1. Articles from Adam de la Zerda

    1-24 of 28 1 2 »
    1. Optical Microscopy and Coherence Tomography of Cancer in Living Subjects

      Optical Microscopy and Coherence Tomography of Cancer in Living Subjects

      Intravital microscopy (IVM) and optical coherency tomography (OCT) are two powerful optical imaging tools that allow visualization of dynamic biological activities in living subjects with subcellular resolutions. Recent advances in labeling and label-free techniques empower IVM and OCT for a wide range of preclinical and clinical cancer imaging, providing profound insights into the complex physiological, cellular, and molecular behaviors of tumors. Preclinical IVM and OCT have elucidated many otherwise inscrutable aspects of cancer biology, while clinical applications of IVM and OCT are revolutionizing cancer diagnosis and therapies. We review important progress in the fields of IVM and OCT for cancer ...

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    2. Angular compounding for speckle reduction in optical coherence tomography using geometric image registration algorithm and digital focusing

      Angular compounding for speckle reduction in optical coherence tomography using geometric image registration algorithm and digital focusing

      Optical coherence tomography (OCT) suffers from speckle noise due to the high spatial coherence of the utilized light source, leading to significant reductions in image quality and diagnostic capabilities. In the past, angular compounding techniques have been applied to suppress speckle noise. However, existing image registration methods usually guarantee pure angular compounding only within a relatively small field of view in the focal region, but produce spatial averaging in the other regions, resulting in resolution loss and image blur. This work develops an image registration model to correctly localize the real-space location of every pixel in an OCT image, for ...

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    3. A Spectral De-mixing Model for Triplex In Vivo Imaging of Optical Coherence Tomography Contrast Agents

      A Spectral De-mixing Model for Triplex In Vivo Imaging of Optical Coherence Tomography Contrast Agents

      The ability to detect multiple contrast agents simultaneously would greatly enhance Optical Coherence Tomography (OCT) images, providing nuanced biological context to physiological structures. However, previous OCT contrast agent work has been limited to scenarios where only a single contrast agent could be robustly detected within each voxel. We present a novel spectroscopic technique for de-mixing the spectral signal from multiple OCT contrast agents within a single voxel. We validate our technique in vitro and also demonstrate in vivo imaging of three spectrally distinct gold nanobipyramids, trafficking within the lymphatic system of a live mouse. This approach opens the door to ...

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    4. Gold Nanobipyramids as Second Near Infrared Optical Coherence Tomography Contrast Agents for In Vivo Multiplexing Studies

      Gold Nanobipyramids as Second Near Infrared Optical Coherence Tomography Contrast Agents for In Vivo Multiplexing Studies

      Developing contrast-enhanced optical coherence tomography (OCT) techniques is important for specific imaging of tissue lesions, molecular imaging, cell-tracking, and highly sensitive microangiography and lymphangiography. Multiplexed OCT imaging in the second near infrared (NIR-II) window is highly desirable since it allows simultaneous imaging and tracking of multiple biological events in high resolution with deeper tissue penetration in vivo . Here we demonstrate that gold nanobipyramids can function as OCT multiplexing contrast agents, allowing high-resolution imaging of two separate lymphatic flows occurring simultaneously from different drainage basins into the same lymph node in a live mouse. Contrast-enhanced multiplexed lymphangiography of a melanoma tumor ...

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    5. Spatiotemporal Tracking of Brain-Tumor-Associated Myeloid Cells in Vivo through Optical Coherence Tomography with Plasmonic Labeling and Speckle Modulation

      Spatiotemporal Tracking of Brain-Tumor-Associated Myeloid Cells in Vivo through Optical Coherence Tomography with Plasmonic Labeling and Speckle Modulation

      By their nature, tumors pose a set of profound challenges to the immune system with respect to cellular recognition and response coordination. Recent research indicates that leukocyte subpopulations, especially tumor-associated macrophages (TAMs), can exert substantial influence on the efficacy of various cancer immunotherapy treatment strategies. To better study and understand the roles of TAMs in determining immunotherapeutic outcomes, significant technical challenges associated with dynamically monitoring single cells of interest in relevant live animal models of solid tumors must be overcome. However, imaging techniques with the requisite combination of spatiotemporal resolution, cell-specific contrast, and sufficient signal-to-noise at increasing depths in tissue ...

