A technique called optical coherence tomography (OCT) has been developed for noninvasive cross-sectional imaging in biological systems. OCT uses low-coherence interferometry to produce a two-dimensional image of optical scattering from internal tissue microstructures in a way that is analogous to ultrasonic pulse-echo imaging. OCT has longitudinal and lateral spatial resolutions of a few micrometers and can detect reflected signals as small as approximately 10(-10) of the incident optical power. Tomographic imaging is demonstrated in vitro in the peripapillary area of the retina and in the coronary artery, two clinically relevant examples that are representative of transparent and turbid media, respectively.

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Optical coherence tomography

Optical coherence tomography (OCT) has developed rapidly since its first realisation in medicine and is currently an emerging technology in the diagnosis of skin disease. OCT is an interferometric technique that detects reflected and backscattered light from tissue and is often described as the optical analogue to ultrasound. The inherent safety of the technology allows for in vivo use of OCT in patients. The main strength of OCT is the depth resolution. In dermatology, most OCT research has turned on non-melanoma skin cancer (NMSC) and non-invasive monitoring of morphological changes in a number of skin diseases based on pattern recognition, and studies have found good agreement between OCT images and histopathological architecture. OCT has shown high accuracy in distinguishing lesions from normal skin, which is of great importance in identifying tumour borders or residual neoplastic tissue after therapy. The OCT images provide an advantageous combination of resolution and penetration depth, but specific studies of diagnostic sensitivity and specificity in dermatology are sparse. In order to improve OCT image quality and expand the potential of OCT, technical developments are necessary. It is suggested that the technology will be of particular interest to the routine follow-up of patients undergoing non-invasive therapy of malignant or premalignant keratinocyte tumours. It is speculated that the continued technological development can propel the method to a greater level of dermatological use.

https://link.springer.com/content/pdf/bfm%3A978-3-319-06419-2%2F1.pdf

Optical Coherence Tomography

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.

/pdf/sensitivity-advantage-of-swept-source-and-fourier-domain-aiocziabas.pdf

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.

/pdf/performance-of-fourier-domain-vs-time-domain-optical-laf792eoow.pdf

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

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

We present what is to our knowledge the first in vivo tomograms of human retina obtained by Fourier domain optical coherence tomography. We would like to show that this technique might be as powerful as other optical coherence tomography techniques in the ophthalmologic imaging field. The method, experimental setup, data processing, and images are discussed.

https://www.spiedigitallibrary.org/journals/Journal-of-Biomedical-Optics/volume-7/issue-03/0000/In-vivo-human-retinal-imaging-by-Fourier-domain-optical-coherence/10.1117/1.1482379.pdf

Adolf Friedrich Fercher

Papers

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

Optical coherence tomography - principles and applications

Measurement of intraocular distances by backscattering spectral interferometry

Measurement of intraocular distances by backscattering spectral interferometry

In vivo human retinal imaging by Fourier domain optical coherence tomography.