer is an associate professor of Biomedical Engineering at Carnegie Mellon University. Her research interests include biomedical optics, neurophotonics, neural sensing, medical devices, and optical imaging of disease.
Learn more about Dr. Kainerstorfer
Development of Optical Imaging Methods to Assess Tissue Perfusion at the Bedside
Bedside monitoring of tissue perfusion is important for a variety of diseases. For cerebral monitoring, cerebral perfusion is important especially for traumatic brain injury, hydrocephalus, sepsis, and stroke, where inadequate perfusion can lead to ischemia and neuronal damage. Diffuse optical methods, such as near-infrared spectroscopy and diffuse correlation spectroscopy, are non-invasive optical techniques which can be used to measure cerebral changes at the bedside. This talk will focus on these optical techniques as applied to clinical measurements to monitor patients and predict treatment outcome. One example of such will be presented which is our recent developments of a non-invasive intracranial pressure (ICP) sensor. For this we have developed an animal model of hydrocephalus, where ICP could be controlled and manipulated. Using diffuse correlation spectroscopy to measure cerebral microvascular blood flow, we developed an algorithm which translates cardiac pulses in blood flow into ICP. Our results show that ICP could be extracted to within ~4 mmHg, making this a clinically useful tool with the opportunity to replace invasive ICP sensors. This talk will summarize our optical imaging methods, experimental procedures, and results, as well as the path towards clinical translation.
Dr. Jayasinghe is a postdoctoral scholar of movement neuroscience and neurorehabilitation at Penn State University.
Learn more about Dr. Jayasinghe
Motor Lateralization and Its Role in Stroke Rehabilitation
Each hemisphere of the brain contributes complementary processes to produce an integrated behavior. The bihemispheric model of motor lateralization suggests that predictive control of trajectory and limb dynamics can be attributed to the left hemisphere, and control of limb impedance to the right hemisphere. Previous research has shown that the ipsilesional arm of severely paretic stroke survivors has substantial deficits in motor control and coordination, and that these deficits are hemisphere-dependent. In this talk, I will first present a recent study on a rare case of peripheral deafferentation that emphasizes the role of proprioception in integrating specific control contributions from each hemisphere during a reaching task. I will then describe some work from an ongoing clinical intervention study designed to understand the relative contributions of both ipsilesional and contralesional arm motor deficits to functional independence in stroke survivors with severe contralesional paresis. Overall, I am interested in understanding how motor control processes are lateralized in order to design non-invasive tools for stroke rehabilitation.
Dr. Randles is an assistant professor of Biomedical Engineering at Duke University. Her research interests include cancer cell migration, cardiovascular mechanics, high-performance computing, and computational modeling.
Massively Parallel Simulations of Hemodynamics in the Human Vasculature
The recognition of the role hemodynamic forces have in the localization and development of disease has motivated large-scale efforts to enable patient-specific simulations. When combined with computational approaches that can extend the models to include physiologically accurate hematocrit levels in large regions of the circulatory system, these image-based models yield insight into the underlying mechanisms driving disease progression and inform surgical planning or the design of next generation drug delivery systems. Building a detailed, realistic model of human blood flow, however, is a formidable mathematical and computational challenge. The models must incorporate the motion of fluid, intricate geometry of the blood vessels, continual pulse-driven changes in flow and pressure, and the behavior of suspended bodies such as red blood cells. In this talk, I will discuss the development of HARVEY, a parallel fluid dynamics application designed to model hemodynamics in patient-specific geometries. I will cover the methods introduced to reduce the overall time-to-solution and enable near-linear strong scaling on some of the largest supercomputers in the world. Finally, I will present the expansion of the scope of projects to address not only vascular diseases, but also treatment planning and the movement of circulating tumor cells in the bloodstream.
Dr. Schaefer is an assistant professor of Biomedical Engineering at Arizona State University. Her research interests include neurorehabilitation, aging, dementia and stroke.
Cognitive and Motor-based Biomarkers in Older Adults: Implications for Neurorehabilitation and Neurodegeneration
It is estimated that 1 out of every 3 physical therapy cases in the US is an adult over age 65. The increased prevalence of cognitive impairment with advancing age raises the question of whether, and to what extent, such impairments interfere with motor rehabilitation. Our work has shown that specific cognitive deficits disrupt motor learning in older adults, suggesting that cognitive assessments may be feasible biomarkers for responsiveness to motor rehabilitation. Our observed interactions between cognition and movement have also led to new research in which motor tasks are being explored as a low-cost biomarker for predicting the progression of Alzheimer’s disease.
Dr. Lynch is an assistant professor of Biomedical Engineering at Colorado University at Boulder. Her research interests include biomechanics, 3-D tissue engineering, and cancer research.
