Biomedical Engineering and Bioengineering Commons^™

Design Of Asic Based Electrical Impedance Tomography Microendoscopic System For Prostate Cancer Surgical Marginal Assessment, Mohsen Shahghasemi

Dartmouth College Ph.D Dissertations

Prostate cancer is the second most common cancer in the United States. It is typically treated by surgically excising the cancerous section of the prostate. Because there is not always a visible distinction between the healthy and cancerous sections, surgery often leaves some cancerous tissue behind. This is referred to as a positive surgical margin and it requires adjuvant treatment with adverse side effects. Electrical impedance tomography (EIT) is a low-cost low-form-factor method that can be used to assess surgical marginal intraoperatively to ensure that no cancerous tissue is left behind. EIT-based surgical margin assessment works on the principle that …

System-Characterized Artificial Intelligence Approaches For Cardiac Cellular Systems And Molecular Signature Analysis, Ziqian Wu

Dartmouth College Ph.D Dissertations

The dissertation presents a significant advancement in the field of cardiac cellular systems and molecular signature systems by employing machine learning and generative artificial intelligence techniques. These methodologies are systematically characterized and applied to address critical challenges in these domains. A novel computational model is developed, which combines machine learning tools and multi-physics models. The main objective of this model is to accurately predict complex cellular dynamics, taking into account the intricate interactions within the cardiac cellular system. Furthermore, a comprehensive framework based on generative adversarial networks (GANs) is proposed. This framework is designed to generate synthetic data that faithfully …

Intraoperative Quantification Of Bone Perfusion In Lower Extremity Injury Surgery, Xinyue Han

Dartmouth College Ph.D Dissertations

Orthopaedic surgery is one of the most common surgical categories. In particular, lower extremity injuries sustained from trauma can be complex and life-threatening injuries that are addressed through orthopaedic trauma surgery. Timely evaluation and surgical debridement following lower extremity injury is essential, because devitalized bones and tissues will result in high surgical site infection rates. However, the current clinical judgment of what constitutes “devitalized tissue” is subjective and dependent on surgeon experience, so it is necessary to develop imaging techniques for guiding surgical debridement, in order to control infection rates and to improve patient outcome.

In this thesis work, computational …

Soil Respiration Measurements Reveal High Retention Of Organic Carbon From Corn Residue Derived High-Lignin Fermentation Byproduct Enabling Sustainable Lignocellulosic Biofuel Production, Michelle Sun Wang

Dartmouth College Master’s Theses

While 2G biofuel production can utilize non-edible, lignocellulosic feedstocks such as agricultural residues to produce liquid fuel, harvesting crop residues is unsustainable without careful management of the soil underneath. By harvesting a fraction of the crop residues left in the field after harvest, soil health can diminish and critically, the soil organic carbon (SOC) stored in agricultural fields can decrease. Currently, in the most popular 2G process models published, the issue of soil degradation remains unresolved with residue harvest strategies receiving considerable attention in the literature and other SOC management strategies receiving far less. Specifically, the strategy of returning the …

Mechanical Design Of A Microwave Imaging Device For Breast Cancer Detection In Mri Scanners, Grace M. Player

Dartmouth College Master’s Theses

This project seeks to develop an updated version of a microwave imaging device for use in conjunction with breast MRI, improving upon existing technology and developing novel concepts for the device. It posits three primary redesign targets for updating the previous system: resizing the system height, making the device more iteration- friendly, and improving the overall manufacturability of the device by replacing custom components with commercially available alternatives. All three of these redesign targets are met in the new design, V2.0. The height is reduced by reducing antenna travel and height, embedding some components, and shortening the tank wall, resulting …

Using Paired-Agent Imaging To Track Changes In Head And Neck Cancers After Undergoing Photodynamic Therapy Treatment, Reeham M. Choudhury

Dartmouth College Master’s Theses

Head and neck cancers affect thousands of people across the world, and photodynamic therapy (PDT) has been shown to have great potential to treat said cancers in a noninvasive manner. However, imaging head and neck cancers has been difficult, and molecular changes caused by PDT are not well-understood. Therefore, we propose the use of paired-agent imaging (PAI) to track changes in these cancers after after PDT treatment. For these studies, we primarily used benzoporphyrin derivative monoacid (BPD) for our photosensitizer, which is activated by a 690 nm laser. We first looked at changes in EGFR expression in vitro, and …

