Biomedical Engineering and Bioengineering Commons^™

Identification Of Prognostic Cancer Biomarkers Through The Application Of Rna-Seq Technologies And Bioinformatics, Nathan Wong

McKelvey School of Engineering Theses & Dissertations

MicroRNAs (miRNAs) are short single-stranded RNAs that function as the guide sequence of the post-transcriptional regulatory process known as the RNA-induced silencing complex (RISC), which targets mRNA sequences for degradation through complementary binding to the guide miRNA. Changes in miRNA expression have been reported as correlated with numerous biological processes, including embryonic development, cellular differentiation, and disease manifestation. In the latter case, dysregulation has been observed in response to infection by human papillomavirus (HPV), which has also been established as both oncogenic in cervical cancers and oropharyngeal cancers and favorable for overall patient survival after tumor formation. The identification of …

Telesurgery: Surgery In The Digital Age, Dylan J. Cahill

Dartmouth Undergraduate Journal of Science

The dawn of the digital age has transformed the way we now receive and provide healthcare. Today, providers have instant access to all of their patients’ information, just as patients can connect with their providers on their smartphones in minutes from nearly anywhere in the world.

Ambulatory Systolic Blood Pressure And Obesity Are Independently Associated With Left Ventricular Hypertrophic Remodeling In Children, Linyuan Jing, Christopher D. Nevius, Cassi M. Friday, Jonathan D. Suever, Arichanah Pulenthiran, Abba Mejia-Spiegeler, H. Lester Kirchner, William J. Cochran, Gregory J. Wehner, Aftab S. Chishti, Christopher M. Haggerty, Brandon K. Fornwalt

Biomedical Engineering Faculty Publications

Background: Children with obesity have hypertrophic cardiac remodeling. Hypertension is common in pediatric obesity, and may independently contribute to hypertrophy. We hypothesized that both the degree of obesity and ambulatory blood pressure (ABP) would independently associate with measures of hypertrophic cardiac remodeling in children.

Methods: Children, aged 8–17 years, prospectively underwent cardiovascular magnetic resonance (CMR) and ABP monitoring. Left ventricular (LV) mass indexed to height^2.7(LVMI), myocardial thickness and end-diastolic volume were quantified from a 3D LV model reconstructed from cine balanced steady state free precession images. Categories of remodeling were determined based on cutoff values for LVMI and …

Computational Sensitivity Investigation Of Hydrogel Injection Characteristics For Myocardial Support, Hua Wang, Christopher B. Rodell, Madonna E. Lee, Neville N. Dusaj, Joseph H. Gorman Iii, Jason A. Burdick, Robert C. Gorman, Jonathan F. Wenk

Mechanical Engineering Faculty Publications

Biomaterial injection is a potential new therapy for augmenting ventricular mechanics after myocardial infarction (MI). Recent in vivo studies have demonstrated that hydrogel injections can mitigate the adverse remodeling due to MI. More importantly, the material properties of these injections influence the efficacy of the therapy. The goal of the current study is to explore the interrelated effects of injection stiffness and injection volume on diastolic ventricular wall stress and thickness. To achieve this, finite element models were constructed with different hydrogel injection volumes (150 µL and 300 µL), where the modulus was assessed over a range of 0.1 kPa …

Pattern Discovery In Brain Imaging Genetics Via Scca Modeling With A Generic Non-Convex Penalty, Lei Du, Kefei Liu, Xiaohui Yao, Jingwen Yan, Shannon L. Risacher, Junwei Han, Lei Guo, Andrew J. Saykin, Li Shen, Michael W. Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, Charles D. Smith, Gregory Jicha, Peter A. Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad

Neurology Faculty Publications

Brain imaging genetics intends to uncover associations between genetic markers and neuroimaging quantitative traits. Sparse canonical correlation analysis (SCCA) can discover bi-multivariate associations and select relevant features, and is becoming popular in imaging genetic studies. The L1-norm function is not only convex, but also singular at the origin, which is a necessary condition for sparsity. Thus most SCCA methods impose ℓ₁-norm onto the individual feature or the structure level of features to pursuit corresponding sparsity. However, the ℓ₁-norm penalty over-penalizes large coefficients and may incurs estimation bias. A number of non-convex penalties are proposed to reduce …

