Bioimaging and Biomedical Optics Commons^™

Biomedical Applications Of Lanthanide Nanomaterials, For Imaging, Sensing And Therapy, Qize Zhang, Stephen O'Brien, Jan Grimm

Publications and Research

The application of nanomaterials made of rare earth elements within biomedical sciences continues to make significant progress. The rare earth elements, also called the lanthanides, play an essential role in modern life through materials and electronics. As we learn more about their utility, function, and underlying physics, we can contemplate extending their applications to biomedicine. This particularly applies to diagnosis and radiation therapy due to their relatively unique features, such as an ultra-wide Stokes shift in the luminescence, variable magnetism and potentially tunable properties, due to the library of lanthanides available and their multivalent oxidation state chemistry. The ability to …

Injectable Ct/Mri Contrast Agent For Gastrointestinal Tumor Tracking, Luna Zhang

McKelvey School of Engineering Graduate Student Theses & Dissertations

Gastrointestinal cancers remain to be of the most common and deadly cancers worldwide. Early detection and treatments are crucial for reducing mortality and improving patient outcome. Radiation therapy is a non-invasive localized tumor treatment method, and utilizes radiation to kill the cancerous cells and shrink tumors at specific sites. Precise localization at the target tumor site is therefore important before radiation therapy, especially for gastrointestinal tumor sites located in the moving bowel. Currently, invasive endoscopies along with ink tattoos are used for identifying tumor location, which often require sedation and bring much discomfort. Imaging tests, including CT and MRI, play …

Quantifying Blood Flow Patterns In The Pediatric Heart Using Blood Speckle Imaging, Harrison Dean

Biomedical Engineering Undergraduate Honors Theses

Congenital Heart Disease (CHD) is the most common type of congenital disease worldwide. Echocardiography using Doppler ultrasound is typically used to diagnose and monitor CHD; however, it is angle-dependent in nature and as a result is limited in its ability to accurately evaluate ventricular function. Blood Speckle Imaging (BSI) is a novel, angle-independent imaging modality that provides detailed blood flow information and visualization within a given area using speckle-tracking. In this study, velocity-field information obtained from BSI was used to calculate flow parameters such as kinetic energy (KE) and circulation using a custom created MATLAB program. BSI was performed on …

Nanoscale Material Interaction With Multicellular 3d Cancer Culture, Emilie Darrigues

Theses and Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer, it is difficult to diagnose, often recurs, has high resistance to chemotherapies, and can be marked by advanced metastatic stages. There is an urgent need to fill the knowledge on nanoparticle penetration, diffusion, and cellular interaction in the context of adaptive PDAC tumor microenvironment to allow the development of new imaging and therapeutic supports. Traditionally, cancer-treating nanoparticles have been engineered and tested on 2D cell cultures, but several studies indicate that this in vitro model does not mimic tumor features closely enough. In contrast, 3D culture models offer …

A Simple, Realistic Walled Phantom For Intravascular And Intracardiac Applications., Hareem Nisar, John Moore, Roberta Piazza, Efthymios Maneas, Elvis C S Chen, Terry M Peters

Robarts Imaging Publications

PURPOSE: This work aims to develop a simple, anatomically and haptically realistic vascular phantom, compatible with intravascular and intracardiac ultrasound. The low-cost, dual-layered phantom bridges the gap between traditional wall-only and wall-less phantoms by showing both the vessel wall and surrounding tissue in ultrasound imaging. This phantom can better assist clinical tool training, testing of intravascular devices, blood flow studies, and validation of algorithms for intravascular and intracardiac surgical systems.

METHODS: Polyvinyl alcohol cryogel (PVA-c) incorporating a scattering agent was used to obtain vessel and tissue-mimicking materials. Our specific design targeted the inferior vena cava and renal bifurcations which were …

C-Molecules: Molecular-Guided Surgery With Fluorescence Imaging, Riley Karp, Joshua Gutow, William Wolfe-Mcguire

ENGS 89/90 Reports

Surgeries may cost lives if performed inadequately, which is why tools such as fluorescence guided surgery exist to improve surgical outcomes. Fluorescence guided surgery (FGS) is the practice of injecting patients with a fluorescent molecule that, in combination with highly sensitive cameras, allows surgeons to clearly identify complex biological structures. While beneficial in procedures such as endoscopy and gallbladder surgery, this technique is most notable for its role in complex cancer surgeries where misidentifying the boundaries of a tumor can have deadly consequences. Although FGS has the potential to revolutionize cancer treatment, highly sensitive imaging systems are necessary to identify …

