Happening @ Michigan https://events.umich.edu/list/rss RSS Feed for Happening @ Michigan Events at the University of Michigan. BME 500: Kelly Stevens (February 27, 2020 4:00pm) https://events.umich.edu/event/70067 70067-17505693@events.umich.edu Event Begins: Thursday, February 27, 2020 4:00pm
Location: Electrical Engineering and Computer Science Building
Organized By: Biomedical Engineering

The notion of building artificial human organs has moved from a far-fetched concept to the forefront of regenerative medicine research. While progress is being made, most tissues created to date are simply not large enough to support clinically meaningful functions, and their structural features remain an magnitude coarser in resolution than native tissues. Few organs better represent this challenge than the liver – the largest visceral organ in the human body, in which hepatocytes are aligned in single cell-width structures entangled with vascular and biliary networks. To address this challenge, we are working to develop a portfolio of tools that integrate 3D printing, synthetic biology, and the innate capacity of cells to self-assemble. We are applying these tools to decode the signals that drive tissue assembly during development, and using this information to build scaled artificial tissues that replicate the features of native tissues.

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Workshop / Seminar Thu, 20 Feb 2020 11:04:16 -0500 2020-02-27T16:00:00-05:00 2020-02-27T17:00:00-05:00 Electrical Engineering and Computer Science Building Biomedical Engineering Workshop / Seminar BME Event
BME 500: Ruobo Zhou (March 5, 2020 4:00pm) https://events.umich.edu/event/73399 73399-18214945@events.umich.edu Event Begins: Thursday, March 5, 2020 4:00pm
Location: Industrial and Operations Engineering Building
Organized By: Biomedical Engineering

Biomolecular interactions are at the root of all biological processes and define the molecular mechanisms of how these processes are accomplished in both physiological and pathological conditions. Recent advances in single molecule detection and super-resolution fluorescence microcopy have uncovered previously unknown properties of biomolecular interactions, including multivalency, transiency, and heterogeneity, and revealed the organizational principles governing the compartmentalization of functional biomolecular interactions in cells and how such compartmentalization and organizations become dysregulated in diseases. In this talk, I will first discuss my postdoctoral work, where I used mass-spectrometry-based analysis and super-resolution imaging to dissect the protein-protein interactions at the plasma membrane of neurons, and discovered that a newly identified membrane-associated periodic skeleton (MPS) structure can function as a signaling platform that coordinates the interactions of signaling proteins at the plasma membrane of neurons. In response to extracellular stimuli, G-protein coupled receptors, cell-adhesion molecules, receptor tyrosine kinases can be recruited to the MPS to form signaling complexes at the plasma membrane, and such recruitment is required for downstream intracellular signaling. This work not only reveals an important, previously unknown function of the newly discovered MPS structure, but also provides novel mechanistic insights into signal transduction in neurons. I will then discuss my graduate work, where I developed a hybrid single molecule technique combining single molecule FRET and optical tweezers, and applied this technique to probe the sub-molecular dynamics of protein-DNA interactions in various biological systems involved in DNA replication, repair and recombination.

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Lecture / Discussion Fri, 28 Feb 2020 11:07:38 -0500 2020-03-05T16:00:00-05:00 2020-03-05T17:00:00-05:00 Industrial and Operations Engineering Building Biomedical Engineering Lecture / Discussion BME Logo
BME 500: Rebecca Wachs (March 12, 2020 4:00pm) https://events.umich.edu/event/70068 70068-17505695@events.umich.edu Event Begins: Thursday, March 12, 2020 4:00pm
Location: Electrical Engineering and Computer Science Building
Organized By: Biomedical Engineering

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.

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Workshop / Seminar Tue, 10 Mar 2020 11:43:59 -0400 2020-03-12T16:00:00-04:00 2020-03-12T17:00:00-04:00 Electrical Engineering and Computer Science Building Biomedical Engineering Workshop / Seminar BME Event
Ph.D. Defense: Ahmad Asif A Jiman (March 24, 2020 10:00am) https://events.umich.edu/event/73841 73841-18426650@events.umich.edu Event Begins: Tuesday, March 24, 2020 10:00am
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be hosted via Zoom. You can log in with this link:

https://umich.zoom.us/j/329580834
Meeting ID: 329-580-834

Diabetic patients suffer from a long-term condition that results in high blood glucose levels (hyperglycemia). Many medications for diabetes lose their glycemic control effectiveness over time and patient compliance to these medications is a major challenge. Glycemic control is a vital continuous process and is innately regulated by the endocrine and autonomic nervous systems. There is an opportunity for developing an implantable and automated treatment for diabetic patients by accurately detecting and altering neural activity in autonomic nerves. The renal and vagus nerves contribute in glycemic control and are potential targets for this proposed treatment. This dissertation investigated stimulation of renal nerves for glycemic control, assembled an implantation procedure for neural interface arrays designed for autonomic nerves, and demonstrated high-fidelity physiological signals in the vagus nerve of rats.

Stimulation of renal nerves at kilohertz frequency (33 kHz) showed a notable average increase in urine glucose excretion (+24.5%). In contrast, low frequency (5 Hz) stimulation of renal nerves showed a decrease in glucose excretion (−40.4%). However, these responses may be associated with urine flow rate.

Kilohertz frequency stimulation (50 kHz) of renal nerves in diabetic rats showed a significant average decrease (-168.4%) in blood glucose concentration rate, and an increase (+18.9%) in the overall average area under the curve for urine glucose concentration, with respect to values before stimulation.

An innovative procedure was assembled for the chronic implantation of novel intraneural MIcroneedle Nerve Arrays (MINAs) in rat vagus nerves. Two array attachment approaches (fibrin sealant and rose-bengal bonding) were investigated to secure non-wired MINAs in rat vagus nerves. The fibrin sealant approach was unsuccessful in securing the MINA-nerve interface for 4- and 8-week implant durations. The rose-bengal coated MINAs were in close proximity to axons (≤ 50 μm) in 75% of 1-week and 14% of 6-week implants with no significant harm to the implanted nerves or the overall health of the rats.

Using Carbon Fiber Microelectrode Arrays (CFMAs), physiological neural activity was recorded on 51% of inserted functional carbon fibers in rat vagus nerves, and 1-2 neural clusters were sorted on each carbon fiber with activity. The mean peak-to-peak amplitudes of the sorted clusters were 15.1-91.7 µV with SNR of 2.0-7.0. Propagation of vagal signals were detected in the afferent direction at conduction velocities of 0.7-1.0 m/sec, and efferent signals at 0.7-8.8 m/sec, which are within the conduction velocity range of myelinated and unmyelinated vagus fibers. Furthermore, changes in vagal nerve activity were monitored in breathing and blood glucose modulated conditions.

Overall, this dissertation investigated modulation of neural activity for glycemic control, assembled a new chronic implantation procedure for nerve interface arrays, and monitored physiological signaling in an autonomic nerve. Future work is needed to fully understand the physiological neural signaling, and evaluate the long-term tissue reactivity and recording integrity of implanted electrodes in autonomic nerves. This work supports the potential development of an alternative implantable treatment modality for diabetic patients by modulating and monitoring neural activity in autonomic nerves.

Date: Tuesday, March 24, 2020
Time: 10:00 AM
Location: North Campus Research Complex (NCRC), B10-G64
Chair: Dr. Tim M. Bruns

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Lecture / Discussion Mon, 23 Mar 2020 14:08:39 -0400 2020-03-24T10:00:00-04:00 2020-03-24T11:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion U-M BME Event
Zhen Xu, PhD: Histotripsy Webinar (March 25, 2020 10:00am) https://events.umich.edu/event/73931 73931-18426654@events.umich.edu Event Begins: Wednesday, March 25, 2020 10:00am
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This will be held online. Click the link below to register.

https://fusfoundation.zoom.us/webinar/register/WN_Hj_R2DMOT8SlOAp0WRLV3A

Oftentimes when we think of focused ultrasound, we imagine using it to heat and kill tissue. Unlike thermal ablation, histotripsy uses focused ultrasound to mechanically disrupt the target tissue without heating. Histotripsy turns the tissue into liquid-appearing acellular debris – which is absorbed by the body over one to two months – resulting in effective tissue removal.

Histotripsy has been shown to stimulate a powerful immune response in cancer treatment studies. In the treatment of neurological diseases, transcranial histotripsy can produce well-confined focal treatment in a wide range of locations and volumes in the brain, offering the potential to increase the treatment envelope while decreasing treatment time.

Please register to join us at 10:00 AM Eastern on Wednesday, March 25, when Zhen Xu, PhD, will discuss the basic mechanism, instrumentation, bioeffects, and applications of histotripsy. She will also cover the latest preclinical and clinical trial results of developing histotripsy for the treatment of cancer and neurological diseases.

About the Speaker

Zhen Xu, PhD, is a tenured Associate Professor in the Department of Biomedical Engineering at the University of Michigan and a primary inventor and pioneer in histotripsy.

She has received many notable awards, including:
IEEE Ultrasonics, Ferroelectrics, and Frequency Control Society Outstanding Paper Award (2006)
American Heart Association Outstanding Research in Pediatric Cardiology (2010)
National Institutes of Health (NIH) New Investigator Award at the First National Institute of Biomedical Imaging and Bioengineering (NIBIB) Edward C. Nagy New Investigator Symposium (2011)
The Federic Lizzi Early Career Award from The International Society of Therapeutic Ultrasound (ISTU) (2015)
Fellow of the American Institute of Medical and Biological Engineering (2019)
Dr. Xu is currently an associate editor for three notable journals: IEEE Transactions on Ultrasound, Ferroelectrics, and Frequency Control (UFFC); Frontiers in Bioengineering; and BME Frontiers. She is an elected board member of ISTU, a charter member of the US NIH study section, and a principal investigator of grants funded by the Focused Ultrasound Foundation, NIH, American Cancer Association, Office of Naval Research, The Hartwell Foundation, and The Coulter Foundation.

She received her PhD from the University of Michigan in 2005.

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Livestream / Virtual Mon, 23 Mar 2020 14:42:17 -0400 2020-03-25T10:00:00-04:00 2020-03-25T11:00:00-04:00 Off Campus Location Biomedical Engineering Livestream / Virtual BME Logo
Ph.D. Defense: Brittany Rodriguez (March 26, 2020 10:00am) https://events.umich.edu/event/73840 73840-18339520@events.umich.edu Event Begins: Thursday, March 26, 2020 10:00am
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: Will be held via BlueJeans.

BlueJeans Link: https://umich.bluejeans.com/478989984

Volumetric muscle loss (VML) is the traumatic or surgical loss of skeletal muscle comprising 20-30% or more of the total muscle volume. By definition, VML exceeds the muscle’s capacity for self-repair and results in persistent functional deficits. Significantly, no treatment options exist that can fully restore native structure and function. To address the limitations of current treatments, our laboratory has developed tissue-engineered skeletal muscle units (SMUs) as a novel treatment for VML repair. SMUs have shown promising regenerative potential in a rat VML model; however, limitations of rodent models necessitated transitioning our technology to a large animal (sheep) model.



Despite substantial heterogeneity of muscle progenitor cell populations obtained from craniofacial, trunk, and limb muscle, engineered skeletal muscle tissues are almost exclusively fabricated from cells derived from hindlimb muscle, making the effects of cell source on engineered muscle tissue unknown. Thus, we conducted a comparison of SMUs fabricated from muscle cells isolated from both craniofacial and hindlimb muscle sources and evaluated the effects of these cell sources on SMU structure and function. Specifically, we showed that the semimembranosus muscle was the most clinically relevant muscle source for the fabrication of SMUs.

We also sought to develop a method to scale our SMUs to clinically relevant sizes. We developed a modular fabrication method that combines multiple smaller SMUs into a larger implantable graft. Consequently, we successfully fabricated of one of the largest engineered skeletal muscle tissues to date while avoiding the formation of a necrotic core. To treat peripheral nerve injuries that often accompany VML, we also developed engineered neural conduits (ENCs) to bridge gaps between healthy native nerve and the injury site. We used scaled-up SMUs and ENCs to treat a 30% VML in the ovine peroneus tertius muscle. After a 3-month recovery, SMU-treated groups restored muscle mass and force production to a level that was statistically indistinguishable from the uninjured contralateral muscle.