The Role of the Mechanical Microenvironment in Bone Metastasis
Approximately 1 in 4 patients with advanced breast cancer develop incurable skeletal metastasis, which is the leading cause of breast cancer-related deaths among women worldwide. Breast cancer metastasis is overwhelmingly osteolytic, causing increased fragility and fracture. Mechanical signals are well-known anabolic stimulus for bone, and they may also protect tumor-induced bone disease while also conferring anti-tumorigenic effects on bone metastatic breast cancer. This talk will discuss models and approaches for investigating the effects of mechanical loading on breast cancer bone metastasis as well as tumor-bone cell interactions.
Dr. Chung is an assistant professor of Biomedical Engineering at the University of Southern California. Her research interests include nanomedicine, regenerative medicine, and tissue engineering.
Exploiting the Body's Barriers for Nanomedicine Targeting
Natural, physiological processes in the body can act as barriers to effective nanoparticle delivery. In this seminar, I will discuss the unique advantages of small, organic micelles and their ability to harness such barriers for the detection and targeted delivery of therapeutics to diseases including cardiovascular and chronic kidney disease. For chronic kidney disease, while small molecule drugs have been proposed as a therapy to manage disease progression, repeated, high dosages are often required to achieve therapeutic efficacy, generating off-target side effects, some of which are lethal. To address these limitations, our lab has designed a kidney-targeting micelle (KM) platform toward drug delivery applications. Specifically, KMs were found to cross the glomerular filtration barrier and bind to specific surface markers present on renal tubule cells. In vivo, KMs were found to be biocompatible and showed higher accumulation in kidneys compared to non-targeted controls in vivo. We provide proof-of-concept studies for their utility in autosomal dominant polycystic kidney disease nanotherapy and their application using various routes of administration including oral and transdermal administration. We discuss the promise of nanomedicine, the tailored design necessary to match such promise, and their potential as next generation platforms for personalized medicine. Development of nanomicelles that can protect and deliver nucleic acid therapies to inhibit transformation into pathogenic cell types in cardiovascular disease will also be discussed.
Dr. Wang is an assistant professor at the MU-MCW Department of Biomedical Engineering. Her research interests include stem cell engineering; hard tissue engineering and 3D bioprinting; and cardiovascular tissue engineering, imaging, modeling, and simulation.
Stem Cell Engineering in Liver and Cardiac Applications
Stem cells are able to proliferate and differentiate into several cell types and have been broadly investigated as an alternative cell source for tissue engineering and regenerative medicine. This study examined the influence of a novel three-dimensional bioartificial microenvironment, which is derived from the decellularized liver extracellular matrix (ECM), on proliferation, hepatic differentiation, and hepatocyte-specific functions of the stem cells (iPSCs and BM-MSCs) during their in vitro culture and differentiation. After long-term in vitro cell culture, the viability, hepatogenic differentiation, and metabolic functions of stem cells cultured in ECM-enriched environment were significantly enhanced when compared with cells cultured in ECM-free environment.
Besides the liver engineering application, we also assessed the potential of decellularized porcine myocardium as a scaffold for thick cardiac patch tissue engineering. With the help of a multi-stimulation bioreactor, which was built to provide coordinated mechanical and electrical stimulation during cell culture, the decellularized myocardial scaffolds were seeded with BM-MSCs and subjected to cardiomyocyte differentiation treatment inside the bioreactor. The results from this study showed that the synergistic stimulations might be beneficial not only for the quality of cardiac construct development but also for patients by reducing the waiting time in future clinical scenarios.
Dr. Wachs is an assistant professor of biological systems engineering at the University of Nebraska—Lincoln. Her research interests include implantable force sensors for orthopaedic implants and tissue engineering.
Developing Models and Targeted Therapies for Low Back Pain
The majority of the population will experience low back pain in their lifetime. Degeneration of the intervertebral disc is highly correlated with low back pain, however, not all disc degeneration is painful. One of the most common forms of low back pain is disc-associated low back pain in which pain originates from intervertebral disc. In disc-associated low back pain, nerve fibers penetrate the previously aneural disc, where they are then thought to be stimulated by the harsh catabolic environment. Repetitive stimulation of these nerve fibers can cause sensitization and chronic pain. The overarching goal of our work is to engineer biomaterials that target these two key areas of disc-associated low back pain: nerve growth and stimulation. Current clinical treatments for chronic low back pain have limited efficacy or are highly invasive. The majority of research to date focuses on regenerating a young healthy disc. We believe our approach to target nerve growth and stimulation independent of disc regeneration has the potential shift the paradigm in the treatment of low back pain.
Dr. Bell is an assistant professor of Biomedical Engineering, Electrical and Computer Engineering, and Computer Science at Johns Hopkins University. Her research interests include ultrasonic imaging, photo-acoustic imaging, coherence-based beamforming, and image formation.
