Chick Chorioallantoic Membrane as a Patient-Derived Xenograft Model for Uveal Melanoma : Imaging Modalities for Growth and Vascular Evaluation

Background: Patient-derived tumor xenografts (PDXs) have emerged as valuable preclinical in vivo models in oncology as they largely retain the polygenomic architecture of the human tumors from which they originate. Although animal models are accompanied by cost and time constraints and a low engraftment rate, PDXs have primarily been established in immunodeficient rodent models for the in vivo assessment of tumor characteristics and of novel therapeutic cancer targets. The chick chorioallantoic membrane (CAM) assay represents an attractive alternative in vivo model that has long been used in the research of tumor biology and angiogenesis, and can overcome some of these limitations. Methods: In this study, we reviewed different technical approaches for the establishment and monitoring of a CAM-based uveal melanoma PDX model. Forty-six fresh tumor grafts were acquired after enucleation from six uveal melanoma patients and were implanted onto the CAM on ED7 with Matrigel and a ring (group 1), with Matrigel (group 2), or natively without Matrigel or a ring (group 3). Real-time imaging techniques, such as various ultrasound modalities, optical coherence tomography, infrared imaging, and imaging analyses with Image J for tumor growth and extension, as well as color doppler, optical coherence angiography, and fluorescein angiography for angiogenesis, were performed on ED18 as alternative monitoring instruments. The tumor samples were excised on ED18 for histological assessment. Results: There were no significant differences between the three tested experimental groups regarding the length and width of the grafts during the development period. A statistically significant increase in volume (p = 0.0007) and weight (p = 0.0216) between ED7 and ED18 was only documented for tumor specimens of group 2. A significant correlation of the results for the cross-sectional area, largest basal diameter, and volume was documented between the different imaging and measurement techniques and the excised grafts. The formation of a vascular star around the tumor and of a vascular ring on the base of the tumor was observed for the majority of the viable developing grafts as a sign of successful engraftment. Conclusion: The establishment of a CAM-PDX uveal melanoma model could elucidate the biological growth patterns and the efficacy of new therapeutic options in vivo. The methodological novelty of this study, investigating different implanting techniques and exploiting advances in real-time imaging with multiple modalities, allows precise, quantitative assessment in the field of tumor experimentation, underlying the feasibility of CAM as an in vivo PDX model

Aerospace Medicine and Biology: Cumulative index, 1979

This publication is a cumulative index to the abstracts contained in the Supplements 190 through 201 of 'Aerospace Medicine and Biology: A Continuing Bibliography.' It includes three indexes-subject, personal author, and corporate source

Development of optical Doppler interferometry for the visualization of ocular elasticity and ciliary activity

Functional optical imaging techniques have become increasingly important due to their high resolution and non-invasive nature, and have been used to address many unmet needs in the biomedical imaging field. In the area of ophthalmology, mechanical properties have been shown to be an early indicator of retinal disease, but current imaging modalities are unable to provide high resolution in-vivo imaging to capture the minute changes in the elasticity of thin tissue layers at the back of the eye. For respiratory diseases, the ciliary cell function inside the airway have been discovered to play an important role in respiratory health and the onset of disease. Similarly, current techniques are not equipped to image and characterize the cellular level changes in in-vivo tissues. Phase-resolved Doppler (PRD) imaging is a technology developed by our F-OCT lab, primarily for visualizing blood flow and angiography. Recently, it has been determined that the PRD technique is able to provide high phase sensitivity, which can be used to obtain the tissue displacement as well as particle motions. Using this principle, we developed two types of imaging systems: confocal acoustic radiation force optical coherence elastography (ARF-OCE) and spectrally-encoded interferometric microscopy (SEIM). Using the confocal ARF-OCE system, we present the first spatially mapped elasticity imaging in a live animal retina, and obtained a better understanding of the elasticity of different retinal layers. With the SEIM system, we introduced a novel method of spatially tracking ciliary activity in real-time of in vitro tracheal and oviduct tissues. We demonstrate that the SEIM system can image and quantify ciliary beating frequency and ciliary beating pattern with high speed and large field of view. While both these technologies use the PRD technique, the optical system has been optimized for the respective applications. The results in this dissertation serve as a stepping stone to the optimization and ultimately, the clinical translation of the PRD technique to diagnostic imaging. The developed technology has great potential for clinical diagnosis and management of a number of ocular disease, such as age related macular degeneration, glaucoma, presbyopia and myopia, as well as airway diseases such as asthma

