Biomedical Engineering and Bioengineering Commons^™

An Algorithm For Extracting The Ppg Baseline Drift In Real-Time, Tuan Ngoc Nguyen

Theses: Doctorates and Masters

Photoplethysmography is an optical technique for measuring the perfusion of blood in skin and tissue arterial vessels. Due to its simplicity, accessibility and abundance of information on an individual’s cardiovascular system, it has been a pervasive topic of research within recent years. With these benefits however there are many challenges concerning the processing and conditioning of the signal in order to allow information to be extracted. One such challenge is removing the baseline drift of the signal, which is caused by respiratory rate, muscle tremor and physiological changes within the body as a response to various stimuli.

Over the years …

The Effect Of Neurostimulation On Ischemic Pain And Methods Of Assessing Pain, Kaylee Keck

Biomedical Engineering

Peripheral arterial disease (PAD) impacts approximately eight million people in the United States [1]. Disease progression leads to chronic ischemic pain, hindering quality of life. Pharmaceuticals are a typical treatment for pain associated with PAD; but as few as 30% of patients have a significant reduction of pain (≥50%) [2].

Neurostimulation is commonly used as a treatment for various diseases and injuries, including Parkinson’s disease and sports-related back and knee injuries [2]. The objective of the study was to explore neurostimulation and its effect on pain and paresthesia for a model of acute peripheral ischemia in young college students.

Pain …

Background Differences In Baseline And Stimulated Mmp Levels Influence Abdominal Aortic Aneurysm Susceptibility, Matthew A. Dale, Melissa K. Suh, Shijia Zhao, Trevor Meisinger, Linxia Gu, Vicki J. Swier, Devendra K. Agrawal, Timothy Greiner, Jeffrey S. Carson, B. Timothy Baxter, Wanfen Xiong

Department of Mechanical and Materials Engineering: Faculty Publications

Objective: Evidence has demonstrated profound influence of genetic background on cardiovascular phenotypes. Murine models in Marfan syndrome (MFS) have shown that genetic background-related variations affect thoracic aortic aneurysm formation, rupture, and lifespan of mice. MFS mice with C57Bl/6 genetic background are less susceptible to aneurysm formation compared to the 129/SvEv genetic background. In this study, we hypothesize that susceptibility to abdominal aortic aneurysm (AAA) will be increased in 129/SvEv mice versus C57Bl/6 mice. We tested this hypothesis by assessing differences in aneurysm size, tissue properties, immune response, and MMP expression.

Methods: Mice of C57Bl/6 or 129/SvEv background underwent AAA induction …

Feasibility Of Using Raman-Based Techniques For Breast Cancer Detection, Sara Mollamohammada

Department of Civil and Environmental Engineering: Dissertations, Theses, and Student Research

Breast cancer is one of the common types of cancer among women all over the world. Early diagnosis is an effective way that improve the treatment process and gives the patients a better chance of survival. Many of the patients infected by breast cancer choose breast conservation surgery (BCS). However, some of those will be subjected to mastectomy, and many will have tumor recurrence as there is no precise technique to show the tumor margins. Raman-based methods are powerful techniques with potential to rapidly differentiate normal from tumor tissues and provides a solution to detect tumor margin. This is because …

Improved Sensitivity To Fluorescence For Cancer Detection In Wide-Field Image-Guided Neurosurgery, Michael Jermyn, Yoann Gosselin, Pablo A. Valdes, Mira Sibai, Kolbein Kolste

Dartmouth Scholarship

In glioma surgery, Protoporphyrin IX (PpIX) fluorescence may identify residual tumor that could be resected while minimizing damage to normal brain. We demonstrate that improved sensitivity for wide-field spectroscopic fluorescence imaging is achieved with minimal disruption to the neurosurgical workflow using an electron-multiplying charge-coupled device (EMCCD) relative to a state-of-the-art CMOS system. In phantom experiments the EMCCD system can detect at least two orders-of-magnitude lower PpIX. Ex vivo tissue imaging on a rat glioma model demonstrates improved fluorescence contrast compared with neurosurgical fluorescence microscope technology, and the fluorescence detection is confirmed with measurements from a clinically-validated spectroscopic probe. Greater PpIX …