Listening to the Sound of Light to Guide Surgeries
Photoacoustic imaging offers “x-ray vision” to see beyond tool tips and underneath tissue during surgical procedures, yet no ionizing x-rays are required. Instead, optical fibers and acoustic receivers enable photoacoustic sensing of major structures – like blood vessels and nerves – that are otherwise hidden from view. The entire process is initiated by delivering laser pulses through optical fibers to illuminate regions of interest, causing an acoustic response that is detectable with ultrasound transducers. Beamforming is then implemented to create a photoacoustic image. In this talk, I will highlight novel light delivery systems, new spatial coherence beamforming theory, deep learning alternatives to beamforming, and robotic integration methods, each pioneered by the Photoacoustic & Ultrasonic Systems Engineering (PULSE) Lab to enable an exciting new frontier of photoacoustic-guided surgery. This new paradigm has the potential to eliminate the occurrence of major complications (e.g., excessive bleeding, paralysis, accidental patient death) during a wide range of delicate surgeries and procedures, including neurosurgery, cardiac catheter-based interventions, liver surgery, spinal fusion surgery, hysterectomies, biopsies, and teleoperative robotic surgeries.
Dr. Jennifer Connelly is a neuro-oncologist from the Medical College of Wisconsin. Her expertise includes the diagnosis and treatment of a wide array of brain and spine tumors. More specifically, she is focused on tumors that begin or have spread (metastasized) to the brain or spine. In addition, her clinical interests include evaluating and treating neurologic complications of cancer and cancer therapies (including paraneoplastic syndromes seizures, and neuropathies).
Engineering from Lab to Clinic - Advancements in Brain Tumor Management
Glioblastoma is the most common primary malignant brain tumor in adults. Although a rare malignancy in general, it is associated with significant neurologic morbidity and is nearly always fatal, with average survival time of 15-18 months. Treatment is challenging for a variety of reasons including the blood-brain barrier and the risk of toxicity or injury to normal brain structure. Monitoring treatment response is equally difficult as pseudoprogression is common. Several clinical cases will be presented to demonstrate how engineering and technology have aided in solving the diagnostic conundrums of brain tumor imaging and led to the most recently FDA-approved treatment modality for glioblastomas.
Dr. Maggie Bennewitz is an assistant professor of Chemical and Biomedical Engineering at West Virginia University.
Tumor and Blood Cell Tracking in Breast Cancer
Mammography is currently the gold standard method for breast cancer screening, but it misses 20% of cancers present and results in 50% of women being falsely diagnosed with breast cancer over 10 years of annual screening. Magnetic resonance imaging (MRI) detects more breast cancers than mammography; however, false positive diagnoses can also remain high with MRI due to the nonspecific and passive nature of the contrast agent. We aim to develop a tumor-targeted, pH-sensitive nanoparticle MRI contrast agent that can enhance diagnostic accuracy and reduce false positives for high risk women during breast cancer screening. Manganese oxide (MnO) nanoparticles can serve as robust pH-sensitive contrast agents for MRI due to Mn2+ release at low pH, which generates a ~30 fold change in T1 relaxivity. We will discuss strategies to control nanoparticle size, composition, and Mn2+ dissolution rates to improve MRI signal generated from pH-responsive MnO nanoparticles. Patients with metastatic breast cancer have a poor prognosis, with a 25% survival rate at 5 years. In addition, breast cancer patients have a 3 to 4 times increased risk of developing venous thromboembolism (VTE) compared to healthy subjects. VTE results in shorter survival and greater tumor recurrence. Neutrophil extracellular traps (NETs) have been identified as a common link to thrombosis, vascular injury, circulating tumor cell capture and metastasis. NETs are released from activated neutrophils and include their DNA, histones and granular content. Activated platelets and soluble tumor mediators are known to cause NET release; however, the role of tumor-derived extracellular vesicles (EVs, small cell fragments) in promoting NETosis is unknown. We have utilized state-of-the-art spinning disk confocal microscopy of the lung microvasculature in live mice to evaluate in real-time if tumor EVs cause neutrophil-platelet aggregation and NET formation. We hypothesize that tumor EVs activate platelets to adhere to neutrophils in lungs to cause NET release and begin metastatic colonization through increased thrombosis and trapping of circulating tumor cells.
Dr. Margaret Bennewitz received her BS degree in Bioengineering from the University of Pittsburgh in 2007 and her PhD from Yale University in Biomedical Engineering in 2012. At Yale, she specialized in MRI cell tracking and contrast agent development for the diagnosis of glioblastoma multiforme. After completing her doctorate, Dr. Bennewitz accepted a postdoctoral fellowship in the M+Visión Program, a collaborative venture between the Massachusetts Institute of Technology and hospitals and laboratories in Madrid, Spain. Unlike a traditional postdoctorate, this program searched globally for scholars who would define their own translational imaging projects centered around clinically relevant unmet needs. One of her projects involved the early detection of ovarian cancer using optical imaging. To diversify her imaging skills, Dr. Bennewitz subsequently accepted a second postdoctoral fellowship in the Vascular Medicine Institute at the University of Pittsburgh-School of Medicine. There, she created a setup to perform multiphoton imaging of the blood vessels in the lungs of live mice with sickle cell disease. Dr. Bennewitz used this technique to study the cellular and molecular mechanism of vascular blockage (vaso-occlusion) in the lungs. Dr. Bennewitz joined the faculty at West Virginia University as an Assistant Professor in the Department of Chemical and Biomedical Engineering in August 2017. Her lab specializes in the development of new MRI contrast agents for early breast cancer detection and the use of in vitro and in vivo fluorescence imaging techniques to elucidate the role of the tumor microenvironment in promoting breast cancer metastasis to the lungs.
