In this article we present a detailed discussion of noise sources in Fourier Domain Optical Coherence Tomography (FDOCT) setups. The performance of FDOCT with charge coupled device (CCD) cameras is compared to current standard time domain OCT systems. We describe how to measure sensitivity in the case of FDOCT and confirm the theoretically obtained values. It is shown that FDOCT systems have a large sensitivity advantage and allow for sensitivities well above 80dB, even in situations with low light levels and high speed detection.

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Performance of fourier domain vs. time domain optical coherence tomography.

1.1 Photodynamic Therapy and Imaging
The purpose of this review is to present the current state of the role of imaging in photodynamic therapy (PDT). In order for the reader to fully appreciate the context of the discussions embodied in this article we begin with an overview of the PDT process, starting with a brief historical perspective followed by detailed discussions of specific applications of imaging in PDT. Each section starts with an overview of the specific topic and, where appropriate, ends with summary and future directions. The review closes with the authors’ perspective of the areas of future emphasis and promise. The basic premise of this review is that a combination of imaging and PDT will provide improved research and therapeutic strategies.

PDT is a photochemistry-based approach that uses a light-activatable chemical, termed a photosensitizer (PS), and light of an appropriate wavelength, to impart cytotoxicity via the generation of reactive molecular species (Figure 1a). In clinical settings, the PS is typically administered intravenously or topically, followed by illumination using a light delivery system suitable for the anatomical site being treated (Figure 1b). The time delay, often referred to as drug-light interval, between PS administration and the start of illumination with currently used PSs varies from 5 minutes to 24 hours or more depending on the specific PS and the target disease. Strictly speaking, this should be referred to as the PS-light interval, as at the concentrations typically used the PS is not a drug, but the drug-light interval terminology seems to be used fairly frequently. Typically, the useful range of wavelengths for therapeutic activation of the PS is 600 to 800 nm, to avoid interference by endogenous chromophores within the body, and yet maintain the energetics necessary for the generation of cytotoxic species (as discussed below) such as singlet oxygen (1O2). However, it is important to note that photosensitizers can also serve as fluorescence imaging agents for which activation with light in the 400nm range is often used and has been extremely useful in diagnostic imaging applications as described extensively in Section 2 of this review. The obvious limitation of short wavelength excitation is the lack of tissue penetration so that the volumes that are probed under these conditions are relatively shallow.






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Figure 1


(A) A schematic representation of PDT where PS is a photoactivatable multifunctional agent, which, upon light activation can serve as both an imaging agent and a therapeutic agent. (B) A schematic representation of the sequence of administration, localization and light activation of the PS for PDT or fluorescence imaging. Typically the PS is delivered systemically and allowed to circulate for an appropriate time interval (the “drug-light interval”), during which the PS accumulates preferentially in the target lesion(s) prior to light activation. In the idealized depiction here the PS is accumulation is shown to be entirely in the target tissue, however, even if this is not the case, light delivery confers a second layer of selectivity so that the cytotoxic effect will be generated only in regions where both drug and light are present. Upon localization of the PS, light activation will result in fluorescence emission which can be implemented for imaging applications, as well as generation cytotoxic species for therapy. In the former case light activation is achieved with a low fluence rate to generate fluorescence emission with little or no cytotoxic effect, while in the latter case a high fluence rate is used to generate a sufficient concentration of cytotoxic species to achieve biological effects.

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Imaging and photodynamic therapy: mechanisms, monitoring, and optimization.