Lastly, we evaluated the efficacy of SMUs in repairing craniofacial VML. Despite reported differences in the regenerative capacity of craniofacial muscle compared to limb muscle, prior to my thesis there were no models of craniofacial VML in either large or small animal models. Thus, we introduced the first model of craniofacial VML and evaluated the ability of SMUs to treat a 30% VML in the zygomaticus major muscle. Despite using the same injury and repair model in both implantation studies, results showed differences in pathophysiology between craniofacial and hindlimb VML. The fibrotic response was increased in the facial muscle model, and there was tissue tethering and intramuscular fat deposition that was not observed in the hindlimb study. The craniofacial model was also confounded by concomitant denervation and ischemia injuries which was too severe for our SMUs to repair. This study highlighted the importance of balancing the use of a clinically realistic model while also maintaining control over variables related to the severity of the injury.

Overall, this work significantly contributed to the field of skeletal muscle tissue engineering by evaluating the effects of muscle source on the structure and function of SMUs, created a modular fabrication method for tissue scale-up, and introduced a new large animal model, and a craniofacial model of VML. The success of this technology demonstrates its potential for treating clinical VML in the future.

Chair: Dr. Lisa Larkin

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Lecture / Discussion Tue, 24 Mar 2020 14:49:10 -0400 2020-03-26T10:00:00-04:00 2020-03-26T11:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion U-M BME Event
Ph.D. Defense: Tyler Gerhardson (March 26, 2020 10:00am) https://events.umich.edu/event/73025 73025-18129601@events.umich.edu Event Begins: Thursday, March 26, 2020 10:00am
Location: Lurie Robert H. Engin. Ctr
Organized By: Biomedical Engineering

NOTICE: Will be held via BlueJeans.

Link: https://umich.bluejeans.com/924142541

Brain pathologies including stroke and cancer are a major cause of death and disability. Intracerebral hemorrhage (ICH) accounts for roughly 12% of all strokes in the US with approximately 200,000 new cases per year. ICH is characterized by the rupture of vessels resulting in bleeding and clotting inside the brain. The presence of the clot causes immediate damage to surrounding brain tissue via mass effect with delayed toxic effects developing in the days following the hemorrhage. This leads ICH patients to high mortality with a 40% chance of death within 30 days of diagnosis and motivates the need to quickly evacuate the clot from the brain. Craniotomy surgery and other minimally invasive methods using thrombolytic drugs are common procedures to remove the clot but are limited by factors such as morbidity and high susceptibility to rebleeding, which ultimately result in poor clinical outcomes.

Histotripsy is a non-thermal ultrasound ablation technique that uses short duration, high amplitude rarefactional pulses (>26 MPa) delivered via an extracorporeal transducer to generate targeted cavitation using the intrinsic gas nuclei existing in the target tissue. The rapid and energetic bubble expansion and collapse of cavitation create high stress and strain in tissue at the focus that fractionate it into an acellular homogenate. This dissertation presents the role of histotripsy as a novel ultrasound technology with potential to address the need for an effective transcranial therapy for ICH and other brain pathologies.

The first part of this work investigates the effects of ultrasound frequency and focal spacing on transcranial clot liquefaction using histotripsy. Histotripsy pulses were delivered using two 256-element hemispherical transducers of different frequency (250 and 500 kHz) with 30-cm aperture diameters. Liquefied clot was drained via catheter and syringe in the range of 6-59 mL in 0.9-42.4 min. The fastest rate was 16.6 mL/min. The best parameter combination was λ spacing at 500 kHz, which produced large liquefaction through 3 skullcaps (~30 mL) with fast rates (~2 mL/min). The temperature-rise through the 3 skullcaps remained below 4°C.

The second part addresses initial safety concerns for histotripsy ICH treatment through investigation in a porcine ICH model. 1.75-mL clots were formed in the frontal lobe of the brain. The centers of the clots were liquefied with histotripsy 48 h after formation, and the content was either evacuated or left within the brain. A control group was left untreated. Histotripsy was able to liquefy the core of clots without direct damage to the perihematomal brain tissue. An average volume of 0.9 ± 0.5 mL (~50%) was drained after histotripsy treatment. All groups showed mild ischemia and gliosis in the perihematomal region; however, there were no deaths or signs of neurological dysfunction in any groups.

The third part presents the development of a novel catheter hydrophone method for transcranial phase aberration correction and drainage of the clot liquefied with histotripsy. A prototype hydrophone was fabricated to fit within a ventriculostomy catheter. Improvements in focal pressure of up to 60% were achieved at the geometric focus and 27%-62% across a range of electronic steering locations. The sagittal and axial -6-dB beam widths decreased from 4.6 to 2.2 mm in the sagittal direction and 8 to 4.4 mm in the axial direction, compared to 1.5 and 3 mm in the absence of aberration. The cores of clots liquefied with histotripsy were readily drained via the catheter.

The fourth part focuses on the development of a preclinical system for translation to human cadaver ICH models. A 360-element, 700 kHz hemispherical array with a 30 cm aperture was designed and integrated with an optical tracker surgical navigation system. Calibrated simulations of the transducer suggest a therapeutic range between 48 – 105 mL through the human skull with the ability to apply therapy pulses at pulse-repetition-frequencies up to 200 Hz. The navigation system allows real-time targeting and placement of the catheter hydrophone via a pre-operative CT or MRI.

The fifth and final part of this work extends transcranial histotripsy therapy beyond ICH to the treatment of glioblastoma. This section presents results from an initial investigation into cancer immunomodulation using histotripsy in a mouse glioblastoma model. The results suggest histotripsy has some immunomodulatory capacity as evidenced by a 2-fold reduction in myeloid derived suppressor cells and large increases in interferon-γ concentrations (3500 pg/mL) within the brain tumors of mice treated with histotripsy.

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Lecture / Discussion Mon, 16 Mar 2020 13:26:52 -0400 2020-03-26T10:00:00-04:00 2020-03-26T11:00:00-04:00 Lurie Robert H. Engin. Ctr Biomedical Engineering Lecture / Discussion BME Logo
BME 500: Zach Danziger (March 26, 2020 4:00pm) https://events.umich.edu/event/70071 70071-17507736@events.umich.edu Event Begins: Thursday, March 26, 2020 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: Online hosting procedure TBD.

Therapeutic and Reparative Neurotechnology

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Workshop / Seminar Mon, 23 Mar 2020 14:23:16 -0400 2020-03-26T16:00:00-04:00 2020-03-26T17:00:00-04:00 Off Campus Location Biomedical Engineering Workshop / Seminar BME Event
BME 500: Alberto Figueroa (April 2, 2020 4:00pm) https://events.umich.edu/event/70072 70072-17507738@events.umich.edu Event Begins: Thursday, April 2, 2020 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be hosted via Blue Jeans. The link will be posted below.

Blue Jeans Link: https://umich.bluejeans.com/763221545

Dr. Figueroa received his PhD in Mechanical Engineering at Stanford University, where he developed computational methods fluid structure interaction simulation of hemodynamics.

His first academic appointment was a King’s College London in the UK, where he was Senior Lecturer in the Division of Biomedical Engineering and Imaging Sciences.

Dr. Figueroa is currently the Edward B. Diethrich M.D. Professor in Biomedical Engineering and Vascular Surgery at the University of Michigan. His laboratory is focused on three main areas: 1) developing tools for advanced modeling of blood flow. His group develops the modeling software CRIMSON (www.crimson.software); 2) studying the link between abnormal biomechanical stimuli and cardiovascular diseases such as hypertension and thrombosis; 3) simulation-based surgical planning to aid with the optimal planning of cardiovascular surgeries.

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Workshop / Seminar Wed, 01 Apr 2020 13:18:41 -0400 2020-04-02T16:00:00-04:00 2020-04-02T17:00:00-04:00 Off Campus Location Biomedical Engineering Workshop / Seminar BME Logo
BME 500: Yannis Paulus (April 9, 2020 4:00pm) https://events.umich.edu/event/70074 70074-17507739@events.umich.edu Event Begins: Thursday, April 9, 2020 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: Online hosting procedure TBD.

Yannis M Paulus, MD, FACS, is a clinician scientist retina surgeon who directs a retinal optical imaging and laser lab. He is an Assistant Professor in the Department of Ophthalmology and Visual Sciences and Biomedical Engineering at the University of Michigan. He completed his undergraduate in chemistry and physics at Harvard University, medical school with a scholarly concentration in bioengineering and ophthalmology residency at Stanford University, and surgical and medical retina fellowship at Johns Hopkins University. His lab develops photoacoustic and molecular imaging of the retina and minimally traumatic retinal laser therapies. He has published over 90 peer-reviewed publications and started-up 3 companies to translate new technologies to patients to help treat and cure vision loss and blindness.

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Workshop / Seminar Mon, 06 Apr 2020 15:45:49 -0400 2020-04-09T16:00:00-04:00 2020-04-09T17:00:00-04:00 Off Campus Location Biomedical Engineering Workshop / Seminar BME Event
Master's Thesis Defense: Mingyang Wang (April 10, 2020 10:30am) https://events.umich.edu/event/73990 73990-18460430@events.umich.edu Event Begins: Friday, April 10, 2020 10:30am
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via Blue Jeans. It will be linked before.

BlueJeans: https://bluejeans.com/315155702

Objectives
We have developed a novel anti-vascular technique, termed photo-mediated ultrasound therapy (PUT), which utilizes nanosecond duration laser pulses synchronized with ultrasound bursts to remove microvasculature through cavitation. The objective of the current study is to explore the potential of PUT in removing cutaneous microvessels.

Methods
The auricular blood vessels of two New Zealand white rabbits were treated by PUT with a peak negative ultrasound pressure of 0.45 MPa at 0.5 MHz, and a laser fluence of 0.056 J/cm2 at 1064 nm for 10 minutes. Blood perfusion in the treated area was measured by a commercial laser speckle imaging (LSI) system before and immediately after treatment, as well as at one hour, three days, two weeks, and four weeks post treatment. Perfusion rates of 38 individual vessels from 4 rabbit ears were tracked during this time period for longitudinal assessment.

Results
The measured perfusion rates of the vessels in the treated areas, as quantified by the relative change in perfusion rate (RCPR), showed a statistically significant decrease for all time points post treatment (p<0.001). The mean decrease in perfusion is 50.79% immediately after treatment and is 32.14% at four weeks post treatment. Immediately after treatment, the perfusion rate decreased rapidly. Following this, there was a partial recovery in perfusion rate up to 3 days post treatment, then followed by a plateau in the perfusion from 3 days to 4 weeks.

Conclusions
The study demonstrated that a single PUT treatment could significantly reduce blood perfusion by 32.14% in the skin for up to 4 weeks. With unique advantages such as low laser fluence as compared with photothermolysis and agent-free treatment as compared with PDT, PUT holds potential to be developed into a new tool for the treatment of microvessels in the skin.

Keywords: laser; ultrasound; anti-vascular treatment; skin microvessels; photo-mediated ultrasound therapy

Chair: Dr. Xueding Wang

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Lecture / Discussion Fri, 27 Mar 2020 13:53:59 -0400 2020-04-10T10:30:00-04:00 2020-04-10T11:30:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Joel Tan (April 14, 2020 2:00pm) https://events.umich.edu/event/73953 73953-18443421@events.umich.edu Event Begins: Tuesday, April 14, 2020 2:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This PhD defense will be taking place via Blue Jeans. Link below.

Blue Jeans: https://bluejeans.com/304616213
Chair: Dr. Xueding Wang

Photoacoustic (PA) imaging is an emerging biomedical imaging modality that combines optical and ultrasound imaging technologies. PA imaging relies on the absorption of electromagnetic energy (usually in the form of visible or near-infrared light) leading to the generation of acoustic waves by thermoelastic expansion, which can be detected with an ultrasound detector. PA imaging can be used to detect endogenous chromophores such as deoxyhemoglobin and oxyhemoglobin, or can be used together with external nanosensors for added functionality. The former is used to measure things like blood oxygenation, while the latter opens up many possibilities for PA imaging, limited only to the availability of optical nanosensors. In this dissertation, I employ the use of PA nanosensors for contrast enhancement and molecular imaging in in vivo small animal cancer models.

In the first section, I introduce a novel PA background reduction technique called the transient triplet differential (TTD) method. The TTD method exploits the fact that phosphorescent dyes possess a triplet state with a unique red-shifted absorption wavelength, distinct from its ordinary singlet state absorption profile. By pumping these dyes into the triplet state and comparing the signal to the unpumped dyes, a differential signal can be obtained which solely originates from these dyes. Since intrinsic chromophores of biological tissue are not able to undergo intersystem crossing and enter the triplet state, the TTD method can facilitate “true” background free molecular imaging by excluding the signals from every other chromophore outside the phosphorescent dye. Here, I demonstrate up to an order of magnitude better sensitivity of the TTD method compared to other existing contrast enhancement techniques in both in vitro experiments and in vivo cancer models.

