Analytical, Diagnostic and Therapeutic Techniques and Equipment Commons^™

Rehabvr: A Virtual Reality System For Upper-Body Orthopaedic Physical Therapy Rehabilitation, Winnie Brenda Wanjiru Waiya

Computer Science Senior Theses

Physical therapy is a central component of rehabilitation for musculoskeletal conditions, yet adherence to prescribed treatment remains persistently poor. Jack et al. identified pain, boredom, and insufficient feedback as key barriers to treatment adherence in physiotherapy outpatient settings,¹ and Rucinski et al. confirmed that non-adherence rates in orthopaedic populations remain between 50 and 70%, with patients who disengage facing elevated risk of reoperation, progressive functional decline, and poor clinical outcomes.² According to the World Health Organization, approximately 1.71 billion people globally live with musculoskeletal conditions,³ with shoulder pain specifically carrying a community prevalence ranging from 0.67 to 55.2% worldwide and …

Pixel-Level Fiber Stratification: Quantitative Imaging Analysis Of Pigmented Lesion Morphology, Alexia R. Gerogiannis, Caroline R. Saint James

Wetterhahn Science Symposium Posters

Using a combined two-photon excitation fluorescence (TPEF) and second-harmonic generation (SHG) approach, our research seeks to further the quantification of skin components in a quest toward diagnostic tools with higher accuracy and reduced invasiveness for patients. Images are taken both ex vivo and in vivo, of healthy and malignant tissues, with a 600 × 600 micron field of view. We demonstrate how computational analysis can effectively exploit signals emitted by skin to provide diagnostic insight.

Quantitative Fluorescence Imaging Using A Paired Agent Approach For Improving Surgical Decision Making, Sanjana Pannem

Dartmouth College Ph.D Dissertations

Surgical resection remains to be the cornerstone of treatment for most solid tumors, where the primary objective is to remove all visible and microscopic disease. However, the extent of tumor resection is inherently limited by the surgeon’s ability to distinguish tumor from normal tissue, intraoperatively. As a result, positive surgical margins (PSM), where residual tumor remains after surgery, are a common occurrence and are associated with increased recurrence, need for adjuvant therapies, dismal patient outcomes, and high healthcare costs.

Fluorescence guided surgery (FGS) has emerged as a promising technique to enhance intraoperative visualization of tumors and may help reduce the …

Advancing Novel Contrast Agents For Applications In Fluorescence-Guided Neurosurgery Using Fluorescence Cryotomography, Augustino Vittorio Scorzo

Dartmouth College Ph.D Dissertations

Fluorescence guided surgery (FGS) is an emerging surgical technique that aims to help surgeons identify tissue types to assist in surgical decision making - ideally providing “cut-by-color” guidance. A primary application for this approach is the identification of tumor tissue to achieve more accurate and complete tumor removal while simultaneously minimizing damage to surrounding normal tissue. The cornerstone of tumor visualization for FGS is the administration of fluorescent contrast agents, or in some cases metabolic precursors, designed to accumulate specifically in tumor tissue, and a wide range of agents that use different targeting mechanisms are currently under investigation. Although these …

Designing Accessible Ui/Ux For Epileptic Patients: A Scalable Solution For Music Therapy Delivery, Amethyst G.H. Mckenzie

Computer Science Senior Theses

How can we design an accessible, scalable UI/UX system tailored to the cognitive, visual, and motor impairments of epileptic patients, that ensures safe and effective interactions with music therapy applications? This research explores the intersection of accessibility, user-centred design, and digital health, using an iterative design process to develop and refine the SONATA app—a clinically deployable music therapy platform.

Through two prototype iterations, usability testing, and quantitative event logging, this study compares the effectiveness of structured versus flexible navigation in improving user experience. Key findings reveal that structured navigation reduces unintended detours, while progressive disclosure techniques enhance instructional clarity. Additionally, …

Smart Toys For Sensing And Soothing Distress In Pediatric Patients, Jonathan Daniel Bonilla

Dartmouth College Master’s Theses

This thesis develops and evaluates child-centered technologies to support remote monitoring of pediatric patients, with an emphasis on childhood cancer and pediatric chronic pain. For these and many other health conditions, current therapies tend to focus on treating physical symptoms yet neglect the psycho-emotional aspects of managing the illness. However, such mental states play a major role in recovery. Research has shown that cancer patients with better mental health have better prognoses, higher possibilities of remission, and faster healing processes, while chronic pain patients with better mental health report lower levels of pain. To enable more personalized, continuous, and scalable …

Towards A Wearable Device For Measuring Impedance Plethysmography Of The Radial Artery, Pritom Chowdhury

Dartmouth College Master’s Theses

Recent advancements in bioimpedance technology have demonstrated significant promise in the application of cardiac health monitoring. This research explores the design and development of a forearm-based wearable bioimpedance device for non-invasive measurement of heart rate and respiratory rate at an accuracy level comparable to medical-grade monitors. It utilizes a tetrapolar electrode configuration to analyze bioimpedance changes in the radial artery due to blood flow.