Dr. Joy Lincoln is the Peter Sommerhauser Chair of Quality, Outcomes and Research Professor for the Department of Pediatrics at the Medical College of Wisconsin and Director of Cardiovascular Research at The Herma Heart Institute, Division of Pediatric Cardiology, Children's Wisconsin.
Discovery Insights for the Development of Calcific Aortic Valve Disease Insights
Calcific Aortic Valve Disease affects up to 13% of the population and accounts for over $20 billion in healthcare spending each year in the US. Despite the prevalence, therapeutic options are limited and to date, the only effective treatment is surgical repair or replacement which comes with insuperable complications and no guarantee of life-long success. Therefore, there is a critical need to develop more efficient alternative treatments, however advancements have been limited by our current poor understanding of the pathobiology of the disease. To address this, our lab is taking multidisciplinary approaches to understand the process of calcification in the aortic valve and these studies consider hemodynamic influences on mechanosensitive cell signaling. From these data, we are working towards the development of mechanistic-based therapies beyond surgical intervention that will improve the outcome of patients affected by this debilitating disease.
Dr. Jeffrey Engelmann is an assistant professor in the department of Psychiatry and Behavioral Medicine at the Medical College of Wisconsin.
Learn more about Dr. Engelmann
Neurobiological Insights into Nicotine Addiction: Evidence from fMRI Research
Tobacco use is the leading preventable cause of disease and death worldwide. In the US, the use of combustible tobacco products such as cigarettes causes over 440,000 deaths and $300 billion in economic costs each year. Tobacco use behavior is driven by dependence on nicotine, the primary psychoactive constituent of tobacco smoke. Current treatments for nicotine dependence have limited efficacy. Neuroscientific research into brain systems and processes that contribute to nicotine dependence has the potential to inform the development of more effective interventions for nicotine dependence and other addictions. One methodology for studying mechanisms that contribute to nicotine dependence is functional magnetic resonance imaging (fMRI). fMRI provides a non-invasive measure of human brain activation. For this presentation, I will discuss two uses of fMRI data to study nicotine dependence. First, fMRI can be used as a dependent (i.e., response) variable. In this case, it is possible to compare the effect of self-reported states (e.g., withdrawal symptoms), behavioral factors (e.g., smoking satiation or short-term deprivation), or pharmacological factors (e.g., medication) on brain activation. Second, fMRI can be used as an independent (i.e., predictor) variable. In this case, fMRI data are used to predict behavioral outcomes (e.g., relapse over the course of a six-month smoking cessation attempt). Using fMRI as a voxel-wise (voxel-by-voxel) predictor variable is new to the area of addiction research. Thus, computational steps involved in this approach will be presented. After this talk, attendees will have a better understanding of brain systems and processes involved in nicotine dependence and other addictions and will have been introduced to computational methods that are used to arrive at these conclusions.
Tobacco use is the leading preventable cause of disease and death worldwide. In the US, the use of combustible tobacco products such as cigarettes causes over 440,000 deaths and $300 billion in economic costs each year. Tobacco use behavior is driven by dependence on nicotine, the primary psychoactive constituent of tobacco smoke. Current treatments for nicotine dependence have limited efficacy. Neuroscientific research into brain systems and processes that contribute to nicotine dependence has the potential to inform the development of more effective interventions for nicotine dependence and other addictions. One methodology for studying mechanisms that contribute to nicotine dependence is functional magnetic resonance imaging (fMRI). fMRI provides a non-invasive measure of human brain activation. For this presentation, I will discuss two uses of fMRI data to study nicotine dependence. First, fMRI can be used as a dependent (i.e., response) variable. In this case, it is possible to compare the effect of self-reported states (e.g., withdrawal symptoms), behavioral factors (e.g., smoking satiation or short-term deprivation), or pharmacological factors (e.g., medication) on brain activation. Second, fMRI can be used as an independent (i.e., predictor) variable. In this case, fMRI data are used to predict behavioral outcomes (e.g., relapse over the course of a six-month smoking cessation attempt). Using fMRI as a voxel-wise (voxel-by-voxel) predictor variable is new to the area of addiction research. Thus, computational steps involved in this approach will be presented. After this talk, attendees will have a better understanding of brain systems and processes involved in nicotine dependence and other addictions and will have been introduced to computational methods that are used to arrive at these conclusions.
Dr. Karthik Somasundaram is a postdoctoral fellow working under Dr. Frank Pintar at the Zablocki VA Medical Center Laboratories. His research focuses on the development of spine injury criteria, response corridors and computational human model to assess armored vehicle occupant injury during underbody blast scenarios.