In the second section, I explore the use of a nanoparticle formulation of a repurposed FDA-approved drug called clofazimine for diagnosis of prostate cancer. Clofazimine nanoparticles have a high optical absorbance at 495 nm and has been known to specifically accumulate in macrophages as they form stable crystal-like inclusions once they are uptaken by macrophages. Due to the presence of tumor associated macrophages, it is expected that clofazimine would accumulate in much higher quantities in the cancerous prostate compared to normal prostates. Here, I show that there was indeed a significantly higher accumulation of clofazimine nanoparticles in cancerous prostates compared to normal prostates in a transgenic mouse model, which was detectable both using histology and ex vivo PA imaging.

In the third and final section, I explore the use of a potassium (K+) nanosensor together with PA imaging in measuring the in vivo K+ distribution in the tumor microenvironment (TME). K+ is the most abundant ion in the body and has recently been shown to be at a significantly higher concentration in the tumor. The reported 5-10 fold elevation (25-50 mM compared to 5 mM) in the tumor has been shown to inhibit immune cell efficacy, and thus immunotherapy. Despite the abundance and importance of K+ in the body, few ways exist to measure it in vivo. In this study, a solvatochromic dye K+ nanoparticle (SDKNP) was used together with PA imaging to quantitatively measure the in vivo distribution of K+ in the TME. Significantly elevated K+ levels were found in the TME, with an average concentration of approximately 29 mM, matching the values found by the previous study. The results were then verified using mass spectrometry.

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Lecture / Discussion Wed, 25 Mar 2020 13:19:15 -0400 2020-04-14T14:00:00-04:00 2020-04-14T15:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
BME 500: Lonnie Shea (April 16, 2020 4:00pm) https://events.umich.edu/event/70076 70076-17507740@events.umich.edu Event Begins: Thursday, April 16, 2020 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be hosted via Blue Jeans. The link will be provided below.

Blue Jeans Link: https://umich.bluejeans.com/902489900

The promise of precision health is typically associated with the early detection of disease, and the identification of an individually tailored therapy to extend healthspan while also reducing costs. I will discuss our work on immune engineering, as the immune system is essential to health, and consequently immune dysregulation can lead to disease. Autoimmune disease has been increasing in prevalence for the past few decades, and results from the immune system attacking healthy tissues, such as in Type 1 Diabetes or Multiple Sclerosis. Current treatments typically involve suppressing the entire immune system, despite the immune system attacking specific proteins. Based on the function of the immune system, we have developed nanoparticles that re-program immune responses to specific antigens leading to tolerance to those antigens and leaving the remainder of the immune system intact. The nanoparticles maintain the antigen until internalization by immune cells, with subsequent presentation of the antigen coincident with down-regulation of the co-stimulatory factors and up-regulation of negative co-stimulators. In addition to reprogramming specific immune responses, a need exists for technologies that can detect autoimmune disease initiation prior to substantial destruction of healthy tissues. We have applied tissue engineering principles to generate tissues subcutaneously that function as an immunological niche, which can be accessed easily to avoids risks associated with biopsy of native tissues (e.g., brain,) and thereby report on immune status within tissues. Technologies for detecting disease at the earliest stages combined with reprogramming specific cellular responses represent major opportunities for Precision Health to improve health while containing costs.

Speaker biography:

Lonnie Shea is the Chair of the Department of Biomedical Engineering at the University of Michigan (U-M), which is joint between the College of Engineering and the School of Medicine. He received his PhD in chemical engineering and scientific computing from U-M in 1997, working with Professor Jennifer Linderman. He then served as a postdoctoral fellow with then ChE Professor David Mooney in the Department of Biologic and Materials Science at the U-M Dental School. Shea was recruited to Northwestern University’s Department of Chemical and Biological Engineering and was on the faculty from 1999 to 2014. In 2014, Shea was recruited back to the University of Michigan as chair of the Department of Biomedical Engineering, with his recruitment coinciding with the endowment of the chair position by William and Valerie Hall. He is the Steven A. Goldstein Collegiate Professor of Biomedical Engineering and is an internationally recognized researcher at the interface of regenerative medicine, drug and gene delivery, and immune-engineering, whose focus is on preventing tissue degeneration or promoting tissue regeneration. His projects include islet transplantation for diabetes therapies, nerve regeneration for treating paralysis, autoimmune diseases and allogeneic cell transplantation, cancer diagnostics, and ovarian follicle maturation for treating infertility. He is currently PI or co-PI on 5 NIH grants (4R01’s, 1 R21). The nanoparticle technology for immune tolerance has led to the formation of a company that is leading a series of clinical trials. Shea has published more than 240 manuscripts, and has numerous inventions to his credit. He is the PI for the Coulter Foundation Translational Research grants committee at the University of Michigan. He served as director of Northwestern’s NIH Biotechnology Training Grant. He has received the Clemson Award from the Society for Biomaterials, is a fellow of the American Institute of Medical and Biological Engineering (AIMBE) and the Biomedical Engineering Society (BMES), a member of the editorial boards for multiple journals such as Molecular Therapy, Biotechnology and Bioengineering, and the Journal of Immunology and Regenerative Medicine.

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Workshop / Seminar Thu, 16 Apr 2020 13:10:30 -0400 2020-04-16T16:00:00-04:00 2020-04-16T17:00:00-04:00 Off Campus Location Biomedical Engineering Workshop / Seminar BME Event
Master's Defense: Jonathan Primeaux (April 21, 2020 2:30pm) https://events.umich.edu/event/74331 74331-18633862@events.umich.edu Event Begins: Tuesday, April 21, 2020 2:30pm
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via Zoom. The link will be placed below.

Zoom Link: https://umich.zoom.us/j/7013698675

Children with hypoplastic left heart syndrome (HLHS) must undergo multiple surgical stages to reconstruct the anatomy to a sustainable single ventricle system. Stage I palliation, or the Norwood procedure, enables circulation to both pulmonary and systemic vasculature. The aorta is reconstructed and attached to the right ventricle and a fraction of systemic flow is redirected to the pulmonary arteries (PAs) through a systemic-to-pulmonary artery shunt. Despite abundant hemodynamic data available 4-5 months after palliation, data is very scarce immediately following stage I. This data is critical in determining post-operative success. In this work, we combined population data and computational fluid dynamics (CFD) to characterize hemodynamics immediately following stage I (post-stage I) and prior to stage II palliation (pre-stage II). A patient-specific model was constructed as a baseline geometry, which was then scaled to reflect population-based morphological data at both time-points. Population-based hemodynamic data was also used to calibrate each model to reproduce blood flow representative of HLHS patients.

The post-stage I simulation produced a mean PA pressure of 22 mmHg and high-frequency oscillations within the flow field indicating highly disturbed hemodynamics. Despite mean PA pressure dropping to 14 mmHg, the pre-stage II model also produced high-frequency flow components and PA wall shear stress increases. These suboptimal conditions result from the need to ensure adequate PA flow throughout the pre-stage II period, as the shunt becomes relatively smaller compared to the growing patient size. In the future, CFD can be used to optimize shunt design and minimize these suboptimal conditions.

Chair: Dr. Alberto Figueroa

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Lecture / Discussion Fri, 17 Apr 2020 13:05:00 -0400 2020-04-21T14:30:00-04:00 2020-04-21T15:30:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
Master's Defense: Xijia Quan (April 21, 2020 3:00pm) https://events.umich.edu/event/74183 74183-18559840@events.umich.edu Event Begins: Tuesday, April 21, 2020 3:00pm
Location:
Organized By: Biomedical Engineering

NOTICE: This event will be held via Blue Jeans. The link will be posted below.

Blue Jeans link: https://bluejeans.com/6788336326

We propose a novel optimization algorithm for radiofrequency (RF) pulse design in magnetic resonance imaging (MRI), that regularizes the magnitude and phase of the target (desired) magnetization pattern separately. This approach may be useful across applications where the relative importance of achieving accurate magnitude or phase excitation varies; for example, saturation pulses "care" only about the magnitude excitation pattern. We apply our new design to the problem of spin "prephasing" in 3D functional MRI using blood-oxygen-level-dependent (BOLD) contrast; spin prephasing pulses can mitigate the signal loss observed near air/tissue boundaries due to the presence of local susceptibility gradients. We show that our algorithm can improve the simulation performance and recover some signal in some regions with steep susceptibility gradients. In all cases, our algorithm shows better phase correction than a conventional design based on minimizing the complex difference between the target and realized patterns. The algorithm is open-source and the computation time is feasible for online applications. In addition, we evaluate the impact of the choice of (initial) excitation k-space trajectories, both in terms of trajectory type (SPINS vs extended KT points) and overall pulse duration.

Chair: Dr. Jon-Fredrik Nielsen

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Lecture / Discussion Thu, 09 Apr 2020 14:11:30 -0400 2020-04-21T15:00:00-04:00 2020-04-21T16:00:00-04:00 Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: David Martel (April 22, 2020 3:00pm) https://events.umich.edu/event/74201 74201-18568320@events.umich.edu Event Begins: Wednesday, April 22, 2020 3:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via Zoom. The link will be provided below.

Zoom: https://umich.zoom.us/j/2019377962

Tinnitus is the disorder of phantom sound perception, while hyperacusis is abnormally increased loudness growth. Tinnitus and hyperacusis are both associated with hearing loss, but hearing loss does not always occur with either condition, implicating central neural activity as the basis for each disorder. Furthermore, while tinnitus and hyperacusis can co-occur, either can occur exclusively, suggesting that separate pathological neural processes underlie each disorder.

Mounting evidence suggests that pathological neural activity in the cochlear nucleus, the first central nucleus in the auditory pathway, underpins hyperacusis and tinnitus. The cochlear nucleus is comprised of a ventral and dorsal subdivision, which have separate principle output neurons with distinct targets. Previous studies have shown that dorsal cochlear nucleus fusiform cells show tinnitus-related increases in spontaneous firing with minimal alterations to sound-evoked responses. In contrast, sound-evoked activity in ventral cochlear nucleus bushy cells is enhanced following noise-overexposure, putatively underlying hyperacusis. While the fusiform-cell contribution to tinnitus has been well characterized with behavioral and electrophysiological studies, the bushy-cell contribution to tinnitus or hyperacusis has been understudied.

This dissertation examines how pathological neural activity in cochlear nucleus circuitry relates to tinnitus and hyperacusis in the following three chapters.

In the first chapter, I characterize the development of a high-throughput tinnitus behavioral model, which combines and optimizes existing paradigms. With this model, I show that animals administered salicylate, a drug that reliably induces tinnitus at high doses in both humans and animals, show behavioral evidence of tinnitus in two separate behavioral tests. Moreover, in these same animals, I show that dorsal-cochlear-nucleus fusiform cells exhibit frequency-specific increases in spontaneous firing activity, consistent with noise-induced tinnitus in animals.

In the second chapter, I show that following noise-overexposure, ventral-cochlear-nucleus bushy cells demonstrate hyperacusis-like neural firing patterns, but not tinnitus-specific increases in spontaneous activity. I contrast the bushy-cell neural activity with established fusiform-cell neural signatures of tinnitus, to highlight the bushy-cell, but not fusiform-cell contribution to hyperacusis. These analyses suggest that tinnitus and hyperacusis likely arise from distinct neural substrates.

In the third chapter, I use computational modelling of the auditory periphery and bushy-cell circuitry to examine potential mechanisms that underlie hyperacusis-like neural firing patterns demonstrated in the second chapter. I then relate enhanced bushy-cell firing patterns to alterations in the auditory brainstem response, a sound-evoked electrical potential generated primarily by bushy cells. Findings in this chapter suggest that there are multiple hyperacusis subtypes, arising from separate mechanisms, which could be diagnosed through fine-tuned alterations to the auditory brainstem response.

Chair: Dr. Susan Shore

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Lecture / Discussion Thu, 09 Apr 2020 14:17:07 -0400 2020-04-22T15:00:00-04:00 2020-04-22T16:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Richard Youngblood (April 29, 2020 2:00pm) https://events.umich.edu/event/74358 74358-18666222@events.umich.edu Event Begins: Wednesday, April 29, 2020 2:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via Blue Jeans. The link will be posted below.

