Bioimaging and Biomedical Optics Commons^™

Microdose Fluorescence Imaging Of Aby-029 On An Operating Microscope Adapted By Custom Illumination And Imaging Modules, Jonathan T. Elliott, Alisha V. Dsouza, Kayla Marra, Brian W. Pogue, David Roberts, Keith Paulsen

Dartmouth Scholarship

Fluorescence guided surgery has the potential to positively impact surgical oncology; current operating microscopes and stand-alone imaging systems are too insensitive or too cumbersome to maximally take advantage of new tumor-specific agents developed through the microdose pathway. To this end, a custom-built illumination and imaging module enabling picomolar-sensitive near-infrared fluorescence imaging on a commercial operating microscope is described. The limits of detection and system specifications are characterized, and in vivo efficacy of the system in detecting ABY-029 is evaluated in a rat orthotopic glioma model following microdose injections, showing the suitability of the device for microdose phase 0 clinical trials.

Diffuse Optical Measurements Of Head And Neck Tumor Hemodynamics For Early Prediction Of Chemoradiation Therapy Outcomes, Lixin Dong, Mahesh Kudrimoti, Daniel Irwin, Li Chen, Sameera Kumar, Yu Shang, Chong Huang, Ellis L. Johnson, Scott D. Stevens, Brent J. Shelton, Guoqiang Yu

Biomedical Engineering Faculty Publications

This study used a hybrid near-infrared diffuse optical instrument to monitor tumor hemodynamic responses to chemoradiation therapy for early prediction of treatment outcomes in patients with head and neck cancer. Forty-seven patients were measured once per week to evaluate the hemodynamic status of clinically involved cervical lymph nodes as surrogates for the primary tumor response. Patients were classified into two groups: complete response (CR) (n = 29) and incomplete response (IR) (n = 18). Tumor hemodynamic responses were found to be associated with clinical outcomes (CR/IR), wherein the associations differed depending on human papillomavirus (HPV-16) status. In HPV-16 …

Low-Cost Compact Diffuse Speckle Contrast Flowmeter Using Small Laser Diode And Bare Charge-Coupled-Device, Chong Huang, Myeongsu Seong, Joshua Paul Morgan, Siavash Mazdeyasna, Jae Gwan Kim, Jeffrey Todd Hastings, Guoqiang Yu

Biomedical Engineering Faculty Publications

We report a low-cost compact diffuse speckle contrast flowmeter (DSCF) consisting of a small laser diode and a bare charge-coupled-device (CCD) chip, which can be used for contact measurements of blood flow variations in relatively deep tissues (up to ∼8  mm). Measurements of large flow variations by the contact DSCF probe are compared to a noncontact CCD-based diffuse speckle contrast spectroscopy and a standard contact diffuse correlation spectroscopy in tissue phantoms and a human forearm. Bland–Altman analysis shows no significant bias with good limits of agreement among these measurements: 96.5% ± 2.2% (94.4% to 100.0%) in phantom experiments and 92.8% …

3d Modeling Of Murine Abdominal Aortic Aneurysms: Quantification Of Segmentation And Volumetric Reconstruction, Paula A. Sarmiento, Amelia R. Adelsperger, Craig J. Goergen Ph.D.

The Summer Undergraduate Research Fellowship (SURF) Symposium

Abdominal Aortic Aneurysms (AAA) cause 5,900 deaths in the United States each year. Surgical intervention is clinically studied by non-invasive techniques such as computed tomography and magnetic resonance imaging. However, three-dimensional (3D) ultrasound imaging has become an inexpensive alternative and useful tool to characterize aneurysms, allowing for reconstruction of the vessel, quantification of hemodynamics through computational fluid dynamics (CFD) simulation, and possible prediction of aortic expansion and rupture. However, current analysis techniques for these images require the use of multiple software platforms for either modeling or simulation, prompting the need for alternatives to improve data processing. This study monitors the …

