Medicine and Health Sciences Commons^™

Macroscopic Optical Imaging Technique For Wide-Field Estimation Of Fluorescence Depth In Optically Turbid Media For Application In Brain Tumor Surgical Guidance, Kolbein K. Kolste, Stephen C. Kanick, Pablo A. Valdés, Michael Jermyn, Brian C. Wilson, David W. Roberts, Keith D. Paulsen, Frederic Leblond

Dartmouth Scholarship

A diffuse imaging method is presented that enables wide-field estimation of the depth of fluorescent molecular markers in turbid media by quantifying the deformation of the detected fluorescence spectra due to the wavelength-dependent light attenuation by overlying tissue. This is achieved by measuring the ratio of the fluorescence at two wavelengths in combination with normalization techniques based on diffuse reflectance measurements to evaluate tissue attenuation variations for different depths. It is demonstrated that fluorescence topography can be achieved up to a 5 mm depth using a near-infrared dye with millimeter depth accuracy in turbid media having optical properties representative of …

Anthropomorphic Breast Phantoms With Physiological Water, Lipid, And Hemoglobin Content For Near-Infrared Spectral Tomography, Kelly E. Michaelsen, Venkataramanan Krishnaswamy, Adele Shenoy, Emily Jordan, Brian W. Pogue, Keith D. Paulsen

Dartmouth Scholarship

Breast mimicking tissue optical phantoms with sufficient structural integrity to be deployed as stand-alone imaging targets are developed and successfully constructed with biologically relevant concentrations of water, lipid, and blood. The results show excellent material homogeneity and reproducibility with inter- and intraphantom variability of 3.5 and 3.8%, respectively, for water and lipid concentrations ranging from 15 to 85%. The phantoms were long-lasting and exhibited water and lipid fractions that were consistent to within 5% of their original content when measured 2 weeks after creation. A breast-shaped three-compartment model of adipose, fibroglandular, and malignant tissues was created with water content ranging …

Impact Of Treatment Response Metrics On Photodynamic Therapy Planning And Outcomes In A Three-Dimensional Model Of Ovarian Cancer, Sriram Anbil, Imran Rizvi, Jonathan P. Celli, Nermina Alagic, Brian W. Pogue, Tayyaba Hasan

Dartmouth Scholarship

Common methods to characterize treatment efficacy based on morphological imaging may misrepresent outcomes and exclude effective therapies. Using a three-dimensional model of ovarian cancer, two functional treatment response metrics are used to evaluate photodynamic therapy (PDT) efficacy: total volume, calculated from viable and nonviable cells, and live volume, calculated from viable cells. The utility of these volume-based metrics is corroborated using independent reporters of photodynamic activity: viability, a common fluorescence-based ratiometric analysis, and photosensitizer photobleaching, which is characterized by a loss of fluorescence due in part to the production of reactive species during PDT. Live volume correlated with both photobleaching …

White Light-Informed Optical Properties Improve Ultrasound-Guided Fluorescence Tomography Of Photoactive Protoporphyrin Ix, Brendan P. Flynn, Alisha V. Dsouza, Stephen C. Kanick, Scott C. Davis, Brian W. Pogue

Dartmouth Scholarship

Subsurface fluorescence imaging is desirable for medical applications, including protoporphyrin-IX (PpIX)-based skin tumor diagnosis, surgical guidance, and dosimetry in photodynamic therapy. While tissue optical properties and heterogeneities make true subsurface fluorescence mapping an ill-posed problem, ultrasound-guided fluorescence-tomography (USFT) provides regional fluorescence mapping. Here USFT is implemented with spectroscopic decoupling of fluorescence signals (auto-fluorescence, PpIX, photoproducts), and white light spectroscopy-determined bulk optical properties. Segmented US images provide a priori spatial information for fluorescence reconstruction using region-based, diffuse FT. The method was tested in simulations, tissue homogeneous and inclusion phantoms, and an injected-inclusion animal model. Reconstructed fluorescence yield was linear with PpIX …

