Optical coherence tomography.

Optical coherence tomography (OCT) is a non-contact method for imaging the topological and internal microstructure of samples in three dimensions. OCT can be configured as a conventional microscope, as an ophthalmic scanner, or using endoscopes and small diameter catheters for accessing internal biological organs. In this Primer, we describe the principles underpinning the different instrument configurations that are tailored to distinct imaging applications and explain the origin of signal, based on light scattering and propagation. Although OCT has been used for imaging inanimate objects, we focus our discussion on biological and medical imaging. We examine the signal processing methods and algorithms that make OCT exquisitely sensitive to reflections as weak as just a few photons and that reveal functional information in addition to structure. Image processing, display and interpretation, which are all critical for effective biomedical imaging, are discussed in the context of specific applications. Finally, we consider image artifacts and limitations that commonly arise and reflect on future advances and opportunities.

Ultrathin side-viewing needle probe for optical coherence tomography.

We present the smallest reported side-viewing needle probe for optical coherence tomography (OCT). Design, fabrication, optical characterization, and initial application of a 30-gauge (outer diameter 0.31 mm) needle probe are demonstrated. Extreme miniaturization is achieved by using a simple all-fiber probe design incorporating an angle-polished and reflection-coated fiber-tip beam deflector. When inserted into biological tissue, aqueous interstitial fluids reduce the probe's inherent astigmatism ratio to 1.8, resulting in a working distance of 300 µm and a depth-of-field of 550 µm with beam diameters below 30 µm. The needle probe was interfaced with an 840 nm spectral-domain OCT system and the measured sensitivity was shown to be only 7 dB lower than that of a comparable galvo-scanning sample arm configuration. 3D OCT images of lamb lungs were acquired over a depth range of ~600 µm, showing individual alveoli and bronchioles.

Measurement, reconstruction, and flow-field computation of the human pharynx with application to sleep apnea.

Repetitive closure of the upper airway characterizes obstructive sleep apnea. It disrupts sleep causing excessive daytime drowsiness and is linked to hypertension and cardiovascular disease. Previous studies simulating the underlying fluid mechanics are based upon geometries, time-averaged over the respiratory cycle, obtained usually via MRI or CT scans. Here, we generate an anatomically correct geometry from data captured in vivo by an endoscopic optical technique. This allows quantitative real-time imaging of the internal cross section with minimal invasiveness. The steady inhalation flow field is computed using a k-ω shear-stress transport (SST) turbulence model. Simulations reveal flow mechanisms that produce low-pressure regions on the sidewalls of the pharynx and on the soft palate within the pharyngeal section of minimum area. Soft-palate displacement and side-wall deformations further reduce the pressures in these regions, thus creating forces that would tend to narrow the airway. These phenomena suggest a mechanism for airway closure in the lateral direction as clinically observed. Correlations between pressure and airway deformation indicate that quantitative prediction of the low-pressure regions for an individual are possible. The present predictions warrant and can guide clinical investigation to confirm the phenomenology and its quantification, while the overall approach represents an advancement toward patient-specific modeling.

Measuring airway dimensions during bronchoscopy using anatomical optical coherence tomography.

Airway dimensions are difficult to quantify bronchoscopically because of optical distortion and a limited ability to gauge depth. Anatomical optical coherence tomography (aOCT), a novel imaging technique, may overcome these limitations. This study evaluated the accuracy of aOCT against existing techniques in phantom, excised pig and in vivo human airways. Three comparative studies were performed: 1) micrometer-derived area measurements in 10 plastic tubes were compared with aOCT-derived area; 2) aOCT-derived airway compliance curves from excised pig airways were compared with curves derived using an endoscopic technique; and 3) airway dimensions from the trachea to subsegmental bronchi were measured using aOCT in four anaesthetised patients during bronchoscopy and compared with computed tomography (CT) measurements. Measurements in plastic tubes revealed aOCT to be accurate and reliable. In pig airways, aOCT-derived compliance measurements compared closely with endoscopic data. In human airways, dimensions measured with aOCT and CT correlated closely. Bland-Altman plots showed that aOCT diameter and area measurements were higher than CT measurements by 7.6% and 15.1%, respectively. Airway measurements using aOCT are accurate, reliable and compare favourably with existing imaging techniques. Using aOCT with conventional bronchoscopy allows real-time measurement of airway dimensions and could be useful clinically in settings where knowledge of airway calibre is required.

