Engineering Commons^™

Optical And X-Ray Technology Synergies Enabling Diagnostic And Therapeutic Applications In Medicine, Brian W. Pogue, Brian C. Wilson

Dartmouth Scholarship

X-ray and optical technologies are the two central pillars for human imaging and therapy. The strengths of x-rays are deep tissue penetration, effective cytotoxicity, and the ability to image with robust projection and computed-tomography methods. The major limitations of x-ray use are the lack of molecular specificity and the carcinogenic risk. In comparison, optical interactions with tissue are strongly scatter dominated, leading to limited tissue penetration, making imaging and therapy largely restricted to superficial or endoscopically directed tissues. However, optical photon energies are comparable with molecular energy levels, thereby providing the strength of intrinsic molecular specificity. Additionally, optical technologies are …

Tissue Oxygen Saturation Predicts Response To Breast Cancer Neoadjuvant Chemotherapy Within 10 Days Of Treatment, Jeffrey M. Cochran, David R. Busch, Anais Leproux, Zheng Zhang, Thomas D. O'Sullivan, Albert E. Cerussi, Philip M. Carpenter, Rita S. Mehta, Darren Roblyer, Wei Yang, Keith D. Paulsen, Brian Pogue, Shudong Jiang, Peter A. Kaufman

Dartmouth Scholarship

Ideally, neoadjuvant chemotherapy (NAC) assessment should predict pathologic complete response (pCR), a surrogate clinical endpoint for 5-year survival, as early as possible during typical 3- to 6-month breast cancer treatments. We introduce and demonstrate an approach for predicting pCR within 10 days of initiating NAC. The method uses a bedside diffuse optical spectroscopic imaging (DOSI) technology and logistic regression modeling. Tumor and normal tissue physiological properties were measured longitudinally throughout the course of NAC in 33 patients enrolled in the American College of Radiology Imaging Network multicenter breast cancer DOSI trial (ACRIN-6691). An image analysis scheme, employing z-score normalization to …

Computational Aerodynamics And Anatomical Characterization Of Laryngotracheal Stenosis In Children, William Poynot

LSU Master's Theses

Laryngotracheal stenosis (LTS) is a health condition in which an obstruction in the upper trachea can cause breathing difficulties and increased incidence of infection, among other symptoms. Occurring most commonly due to intubation in infants, LTS often requires corrective surgery. Currently, clinical methods of assessing the blockage region are simplistic and subjective, and it is challenging to determine the most effective surgical strategy for any given patient. In the present work, a comprehensive methodology is proposed for characterizing the stenosis region both in terms of its anatomical parameters and its corresponding aerodynamic properties. The combination of computational fluid dynamics (CFD) …

Papaverine And Its Derivatives Radiosensitize Solid Tumors By Inhibiting Mitochondrial Metabolism, Martin Benej, Xiangqian Hong, Sandip Vibhute, Sabina Scott, Jinghai Wu, Edward Graves, Quynh-Thu Le, Albert C. Koong, Amato J. Giaccia, Bing Yu, Ching-Shih Chen, Ioanna Papandreou, Nicholas C. Denko

Biomedical Engineering Faculty Research and Publications

Tumor hypoxia reduces the effectiveness of radiation therapy by limiting the biologically effective dose. An acute increase in tumor oxygenation before radiation treatment should therefore significantly improve the tumor cell kill after radiation. Efforts to increase oxygen delivery to the tumor have not shown positive clinical results. Here we show that targeting mitochondrial respiration results in a significant reduction of the tumor cells’ demand for oxygen, leading to increased tumor oxygenation and radiation response. We identified an activity of the FDA-approved drug papaverine as an inhibitor of mitochondrial complex I. We also provide genetic evidence that papaverine’s complex I inhibition …

Novel Devices For Studying Acute And Chronic Mechanical Stress In Retinal Pigment Epithelial Cells, Farhad Farjood, Elizabeth Vargis