Advancing Fluorescent Contrast Agent Recovery Methods For Surgical Guidance Applications, Brook Kennedy Byrd

Dartmouth College Ph.D Dissertations

Fluorescence-guided surgery (FGS) utilizes fluorescent contrast agents and specialized optical instruments to assist surgeons in intraoperatively identifying tissue-specific characteristics, such as perfusion, malignancy, and molecular function. In doing so, FGS represents a powerful surgical navigation tool for solving clinical challenges not easily addressed by other conventional imaging methods. With growing translational efforts, major hurdles within the FGS field include: insufficient tools for understanding contrast agent uptake behaviors, the inability to image tissue beyond a couple millimeters, and lastly, performance limitations of currently-approved contrast agents in accurately and rapidly labeling disease. The developments presented within this thesis aim to address such …

Color Resolved Cherenkov Imaging Allows For Differential Signal Detection In Blood And Melanin Content, Vihan A. Wickramasinghe

Dartmouth College Master’s Theses

Cherenkov imaging in radiation therapy allows a video display of the irradiation beam on the patient’s tissue, for visualization of the treatment. High energy radiation from a linear accelerator (Linac) results in the production of spectrally-continuous broadband light inside tissue due to the Cherenkov effect; this light is then attenuated by tissue features from transport and exits from the delivery site. Progress with the development of color Cherenkov imaging has opened the possibility for some level of spectroscopic imaging of the light-tissue interaction and interpretation of the specific nature of the tissue being irradiated. Generally, there is a linear relationship …

Multimodal Ultrasound Imaging For Improved Metastatic Lymph Node Detection, Sidhartha Jandhyala

Dartmouth College Ph.D Dissertations

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and is complex in nature due to the variety of organs located in the head and neck region. Knowing the metastatic state of the lymph nodes is paramount in accurately staging and treating HNSCC patients. Currently, metastatic lymph node detection involves the use of magnetic resonance imaging and/or x-ray computed tomography, followed by biopsies for histological confirmation. The main diagnostic criteria is the size of the nodes; however, current imaging methods are not 100% accurate due natural lymph node variability. Ultrasound imaging is able to provide …

Phase-Changing Nanodroplets As Nanotheranostic Platform For Combination Cancer Therapy, Catalina-Paula Spatarelu

Dartmouth College Ph.D Dissertations

Cancer is a cluster of diseases, and 1.8 million Americans are newly diagnosed each year. Treatment issues such as drug instability, the occurrence of severe side effects, as well as resistance make the need for solutions to improve conventional methods, like chemotherapy, apparent. Nano-sized drug-delivery platforms, particles loaded with therapeutic molecules that escape the immune system clearance and accumulate at the tumor site, were proposed as one of these solutions. Despite the expansion of the field, several aspects still need to be addressed: inconsistent delivery of the drugs, inability of measuring the effective dose being delivered to the tumor, lack …

Advancing Combined Radiological And Optical Scanning For Breast-Conserving Surgery Margin Guidance, Samuel Stewart Streeter

Dartmouth College Ph.D Dissertations

Breast cancer is one of the most common types of cancer worldwide, and standard-of-care for early-stage disease typically involves a lumpectomy or breast-conserving surgery (BCS). BCS involves the local resection of cancerous tissue, while sparring as much healthy tissue as possible. State-of-the-art methods for intraoperatively evaluating BCS margins are limited. Approximately 20% of BCS cases result in a tissue resection with cancer at or near the resection surface (i.e., a positive margin). A two-fold increase in ipsilateral breast cancer recurrence is associated with the presence of one or more positive margins. Consequently, positive margins often necessitate costly re-excision procedures to …

Modeling The Effect Of Igg Subclasses And Specificity In The Translocation Of Monoclonal Antibodies Across The Placental Barrier, Sayuri Tais Miyamoto Magnabosco

ENGS 88 Honors Thesis (AB Students)