Occupant Injury and Response on Oblique-facing Aircraft Seat—A Computational Study
In recent years, the airline industry in transitioning the seat configuration of first and business class seats from the traditional side-by-side parallel row seating to a configuration that mounts the seats at an angle relative to the aircraft centerline. This oblique orientation allows the airlines to simultaneously add passenger seating capacity and increase comfort by accommodating a lie flat configuration for sleeping. Preliminary whole-body PMHS sled tests with oblique-facing seat configuration reported high risk of lumbar and flailing injuries. These sled tests did provide an insight into occupant kinematics; however, there is a lack of segmental level kinematic and biomechanical responses to fully understand the mechanism of injury. To address this, I used computational modeling approach to understand the component level kinematic and load generated in the spine due to oblique loading. In house developed 75 year old male GHBMC model was selected for this study. The validation of the model biofidelity was based on the resultant acceleration, angular velocity and displacement of the spine and pelvis obtained from PMHS tests. With this validated model, I am working on parametric simulations that will assist in designing boundary conditions for future PMHS tests and in the development potential injury threshold. Further, the validated model can be used as an assessment tool in injury mitigation and aircraft seat energy management studies.
Dr. Priyanka Shah-Basak is a biomedical engineer and cognitive neuroscientist whose work focuses on optimizing neurorehabilitation approaches for the treatment of cognitive disorders in acquired and neurodegenerative diseases.
Learn more about Dr. Shah-Basak
Stroke is a leading cause of aphasia, a language impairment affecting multiple aspects of human communication including language production, comprehension, reading and writing. Approximately 180,000 new cases of aphasia are identified per year, and 1 million or 1 in 250 are currently living with aphasia in the United States. In the weeks and months following stroke, a majority of patients experience partial recovery and regain some language functions, but they seldom make a full recovery. Some patients continue to experience moderate to severe impairments, which undermine their social, vocational, and emotional well-being. They find everyday conversations difficult resulting in increased dependency on caregivers for daily activities, inability to work, social isolation and often depressive symptoms. While outpatient speech and language therapies are available, the observed treatment effects are often inconsistent across patients, and modest at best. There is a need to develop new treatment strategies that can effectively boost therapeutic benefits. Neurorehabilitation approaches guided by theoretical models of language impairments and our understanding of neural changes underlying aphasia recovery are needed to enhance language recovery after stroke. One approach that is being widely investigated is pairing noninvasive brain stimulation, particularly transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS), with language therapies for therapeutic enhancements. However, a number of mechanistic questions such as where to target stimulation for best results and the neural bases of stimulation-induced therapeutic gains, remain open. In this talk, I will review the existing literature on the use of tDCS and TMS as treatment boosters in post-stroke aphasia. I will then focus on tDCS and tDCS parameters that are crucial for neurorehabilitation applications in aphasia. Finally, I will discuss results from my studies using resting-state magnetoencephalography (MEG) to investigate the neural underpinnings of tDCS, and end with future directions.
Dr. Adam Wang develops technologies for advanced x-ray and CT imaging, including novel system design, model-based image reconstruction, spectral imaging, and radiation transport methods.
Learn more about Dr. Adam Wang
Advances in x-ray and CT Imaging Enabled by Academic-industrial Collaborations
This talk will discuss two examples of successful academic-industrial collaborations in the areas of x-ray and computed tomography (CT) imaging. In the first, I will share my prior perspective from industry, collaborating with Prof. Taly Schmidt, and how tools developed in image-guided radiation therapy led to fast and accurate radiation dose reporting for CT imaging. In the second, I will share my perspective from academia, collaborating with industry on a novel dual-layer x-ray detector that provides simultaneous dual-energy x-ray images. With these dual-energy images, we can uniquely identify different materials such as soft tissue, bone, or contrast agents for better image guidance. Lastly, I will present on our recent efforts to improve chest x-ray imaging of COVID patients using the dual-layer detector.
Dr. Shelli Kesler is an Associate Professor, University of Texas—Austin; Director of Statistical Services, Cain Center for Nursing Research; Co-Chair of Survivorship and Supportive Care Research, LIVESTRONG Cancer Institutes; and Director, Cancer Neuroscience Lab.
Chemobrain Facts and Fictions
Cognitive impairment is one of the most common adverse events associated with cancer treatments. Patients with cognitive impairment demonstrate reduced quality of life and increased psychological distress as well as decreased survival. Research in this area has progressed significantly over the past 5–10 years but was previously very limited due to the controversy surrounding this syndrome. In this presentation, I will review three of the most common arguments that have been presented against the existence of cancer-related cognitive impairment, or “chemobrain” as it is colloquially known. I will show how my group’s neuroimaging research has helped to debunk these myths and validate patients’ experiences following cancer diagnosis and treatment. I will discuss results of our clinical cohort and preclinical rodent studies as well as some clinical and preclinical randomized controlled trials. Attendees will gain understanding regarding the “chemobrain” syndrome and its neural phenotypes and hear about emerging efforts to prevent and address these symptoms.
