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Biomedical photonics is currently one of the fastest growing fields, connecting research in physics, optics, and electrical engineering coupled with medical and biological applications. It allows for the structural and functional analysis of tissues and cells with resolution and contrast unattainable by any other methods. However, the major challenges of many biophotonics techniques are associated with the need to enhance imaging resolution even further to the sub-cellular level as well as translate them for in vivo studies. The tissue optical clearing method uses immersion of tissues into optical clearing agents (OCAs) that reduces the scattering of tissue and makes tissue more transparent and this method has been successfully used ever since. This book is a self-contained introduction to tissue optical clearing, including the basic principles and in vitro biological applications, from in vitro to in vivo tissue optical clearing methods, and combination of tissue optical clearing and various optical imaging for diagnosis. The chapters cover a wide range of issues related to the field of tissue optical clearing: mechanisms of tissue optical clearing in vitro and in vivo; traditional and innovative optical clearing agents; recent achievements in optical clearing of different tissues (including pathological tissues) and blood for optical imaging diagnosis and therapy. This book provides a comprehensive account of the latest research and possibilities of utilising optical clearing as an instrument for improving the diagnostic effectiveness of modern optical diagnostic methods. The book is addressed to biophysicist researchers, graduate students and postdocs of biomedical specialties, as well as biomedical engineers and physicians interested in the development and application of optical methods in medicine. Key features: The first collective reference to collate all known knowledge on this topic Edited by experts in the field with chapter contributions from subject area specialists Brings together the two main approaches in immersion optical clearing into one cohesive book
Optical light propagation in biological tissues guides medical instrument design for diagnosis and treatment of disease. While many instruments are already commercially available and approved for patient use, it is important to continue to push the envelope of new technology development by analyzing new techniques and phenomena of light-tissue interaction. Technology development is necessary for endoscopic surgery because there are still occurrences of injury due to inadequate imaging of anatomy. To aid in future endoscopic instrument design, this dissertation explores the propagation of 1430-1450 nm light in visceral fat, gall bladder, and water as it relates to endoscopic gastroenterological surgery. Technology development is also necessary for traumatic brain injury (TBI) because diagnosis outside of hospitals is currently inadequate to catch all occurrences of the injury. To guide future instrument development, this dissertation explores the propagation of 750-1050 nm light in cranium, brain, and blood as it relates to detection and monitoring of hematomas associated with TBI. The dissertation is organized into two parts of three chapters each: (Part I) Diffuse Optical Transmission through Visceral Fat Tissue, and (Part II) Diffuse Optical Reflectance for Traumatic Brain Injury. Within Part I, the chapters are: (1) Introduction and Modeling of Transmission, (2) Instrumentation Setup and Experimentation Results, and (3) Exploration of Heterogeneities. Within Part II, the chapters are: (4) Introduction and Modeling of Reflectance, (5) Simulation Results and Applications to TBI, and (6) Modeling Optical Probe Efficiency through Hair.
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.
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].
Biomedical optical imaging is a rapidly emerging research area with widespread fundamental research and clinical applications. This book gives an overview of biomedical optical imaging with contributions from leading international research groups who have pioneered many of these techniques and applications. A unique research field spanning the microscopic to the macroscopic, biomedical optical imaging allows both structural and functional imaging. Techniques such as confocal and multiphoton microscopy provide cellular level resolution imaging in biological systems. The integration of this technology with exogenous chromophores can selectively enhance contrast for molecular targets as well as supply functional information on processes such as nerve transduction. Novel techniques integrate microscopy with state-of-the-art optics technology, and these include spectral imaging, two photon fluorescence correlation, nonlinear nanoscopy; optical coherence tomography techniques allow functional, dynamic, nanoscale, and cross-sectional visualization. Moving to the macroscopic scale, spectroscopic assessment and imaging methods such as fluorescence and light scattering can provide diagnostics of tissue pathology including neoplastic changes. Techniques using light diffusion and photon migration are a means to explore processes which occur deep inside biological tissues and organs. The integration of these techniques with exogenous probes enables molecular specific sensitivity.
The book introduces readers to the basic principle of optical imaging technologies. Focusing on human disease diagnostics using optical imaging methods, it provides essential information for researchers in various fields and discusses the latest trends in optical imaging. In recent decades, there has been a huge increase in imaging technologies and their applications in human diseases diagnostics, including magnetic resonance imaging, x-ray computed tomography, and nuclear tomographic imaging. This book promotes further developments to extend optical imaging to a wider range of disease diagnostics. It is a valuable resource for researchers and students in the field of biomedical optics, as well as for clinicians.