Desarrollo de un modelo animal in vitro para evaluar nuevos fármacos para el tratamiento del ojo seco

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Óptica y Optometría, leída el 19/02/2019In the ophthalmic field, multifactorial pathologies such as Dry Eye Disease (DED) and cataract are largely studied in living animal models that can fail to precisely mirror the complexity of these conditions in humans. Recent advances in biomedical technologies have improved the reliability of in-vitro/ex-vivo animal alternatives, and to date, the corneal and crystalline lens tissue have been independently maintained physiologicallystable for 10 days. This thesis details the development of a novel and complete ex-vivo anterior eye model, which is capable of sustaining both the cornea and crystalline lens in a physiologically stable state in loco for 7 days. The platform is based on porcine eyes, which represent a high quality and reliable human tissue source substitute, and being slaughterhouse waste, also perfectly align the project with the 3Rs principle of replacing, refining and reducing living animal experimentation...Dentro del campo oftalmológico, patologías multifactoriales como Enfermedad del Ojo Seco (EOS) y Cataratas son ampliamente estudiadas a través de modelos animales que no reproducen con exactitud estas condiciones en humanos debido a su complejidad. Los recientes avances en la tecnología biomédica han mejorado la fiabilidad de modelos animales in-vitro/ex-vivo, y hasta el momento, el tejido de la córnea y cristalino se han mantenido fisiológicamente estables de forma independiente durante 10 días. Esta tesis describe el desarrollo de un nuevo y completo modelo de ojo anterior ex vivo, que es capaz de mantener tanto la córnea como el cristalino en un estado fisiológico estable durante 7 días. La plataforma se basa en ojos porcinos, que representan una fuente alternativa al tejido humano de alta calidad y fiable, y al tratarse de residuos de matadero, también alinea perfectamente el proyecto con el principio 3Rs de reemplazar, refinar y reducir la experimentación con animales vivos...Fac. de Óptica y OptometríaTRUEunpu

Aerospace medicine and biology. A continuing bibliography (supplement 231)

This bibliography lists 284 reports, articles, and other documents introduced into the NASA scientific and technical information system in March 1982

Low-cost, High-contrast, and Miniature Optical Imaging Systems for Clinical Applications

Reducing the cost and size and enhancing the contrast of optical imaging systems improve their potentials for clinical applications. In this dissertation, we describe our endeavors towards development of low-cost and compact photoacoustic microscopy and spatial frequency domain imaging systems as well as improvement of photoacoustic tumor imaging using a specifically designed photoacoustic contrast agent. Chapters two and three focus on the development of low-cost and compact laser diode based photoacoustic microscopy systems. We first provided an improvement in light delivery of laser diode based photoacoustic microscopy systems that enables imaging biological tissue with high signal to noise ratio. We then developed a laser scanning laser diode based photoacoustic microscopy system that provides substantial improvement of imaging speed and eliminates the need for mechanical scanning of the sample, hence improving the potentials of low-cost and compact laser diode based photoacoustic microscopy for clinical applications. Chapter four describes synthesis and evaluation of a monomeric porphyrin-based photoacoustic contrast agent for improvement of in vivo tumor imaging. Absorption in near infrared wavelength range, solubility, stability, nontoxicity, and high photoacoustic generation efficiency of the dye were demonstrated. The contrast agent was evaluated for enhancing the photoacoustic images of implanted murine tumors revealing a multi-fold stronger enhancement and a slower washout compared to the benchmark FDA approved indocyanine green (ICG) dye. Favorable filtration and tumor accumulation of the dye further demonstrated its potential as a photoacoustic contrast agent for in vivo tumor imaging. Finally, chapter 5 describes development of a very low-cost, handheld, and multispectral spatial frequency domain imaging system that incorporates nine different light emitting diodes and all illumination and detection optical components in a small 3D-printed probe. The system performance was evaluated on biological tissue to assess its potentials

Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 192

This bibliography lists 247 reports, articles, and other documents introduced into the NASA scientific and technical information system in March 1979

Biomedical Image Processing and Classification

Biomedical image processing is an interdisciplinary field involving a variety of disciplines, e.g., electronics, computer science, physics, mathematics, physiology, and medicine. Several imaging techniques have been developed, providing many approaches to the study of the human body. Biomedical image processing is finding an increasing number of important applications in, for example, the study of the internal structure or function of an organ and the diagnosis or treatment of a disease. If associated with classification methods, it can support the development of computer-aided diagnosis (CAD) systems, which could help medical doctors in refining their clinical picture