Biological Engineering Faculty Publications

Choroidal neovascularization (CNV) is a major cause of blindness in patients with age-related macular degeneration (AMD). Overexpression of vascular endothelial growth factor (VEGF), a potent angiogenic protein, by retinal pigment epithelial (RPE) cells is a key stimulator of CNV. Mechanical stress occurs during different stages of AMD and is a possible inducer of VEGF expression in RPE cells. However, robust and realistic approaches to studying acute and chronic mechanical stress under various AMD stages do not exist.The majority of previous work has studied cyclic stretching of RPE cells grown on flexible substrates, but an ideal model must be able to …

Perspective Review Of What Is Needed For Molecular-Specific Fluorescence-Guided Surgery, Brian W. Pogue, Eben L. Rosenthal, Samuel Achilefu, Gooitzen M. Van Dam

Dartmouth Scholarship

Molecular image-guided surgery has the potential for translating the tools of molecular pathology to real-time guidance in surgery. As a whole, there are incredibly positive indicators of growth, including the first United States Food and Drug Administration clearance of an enzyme-biosynthetic-activated probe for surgery guidance, and a growing number of companies producing agents and imaging systems. The strengths and opportunities must be continued but are hampered by important weaknesses and threats within the field. A key issue to solve is the inability of macroscopic imaging tools to resolve microscopic biological disease heterogeneity and the limitations in microscopic systems matching surgery …

Pneumatospinning Of Collagen Microfibers From Benign Solvents, Seth Polk, Nardos Sori, Nick Thayer, Yas Maghdouri-White, Anna A. Bulysheva, Michael P. Francis

School of Medical Diagnostics & Translational Sciences Publications

Introduction. Current collagen fiber manufacturing methods for biomedical applications, such as electrospinning and extrusion, have had limited success in clinical translation, partially due to scalability, cost, and complexity challenges. Here we explore an alternative, simplified and scalable collagen fiber formation method, termed 'pneumatospinning,' to generate submicron collagen fibers from benign solvents. Methods and results. Clinical grade type I atelocollagen from calf corium was electrospun or pneumatospun as sheets of aligned and isotropic fibrous scaffolds. Following crosslinking with genipin, the collagen scaffolds were stable in media for over a month. Pneumatospun collagen samples were characterized using Fourier-transform infrared spectroscopy, circular dichroism, …

Hypothesis Paper: Mechanism For Primary Blast Induced Traumatic Brain Injury With Minimal Head Motion, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Working Papers

Transit of the human skull by blast waves produces diffuse brain injury. The exact mechanisms are unknown. This paper describes plausible mechanisms in which steep intracranial pressure gradients, demonstrated in prior computational models of blast-skull interaction, produce subsequent deformation and motion of the whole brain within the skull, without obvious movement of the head. Equations of motion are derived to describe the acceleration, velocity, and relative position of both the skull and the brain in response to known extracranial and intracranial pressures both during and several hundred milliseconds after blast wave passage. A finite element model is solved to visualize …

Fall 2018 Biomedical Engineering Newsletter, Department Of Biomedical Engineering, Michigan Technological University

Department of Biomedical Engineering Newsletters

Table of Contents

• Global Research, Local Impact: Keat Ghee Ong
• Mechanobiology: Sangyoon Han Measures Cellular Force
• Rupak Rajachar Accelerates Healing in Humans - and Whales
• Optical Elastography Gathers Better Data for Avon
• Making Stents: NSF Graduate Research Fellow Roger Guillory

Consistent And Reproducible Cultures Of Large-Scale 3d Mammary Epithelial Structures Using An Accessible Bioprinting Platform, John A. Reid, Peter M. Mollica, Robert D. Bruno, Patrick C. Sachs

School of Medical Diagnostics & Translational Sciences Publications

Background: Standard three-dimensional (3D) in vitro culture techniques, such as those used for mammary epithelial cells, rely on random distribution of cells within hydrogels. Although these systems offer advantages over traditional 2D models, limitations persist owing to the lack of control over cellular placement within the hydrogel. This results in experimental inconsistencies and random organoid morphology. Robust, high-throughput experimentation requires greater standardization of 3D epithelial culture techniques.