An ongoing aspect of this work involves the preliminary development of an embedded framework intended to integrate signal generation, acquisition, and processing within the device to achieve compact and efficient system design, anticipated to contribute to …

Investigating The Role Of Anesthesia In Radiation Therapy, William Walter Daley

ENGS 88 Honors Thesis (AB Students)

Purpose:

Cancer claims 7.6 million lives worldwide annually, affecting millions more. Conventional (CONV) radiation therapy (RT) is a key weapon in the oncological arsenal. A novel mode of radiation delivery, utilizing ultra-high dose rates (UHDR), is associated with enhancing the RT therapeutic ratio by selectively sparing normal tissue without sparing tumor tissue. However, there are many roadblocks to the clinical implementation of UHDR RT —namely the lack of standardization of experimental conditions and the inconsistency of published and unpublished results. This thesis investigates variables that affect preclinical biological outcomes to radiation.

Materials/Methods:

Eight groups of 10 C57BL/6 mice were stratified …

Near-Infrared Paired-Agent Imaging For In Vivo Quantification Of Receptor Occupancy In Tumor, Yichen Feng

Dartmouth College Ph.D Dissertations

Accurate assessment of drug receptor occupancy (RO) holds significant importance in both drug development and personalized medicine, as it facilitates quantitative characterization of dose-response relationship for a given drug. This information not only aids appropriate dose selection for clinical trials but also guides personalized dose optimization in precision medicine.

Molecular imaging, utilizing receptor-specific imaging agents for tissue visualization, has emerged as the major option for in vivo measurement of tissue RO. Nonetheless, the abnormal yet complex structure and hemodynamics of tumors often lead to substantial non-specific uptake and retention of imaging agents, thus introducing significant bias to RO measurements. To …

Deutj: An Imagej Plugin For Improved Automatic Masking And Segmentation Of Images From Confocal Microscopy, Sunny Cui

Independent Student Projects and Publications

Due to advances in microscopic imaging, there are a plethora of biological molecules that can now be tagged and subsequentially imaged from almost any cell, organism, or tissue. However, the ability of software to analyze these images remains to be a challenge. ImageJ is open source software that allows for the processing of these images, but faces challenges when dealing with images that show weak contrast between objects of interest and background. DeutJ is an ImageJ plugin that color corrects and brightness corrects gradients that inhibit segmentation in confocal microscopy images. It can analyze hundreds of images from a given …

Hrmobile: A Lightweight, Local Architecture For Heart Rate Measurement, Sam Morton, Sam Morton

Dartmouth College Master’s Theses

Heart rate and heart rate variability (HRV) are important metrics in the study of numerous physical and psychiatric conditions. Previously, measurement of heart rate was relegated to clinical settings, and was neither convenient nor captured a patient’s typical resting state. In effect, this made gathering heart rate data costly and introduced noise. The current prevalence of mobile phone technology and Internet access has increased the viability of remote health monitoring, thus presenting an opportunity to substantially improve the speed, convenience, and reliability of heart rate readings. Recent attention has focused on different methods for remote, non-contact heart rate measurement. Of …

Informative Journaling Application (Unwind) For Ambient Awareness On Mood In Young Adults To Reduce Anxiety And Depression: A Randomized, Placebo-Controlled Trial, Jalen Wang

Dartmouth College Undergraduate Theses

The mental health of young adults in America is worsening. Technology-based interventions may offer an accessible way to help with this problem. The objective of the study was to determine the feasibility and preliminary efficacy of an informative journaling application to reduce symptoms of anxiety and depression for young adults. In an unblinded trial, 20 individuals age 18-22 were recruited from Dartmouth College and were randomized to either participate in using the informative journaling application (Unwind) (n=10) or were directed to a National Institute of Mental Health pamphlet as part of the control group (n=10). All participants completed the 9-item …

Assessing Daylight & Low-Dose Rate Photodynamic Therapy Efficacy, Using Biomarkers Of Photophysical, Biochemical And Biological Damage Metrics In Situ., Ana Luiza Ribeiro De Souza, Ethan Larochelle, Kayla Marra, Jason Gunn, Scott C. Davis, Kimberley S. Samoke, M. Shane Chapman, Edward V. Maytin, Tayyaba Hasan, Brian W. Pogue

Dartmouth Scholarship

Background

Sunlight can activate photodynamic therapy (PDT), and this is a proven strategy to reduce pain caused by conventional PDT treatment, but assessment of this and other alternative low dose rate light sources, and their efficacy, has not been studied in an objective, controlled pre-clinical setting. This study used three objective assays to assess the efficacy of different PDT treatment regimens, using PpIX fluorescence as a photophysical measure, STAT3 cross-linking as a photochemical measure, and keratinocyte damage as a photobiological measure.

