Bioimaging and Biomedical Optics Commons^™

Raman Spectroscopy Detects Distant Invasive Brain Cancer Cells Centimeters Beyond Mri Capability In Humans, Michael Jermyn, Joannie Desroches, Jeanne Mercier, Karl St-Arnaud

Dartmouth Scholarship

Surgical treatment of brain cancer is limited by the inability of current imaging capabilities such as magnetic resonance imaging (MRI) to detect the entirety of this locally invasive cancer. This results in residual cancer cells remaining following surgery, leading to recurrence and death. We demonstrate that intraoperative Raman spectroscopy can detect invasive cancer cells centimeters beyond pathological T1-contrast-enhanced and T2-weighted MRI signals. This intraoperative optical guide can be used to detect invasive cancer cells and minimize post-surgical cancer burden. The detection of distant invasive cancer cells beyond MRI signal has the potential to increase the effectiveness of surgery and directly …

A Fourier Description Of Covariance, And Separation Of Simultaneously Encoded Slices With In-Plane Acceleration In Fmri, Mary C. Kociuba

Dissertations (1934 -)

Functional magnetic resonance imaging (fMRI) studies aim to identify localized neural regions associated with a cognitive task performed by the subject. An indirect measure of the brain activity is the blood oxygenation level dependent (BOLD) signal fluctuations observed within the complex-valued spatial frequencies measured over time. The standard practice in fMRI is to discard the phase information after image reconstruction, even with evidence of biological task-related change in the phase time-series. In the first aim of this dissertation, a complex-valued time-series covariance is derived as a linear combination of second order temporal Fourier frequency coefficients. As opposed to magnitude-only analysis, …

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 …

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 …

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 …

Toward Magnetic Resonance Only Treatment Planning: Distortion Mitigation And Image-Guided Radiation Therapy Validation, Ryan Glen Price

Wayne State University Dissertations

While MR-only treatment planning has shown promise, there are still several well-known challenges that are currently limiting widespread clinical implementation.

Firstly, MR images are affected by both patient-induced and system-level geometric distortions that can significantly degrade treatment planning accuracy. . In addition, the availability of comprehensive distortion analysis software is currently limited. Also while many groups have been working toward a synthetic CT solution, further study is needed on the implementation of synCTs as the reference datasets for linac-based image-guided radiation therapy (IGRT) to help determine their robustness in an MR-only workflow.

A 36×43×2 cm3 phantom with 255 known landmarks …

Categorizing Fetal Heart Rate Variability With And Without Visual Aids, Amanda J. Ashdown, Mark W. Scerbo, Lee A. Belfore Ii, Stephen S. Davis, Alfred Z. Abuhamad

Psychology Faculty Publications

Objective This study examined the ability of clinicians to correctly categorize images of fetal heart rate (FHR) variability with and without the use of exemplars.

Study Design A sample of 33 labor and delivery clinicians inspected static FHR images and categorized them into one of four categories defined by the National Institute of Child Health and Human Development (NICHD) based on the amount of variability within absent, minimal, moderate, or marked ranges. Participants took part in three conditions: two in which they used exemplars representing FHR variability near the center or near the boundaries of each range, and a third …

Feasibility Of Using Raman-Based Techniques For Breast Cancer Detection, Sara Mollamohammada

Department of Civil and Environmental Engineering: Dissertations, Theses, and Student Research

Breast cancer is one of the common types of cancer among women all over the world. Early diagnosis is an effective way that improve the treatment process and gives the patients a better chance of survival. Many of the patients infected by breast cancer choose breast conservation surgery (BCS). However, some of those will be subjected to mastectomy, and many will have tumor recurrence as there is no precise technique to show the tumor margins. Raman-based methods are powerful techniques with potential to rapidly differentiate normal from tumor tissues and provides a solution to detect tumor margin. This is because …

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 …

Calibration And Optimization Of 3d Digital Breast Tomosynthesis Guided Near Infrared Spectral Tomography, Kelly E. Michaelsen, Venkataramanan Krishnaswamy, Linxi Shi, Srinivasan Vedantham, Steven Poplack, Andrew Karellas, Brian Pogue, Keith Paulsen

Dartmouth Scholarship

Calibration of a three-dimensional multimodal digital breast tomosynthesis (DBT) x-ray and non-fiber based near infrared spectral tomography (NIRST) system is challenging but essential for clinical studies. Phantom imaging results yielded linear contrast recovery of total hemoglobin (HbT) concentration for cylindrical inclusions of 15 mm, 10 mm and 7 mm with a 3.5% decrease in the HbT estimate for each 1 cm increase in inclusion depth. A clinical exam of a patient's breast containing both benign and malignant lesions was successfully imaged, with greater HbT was found in the malignancy relative to the benign abnormality and fibroglandular regions (11 μM vs. …

Initial Validation Of A Novel Method Of Presurgical Language Localization Through Functional Connectivity (Fcmri), Stephanie M. Noble, Dustin Scheinost, Susan Y. Bookheimer, Patricia Walshaw, R Todd Constable, Christopher F. Benjamin

Yale Day of Data

OBJECTIVE: Neurosurgery is potentially curative in chronic epilepsy but can only be offered to patients if the surgical risk to language is known. Clinical functional magnetic resonance imaging (fMRI) is an ideal, noninvasive method for localizing language cortex yet remains to be validated for this purpose. We have recently presented a novel method for localizing language cortex. Here we present a preliminary evaluation of this method’s validity. We hypothesized language regions identified using this novel method would demonstrate stronger functional connectivity than randomly generated set of proximal networks. METHOD: fMRI data were collected from sixteen temporal lobe patients …

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.