Methods: Here, we detail the use of a 3D bioprinting platform as an investigative tool to control the 3D formation of organoids through the "self-assembly" of human mammary epithelial cells. Experimental bioprinting procedures …

Turning Up Antitumor Immunity Against Breast Cancer, Johnie Hodge

Theses and Dissertations

Breast cancer is the most common cancer in women worldwide, and is the second leading cause of cancer-related death in spite of significant advances in treatment and emphasis on early diagnosis. While treatment of localized disease is often successful, metastatic breast cancer, especially of the triple negative molecular subtype, carries a much poorer prognosis. The significant role of the immune system in the progression from localized to metastatic disease is becoming more and more appreciated. Tumor escape from immune surveillance and immune suppression in the tumor microenvironment have become therapeutic targets in addition to the traditional goals of directly killing …

Identification Of The Mechanisms Through Which Botanicals Attenuate Pathogenesis Of Human Diseases, Esraah Alharris

Theses and Dissertations

Plant products have been used for a long time in treatment of diseases. In fact, more than half of approved medicines are derived from plants or other natural products. Even though the synthetic drugs are effective in treating many human diseases, there is no cure against several clinical disorders. Moreover, a significant number of diseases can be prevented thereby causing less burden on societal healthcare costs as well as promoting healthy lifestyles. Thus, botanicals offer a unique opportunity to explore novel compounds to prevent and treat various clinical disorders as well as understand their mode of action so that new …

A Hard-Real-Time Juggling Simulator To Shape Human Sensitivity To Cues And Coordination Of Muscles, Robert W. Nickl

Link Foundation Modeling, Simulation and Training Fellowship Reports

Many virtual reality tasks incorporate auditory and haptic (or touch) feedback, in addition to visual displays of spatial information. Non-visual feedback modalities such as the former increase realism; but they may have an ancillary benefit of increasing human motor performance and learning. One task for which this has been exhibited is paddle juggling, or vertically bouncing a ball off of a rigid elastic planar surface. For the objective of hitting the ball toward a target height, visual feedback is sufficient. Yet, previous studies have shown that non-visual feedback----specifically haptic---both is sufficient in the absence of vision to maintain stable ball …

Detection Of Hydrogen Peroxide Production In The Isolated Rat Lung Using Amplex Red, Said H. Audi, Nina Friedly, Ranjan K. Dash, Andreas M. Beyer, Anne V. Clough, Elizabeth R. Jacobs

Biomedical Engineering Faculty Research and Publications

The objectives of this study were to develop a robust protocol to measure the rate of hydrogen peroxide (H₂O₂) production in isolated perfused rat lungs, as an index of oxidative stress, and to determine the cellular sources of the measured H₂O₂ using the extracellular probe Amplex red (AR). AR was added to the recirculating perfusate in an isolated perfused rat lung. AR’s highly fluorescent oxidation product resorufin was measured in the perfusate. Experiments were carried out without and with rotenone (complex I inhibitor), thenoyltrifluoroacetone (complex II inhibitor), antimycin A (complex III inhibitor), potassium …

Light Scattering Measured With Spatial Frequency Domain Imaging Can Predict Stromal Versus Epithelial Proportions In Surgically Resected Breast Tissue, David M. Mcclatchy, Elizabeth J. Rizzo, Wendy A. Wells, Candice C. Black, Keith D. Paulsen, Stephen C. Kanick, Brian W. Pogue

Dartmouth Scholarship

This study aims to determine if light scatter parameters measured with spatial frequency domain imaging (SFDI) can accurately predict stromal, epithelial, and adipose fractions in freshly resected, unstained human breast specimens. An explicit model was developed to predict stromal, epithelial, and adipose fractions as a function of light scattering parameters, which was validated against a quantitative analysis of digitized histology slides for N  =  31 specimens using leave-one-out cross-fold validation. Specimen mean stromal, epithelial, and adipose volume fractions predicted from light scattering parameters strongly correlated with those calculated from digitized histology slides (r  =  0.90, 0.77, and 0.91, respectively, p-value× …

Noncontact Speckle Contrast Diffuse Correlation Tomography Of Blood Flow Distributions In Tissues With Arbitrary Geometries, Siavash Mazdeyasna, Chong Huang, Mingjun Zhao, Nneamaka B. Agochukwu, Ahmed A. Bahrani, Lesley Wong, Guoqiang Yu

