Bioimaging and Biomedical Optics Commons^™

Fluorescence Cryotomography For Preclinical Validation: Applications In Gene Therapy And Fluorescence-Guided Surgery, Caleb Y. J. Kwon

Dartmouth College Ph.D Dissertations

Fluorescence imaging has become a powerful tool in biomedical research and clinical practice, offering molecular specificity and high sensitivity for visualizing biological processes in real time, However, the successful translation of novel fluorescent probes or medicines from preclinical development to clinical applications requires rigorous validation of their biodistribution and target specificity. Traditional methods for assessing performance, such as bulk excised organ analysis or two-dimensional histology, provide limited information as they cannot capture the complete, organism-wide distribution of these probes or medicines. This thesis aims to improve this analysis pipeline through the application and optimization of fluorescence cryotomography for quantitative, high-resolution …

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 Computational Analysis Of Fluorescence Imaging For Head And Neck Cancer Surgical Guidance, Yao Chen

Dartmouth College Ph.D Dissertations

The main goal of surgery for head and neck squamous cell carcinoma (HNSCC) is to remove the tumor completely while preserving as much healthy tissue as possible to enhance patient survival and reduce complications. However, achieving clear surgical margins is difficult due to the complex anatomy of the head and neck and the reliance on a surgeon’s visual and tactile assessments. Recently, near-infrared (NIR) fluorescence molecular imaging has shown potential for better tumor visualization during surgery, using targeted imaging agents like epidermal growth factor receptor (EGFR) probes. This has led to the development of fluorescence-guided surgery (FGS), which helps surgeons …

Methods For Radiation-Sparing Navigation In Endovascular And Spine Surgery, William Ross Warner

Dartmouth College Ph.D Dissertations

Modern surgical navigation systems improve procedural accuracy, limit complications, and can reduce reliance on intraoperative ionizing radiation, yet their adoption remains uneven across surgical domains. Informed by clinical immersion, this thesis identifies and addresses two unmet needs revealed through contrasting image-guidance practices in endovascular and spine surgery, where existing guidance techniques are costly, intermittent, or fundamentally limited. Specifically, these needs include (1) the absence of radiation-sparing navigation techniques for endovascular procedures, which rely heavily on 2D x-ray angiography, and (2) the need for dynamic registration methods in open spine surgery, where navigation accuracy can degrade after initial registration and intraoperative …

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 …

Intraoperative Dynamic Contrast-Enhanced Fluorescence Imaging For Navigating Open Orthopedic Surgeries, Yue Tang

Dartmouth College Ph.D Dissertations

Infection following trauma is one of the most prevalent and challenging complications faced by orthopedic surgeons. Inadequate tissue perfusion plays a critical role in this complication, as poorly perfused bone can be a nidus for bacterial biofilm formation and promote resistance to antibiotic treatments. Consequently, the management of open fractures and fracture-related infections relies on aggressive and thorough debridement to remove all poorly perfused bone. This thesis focuses on developing an indocyanine green (ICG)-based dynamic contrast-enhanced fluorescence imaging (DCE-FI) to objectively measure bone perfusion during open orthopedic surgeries and guide surgical debridement of devitalized bone.

Novel methodologies were developed to …

Optical Methods For Time-Resolved Dosimetry And Oximetry Of Ultra-High Dose Rate Radiation Therapy, Megan A. Clark

Dartmouth College Ph.D Dissertations

Radiotherapy (RT) is a cornerstone method used to treat over 50% of the 2 million new cancer diagnoses each year in the United States. The success of RT directly relies on an optimal balance between maximizing the dose to the tumor while minimizing dose to surrounding normal tissues. Achieving this balance is often challenging due to underlying radiation transport and the presence of anatomical constraints that limit the beam delivery geometry. In turn, minimizing healthy tissue toxicity prevents use of a more aggressive tumor killing approach, and even in curative cases may decrease the patient’s quality of life due to …

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 …

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 …

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 …

Expanding Cherenkov Imaging Applications In Radiotherapy: Clinic-Wide In Vivo Treatment Monitoring And Mr-Linac Quality Assurance, Daniel A. Alexander

Dartmouth College Ph.D Dissertations

Radiation therapy treatments have become increasingly complex, striving to improve patient outcomes by delivering sufficient dose for tumor control while sparing more normal tissue. This trend has necessitated the development of additional workflows, such as multilayered incident mitigation strategies and advanced techniques for adapting treatments to account for time-sensitive patient factors. Novel technologies such as optical 3D surface monitoring and magnetic resonance-guided linear accelerators have been developed to assist clinicians in implementing these workflows. We hypothesize that optical imaging methods developed for radiotherapy dose monitoring and measurement can be used to positively impact modern radiation therapy challenges. Cherenkov imaging allows …

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 …

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 …