The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders

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.

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Optical coherence tomography - principles and applications

Plethysmographic signals were measured remotely (>1m) using ambient light and a simple consumer level digital camera in movie mode. Heart and respiration rates could be quantified up to several harmonics. Although the green channel featuring the strongest plethysmographic signal, corresponding to an absorption peak by (oxy-) hemoglobin, the red and blue channels also contained plethysmographic information. The results show that ambient light photo-plethysmography may be useful for medical purposes such as characterization of vascular skin lesions (e.g., port wine stains) and remote sensing of vital signs (e.g., heart and respiration rates) for triage or sports purposes.

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Remote plethysmographic imaging using ambient light

Current medical imaging technologies allow visualization of tissue anatomy in the human body at resolutions ranging from 100 micrometers to 1 millimeter. These technologies are generally not sensitive enough to detect early-stage tissue abnormalities associated with diseases such as cancer and atherosclerosis, which require micrometer-scale resolution. Here, optical coherence tomography was adapted to allow high-speed visualization of tissue in a living animal with a catheter-endoscope 1 millimeter in diameter. This method, referred to as "optical biopsy," was used to obtain cross-sectional images of the rabbit gastrointestinal and respiratory tracts at 10-micrometer resolution.

In Vivo Endoscopic Optical Biopsy 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

A high-speed single-mode fiber-based polarization-sensitive optical coherence tomography (PS OCT) system was developed. With a polarization modulator, Stokes parameters of reflected flight for four input polarization states are measured as a function of depth. A phase modulator in the reference arm of a Michelson interferometer permits independent control of the axial scan rate and carrier frequency. In vivo PS OCT images of human skin are presented, showing subsurface structures that are not discernible in conventional OCT images. A phase retardation image in tissue is calculated based on the reflected Stokes parameters of the four input polarization states.

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High-speed fiber–based polarization-sensitive optical coherence tomography of in vivo human skin

In optical coherence tomography, axial and lateral resolutions are determined by the source coherence length and the numerical aperture of the sampling lens, respectively. Whereas axial resolution can be improved by use of a broadband light source, there is a trade-off between lateral resolution and focusing depth when conventional optical elements are used. We report on the incorporation of an axicon lens into the sample arm of an interferometer to overcome this limitation. Using an axicon lens with a top angle of 160 degrees , we maintained 10-microm or better lateral resolution over a focusing depth of at least 6 mm. In addition to having high lateral resolution, the focusing spot has an intensity that is approximately constant over a greater depth range than when a conventional lens is used.

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High-resolution optical coherence tomography over a large depth range with an axicon lens.

We used a novel phase-resolved optical Doppler tomographic (ODT) technique with very high flow-velocity sensitivity (10microm/s) and high spatial resolution (10microm) to image blood flow in port-wine stain (PWS) birthmarks in human skin. In addition to the regular ODT velocity and structural images, we use the variance of blood flow velocity to map the PWS vessels. Our device combines ODT and therapeutic systems such that PWS blood flow can be monitored in situ before and after laser treatment. To the authors' knowledge this is the first clinical application of ODT to provide a fast semiquantitative evaluation of the efficacy of PWS laser therapy in situ and in real time.

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Doppler standard deviation imaging for clinical monitoring of in vivo human skin blood flow

We have developed an ultrahigh-resolution optical coherence tomographic system in which broadband continuum generation from a photonic crystal fiber is used to produce high longitudinal resolution. Longitudinal resolution of 1.3-microm has been achieved in a biological tissue by use of continuum light from 800 to 1400 nm. The system employed a dynamic-focusing tracking method to maintain high lateral resolution over a large imaging depth. Subcellular imaging is demonstrated.

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Ultrahigh-resolution optical coherence tomography by broadband continuum generation from a photonic crystal fiber

Optical Doppler tomography (ODT) is an imaging modality that takes advantage of the short coherence length of a broad-band light sources to perform micrometer-scale, cross-sectional imaging of tissue structure and blood flow dynamics simultaneously. The authors review in this paper the principal of ODT and its applications. Results from in vitro and in vivo model studies demonstrated that ODT can map the blood flow velocity profile with high spatial resolution in scattering medium. ODT detection mechanisms are illustrated using Monte Carlo simulations. The application of ODT to image brain hemodynamics is demonstrated. Finally, the authors discuss the limitations of the current technology and application of a phase resolved technique to improve image speed and quality.

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Yonghua Zhao

Papers

High-speed fiber–based polarization-sensitive optical coherence tomography of in vivo human skin

High-resolution optical coherence tomography over a large depth range with an axicon lens.

Doppler standard deviation imaging for clinical monitoring of in vivo human skin blood flow

Ultrahigh-resolution optical coherence tomography by broadband continuum generation from a photonic crystal fiber

Optical Doppler tomography