BlueJeans: https://bluejeans.com/855683101

Human pluripotent stem cells (hPSCs) differentiated into complex three-dimensional (3D) structures, referred to as ‘organoids’ due to their organ-like properties, offer ideal platforms to study human development, disease and regeneration. However, studying organ morphogenesis has been hindered by the lack of appropriate culture systems that can spatially enable cellular interactions that are needed for organ formation. Many organoid cultures rely on decellularized extracellular matrices as supportive scaffolds, which are often poorly chemically defined and allow only limited tunability and reproducibility. By contrast, engineered synthetic matrices can be tuned and optimized to mimic the embryo environment in order to enhance development and maturation of organoid cultures. Herein, this work primarily focuses on using synthetic polymer matrices to investigate how the design of biomaterials can guide key interactions guiding stem-cell decisions for the reproducible generation and control of organoid cultures.
Microporous biomaterials comprised of synthetic polymer materials were shown to guide the assembly of pancreatic progenitors into insulin-producing clusters that further developed into islet organoids. The scaffold culture facilitated cell-cell interactions enabled by the scaffold design and supported cell-mediated matrix deposition of extracellular matrix (ECM) proteins associated with the basement membrane of islet cells. Furthermore, when compared to suspension cultures, the scaffold culture showed increased insulin secretion in response to glucose stimulus indicating the development of functional β-cells. By modifying the stage that cells were seeded on scaffolds from pancreatic progenitor to pancreatic endoderm, islet organoids showed increased amounts of insulin secreted per cell. In addition, seeding scaffolds with dense clusters instead of a single suspension minimized cell manipulation during the differentiation, which was shown to be influential to the development of the islet organoids. An engineered insulin reporter further identified how mechanistic changes in vitro influenced function within individual cells by measuring insulin storage and secretion through non-invasive imaging.
hPSC-derived lung organoids (HLOs) were also evaluated for in vivo maturation on biomaterial scaffolds, where HLOs were shown improved tissue structure and cellular differentiation. Investigative studies demonstrated that scaffold pore interconnectivity and polymer degradation contributed to in vivo maturation, the size of the airway structures and the total size of the transplanted tissue. Polymer biomaterials were also developed to modulate local tissue and systemic inflammation through local delivery of human interleukin 4 (hIL-4)-expressing lentivirus. Microporous scaffold culture strategies improve organoid complexity and exert fine control over the system using engineering solutions, thus, allowing the community to build more realistic organoid tools. Taken together, the microporous scaffold culture demonstrates the feasibility to translate organoid culture to the clinic as a biomanufacturing platform.

Chair: Dr. Lonnie Shea

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Lecture / Discussion Tue, 21 Apr 2020 13:21:55 -0400 2020-04-29T14:00:00-04:00 2020-04-29T15:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
Master's Defense: Manan Parag Anjaria (April 30, 2020 1:15pm) https://events.umich.edu/event/74435 74435-18714559@events.umich.edu Event Begins: Thursday, April 30, 2020 1:15pm
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via Blue Jeans. The link will be provided below.

Blue Jeans Link: https://bluejeans.com/126133694

Individual muscle contributions to facilitate limb motion are altered in people with transtibial amputation. Specifically, proximal muscles on the residual limb and muscles on the intact limb compensate for the lack of plantarflexor muscles on the residual limb. Powered ankle prostheses have been developed to replace the function of the ankle plantarflexor muscles. As powered prostheses can help people with amputation walk faster, and replicate local ankle joint mechanics similar to biological ankles, we expect that muscle activity would also differ when using powered prostheses compared to unpowered prosthesis. Exploring muscle synergies, or the patterns of co-activation of muscles recruited by a single neural command signal, can provide insight into the neural control strategies used to walk with different types of prostheses. The goal of this study was to determine if the use of a powered ankle prosthesis affected muscle coordination and coactivation in comparison to the use of unpowered prosthesis. Nine people with unilateral transtibial amputation and 9 age-matched, non-amputee controls walked on a treadmill while muscle activity from 16 lower limb muscles were collected. Participants with amputation performed two trials, one with an unpowered and one with a powered prosthesis, on the same day. People with transtibial amputation had higher thigh muscle co-contraction when walking with powered prostheses. They also had the same number of synergies in both prostheses as the non-amputee group, which suggests that the complexity of the motor control strategy is not affected by amputation or prosthesis type. The first three synergies in the intact limb were similar, however, the contribution of different muscles to the fourth synergy varied in people with amputation as they used more knee flexors than ankle dorsiflexors in the late swing phase. We also explored the time-varying pattern of the synergies across the gait cycle. There were some phases of the gait cycle where activation profiles for all the synergies were significantly different between the groups with and without amputation. However, there were strong correlations between muscle weightings for each synergy between the groups with and without amputation, with both prostheses. This indicates that they used a similar muscle recruitment strategy. The use of powered prosthesis reduced the compensatory activity of the proximal muscles making the intact limb synergies muscle weightings more similar to healthy individuals with prolonged or delayed activation profiles. The study could not offer any interpretations of the synergies of the residual limb due to lesser muscle activity data available. Future work should be focused including a larger set of muscles including the lumbar muscles and residual leg muscles to get a better look at the muscle synergy.

Chair: Dr. Deanna Gates

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Lecture / Discussion Mon, 27 Apr 2020 13:44:40 -0400 2020-04-30T13:15:00-04:00 2020-04-30T14:15:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Xianglong Wang (May 5, 2020 1:00pm) https://events.umich.edu/event/74357 74357-18666221@events.umich.edu Event Begins: Tuesday, May 5, 2020 1:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be via Zoom. The link will be provided below.

Zoom: https://umich.zoom.us/j/99315883529

Biological transport processes often involve a boundary acting as separation of flow, most commonly in transport involving blood-contacting medical devices. The separation of flow creates two different scenarios of mass transport across the interface. No flow exists within the medical device and diffusion governs mass transport; both convection and diffusion exist when flow is present. The added convection creates a large concentration gradient around the interface. Computer simulation of such cases prove to be difficult and require proper shock capturing methods for the solutions to be stable, which is typically lacking in commercial solvers. In this talk, we propose a second-order accurate numerical method for solving the convection-diffusion equation by using a gradient-limited Godunov-type convective flux and the multi-point flux approximation (MPFA) L-Method for the diffusion flux. We applied our solver towards simulation of a nitric oxide-releasing intravascular catheter.

Intravascular catheters are essential for long-term vascular access in both diagnosis and treatment. Use of catheters are associated with risks for infection and thrombosis. Risk management dictates that the catheters to be often replaced on a 3 to 5-day cycle, which is bothersome to both patients and physicians. Nitric oxide (NO) is a potent antimicrobial and antithrombotic agent produced by vascular endothelial cells. The production level in vivo is so low that the physiological effects can only be seen around the endothelial cells. The catheter can incorporate a NO source in two major ways: by impregnating the catheter with NO-releasing compounds such as S-nitroso-N-acetyl penicillamine (SNAP) or using electrochemical reactions to generate NO from nitrites. We applied our solver to both situations to guide the design of the catheter.

Lung edema is often present in patients with end-stage renal disease due to reduced filtration functions of the kidney. These patients require regular dialysis sessions to manage their fluid status. The clinical gold standard to quantify lung edema is to use CT, which exposes patients to high amounts of radiation and is not cost efficient. Fluid management in such patients becomes very challenging without a clear guideline of fluid to be removed during dialysis sessions. Aggressive fluid removal can cause both exacerbations of congestive failure and hypotension resulting from low blood volume.

Recently, reverberations in ultrasound signals, referred to as “lung ultrasound comets” have emerged as a potential quantitative way to measure lung edema. Increased presence of lung comets is associated with higher amounts of pulmonary edema, higher mortality, and more adverse cardiac events. However, the lung comets are often counted by hand by physicians with single frames in lung ultrasound and high subjectivity has been found to exist among the counting by physicians. We applied image processing and neural network techniques as an attempt to provide an objective and accurate measurement of the amount of lung comets present. Our quantitative results are significantly correlated with a few clinical parameters, including diastolic blood pressure and ejection fraction.

Co-Chairs: Dr. Joseph Bull and Dr. Alberto Figueroa

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Lecture / Discussion Tue, 21 Apr 2020 13:16:12 -0400 2020-05-05T13:00:00-04:00 2020-05-05T14:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
Ph.D. Defense: Kevin Hughes (May 8, 2020 10:00am) https://events.umich.edu/event/74436 74436-18714560@events.umich.edu Event Begins: Friday, May 8, 2020 10:00am
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via Blue Jeans. The link will be provided below.

Blue Jeans Link: https://bluejeans.com/302652230

A variety of immunological disorders are characterized by inappropriate responses to innocuous protein. This is particularly relevant in autoimmune disease, allergy, and transplant rejection. For these, the therapeutic options that exist are minimal or involve broadly immunosuppressive regimens which are often characterized by undesirable side effects. This dissertation highlights advances in the design of a biodegradable poly-lactide-co-glycolide (PLG) nanoparticle (NP) platform to provide antigen-specific tolerance in these disease models.

Strategies to incorporate multiple antigens conjugated to bulk PLG were investigated in a murine model of multiple sclerosis with the observation that a minimum antigen loading of 8µg of antigen per mg of nanoparticle was sufficient to induce maximally observed efficacy. Insights gathered from development of these particles were critical to the design of experiments related to food allergy in mice. Importantly, we demonstrate that it is possible to delivery peanut extract via nanoparticles intravenously without induction of anaphylactic response. Prophylactic and therapeutic administration of particles resulted in improved clinical outcomes and reduction in Th2 markers, including IL-4, IL-5, and IL-13. Interestingly, administration of PLG NPs to deliver allergen did not induce skewing of immunological responses towards Th1/Th17, which is a common approach to treat allergy in pre-clinical models and certain clinical immunotherapy regimens. Studies in a murine model of allogeneic skin transplant rejection demonstrated that the method of incorporation of antigen into the PLG NP resulted in statistically significant delay in graft rejection. These studies also demonstrated shortcomings in the platform’s ability to completely prevent rejection, which we hypothesize is the result of an inability to prevent direct rejection.

Development of FasL-conjugated implantable polymeric discs provided an immunologically privileged site on which to transplant islet cells, which may represent an opportunity to supplement tolerogenic therapies like our PLG NPs. A similar polymeric, implantable technology was designed to enable analysis of the function of inflammatory immune cells, a novel finding which has provided a method to monitor disease progression and response to therapy in a murine model of multiple sclerosis. Collectively, this work has provided several novel strategies to improve polymeric nanoparticle therapies and an implantable, biodegradable platform that shows promise as a companion diagnostic for therapies that impact immune function, including PLG NPs.

Chair: Dr. Lonnie Shea

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Lecture / Discussion Mon, 27 Apr 2020 13:54:09 -0400 2020-05-08T10:00:00-04:00 2020-05-08T11:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Matthew S. Willsey (June 29, 2020 10:00am) https://events.umich.edu/event/74994 74994-19128257@events.umich.edu Event Begins: Monday, June 29, 2020 10:00am
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via Zoom. The link will be placed below.

Zoom: https://umich.zoom.us/j/91278019863

Many diseases and injuries irreparably harm the brain or spinal cord and result in motor paralysis, widespread sensory deficits, and pain. Often, there are no treatments for these injuries, and therapies revolve around rehabilitation and adapting to the acquired deficits. In this work, we investigate brain machine interfaces (BMIs) as a future therapy to restore sensorimotor function, use BMIs to understand sensorimotor circuits, and use novel imaging algorithms to assess structural damage of somatosensory inputs into the brain.

Brain-controlled robotic arms have progressed rapidly from the first prototype devices in animals; however, these arms are often slow-moving compared to normal hand and arm function. In the first study, we attempt to restore higher-velocity movements during real-time control of virtual fingers using a novel feedforward neural network algorithm to decode the intended motor movement from the brain. In a non-human primate, the neural network decoder was compared with a linear decoder, the ReFIT Kalman filter (RFKF), that we believe represents the state-of-the-art in real-time finger decoding. The neural network decoder outperformed RFKF by acquiring more targets at faster velocities. This neural network architecture may also provide a blueprint for additional advances.

Somatosensory feedback from robotic arms is an important step to improve the realism and overall functioning. The use of somatosensory thalamus was investigated as a site of implantation for a sensory prosthesis in subjects undergoing awake deep brain stimulation surgery (DBS). In this study, electrical stimulation of the thalamus was performed using different stimulation patterns and the evoked sensations were compared. We found that the sensations evoked by bursting (a burst of pulses followed by a rest period) and tonic (regularly repeating pulses) stimulation were often in different anatomic regions and often with differing sensory qualities. These techniques for controlling percept location and quality may be useful in not only in BMI applications but also in DBS therapies to better relieve symptoms and avoid unwanted side effects.

Given the importance of sensory integration in motor functioning, the third study investigated the impact of a pharmacological perturbation on somatosensory content in primary motor cortex measured with Utah arrays implanted in two NHPs. Specifically, during continuous administration of nitrous oxide (N2O), somatosensory content was assessed by using the neural activity in primary motor cortex to classify finger brushings with a cotton-tip applicator. N2O degraded but did not eliminate somatosensory content in motor cortex. These findings provide insight into N2O mechanisms and may lead to further study of somatosensory afferents to motor cortex.

