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DEVELOPMENT OF OPTICAL COHERENCE TOMOGRAPHY FOR TISSUE DIAGNOSTICS
Title
DEVELOPMENT OF OPTICAL COHERENCE TOMOGRAPHY FOR TISSUE DIAGNOSTICS.
Creator
Meemon, Panomsak, Rolland, Jannick, University of Central Florida
Abstract / Description
Microvasculature can be found in almost every part of the human body, including the internal organs. Importantly, abnormal changes in microvasculature are usually related to pathological development of the tissue cells. Monitoring of changes in blood flow properties in microvasculature, therefore, provides useful diagnostic information about pathological conditions in biological tissues as exemplified in glaucoma, diabetes, age related macular degeneration, port wine stains, burn-depth, and...
Show moreMicrovasculature can be found in almost every part of the human body, including the internal organs. Importantly, abnormal changes in microvasculature are usually related to pathological development of the tissue cells. Monitoring of changes in blood flow properties in microvasculature, therefore, provides useful diagnostic information about pathological conditions in biological tissues as exemplified in glaucoma, diabetes, age related macular degeneration, port wine stains, burn-depth, and potentially skin cancer. However, the capillary network is typically only one cell in wall thickness with 5 to 10 microns in diameter and located in the dermis region of skin. Therefore, a non-invasive flow imaging technique that is capable of depth sectioning at high resolution and high speed is demanded. Optical coherence tomography (OCT), particularly after its advancement in frequency domain OCT (FD-OCT), is a promising tool for non-invasive high speed, high resolution, and high sensitivity depth-resolved imaging of biological tissues. Over the last ten years, numerous efforts have been paid to develop OCT-based flow imaging techniques. An important effort is the development of phase-resolved Doppler OCT (PR-DOCT). Phase-resolved Doppler imaging using FD-OCT is particularly of interest because of the direct access to the phase information of the depth profile signal. Furthermore, the high speed capability of FD-OCT is promising for real time flow monitoring as well as 3D flow segmentation applications. However, several challenges need to be addressed; 1) Flow in biological samples exhibits a wide dynamic range of flow velocity caused by, for example, the variation in the flow angles, flow diameters, and functionalities. However, the improvement in imaging speed of FD-OCT comes at the expense of a reduction in sensitivity to slow flow information and hence a reduction in detectable velocity range; 2) A structural ambiguity so-called 'mirror image' in FD-OCT prohibits the use of maximum sensitivity and imaging depth range; 3) The requirement of high lateral resolution to resolve capillary vessels requires the use of an imaging optics with high numerical aperture (NA) that leads to a reduction in depth of focus (DOF) and hence the imaging depth range (i.e. less than 100 microns) unless dynamic focusing is performed. Nevertheless, intrinsic to the mechanism of FD-OCT, dynamic focusing is not possible. In this dissertation, the implementation of PR-DOCT in a high speed swept-source based FD-OCT is investigated and optimized. An acquisition scheme as well as a processing algorithm that effectively extends the detectable velocity dynamic range of the PR-DOCT is presented. The proposed technique increased the overall detectable velocity dynamic range of PR-DOCT by about five times of that achieved by the conventional method. Furthermore, a novel technique of mirror image removal called ÂÂ'Dual-Detection FD-OCTÂÂ' (DD-FD-OCT) is presented. One of the advantages of DD-FD-OCT to Doppler imaging is that the full-range signal is achieved without manipulation of the phase relation between consecutive axial lines. Hence the full-range DD-FD-OCT is fully applicable to phase-resolved Doppler detection without a reduction in detectable velocity dynamic range as normally encountered in other full-range techniques. In addition, PR- DOCT can utilize the maximum signal-to-noise ratio provided by the full-range capability. This capability is particularly useful for imaging of blood flow that locates deep below the sample surface, such as blood flow at deep posterior human eye and blood vessels network in the dermis region of human skin. Beside high speed and functional imaging capability, another key parameter that will open path for optical diagnostics using OCT technology is high resolution imaging (i.e. in a regime of a few microns or sub-micron). Even though the lateral resolution of OCT can be independently improved by opening the NA of the imaging optics, the high lateral resolution is maintained only over a short range as limited by the depth of focus that varies inversely and quadratically with NA. Recently developed by our group, ÂÂ'Gabor-Domain Optical Coherence MicroscopyÂÂ' (GD-OCM) is a novel imaging technique capable for invariant resolution of about 2-3 microns over a 2 mm cubic field-of-view. This dissertation details the imaging protocol as well as the automatic data fusion method of GD-OCM developed to render an in-focus high-resolution image throughout the imaging depth of the sample in real time. For the application of absolute flow measurement as an example, the precise information about flow angle is required. GD-OCM provides more precise interpretation of the tissue structures over a large field-of-view, which is necessary for accurate mapping of the flow structure and hence is promising for diagnostic applications particularly when combined with Doppler imaging. Potentially, the ability to perform high resolution OCT imaging inside the human body is useful for many diagnostic applications, such as providing an accurate map for biopsy, guiding surgical and other treatments, monitoring the functional state and/or the post-operative recovery process of internal organs, plaque detection in arteries, and early detection of cancers in the gastrointestinal tract. Endoscopic OCT utilizes a special miniature probe in the sample arm to access tubular organs inside the human body, such as the cardiovascular system, the lung, the gastrointestinal tract, the urinary tract, and the breast duct. We present an optical design of a dynamic focus endoscopic probe that is capable of about 4 to 6 microns lateral resolution over a large working distance (i.e. up to 5 mm from the distal end of the probe). The dynamic focus capability allows integration of the endoscopic probe to GD-OCM imaging to achieve high resolution endoscopic tomograms. We envision the future of this developing technology as a solution to high resolution, minimally invasive, depth-resolved imaging of not only structure but also the microvasculature of in vivo biological tissues that will be useful for many clinical applications, such as dermatology, ophthalmology, endoscopy, and cardiology. The technology is also useful for animal study applications, such as the monitoring of an embryoÂÂ's heart for the development of animal models and monitoring of changes in blood circulation in response to external stimulus in small animal brains.