Infections are responsible for over half a million neonatal deaths every year (Lawn et al., 2014). Thus, there is huge interest in leveraging maternal immunization against infectious diseases to grant fetal protection during its development through the vertical transferring of IgG antibodies, the only Ig subclass that can significantly cross the placental barrier. Studies about vertical immunization rely on in-vitro models to extrapolate physiological conditions of the human placenta. The BeWo Transwell model (Bode et al., 2006) presents itself as a reliable model to mimic the transplacental transport mechanism of antibodies (Ellinger et al., 1999; Poulsen et al., 2009) …

Flash Radiotherapy: Skin Pigmentation As A Non-Invasive Indicator For Radiation-Induced Damage, Brady Mccallister

ENGS 88 Honors Thesis (AB Students)

FLASH ultra-high dose rate radiotherapy (RT) is one of the most rapidly growing subfields of radiation oncology today due to its potential to increase the limits of the therapeutic ratio. The FLASH effect, which includes heightened normal tissue sparing paired with iso-effective tumor cell killing, has been literature documented, in a limited manner, in rodent models, a few large animals, and one clinical patients.

A porcine-based experiment was conducted to test the effects of FLASH RT on normal tissue compared to conventional (CONV) RT. A clinical linear accelerator (LINAC) was reversibly converted to be capable of FLASH RT. A female …

Classifying Common Knee Rehabilitation Exercise Mistakes Using Imu Data, Fedor Myagkov

Dartmouth College Undergraduate Theses

Physical therapy following major surgeries is a branch of medicine that has seen its fair share of technologically inspired advances. One important facet of physical therapy, the “at-home exercises” patients are prescribed to do, is still somewhat of a “black box” to many physical therapists (PTs). PTs have no way of knowing (1) whether the patient is doing the home exercises, or (2) whether the patient is doing the exercises in the correct and healthy manner. This lack of awareness makes it difficult for the PT to guide the patient, which can often lead to prolonged rehabilitation periods or (sometimes) …

Using Natural Language Processing And Sentiment Analysis To Augment Traditional User-Centered Design: Development And Usability Study, Curtis L. Petersen, Ryan Halter, David Kotz, Lorie Loeb, Summer B. Cook, Dawna M. Pidgeon, Brock Christensen, John A. Batsis

Dartmouth Scholarship

Background: Sarcopenia, defined as the age-associated loss of muscle mass and strength, can be effectively mitigated through resistance-based physical activity. With compliance at approximately 40% for home-based exercise prescriptions, implementing a remote sensing system would help patients and clinicians to better understand treatment progress and increase compliance. The inclusion of end users in the development of mobile apps for remote-sensing systems can ensure that they are both user friendly and facilitate compliance. With advancements in natural language processing (NLP), there is potential for these methods to be used with data collected through the user-centered design process.

Objective: This study aims …

Bio Circuits For Evolutionary Biotech, Camilo Toruno

ENGS 86 Independent Projects (AB Students)

The field of bioengineering has much promise for renewable chemical production, bioremediation, and of course medical applications. Developing new useful microorganisms is extremely time and capital intensive, typically taking 50 million USD and eight years. This is due in large part to the low throughput techniques that are characteristic of the field of metabolic engineering. Here we describe the modification of an existing synthetic biosensor to measure the pharmaceutical dopamine, and the use of a circuit simulator Cadence to predict improvements to the biosensor. This biosensor paired with directed evolution techniques could reach throughputs of 5 million cells per day …

A Convolutional Neural Network For Fast Fluence Estimation In Complex Tissues, Nicholas Blasey, Geoffrey P. Luke

ENGS 88 Honors Thesis (AB Students)

Photoacoustic (PA) imaging is a non-invasive diagnostic imaging technique that gives images of photoabsorbers based on their absorption of optical energy. These optical absorption properties can then be linked to important tissue properties. For the method to be quantitative, however, it is necessary to have an accurate estimation of the light fluence in the tissue. The current gold standard in addressing the fluence estimation problem, a Monte Carlo Simulation, is costly in time and computation. In this work, we developed a deep neural network to quickly and accurately estimate light fluence in arbitrary tissue types and geometries. The network was …

Utilizing Neural Networks And Wearables To Quantify Hip Joint Angles And Moments During Walking And Stair Ascent, Megan V. Mccabe

ENGS 88 Honors Thesis (AB Students)