A debilitating facial pain syndrome, called trigeminal neuralgia (TN), is thought to be caused by vascular compression of the sensory root that provides somatosensory feedback from the face. In this final study, magnetic resonance diffusion tensor imaging was used to assess the structural damage of this sensory root. In a retrospective manner, we developed and tested an algorithm that predicted the likelihood of pain relief after surgical treatment of TN. This algorithm could help select patients for surgery with the best chance for pain relief.

Together, these studies advance BMI technologies that attempt to restore realistic function to those with irreparable damage to sensorimotor pathways. Furthermore, using BMIs and novel imaging, this work provides a better understanding of sensorimotor circuits and how sensory pathways can be damaged in disease states.

Co-Chairs: Parag G. Patil and Cynthia A. Chestek

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Lecture / Discussion Thu, 18 Jun 2020 15:24:23 -0400 2020-06-29T10:00:00-04:00 2020-06-29T11:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Daniel Quevedo (July 1, 2020 9:30am) https://events.umich.edu/event/74977 74977-19118435@events.umich.edu Event Begins: Wednesday, July 1, 2020 9:30am
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held digitally via Blue Jeans. The link will be placed below.

BlueJeans: https://bluejeans.com/863787871

Nanomedicine- where a therapeutic is loaded into nanoparticles to increase therapeutic efficiency and improve patient outcomes- has long had the potential to revolutionize medicine. With all of their promise, nanoparticle carrier technologies have yet to make a significant clinical impact, emphasizing the need for new technologies and approaches. In this dissertation, electrohydrodynamic (EHD) co-jetting was used to develop various methods to create novel Synthetic Protein Nanoparticles (SPNPs), which were then applied to the delivery of therapeutic enzymes, and characterized using a microfluidic technique. It was found that SPNPs can be made from various proteins, such as Human Transferrin, Hemoglobin, and others, and that various macromers can be selected, such as a stimuli responsive NHS-Ester based macromer that can detect oxidative environments and show signs of degradation within 30 minutes of being taken up by HeLa cells. SPNPs were then loaded with medically relevant enzymes, such as the antioxidant enzyme catalase. The enzymes showed high activity retention rates, with catalase SPNPs maintaining up to 82% of their original enzymatic activity. Additionally, antibody-targeted catalase SPNPs were able to protect up to 80% of REN cells in an inflammatory disease model. Next, an electrokinetic microfluidic system was adapted for the characterization of SPNPs based on their protein composition and anisotropy, and was able to differentiate bicompartmental particles made from two different proteins from single compartment SPNPs made of an equivalent isotropic mixture of the same two proteins, with a voltage difference of 900 V between the two particle types, in contrast to the 50 V step sizes possible in these systems. Finally, preliminary work was conducted on using a small targeting molecule, meta-acetylenbenzylguanidine (MABG), for the treatment of neuroblastoma, and a system for validating MABG targeting in SK-N-BE(2) cells (a neuroblastoma cell line) was developed. Work done in this dissertation presents the development of multifunctional protein nanocarriers and lays the groundwork for the targeted delivery of active therapeutics using these particles.

Chair: Dr. Joerg Lahann

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Lecture / Discussion Thu, 18 Jun 2020 15:24:54 -0400 2020-07-01T09:30:00-04:00 2020-07-01T10:30:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Charles Lu (July 23, 2020 2:00pm) https://events.umich.edu/event/75199 75199-19324453@events.umich.edu Event Begins: Thursday, July 23, 2020 2:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via Zoom. The link will be placed below.

Zoom: https://umich-health.zoom.us/j/95667535536

Therapeutic neuromodulation has an established history for clinical indications, such as deep brain stimulation for movement disorders and spinal cord stimulation for pain, despite an incomplete understanding of its mechanism of action. Novel neuroprosthetics have the potential to enable wholly new therapies, including sensory restoration and treatment of affective disorders. In order to fully realize the potential of these interventions, precise parameterization of stimulation, informed by better understanding of underlying processes, is required. This dissertation explores the temporal and spatial determinants of outcomes for stimulation within the context of clinical and experimental sensorimotor neuromodulation.

The first study of the dissertation defines a new functional target for subthalamic deep brain stimulation for Parkinson disease treatment. While optimal sites of stimulation are often analyzed as discrete points in space, therapeutic tissue activation is known to activate entire volumes of surrounding tissue. To identify markers of these volumes, we used machine learning tools to identify associations between features of wideband neural recordings and regions of clinically validated stimulation regions derived from patient-specific tissue activation models. The study identified several electrophysiological markers of therapeutic activation regions, providing a tool for efficient optimization of stimulation programming.

Despite the importance of spatially precise stimulation, conventional stereotactic methods are limited by intrinsic sources of error. The second study assessed a novel form of lead localization utilizing local impedance at deep brain sites. We demonstrated that in vivo impedance measurements generally match patterns observed in electrostatic simulations and showed that these values can be efficiently estimated using diffusion tensor data. Impedances measured using a clinical macroelectrode provided spatial information at the resolution of millimeters and could be used to roughly localize deep brain trajectories, presenting a prototype method to complement existing targeting technologies.

The final study evaluated a novel form of deep brain stimulation for modulation of pain. Previous rodent studies show that stimulation of zona incerta can provide analgesic effect, and clinical evidence suggests that stimulation of a nearby nucleus, nominally used to treat motor manifestations of Parkinson disease, often also results in improvement of pain symptoms. We directly tested the analgesic effect of zona incerta stimulation in humans and demonstrated that stimulation at the physiological spiking frequency of zona incerta selectively reduces perceived heat pain.

Chair: Dr. Parag G. Patil

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Lecture / Discussion Mon, 13 Jul 2020 15:30:00 -0400 2020-07-23T14:00:00-04:00 2020-07-23T15:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Benjamin Juliar (July 28, 2020 1:00pm) https://events.umich.edu/event/75205 75205-19330337@events.umich.edu Event Begins: Tuesday, July 28, 2020 1:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via BlueJeans. The link will be placed below.

BlueJeans Link: https://bluejeans.com/358462383

Engineering large viable tissues requires techniques for encouraging rapid capillary bed formation to prevent necrosis. A convenient means of creating this micro-vascular network is through spontaneous neovascularization, which occurs when endothelial cells (ECs) and supportive stromal cells are co-encapsulated within a variety of hydrogel-based extracellular matrices (ECM) and self-assemble into an interconnected network of endothelial tubules. Although this is a robust phenomenon, the environmental and cell-specific determinants that affect the rate and quality of micro-vascular network formation still require additional characterization to improve clinical translatability. This thesis investigates how the proteolytic susceptibility of engineered matrices effects neovascular self-assembly in poly(ethylene glycol) (PEG) hydrogels and provides characterization of changes to matrix mechanics that accompany neovascular morphogenesis in fibrin and PEG hydrogels.

Proteolytic ECM remodeling is essential for the process of capillary morphogenesis. Pharmacological inhibitor studies suggested a role for both matrix metalloproteinases (MMP)- and plasmin-mediated mechanisms of ECM remodeling in an EC-fibroblast co-culture model of vasculogenesis in fibrin. To further investigate the potential contribution of plasmin mediated matrix degradation in facilitating capillary morphogenesis we employed PEG hydrogels engineered with proteolytic specificity to either MMPs, plasmin, or both. Although fibroblasts spread in plasmin-selective hydrogels, we only observed robust capillary morphogenesis in MMP-sensitive matrices, with no added benefit in dual susceptible hydrogels. Enhanced capillary morphogenesis was observed, however, in PEG hydrogels engineered with increased susceptibility to MMPs without altering proteolytic selectivity or hydrogel mechanical properties. These findings highlight the critical importance of MMP-mediated ECM degradation during vasculogenesis and justify the preferential selection of MMP-degradable peptide crosslinkers in the design of synthetic hydrogels used to promote vascularization.

Matrix stiffness is a well-established cue in cellular morphogenesis, however, the converse effect of cellular remodeling on environmental mechanics is comparatively under characterized. In fibrin hydrogels, we applied traditional bulk rheology and laser tweezers-based active microrheology to demonstrate that both ECs and fibroblasts progressively stiffen the ECM across length scales, with the changes in bulk properties dominated by fibroblasts. Despite a lack of fibrillar architecture, a similar stiffening effect was observed in MMP-degradable PEG hydrogels. This stiffening tightly correlated with degree of vessel formation and critically depended on active cellular contractility. To a lesser degree, deposition of ECM proteins also appeared to contribute to progressive hydrogel stiffening. Blocking cell-mediated hydrogel degradation abolished stiffening, demonstrating that matrix metalloproteinase (MMP)-mediated remodeling is required for stiffening to occur. EC co-culture with mesenchymal stem cells (MSCs) in PEG resulted in reduced vessel formation compared to fibroblast co-cultures and no change in hydrogel mechanics over time. The correlation between matrix stiffening and enhanced vessel formation, and dependence on cellular contractility, suggests differences in vessel formation between fibroblasts and MSCs may be partially mediated by differences in cellular contractility. Collectively, these findings provide a deeper understanding of mechanobiological effects during capillary morphogenesis and highlight the dynamic reciprocity between cells and their mechanical environment.

Chair: Dr. Andrew Putnam

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Lecture / Discussion Tue, 14 Jul 2020 11:02:36 -0400 2020-07-28T13:00:00-04:00 2020-07-28T14:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Katy Norman (July 30, 2020 10:00am) https://events.umich.edu/event/75267 75267-19395124@events.umich.edu Event Begins: Thursday, July 30, 2020 10:00am
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via BlueJeans. The link will be posted below.

BlueJeans: https://bluejeans.com/516255948

Mucosal surfaces in the lung interface with the outside environment for breathing purposes, but also provide the first line of defense against invading pathogens. The intricate balance of effective immune protection at the pulmonary epithelium without problematic inflammation is not well understood, but is an important consideration in complex lung diseases such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Although IPF is a fibrotic interstitial lung disease of unknown origin and COPD is an obstructive lung disease, they do share some similarities. Both are heterogeneous and progressive in nature, have no cure and few treatment options, advance through unknown mechanisms, and involve an aberrant immune response. As research has focused into the role the immune system plays in IPF and COPD, it has become clear that disease progression is caused by a complex dysregulation of immune factors and cells across the tissue compartments of the lungs and blood.

Data-driven modeling approaches offer the opportunity to infer protein interaction networks, which are able to identify diagnostic and prognostic biomarkers and also serve as the basis for new insight into systems-level mechanisms that define a disease state. Additionally, these approaches are able to integrate data from across multiple tissue compartments, allowing for a more holistic picture of a disease to be formed. Here, we have applied data-driven modeling approaches including partial least squares discriminant analysis, principal component analysis, decision tree analysis, and hierarchical clustering to high-throughput cell and cytokine measurements from human blood and lung samples to gain systems-level insight into IPF and COPD.

Overall we found that these approaches were useful for identifying signatures of proteins that differentiated disease state and progression better than current classifiers. We also found that integrating protein and cell measurements across tissue compartments generally improved classification and was useful for generating new mechanistic insight into progression and exacerbation events. In evaluating IPF progression, we showed that the blood proteome of progressors, but not of non-progressors, changes over time, and that our data-driven modeling techniques were able to capture these changes. Curiously, our models showed that complement system components may be associated with both COPD and IPF disease progression. Lastly, though our analysis suggested that circulating blood cytokines were not useful for differentiating disease state or progression, preliminary work suggested that cell-cell communication networks arising from stimulated peripheral blood proteins may be more useful for classification and gaining mechanistic insight from minimally invasive blood samples. Overall, we believe that this approach will be useful for studying the mucosal immune response present in other diseases that are also progressive or heterogeneous in nature.

Chair: Dr. Kelly Arnold

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Lecture / Discussion Wed, 22 Jul 2020 16:19:44 -0400 2020-07-30T10:00:00-04:00 2020-07-30T11:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Josiah Simeth (August 5, 2020 2:00pm) https://events.umich.edu/event/75278 75278-19402991@events.umich.edu Event Begins: Wednesday, August 5, 2020 2:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Notice: This event will be held via BlueJeans. The link will be placed below.