Mobile Cloud Computing Based Non Rigid Registration For Image Guided Surgery, Arun Brahmavar Vishwanatha

Computer Science Theses & Dissertations

In this thesis we present the design and implementation of a Mobile Cloud computing platform for non-rigid registration required in Image Guided Surgery (MCIGS). MCIGS contributes in flexible, portable and accurate alignment of pre-operative brain data with intra-operative MRI, for image guided diagnosis and therapy and endoscopic skull base surgery. Improved precision of image guided therapy and specifically neurosurgery procedures is known to result in the improved prognosis for brain tumor patients. MCI GS system is tested with Physics Based Non-Rigid Registration method form ITK. Our preliminary results for brain images indicate that the proposed system over Wi-Fi can be …

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 …

Computer Aided Detection Of Oral Lesions On Ct Images, Shaikat Mahmood Galib

Masters Theses

"Oral lesions are important findings on computed tomography images. They are difficult to detect on CT images because of low contrast, arbitrary orientation of objects, complicated topology and lack of clear lines indicating lesions. In this thesis, a fully automatic method to detect oral lesions from dental CT images is proposed to identify (1) Closed boundary lesions and (2) Bone deformation lesions. Two algorithms were developed to recognize these two types of lesions, which cover most of the lesion types that can be found on CT images. The results were validated using a dataset of 52 patients. Using non training …

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.

Multi-Surface Simplex Spine Segmentation For Spine Surgery Simulation And Planning, Rabia Haq

Computational Modeling & Simulation Engineering Theses & Dissertations

This research proposes to develop a knowledge-based multi-surface simplex deformable model for segmentation of healthy as well as pathological lumbar spine data. It aims to provide a more accurate and robust segmentation scheme for identification of intervertebral disc pathologies to assist with spine surgery planning. A robust technique that combines multi-surface and shape statistics-aware variants of the deformable simplex model is presented. Statistical shape variation within the dataset has been captured by application of principal component analysis and incorporated during the segmentation process to refine results. In the case where shape statistics hinder detection of the pathological region, user-assistance is …

Computer Aided Diagnosis Of Oral Cancer: Using Time-Step Ct Images, Jonathan T. Scott

Masters Theses

"In medical imaging it is a very common practice to use a technique known as Time-Step imaging in patients who might develop cancer. Time-Step imaging it a very powerful technique, however it can lead to unmanageable amounts of image data. Previously the only way to search all of this data was to manually look through all of the files. This had to be done by trained professionals who knew what to look for within the images and make a judgment about the patient based on the images. This paper discusses the development of an algorithm to have a computer search …

Sensitivity Of Mri-Guided Near-Infrared Spectroscopy Clinical Breast Exam Data And Its Impact On Diagnostic Performance, Michael A. Mastanduno, Junqing Xu, Fadi El-Ghussein, Shudong Jiang, Hong Yin, Yan Zhao, Kelly E. Michaelson, Ke Wang, Fang Ren, Brian W. Pogue, Keith D. Paulsen

Dartmouth Scholarship

In this study, data from breast MRI-guided near infrared spectroscopy (NIRS) exams delivered to 44 patients scheduled for surgical resection (ending in 16 benign and 28 malignant diagnoses) were analyzed using a spatial sensitivity metric to quantify the adequacy of the optical measurements for interrogating the tumor region of interest, as derived from the concurrent MRI scan. Along with positional sensitivity, the incorporation of spectral priors and the selection of an appropriate regularization parameter in the image reconstruction were considered, and found to influence the diagnostic accuracy of the recovered images. Once optimized, the MRI/NIRS data was able to differentiate …

Frontal White Matter Integrity In Adults With Down Syndrome With And Without Dementia, David K. Powell, Allison Caban-Holt, Greg A. Jicha, William C. Robertson, Roberta Davis, Brian T. Gold, Frederick A. Schmitt, Elizabeth Head

Magnetic Resonance Imaging and Spectroscopy Center Faculty Publications

Adults with Down syndrome (DS) are at high risk for developing Alzheimer's disease after the age of 40 years. To detect white matter (WM) changes in the brain linked to dementia, fractional anisotropy (FA) from diffusion tensor imaging was used. We hypothesized that adults with DS without dementia (DS n = 10), DS with dementia (DSAD n = 10) and age matched non-DS subjects (CTL n = 10) would show differential levels of FA and an association with scores from the Brief Praxis Test and the Severe Impairment Battery. WM integrity differences in DS compared with CTL were found predominantly …

Utilizing Fast Spin Echo Mri To Reduce Image Artifacts And Improve Implant/Tissue Interface Detection In Refractory Parkinson’S Patients With Deep Brain Stimulators, Subhendra N. Sarkar, Pooja R. Sarkar, Efstathios Papavassiliou, Rafael Rojas

Publications and Research

Introduction. In medically refractory Parkinson’s disease (PD) deep-brain stimulation (DBS) is an effective therapeutic tool. Postimplantation MRI is important in assessing tissue damage and DBS lead placement accuracy. We wanted to identify which MRI sequence can detectDBS leads with smallest artifactual signal void, allowing better tissue/electrode edge conspicuity.