Angular Domain Imaging (ADI) is a technique for performing optical imaging through highly scattering media. The basis for the technique is the micro-machined Angular Filter Array (AFA), which provides a parallel collection of micro-tunnels that accept ballistic/quasi-ballistic image-bearing photons and reject multiply scattered photons that result in image-destroying background noise. At high scattering levels, ADI image contrast declines due to the non-uniform scattered background light within the acceptance angle of the AFA. In this thesis, I developed multiple methodologies to correct for this problem and enhance ADI image contrast at higher scattering levels. These methodologies included combining ADI with time gating, polarization gating and employing image processing to estimate the background scattered light and use this information to enhance ADI image contrast and resolution. Furthermore, I conducted a comprehensive experimental investigation on a new AFA geometry designed to reduce the reflections within the micro-tunnels to reduce the unwanted background noise caused by multiply scattered photons. Building on previous studies with ADI in a trans-illumination configuration, I demonstrated that ADI could also be used to capture information-carrying photons from diffuse light back-reflected from tissue, where illumination was from the same side as the AFA. This mode of operation will enable applications of ADI where trans-illumination of samples is not possible. I also developed a tomographic ADI modality that rotated the sample and compiled ADI shadowgrams at each angle into a sinogram, followed by reconstruction of a transverse image with depth information. I also exploited the collimation detection capabilities of the AFA to extract photons emitted by a fluorophore embedded at depth within a turbid medium. The fluorescent imaging system using AFA offered higher resolution and contrast compared to a conventional lens and lens-pinhole fluorescent detection system in both in vitro and animal tests. Optical imaging with an AFA does not depend on coherence of the light source or the wavelength of light. Therefore, it is a promising candidate for multispectral/hyperspectral imaging to localize absorption and/or fluorescence in tissue and may have particular importance in cancer optical imaging.
The early detection and subsequent prevention of cancer have been a challenging task for researchers all over the world. Some of the conventional techniques used for the diagnosis of cancer are mammography, ultrasonography, magnetic resonance imaging (MRI), positron emission tomography (PET) and histopathology. In recent years, optical imaging is being developed as powerful techniques for the early and quick diagnosis of cancer. This book provides the information about polarimetric techniques and their applications in diagnosis of cancer in biological tissues. Polarization gating and Mueller decomposition imaging technique were addressed in the detail with their applications on cervical tissues and mimic of tissues (tissue phantoms). Polarization gated imaging can be used to detect mature tumors in the superficial layers. However, Mueller decomposition images have shown promising results about dysplasia in human cervical tissues. These images can be used to discriminate normal cervical tissue against the dysplastic (pre-cancerous) tissue. These results can be useful for clinical purposes and in the research work for diagnostic tools
Supported with 119 illustrations, this milestone work discusses key optical imaging techniques in self-contained chapters; describes the integration of optical imaging techniques with other modalities like MRI, X-ray imaging, and PET imaging; provides a software platform for multimodal integration; presents cutting-edge computational and data processing techniques that ensure rapid, cost-effective, and precise quantification and characterization of the clinical data; covers advances in photodynamic therapy and molecular imaging, and reviews key clinical studies in optical imaging along with regulatory and business issues.
In this thesis, a new time-dependent model for describing light propagation in biological media is proposed. The model is based on the simplified spherical harmonics approximation and is represented by a set of coupled parabolic partial differential equations (TD-pSPN equations). In addition, the model is extended for modeling the time-dependent response of fluorescent agents in biological tissues and the ensuing time-domain propagation of light therein. In a comparison with Monte Carlo simulations, it is shown that the TD-pSPN equations present unique features in its derivation that makes it a more accurate alternative to the diffusion equation (DE). The TD-pSPN model (for orders N > 1) outperforms the DE in the description of the propagation of light in near-nondiffusive media and in all the physical situations where DE fails. Often, only small orders of the SP N approximation are needed to obtain accurate results. A diffuse optical tomography (DOT) algorithm is also implemented based on the TD-pSPN equations as the forward model using constrained optimization methods. The algorithm uses time-dependent (TD) data directly. Such an approach is benefited from both the accuracy of the SPN models and the richness of TD data. In the calculation of the gradient of the objective function, a time-dependent adjoint differentiation method is introduced that reduces computation time. Several numerical experiments are performed for small geometry media with embedded inclusions that mimic small animal imaging. In these experiments, the values of the optical coefficients are varied within realistic bounds that are representative of those found in the range of the near-infrared spectrum, including high absorption values. Single and multi-parameter reconstructions (absorption and diffusion coefficients) are performed. The reconstructed images based on the TD-pSPN equations (N > 1) give better estimates of the optical properties of the media than the DE. On the other hand, crosstalk effects and small artifacts appeared in all the cases (more intense in the DE images). Comparatively, the reconstructed images show a lesser influence of these undesirable 'effects than other approaches found in the literature. The results suggest that the DOT algorithm based on the TD-pSPN model is an accurate alternative to the DE for imaging optical properties of biological media. These results directly benefict the fields of therapeutics and time-domain optical imaging of biological tissues. Particularly, the presented work is a decisive step in the elaboration of an optical scanner for small animal imaging at our lab. Thus, a positive impact in the areas of clinical diagnosis and biomedical research are expected.