Wearable sensors were leveraged to develop two methods for computing hip joint angles and moments during walking and stair ascent that are more portable than the gold standard. The Insole-Standard (I-S) approach replaced force plates with force-measuring insoles and achieved results that match the curvature of results from similar studies. Peaks in I-S kinetic results are high due to error induced by applying the ground reaction force to the talus. The Wearable-ANN (W-A) approach combines wearables with artificial neural networks to compute the same results. Compared against the I-S, the W-A approach performs well (average rRMSE = 18%, R^{2 …}

Developing A Control System To Better Understand The Effects Of Pyruvate Decarboxylase Activity On Clostridium Thermocellum Metabolism, Nicholas Cervenka

ENGS 88 Honors Thesis (AB Students)

In order for cellulosic biofuels from Clostridium thermocellum to be commercially viable, the ethanol yield and titer of the microbe must be increased. To accomplish this, it has been suggested to introduce the Pyruvate Decarboxylase (PDC) enzyme into C. thermocellum. In order to demonstrate effects on ethanol production by PDC prior to genetic modification, a cell free system (CFS) has been developed. A purified enzyme system was developed with the CFS to function as a control. Using the purified enzyme system, PDC from Saccharomyces cerevisiae was demonstrated to be a good candidate for further testing in the CFS.

A Physical And Computational Reverse-Engineering Approach To Determine Dimensional Change And Its Relationship To Oxidation In Retrieved Orthopedic Implants, Josephine Kalshoven

ENGS 88 Honors Thesis (AB Students)

Oxidation of the Ultra-High Molecular Weight Polyethylene (UHMWPE) tibial inserts of total knee arthroplasty devices is a major factor underlying multiple modes of failure for these devices, including delamination, wear, and fracture. Previous research has demonstrated that oxidation of UHMWPE is driven by a high concentration of free radicals in the polyethylene. However, even new devices created with undetectable amounts of free radicals are oxidizing in vivo. One theory is that, in the absence of residual free radicals, oxidation is facilitated by absorbed species (e.g. lipids, ROS) delivered or exacerbated by contact stress. However, no method exists to comprehensively …

Spatial Frequency Domain Imaging Of Short-Wave Infrared Fluorescence For Biomedical Applications, Joseph P. Leonor

ENGS 88 Honors Thesis (AB Students)

Fluorescence imaging has become a standard in many clinical applications, such as tumor and vasculature imaging. One application that is becoming more prominent in cancer treatment is fluorescence-guided surgery (FGS). Currently, FGS allows surgeons the ability to visually navigate tumors and tissue structures intraoperatively. As a result, they can remove tumor more efficiently while maintaining critical structures within the patient, creating better outcomes and lower recovery times. However, background fluorescence and inability to localize depth create challenges when determining resection boundaries.

Different techniques, such as spatially modulating the illumination and imaging at longer light wavelengths, have been developed to accurately …

Biomedical Engineering Or Biomedical Optics: Will The Real Discipline Please Stand Up?, Brian W. Pogue

Dartmouth Scholarship

This editorial reflects on the shape of biomedical engineering as a discipline, and its relation to biomedical optics.

Characterizing Short-Wave Infrared Fluorescence Of Conventional Near-Infrared Fluorophores, Brook K. Byrd, Margaret R. Folaron, Joseph P. Leonor, Rendall R. Strawbridge, Xu Cao, Petr Bruza, Scott C. Davis

Dartmouth Scholarship

The observed behavior of short-wave infrared (SWIR) light in tissue, characterized by relatively low scatter and subdiffuse photon transport, has generated considerable interest for the potential of SWIR imaging to produce high-resolution, subsurface images of fluorescence activity in vivo. These properties have important implications for fluorescence-guided surgery and preclinical biomedical research. Until recently, translational efforts have been impeded by the conventional understanding that fluorescence molecular imaging in the SWIR regime requires custom molecular probes that do not yet have proven safety profiles in humans. However, recent studies have shown that two readily available near-infrared (NIR-I) fluorophores produce measurable SWIR fluorescence, …

Diagnostic Performance Of Receptor-Specific Surgical Specimen Staining Correlates With Receptor Expression Level, Jasmin M. Schaefer, Connor W. Barth, Scott C. Davis, Summer L. Gibbs