Parallelization Of A Three-Dimensional Full Multigrid Algorithm To Simulate Tumor Growth, Dylan Goodin, Chin F. Ng, Hermann B. Frieboes

Commonwealth Computational Summit

We present the performance gains of an openMP implementation of a fully adaptive nonlinear full multigrid (FMG) algorithm to simulate three-dimensional multispecies desmoplastic tumor growth on computer systems of varying processing capabilities. The FMG algorithm is applied to solve a recently published thermodynamic mixture model that uses a diffuse interface approach with fourth-order reaction-advection-diffusion PDEs (Cahn-Hilliard-type equations) that are coupled, nonlinear, and numerically stiff. The model includes multiple cell species and extracellular matrix (ECM), with adhesive and elastic energy contributions in chemical potential terms, as well as including blood and lymphatic vessels represented as continuous vasculatures. Advection-reaction-diffusion PDEs are employed …

Development And Validation Of A Hybrid Virtual/Physical Nuss Procedure Surgical Trainer, Mohammad F. Obeid

Computational Modeling & Simulation Engineering Theses & Dissertations

With continuous advancements and adoption of minimally invasive surgery, proficiency with nontrivial surgical skills involved is becoming a greater concern. Consequently, the use of surgical simulation has been increasingly embraced by many for training and skill transfer purposes. Some systems utilize haptic feedback within a high-fidelity anatomically-correct virtual environment whereas others use manikins, synthetic components, or box trainers to mimic primary components of a corresponding procedure.

Surgical simulation development for some minimally invasive procedures is still, however, suboptimal or otherwise embryonic. This is true for the Nuss procedure, which is a minimally invasive surgery for correcting pectus excavatum (PE) – …

Motion Artifact Evaluation Of Coronary Ct Angiography Images, Hongfeng Ma

Dissertations (1934 -)

The objective of this dissertation was to develop and validate an automated algorithm to quantify motion artifact level on coronary CT angiography (CCTA) images. Unlike existing motion artifact reduction techniques that evaluate the relative level of motion artifacts within one exam, this dissertation aims to quantify the absolute level of motion artifacts across exams from varying patients. The ability to quantify absolute motion artifact level enables several potential applications, for example, assessing and comparing two motion artifact reduction techniques. This dissertation includes three specific aims. Aim 1 investigated the absolute motion artifact quantification effectiveness of six motion artifact metrics using …

Effects Of Random Oscillations On Balance Control In Healthy Young Adults, Jacob Van Dehy

Master's Theses (2009 -)

In human walking, balance control is managed through proactive changes in spatio-temporal parameters of stepping [1]. It has been suggested that continuous disruptions to healthy young adult balance cause greater changes to overall variability of these parameters than a shift in the mean stepping parameters [2]. This suggests that walking may be occurring in a more reactive manner, modulating to maintain balance without increasing the mean significantly. Work using continuous oscillations to treadmill walking suggest there is an interplay between the predictability of a signal used to disrupt subject balance and the degree to which compensation occurs [3]. To determine …

Computational Modeling For Abnormal Brain Tissue Segmentation, Brain Tumor Tracking, And Grading, Syed Mohammad Shamin Reza

Electrical & Computer Engineering Theses & Dissertations

This dissertation proposes novel texture feature-based computational models for quantitative analysis of abnormal tissues in two neurological disorders: brain tumor and stroke. Brain tumors are the cells with uncontrolled growth in the brain tissues and one of the major causes of death due to cancer. On the other hand, brain strokes occur due to the sudden interruption of the blood supply which damages the normal brain tissues and frequently causes death or persistent disability. Clinical management of these brain tumors and stroke lesions critically depends on robust quantitative analysis using different imaging modalities including Magnetic Resonance (MR) and Digital Pathology …

