Graduate Seminar Series

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.

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Abstract

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. 

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Abstract

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.

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Abstract

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.

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Abstract

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.

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Abstract

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.

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Abstract

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.

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Abstract

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. 

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Abstract

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 nontargeted 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.

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Abstract

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.

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Abstract

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.

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Abstract

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).

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Abstract

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.