Dartmouth Scholarship

Intraoperative margin assessment is imperative to cancer cure but is a continued challenge to successful surgery. Breast conserving surgery is a relevant example, where a cosmetically improved outcome is gained over mastectomy, but re-excision is required in >25  %   of cases due to positive or closely involved margins. Clinical translation of margin assessment modalities that must directly contact the patient or required administered contrast agents are time consuming and costly to move from bench to bedside. Tumor resections provide a unique surgical opportunity to deploy margin assessment technologies including contrast agents on the resected tissues, substantially shortening the path to …

Ensuring Scientific Publishing Credibility In Translational Biomedical Optics., Brian W. Pogue

Dartmouth Scholarship

Optics has consistently been the largest singular technology sector used in medicine, and major advances in biomedical optics are documented daily in peer-reviewed publications. However, the academic stature of this field can be damaged by weaknesses in scientific publishing, where a “credibility crisis” has emerged as a popularized and increasingly studied dialogue. While there are still relatively few overt cases of fraud or erroneous research, more insidious aspects are seen in papers with results that have either low statistical power, selective reporting of observations, or data or computer codes that cannot be independently verified. Interestingly, the same solutions that improve …

Impact In Practice, Maria Garman

ENGS 88 Honors Thesis (AB Students)

Medial Tibial Stress Syndrome (Shin splits) is an overuse injury caused by repetitive impact. If ignored it can lead to stress reactions and then stress fractures in the shins. This nagging injury is something that plagues many track athletes especially as they start to wear their competition shoes more frequently at practice to work on technical aspects of their events.

This paper investigates the relationship between ground reaction forces experienced by the athletes in each stride and what shoes they are wearing on their feet. Due to the fact that repetitive impact is a cause for shin splints, the conclusion …

Abso2luteu-Net: Tissue Oxygenation Calculation Using Photoacoustic Imaging And Convolutional Neural Networks, Kevin Hoffer-Hawlik, Geoffrey P. Luke

ENGS 88 Honors Thesis (AB Students)

Photoacoustic (PA) imaging uses incident light to generate ultrasound signals within tissues. Using PA imaging to accurately measure hemoglobin concentration and calculate oxygenation (sO₂) requires prior tissue knowledge and costly computational methods. However, this thesis shows that machine learning algorithms can accurately and quickly estimate sO₂. absO₂luteU-Net, a convolutional neural network, was trained on Monte Carlo simulated multispectral PA data and predicted sO₂ with higher accuracy compared to simple linear unmixing, suggesting machine learning can solve the fluence estimation problem. This project was funded by the Kaminsky Family Fund and the Neukom Institute.

Cherenkov Excited Short-Wavelength Infrared Fluorescence Imaging In Vivo With External Beam Radiation, Xu Cao, Shudong Jiang, Mengyu Jeremy Jia, Jason R. Gunn, Tianshun Miao, Scott C. Davis, Petr Bruza, Brian W. Pogue

Dartmouth Scholarship

Cherenkov emission induced by external beam radiation therapy from a clinical linear accelerator (LINAC) can be used to excite phosphors deep in biological tissues. As with all luminescence imaging, there is a desire to minimize the spectral overlap between the excitation light and emission wavelengths, here between the Cherenkov and the phosphor. Cherenkov excited short-wavelength infrared (SWIR, 1000 to 1700 nm) fluorescence imaging has been demonstrated for the first time, using long Stokes-shift fluorophore PdSe quantum dots (QD) with nanosecond lifetime and an optimized SWIR detection. The 1  /  λ2 intensity spectrum characteristic of Cherenkov emission leads to low overlap …

Review Of Methods For Intraoperative Margin Detection For Breast Conserving Surgery, Benjamin W. Maloney, David M. Mcclatchy, Brian W. Pogue, Keith D. Paulsen, Wendy A. Wells, Richard J. Barth

Dartmouth Scholarship

Breast conserving surgery (BCS) is an effective treatment for early-stage cancers as long as the margins of the resected tissue are free of disease according to consensus guidelines for patient management. However, 15% to 35% of patients undergo a second surgery since malignant cells are found close to or at the margins of the original resection specimen. This review highlights imaging approaches being investigated to reduce the rate of positive margins, and they are reviewed with the assumption that a new system would need high sensitivity near 95% and specificity near 85%. The problem appears to be twofold. The first …

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 …