Endothelial Function Is Associated With White Matter Microstructure And Executive Function In Older Adults, Nathan F. Johnson, Brian T. Gold, Christopher A. Brown, Emily F. Anggelis, Alison L. Bailey, Jody L. Clasey, David K. Powell

Physical Therapy Faculty Publications

Age-related declines in endothelial function can lead to cognitive decline. However, little is known about the relationships between endothelial function and specific neurocognitive functions. This study explored the relationship between measures of endothelial function (reactive hyperemia index; RHI), white matter (WM) health (fractional anisotropy, FA, and WM hyperintensity volume, WMH), and executive function (Trail Making Test (TMT); Trail B - Trail A). Participants were 36 older adults between the ages of 59 and 69 (mean age = 63.89 years, SD = 2.94). WMH volume showed no relationship with RHI or executive function. However, there was a positive relationship between RHI …

Biomechanical Testing Of An Exercise For Strengthening The Proximal Femur., Alyssa Osbourne

Electronic Theses and Dissertations

Based on the principles of cutting edge bone remodeling research, a unique therapeutic exercise device was designed specifically to improve bone quality at the most critical location of the proximal femur prone to fracture: the superior-lateral femoral neck where the fracture first initiates during a fall. The exercise/device is intended to work by inducing enough strain in the bone to stimulate the body’s natural bone remodeling mechanisms to increase bone density in the proximal femur and consequently prevent a fracture from arising if a fall to the side does occur.

In order to test the proposed exercise, experiments simulating the …

Custom Software For The 3d Printing Of Patient Specific Plate Bending Templates In Pelvic Fracture Repair., Gordon B Lents

Electronic Theses and Dissertations

The purpose of this work is to reduce the operative time and blood loss incurred during open reduction and internal fixation (ORIF) of traumatic pelvic injuries through the creation of patient specific bending templates for reconstruction plates. These templates are 3D printed in a resin capable of being sterilized and taken into the operating room so that bending may be performed by the surgeon before the patient is opened or by another team member in parallel with the surgeon.

A novel software extension was created in 3D modeling software to allow a surgeon to individually position screws on a pelvic …

Chelator-Free Radiolabeling Of Serrs Nanoparticles For Whole-Body Pet And Intraoperative Raman Imaging, Matthew A. Wall, Travis Shaffer, Stefan Harmsen, Darjus-Felix Tschaharganeh, Chun-Hao Huang, Scott W. Lowe, Charles Michael Drain, Moritz F. Kircher

Publications and Research

A single contrast agent that offers whole-body non-invasive imaging along with the superior sensitivity and spatial resolution of surface-enhanced resonance Raman scattering (SERRS) imaging would allow both pre-operative mapping and intraoperative imaging and thus be highly desirable. We hypothesized that labeling our recently reported ultrabright SERRS nanoparticles with a suitable radiotracer would enable pre-operative identification of regions of interest with whole body imaging that can be rapidly corroborated with a Raman imaging device or handheld Raman scanner in order to provide high precision guidance during surgical procedures. Here we present a straightforward new method that produces radiolabeled SERRS nanoparticles for …

Evaluating Wall Shear Stress Indices To Uncover Stimuli For Restenosis And Malapposition In Stented Coronary Arteries, Ali A. Aleiou

Master's Theses (2009 -)

The cause of coronary artery neointimal thickening leading to restenosis in ~10% of drug-eluting stents is unknown. Although research suggests adverse values of traditional wall shear stress (WSS) indices may contribute, studies to date have not accounted for stent geometry, which dictates local WSS patterns influencing drug concentration. Recently proposed WSS indices such as WSS variability and WSS exposure time (WSSET) may shed further light on restenosis or, the opposite effect, resorption. The objective of this investigation was to locally evaluate traditional and recently proposed post-stenting metrics and their respective impact on restenosis or resorption. This study used de-identified data …

The Specific Vulnerabilities Of Cancer Cells To The Cold Atmospheric Plasma-Stimulated Solutions., Dayun Yan, Haitao Cui, Wei Zhu, Niki Nourmohammadi, Julian Milberg, Lijie G Zhang, Jonathan H Sherman, Michael Keidar