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    6. Upper limit for angular compounding speckle reduction

      Upper limit for angular compounding speckle reduction

      Angular compounding is a technique for reducing speckle noise in optical coherence tomography that is claimed to significantly improve the signal-to-noise ratio (SNR) of images without impairing their spatial resolution. Here, we examine how focal point movements caused by optical aberrations in an angular compounding system may produce unintended spatial averaging and concomitant loss of spatial resolution. Experimentally, we accounted for such aberrations by aligning our system and measuring distortions in images and found that when the distortions were corrected, the speckle reduction by angular compounding was limited. Our theoretical analysis using Monte Carlo simulations indicates that “pure” angular compounding ...

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    7. Gold Nanobipyramids as Second Near Infrared Optical Coherence Tomography Contrast Agents for Multiplexed In Vivo Lymphangiography

      Gold Nanobipyramids as Second Near Infrared Optical Coherence Tomography Contrast Agents for Multiplexed In Vivo Lymphangiography

      Developing contrast-enhanced optical coherence tomography (OCT) techniques is important for specific imaging of tissue lesions, molecular imaging, cell-tracking, and highly sensitive microangiography and lymphangiography. Multiplexed OCT imaging in the second near infrared (NIR-II) window is highly desirable since it allows simultaneous imaging and tracking of multiple biological events in high resolution with deeper tissue penetration in vivo. Here we demonstrate that gold nanobipyramids can function as OCT multiplexing contrast agents, allowing the visualization of two separate lymphatic flows occurring simultaneously from different drainage basins into the same lymph node in a live mouse. Contrast-enhanced multiplexed lymphangiography of a melanoma tumor ...

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    8. Real-time detection of circulating tumor cells in living animals using functionalized large gold nanorods

      Real-time detection of circulating tumor cells in living animals using functionalized large gold nanorods

      Optical coherence tomography (OCT) can be utilized with significant speckle reduction techniques and highly-scattering contrast agents for noninvasive, contrast-enhanced imaging of living tissues at the cellular scale. The advantages of reduced speckle noise and improved targeted contrast can be harnessed to track objects as small as 2 μm in vivo, which enables applications for cell tracking and quantification in living subjects. Here we demonstrate the use of Large Gold Nanorods (LGNRs) as contrast agents for detecting individual micron-sized polystyrene beads and single myeloma cells in blood circulation using speckle modulating-OCT (SM-OCT). This report marks the first time that OCT has ...

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    9. Gold Nanoprisms as Optical Coherence Tomography Contrast Agents in the Second Near-Infrared Window for Enhanced Angiography in Live Animals

      Gold Nanoprisms as Optical Coherence Tomography Contrast Agents in the Second Near-Infrared Window for Enhanced Angiography in Live Animals

      Optical coherence tomography angiography (OCTA) is an important tool for investigating vascular networks and microcirculation in living tissue. Traditional OCTA detects blood vessels via intravascular dynamic scattering signals derived from the movements of red blood cells (RBCs). However, the low hematocrit and long latency between RBCs in capillaries make these OCTA signals discontinuous, leading to incomplete mapping of the vascular networks. OCTA imaging of microvascular circulation is particularly challenging in tumors due to the abnormally slow blood flow in angiogenic tumor vessels and strong attenuation of light by tumor tissue. Here, we demonstrate in vivo that gold nanoprisms (GNPRs) can ...

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    10. Intraoperative Imaging Modalities and the Potential Role of Speckle Modulating Optical Coherence Tomography

      Intraoperative Imaging Modalities and the Potential Role of Speckle Modulating Optical Coherence Tomography

      Maximizing extent of resection has been correlated with improved outcomes in a variety of pediatric and adult brain tumors. 1-11 While gross total resections are often achieved without the use of intraoperative adjuncts, difficulty in distinguishing tumor from normal brain can at times prevent the complete resection of brain tumors. Intraoperative imaging tools have increasingly been embraced with the goal of improving rates of gross total resection. In this review, we will discuss several currently used intraoperative imaging modalities, including intraoperative magnetic resonance imaging (iMRI), wide-field fluorescence, high-resolution fluorescence microscopy, and optical coherence tomography (OCT). 12-17 We will also discuss ...