Quantification Of Blood Flow Velocity Using Color Sensing, Aditya Deepak Sanghani

Master's Theses

Blood flow velocity is an important parameter that can give information on several pathologies including atherosclerosis, glaucoma, Raynaud’s phenomenon, and ischemic stroke [2,5,6,10]. Present techniques of measuring blood flow velocity involve expensive procedures such as Doppler echocardiography, Doppler ultrasound, and magnetic resonance imaging [11,12]. They cost from $8500-$20000. It is desired to find a low-cost yet equally effective solution for measuring blood flow velocity. This thesis has a goal of creating a proof of concept device for measuring blood flow velocity.

Finger blood flow velocity is investigated in this project. The close proximity to the skin of the finger’s arteries …

Lpcoms: Towards A Low Power Wireless Smart-Shoe System For Gait Analysis In People With Disabilities, Ishmat Zerin

Master's Theses (2009 -)

Gait analysis using smart sensor technology is an important medical diagnostic process and has many applications in rehabilitation, therapy and exercise training. In this thesis, we present a low power wireless smart-shoe system (LPcomS) to analyze different functional postures and characteristics of gait while walking. We have designed and implemented a smart-shoe with a Bluetooth communication module to unobtrusively collect data using smartphone in any environment. With the design of a shoe insole equipped with four pressure sensors, the foot pressure is been collected, and those data are used to obtain accurate gait pattern of a patient. With our proposed …

Initial Validation Of A Novel Method Of Presurgical Language Localization Through Functional Connectivity (Fcmri), Stephanie M. Noble, Dustin Scheinost, Susan Y. Bookheimer, Patricia Walshaw, R Todd Constable, Christopher F. Benjamin

Yale Day of Data

OBJECTIVE: Neurosurgery is potentially curative in chronic epilepsy but can only be offered to patients if the surgical risk to language is known. Clinical functional magnetic resonance imaging (fMRI) is an ideal, noninvasive method for localizing language cortex yet remains to be validated for this purpose. We have recently presented a novel method for localizing language cortex. Here we present a preliminary evaluation of this method’s validity. We hypothesized language regions identified using this novel method would demonstrate stronger functional connectivity than randomly generated set of proximal networks. METHOD: fMRI data were collected from sixteen temporal lobe patients …

Review Of Fluorescence Guided Surgery Visualization And Overlay Techniques, Jonathan T. Elliott, Alisha V. Dsouza, Scott C. Davis, Jonathan D. Olson, Keith Paulsen, David Roberts, Brian Pogue

Dartmouth Scholarship

In fluorescence guided surgery, data visualization represents a critical step between signal capture and display needed for clinical decisions informed by that signal. The diversity of methods for displaying surgical images are reviewed, and a particular focus is placed on electronically detected and visualized signals, as required for near-infrared or low concentration tracers. Factors driving the choices such as human perception, the need for rapid decision making in a surgical environment, and biases induced by display choices are outlined. Five practical suggestions are outlined for optimal display orientation, color map, transparency/alpha function, dynamic range compression, and color perception check.

A Non-Invasive Method Of Measuring Respiration While Providing Wireless Power For Rodents With Implantable Devices, Jynx O. Boyne, Daniel J. Pederson, Zhi Wang, Pedro Irazoqui Dr.