Neurological Surgery Faculty Publications

Cold atmospheric plasma (CAP), a novel promising anti-cancer modality, has shown its selective anti-cancer capacity on dozens of cancer cell lines in vitro and on subcutaneous xenograft tumors in mice. Over the past five years, the CAP-stimulated solutions (PSS) have also shown their selective anti-cancer effect over different cancers in vitro and in vivo. The solutions used to make PSS include several bio-adaptable solutions, mainly cell culture medium and simple buffered solutions. Both the CAP-stimulated medium (PSM) and the CAP-stimulated buffered solution (PSB) are able to significantly kill cancer cells in vitro. In this study, we systematically compared the anti-cancer …

Impaired Right Ventricular Contractile Function In Childhood Obesity And Its Association With Right And Left Ventricular Changes: A Cine Dense Cardiac Magnetic Resonance Study, Linyuan Jing, Arichanah Pulenthiran, Christopher D. Nevius, Abba Mejia-Spiegeler, Jonathan D. Suever, Gregory J. Wehner, H. Lester Kirchner, Christopher M. Haggerty, Brandon K. Fornwalt

Biomedical Engineering Faculty Publications

Background: Pediatric obesity is a growing public health problem, which is associated with increased risk of cardiovascular disease and premature death. Left ventricular (LV) remodeling (increased myocardial mass and thickness) and contractile dysfunction (impaired longitudinal strain) have been documented in obese children, but little attention has been paid to the right ventricle (RV). We hypothesized that obese/overweight children would have evidence of RV remodeling and contractile dysfunction.

Methods: One hundred and three children, ages 8–18 years, were prospectively recruited and underwent cardiovascular magnetic resonance (CMR), including both standard cine imaging and displacement encoding with stimulated echoes (DENSE) imaging, which allowed …

Recombinant Aav Serotype And Capsid Mutant Comparison For Pulmonary Gene Transfer Of Alpha-1-Antitrypsin Using Invasive And Noninvasive Delivery, Rejean Liqun Wang, Thomas J. Mclaughlin, Travis Cossette, Qiushi Tang, Kevin Foust, Martha Campbell-Thompson, Ashley Martino, Pedro Cruz, Scott Loiler, Christian Mueller, Terence R. Flotte

Christian Mueller

Recombinant adeno-associated viral (rAAV) vectors have been widely used in pulmonary gene therapy research. In this study, we evaluated the transduction and expression efficiencies of several AAV serotypes and AAV2 capsid mutants with specific pulmonary targeting ligands in the mouse lung. The noninvasive intranasal delivery was compared with the traditional intratracheal lung delivery. The rAAV8 was the most efficient serotype at expressing alpha-1-antitrypsin (AAT) in the lung among all the tested serotypes and mutants. A dose of 1 x 1010 vg of rAAV8-CB-AAT transduced a high percentage of cells in the lung when delivered intratrachealy. The serum and the broncho-alveolar …

Sensitivity Of Diffuse Reflectance Spectroscopy To Dose- And Depth-Dependent Changes In Tumor Oxygenation After Radiation Therapy, Daria Semeniak

Graduate Theses and Dissertations

Along with chemotherapy, immunotherapy, and surgery, radiotherapy is one of the most common treatments used against cancer. Around 50% of all cancer patients undergo radiation therapy. While for some patients radiotherapy works efficiently and lead to a complete cancer disappearance, for others treatment outcome may be less favorable due to radioresistance processes happening within a tumor on the molecular level. Radioresistance remains a big challenge for modern oncology. The ability to identify radioresistance at the early stage of radiotherapy would help physicians to improve therapy efficiency. At the current moment, despite the rapid progress in cancer understanding and diagnostic modalities, …

Characterization Of Murine Breast Cancer Cell Lines For Anti-Cancer Vaccine, Haven N. Frazier