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    11. Developing in vivo Functional Imaging Technology with Micron-Scale Resolution Using Optical Coherence Tomography

      Developing in vivo Functional Imaging Technology with Micron-Scale Resolution Using Optical Coherence Tomography

      Researchers and physicians rely on functional imaging to better understand tumors and other structures within the human body. However, imaging technologies that capture deep structures have poor resolution, while those that provide high resolution have limited depth. Positron emission tomography (PET), for example, reveals details deep within tissue but suffers from poor spatial resolution, with each voxel of a PET scan representing thousands or even millions of cells. In contrast, optical microscopy can deliver subcellular spatial resolution but is usually limited to a depth of tens of microns. Optical coherence tomography (OCT) helps bridge the gap between low-resolution/high-penetration and ...

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    12. Optical coherence tomography of lymphatic vessel endothelial hyaluronan receptors in vivo

      Optical coherence tomography of lymphatic vessel endothelial hyaluronan receptors in vivo

      Optical Coherence Tomography (OCT) imaging of living subjects offers millimeters depth of penetration into tissue while maintaining high spatial resolution. However, because most molecular biomarkers do not produce inherent OCT contrast signals, exogenous contrast agents must be employed to achieve molecular imaging. Here we demonstrate that microbeads (μBs) can be used as effective contrast agents to target cellular biomarkers in lymphatic vessels and can be detected by OCT using a phase variance algorithm. We applied this technique to image the molecular dynamics of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) in vivo , which showed significant down-regulation during tissue inflammation.

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    13. Developing in vivo Functional Imaging Technology with Micron-Scale Resolution Using Optical Coherence Tomography

      Developing in vivo Functional Imaging Technology with Micron-Scale Resolution Using Optical Coherence Tomography

      Researchers and physicians rely on functional imaging to better understand tumors and other structures within the human body. However, imaging technologies that capture deep structures have poor resolution, while those that provide high resolution have limited depth. Positron emission tomography (PET), for example, reveals details deep within tissue but suffers from poor spatial resolution, with each voxel of a PET scan representing thousands or even millions of cells. In contrast, optical microscopy can deliver subcellular spatial resolution but is usually limited to a depth of tens of microns. Optical coherence tomography (OCT) helps bridge the gap between low-resolution/high-penetration and ...

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    14. Speckle-modulating optical coherence tomography in living mice and humans

      Speckle-modulating optical coherence tomography in living mice and humans

      Optical coherence tomography (OCT) is a powerful biomedical imaging technology that relies on the coherent detection of backscattered light to image tissue morphology in vivo . As a consequence, OCT is susceptible to coherent noise (speckle noise), which imposes significant limitations on its diagnostic capabilities. Here we show speckle-modulating OCT (SM-OCT), a method based purely on light manipulation that virtually eliminates speckle noise originating from a sample. SM-OCT accomplishes this by creating and averaging an unlimited number of scans with uncorrelated speckle patterns without compromising spatial resolution. Using SM-OCT, we reveal small structures in the tissues of living animals, such as ...

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    15. In Vivo Molecular Optical Coherence Tomography of Lymphatic Vessel Endothelial Hyaluronan Receptors

      In Vivo Molecular Optical Coherence Tomography of Lymphatic Vessel Endothelial Hyaluronan Receptors

      Optical Coherence Tomography (OCT) imaging of living subjects offers increased depth of penetration while maintaining high spatial resolution when compared to other optical microscopy techniques. However, since most protein biomarkers do not exhibit inherent contrast detectable by OCT, exogenous contrast agents must be employed for imaging specific cellular biomarkers of interest. While a number of OCT contrast agents have been previously studied, demonstrations of molecular targeting with such agents in live animals have been historically challenging and notably limited in success. Here we demonstrate for the first time that microbeads (µBs) can be used as contrast agents to target cellular ...