The Summer Undergraduate Research Fellowship (SURF) Symposium

Respiratory measurements can be used as diagnostic and research tools. Spirometry is the gold standard for gaining these measurements, but is difficult to use in rodents as it requires an invasive procedure. Total Body Plethysmograpy (TBP) is a non-invasive way to measure respiration rates that does not cause stress to the rodent. In this system, the subject is encased in a solid, constant volume chamber with measurements determining the subject’s respiration. When using TBP in medical or research settings, challenges occur in powering devices within the TBP chamber as wires and other recording equipment compromise the airtightness of the chamber. …

Quantification Of Analyte Concentration From A Paper-Based Lateral Flow Assay Device Using Reflective Sensors, Megan Z. Chiu, Jacqueline Linnes

The Summer Undergraduate Research Fellowship (SURF) Symposium

Paper-based point-of-care (POC) diagnostics is a growing field in global health due to the extreme portability, accuracy, affordability, and ease of use of these tests. Advancements in recent years have led to more accurate detection and improved functionality using multistep molecular diagnostics. Many such assays utilize lateral flow detection strips for visualization of diagnostic results by eye, which limits the results to qualitative Yes/No readouts. This project focused on combining recent developments in paper-based POC diagnostics to develop and optimize an in-house built quantitative paper-based diagnostic reader for lateral flow detection in low-resource settings. Initially different sensors, including photocell sensors, …

Review Of Biomedical Čerenkov Luminescence Imaging Applications, Kaveh Tanha, Ali Mahmoud Pashazadeh, Brian W. Pogue

Dartmouth Scholarship

Čerenkov radiation is a fascinating optical signal, which has been exploited for unique diagnostic biological sensing and imaging, with significantly expanded use just in the last half decade. Čerenkov Luminescence Imaging (CLI) has desirable capabilities for niche applications, using specially designed measurement systems that report on radiation distributions, radiotracer and nanoparticle concentrations, and are directly applied to procedures such as medicine assessment, endoscopy, surgery, quality assurance and dosimetry. When compared to the other imaging tools such as PET and SPECT, CLI can have the key advantage of lower cost, higher throughput and lower imaging time. CLI can also provide imaging …

Design And Development Of Two Component Hydrogel Ejector For Three-Dimensional Cell Growth, Thomas Dunkle, Jessica Deschamps, Connie Dam

Honors Scholar Theses

Hydrogels are useful in wound healing, drug delivery, and tissue engineering applications, but the available methods of injecting them quickly and noninvasively are limited. The medical industry does not yet have access to an all-purpose device that can quickly synthesize hydrogels of different shapes and sizes. Many synthesis procedures that have been developed result in the formation of amorphous hydrogels. While generally useful, amorphous hydrogels exhibit limited capability in tissue engineering applications, especially due to their viscous properties. This endeavor aims to modulate the appropriate gelation parameters, optimize the injection process, and create a prototype that allows for the extrusion …

Next-Generation Raman Tomography Instrument For Non-Invasive In Vivo Bone Imaging, Jennifer-Lynn H. Demers, Francis W. L. Esmonde-White, Karen A. Esmonde-White, Michael D. Morris, Brian Pogue

Dartmouth Scholarship

Combining diffuse optical tomography methods with Raman spectroscopy of tissue provides the ability for in vivo measurements of chemical and molecular characteristics, which have the potential for being useful in diagnostic imaging. In this study a system for Raman tomography was developed and tested. A third generation microCT coupled system was developed to combine 10 detection fibers and 5 excitation fibers with laser line filtering and a Cytop reference signal. Phantom measurements of hydroxyapatite concentrations from 50 to 300 mg/ml had a linear response. Fiber placement and experiment design was optimized using cadaver animals with live animal measurements acquired to …

Noncontact Diffuse Correlation Tomography Of Breast Tumor, Lian He

Theses and Dissertations--Biomedical Engineering

Since aggressive cancers are frequently hypermetabolic with angiogenic vessels, quantification of blood flow (BF) can be vital for cancer diagnosis. Our laboratory has developed a noncontact diffuse correlation tomography (ncDCT) system for 3-D imaging of BF distribution in deep tissues (up to centimeters). The ncDCT system employs two sets of optical lenses to project source and detector fibers respectively onto the tissue surface, and applies finite element framework to model light transportation in complex tissue geometries. This thesis reports our first step to adapt the ncDCT system for 3-D imaging of BF contrasts in human breast tumors. A commercial 3-D …