Biomedical Engineering Faculty Publications

A noncontact electron multiplying charge-coupled-device (EMCCD)-based speckle contrast diffuse correlation tomography (scDCT) technology has been recently developed in our laboratory, allowing for noninvasive three-dimensional measurement of tissue blood flow distributions. One major remaining constraint in the scDCT is the assumption of a semi-infinite tissue volume with a flat surface, which affects the image reconstruction accuracy for tissues with irregular geometries. An advanced photometric stereo technique (PST) was integrated into the scDCT system to obtain the surface geometry in real time for image reconstruction. Computer simulations demonstrated that a priori knowledge of tissue surface geometry is crucial for precisely reconstructing the …

Comparison Of Left Ventricular Strains And Torsion Derived From Feature Tracking And Dense Cmr, Gregory J. Wehner, Linyuan Jing, Christopher M. Haggerty, Jonathan D. Suever, Jing Chen, Sean M. Hamlet, Jared A. Feindt, Walter Dimitri Mojsejenko, Mark A. Fogel, Brandon K. Fornwalt

Biomedical Engineering Faculty Publications

Background: Cardiovascular magnetic resonance (CMR) feature tracking is increasingly used to quantify cardiac mechanics from cine CMR imaging, although validation against reference standard techniques has been limited. Furthermore, studies have suggested that commonly-derived metrics, such as peak global strain (reported in 63% of feature tracking studies), can be quantified using contours from just two frames – end-diastole (ED) and end-systole (ES) – without requiring tracking software. We hypothesized that mechanics derived from feature tracking would not agree with those derived from a reference standard (displacement-encoding with stimulated echoes (DENSE) imaging), and that peak strain from feature tracking would agree with …

Quantifying Cancer Cell Receptors With Paired-Agent Fluorescent Imaging: A Novel Method To Account For Tissue Optical Property Effects., Negar Sadeghipour, Scott C. Davis, Kenneth M. Tichauer

Dartmouth Scholarship

Dynamic fluorescence imaging approaches can be used to estimate the concentration of cell surface receptorsin vivo. Kinetic models are used to generate the final estimation by taking the targeted imaging agent concentration as a function of time. However, tissue absorption and scattering properties cause the final readout signal to be on a different scale than the real fluorescent agent concentration. In paired-agent imaging approaches, simultaneous injection of a suitable control imaging agent with a targeted one can account for non-specific uptake and retention of the targeted agent. Additionally, the signal from the control agent can be a normalizing …

Using Electromyography Of Five Muscles And Joint Angle To Predict Knee Joint Moment, Mohamadreza Karimi Bokti, Alireza Hashemi Oskouei

Conference Presentations

Forces and moments acting on joints is of great importance in different fields of biomechanics such as ergonomics, sports biomechanics, and rehabilitation. EMG driven models can be used to estimate forces and moments acting on joints. The current study aimed to propose a model for prediction of knee joint moment using EMG signals detected from muscles and knee joint angle. Electromyography of knee muscles, knee joint angle and moment were recorded simultaneously during the extension-flexion movement in three young men using an isokinetic system. The model for estimating knee joint moment was developed using multiple linear regression. In order to …

In Vivo Brainstem Imaging In Alzheimer’S Disease: Potential For Biomarker Development, David J. Braun, Linda J. Van Eldik

Neuroscience Faculty Publications

The dearth of effective treatments for Alzheimer’s disease (AD) is one of the largest public health issues worldwide, costing hundreds of billions of dollars per year. From a therapeutic standpoint, research efforts to date have met with strikingly little clinical success. One major issue is that trials begin after substantial pathological change has occurred, and it is increasingly clear that the most effective treatment regimens will need to be administered earlier in the disease process. In order to identify individuals within the long preclinical phase of AD who are likely to progress to dementia, improvements are required in biomarker development. …

Hydrodeoxygenation Of Aqueous Phase Catalytic Pyrolysis Oil To Liquid Hydrocarbons Using Multi-Functional Nickel Catalyst, Hossein Jahromi, Foster A. Agblevor

