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Full-Text Articles in Medicine and Health Sciences
An Imaging-Based Platform For High-Content, Quantitative Evaluation Of Therapeutic Response In 3d Tumour Models, Jonathan P. Celli, Imran Rizvi, Adam R. Blanden, Iqbal Massodi, Iqbal Massodi, Michael D. Glidden, Brian Pogue, Tayyaba Hasan
An Imaging-Based Platform For High-Content, Quantitative Evaluation Of Therapeutic Response In 3d Tumour Models, Jonathan P. Celli, Imran Rizvi, Adam R. Blanden, Iqbal Massodi, Iqbal Massodi, Michael D. Glidden, Brian Pogue, Tayyaba Hasan
Dartmouth Scholarship
While it is increasingly recognized that three-dimensional (3D) cell culture models recapitulate drug responses of human cancers with more fidelity than monolayer cultures, a lack of quantitative analysis methods limit their implementation for reliable and routine assessment of emerging therapies. Here, we introduce an approach based on computational analysis of fluorescence image data to provide high-content readouts of dose-dependent cytotoxicity, growth inhibition, treatment-induced architectural changes and size-dependent response in 3D tumour models. We demonstrate this approach in adherent 3D ovarian and pancreatic multiwell extracellular matrix tumour overlays subjected to a panel of clinically relevant cytotoxic modalities and appropriately designed controls …
Spatial Frequency Analysis Of Anisotropic Drug Transport In Tumor Samples, Stewart Russell, Kimberley S. Samkoe, Jason R. Gunn, P Jack Hoopes, Thienan A. Nguyen, Milo J. Russell, Robert R. Alfano, Brian W. Pogue
Spatial Frequency Analysis Of Anisotropic Drug Transport In Tumor Samples, Stewart Russell, Kimberley S. Samkoe, Jason R. Gunn, P Jack Hoopes, Thienan A. Nguyen, Milo J. Russell, Robert R. Alfano, Brian W. Pogue
Dartmouth Scholarship
Directional Fourier spatial frequency analysis was used on standard histological sections to identify salient directional bias in the spatial frequencies of stromal and epithelial patterns within tumor tissue. This directional bias is shown to be correlated to the pathway of reduced fluorescent tracer transport. Optical images of tumor specimens contain a complex distribution of randomly oriented aperiodic features used for neoplastic grading that varies with tumor type, size, and morphology. The internal organization of these patterns in frequency space is shown to provide a precise fingerprint of the extracellular matrix complexity, which is well known to be related to the …
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
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 …
Scanning In Situ Spectroscopy Pplatform For Imaging Surgical Breast Tissue Specimens, Venkataramanan Krishnaswamy, Ashley M. Laughney, Wendy A. Wells, Keith D. Paulsen, Brian W. Pogue
Scanning In Situ Spectroscopy Pplatform For Imaging Surgical Breast Tissue Specimens, Venkataramanan Krishnaswamy, Ashley M. Laughney, Wendy A. Wells, Keith D. Paulsen, Brian W. Pogue
Dartmouth Scholarship
A non-contact localized spectroscopic imaging platform has been developed and optimized to scan 1 x 1 cm² square regions of surgically resected breast tissue specimens with ~150-micron resolution. A color corrected, image-space telecentric scanning design maintained a consistent sampling geometry and uniform spot size across the entire imaging field. Theoretical modeling in ZEMAX allowed estimation of the spot size, which is equal at both the center and extreme positions of the field with ~5% variation across the designed waveband, indicating excellent color correction. The spot sizes at the center and an extreme field position were also measured experimentally using the …
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
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
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 …
Comparing Implementations Of Magnetic-Resonance-Guided Fluorescence Molecular Tomography For Diagnostic Classification Of Brain Tumors, Scott C. Davis, Kimberley S. Samkoe, Julia A. O’Hara, Summer L. Gibbs-Strauss, Keith D. Paulsen, Brian W. Pogue
Comparing Implementations Of Magnetic-Resonance-Guided Fluorescence Molecular Tomography For Diagnostic Classification Of Brain Tumors, Scott C. Davis, Kimberley S. Samkoe, Julia A. O’Hara, Summer L. Gibbs-Strauss, Keith D. Paulsen, Brian W. Pogue
Dartmouth Scholarship
Fluorescence molecular tomography (FMT) systems coupled to conventional imaging modalities such as magnetic resonance imaging (MRI) and computed tomography provide unique opportunities to combine data sets and improve image quality and content. Yet, the ideal approach to combine these complementary data is still not obvious. This preclinical study compares several methods for incorporating MRI spatial prior information into FMT imaging algorithms in the context of in vivo tissue diagnosis. Populations of mice inoculated with brain tumors that expressed either high or low levels of epidermal growth factor receptor (EGFR) were imaged using an EGF-bound near-infrared dye and a spectrometer-based MRI-FMT …
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
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 …
Improved Quantification Of Small Objects In Near-Infrared Diffuse Optical Tomography, Subhadra Srinivasan, Brian W. Pogue, Hamid Dehghani, Shudong Jiang, Xiaomei Song, Keith D. Paulsen
Improved Quantification Of Small Objects In Near-Infrared Diffuse Optical Tomography, Subhadra Srinivasan, Brian W. Pogue, Hamid Dehghani, Shudong Jiang, Xiaomei Song, Keith D. Paulsen
Dartmouth Scholarship
Diffuse optical tomography allows quantification of hemoglobin, oxygen saturation, and water in tissue, and the fidelity in this quantification is dependent on the accuracy of optical properties determined during image reconstruction. In this study, a three-step algorithm is proposed and validated that uses the standard Newton minimization with Levenberg-Marquardt regularization as the first step. The second step is a modification to the existing algorithm using a two-parameter regularization to allow lower damping in a region of interest as compared to background. This second stage allows the recovery of the actual size of an inclusion. A region-based reconstruction is the final …