Methods. Using an IRB approved protocol 8 advanced PDpatientswere imagedwithinMRconditional safety guidelines at lowRF power (SAR ≤ 0.1 W/kg) in coronal plane at 1.5T by various sequences.The image slices were subjectively evaluated for diagnostic quality and the lead contact diameters were compared to identify a sequence least affected by metallic leads.

Results …

Cervical Cancer Histology Image Feature Extraction And Classification, Peng Guo

Masters Theses

"Cervical cancer, the second most common cancer affecting women worldwide and the most common in developing countries can be cured if detected early and treated. Expert pathologists routinely visually examine histology slides for cervix tissue abnormality assessment. In previous research, an automated, localized, fusion-based approach was investigated for classifying squamous epithelium into Normal, CIN1, CIN2, and CIN3 grades of cervical intraepithelial neoplasia (CIN) based on image analysis of 62 digitized histology images obtained through the National Library of Medicine. In this research, CIN grade assessments from two pathologists are analyzed and are used to facilitate atypical cell concentration feature development …

A Nonrigid Registration Method For Correcting Brain Deformation Induced By Tumor Resection, Yixun Liu, Chengjun Yao, Fotis Drakopoulos, Jinsong Wu, Liangfu Zhou, Nikos Chrisochoides

Computer Science Faculty Publications

Purpose: This paper presents a nonrigid registration method to align preoperative MRI with intraoperative MRI to compensate for brain deformation during tumor resection. This method extends traditional point-based nonrigid registration in two aspects: (1) allow the input data to be incomplete and (2) simulate the underlying deformation with a heterogeneous biomechanical model.

Methods: The method formulates the registration as a three-variable (point correspondence, deformation field, and resection region) functional minimization problem, in which point correspondence is represented by a fuzzy assign matrix; Deformation field is represented by a piecewise linear function regularized by the strain energy of a heterogeneous biomechanical …

Dopaminergic Modulation Of Memory And Affective Processing In Parkinson Depression, Lee X. Blonder, John T. Slevin, Richard J. Kryscio, Catherine A. Martin, Anders H. Andersen, Charles D Smith, Frederick A. Schmitt

Magnetic Resonance Imaging and Spectroscopy Center Faculty Publications

Depression is common in Parkinson's disease and is associated with cognitive impairment. Dopaminergic medications are effective in treating the motor symptoms of Parkinson's disease; however, little is known regarding the effects of dopaminergic pharmacotherapy on cognitive function in depressed Parkinson patients. This study examines the neuropsychological effects of dopaminergic pharmacotherapy in Parkinsonian depression. We compared cognitive function in depressed and non-depressed Parkinson patients at two time-points: following overnight withdrawal and after the usual morning regimen of dopaminergic medications. A total of 28 non-demented, right-handed patients with mild to moderate idiopathic Parkinson's disease participated. Ten of these patients were depressed according …

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.

Dynamic Dual-Tracer Mri-Guided Fluorescence Tomography To Quantify Receptor Density In Vivo, Scott C. Davis, Kimberley S. Samkoe, Kenneth M. Tichauer, Kristian J. Sexton, Jason R. Gunn, Sophie J. Deharvengt, Tayyaba Hasan, Brian W. Pogue

Dartmouth Scholarship

The up-regulation of cell surface receptors has become a central focus in personalized cancer treatment; however, because of the complex nature of contrast agent pharmacokinetics in tumor tissue, methods to quantify receptor binding in vivo remain elusive. Here, we present a dual-tracer optical technique for noninvasive estimation of specific receptor binding in cancer. A multispectral MRI-coupled fluorescence molecular tomography system was used to image the uptake kinetics of two fluorescent tracers injected simultaneously, one tracer targeted to the receptor of interest and the other tracer a nontargeted reference. These dynamic tracer data were then fit to a dual-tracer compartmental model …

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 …

Multimodal Imaging Evidence For Axonal And Myelin Deterioration In Amnestic Mild Cognitive Impairment, Brian T. Gold, Yang Jiang, David K. Powell, Charles D. Smith

Neuroscience Faculty Publications

White matter (WM) microstructural declines have been demonstrated in Alzheimer's disease and amnestic mild cognitive impairment (aMCI). However, the pattern of WM microstructural changes in aMCI after controlling for WM atrophy is unknown. Here, we address this issue through joint consideration of aMCI alterations in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity, as well as macrostructural volume in WM and gray matter compartments. Participants were 18 individuals with aMCI and 24 healthy seniors. Voxelwise analyses of diffusion tensor imaging data was carried out using tract-based spatial statistics (TBSS) and voxelwise analyses of high-resolution structural data was conducted using …