Tracking the health of the retina with noninvasive imaging: Beyond the fundus image
The advent of adaptive optics (AO) ophthalmoscopy has enabled noninvasive visualization of cone structure in both health and disease. In this talk, I will introduce adaptive optics as a technique and show its evolution as an essential tool for researchers and clinicians alike. Additionally, I will discuss the structural and functional measurements currently in use in the field. Next, I will examine the utility and limitations of structural measurements for assessing disease. Finally, I will show how nascent functional measurements can be obtained using an AO ophthalmoscope, and explore how well these functional measurements align with our current understanding of retinal function.
Object Perception in Humans and Machines
To navigate a complex and dynamic visual environment, our brain has to solve many different perceptual problems. One fundamental goal of our perceptual system is to partition the world into objects that can be identified and acted on. While this may seem straightforward because we see and interact with objects so effortlessly, most objects comprise many features (like color, shape and size) that we can view from many viewpoints, with many other objects and in many different contexts. How does the brain integrate different features into a coherent object representation, and how are such representations transformed to accommodate differences in viewpoint and context? I will present a series of studies that investigate the nature of the neural representations and operations that underlie such challenges of object perception. I will also discuss some new research that explores the emergence of perceptual operations by investigating failures of object perception—visual illusions—in artificial deep neural networks.
Patient-Specific Numerical Analysis of Coronary Blood Flow in Children with Intramural Anomalous Aortic Origin of Coronary Arteries
Intramural anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital heart defect where the origin of a coronary artery originates from the wrong sinus of Valsalva with an acute angle (angle of origin) and follows a course within the aortic wall. A surgical technique, known as “unroofing”, addresses this pathology by removing the intramural coronary segment and opening the potentially restrictive anomalous coronary orifice with the creation of a large neo-orifice designed to arise perpendicularly from appropriate aortic sinus. Recent reports of sudden cardiac arrest after surgical unroofing have raised questions about the long-term consequences of this treatment, but the exact mechanism of ischemia and morbidity in these patients is unclear. Although abnormal angle of origin has been assumed to be a contributing factor in changing coronary artery blood flow patterns (i.e. hemodynamics), the effects of this anatomic feature on resulting hemodynamics have not been investigated in detail. The objectives of this study are to 1) analyze morphology and coronary blood flow patterns in AAOCA patients pre-operatively as well as post-unroofing, and 2) determine the effect of angle of origin on indices related to ischemia in a virtually manipulated model. The results of this study will characterize hemodynamic parameters previously linked to morbidity in AAOCA patients for the first time and determine the altered hemodynamics for risk stratification after unroofing surgery.
Advancing Neurorehabilitation for Children and Infants with Stroke: Non-invasive Brain stimulation to Assess Modulate the Developing Brain
Stroke occurring at or around the time of birth, termed perinatal stroke, often leads to a diagnosis of cerebral palsy, a condition associated with permanent impairments in movement, sensory, and cognitive function. Despite the increased neuroplastic state of the developing brain after perinatal stroke relative to adult stroke, the outcomes after perinatal stroke are still not optimal, as about 50% will experience some form of movement disability. The best rehabilitative therapies currently available for children with perinatal stroke are time-intensive and are not necessarily tailored to each individual. In this presentation, I will first describe how we use non-invasive techniques such as MRI and transcranial magnetic stimulation to understand how the brain has developed and reorganized after perinatal stroke, providing potential biomarkers to assess responses to therapy. Then I will share our lab’s unique work in exploring novel combined therapies of rehabilitation and non-invasive brain stimulation to influence brain circuits that are essential for recovery of movement function. Finally, I will describe my future research plans, which involve identifying the role of non-invasive stimulation for neurorehabilitation therapies in people with neurological injury across the lifespan.
Using Computational Neuroscience to Uncover the Brain Mechanisms Subserving Human Behavior
The modern world regularly bombards the sensory organs with far more information than the brain can process at any moment in time. It is, therefore, critical that some degree of data reduction take place so that only behaviorally relevant information is processed, and irrelevant information is ignored. Attention is the process that accomplishes the selection of pertinent sensory signals, at the expense of distractors, guiding our perception of the environment and virtually all of our movements, decisions, and memories. My research program aims to specify (1) the effects of attention on behavior, (2) the cortical architecture of attention, and (3) the resultant perceptual representation after attentional selection. Through the use of functional neuroimaging, machine learning techniques, brain stimulation, and high-resolution structural imaging measures, I will provide evidence for specialization within the frontoparietal attention network that is tied directly to behavior. I will further specify a cortical architecture that explains how attention signals can directly modulate visuospatial processing. I will also show how we use computational models to ascribe specific behaviors to functional neural units. Together, this demonstration of neural specialization and communication outlines a comprehensive model that links behavioral measures with the brain structures in which they are implemented and has direct implications for understanding a range of behavioral deficits.