Lipid Detection In Pig Arteries Using Intravascular Photoacoustic Imaging, Jieying Mai, Yingchun Cao, Ayeeshik Kole, Michael Sturek, Ji-Xin Cheng

The Summer Undergraduate Research Fellowship (SURF) Symposium

Heart disease is the leading cause of death in the United States and worldwide. Each year over 370,000 people died from coronary artery disease in America. As the primary form of coronary artery disease, atherosclerosis behaves as lipid-rich plaque development inside an artery wall. Vulnerable plaques are those prone to rupture, which may result in thrombus or even death. Typical hallmarks of a vulnerable plaque include thin fibrous cap, a large lipid-rich necrotic core and inflammatory infiltrate. The identification and accurate detection of these lipid depositions in the arterial wall is crucial in the diagnosis of atherosclerosis. However, none of …

Diagnostic Quality Assessment Of Compressed Sensing Accelerated Magnetic Resonance Neuroimaging., Mohammad Kayvanrad, Amy Lin, Rohit Joshi, Jack Chiu, Terry Peters

Robarts Imaging Publications

PURPOSE: To determine the efficacy of compressed sensing (CS) reconstructions for specific clinical magnetic resonance neuroimaging applications beyond more conventional acceleration techniques such as parallel imaging (PI) and low-resolution acquisitions.

MATERIALS AND METHODS: Raw k-space data were acquired from five healthy volunteers on a 3T scanner using a 32-channel head coil using T2 -FLAIR, FIESTA-C, time of flight (TOF), and spoiled gradient echo (SPGR) sequences. In a series of blinded studies, three radiologists independently evaluated CS, PI (GRAPPA), and low-resolution images at up to 5× accelerations. Synthetic T2 -FLAIR images with artificial lesions were used to assess diagnostic accuracy for …

Blinking Phase-Change Nanocapsules Enable Background-Free Ultrasound Imaging, Alexander S. Hannah, Geoffrey P. Luke, Stanislav Y. Emelianov

Dartmouth Scholarship

Microbubbles are widely used as contrast agents to improve the diagnostic capability of conventional, highly speckled, low-contrast ultrasound imaging. However, while microbubbles can be used for molecular imaging, these agents are limited to the vascular space due to their large size (> 1 μm). Smaller microbubbles are desired but their ultrasound visualization is limited due to lower echogenicity or higher resonant frequencies. Here we present nanometer scale, phase changing, blinking nanocapsules (BLInCs), which can be repeatedly optically triggered to provide transient contrast and enable background-free ultrasound imaging. In response to irradiation by near-infrared laser pulses, the BLInCs undergo cycles of …

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 …

Portable, Parallel 9-Wavelength Near-Infrared Spectral Tomography (Nirst) System For Efficient Characterization Of Breast Cancer Within The Clinical Oncology Infusion Suite, Yan Zhao, Brian W. Pogue, Steffen J. Haider, Jiang Gui, Roberta Diflorio-Alexander, Keith Paulsen, Shudong Jiang

Dartmouth Scholarship

A portable near-infrared spectral tomography (NIRST) system was developed with simultaneous frequency domain (FD) and continuous-wave (CW) optical measurements for efficient characterization of breast cancer in a clinical oncology setting. Simultaneous FD and CW recordings were implemented to speed up acquisition to 3 minutes for all 9 wavelengths, spanning a range from 661nm to 1064nm. An adjustable interface was designed to fit various breast sizes and shapes. Spatial images of oxy- and deoxy-hemoglobin, water, lipid, and scattering components were reconstructed using a 2D FEM approach. The system was tested on a group of 10 normal subjects, who were examined bilaterally …

Pilot Study To Assess Breathing During Sight-Read Stringed Instrument Performance, Collin T. Erickson, Clark Potter, Gregory Bashford