In Vivo Metabolic And Vascular Response To Hypoxia In Twist Knockdown Murine Breast Cancer, Brandon Sturgill

Graduate Theses and Dissertations

Twist transcription factor is often overexpressed in aggressive tumors. Although needed in early embryonic development for organogenesis, Twist is known to induce an epithelial to mesenchymal transition in cells. In cancer, epithelial to mesenchymal transitions can lead to increased motility and invasiveness. It has also been linked to metabolic reprogramming and increased metastatic risk. Furthermore, metabolic preferences can increase proliferation, enhance metastatic potential, and influence the site of metastasis. We hypothesize that Twist directly affects the metabolism of cancer cells. We expect to see in vivo what we have seen in vitro; Twist overexpression should promote a shift away from …

Modeling And Validation Of Tissue Optical Properties In The Photon Transport Regime, Katelyn Heath

Biomedical Engineering Undergraduate Honors Theses

Early detection of changes in epithelial cells, such as the development of neoplastic formations seen in epithelial dysplasia, can indicate regions of the epithelial tissue that are at a high risk for cancerous formation. Using concepts from diffuse reflectance spectroscopy, a Monte Carlo model was developed to predict the reflectance measured by a detector at a small source-detector separation on a microendoscope. The Monte Carlo results were then used to calculate a mathematical relationship between the reflectance and distance that can be used to determine optical properties in a tissue sample. This model was validated with liquid phantoms of specified …

Vector Flow Imaging In Pediatric Cardiology - Extracting And Validating Data, Mason Belue

Biomedical Engineering Undergraduate Honors Theses

In the field of bedside cardiac diagnostic imaging, Doppler Ultrasound (DU) is the gold standard for diagnosing heart conditions. The largest benefit of DU is its ability to noninvasively image cardiac flow and allow the estimation of blood velocity and quantification of anatomical disease. However, to get correct velocity estimation, the position of the transducer in relation to the flow field needs to be known. This is the problem of angle/direction dependency and limits DUs accuracy when imaging in areas where perfect alignment or exact position of the transducer in relation to flow field is not possible or known, such …

Optical Vortex And Poincaré Analysis For Biophysical Dynamics, Anindya Majumdar

Dissertations, Master's Theses and Master's Reports

Coherent light - such as that from a laser - on interaction with biological tissues, undergoes scattering. This scattered light undergoes interference and the resultant field has randomly added phases and amplitudes. This random interference pattern is known as speckles, and has been the subject of multiple applications, including imaging techniques. These speckle fields inherently contain optical vortices, or phase singularities. These are locations where the intensity (or amplitude) of the interference pattern is zero, and the phase is undefined.

In the research presented in this dissertation, dynamic speckle patterns were obtained through computer simulations as well as laboratory setups …

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. …

Fluorescence Guided Tumor Imaging: Foundations For Translational Applications, Jessica P. Miller

McKelvey School of Engineering Graduate Student Theses & Dissertations

Optical imaging for medical applications is a growing field, and it has the potential to improve medical outcomes through its increased sensitivity and specificity, lower cost, and small instrumentation footprint as compared to other imaging modalities. The method holds great promise, ranging from direct clinical use as a diagnostic or therapeutic tool, to pre-clinical applications for increased understanding of pathology. Additionally, optical imaging uses non-ionizing radiation which is safe for patients, so it can be used for repeated imaging procedures to monitor therapy, guide treatment, and provide real-time feedback. The versatile features of fluorescence-based optical imaging make it suited for …

Experimental And Model-Based Terahertz Imaging And Spectroscopy For Mice, Human, And Phantom Breast Cancer Tissues, Tyler Bowman

Graduate Theses and Dissertations

The goal of this work is to investigate terahertz technology for assessing the surgical margins of breast tumors through electromagnetic modeling and terahertz experiments. The measurements were conducted using a pulsed terahertz system that provides time and frequency domain signals. Three types of breast tissues were investigated in this work. The first was formalin-fixed, paraffin-embedded tissues from human infiltrating ductal and lobular carcinomas. The second was human tumors excised within 24-hours of lumpectomy or mastectomy surgeries. The third was xenograft and transgenic mice breast cancer tumors grown in a controlled laboratory environment to achieve more data for statistical analysis.