Biological Sciences Undergraduate Honors Theses

Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of cancer death among women in the United States (1). While treatments involving radiation and chemotherapy currently exist, disease must be detected early in order for the treatments to be somewhat effective, and there is no effective treatment after metastasis occurs (2). Additionally, current therapies do not mitigate tumor immunosuppression. Decreasing the tumor-associated immunosuppressive conditions while activating antitumor immunity could prevent recurrence and metastasis, possibly leading to an effective treatment for cancer (3). Tumor cell vaccines could possibly address this issue and have become a …

Optical Imaging Of Metabolic Adaptability As A Biomarker For Metastatic Potential In Breast Cancer Cells, Mason G. Harper

Biomedical Engineering Undergraduate Honors Theses

Breast cancer metastasis is the main cause for mortality in breast cancer patients. However, knowledge of metastatic recurrence is limited, and there is a need to understand metastatic recurrence in order to treat breast cancer patients more effectively. Highly invasive metastatic breast cancer has shown to exhibit metabolic adaptability, transitioning from glycolysis to oxidative phosphorylation in the presence of microenvironmental stress. NADH and FAD are naturally occurring cofactor products during glycolysis and oxidative phosphorylation, respectively, and they are of particular importance during these metabolic processes due to their endogenous fluorescence. Measuring the ratio of fluorescence intensities of these cofactors through …

Optimization Of Fluorescent Imaging In The Operating Room Through Pulsed Acquisition And Gating To Ambient Background Cycling, Kristian J. Sexton, Yan Zhao, Scott C. Davis, Shudong Jiang, Brian Pogue

Dartmouth Scholarship

The design of fluorescence imaging instruments for surgical guidance is rapidly evolving, and a key issue is to efficiently capture signals with high ambient room lighting. Here, we introduce a novel time-gated approach to fluorescence imaging synchronizing acquisition to the 120 Hz light of the room, with pulsed LED excitation and gated ICCD detection. It is shown that under bright ambient room light this technique allows for the detection of physiologically relevant nanomolar fluorophore concentrations, and in particular reduces the light fluctuations present from the room lights, making low concentration measurements more reliable. This is particularly relevant for the light …

Exploring Therapeutic Approaches For Marfan Syndrome Associated Aortic Aneurysm, Mitra Esfandiarei

Science Seminar Series

Esfandiearei will be discussing her research on understanding the underlying mechanisms contributing to the progression of aortic aneurysm in Marfan syndrome and the protective effects that exercise may have on the disease process in both laboratory animal models and human patients. Her research has been supported by the Canadian Institutes of Health Research (CIHR), Rare Diseases Foundation, and the Marfan Foundation.

White Matter Hyperintensity Associations With Cerebral Blood Flow In Elderly Subjects Stratified By Cerebrovascular Risk, Ahmed A. Bahrani, David K. Powell, Guoqiang Yu, Eleanor S. Johnson, Gregory A. Jicha, Charles D. Smith

Biomedical Engineering Faculty Publications

Objective: This study aims to add clarity to the relationship between deep and periventricular brain white matter hyperintensities (WMHs), cerebral blood flow (CBF), and cerebrovascular risk in older persons. Methods: Deep white matter hyperintensity (dWMH) and periventricular white matter hyperintensity (pWMH) and regional gray matter (GM) and white matter (WM) blood flow from arterial spin labeling were quantified from magnetic resonance imaging scans of 26 cognitively normal elderly subjects stratified by cerebrovascular disease (CVD) risk. Fluidattenuated inversion recovery images were acquired using a high-resolution 3-dimensional (3-D) sequence that reduced partial volume effects seen with slicebased techniques. Results: dWMHs but not …

Heart Pump Modelling: Design Of Pulsatile Flow Phantoms, Olivia Coiado, Kevin Jones, Parker Schibel, Nicolas De Almeida

Biomedical Engineering Western Regional Conference

The purpose of this project is to build a model, which mimics physiological conditions of the human cardiovascular system in order to simulate the parameters of the human heart in vivo. For this project, it was developed a flow phantom with vessel mimicking material, as well as blood-mimicking and tissue-mimicking fluid. Phantoms in general are specifically designed objects involving dedicated biomaterials to simulate special realistic circuits of human beings. To develop the flow phantom, low-priced biomaterials for blood mimicking fluid, tissue mimicking, and vessel mimicking material was researched.