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Date Issued
2010
Identifier
CFE0003442, ucf:48392
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0003442
GABOR DOMAIN OPTICAL COHERENCE MICROSCOPY
Title
GABOR DOMAIN OPTICAL COHERENCE MICROSCOPY.
Creator
Murali, Supraja, Rolland, Jannick, University of Central Florida
Abstract / Description
Time domain Optical Coherence Tomography (TD-OCT), first reported in 1991, makes use of the low temporal coherence properties of a NIR broadband laser to create depth sectioning of up to 2mm under the surface using optical interferometry and point to point scanning. Prior and ongoing work in OCT in the research community has concentrated on improving axial resolution through the development of broadband sources and speed of image acquisition through new techniques such as Spectral domain OCT ...
Show moreTime domain Optical Coherence Tomography (TD-OCT), first reported in 1991, makes use of the low temporal coherence properties of a NIR broadband laser to create depth sectioning of up to 2mm under the surface using optical interferometry and point to point scanning. Prior and ongoing work in OCT in the research community has concentrated on improving axial resolution through the development of broadband sources and speed of image acquisition through new techniques such as Spectral domain OCT (SD-OCT). In SD-OCT, an entire depth scan is acquired at once with a low numerical aperture (NA) objective lens focused at a fixed point within the sample. In this imaging geometry, a longer depth of focus is achieved at the expense of lateral resolution, which is typically limited to 10 to 20 µm. Optical Coherence Microscopy (OCM), introduced in 1994, combined the advantages of high axial resolution obtained in OCT with high lateral resolution obtained by increasing the NA of the microscope placed in the sample arm. However, OCM presented trade-offs caused by the inverse quadratic relationship between the NA and the DOF of the optics used. For applications requiring high lateral resolution, such as cancer diagnostics, several solutions have been proposed including the periodic manual re-focusing of the objective lens in the time domain as well as the spectral domain C-mode configuration in order to overcome the loss in lateral resolution outside the DOF. In this research, we report for the first time, high speed, sub-cellular imaging (lateral resolution of 2 µm) in OCM using a Gabor domain image processing algorithm with a custom designed and fabricated dynamic focus microscope interfaced to a Ti:Sa femtosecond laser centered at 800 nm within an SD-OCM configuration. It is envisioned that this technology will provide a non-invasive replacement for the current practice of multiple biopsies for skin cancer diagnosis. The research reported here presents three important advances to this technology all of which have been demonstrated in full functional hardware conceived and built during the course of this research. First, it has been demonstrated that the coherence gate created by the femtosecond laser can be coupled into a scanning optical microscope using optical design methods to include liquid lens technology that enables scanning below the surface of skin with no moving parts and at high resolution throughout a 2×2×2 mm imaging cube. Second, the integration the variable-focus liquid lens technology within a fixed-optics microscope custom optical design helped increase the working NA by an order of magnitude over the limitation imposed by the liquid lens alone. Thus, this design has enabled homogenous axial and lateral resolution at the micron-level (i.e., 2 µm) while imaging in the spectral domain, and still maintaining in vivo speeds. The latest images in biological specimens clearly demonstrate sub-cellular resolution in all dimensions throughout the imaging volume. Third, this new modality for data collection has been integrated with an automated Gabor domain image registration and fusion algorithm to provide full resolution images across the data cube in real-time. We refer to this overall OCM method as Gabor domain OCM (GD-OCM). These advantages place GD-OCM in a unique position with respect to the diagnosis of cancer, because when fully developed, it promises to enable fast and accurate screening for early symptoms that could lead to prevention. The next step for this technology is to apply it directly, in a clinical environment. This step is underway and is expected to be reported by the next generation of researchers within this group.
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Date Issued
2009
Identifier
CFE0002771, ucf:48137
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0002771