BlueJeans: https://bluejeans.com/715371816

Measures of regional and global liver function are critical in guiding treatments for intrahepatic cancers, and liver function is a dominant factor in the survival of patients with hepatocellular carcinoma (HCC). Global and regional liver function assessments are important for defining the magnitude and spatial distribution of radiation dose to preserve functional liver parenchyma and reduce incidence of hepatotoxicity from radiation therapy (RT) for intrahepatic cancer treatment. This individualized liver function-guided RT strategy is critical for patients with heterogeneous and poor liver function, often observed in cirrhotic patients treated for HCC. Dynamic gadoxetic-acid enhanced (DGAE) magnetic resonance imaging (MRI) allows investigation of liver function through observation of the uptake of contrast agent into the hepatocytes.

This work seeks to determine if gadoxetic uptake rate can be used as a reliable measure of liver function, and to develop robust methods for uptake estimation with an interest in the therapeutic application of this knowledge in the case of intrahepatic cancers. Since voxel-by voxel fitting of the preexisting nonlinear dual-input two-compartment model is highly susceptible to over fitting, and highly dependent on data that is both temporally very well characterized and low in noise, this work proposes and validates a new model for quantifying the voxel-wise uptake rate of gadoxetic acid as a measure of regional liver function. This linearized single-input two-compartment (LSITC) model is a linearization of the pre-existing dual-input model but is designed to perform uptake quantification in a more robust, computationally simpler, and much faster manner. The method is validated against the preexisting dual-input model for both real and simulated data. Simulations are used to investigate the effects of noise as well as issues related to the sampling of the arterial peak in the characteristic input functions of DGAE MRI.

Further validation explores the relationship between gadoxetic acid uptake rate and two well established global measures of liver function, namely: Indocyanine Green retention (ICGR) and Albumin-Bilirubin (ALBI) score. This work also establishes the relationships between these scores and imaging derived measures of whole liver function using uptake rate. Additionally, the same comparisons are performed for portal venous perfusion, a pharmacokinetic parameter that has been observed to correlate with function, and has been used as a guide for individualized liver function-guided RT. For the patients assessed, gadoxetic acid uptake rate performs significantly better as a predictor of whole liver function than portal venous perfusion.
This work also investigates the possible gains that could be introduced through use of gadoxetic uptake rate maps in the creation of function-guided RT plans. To this end, plans were created using both perfusion and uptake, and both were compared to plans that did not use functional guidance. While the plans were generally broadly similar, significant differences were observed in patients with severely compromised uptake that did not correspond with compromised perfusion.

This dissertation also deals with the problem of quantifying uptake rate in suboptimal very temporally sparse or short DGAE MRI acquisitions. In addition to testing the limits of the LSITC model for these limited datasets (both realistic and extreme), a neural network-based approach to quantification of uptake rate is developed, allowing for increased robustness over current models.

Chair: Dr. Yue Cao

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Lecture / Discussion Thu, 23 Jul 2020 17:51:41 -0400 2020-08-05T14:00:00-04:00 2020-08-05T15:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Ziwen Zhu (August 26, 2020 9:30am) https://events.umich.edu/event/75720 75720-19576537@events.umich.edu Event Begins: Wednesday, August 26, 2020 9:30am
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via Zoom. The link will be placed below.

Zoom: umich.zoom.us/j/92149340369

Branched Chain amino acids (BCAAs) play an essential role in cell metabolism supplying both carbon and nitrogen in pancreatic cancers, and their increased levels have been associated with increased risk of pancreatic ductal adenocarcinomas (PDACs). It remains unclear how stromal cells regulate BCAA metabolism in PDAC cells and how mutualistic determinants control BCAA metabolism in the tumor milieu. In chapter 1, we present an overview of PDAC biology, tumor microenvironment (TME), altered cancer metabolism and BCAA metabolism. In chapter 2, we uncover differential gene expression of enzymes involved in BCAA metabolism accompanied by distinct catabolic, oxidative, and protein turnover fluxes between cancer-associated fibroblasts (CAFs) and cancer cells with a marked branched-chain keto acids (BCKA)-addiction in PDAC cells. In chapter 3, we showed that cancer-induced stromal reprogramming fuels this BCKA-addiction. We then show the functions of BCAT2 and DBT in the PDAC cells in chapters 3 and 4. We identify BCAT1 as the BCKA regulator in CAFs in chapter 5. In chapter 6, we dictated the internalization of the extracellular matrix from the tumor microenvironment to supply amino acid precursors for BCKA secretion by CAFs. We also showed that the TGF-β/SMAD5 axis directly targets BCAT1 in CAFs in chapter 7. In chapter 8, we validate the in vitro results in human patient-derived circulating tumor cells (CTCs) model. Furthermore, the same results were also validated in PDAC tissue slices, which recapitulate tumor heterogeneity and mimic the in vivo microenvironment in chapter 9. We conclude this manuscript with chapter 10 in which we propose future studies and present directions towards pancreatic cancer research. In summary, our findings reveal therapeutically actionable targets in stromal and cancer cells to regulate the symbiotic BCAA coupling among the cellular constituents of the PDAC microenvironment.

Chair: Dr. Deepak Nagrath

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Lecture / Discussion Fri, 14 Aug 2020 12:02:15 -0400 2020-08-26T09:30:00-04:00 2020-08-26T10:30:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
BME Seminar Series: Ben Cosgrove (September 3, 2020 4:00pm) https://events.umich.edu/event/75894 75894-19623813@events.umich.edu Event Begins: Thursday, September 3, 2020 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Join us for our virtual seminar series on Thursdays from 4-5pm!
These events will take place on BlueJeans at this link: https://bluejeans.com/628109990

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Workshop / Seminar Thu, 20 Aug 2020 14:01:44 -0400 2020-09-03T16:00:00-04:00 2020-09-03T17:00:00-04:00 Off Campus Location Biomedical Engineering Workshop / Seminar BME
BME Seminar Series: Ranu Jung (September 10, 2020 4:00pm) https://events.umich.edu/event/75902 75902-19623820@events.umich.edu Event Begins: Thursday, September 10, 2020 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Join us for our virtual seminar series on Thursdays from 4-5pm!
These events will take place on BlueJeans at this link: https://bluejeans.com/628109990

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Workshop / Seminar Thu, 20 Aug 2020 13:36:24 -0400 2020-09-10T16:00:00-04:00 2020-09-10T17:00:00-04:00 Off Campus Location Biomedical Engineering Workshop / Seminar BME
BME Seminar Series: Orlando Hoilett (September 17, 2020 4:00pm) https://events.umich.edu/event/75903 75903-19623821@events.umich.edu Event Begins: Thursday, September 17, 2020 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Join us for our virtual seminar series on Thursdays from 4-5pm!
These events will take place on BlueJeans at this link: https://bluejeans.com/628109990

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Workshop / Seminar Thu, 20 Aug 2020 13:51:27 -0400 2020-09-17T16:00:00-04:00 2020-09-17T17:00:00-04:00 Off Campus Location Biomedical Engineering Workshop / Seminar BME
U-M BME Virtual Graduate Program Fair (September 24, 2020 10:00am) https://events.umich.edu/event/77635 77635-19893775@events.umich.edu Event Begins: Thursday, September 24, 2020 10:00am
Location: Off Campus Location
Organized By: Biomedical Engineering

In this Virtual Fair event, we will share with you what is great about BME at the University of Michigan and your options for graduate studies. With our top-tier medical and engineering program, there is a broad set of opportunities for participating in cutting edge research across a spectrum of disciplines! This event will also include panel discussions with current faculty and current graduate students, giving you a forum for asking questions about our programs. We look forward to welcoming you to this event!

Presentation open to students interested in: PhD, Master's

Meeting Room Link: https://umich-health.zoom.us/j/94033188012?pwd=V2xHclpXWTV4a1BBSFVneEhaa0ZMdz09
Meeting ID#: 940 3318 8012
Meeting Passcode: 925334

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Other Wed, 23 Sep 2020 15:03:01 -0400 2020-09-24T10:00:00-04:00 2020-09-24T11:30:00-04:00 Off Campus Location Biomedical Engineering Other BME Event
BME Seminar Series: Jane Grande-Allen (September 24, 2020 4:00pm) https://events.umich.edu/event/75904 75904-19623822@events.umich.edu Event Begins: Thursday, September 24, 2020 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Join us for our virtual seminar series on Thursdays from 4-5pm!
These events will take place on BlueJeans at this link: https://bluejeans.com/628109990

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Workshop / Seminar Thu, 20 Aug 2020 13:53:40 -0400 2020-09-24T16:00:00-04:00 2020-09-24T17:00:00-04:00 Off Campus Location Biomedical Engineering Workshop / Seminar BME
BME Seminar Series: Gautam Parthasarathy (October 1, 2020 4:00pm) https://events.umich.edu/event/75905 75905-19623823@events.umich.edu Event Begins: Thursday, October 1, 2020 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Join us for our virtual seminar series on Thursdays from 4-5pm!
These events will take place on BlueJeans at this link: https://bluejeans.com/628109990

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Workshop / Seminar Thu, 20 Aug 2020 13:56:48 -0400 2020-10-01T16:00:00-04:00 2020-10-01T17:00:00-04:00 Off Campus Location Biomedical Engineering Workshop / Seminar BME
BME Seminar Series: Nathan Price (October 8, 2020 4:00pm) https://events.umich.edu/event/75906 75906-19623824@events.umich.edu Event Begins: Thursday, October 8, 2020 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Join us for our virtual seminar series on Thursdays from 4-5pm!
These events will take place on BlueJeans at this link: https://bluejeans.com/628109990

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Workshop / Seminar Thu, 20 Aug 2020 14:01:08 -0400 2020-10-08T16:00:00-04:00 2020-10-08T17:00:00-04:00 Off Campus Location Biomedical Engineering Workshop / Seminar BME
BME Seminar Series: Tyrone Porter (October 22, 2020 4:00pm) https://events.umich.edu/event/75907 75907-19623825@events.umich.edu Event Begins: Thursday, October 22, 2020 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Join us for our virtual seminar series on Thursdays from 4-5pm!
These events will take place on BlueJeans at this link: https://bluejeans.com/628109990

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Workshop / Seminar Thu, 20 Aug 2020 14:06:51 -0400 2020-10-22T16:00:00-04:00 2020-10-22T17:00:00-04:00 Off Campus Location Biomedical Engineering Workshop / Seminar BME
BME Seminar Series: Sudin Bhattacharya (October 29, 2020 4:00pm) https://events.umich.edu/event/75908 75908-19623826@events.umich.edu Event Begins: Thursday, October 29, 2020 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Join us for our virtual seminar series on Thursdays from 4-5pm!
These events will take place on BlueJeans at this link: https://bluejeans.com/628109990

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Workshop / Seminar Thu, 20 Aug 2020 14:09:37 -0400 2020-10-29T16:00:00-04:00 2020-10-29T17:00:00-04:00 Off Campus Location Biomedical Engineering Workshop / Seminar BME
BME Seminar Series: Lori Setton (November 5, 2020 4:00pm) https://events.umich.edu/event/75909 75909-19623827@events.umich.edu Event Begins: Thursday, November 5, 2020 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Join us for our virtual seminar series on Thursdays from 4-5pm!
These events will take place on BlueJeans at this link: https://bluejeans.com/628109990

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Workshop / Seminar Thu, 20 Aug 2020 14:14:30 -0400 2020-11-05T16:00:00-05:00 2020-11-05T17:00:00-05:00 Off Campus Location Biomedical Engineering Workshop / Seminar BME
BME PhD Defense: Zhonghua (Aileen) Ouyang (November 6, 2020 10:00am) https://events.umich.edu/event/78398 78398-20022735@events.umich.edu Event Begins: Friday, November 6, 2020 10:00am
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via Zoom. The link will be provided below.

Zoom: https://umich-health.zoom.us/j/94734899583?pwd=MDNEMjE3QU5xVGgwZzNQajE4UlJQUT09

Overactive bladder (OAB) is a highly prevalent condition which negatively affects the physical and mental health of millions of people worldwide. Sacral neuromodulation (SNM), currently serving ~300,000 patients worldwide, is a promising third-line therapy that provides improved efficacy and minimum adherence issue compared to conventional treatments. While current SNM is delivered in an open-loop fashion, the therapy could have improved clinical efficacy by adopting a closed-loop stimulation paradigm that uses objective physiological feedback. Therefore, this dissertation work focuses on using sacral level dorsal root ganglia neural signals to provide sensory feedback for adaptive SNM a feline model.

This work began with exploring machine learning algorithms and feature selection methods for bladder pressure decoding. A Kalman filter delivered the highest performance based on correlation coefficient between the pressure measurements and algorithm estimation. Additionally, firing rate normalization significantly contributed to lowering the normalized error, and a correlation coefficient-based channel selection method provided the lowest error compared to other channel selection methods.