Compliant Head Probe For Positioning Electroencephalography Electrodes And Near-Infrared Spectroscopy Optodes, Paolo Giacometti, Solomon G. Diamond

Dartmouth Scholarship

A noninvasive head probe that combines near-infrared spectroscopy (NIRS) and electroencephalography (EEG) for simultaneous measurement of neural dynamics and hemodynamics in the brain is presented. It is composed of a compliant expandable mechanism that accommodates a wide range of head size variation and an elastomeric web that maintains uniform sensor contact pressure on the scalp as the mechanism expands and contracts. The design is intended to help maximize optical and electrical coupling and to maintain stability during head movement. Positioning electrodes at the inion, nasion, central, and preauricular fiducial locations mechanically shapes the probe to place 64 NIRS optodes and …

Dual-Tracer Background Subtraction Approach For Fluorescent Molecular Tomography, Kenneth M. Tichauer, Robert W. Holt, Fadi El-Ghussein, Scott C. Davis, Kimberly S. Samkoe, Jason R. Gunn, Frederic Leblond, Brian W. Pogue

Dartmouth Scholarship

Diffuse fluorescence tomography requires high contrast-to-background ratios to accurately reconstruct inclusions of interest. This is a problem when imaging the uptake of fluorescently labeled molecularly targeted tracers in tissue, which can result in high levels of heterogeneously distributed background uptake. We present a dual-tracer background subtraction approach, wherein signal from the uptake of an untargeted tracer is subtracted from targeted tracer signal prior to image reconstruction, resulting in maps of targeted tracer binding. The approach is demonstrated in simulations, a phantom study, and in a mouse glioma imaging study, demonstrating substantial improvement over conventional and homogenous background subtraction image reconstruction …

A Digital X-Ray Tomosynthesis Coupled Near Infrared Spectral Tomography System For Dual-Modality Breast Imaging, Venkataramanan Krishnaswamy, Kelly E. Michaelsen, Brian W. Pogue, Steven P. Poplack, Ian Shaw, Ken Defrietas, Ken Brooks, Keith D. Paulsen

Dartmouth Scholarship

A Near Infrared Spectral Tomography (NIRST) system has been developed and integrated into a commercial Digital Breast Tomosynthesis (DBT) scanner to allow structural and functional imaging of breast in vivo. The NIRST instrument uses an 8-wavelength continuous wave (CW) laser-based scanning source assembly and a 75-element silicon photodiode solid-state detector panel to produce dense spectral and spatial projection data from which spectrally constrained 3D tomographic images of tissue chromophores are produced. Integration of the optical imaging system into the DBT scanner allows direct co-registration of the optical and DBT images, while also facilitating the synergistic use of x-ray contrast as …

Improved Tumor Contrast Achieved By Single Time Point Dual-Reporter Fluorescence Imaging, Kenneth M. Tichauer, Kimberley S. Samkoe, Kristian J. Sexton, Jason R. Gunn, Tayyaba Hasan, Brian W. Pogue

Dartmouth Scholarship

In this study, we demonstrate a method to quantify biomarker expression that uses an exogenous dual-reporter imaging approach to improve tumor signal detection. The uptake of two fluorophores, one nonspecific and one targeted to the epidermal growth factor receptor (EGFR), were imaged at 1 h in three types of xenograft tumors spanning a range of EGFR expression levels (n  =  6 in each group). Using this dual-reporter imaging methodology, tumor contrast-to-noise ratio was amplified by >6 times at 1 h postinjection and >2 times at 24 h. Furthermore, by as early as 20 min postinjection, the dual-reporter imaging signal …

Combined Fluorescence And Reflectance Spectroscopy For In Vivo Quantification Of Cancer Biomarkers In Low- And High-Grade Glioma Surgery, Pablo A. ValdéS, Anthony Kim, Keith D. Paulsen, Frederic Leblond, Olga M. Conde, Brent T. Harris, David W. Roberts