Biological Engineering Faculty Publications

Herein we investigated the hydrodeoxygenation (HDO) of aqueous phase pinyon-juniper catalytic pyrolysis oil (APPJCPO) using a new multifunctional red mud-supported nickel (Ni/RM) catalyst. The organic liquid yield after HDO of APPJCPO using 30 wt. % Ni/RM at reaction temperature of 350 °C was 47.8 wt. % with oxygen content of 1.14 wt. %. The organic liquid fraction consisted of aliphatics, aromatics, and alkylated aromatic hydrocarbons as well as small amounts of oxygenates. The RM support catalyzed ketonization of carboxylic acids. The Ni metal catalyzed partial reduction of oxygenates that underwent carbonyl alkylation with aldehydes and ketones on the RM. Catalyst …

Synthesis And Characterization Of Controlled Nitric Oxide Release From S-Nitroso-N-Acetyl-D-Penicillamine Covalently Linked To Polyvinyl Chloride (Snap-Pvc), Sean Hopkins, Megan C. Frost

Michigan Tech Publications, Part 1

Polyvinyl chloride (PVC) is one of the most widely used polymers in medicine but has very poor biocompatibility when in contact with tissue or blood. To increase biocompatibility, controlled release of nitric oxide (NO) can be utilized to mitigate and reduce the inflammatory response. A synthetic route is described where PVC is aminated to a specified degree and then further modified by covalently linking S-nitroso-N-acetyl-d-penicillamine (SNAP) groups to the free primary amine sites to create a nitric oxide releasing polymer (SNAP-PVC). Controllable release of NO from SNAP-PVC is described using photoinitiation from light emitting diodes (LEDs). Ion-mediated NO release is …

An Efficient Process For Co-Production Of Γ-Aminobutyric Acid And Probiotic Bacillus Subtilis Cells, Hongbo Wang, Jinge Huang, Lei Sun, Fuchao Xu, Wei Zhang, Jixun Zhan

Biological Engineering Faculty Publications

This study was to establish an integrated process for the co-production of γ-aminobutyric acid (GABA) and live probiotics. Six probiotic bacteria were screened and Bacillus subtilis ATCC 6051 showed the highest GABA-producing capacity. The optimal temperature and initial pH value for GABA production in B. subtilis were found to be 30 °C and 8.0, respectively. A variety of carbon and nitrogen sources were tested, and potato starch and peptone were the preferred carbon and nitrogen sources for GABA production, respectively. The concentrations of carbon source, nitrogen source and substrate (sodium L-glutamate) were then optimized using the response surface methodology. The …

Wave Energy Converter Array Optimization: A Genetic Algorithm Approach And Minimum Separation Distance Study, Chris Sharp, Bryony Dupont

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

With the need to integrate renewable energy sources into the current energy portfolio and the proximity of power consumers to ocean coastlines, it is important to evaluate marine energy systems, specifically wave energy converters (WECs), as potential solutions for meeting electricity needs. The ability to model these systems computationally is vital to their eventual deployment. The power development, economics, grid integration requirements, operations and maintenance requirements, and ecological impacts must be understood before these devices are physically installed. However, the research area of WEC array optimization is young, and the few available results of previously implemented optimization methods are preliminary. …

Nonprehensile Manipulation Of Deformable Objects: Achievements And Perspectives From The Rodyman Project, Aykut C. Satici

Mechanical and Biomedical Engineering Faculty Publications and Presentations

The goal of this work is to disseminate the results achieved so far within the RODYMAN project related to planning and control strategies for robotic nonprehensile manipulation. The project aims at advancing the state of the art of nonprehensile dynamic manipulation of rigid and deformable objects to future enhance the possibility of employing robots in anthropic environments. The final demonstrator of the RODYMAN project will be an autonomous pizza maker. This article is a milestone to highlight the lessons learned so far and pave the way towards future research directions and critical discussions.