UCARE: Research Products

For many musicians, one common occurrence during a performance is the presence of stage fright. Stage fright, though not always expressed can influence the confidence and self-esteem of a performer, and thus can affect the quality of the performance. Every day musicians are affected by stage fright, and there has been no exact solution as to how to lessen the feeling of anxiety musicians feel before performing. No data has been collected to find the correlation between the regularity of breathing and the level of stage fright that a person feels during their performance. A way to quantify regularity of …

Multiphoton Imaging Of Labeled Breast Cancer Cells To Quantify Intra And Extracellular Receptors, Sydney C. Wiggins

Biomedical Engineering Undergraduate Honors Theses

Every year 200,000 women in the United States are diagnosed with breast cancer. Of the cases diagnosed, 10% -15% are classified as triple negative breast cancer (TNBC) due to the absence of estrogen, progesterone, and HER-2/Neu receptors. This breast cancer sub-type is markedly more aggressive and twice as likely to develop in premenopausal women. TNBC is resistant to endocrine therapies and current targeted agents, making clinical need for the development of validated therapeutics for TNBC a pressing matter. To initiate drug development, the internalization of directly immunolabeled epidermal growth factor receptors (EGFR) in SK-BR-3 human breast adenocarcinoma cells was quantitated …

Intravital Microscopy Of Tumor Oxygenation And Glycolytic Demand, Jesse D. Ivers

Biomedical Engineering Undergraduate Honors Theses

There is growing concern about the over treatment of cancer because treatments are based primarily on tumor anatomy. In this study, we aim to begin the process of addressing that issue by developing an intravital technique for optically analyzing tumor biology. Two traits were identified as having significant importance in the aggression of a tumor, vascular oxygenation (SO2) and glycolytic demand. Dorsal skin flap window chambers were implanted and 4T1 and 67NR cancer cells were injected to provide a tumor model for the development of this intravital quantification technique. This study provides a detailed protocol from instrumentation setup to surgical …

Determining The Effect Of Delivery Rate On Glucose Uptake By Cancer Cells, Luke Felton

Biomedical Engineering Undergraduate Honors Theses

Radiation therapy is one of the most commonly performed cancer treatment therapies today. Radiation therapy can cause can changes to tumor vasculature and affect blood flow rates. It is important to determine how changes in blood flow rates affect tumor glycolytic uptake to better understand tumor response to radiation therapy (1). The goal of this study was to use a fluorescent analog of glucose, 2-NBDG, to study the effect of varying flow rates on glucose uptake. A microfluidic device was constructed to flow 2-NBDG through. A murine metastatic breast cancer cell line was then cultured inside this microfluidic channel, and …

Lesion Identification And The Effect Of Lesion On Motor Mapping After Stroke, Ruixi Zhou

McKelvey School of Engineering Graduate Student Theses & Dissertations

Stroke is the most common cause of long-term severe disability and the motor system that is most commonly affected in stroke. One of the mechanisms that underlies recovery of motor deficits is reorganization or remapping of functional representations around the motor cortex. This mechanism has been shown in monkeys, but results in human subjects have been variable. In this thesis, I used a database that includes longitudinal behavioral and multimodal imaging data in both stroke patients and healthy controls for two research projects. Firstly, I improved an automatic lesion segmentation method to aid in the identification of the location and …

Atomic Force Microscopy Based Dna Analysis, Drew Creighton

Mechanical Engineering Undergraduate Honors Theses

This report explores dry and wet scanning of a surface and DNA pickup using an AFM, as well as fluorescent staining of DNA. Dry and wet scans of DNA were obtained using a cantilever AFM tip in tapping mode. Dry scans were found to be clearer than wet scans; however, the drying process was found to decrease the thickness of DNA 2–4 times less than its original thickness. Alternately, wet scans were found to be less clear than dry scans and introduced more noise into the images obtained. Additionally, DNA kept its initial thickness during wet scanning. DNA was capable …

Optimized Protocol For Measuring 2-Nbdg Uptake As A Cellular Marker Of Glycolytic Demand, Drew Folgmann