There have been three basic approaches to optical tomography since the early 1980s: diffraction tomography, diffuse optical tomography and optical coherence tomography (OCT). Optical techniques are of particular importance in the medical field, because these techniques promise to be safe and cheap and, in addition, offer a therapeutic potential. Advances in OCT technology have made it possible to apply OCT in a wide variety of applications but medical applications are still dominating. Specific advantages of OCT are its high depth and transversal resolution, the fact, that its depth resolution is decoupled from transverse resolution, high probing depth in scattering media, contact-free and non-invasive operation, and the possibility to create various function dependent image contrasting methods. This report presents the principles of OCT and the state of important OCT applications. OCT synthesises cross-sectional images from a series of laterally adjacent depth-scans. At present OCT is used in three different fields of optical imaging, in macroscopic imaging of structures which can be seen by the naked eye or using weak magnifications, in microscopic imaging using magnifications up to the classical limit of microscopic resolution and in endoscopic imaging, using low and medium magnification. First, OCT techniques, like the reflectometry technique and the dual beam technique were based on time-domain low coherence interferometry depth-scans. Later, Fourier-domain techniques have been developed and led to new imaging schemes. Recently developed parallel OCT schemes eliminate the need for lateral scanning and, therefore, dramatically increase the imaging rate. These schemes use CCD cameras and CMOS detector arrays as photodetectors. Video-rate three-dimensional OCT pictures have been obtained. Modifying interference microscopy techniques has led to high-resolution optical coherence microscopy that achieved sub-micrometre resolution. This report is concluded with a short presentation of important OCT applications. Ophthalmology is, due to the transparent ocular structures, still the main field of OCT application. The first commercial instrument too has been introduced for ophthalmic diagnostics (Carl Zeiss Meditec AG). Advances in using near-infrared light, however, opened the path for OCT imaging in strongly scattering tissues. Today, optical in vivo biopsy is one of the most challenging fields of OCT application. High resolution, high penetration depth, and its potential for functional imaging attribute to OCT an optical biopsy quality, which can be used to assess tissue and cell function and morphology in situ. OCT can already clarify the relevant architectural tissue morphology. For many diseases, however, including cancer in its early stages, higher resolution is necessary. New broad-bandwidth light sources, like photonic crystal fibres and superfluorescent fibre sources, and new contrasting techniques, give access to new sample properties and unmatched sensitivity and resolution.

/pdf/optical-coherence-tomography-principles-and-applications-17y32cabbm.pdf

Optical coherence tomography - principles and applications

Objective: To demonstrate optical coherence tomography for high-resolution, noninvasive imaging of the human retina. Optical coherence tomography is a new imaging technique analogous to ultrasound B scan that can provide cross-sectional images of the retina with micrometer-scale resolution. Design: Survey optical coherence tomographic examination of the retina, including the macula and optic nerve head in normal human subjects. Settings Research laboratory. Participants: Convenience sample of normal human subjects. Main Outcome Measures: Correlation of optical coherence retinal tomographs with known normal retinal anatomy. Results: Optical coherence tomographs can discriminate the cross-sectional morphologic features of the fovea and optic disc, the layered structure of the retina, and normal anatomic variations in retinal and retinal nerve fiber layer thicknesses with 10- μm depth resolution. Conclusion: Optical coherence tomography is a potentially useful technique for high depth resolution, cross-sectional examination of the fundus.

Optical Coherence Tomography of the Human Retina

This paper reviews the state of the art of optical coherence tomography (OCT), an interferometric imaging technique that provides cross-sectional views of the subsurface microstructure of biological tissue. Following a discussion of the basic theory of OCT, an overview of the issues involved in the design of the main components of OCT systems is presented. The review concludes by introducing new imaging modes being developed to extract additional diagnostic information.

Optical coherence tomography (OCT): a review

We describe a novel optical system for bidirectional color Doppler imaging of flow in biological tissues with micrometer-scale resolution and demonstrate its use for in vivo imaging of blood flow in an animal model. Our technique, color Doppler optical coherence tomography (CDOCT), performs spatially localized optical Doppler velocimetry by use of scanning low-coherence interferometry. CDOCT is an extension of optical coherence tomography (OCT), employing coherent signal-acquisition electronics and joint time-frequency analysis algorithms to perform flow imaging simultaneous with conventional OCT imaging. Cross-sectional maps of blood flow velocity with <50-µm spatial resolution and <0.6-mm/s velocity precision were obtained through intact skin in living hamster subdermal tissue. This technology has several potential medical applications.

In vivo bidirectional color Doppler flow imaging of picoliter blood volumes using optical coherence tomography.