Experimental …

Chelator-Free Radiolabeling Of Serrs Nanoparticles For Whole-Body Pet And Intraoperative Raman Imaging, Matthew A. Wall, Travis Shaffer, Stefan Harmsen, Darjus-Felix Tschaharganeh, Chun-Hao Huang, Scott W. Lowe, Charles Michael Drain, Moritz F. Kircher

Publications and Research

A single contrast agent that offers whole-body non-invasive imaging along with the superior sensitivity and spatial resolution of surface-enhanced resonance Raman scattering (SERRS) imaging would allow both pre-operative mapping and intraoperative imaging and thus be highly desirable. We hypothesized that labeling our recently reported ultrabright SERRS nanoparticles with a suitable radiotracer would enable pre-operative identification of regions of interest with whole body imaging that can be rapidly corroborated with a Raman imaging device or handheld Raman scanner in order to provide high precision guidance during surgical procedures. Here we present a straightforward new method that produces radiolabeled SERRS nanoparticles for …

A Structural And Functional Analysis Of Human Brain Mri With Attention Deficit Hyperactivity Disorder, Arjun A. Watane

Honors Undergraduate Theses

Attention Deficit Hyperactivity Disorder (ADHD) affects 5-10% of children worldwide. Its effects are mainly behavioral, manifesting in symptoms such as inattention, hyperactivity, and impulsivity. If not monitored and treated, ADHD may adversely affect a child's health, education, and social life. Furthermore, the neurological disorder is currently diagnosed through interviews and opinions of teachers, parents, and physicians. Because this is a subjective method of identifying ADHD, it is easily prone to error and misdiagnosis. Therefore, there is a clear need to develop an objective diagnostic method for ADHD.

The focus of this study is to explore the use of machine language …

Machine Learning Methods For Medical And Biological Image Computing, Rongjian Li

Computer Science Theses & Dissertations

Medical and biological imaging technologies provide valuable visualization information of structure and function for an organ from the level of individual molecules to the whole object. Brain is the most complex organ in body, and it increasingly attracts intense research attentions with the rapid development of medical and bio-logical imaging technologies. A massive amount of high-dimensional brain imaging data being generated makes the design of computational methods for efficient analysis on those images highly demanded. The current study of computational methods using hand-crafted features does not scale with the increasing number of brain images, hindering the pace of scientific discoveries …

Increasing 18f-Fdg Pet/Ct Capabilities In Radiotherapy For Lung And Esophageal Cancer Via Image Feature Analysis, Jasmine Alexandria Oliver

USF Tampa Graduate Theses and Dissertations

Positron Emission Tomography (PET) is an imaging modality that has become increasingly beneficial in Radiotherapy by improving treatment planning (1). PET reveals tumor volumes that are not well visualized on computed tomography CT or MRI, recognizes metastatic disease, and assesses radiotherapy treatment (1). It also reveals areas of the tumor that are more radiosensitive allowing for dose painting - a non-homogenous dose treatment across the tumor (1). However, PET is not without limitations. The quantitative unit of PET images, the Standardized Uptake Value (SUV), is affected by many factors such as reconstruction algorithm, patient weight, and tracer uptake time (2). …

Europium(Ii)-Containing Complexes For Responsive Magnetic Resonance Imaging, Levi Alexander Ekanger

Wayne State University Dissertations

The research projects described in this dissertation are focused on studying the oxidation of EuII-containing complexes within the context of responsive MRI. Prior to this research, EuII had not been explored within the context of oxidation-responsive MRI nor had the use of this ion been reported in vivo. The results of these studies enable predictions about the oxidation-responsive behavior of EuII-containing complexes in vitro and in vivo.

The EuII-containing cryptate 1.33 was used to evaluate EuII-based positive contrast enhancement after intravenous, intraperitoneal, and subcutaneous injections. The transitory behavior of the positive contrast enhancement correlated with reported levels of oxygenation and …

Recent Advances In Optical Spectroscopic And Imaging Methods For Medicine And Biology, Yu Shang, Zhiyu Qian, Rickson C. Mesquita, Mathieu Dehaes

Biomedical Engineering Faculty Publications

No abstract provided.