Methods

Nude mouse skin was used along with in vivo measures of photosensitizer fluorescence, keratinocyte nucleus damage from pathology, …

Quantity Over Quality—Findings From A Systematic Review And Environmental Scan Of Patient Decision Aids On Early Abortion Methods, Kyla Z. Donnelly, Glyn Elwyn, Rachel Thompson

Dartmouth Scholarship

Background: The availability and effectiveness of decision aids (DAs) on early abortion methods remain unknown, despite their potential for supporting women’s decision making. Objective: To describe the availability, impact and quality of DAs on surgical and medical early abortion methods for women seeking induced abortion. Search strategy: For the systematic review, we searched MEDLINE, Cochrane Library, CINAHL, EMBASE and PsycINFO. For the environmental scan, we searched Google and App Stores and consulted key informants. Inclusion criteria: For the systematic review, we included studies evaluating an early abortion method DA (any format and language) vs a comparison group on women’s decision …

“Provoking Conversations”: Case Studies Of Organizations Where Option Grid™ Decision Aids Have Become ‘Normalized’, Peter Scalia, Glyn Elwyn, Marie-Anne Durand

Dartmouth Scholarship

Background: Implementing patient decision aids in clinic workflow has proven to be a challenge for healthcare organizations and physicians. Our aim was to determine the organizational strategies, motivations, and facilitating factors to the routine implementation of Option Grid™ encounter decision aids at two independent settings. Method: Case studies conducted by semi-structured interview, using the Normalization Process Theory (NPT) as a framework for thematic analysis. Twenty three interviews with physicians, nurses, hospital staff and stakeholderswere conducted at: 1) CapitalCare Medical Group in Albany, New York; 2) HealthPartners Clinics in Minneapolis, Minnesota. Results: ‘Coherent’ motivations were guided by financial incentives at CapitalCare, …

Patient‐Defined Goals For The Treatment Of Severe Aortic Stenosis: A Qualitative Analysis, Megan Coylewright, Roseanne Palmer, Elizabeth S. O'Neill, John F. Robb, Terri Fried

Dartmouth Scholarship

Patients with severe aortic stenosis (AS) at high risk for aortic valve replacement are a unique population with multiple treatment options, including medical therapy, surgical aortic valve replacement and transcatheter aortic valve replacement (TAVR). Traditionally, in elderly populations, goals of treatment may favour quality of life over survival. Professional guidelines recommend that clinicians engage patients in shared decision making, a process that may lead to decisions more aligned with patient-defined goals of care. Goals of care for high-risk patients with AS are not well defined in the literature, and patient-reported barriers to shared decision making highlight the need for explicit …

Signaling In Effector Lymphocytes: Insights Toward Safer Immunotherapy, Kamalakannan Rajasekaran, Matthew J. Riese, Sridhar Rao, Li Wang, Monica Thakar, Charles Sentman, Subramaniam Malarkannan

Dartmouth Scholarship

Receptors on T and NK cells systematically propagate highly complex signaling cascades that direct immune effector functions, leading to protective immunity. While extensive studies have delineated hundreds of signaling events that take place upon receptor engagement, the precise molecular mechanism that differentially regulates the induction or repression of a unique effector function is yet to be fully defined. Such knowledge can potentiate the tailoring of signal transductions and transform cancer immunotherapies. Targeted manipulations of signaling cascades can augment one effector function such as antitumor cytotoxicity while contain the overt generation of pro-inflammatory cytokines that contribute to treatment-related toxicity such as …

Analyzing Clustered Data: Why And How To Account For Multiple Observations Nested Within A Study Participant?, Erika L. Moen, Catherine J. Fricano-Kugler, Bryan W. Luikart, A. James O’Malley

Dartmouth Scholarship

A conventional study design among medical and biological experimentalists involves col- lecting multiple measurements from a study subject. For example, experiments utilizing mouse models in neuroscience often involve collecting multiple neuron measurements per mouse to increase the number of observations without requiring a large number of mice. This leads to a form of statistical dependence referred to as clustering. Inappropriate analy- ses of clustered data have resulted in several recent critiques of neuroscience research that suggest the bar for statistical analyses within the field is set too low. We compare naïve ana- lytical approaches to marginal, fixed-effect, and mixed-effect models …

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 …

Mice Null For The Deubiquitinase Usp18 Spontaneously Develop Leiomyosarcomas, Fadzai Chinyengetere, David J. Sekula, Yun Lu, Andrew J. Giustini, Aarti Sanglikar, Masanori Kawakami, Tian Ma

Dartmouth Scholarship

USP18 (ubiquitin-specific protease 18) removes ubiquitin-like modifier interferon stimulated gene 15 (ISG15) from conjugated proteins. USP18 null mice in a FVB/N background develop tumors as early as 2 months of age. These tumors are leiomyosarcomas and thus represent a new murine model for this disease.