An optical coherence tomography system is described which can image up to video rate. The system utilizes a high power broadband source and real time image acquisition hardware and features a high speed scanning delay line in the reference arm based on Fourier-transform pulse shaping technology. The theory of low coherence interferometry with a dispersive delay line, and the operation of the delay line are detailed and the design equations of the system are presented. Real time imaging is demonstrated in vivo in tissues relevant to early human disease diagnosis (skin, eye) and in an important model in developmental biology (Xenopus laevis).

In vivo video rate optical coherence tomography.

We describe a novel optical system for bidirectional color Doppler imaging of flow in biological tissues with micrometer-scale resolution and demonstrate its use for in vivo imaging of blood flow in an animal model. Our technique, color Doppler optical coherence tomography (CDOCT), performs spatially localized optical Doppler velocimetry by use of scanning low-coherence interferometry. CDOCT is an extension of optical coherence tomography (OCT), employing coherent signal-acquisition electronics and joint time-frequency analysis algorithms to perform flow imaging simultaneous with conventional OCT imaging. Cross-sectional maps of blood flow velocity with <50-μm spatial resolution and <0.6-mm/s velocity precision were obtained through intact skin in living hamster subdermal tissue. This technology has several potential medical applications.

In vivo bidirectional color Doppler flow imaging of picoliter blood volumes using optical coherence tomography

Optical coherence tomography (OCT) and optical coherence microscopy (OCM) are novel techniques for noninvasive biomedical imaging based on low-coherence interferometry. OCT achieves high-spatial resolution ( 100 dB) in a fiber-optically integrated system which is suitable for application in minimally invasive diagnostics, including endoscopy. The technique of OCM combines the depth-ranging capability of OCT with the micron-scale resolution imaging capability of confocal microscopy to extend the available imaging depth of confocal microscopy up to several hundred micrometers deep in highly scattering tissues. The theoretical and technical bases for OCT and OCM imaging are described. Example OCT images are provided in gastrointestinal (GI) tissues to illustrate contrast between histological layers of the GI mucosa and differentiation of the mucosa from submucosa. Example OCM images revealing cellular-level microstructure up to several hundred micrometers deep in GI tissue are presented for the first time. The potential applications of OCT and OCM imaging in clinical diagnostic medicine are discussed.

Optical coherence tomography and microscopy in gastrointestinal tissues

The present invention provides an improved optical coherence tomography system and involves estimating the impulse response (which is indicative of the actual reflecting and scattering sites within a tissue sample) from the output interferometric signal of an interferometer according to the following steps: (a) acquiring auto-correlation data from the interferometer system; (b) acquiring cross-correlation data from the interferometer system having the biological tissue sample in the sample arm; and (c) processing the auto-correlation data and the cross correlation data to produce an optical impulse response of the tissue The impulse response may be obtained from the cross-correlation and auto-correlation data by: (d) obtaining an auto-power spectrum from the auto-correlation data by performing a Fourier transform on the auto-correlation data; (e) obtaining a cross-power spectrum from the cross-correlation data by performing a Fourier transform on the cross-correlation data; (f) obtaining a transfer function of the LSI system by taking a ratio of the cross-power spectrum to the auto-power spectrum; and (g) obtaining the optical impulse response of the LSI system by performing an inverse-Fourier transform on the transfer function Preferably, coherent demodulation is used in combination with the above deconvolution technique to resolve closely-spaced reflecting sites in the sample By utilizing both the magnitude and phase data of the demodulated interferometric signals, the OCT system of the present invention is able to distinguish between closely spaced reflecting sites within the sample

Manish D. Kulkarni

Papers

In vivo bidirectional color Doppler flow imaging of picoliter blood volumes using optical coherence tomography.

In vivo video rate optical coherence tomography.

In vivo bidirectional color Doppler flow imaging of picoliter blood volumes using optical coherence tomography

Optical coherence tomography and microscopy in gastrointestinal tissues

Image enhancement in optical coherence tomography using deconvolution