Learn more about Dr. Greenberg
Ankle Joint Complex Kinematics following Surgical Intervention in Patients with End-Stage Ankle Osteoarthritis
Ankle osteoarthritis (OA) affects 100,000 individuals per year. Most cases of ankle OA are secondary to trauma, and thus, patients are typically younger than those with knee OA. Two surgical options are available: ankle arthrodesis (i.e., fusion of the tibia to the talus) or total ankle replacement (TAR). Arthrodesis provides pain relief, but 50% of patients are unable to return to their desired activities. Furthermore, 100% of patients suffer from painful adjacent subtalar joint OA 20 years post-op. TAR is an attractive alternative to arthrodesis, as it enables tibiotalar motion. Unfortunately, TAR survival rates are much lower than knee or hip arthroplasty: 29% of TAR implants fail within 10 years and 38% need at least one revision of the prosthetic components. With neither surgical option being an optimal solution, we aim to study post-operative ankle joint complex kinematics in these two surgical populations using a biplane fluoroscopy imaging system to investigate subtalar joint compensations and TAR implant motion. In this presentation, I will first describe the post-operative subtalar kinematics in patients following tibiotalar arthrodesis. Then I will share our lab’s newly developed approach to apply novel image tracking methods to biplane fluoroscopy images using a hybrid model of patient specific TAR bone and implant models. Finally, I will describe our preliminary kinematic results in patients following TAR and compare the kinematics to the arthrodesis cohort and to healthy controls. Ultimately our goal is to improve the understanding of ankle joint complex motion during dynamic tasks to improve surgical outcomes and quality of life for patients with end-stage ankle OA.
Biomarkers for the acute and cumulative effects of sport-related concussion
Sport-related concussion (SRC) is a major public health concern given the millions of at-risk youth and young adult athletes. Currently, clinical management of SRC is largely dependent on self-reported symptoms, highlighting the need to identify objective biomarkers to track the time course of physiological recovery following SRC. In addition, there is growing concern that repeated concussion and potentially even contact sport exposure without concussion may be associated with adverse outcomes. This talk will describe work aimed at identifying neuroimaging and blood-based biomarkers of the acute and chronic effects of SRC. Recent work characterizing the time course of neurophysiological recovery following a single SRC across different aspects of the neurometabolic cascade of concussion and their relationship with clinical recovery will be highlighted. In addition, emerging evidence supporting the hypothesis that repeated concussion and contact sport exposure are associated with differences in brain structure and function in young, active athletes will be presented.
mHealth Projects
The opportunities for interdisciplinary mobile health (mHealth) research are extraordinary, bringing computer science together with the health researchers and practitioners to dramatically improve public health, global health and well-being of individuals and populations around the world. The goal of mHealth is to connect data, people and systems towards the development and integration of innovative computer, software and applications to support the transformation of health and medicine. Advances in communications, computer, and medical technology have facilitated the practice of personalized health, which utilizes sensory computational communication systems to support improved basic care and more personalized healthcare and healthy lifestyle choices. The proliferation of broadband wireless services, along with more powerful and convenient handheld devices, is helping to introduce real-time monitoring and guidance for a wide array of patients. The smart health research community and industry are now connecting medical care with technology developers, vendors of wireless and sensing hardware systems, network service providers, and data management communities. The UbiComp Laboratory at Marquette University, USA encourages research and breakthrough ideas in areas of mHealth such as networking, pervasive computing, analytics, sensor integration, privacy and security, socio-behavioral models, and cognitive processes and system and process modeling. In this talk, a few mHealth projects including two global mHealth projects will be presented.
Technology in MS care—An Opportunity to Make an Impact
Multiple sclerosis (MS) is a chronic, lifelong, neurodegenerative and demyelinating disease of the central nervous system. It mostly affects young adults and can result in significant impairments and loss of abilities. Symptoms may include disturbances in the visual system, motor abilities, sensory perception, balance, bowel/bladder/sexual functions, fatigue, cognitive impairments, among others. Accurate diagnosis is not straightforward and often includes the art of combining clinical assessments with laboratory and imaging findings. The disease course is unpredictable, and current treatments have a variable degree of success in reducing “relapses,” which are the hallmark of the majority of cases. During these relapses, patients accumulate difficulties and may not recover well. Despite treatment, some patients progress, and the disease gets worse over time due to accelerated neuronal loss. Symptomatic therapy is key for successful management of the disease. Prosthetics and other innovations play a major role in helping individuals living with MS to navigate their daily life and remain functional in society. There are several examples of existing technologies that are available, but there are many unmet needs for the care of individuals living with MS in the USA and globally.