Determining The Respiratory State From A Seismocardiographic Signal - A Machine Learning Approach, Christian Ulrich, Martin Jensen, Rolf Oberlin, Kouhyar Tavakolian, Farzad Khosrow-Khavar, Andrew Blaber, Kasper Sørensen, Samuel Schmidt

Electrical Engineering Faculty Publications

Seismocardiography (SCG) is a non-invasive method for measurement of vibrations on the chest wall originating from the heart. Respiration changes the morphology of the SCG-signal and analyzing these changes could improve the diagnostic value of SCG. This study aimed to determine the nasal respiration signal amplitude at mitral closure (MC) and aortic opening (AO) using SCG features. The three proposed methods for this were multiple regression analysis (MRA), support vector regression (SVR), and a neural network (NN). SCG, Electrocardiography and nasal-catheter flow signals were acquired from 18 healthy subjects (age 29± 6). SCG-signal fiducial points were used as features and …

Voltage Effects On Muscarinic Acetylcholine Receptor-Mediated Contractions Of Airway Smooth Muscle, Iurii Semenov, Robert Brenner

Bioelectrics Publications

Studies have shown that the activity of muscarinic receptors and their affinity to agonists are sensitive to membrane potential. It was reported that in airway smooth muscle (ASM) depolarization evoked by high K⁺ solution increases contractility through direct effects on M3 muscarinic receptors. In this study, we assessed the physiological relevance of voltage sensitivity of muscarinic receptors on ASM contractility. Our findings reveal that depolarization by high K⁺ solution induces contraction in intact mouse trachea predominantly through activation of acetylcholine release from embedded nerves, and to a lesser extent by direct effects on M3 receptors. We therefore devised …

Moderate Heat Application Enhances The Efficacy Of Nanosecond Pulse Stimulation For The Treatment Of Squamous Cell Carcinoma, Chelsea M. Edelblute, Sigi Guo, Embo Yang, Chunqi Jiang, Karl Schoenbach, Richard Heller

Bioelectrics Publications

Nanosecond pulse stimulation as a tumor ablation therapy has been studied for the treatment of various carcinomas in animal models and has shown a significant survival benefit. In the current study, we found that moderate heating at 43°C for 2 minutes significantly enhanced in vitro nanosecond pulse stimulation-induced cell death of KLN205 murine squamous cell carcinoma cells by 2.43-fold at 600 V and by 2.32-fold at 900 V, as evidenced by propidium iodide uptake. Furthermore, the ablation zone in KLN205 cells placed in a 3-dimensional cell-culture model and pulsed at a voltage of 900 V at 43°C was 3 times …

Technical Note: Enhancing Soft Tissue Contrast And Radiation‐Induced Image Changes With Dual‐Energy Ct For Radiation Therapy, George Noid, An Tai, Diane Schott, Nilesh Mistry, Yu Liu, Taly Gilat Schmidt, Jared R. Robbins, X. Allen Li

Biomedical Engineering Faculty Research and Publications

Purpose

The purpose of this work is to investigate the use of low‐energy monoenergetic decompositions obtained from dual‐energy CT (DECT) to enhance image contrast and the detection of radiation‐induced changes of CT textures in pancreatic cancer.

Methods

The DECT data acquired for 10 consecutive pancreatic cancer patients during routine nongated CT‐guided radiation therapy (RT) using an in‐room CT (Definition AS Open, Siemens Healthcare, Malvern, PA) were analyzed. With a sequential DE protocol, the scanner rapidly performs two helical acquisitions, the first at a tube voltage of 80 kVp and the second at a tube voltage of 140 kVp. Virtual monoenergetic …

Microfluidic Electrical Impedance Spectroscopy, John J. Foley

Master's Theses

The goal of this study is to design and manufacture a microfluidic device capable of measuring changes in impedance valuesof microfluidic cell cultures. Tocharacterize this, an interdigitated array of electrodes was patterned over glass, where it was then bonded to a series of fluidic networks created in PDMS via soft lithography. The device measured ethanol impedance initially to show that values remain consistent over time. Impedance values of water and 1% wt. saltwater were compared to show that the device is able to detect changes in impedance, with up to a 60% reduction in electrical impedance in saltwater. Cells were …