Diffuse Optical Measurements Of Head And Neck Tumor Hemodynamics For Early Prediction Of Chemo-Radiation Therapy Outcomes, Lixin Dong

Theses and Dissertations--Biomedical Engineering

Chemo-radiation therapy is a principal modality for the treatment of head and neck cancers, and its efficacy depends on the interaction of tumor oxygen with free radicals. In this study, we adopted a novel hybrid diffuse optical instrument combining a commercial frequency-domain tissue oximeter (Imagent) and a custom-made diffuse correlation spectroscopy (DCS) flowmeter, which allowed for simultaneous measurements of tumor blood flow and blood oxygenation. Using this hybrid instrument we continually measured tumor hemodynamic responses to chemo-radiation therapy over the treatment period of 7 weeks. We also explored monitoring dynamic tumor hemodynamic changes during radiation delivery. Blood flow data analysis …

Quantitative Spatial Frequency Fluorescence Imaging In The Sub-Diffusive Domain For Image-Guided Glioma Resection, Mira Sibai, Israel Veilleux, Jonathan T. Elliott, Frederic Leblond, Brian Wilson

Dartmouth Scholarship

Intraoperative 5- aminolevulinic acid induced-Protoporphyrin IX (PpIX) fluorescence guidance enables maximum safe resection of glioblastomas by providing surgeons with real-time tumor optical contrast. However, visual assessment of PpIX fluorescence is subjective and limited by the distorting effects of light attenuation and tissue autofluorescence. We have previously shown that non-invasive point measurements of absolute PpIX concentration identifies residual tumor that is otherwise non-detectable. Here, we extend this approach to wide-field quantitative fluorescence imaging by implementing spatial frequency domain imaging to recover tissue optical properties across the field-of-view in phantoms and ex vivo tissue.

Femtosecond Laser Beam Propagation Through Corneal Tissue: Evaluation Of Therapeutic Laser-Stimulated Second And Third-Harmonic Generation, William R. Calhoun Iii

Theses and Dissertations

One of the most recent advancements in laser technology is the development of ultrashort pulsed femtosecond lasers (FSLs). FSLs are improving many fields due to their unique extreme precision, low energy and ablation characteristics. In the area of laser medicine, ophthalmic surgeries have seen very promising developments. Some of the most commonly performed surgical operations in the world, including laser-assisted in-situ keratomileusis (LASIK), lens replacement (cataract surgery), and keratoplasty (cornea transplant), now employ FSLs for their unique abilities that lead to improved clinical outcome and patient satisfaction.

The application of FSLs in medical therapeutics is a recent development, and although …

Bioactive Lipid Coating Of Bone Allografts Direct Engraftment And Fate Determination Of Bone Marrow-Derived Cells In Rat Gfp Chimeras, Anusuya Das, Claire E. Segar, Yihsuan Chu, Tiffany W. Wang, Yon Lin, Chunxi Yang, Roy C. Ogle

School of Medical Diagnostics & Translational Sciences Publications

Bone grafting procedures are performed to treat wounds incurred during wartime trauma, accidents, and tumor resections. Endogenous mechanisms of repair are often insufficient to ensure integration between host and donor bone and subsequent restoration of function. We investigated the role that bone marrow-derived cells play in bone regeneration and sought to increase their contributions by functionalizing bone allografts with bioactive lipid coatings. Polymer-coated allografts were used to locally deliver the immunomodulatory small molecule FTY720 in tibial defects created in rat bone marrow chimeras containing genetically-labeled bone marrow for monitoring cell origin and fate. Donor bone marrow contributed significantly to both …

Design And Creation Of A Device To Induce Vergence Eye Movements, Jacob B. Jaminet, Paul A. Wetzel

UROP Posters

Automated eye-tracking systems can detect and analyze eye movements as a means to accurately diagnose more than 20 neurological diseases including mild traumatic brain injury. Mild traumatic brain injury is an occurrence of injury to the head resulting from blunt trauma or from acceleration or deceleration forces. Eye movement refers to the voluntary or involuntary movement of the eyes, helping in acquiring, fixating and tracking visual stimuli. There are three types of voluntary eye movement to track objects: smooth pursuit, vergence shifts and saccades. Vergence shifts are eye movements where the eyes move in opposite directions: moving to the midline …