Characterization Of Low Density Intracranial Lesions Using Dual-Energy Computed To Mography, Jessica L. Nute

Dissertations and Theses (Open Access)

Calcific and hemorrhagic foci of susceptibility are frequently encountered on routine brain MR studies. Both etiologies cause variations in local magnetic field strength, leading to dark regions on the MR images that cannot be classified. Single-energy CT (SECT) can be used to identify lesions with attenuation over 100 HU as calcific, however lesions with lower attenuation cannot be reliably identified. While calcific lesions are unlikely to cause harm, hemorrhagic lesions carry a risk of subsequent intracranial bleeding; as such, identification of hemorrhage is vital in preventing the inappropriate use of anticoagulant medications in patients with hemorrhagic lesions.

Given there currently …

Three Dimensional Quantification Of Angiotensin Ii-Induced Murine Abdominal Aortic Aneurysms Using High Frequency Ultrasound, Amelia R. Adelsperger, Alexa A. Yrineo, Hilary D. Schroeder, Ashley Nicole Blaize, Katherine E. Wilson, Evan H. Phillips, Frederick W. Damen, Craig J. Goergen

The Summer Undergraduate Research Fellowship (SURF) Symposium

Abdominal aortic aneurysms (AAAs), a localized dilation of the vessel wall of 50% or more above normal, claims approximately 14,000 U.S. lives yearly due to aortic rupture. This commonly asymptomatic disease can only be treated by endovascular stent grafts or invasive surgery, usually after the AAA diameter reaches 5 cm. Because these treatment methods carry serious risk, stem cell therapy is being explored in order to provide a low risk option for managing smaller AAAs. To determine if stem cell therapy, once administered, could stabilize or reduce AAA growth, baseline 3D ultrasound measurements in a control group were first needed. …

Image Registration Of Ex-Vivo Mri To Sparsely Sectioned Histology Of Hippocampal And Neocortical Temporal Lobe Specimens., Maged Goubran, Cathie Crukley, Sandrine De Ribaupierre, Terence M Peters, Ali R Khan

Robarts Imaging Publications

Intractable or drug-resistant epilepsy occurs in up to 30% of epilepsy patients, with many of these patients undergoing surgical excision of the affected brain region to achieve seizure control. Recent magnetic resonance imaging (MRI) sequences and analysis techniques have the potential to detect abnormalities not identified with diagnostic MRI protocols. Prospective studies involving pre-operative imaging and collection of surgically-resected tissue provide a unique opportunity for verification and tuning of these image analysis techniques, since direct comparison can be made against histopathology, and can lead to better prediction of surgical outcomes and potentially less invasive procedures. To carry out MRI and …

Automated Point-Of-Care Image Processing Methodology For The Diagnosis Of Malaria, Michael B. Jorgensen

Master's Theses

Malaria has profoundly influenced human history for over four thousand years and despite numerous attempts at eradication, the prevention, diagnosis, and treatment of malaria have been largely ineffective. More than five hundred million people are affected by malaria every year resulting in over one million deaths. Drug resistance development by the parasite has diminished the effectiveness of numerous treatment options due, in part, to overtreatment of negative patients based on insufficient clinical algorithms and diagnostic methods. The goal of this research was to develop an image analysis algorithm to diagnose malaria with a high degree of sensitivity and specificity in …

Quantitative, Spectrally-Resolved Intraoperative Fluorescence Imaging, Pablo A. Valdés, Frederic Leblond, Valerie L. Jacobs, Brian C. Wilson, Keith D. Paulsen, David W. Roberts

Dartmouth Scholarship

Intraoperative visual fluorescence imaging (vFI) has emerged as a promising aid to surgical guidance, but does not fully exploit the potential of the fluorescent agents that are currently available. Here, we introduce a quantitative fluorescence imaging (qFI) approach that converts spectrally-resolved data into images of absolute fluorophore concentration pixel-by-pixel across the surgical field of view (FOV). The resulting estimates are linear, accurate, and precise relative to true values, and spectral decomposition of multiple fluorophores is also achieved. Experiments with protoporphyrin IX in a glioma rodent model demonstrate in vivo quantitative and spectrally-resolved fluorescence imaging of infiltrating tumor margins for the …

