We present theoretical and experimental results which demonstrate the superior sensitivity of swept source (SS) and Fourier domain (FD) optical coherence tomography (OCT) techniques over the conventional time domain (TD) approach. We show that SS- and FD-OCT have equivalent expressions for system signal-to-noise ratio which result in a typical sensitivity advantage of 20-30dB over TD-OCT. Experimental verification is provided using two novel spectral discrimination (SD) OCT systems: a differential fiber-based 800nm FD-OCT system which employs deep-well photodiode arrays, and a differential 1300nm SS-OCT system based on a swept laser with an 87nm tuning range.

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Sensitivity advantage of swept source and Fourier domain optical coherence tomography

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.

/pdf/imaging-and-photodynamic-therapy-mechanisms-monitoring-and-76rc7acuq5.pdf

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

Amplitude decorrelation measurement is sensitive to transverse flow and immune to phase noise in comparison to Doppler and other phase-based approaches. However, the high axial resolution of OCT makes it very sensitive to the pulsatile bulk motion noise in the axial direction. To overcome this limitation, we developed split-spectrum amplitude-decorrelation angiography (SSADA) to improve the signal-to-noise ratio (SNR) of flow detection. The full OCT spectrum was split into several narrower bands. Inter-B-scan decorrelation was computed using the spectral bands separately and then averaged. The SSADA algorithm was tested on in vivo images of the human macula and optic nerve head. It significantly improved both SNR for flow detection and connectivity of microvascular network when compared to other amplitude-decorrelation algorithms.

/pdf/split-spectrum-amplitude-decorrelation-angiography-with-5066x1kwi2.pdf

Split-spectrum amplitude-decorrelation angiography with optical coherence tomography

The diffraction tomography theorem is adapted to one-dimensional length measurement. The resulting spectral interferometry technique is described and the first length measurements using this technique on a model eye and on a human eye in vivo are presented.

Measurement of intraocular distances by backscattering spectral interferometry

https://stuff.mit.edu/afs/athena/course/2/2.717/www/sp_oct_fercher_95.pdf

Determination of the complex refractive index of a thick slab material from its spectral reflectance and transmittance at normal incidence

Glasses having composition (B 2 O 3 ) 25 (PbO) 70 (Al 2 O 3 ) 5 (Sm 2 O 3 ) x ,where x =0, 0.5, 1, 2, 3 and 5 g were prepared using the normal melt quench technique. Spectral reflectance and transmittance at normal incidence of the glass samples are recorded with a spectrophotometer in the spectral range 220–2200 nm. These measured values are introduced into analytical expressions to calculate the real and imaginary parts of the refractive indices. Wemple–DiDomenico single oscillator model and one-term Sellmeier dispersion relations are used to model the real refractive indices. Dispersion parameters such as: single oscillator energy, dispersion energy, lattice oscillating strength, average oscillator wavelength, average oscillator strength and Abbe's number are deduced and compared. Absorption dispersion parameters such as: Fermi energy, optical energy gap for direct and indirect transitions, Urbach energy and steepness parameter are calculated. Effects of doping Sm 2 O 3 on these linear optical parameters are investigated and interpreted.

S.Y. El-Zaiat

Papers

Measurement of intraocular distances by backscattering spectral interferometry

Measurement of intraocular distances by backscattering spectral interferometry

Determination of the complex refractive index of a thick slab material from its spectral reflectance and transmittance at normal incidence

Spectral dispersion of linear optical properties for sm2o3 doped b2o3–pbo–al2o3 glasses

Interferometric determination of the birefringence dispersion of anisotropic materials