Nanopulse Generators: Their Design And Application To Cancer Therapy Studies, Daniel P. Wernig

Senior Honors Theses

Effective nanopulse generators have become critical in recent decades concerning the study of subcellular affects in response to nanosecond pulsed electric fields. It has been observed that nanosecond duration electric pulses can target intracellular organelles, ultimately leading to cell apoptosis, suggesting the possibility of a new, minimally invasive, low risk cancer therapy methodology. The standard topology for developing a medical nanopulser is the Blumlein “transmission line” approach. This approach relies on the nearly infinitesimal, yet finite amount of time required for an electromagnetic field to propagate down a short transmission line. Prior to design, requirements and constraints must be defined …

Design And Development Of A Miniature In Vivo Surgical Robot With Distributed Motor Control For Laparoendoscopic Single-Site Surgery, Eric J. Markvicka

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

Paradigm shifts in invasiveness, recovery time, cosmesis, and cost have been seen within the field of general surgery through major advances in surgical technology. Some of the most advanced types of general surgery now include Minimally Invasive Surgery (MIS), LaparoEndoscopic Single-Site (LESS) surgery, and Natural Orifice Translumenal Endoscopic Surgery (NOTES). One of the newest and rapidly developing catalysts is robotic platforms. Such platforms have improved ergonomics and control, increased workspace and dexterity, and have surpassed the efficacy of many non-robotic platforms such as traditional laparoscopic surgical tools. This thesis presents the design and development of a four-degree-of-freedom (4- DOF) miniature …

Nerve Fiber Diameter Measurements Using Hematoxylin And Eosin Staining And Brightfield Microscopy To Assess The Novel Method Of Characterizing Peripheral Nerve Fiber Distributions By Group Delay, Jorge Arturo Vazquez

Master's Theses

Peripheral neuropathies are a set of common diseases that affect the peripheral nervous system, causing damage to vital connections between various parts of the body and the brain and spinal cord. Different clinical conditions are known to selectively impact various size nerve fibers, which often makes it difficult to diagnose which peripheral neuropathy a patient might have. The nerve conduction velocity diagnostic test provides clinically useful information in the diagnosis of some peripheral neuropathies. This method is advantageous because it tends to be minimally invasive yet it provides valuable diagnostic information. However, this test does not determine characteristics of peripheral …

Fluid Powered Miniature In Vivo Robots For Minimally Invasive Surgery (Mis), Abolfazl Pourghodrat

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

Minimizing the invasiveness of surgery is believed to improve patient outcomes. Bleeding, infection, and pain are major concerns in surgery afflicting patients for decades. Minimally invasive techniques have come into play to reduce these concerns and smooth the evolution of abdominal surgery to a scarless process where nearly all surgeries can be performed without a skin incision. Technology continually advances the frontier of development of novel surgical devices to implement less invasive surgical techniques.

Fusion of robotics and Minimally Invasive Surgery (MIS) has created new opportunities to develop diagnostic and therapeutic tools. Surgical robotics is advancing from externally actuated systems …

Utilizing Fast Spin Echo Mri To Reduce Image Artifacts And Improve Implant/Tissue Interface Detection In Refractory Parkinson’S Patients With Deep Brain Stimulators, Subhendra N. Sarkar, Pooja R. Sarkar, Efstathios Papavassiliou, Rafael Rojas

Publications and Research

Introduction. In medically refractory Parkinson’s disease (PD) deep-brain stimulation (DBS) is an effective therapeutic tool. Postimplantation MRI is important in assessing tissue damage and DBS lead placement accuracy. We wanted to identify which MRI sequence can detectDBS leads with smallest artifactual signal void, allowing better tissue/electrode edge conspicuity.