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    16. Spectral contrast-enhanced optical coherence tomography for improved detection of tumor microvasculature and functional imaging of lymphatic drainage

      Spectral contrast-enhanced optical coherence tomography for improved detection of tumor microvasculature and functional imaging of lymphatic drainage

      Optical Coherence Tomography (OCT) is well-suited to study in vivo dynamics of blood circulation and lymphatic flow because of the technique’s combination of rapid image acquisition, micron spatial resolution, and penetration depth in turbid tissues. However, OCT has been historically constrained by a dearth of contrast agents that are readily distinguished from the strong scattering intrinsic to biological tissues. In this study, we demonstrate large gold nanorods (LGNRs) as optimized contrast agents for OCT. LGNRs produce 32-fold greater backscattering than GNRs previously tested for contrast-enhanced OCT. Furthermore, LGNRs exhibit 110-fold stronger spectral signal than conventional GNRs when coupled with ...

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    17. Reconstruction and Spectral Analysis for Optical Coherence Tomography

      Reconstruction and Spectral Analysis for Optical Coherence Tomography

      MATLAB code for reconstruction and spectral analysis of spectral domain OCT images. This code can be used as part of a platform for molecular imaging with OCT, which we call MOZART. This code was created to read raw interferograms from Thorlabs OCTs (SW version 4 works best, but version 3 is also supported with a few changes). It reconstructs the raw interferograms into OCT images, and supports both 2D, 3D and speckle variance. In addition to reconstructing the images this code: Calculates the normalized spcekle variance (useful for detecting blood vessels) Calculates dispersion compensation Calculates a map of spectral contras ...

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    18. A model for quantifying contrast enhancement in optical coherence tomography (OCT)

      A model for quantifying contrast enhancement in optical coherence tomography (OCT)

      We have developed a model to accurately quantify the signals produced by exogenous scattering agents used for contrast-enhanced Optical Coherence Tomography (OCT). This model predicts distinct concentration-dependent signal trends that arise from the underlying physics of coherence-based detection. Accordingly, we show that real scattering particles can be described as simplified ideal scatterers with modified scattering intensity and concentration. The relation between OCT signal and particle concentration is approximately linear at concentrations lower than 0.8 particles per imaging voxel. However, at higher concentrations, interference effects cause signal to increase with a square root dependence on the number of particles within ...

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    19. High sensitivity contrast enhanced optical coherence tomography for functional in vivo imaging

      High sensitivity contrast enhanced optical coherence tomography for functional in vivo imaging

      In this study, we developed and applied highly-scattering large gold nanorods (LGNRs) and custom spectral detection algorithms for high sensitivity contrast-enhanced optical coherence tomography (OCT). We were able to detect LGNRs at a concentration as low as 50 pM in blood. We used this approach for noninvasive 3D imaging of blood vessels deep in solid tumors in living mice. Additionally, we demonstrated multiplexed imaging of spectrally-distinct LGNRs that enabled observations of functional drainage in lymphatic networks. This method, which we call MOZART, provides a platform for molecular imaging and characterization of tissue noninvasively at cellular resolution

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    20. Developing in vivo Functional Imaging Technology with Micron-Scale Resolution Using Optical Coherence Tomography

      Developing in vivo Functional Imaging Technology with Micron-Scale Resolution Using Optical Coherence Tomography

      Researchers and physicians rely on functional imaging to better understand tumors and other structures within the human body. However, imaging technologies that capture deep structures have poor resolution, while those that provide high resolution have limited depth. Positron emission tomography (PET), for example, reveals details deep within tissue but suffers from poor spatial resolution, with each voxel of a PET scan representing thousands or even millions of cells. In contrast, optical microscopy can deliver subcellular spatial resolution but is usually limited to a depth of tens of microns. Optical coherence tomography (OCT) helps bridge the gap between low-resolution/high-penetration and ...