Following algorithm optimization, this work implemented the optimized algorithm and feature selection method in real-time in anesthetized healthy and simulated OAB feline models. A 0.88 ± 0.16 correlation coefficient fit was achieved by the decoding algorithm across 35 normal and simulated OAB bladder fills in five experiments. Closed-loop neuromodulation was demonstrated using the estimated pressure to trigger pudendal nerve stimulation, which increased bladder capacity by 40% in two trials.

Finally, closed-loop SNM stimulation with DRG sensory feedback was performed in a series of anesthetized experiments. It increased bladder capacity by 13.8% over no stimulation (p < 0.001). While there was no statistical difference in bladder capacity between closed-loop and continuous stimulation (p = 0.80), closed-loop stimulation reduced stimulation time by 57.7%. Interestingly, bladder single units had a reduced sensitivity during stimulation, suggesting a potential mechanism of SNM.

Overall, this work demonstrated that sacral level DRG are a viable sensory feedback target for adaptive SNM. Validation in awake and chronic experiments is a crucial step prior to clinical translation of this method.

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Lecture / Discussion Fri, 09 Oct 2020 22:08:12 -0400 2020-11-06T10:00:00-05:00 2020-11-06T11:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
BME Seminar Series: Eytan Ruppin (November 12, 2020 4:00pm) https://events.umich.edu/event/75910 75910-19623828@events.umich.edu Event Begins: Thursday, November 12, 2020 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Join us for our virtual seminar series on Thursdays from 4-5pm!
These events will take place on BlueJeans at this link: https://bluejeans.com/628109990

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Workshop / Seminar Thu, 20 Aug 2020 14:22:54 -0400 2020-11-12T16:00:00-05:00 2020-11-12T17:00:00-05:00 Off Campus Location Biomedical Engineering Workshop / Seminar BME
BME Seminar Series: Maciek Antoniewicz (November 19, 2020 4:00pm) https://events.umich.edu/event/75911 75911-19623829@events.umich.edu Event Begins: Thursday, November 19, 2020 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Join us for our virtual seminar series on Thursdays from 4-5pm!
These events will take place on BlueJeans at this link: https://bluejeans.com/628109990

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Workshop / Seminar Thu, 20 Aug 2020 14:25:40 -0400 2020-11-19T16:00:00-05:00 2020-11-19T17:00:00-05:00 Off Campus Location Biomedical Engineering Workshop / Seminar BME
BME Seminar Series: Jae-Won Shin (December 3, 2020 4:00pm) https://events.umich.edu/event/75912 75912-19623830@events.umich.edu Event Begins: Thursday, December 3, 2020 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Join us for our virtual seminar series on Thursdays from 4-5pm!
These events will take place on BlueJeans at this link: https://bluejeans.com/628109990

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Workshop / Seminar Thu, 20 Aug 2020 14:28:28 -0400 2020-12-03T16:00:00-05:00 2020-12-03T17:00:00-05:00 Off Campus Location Biomedical Engineering Workshop / Seminar BME
PhD Defense: Sabrina Lynch (December 15, 2020 10:00am) https://events.umich.edu/event/79855 79855-20509613@events.umich.edu Event Begins: Tuesday, December 15, 2020 10:00am
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via Zoom. The link will be provided below.

Zoom link: https://umich-health.zoom.us/j/94668154127

Thrombosis is a process whereby a blood clot forms in situ within a vessel and impedes flow. Although necessary to maintain hemostasis, the human thrombotic system often becomes unstable leading to scenarios of thrombosis and subsequent diseases such as myocardial infarction, stroke, pulmonary embolism, and deep vein thrombosis. Computational modeling is a powerful tool to understand the complexity of thrombosis initiation and provides both temporal and spatial resolution that cannot be obtained in vivo. The goal of this investigation is to develop a computational model of thrombosis initiation in patient-specific models that includes both a complex description of the hemodynamics and biochemistry of thrombin formation. We argue that the complex hemodynamics occurring in vivo significantly alter the initiation and progression of thrombosis.



While blood viscosity is known to exhibit nonlinear behavior, a Newtonian assumption is often employed in computational analyses. This assumption is valid in healthy arteries where shear rates are high and recirculation is low. However, in pathological geometries, such as aneurysms, and venous geometries, this assumption fails, and nonlinear viscous effects become exceedingly important. Previous computational models of thrombosis have investigated coagulation through chemistry based formulations focusing on protein dynamics but have generally excluded complex 3D hemodynamics.



A computational framework was developed to investigate the interplay between 3D hemodynamics and the biochemical reactions involved in thrombosis initiation in patient-specific models under transient flow. The salient features of the framework are: i) nonlinear rheological models of blood flow; ii) a stabilized numerical framework for scalar mass transport; and iii) a computational interface for nonlinear scalar models of protein dynamics that can be easily customized to include an arbitrary number of species and protein interactions.



We implemented and verified nonlinear rheological models of viscosity into CRIMSON and investigated the effects of non-Newtonian viscosity on both hemodynamic and transport metrics in an arterial and venous patient-specific model. Results demonstrated the importance of considering accurate rheological models.



A stabilized finite element (FE) framework was developed to solve scalar mass transport problems in CRIMSON. Simulation of cardiovascular scalar mass transport problems offers significant numerical challenges such as highly advective flows and flow reversal at outlet boundaries. Furthermore, little attention has been given to the identification of appropriate outflow boundary conditions that preserve the accuracy of the solution. These issues were resolved by developing a stabilized FE framework that incorporates backflow stabilization for Neumann outlet boundaries; a consistent flux boundary condition that minimally disturbs the local physics of the problem; and front-capturing stabilization to regularize solutions in high Pe number flows. The efficacy of these formulations was investigated for both idealized and patient-specific geometries.



Next, a flexible arbitrary reaction-advection-diffusion (ARAD) interface was implemented that enables prototyping nonlinear biochemical models of thrombin generation. After verifying the ARAD interface, the performance was compared against the original hardcoded FORTRAN implementation for speed and accuracy using a 4-scalar nonlinear reaction model of thrombosis. Three different biochemical models of thrombin generation were investigated in idealized geometries. Finally, we implemented the 18 scalar model in both idealized and patient-specific geometries to determine the effects of complex 3D hemodynamics on thrombin generation.



The computational framework for thrombosis initiation presented in this work has three key features: i) non-Newtonian hemodynamics; ii) a stabilized numerical framework for scalar RAD problems; and iii) a method to rapidly prototype custom reaction models using Python with negligible associated computational expense.

Chair: Prof. Alberto C. Figueroa

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Lecture / Discussion Thu, 10 Dec 2020 12:16:10 -0500 2020-12-15T10:00:00-05:00 2020-12-15T11:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Jared Scott (December 22, 2020 2:00pm) https://events.umich.edu/event/79866 79866-20509634@events.umich.edu Event Begins: Tuesday, December 22, 2020 2:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via Zoom. The link will be placed below.

https://umich-health.zoom.us/j/97604985906?pwd=N1Y1UXEvNXMxdjlnVkpjUFZHQkRhdz09

Epilepsy is a debilitating neurological disorder characterized by recurrent spontaneous seizures. While seizures themselves adversely affect physiological function for short time periods relative to normal brain states, their cumulative impact can significantly decrease patient quality of life in myriad ways. For many, anti-epileptic drugs are effective first-line therapies. One third of all patients do not respond to chemical intervention, however, and require invasive resective surgery to remove epileptic tissue. While this is still the most effective last-line treatment, many patients with ‘refractory’ epilepsy still experience seizures afterward, while some are not even surgical candidates. Thus, a significant portion of patients lack further recourse to manage their seizures – which additionally impacts their quality of life.



High-frequency oscillations (HFOs) are a recently discovered electrical biomarker with significant clinical potential in refractory human epilepsy. As a spatial biomarker, HFOs occur more frequently in epileptic tissue, and surgical removal of areas with high HFO rates can result in improved outcomes. There is also limited preliminary evidence that HFOs change prior to seizures, though it is currently unknown if HFOs function as temporal biomarkers of epilepsy and imminent seizure onset. No such temporal biomarker has ever been identified, though if it were to exist, it could be exploited in online seizure prediction algorithms. If these algorithms were clinically implemented in implantable neuromodulatory devices, improvements to quality of life for refractory epilepsy patients might be possible. Thus, the overall aim of this work is to investigate HFOs as potential temporal biomarkers of seizures and epilepsy, and further to determine whether their time-varying properties can be exploited in seizure prediction.



In the first study we explore population-level evidence for the existence of this temporal effect in a large clinical cohort with refractory epilepsy. Using sophisticated automated HFO detection and big-data processing techniques, a continuous measure of HFO rates was developed to explore gradual changes in HFO rates prior to seizures, which were analyzed in aggregate to assess their stereotypical response. These methods resulted in the identification of a subset of patients in whom HFOs from epileptic tissue gradually increased before seizures.



In the second study, we use machine learning techniques to investigate temporal changes in HFO rates within individuals, and to assess their potential usefulness in patient-specific seizure prediction. Here, we identified a subset of patients whose predictive models sufficiently differentiated the preictal (before seizure) state better than random chance.



In the third study, we extend our prediction framework to include the signal properties of HFOs. We explore their ability to improve the identification of preictal periods, and additionally translate their predictive models into a proof-of-concept seizure warning system. For some patients, positive results from this demonstration show that seizure prediction using HFOs could be possible.



These studies overall provide convincing evidence that HFOs can change in measurable ways prior to seizure start. While this effect was not significant in some individuals, for many it enabled seizures to be predicted above random chance. Due to data limitations in overall recording duration and number of seizures captured, these findings require further validation with much larger high-density intracranial EEG datasets. Still, they provide a preliminary framework for the eventual use of HFOs in patient-specific seizure prediction with the potential to improve the lives of those with refractory epilepsy.

Chair: Dr. William Stacey

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Lecture / Discussion Thu, 10 Dec 2020 14:13:29 -0500 2020-12-22T14:00:00-05:00 2020-12-22T15:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Tianrui Luo (December 22, 2020 3:00pm) https://events.umich.edu/event/79858 79858-20509623@events.umich.edu Event Begins: Tuesday, December 22, 2020 3:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via Zoom. The link will be placed below.

https://umich.zoom.us/j/92217348735

Excitation pulse design and image reconstruction are two important topics in MR research for enabling faster imaging. On the pulse design side, selective excitations that confine signals to be within a small region-of-interest (ROI) instead of the full imaging field-of-view (FOV) can be used to reduce sampling density in the k-space, which is a direct outcome of the change in the underlying Nyquist sampling rate. On the reconstruction side, besides improving imaging algorithms’ ability to restore images from less data, another objective is to reduce the reconstruction time, particularly for dynamic imaging applications.



This dissertation focuses on these two perspectives: The first part is devoted to the excitation pulse design. Specifically, we derived and developed a computationally efficient auto-differentiable Bloch-simulator and its explicit Bloch simulation Jacobian operations. This simulator can yield numerical derivatives with respect to pulse RF and gradient waveforms given arbitrary subdifferentiable excitation objective functions. We successfully applied this pulse design approach for jointly designing RF and gradient waveforms for 3D spatially tailored large-tip excitation objectives.



The auto-differentiable pulse design method can yield superior 3D spatially tailored excitation profiles that are useful for inner volume (IV) imaging. We propose and develop a novel steady-state IV imaging strategy which suppresses aliasing by saturating the outer volume (OV) magnetizations via a 3D tailored OV excitation pulse that is followed by a signal crusher gradient. This method substantially suppresses the unwanted OV aliasing for common steady-state imaging sequences.



The second part focuses on non-iterative image reconstruction. In dynamic imaging (e.g., fMRI), where a time series is to be reconstructed, such algorithms may offer savings in overall reconstruction time. We extend the conventional GRAPPA algorithm to work efficiently for general non-Cartesian acquisitions. It attains reconstruction quality that can rival classical iterative imaging methods such as conjugate gradient SENSE and SPIRiT.



In summary, this dissertation has proposed and developed multiple methods for accelerating MR imaging, from pulse design to reconstruction. While devoted to neuroimaging, the proposed methods are general and should also be useful for other applications.

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Lecture / Discussion Thu, 10 Dec 2020 12:29:18 -0500 2020-12-22T15:00:00-05:00 2020-12-22T16:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
Finding Funding: Identifying Opportunities & Scoping the Grants Landscape (January 13, 2021 12:00pm) https://events.umich.edu/event/79630 79630-20436378@events.umich.edu Event Begins: Wednesday, January 13, 2021 12:00pm
Location: Off Campus Location
Organized By: OVPR Office of Research Development

This workshop will help investigators at all levels to be proactive in using tools to identify federal, state, and foundation research funding. Topics covered will include efficient searching of funding databases and setting up funding alerts through examining the special features of Foundation Directory Online and Pivot. The workshop will also direct researchers to units at the University of Michigan that will support their grantseeking endeavors.