Methods. Using an IRB approved protocol 8 advanced PDpatientswere imagedwithinMRconditional safety guidelines at lowRF power (SAR ≤ 0.1 W/kg) in coronal plane at 1.5T by various sequences.The image slices were subjectively evaluated for diagnostic quality and the lead contact diameters were compared to identify a sequence least affected by metallic leads.

Results …

Functional 3-D Cellulose & Nitrocellulose Paper-Based, Multiplex Diagnostic Platforms Without Coupling Agents, Mackenzie Elizabeth Tageson

Master's Theses

The purpose of this thesis was to demonstrate device functionality of 3-D paper-based, multiplex platforms, µPADs, without the use of coupling agents between layers. Previously, these platforms were fabricated with double-sided tape and cellulose powder to try to augment proper fluid routing, but difficulties with this method occurred. An acrylic housing unit with strategically placed pressure tabs was designed to aid horizontal and vertical fluid routing through the platform, thus eliminating the inconsistencies associated with coupling agents. Channel characterization studies, a COMSOL^TM simulation, and development time studies were performed to aid device design and demonstrate device functionality.

The implementation …

Direct Quantitative Analysis Of Biomarkers Using Mass Spectrometry, Morgan N. Mcluckey, Zheng Ouyang

The Summer Undergraduate Research Fellowship (SURF) Symposium

Point-of-care (POC) diagnostics describes a step in the medical treatment process where drugs can be monitored in a patient’s body on-site and in a timely fashion. Mass spectrometry (MS) can provide a quick, efficient, and highly accurate method of analysis of patient biofluids and tissues. Developing methods to bring this diagnostic mechanism to hospitals and clinics has the potential to improve patient care through, for example, personalized medicine. Our goal was to develop a way to effectively introduce internal standard (IS), a necessary chemical for the analytical process, to low-volume biofluid samples. Additionally, the effective direct quantitation of biomarkers with …

Spectral Discrimination Of Breast Pathologies In Situ Using Spatial Frequency Domain Imaging, Ashley M. Laughney, Venkataramanan Krishnaswamy, Elizabeth J. Rizzo, Mary C. Schwab, Richard J. Barth, David J. Cuccia, Bruce J. Tromberg, Keith D. Paulsen, Brian W. Pogue, Wendy A. Wells

Dartmouth Scholarship

Introduction: Nationally, 25% to 50% of patients undergoing lumpectomy for local management of breast cancer require a secondary excision because of the persistence of residual tumor. Intraoperative assessment of specimen margins by frozen-section analysis is not widely adopted in breast-conserving surgery. Here, a new approach to wide-field optical imaging of breast pathology in situ was tested to determine whether the system could accurately discriminate cancer from benign tissues before routine pathological processing.

Fluorescence Characterization Of Quantum Dots For Use As Biomarkers, Logan M. Grimes

Materials Engineering

Fluorescence profiles of quantum dots (QDs) were characterized to select the ideal QDs for encapsulation in phospholipids for use as biomarkers to selectively adhere to cancer cells. QDs were synthesized and extracted 0, 30, 60, and 90 seconds after precursor compounds were mixed. These extractions were isolated by extraction time. Portions from each vial were coated in a zinc sulfide shelling procedure, leaving at least half of the QD solution unshelled. These samples were characterized over four days to monitor fluctuations in fluorescence. This was done utilizing an Ocean Optics spectrometer in conjunction with Spectra Suite software. The central wavelength, …

Beach Wheelchair Project, Rory Aronson, Joshua Marcum, Samuel Coyne, Alex Hayes, Alexa Colburn, Max Hessel, Benedikt Strauss, Marvin Rimmele, Marco Pietsch

Mechanical Engineering

The Beach Wheelchair, Sandcrawler, is a machine intended to help give people with disabilities the full beach experience. The non-profit organization Bridge II Sports sponsored this project, and tasked us with developing the design and fabricating a prototype. This chair has several features including a linkage mechanism that raises and lowers a chair relative to an external frame, hand crank drive with Gates Carbondrive belt and sprockets, buoyant Wheeleez balloon tires, and much more.