Dartmouth Scholarship

Biomarkers are indicators of biological processes and hold promise for the diagnosis and treatment of disease. Gliomas represent a heterogeneous group of brain tumors with marked intra- and inter-tumor variability. The extent of surgical resection is a significant factor influencing post-surgical recurrence and prognosis. Here, we used fluorescence and reflectance spectral signatures for in vivo quantification of multiple biomarkers during glioma surgery, with fluorescence contrast provided by exogenously-induced protoporphyrin IX (PpIX) following administration of 5-aminolevulinic acid. We performed light-transport modeling to quantify multiple biomarkers indicative of tumor biological processes, including the local concentration of PpIX and associated photoproducts, total hemoglobin …

Quantitative Imaging Reveals Heterogeneous Growth Dynamics And Treatment-Dependent Residual Tumor Distributions In A Three-Dimensional Ovarian Cancer Model, Jonathan P. Celli, Imran Rizvi, Conor L. Evans, Adnan O. Abu-Yousif, Tayyaba Hasan

Dartmouth Scholarship

Three-dimensional tumor models have emerged as valuable in vitro research tools, though the power of such systems as quantitative reporters of tumor growth and treatment response has not been adequately explored. We introduce an approach combining a 3-D model of disseminated ovarian cancer with high-throughput processing of image data for quantification of growth characteristics and cytotoxic response. We developed custom MATLAB routines to analyze longitudinally acquired dark-field microscopy images containing thousands of 3-D nodules. These data reveal a reproducible bimodal log-normal size distribution. Growth behavior is driven by migration and assembly, causing an exponential decay in spatial density concomitant with …

Vesicles In Poiseuille Flow, Gerrit Danker, Petia M. Vlahovska, Chaouqi Misbah

Dartmouth Scholarship

Blood microcirculation critically depends on the migration of red cells towards the flow centerline. We identify theoretically the ratio of the inner over the outer fluid viscosities λ as a key parameter. At low λ, the vesicle deforms into a tank-treading ellipsoid shape far away from the flow centerline. The migration is always towards the flow centerline, unlike drops. Above a critical λ, the vesicle tumbles or breaths and migration is suppressed. A surprising coexistence of two types of shapes at the centerline, a bulletlike and a parachutelike shape, is predicted.

Non-Invasive Raman Tomographic Imaging Of Canine Bone Tissue, Matthew V. Schulmerich, Jacqueline H. Cole, Kathryn A. Dooley, Michael D. Morris, Jaclynn M. Kreider, Steven A. Goldstein, Subhadra Srinivasan, Brian W. Pogue

Dartmouth Scholarship

Raman spectroscopic diffuse tomographic imaging has been demonstrated for the first time. It provides a noninvasive, label-free modality to image the chemical composition of human and animal tissue and other turbid media. This technique has been applied to image the composition of bone tissue within an intact section of a canine limb. Spatially distributed 785-nm laser excitation was employed to prevent thermal damage to the tissue. Diffuse emission tomography reconstruction was used, and the location that was recovered has been confirmed by micro-computed tomography (micro-CT) images.

With recent advances, diffuse tomography shows promise for in vivo clinical imaging.^{1, …}

Receiver Operating Characteristic And Location Analysis Of Simulated Near-Infrared Tomography Images, Xiaomei Song, Brian W. Pogue, Hamid Dehghani, Shudong Jiang, Keith D. Paulsen, Tor D. Tosteson

Dartmouth Scholarship

Receiver operating characteristic (ROC) analysis was performed on simulated near-infrared tomography images, using both human observer and contrast-to-noise ratio (CNR) computational assessment, for application in breast cancer imaging. In the analysis, a nonparametric approach was applied for estimating the ROC curves. Human observer detection of objects had superior capability to localize the presence of heterogeneities when the objects were small with high contrast, with a minimum detectable threshold of CNR near 3.0 to 3.3 in the images. Human observers were able to detect heterogeneities in the images below a size limit of 4 mm, yet could not accurately find the …