‘The Thing Is Not Knowing’: Patients' Perspectives On Surveillance Of An Indeterminate Pulmonary Nodule, Renda Soylemez Wiener, Michael K. Gould, Steven Woloshin, Lisa M. Schwartz, Jack Clark

Dartmouth Scholarship

Background: The hundreds of thousands of patients found to have a potentially malignant pulmonary nodule each year are faced with tremendous uncertainty regarding what the nodule is and how it should be evaluated.

Objective: To explore patients' responses to the detection and evaluation of a pulmonary nodule.

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.

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 …

A Novel Caspase 8 Selective Small Molecule Potentiates Trail-Induced Cell Death, Octavian Bucur, Gabriel Gaidos, Achani Yatawara, Bodvael Pennarun, Chamila Rupasinghe, Jérémie Roux, Stefan Andrei, Bingqian Guo, Alexandra Panaitiu, Maria Pellegrini, Dale Mierke, Roya Khosravi-Far

Dartmouth Scholarship

Recombinant soluble TRAIL and agonistic antibodies against TRAIL receptors (DR4 and DR5) are currently being created for clinical cancer therapy, due to their selective killing of cancer cells and high safety characteristics. However, resistance to TRAIL and other targeted therapies is an important issue facing current cancer research field. An attractive strategy to sensitize resistant malignancies to TRAIL-induced cell death is the design of small molecules that target and promote caspase 8 activation. For the first time, we describe the discovery and characterization of a small molecule that directly binds caspase 8 and enhances its activation when combined with TRAIL, …

Site-Specific Immunomodulator: A Novel Treatment For Crohn's Disease, Brian Bressler, Kevin P. Bethel, Ralf Kleef, Sophie L. Reynolds, Simon Sutcliffe, David W. Mullins, Hal Gunn

Dartmouth Scholarship

We investigated the mechanism of action, safety, and efficacy of the Site-Specific Immunomodulator (SSI) QBECO, a novel immunotherapy for Crohn’s disease (CD). Using human monocytic THP-1 cells, we demonstrate that SSI QBECO (derived from the common colon bacteria E. coli) activates macrophages to an M1 phenotype (associated with enhanced capacity to eliminate bacteria and activate innate immune responses). We assessed SSI QBECO in a compassionate use protocol of ten adult patients with active CD. Patients with moderate to severe clinical symptoms receiving conventional CD treatments and/or complementary therapies were included, except patients receiving anti-TNF medications. SSI QBECO was self-administered subcutaneously …

The Preparatory Set: A Novel Approach To Understanding Stress, Trauma, And The Bodymind Therapies, Peter Payne, Mardi A. Crane-Godreau

Dartmouth Scholarship

Basic to all motile life is a differential approach/avoid response to perceived features of environment. The stages of response are initial reflexive noticing and orienting to the stimulus, preparation, and execution of response. Preparation involves a coordination of many aspects of the organism: muscle tone, posture, breathing, autonomic functions, motivational/emotional state, attentional orientation, and expectations. The organism organizes itself in relation to the challenge. We propose to call this the "preparatory set" (PS). We suggest that the concept of the PS can offer a more nuanced and flexible perspective on the stress response than do current theories. We also hypothesize …

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 …

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.

Predicting Targeted Drug Combinations Based On Pareto Optimal Patterns Of Coexpression Network Connectivity, Nadia M. Penrod, Casey S. Greene, Jason H. Moore

Dartmouth Scholarship

Molecularly targeted drugs promise a safer and more effective treatment modality than conventional chemotherapy for cancer patients. However, tumors are dynamic systems that readily adapt to these agents activating alternative survival pathways as they evolve resistant phenotypes. Combination therapies can overcome resistance but finding the optimal combinations efficiently presents a formidable challenge. Here we introduce a new paradigm for the design of combination therapy treatment strategies that exploits the tumor adaptive process to identify context-dependent essential genes as druggable targets. We have developed a framework to mine high-throughput transcriptomic data, based on differential coexpression and Pareto optimization, to investigate drug-induced …

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.