Objectives:
1. To provide an overview and discussion of MS from a clinical perspective.
2. To discuss unmet needs and opportunities for innovation locally and globally.
Endothelialization of Implantable Cardiovascular Devices by Magnetic Cell Targeting
Regenerative engineering promises to deliver next-generation tissue and organ replacements capable of remodeling, repair, and growth. Such capabilities would provide for improved safety and durability compared to existing treatment options. Emerging nanotechnologies are enabling this exciting paradigm shift in medicine by allowing for designed control over cellular activities. This seminar will cover the development of nanoparticles and nanofibers used to capture and retain endothelial cells with magnetic force. This approach is being applied to implantable cardiovascular devices including coronary stents, stent-grafts, vascular grafts, and heart valves for the purpose of improving healing and blood-compatibility. Both in vitro and large-animal implantation studies will be presented.
Advancing MRI Techniques for Spinal Cord Injury
Spinal cord injury (SCI) is a devastating injury with a pronounced long-term impact on quality of life. Medical care in the acute period is critical to outcomes, and a primary goal is to minimize damage occurring beyond the initial insult (i.e., secondary injury). While advanced MRI methods including diffusion- and perfusion-weighted imaging have emerged as integral tools for patient care in other acute injuries, especially cerebral ischemia, similar advances have not been realized for the spinal cord. MRI of the spinal cord is more challenging given its small size, the effects of motion, and the presence of bony structures that perturb the magnetic field. This talk will discuss the work of my lab to advance MRI of the spinal cord aimed at detecting the degree of injury, predicting neurological outcomes, and potentially guiding established and emerging therapies. I will describe how we use a variety of approaches across the translational spectrum, from computational modeling of neuronal injury to animal models and, more recently, clinical studies of human SCI. Our ultimate goal is to enhance MRI as a clinical tool that can aid in improving outcomes of those that suffer from such a potentially life-altering injury.
Finite Element Modeling of Human Lower Leg Impacts: Development and Applications
Lower leg fractures are common injuries in both the civilian and military fields. Such injuries are often caused by axial loading via falls, vehicle collisions, or underbody blast events. After treatment, these injuries are associated with long-term disability, chronic pain, and impaired mobility. Avoiding or minimizing injuries are both valid avenues for minimizing the harm from these incidents. Finite element modeling offers tools to reconstruct injurious events to facilitate injury mitigation and prevention. This talk describes the development of a lower-leg finite element model derived from medical images and validated against cadaveric experimental data. Following, applications of the model to evaluate the protective capabilities of combat boots, the effects of foot arch height, and the likelihood of calcaneal fractures in axial impacts are reviewed. This talk will then conclude with a discussion of potential topics for future work such as scaling, material characterization, and additional body regions.
Tissue Engineering Applications of an Amnion-based Barrier Membrane
Cleft lips and/or palates are the most common oral and craniomaxillofacial birth defects. Properly restoring the severe cleft palates remains a major challenge insufficient autologous soft tissues to close the open wounds. Furthermore, since the ideal time for renovating cleft palate is shortly after birth, surgeries should cause minimal disruption of the skeleton to allow tissue growth in children. This study aims to create a barrier for cleft palate repair through incorporating poly (1,8-octamethylene-citrate) (POC) onto the decellularized amnion membrane (DAM) in order to improve both biological and mechanical properties of the native amnion tissue. The success of POC incorporation onto the DAM was confirmed by laser-induced breakdown spectroscopy (LIBS) and fluorescence detecting. The DAM-POC scaffold preserved the basic structural and biomechanical integrity and showed a prolonged degradation period as compared to the natural amnion material. The DAM-POC scaffold is cell compatible when seeded with human mesenchymal stem cells (hMSCs), as evidenced by high cell viability, and promotes osteogenic differentiation and matrix mineralization. When applied for repairing the cleft palate in a young rat model, the DAM-POC scaffold showed good biocompatibility and improved tissue integration, angiogenesis, and bone regeneration. Importantly, the DAM-POC scaffold could further facilitate the ongoing tissue regeneration and reduce the associated complications and healing time after surgery. In conclusion, modification of the natural DAM scaffold with POC may contribute to the overall beneficial effect in retaining the matrix structure, mechanical property, and stability for developing a proper, cell-free DAM-based barrier with structural, mechanical, and biological properties suitable for repairing cleft palate in the oral cavity.
Learning and Error in Human-Machine Interfaces
An intracortical brain-computer interface (iBCI) is a system that interprets a person’s intentions from electrical recordings of neurons in their brain and is designed to enhance a paralyzed person’s ability to interact with world. But designing algorithms that “decode” recorded neural activity into useful commands to an assistive device (like a computer cursor or power wheelchair) is a big unsolved problem. Dr. Danziger constructs interactive, closed-loop models used for designing iBCI decoders without the need to implant electrodes in people’s brains, which facilitates rapid prototyping and scientifically rigorous performance evaluation. The iBCI models have shown that the scientific community’s seemingly reasonable assumptions about how people interact with adaptive decoders, such as “they try to minimize error” or “they try to move their devices in straight lines”, are insufficient to describe people’s actual control strategies. These results are helping to guide the next generation of neural decoders to account for high-level user control strategies and the interaction between human learning and decoder adaptation.