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    21. High-resolution contrast-enhanced optical coherence tomography in mice retinae

      High-resolution contrast-enhanced optical coherence tomography in mice retinae

      Optical coherence tomography (OCT) is a noninvasive interferometric imaging modality providing anatomical information at depths of millimeters and a resolution of micrometers. Conventional OCT images limit our knowledge to anatomical structures alone, without any contrast enhancement. Therefore, here we have, for the first time, optimized an OCT-based contrast-enhanced imaging system for imaging single cells and blood vessels in vivo inside the living mouse retina at subnanomolar sensitivity. We used bioconjugated gold nanorods (GNRs) as exogenous OCT contrast agents. Specifically, we used anti-mouse CD45 coated GNRs to label mouse leukocytes and mPEG-coated GNRs to determine sensitivity of GNR detection in vivo ...

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    22. Feature of the Week 04/02/2016: Contrast-Enhanced Optical Coherence Tomography with Picomolar Sensitivity for Functional in vivo Imaging (with Audio)

      Feature of the Week 04/02/2016:  Contrast-Enhanced Optical Coherence Tomography with Picomolar Sensitivity for Functional in vivo Imaging (with Audio)

      Optical Coherence Tomography (OCT) enables real-time imaging of living tissues with cellular resolution over large 3D fields of view.[1] However, functional and molecular capabilities for OCT remain elusive due to the difficulties of distinguishing exogenous contrast agents from intrinsic tissue scattering and absorption. Previous reports have detailed the use of magnetic probes,[2] absorbent dyes,[3] and gold nanoparticles[4] to produce OCT contrast enhancement through various mechanisms. In the current study, optimized large gold nanorods (LGNRs) and a customized aberration-free spectral detection algorithm were developed to demonstrate an improved platform for molecular imaging with OCT. LGNRs, which produce ...

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    23. Contrast-enhanced optical coherence tomography with picomolar sensitivity for functional in vivo imaging

      Contrast-enhanced optical coherence tomography with picomolar sensitivity for functional in vivo imaging

      Optical Coherence Tomography (OCT) enables real-time imaging of living tissues at cell-scale resolution over millimeters in three dimensions. Despite these advantages, functional biological studies with OCT have been limited by a lack of exogenous contrast agents that can be distinguished from tissue. Here we report an approach to functional OCT imaging that implements custom algorithms to spectrally identify unique contrast agents: large gold nanorods (LGNRs). LGNRs exhibit 110-fold greater spectral signal per particle than conventional GNRs, which enables detection of individual LGNRs in water and concentrations as low as 250 pM in the circulation of living mice. This translates to ...

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    24. Quantitative contrast-enhanced optical coherence tomography

      Quantitative contrast-enhanced optical coherence tomography

      We have developed a model to accurately quantify the signals produced by exogenous scattering agents used for contrast-enhanced Optical Coherence Tomography (OCT). This model predicts distinct concentration-dependent signal trends that arise from the underlying physics of OCT detection. Accordingly, we show that real scattering particles can be described as simplified ideal scatterers with modified scattering intensity and concentration. The relation between OCT signal and particle concentration is approximately linear at concentrations lower than 0.8 particle per imaging voxel. However, at higher concentrations, interference effects cause signal to increase with a square root dependence on the number of particles within ...

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    1-24 of 28 1 2 »
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    System And Method For Molecular In Vivo Imaging And Theranostics Post-doc position at the de la Zerda Lab – Stanford Medical School Optical coherence contrast imaging using gold nanorods in living mice eyes Biofunctionalization of Large Gold Nanorods Realizes Ultrahigh-Sensitivity Optical Imaging Agents Quantitative contrast-enhanced optical coherence tomography Contrast-enhanced optical coherence tomography with picomolar sensitivity for functional in vivo imaging Feature of the Week 04/02/2016:  Contrast-Enhanced Optical Coherence Tomography with Picomolar Sensitivity for Functional in vivo Imaging (with Audio) High-resolution contrast-enhanced optical coherence tomography in mice retinae High sensitivity contrast enhanced optical coherence tomography for functional in vivo imaging Speckle-modulating optical coherence tomography in living mice and humans Non Exudative AMD Imaged With SS-OCT- Extension High space-bandwidth in quantitative phase imaging using partially spatially coherent optical coherence microscopy and deep neural network