Towards Omni-Tomography -- Grand Fusion Of Multiple Modalities For Simultaneous Interior Tomography, Ge Wang, Jie Zhang, Hao Gao, Victor Weir, Hengyong Yu, Wenxiang Cong, Xiaochen Xu, Haiou Shen, James Bennett, Mark Furth, Yue Wang, Michael Vannier

Radiology Faculty Publications

We recently elevated interior tomography from its origin in computed tomography (CT) to a general tomographic principle, and proved its validity for other tomographic modalities including SPECT, MRI, and others. Here we propose "omni-tomography", a novel concept for the grand fusion of multiple tomographic modalities for simultaneous data acquisition in a region of interest (ROI). Omni-tomography can be instrumental when physiological processes under investigation are multi-dimensional, multi-scale, multi-temporal and multi-parametric. Both preclinical and clinical studies now depend on in vivo tomography, often requiring separate evaluations by different imaging modalities. Over the past decade, two approaches have been used for multimodality …

Fusion And Visualization Of Intraoperative Cortical Images With Preoperative Models For Epilepsy Surgical Planning And Guidance., A Wang, S M Mirsattari, A G Parrent, T M Peters

Robarts Imaging Publications

OBJECTIVE: During epilepsy surgery it is important for the surgeon to correlate the preoperative cortical morphology (from preoperative images) with the intraoperative environment. Augmented Reality (AR) provides a solution for combining the real environment with virtual models. However, AR usually requires the use of specialized displays, and its effectiveness in the surgery still needs to be evaluated. The objective of this research was to develop an alternative approach to provide enhanced visualization by fusing a direct (photographic) view of the surgical field with the 3D patient model during image guided epilepsy surgery.

MATERIALS AND METHODS: We correlated the preoperative plan …

Characterization And Analysis Techniques Of A Dynamic In Vitro Blood-Brain Barrier Model, Ryan Everett Woodhouse

Biomedical Engineering

The blood-brain barrier (BBB) is responsible for maintaining the sensitive environment required by the brain. Although the BBB is necessary for proper functioning of the brain, it acts as an obstacle for doctors attempting to treat neurological disease. For a drug to act upon the brain, it must first pass through the discriminating BBB. For this reason, much research has been performed in recent years in order to create an in vitro model of the BBB on which drugs targeted for the central nervous system may be tested. The main goal of this project is to create an in vitro …

Methodology Development For Three-Dimensional Mr-Guided Near Infrared Spectroscopy Of Breast Tumors, Colin M. Carpenter, Subhadra Srinivasan, Brian W. Pogue, Keith D. Paulsen

Dartmouth Scholarship

Combined Magnetic Resonance (MR) and Near Infrared Spectroscopy (NIRS) has been proposed as a unique method to quantify hemodynamics, water content, and cellular size and packing density of breast tumors, as these tissue constituents can be quantified with increased resolution and overlaid on the structural features identified by the MR. However, the choices in how to reconstruct and visualize this information can have a dramatic impact on the feasibility of implementing this modality in the clinic. This is especially true in 3 dimensions, as there is often limited optical sampling of the breast tissue, and methods need to accurately reflect …

Interpreting Hemoglobin And Water Concentration, Oxygen Saturation, And Scattering Measured In Vivo By Near-Infrared Breast Tomography, Subhadra Srinivasan, Brian W. Pogue, Shudong Jiang, Hamid Dehghani, Christine Kogel, Sandra Soho, Jennifer J. Gibson, Tor D. Tosteson, Steven P. Poplack, Keith D. Paulsen

Dartmouth Scholarship

Near-infrared spectroscopic tomography was used to measure the properties of 24 mammographically normal breasts to quantify whole-breast absorption and scattering spectra and to evaluate which tissue composition characteristics can be determined from these spectra. The absorption spectrum of breast tissue allows quantification of (i) total hemoglobin concentration, (ii) hemoglobin oxygen saturation, and (iii) water concentration, whereas the scattering spectrum provides information about the size and number density of cellular components and structural matrix elements. These property data were tested for correlation to demographic information, including subject age, body mass index, breast size, and radiographic …