Speakers: Judy Smith, Informationist, Taubman Health Sciences Library; Paul Barrow, Librarian, U-M Library.

This event is open to anyone in the U-M research community.

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Workshop / Seminar Tue, 01 Dec 2020 09:05:07 -0500 2021-01-13T12:00:00-05:00 2021-01-13T13:00:00-05:00 Off Campus Location OVPR Office of Research Development Workshop / Seminar RD
PhD Defense: Charles Park (January 15, 2021 1:00pm) https://events.umich.edu/event/80413 80413-20719667@events.umich.edu Event Begins: Friday, January 15, 2021 1:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held remotely via Zoom. The link will be placed below.

Zoom: https://umich-health.zoom.us/j/97318374664?pwd=YTB4dzNTVXdRZDZQcGR1dVRLZi9JUT09

With the recent progress in technologies, analyzing detailed cellular interactions that constitute the immune system have become possible, and many more biological and engineering tools became within reach for precise investigation and modulation of immune responses. As a result, immunotherapies, such as anti-PD-1 antibody and chimeric antigen receptor T cells, have revolutionized cancer immunotherapy, while genome sequencing and nanotechnology allowed for the rapid development of various vaccines in response to the recent outbreak of Coronavirus Disease 2019. Here, first discussed is modulation of the immune responses using biomaterials, such as silica- or lipid-based nanoparticles and immunomodulating agents for cancer immunotherapy. My approach for immune modulation was to deliver vaccine or pattern recognition receptor-stimulating drugs using nanoparticles to enhance the activation of antigen presenting cells at the innate immune response stage, which leads to stronger adaptive immune responses. In addition, induction of a stronger chemokine gradient to recruit more T cells to tumor from the blood circulation was investigated. In the next study, use of lipid-based nanoparticle to formulate vaccines against infectious diseases, such as human immunodeficiency virus-1 (HIV-1) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is introduced. Nanoparticle-mediated vaccine delivery increases the amount of antigen reaching lymph nodes to interact with immune cells. Also, co-delivery of adjuvants further induces stronger adaptive immune responses. Meanwhile, it is critical to preserve the epitope conformation when protein antigens are used for vaccine formulation, in order to induce functional neutralizing antibodies. The aim of the study was to co-load a subunit protein and an adjuvant into lipid-based nanoparticles while maintaining the structural intactness and induce enhanced antibody responses when vaccinated to animals. Overall, immune modulation strategies are introduced in therapeutic or prophylactic settings, where innate and adaptive immune responses were enhanced using biomaterials-based treatments.

Chair: Dr. James J. Moon

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Lecture / Discussion Wed, 06 Jan 2021 08:23:34 -0500 2021-01-15T13:00:00-05:00 2021-01-15T14:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
BME 500 Seminar - Xiaoning Jiang (January 21, 2021 4:00pm) https://events.umich.edu/event/80996 80996-20830794@events.umich.edu Event Begins: Thursday, January 21, 2021 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via Blue Jeans. The link will be placed below.

Blue Jeans Link: https://bluejeans.com/628109990

Xiaoning Jiang, Ph.D.

North Carolina State University

Seminar Abstract:

Cardiovascular disease (CVD) remains the number one cause of death and the search for more effective diagnosis and treatment techniques has been of a great interest. Ultrasound present a great potential in imaging and therapy for CVD. In this talk, small aperture transducers were designed, fabricated and tested for advanced intravascular ultrasound imaging (IVUS) and effective and safe intravenous sonothrombolysis. In specific, we investigated high frequency (40-60 MHz) micromachined piezoelectric composite transducers and arrays with broad bandwidth (-6 dB fraction bandwidth ~ 80%) for intravascular ultrasound (IVUS) imaging. Dual frequency transducers and arrays (6.5 MHz/30 MHz, 3 MHz/30 MHz) were also successfully demonstrated for contrast enhanced intravascular superharmonic imaging (or acoustic angiography) toward detection of plaque vulnerability. For the case of intravascular thrombolysis, small aperture (diameter &lt;2 mm) sub-MHz forward-looking transducers were successfully developed with peak-negative-pressure of &gt; 1.5 MPa. Significantly enhanced thrombolysis rate was observed by using microbubbles and nanodroplets in in-vitro tests. Other transducer techniques such as optical fiber laser ultrasound transducers were also investigated for intravenous sonothrombolysis. These new findings suggest that small aperture ultrasound transducers are increasingly important in advancing intravascular ultrasound imaging, intravenous therapy, minimal invasive diagnosis and therapy, and image guided drug delivery and surgery.

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Lecture / Discussion Wed, 20 Jan 2021 10:42:47 -0500 2021-01-21T16:00:00-05:00 2021-01-21T17:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
BME 500 Seminar: Aaron Morris, Ph.D. (January 28, 2021 4:00pm) https://events.umich.edu/event/81261 81261-20879893@events.umich.edu Event Begins: Thursday, January 28, 2021 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via Zoom. The link will be posted below.
https://umich.zoom.us/j/94405051853

Seminar Abstract:

My research program, the Precision Immune Microenvironment (PIM) Lab, will create a minimally invasive toolset for monitoring immune responses within tissues. In my research seminar I will begin by briefly discussing the work I performed with Dr. Themis Kyriakides as a PhD student at Yale - strategies to manipulate the early stages of the foreign body response (FBR) to implanted materials. I will next discuss my work as a postdoctoral fellow at the University of Michigan with Dr. Lonnie Shea. I focus on harnessing the chronic phase of the FBR, as a tool to monitor the immune system. I use biomaterial-based immunological niches to provide insights into the phenotype of innate immune cells that control disease activity. Cells harvested from these niches exhibit differential gene expression sufficient to monitor disease dynamics and to gauge the effectiveness of treatment. I will then discuss work developing sensors for secreted proteins to non-invasively measure protein expression in vivo via luminescence and FRET. I will conclude my talk with a brief discussion of my planned research
program that aims to leverage my materials and immune engineering experience to harness bio-responsive materials as translatable tools for real-time monitoring of tissue immunity.

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Lecture / Discussion Tue, 26 Jan 2021 12:39:22 -0500 2021-01-28T16:00:00-05:00 2021-01-28T17:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
BME 500 Seminar: Maria Coronel (February 4, 2021 4:00pm) https://events.umich.edu/event/81382 81382-20889813@events.umich.edu Event Begins: Thursday, February 4, 2021 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

BME Faculty Candidate
Maria Coronel, Ph.D.
Georgia Institute of Technology

Seminar Abstract:
Two major challenges to the translation of cellular-based tissue-engineered therapies are the lack of adequate oxygen support post-implantation and the need for systemic immunosuppression to halt the strong inflammatory and immunological response of the host. As such, strategies that aim at addressing oxygen demand, and local immunological responses can be highly beneficial in the translation of these therapies. In this seminar, I will focus on two biomaterial strategies to create a more favorable transplant niche for pancreatic islet transplantation. The first half will describe an in-situ oxygen-releasing biomaterial fabricated through the incorporation of solid peroxides in a silicone polymer. The implementation of this localized, controlled and sustained oxygen-generator mitigates the activation of detrimental hypoxia-induced pathways in islets and enhances the potency of extrahepatic 3D islet- loaded devices in a diabetic animal model. In the second part, I will focus on engineering synthetic biomaterials for the delivery of immunomodulatory signals for transplant acceptance. Biomaterial carriers fabricated with polyethylene glycol microgels are used to deliver immunomodulatory signals to regulate the local microenvironment and prevent allograft rejection in a clinically relevant pre-clinical transplant model. The use of synthetic materials as an off-the-shelf platform, without the need for manipulating the biological cell product, improves the clinical translatability of this engineered approach. Designing safer, responsive biomaterials to boost the delivery of targeted therapeutics will significantly reinvigorate interventional cell-based tissue-engineered therapies.

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Lecture / Discussion Fri, 29 Jan 2021 17:14:27 -0500 2021-02-04T16:00:00-05:00 2021-02-04T17:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
BME 500 Seminar: Gloria Kim (February 11, 2021 4:00pm) https://events.umich.edu/event/81383 81383-20889814@events.umich.edu Event Begins: Thursday, February 11, 2021 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Seminar Abstract:

The major problems in the current therapy for oncologic diseases include its inability to selectively target specific tumor cells in the surrounding tissues that make it hard for the drugs and treatment to reach the tumor cells. Despite the significant progress in the discovery of surface markers, targeting ligands, and biomaterial carriers, very few nanoparticle drugs are truly tumor-specific after intravenous injection and their targeting is still not fully reliable, which results in a wide distribution of nanoparticles throughout the body and increases the chance of adverse side effects. To overcome such limitations, my graduate research implemented immune cells as living targeting and delivery vehicles that deliver therapeutic biodegradable photoluminescent polymer (BPLP)-based nanoparticles to two tumor models, melanoma and glioblastoma. This system takes advantage of the inherent targeting and penetrating capabilities of immune cells into the tumor target and the fluorescent properties of BPLP nanoparticles for in vivo imaging. Our platform technology allows assembling various types of nanoparticles, drugs, imaging agents, and immune cells as a treatment for different diseases in the future. The second part of the seminar introduces how the immune cells can also be genetically engineered for cancer immunotherapy in vivo. Even with huge success in the development of CD19-targeting chimeric antigen receptor (CAR) T cells for B-cell hematological malignancies, we still face major challenges in expanding adoptive cell transfer for solid tumors. To expand this adoptive cell therapy, finding the right targets for solid tumors that are tumor- and tumor microenvironment-specific is the foremost important step. During my postdoctoral work, we have found an epitope within the collagen alpha-3(VI) (COL6A3) gene, which can be used as a biomarker to target stromal cells associated with multiple solid tumors. COL6A3-specific TCRs were isolated and one of these TCRs was affinity enhanced so that the T cells expressing TCR variants that preserved COL6A3 specificity and endowed both CD4 and CD8 T cells with augmented effector functions were able to specifically eliminate tumors in vivo that expressed similar amount of peptide-human leukocyte antigen (pHLA) as primary tumor specimens with favorable safety profile with no detectable off-target reactivity. These preclinical findings serve as the basis and rationale to initiate clinical trials using COL6A3-specific TCRs to target an array of solid tumors. As a principal investigator, my lab will first focus on merging immunology, synthetic biology, genetic engineering, material science, and biomedical engineering to develop and evaluate the next generation T cell-based therapies that target and kill solid tumors with enhanced specificity, reduced toxicity, and the ability to overcome tumor-associated immunosuppression.

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Lecture / Discussion Fri, 05 Feb 2021 16:15:40 -0500 2021-02-11T16:00:00-05:00 2021-02-11T17:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
BME 500 Seminar: Adam Glaser (February 18, 2021 4:00pm) https://events.umich.edu/event/81384 81384-20889815@events.umich.edu Event Begins: Thursday, February 18, 2021 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Seminar Abstract:

New developments in microscopy, tissue clearing, and fluorescent labeling are enabling unprecedented access to the structural and molecular contents of biological tissues. These technologies are now opening new doors in scientific research and shedding light on the critical factors which underpin complex disease processes. In this presentation, I will present my recent work in these areas, with a focus on applications to cancer at both the clinical and preclinical level.

ZOOM LINK: https://umich.zoom.us/j/94405051853

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Lecture / Discussion Sat, 13 Feb 2021 20:04:17 -0500 2021-02-18T16:00:00-05:00 2021-02-18T17:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
BME 500 Seminar: Jorge Marchand (February 25, 2021 4:00pm) https://events.umich.edu/event/81385 81385-20889816@events.umich.edu Event Begins: Thursday, February 25, 2021 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Seminar Abstract:

In living organisms, translation of genetic information by the ribosome transforms
the information embedded in DNA into actuating components, namely proteins. Though life itself is incredibly diverse at the macroscopic level, at the molecular level, all of life uses the same set of machinery for translation - 20 standard amino acid building blocks (with minor exceptions), transfer RNAs (tRNA), and ribosomes. The convergence and association of these interdependent biomolecules is neatly captured in a table known as the ‘standard genetic code’. Even after billions of years of genetic drift, the ‘standard genetic code’ has been largely refractory to change. In this talk, I will be discussing strategies and methods for building organisms that can make and use non-standard amino acids to make proteins with enhanced or expanded function.

ZOOM LINK: https://umich.zoom.us/j/94405051853

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Lecture / Discussion Sun, 21 Feb 2021 22:07:28 -0500 2021-02-25T16:00:00-05:00 2021-02-25T17:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo