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Experiments directed towards a clinically useful optical imaging system use long-pulse near-infrared lasers and a correlation time gate based on degenerate four-wave mixing in a nonlinear medium.
This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The authors have demonstrated the use of a degenerate-four-wave-mixing time gate to allow imaging through turbid media, with potential application to tissue imaging. A near infrared (NIR), long-pulse Cr{sup +3}:Li2SrAlF6 laser was used as the light source (during most the project) for imaging through clear and turbid media. Preliminary experiments were also carried out with a continuous diode laser.
The use of light for probing and imaging biomedical media is promising for the development of safe, noninvasive, and inexpensive clinical imaging modalities with diagnostic ability. The advent of ultrafast lasers has enabled applications of nonlinear optical processes, which allow deeper imaging in biological tissues with higher spatial resolution. This book provides an overview of emerging novel optical imaging techniques, Gaussian beam optics, light scattering, nonlinear optics, and nonlinear optical tomography of tissues and cells. It consists of pioneering works that employ different linear and nonlinear optical imaging techniques for deep tissue imaging, including the new applications of single- and multiphoton excitation fluorescence, Raman scattering, resonance Raman spectroscopy, second harmonic generation, stimulated Raman scattering gain and loss, coherent anti-Stokes Raman spectroscopy, and near-infrared and mid-infrared supercontinuum spectroscopy. The book is a comprehensive reference of emerging deep tissue imaging techniques for researchers and students working in various disciplines.
SPIE Milestones are collections of seminal papers from the world literature covering important discoveries and developments in optics and photonics.
This entry-level textbook, covering the area of tissue optics, is based on the lecture notes for a graduate course (Bio-optical Imaging) that has been taught six times by the authors at Texas A&M University. After the fundamentals of photon transport in biological tissues are established, various optical imaging techniques for biological tissues are covered. The imaging modalities include ballistic imaging, quasi-ballistic imaging (optical coherence tomography), diffusion imaging, and ultrasound-aided hybrid imaging. The basic physics and engineering of each imaging technique are emphasized. A solutions manual is available for instructors; to obtain a copy please email the editorial department at [email protected].
"Nonlinear optical biomedical imaging techniques have attracted a great amount of interest starting with the first demonstration of two-photon fluorescence (TPF) imaging by Webb's group in the 1990s. The various imaging formats and applications reported have revolutionized the field of biomedical imaging, offering great advantages including high resolution, internal three-dimensional sectioning ability, and functional imaging capability. This thesis focuses on exploring the development and novel application of nonlinear optical techniques and extending previous work in transmission mode nonlinear absorption imaging. The topical pharmacological introduction of molecules and drugs to the ocular surface is a common means of assessing and treating a variety of pathological ocular conditions. However, no reliable method exists to date for the quantification of actual delivered dosage with high enough resolution. We developed a two-photon fluorescence (TPF) system capable of quantifying, with micron-level axial resolution, the distribution and concentration of fluorescent or fluorescently-tagged chemicals and drugs in live feline corneas. With this high-resolution method, we were able to measure, for the first time, both the penetration depth and concentrations of molecules applied topically to the ocular surface, either with an intact or removed epithelial layer. As a proof of concept, we tested two classes of fluorescent molecules- Fluorescein and Riboflavin- which are commonly used in ophthalmologic practice. Finally, we used our TPF instrument to test the barrier function of the corneal epithelium and to measure the concentration of non-fluorescent molecules (in this case, dextrans) conjugated to fluorescent dyes as they diffused across the cornea. A pump-probe based technique has been applied in biomedical imaging by Prof. Warren Warren's group recently. They reported images with endogenous contrast agents (hemoglobin and melanin) in biological tissue in a transmission mode with two pulsed laser systems to generate two wavelengths for the pump and probe beam. We built two simplified systems with only one Ti:Sapphire laser. In both systems, the pump and probe beam were selected from a broadband source, which was generated by either broadening the spectrum with a holey fiber or a 27 fs KM laser, which has a broad spectrum itself. We explored the capability of imaging in tissue-like turbid media in the backscattering mode, and studied the achievable imaging depth for the first time. By simulating using Monte Carlo based methods, we further optimized the detection geometry and improved the photon collection efficiency. Also, we compared this nonlinear absorption technique with the more commonly used TPF method. We finally obtained pump probe signals and images using quantum dots as a nonlinear medium. This could be important in future studies of toxicity in skin-care products"--Leaves vi-vii.