Keywords: Cardiovascular system, heart pump, modelling, pulsatile.

Cold Atmospheric Plasma, A Novel Promising Anti-Cancer Treatment Modality., Dayun Yan, Jonathan H Sherman, Michael Keidar

Neurological Surgery Faculty Publications

Over the past decade, cold atmospheric plasma (CAP), a near room temperature ionized gas has shown its promising application in cancer therapy. Two CAP devices, namely dielectric barrier discharge and plasma jet, show significantly anti-cancer capacity over dozens of cancer cell lines in vitro and several subcutaneous xenograft tumors in vivo. In contrast to conventional anti-cancer approaches and drugs, CAP is a selective anti-cancer treatment modality. Thus far establishing the chemical and molecular mechanism of the anti-cancer capacity of CAP is far from complete. In this review, we provide a comprehensive introduction of the basics of CAP, state of the …

Design Of Radio-Frequency Arrays For Ultra-High Field Mri, Ian R O Connell

Electronic Thesis and Dissertation Repository

Magnetic Resonance Imaging (MRI) is an indispensable, non-invasive diagnostic tool for the assessment of disease and function. As an investigational device, MRI has found routine use in both basic science research and medicine for both human and non-human subjects.

Due to the potential increase in spatial resolution, signal-to-noise ratio (SNR), and the ability to exploit novel tissue contrasts, the main magnetic field strength of human MRI scanners has steadily increased since inception. Beginning in the early 1980’s, 0.15 T human MRI scanners have steadily risen in main magnetic field strength with ultra-high field (UHF) 8 T MRI systems deemed to …

Pet Imaging Of Early Therapeutic Response In Solid Tumors, Stephanie J. Blocker

Wayne State University Dissertations

An important pillar of precision medicine for oncology is the ability to identify patients who respond to treatment early into their therapy. Positron emission tomography (PET) allows physicians and researchers to measure changes in tumor behavior prior to noticeable differences in morphology.

Objective: Determine the utility of multiple tracers for PET in assessing early changes in tumor activity that result from treatment.

Methods: Two tracers for PET were studied. 64Cu-labeled liposomes were used to assess changes in liposome delivery two solid colon tumors early into treatment with bevacizumab (Bev). 18F-FMAU thymidine analog (1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)thymine), was utilized to detect early response to …

A Modified Fasp Protocol For High-Throughput Preparation Of Protein Samples For Mass Spectrometry., Jeremy Potriquet, Marut Laohaviroj, Jeffrey M Bethony, Jason Mulvenna

Microbiology, Immunology, and Tropical Medicine Faculty Publications

o facilitate high-throughput proteomic analyses we have developed a modified FASP protocol which improves the rate at which protein samples can be processed prior to mass spectrometry. Adapting the original FASP protocol to a 96-well format necessitates extended spin times for buffer exchange due to the low centrifugation speeds tolerated by these devices. However, by using 96-well plates with a more robust polyethersulfone molecular weight cutoff membrane, instead of the cellulose membranes typically used in these devices, we could use isopropanol as a wetting agent, decreasing spin times required for buffer exchange from an hour to 30 minutes. In a …

Human Liver Sinusoid On A Chip For Hepatitis B Virus Replication Study, Young Bok (Abraham) Kang, Siddhartha Rawat, Nicholas Duchemin, Michael Bouchard, Moses Noh

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

We have developed a miniature human liver (liver-sinusoid-on-a-chip) model using a dual microchannel separated by a porous membrane. Primary human hepatocytes and immortalized bovine aortic endothelial cells were co-cultured on opposite sides of a microporous membrane in a dual microchannel with continuous perfusion. Primary human hepatocytes in this system retained their polygonal morphology for up to 26 days, while hepatocytes cultured in the absence of bovine aortic endothelial cells lost their morphology within a week. In order to demonstrate the utility of our human-liver-sinusoid-on-a-chip, human hepatocytes in this system were directly infected by Hepatitis B Virus (HBV). Expression of the …