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

Femtosecond filamentation in transparent media

Noble metal nanoparticles are capable of confining resonant photons in such a manner as to induce coherent surface plasmon oscillation of their conduction band electrons, a phenomenon leading to two important properties. Firstly, the confinement of the photon to the nanoparticle's dimensions leads to a large increase in its electromagnetic field and consequently great enhancement of all the nanoparticle's radiative properties, such as absorption and scattering. Moreover, by confining the photon's wavelength to the nanoparticle's small dimensions, there exists enhanced imaging resolving powers, which extend well below the diffraction limit, a property of considerable importance in potential device applications. Secondly, the strongly absorbed light by the nanoparticles is followed by a rapid dephasing of the coherent electron motion in tandem with an equally rapid energy transfer to the lattice, a process integral to the technologically relevant photothermal properties of plasmonic nanoparticles. Of all the possible nanoparticle shapes, gold nanorods are especially intriguing as they offer strong plasmonic fields while exhibiting excellent tunability and biocompatibility. We begin this review of gold nanorods by summarizing their radiative and nonradiative properties. Their various synthetic methods are then outlined with an emphasis on the seed-mediated chemical growth. In particular, we describe nanorod spontaneous self-assembly, chemically driven assembly, and polymer-based alignment. The final section details current studies aimed at applications in the biological and biomedical fields.

Gold Nanorods: From Synthesis and Properties to Biological and Biomedical Applications

The interaction of light within tissue has been used to recognize disease since the mid-1800s. The recent developments of small light sources, detectors, and fiber optic probes provide opportunities to quantitatively measure these interactions, which yield information for diagnosis at the biochemical, structural, or (patho)physiological level within intact tissues. However, because of the strong scattering properties of tissues, the reemitted optical signal is often influenced by changes in biochemistry (as detected by these spectroscopic approaches) and by physiological and pathophysiological changes in tissue scattering. One challenge of biomedical optics is to uncouple the signals influenced by biochemistry, which themselves provide specificity for identifying diseased states, from those influenced by tissue scattering, which are typically unspecific to a pathology. In this review, we describe optical interactions pursued for biomedical applications (fluorescence, fluorescence lifetime, phosphorescence, and Raman from cells, cultures, and tissues) and then provide a descriptive framework for light interaction based upon tissue absorption and scattering properties. Finally, we review important endogenous and exogenous biological chromophores and describe current work to employ these signals for detection and diagnosis of disease.

Quantitative optical spectroscopy for tissue diagnosis

The transport of photons through a slab of random medium is shown to deviate from the diffusion approximation when z/${\mathit{l}}_{\mathit{t}}$ is small, where z is the thickness of the slab and ${\mathit{l}}_{\mathit{t}}$ is the transport mean free path. When z/${\mathit{l}}_{\mathit{t}}$=10 and z=10 mm, the average time of arrival is about 0.9 times that predicted by diffusion theory. Photons are found to arrive earlier than that predicted by the diffusion theory as z/${\mathit{l}}_{\mathit{t}}$ becomes smaller or the anisotropic scattering increases.

When does the diffusion approximation fail to describe photon transport in random media

Studies of Raman scattering, fluorescence and time-resolved light scattering were conducted on cancer and normal biomedical media. Fourier transform Raman spectroscopic measurements were performed on human normal, benign and cancerous tissues from gynecological (GYN) tracts. A comparison of the intensity differences between various Raman modes as well as the number of Raman lines, enables one to distinguish normal GYN tissues from diseased tissues. Fluorescence spectroscopic measurements on human breast tissues show that the ratio of fluorescence intensity at 340 nm to that at 440 nm can be used to distinguish between cancerous and non-cancerous tissues. Separate studies on normal and cancerous breast cell lines show spectral differences. The measurements of back-scattered ultrafast laser pulses from human breast tissues show differences in the scattered pulse profiles for different tissues. These studies show that various optical techniques have the potential to be used in medical diagnostic applications.

Raman, fluorescence, and time-resolved light scattering as optical diagnostic techniques to separate diseased and normal biomedical media.

With an ultrafast time-gated optical detection method, a thin translucent strip of fat (2.5 mm thick) hidden inside a 4-cm-thick tissue is located with millimeter spatial resolution.

Ultrafast time-gated imaging in thick tissues: a step toward optical mammography.

A combination of 100-fs cross-correlation time gating and lock-in amplifier detection is shown to be a versatile technique to image objects hidden in highly scattering media. The image is formed from the ballistic component of the ultrafast laser pulse while the diffuse component is eliminated by time gating using cross-correlation second-harmonic generation. The low-noise lock-in amplifier detection method and the high-repetition-rate milliwatt pulsed laser enable us to image through a random medium as thick as 28 scattering mean free paths with submillimeter resolution.

Imaging objects hidden in highly scattering media using femtosecond second-harmonic-generation cross-correlation time gating.

The transmission of 100-fs ultrafast laser pulses through biological tissues was measured by using femtosecond and picosecond time-resolved detection techniques. The broadening of transmitted pulses was found to increase as the thickness of the biological tissue increases. The absence of a distinct ballistic pulse transmitted through a relatively thin tissue is in sharp contrast with the pulse transmission through a random medium of discrete scatterers. Because of the continuous variation of the dielectric constant in tissue, the photons undergo scattering through the tissue, travel in various small zigzag least optical paths, and form a broadened early-arriving portion of the transmitted pulse. Even in the absence of a well-defined ballistic pulse, we can image an opaque object hidden inside a tissue as thick as 6.5 mm with submillimeter resolution by selecting the early-arriving portion of the transmitted pulse.

K. M. Yoo

Papers

When does the diffusion approximation fail to describe photon transport in random media

Raman, fluorescence, and time-resolved light scattering as optical diagnostic techniques to separate diseased and normal biomedical media.

Ultrafast time-gated imaging in thick tissues: a step toward optical mammography.

Imaging objects hidden in highly scattering media using femtosecond second-harmonic-generation cross-correlation time gating.

Ultrafast laser-pulse transmission and imaging through biological tissues