Biomedical Engineering Undergraduate Honors Theses

2[N-(7-nitrobenz-2-oxa-1,2-diaxol-4-yl)amino]-2-deoxyglucose (2-NBDG) a fluorescently tagged analog of FDG is ideal for in vitro studies and imaging. 2-NBDG has been proven to be an adequate marker for glucose uptake in many different types of cells [1]. However, across the spectrum of 2-NBDG use a lack of consensus is observed for the following questions. What is the ideal time to fast cells to optimize cellular uptake of 2-NBDG? Also, what is the ideal concentration of 2-NBDG to be used when quantifying glucose uptake? Finally, what is the effect of serum on the uptake of 2-NBDG? To answer these questions and understand glucose …

Design Of A 3d-Printed Device For Diffuse Reflectance Spectroscopy Calibration As A Step Towards Clinical Translation, Nontapoth Vongkittiargorn

Biomedical Engineering Undergraduate Honors Theses

The diffusive reflectance and spectroscopic microendoscopy (DRSME) is a multimodal imaging system that harnesses its usefulness from different light sources. One of the modalities, diffuse reflectance spectroscopy (DRS), has been used in our lab to investigate optical properties of epithelial tissues using a broadband white light as the main source. Calibration of DRS is required as it can obtain the maximum intensity and convert it to absolute reflectance. Current manual-adjusted calibration can be lengthy and often lead to inconsistent results. Therefore, a new method of calibration is introduced where additive manufacturing (or 3D printing) technology is fully utilized.

The instrumentation …

Experimental Assessment Of Mouse Sociability Using An Automated Image Processing Approach, Frency Varghese, Jessica A. Burket, Andrew D. Benson, Stephen I. Deutsch, Christian W. Zemlin

Electrical & Computer Engineering Faculty Publications

Mouse is the preferred model organism for testing drugs designed to increase sociability. We present a method to quantify mouse sociability in which the test mouse is placed in a standardized apparatus and relevant behaviors are assessed in three different sessions (called session I, II, and III). The apparatus has three compartments (see Figure 1), the left and right compartments contain an inverted cup which can house a mouse (called “stimulus mouse”). In session I, the test mouse is placed in the cage and its mobility is characterized by the number of transitions made between compartments. In session II, a …

The Connectivity Domain: Analyzing Resting State Fmri Data Using Feature-Based Data-Driven And Model-Based Methods, Armin Iraji, Vince D. Calhoun, Natalie M. Wiseman, Esmaeil Davoodi-Bojd, Mohammad R. N. Avanaki, Zhifeng Kou

Biomedical Engineering Faculty Research Publications

Spontaneous fluctuations of resting state functional MRI (rsfMRI) have been widely used to understand the macro-connectome of the human brain. However, these fluctuations are not synchronized among subjects, which leads to limitations and makes utilization of first-level model-based methods challenging. Considering this limitation of rsfMRI data in the time domain, we propose to transfer the spatiotemporal information of the rsfMRI data to another domain, the connectivity domain, in which each value represents the same effect across subjects. Using a set of seed networks and a connectivity index to calculate the functional connectivity for each seed network, we transform data into …

Optimization-Based Interactive Segmentation Interface For Multiregion Problems., John S H Baxter, Martin Rajchl, Terry M Peters, Elvis C S Chen

Robarts Imaging Publications

Interactive segmentation is becoming of increasing interest to the medical imaging community in that it combines the positive aspects of both manual and automated segmentation. However, general-purpose tools have been lacking in terms of segmenting multiple regions simultaneously with a high degree of coupling between groups of labels. Hierarchical max-flow segmentation has taken advantage of this coupling for individual applications, but until recently, these algorithms were constrained to a particular hierarchy and could not be considered general-purpose. In a generalized form, the hierarchy for any given segmentation problem is specified in run-time, allowing different hierarchies to be quickly explored. We …