Quantifying tracheobronchial tree dimensions: methods, limitations and emerging techniques.

The ability to measure airway dimensions is important for clinicians, interventional bronchoscopists and researchers in order to accurately quantify structural abnormalities and track their changes over time or in response to treatment. Most quantitative airway measurements are based on X-ray computed tomography and, more recently, on multidetector computed tomography. Quantitative bronchoscopic techniques have also been developed, although these are less widely employed. Emerging techniques, including magnetic resonance imaging, endoscopic optical coherence tomography, endobronchial ultrasound and confocal endomicroscopy, provide new research tools with potential clinical applications. An understanding of issues related to the acquisition, processing and analysis of images, and how such issues impact on imaging the tracheobronchial tree, is essential in order to assess measurement accuracy and to make effective use of the newer methods. This article contributes to this understanding by providing a comprehensive review of current and emerging techniques for quantifying airway dimensions.

In vitro and in vivo tissue repair with laser-activated chitosan adhesive.

BACKGROUND AND OBJECTIVES: Sutures are currently the gold standard for wound closure but they are still unable to seal tissue and may induce scarring or inflammation. Biocompatible glues, based on polysaccharides such as chitosan, are a possible alternative to conventional wound closure. In this study, the adhesion of laser-activated chitosan films is investigated in vitro and in vivo. In particular we examine the effect of varying the laser power, as well as adding a natural cross-linker (genipin) to the adhesive composition. STUDY DESIGN/MATERIALS AND METHODS: Flexible and insoluble strips of chitosan films (surface area approximately 34 mm(2), thickness approximately 20 microm) were bonded to sheep intestine using several laser powers (0, 80, 120, and 160 mW) at 808-nm wavelength. The strength of repaired tissue was tested by a calibrated tensiometer to select the best power. A natural cross-linker (genipin) was also added to the film and the tissue repair strength compared with the strength of plain films. The adhesive was also bonded in vivo to the sciatic nerve of rats and the thermal damage induced by the laser assessed 4 days post-operatively. RESULTS: Chitosan adhesives successfully repaired intestine tissue, attaining a maximum repair strength of 14.7+/-4.3 kPa (n = 30) at the laser power of 120 mW. The chitosan-genipin films achieved lower repair strength (9.1+/-2.9 kPa). The laser caused partial demyelination of axons at the site of operation, but the myelinated axons retained a normal morphology proximally and distally. CONCLUSIONS: The chitosan adhesive effectively bonded to tissue causing only localized thermal damage in vivo, when the appropriate laser parameters were selected.

Semiconductor line source for low-coherence interferometry.

The suitability for low-coherence interferometry of a high-power, semiconductor laser line source operated at a forward bias current below threshold is demonstrated. Measurements of the important characteristics of the source are presented. For example, the source produces an output power of 1.3 mW and a spatially uniform coherence length of 16 mum at a bias current of 86% of threshold (250 mA) at 20 degrees C. The usefulness of the source is verified by measurement of the line profile of a contact lens.

Achromatic optical phase shifter-modulator.

We propose and demonstrate, theoretically and experimentally, a novel achromatic optical phase shifter-modulator based on a frequency-domain optical delay line configured to maintain zero group delay as variable phase delay is generated by means of tilting a mirror. Compared with previously reported phase shifter-modulators, e.g., based on the Pancharatnam (geometric) phase, our device is high speed and polarization insensitive and produces a large, bounded phase delay that, uniquely, is one-to-one mapped to a measurable parameter, the tilt angle.

Real-time detection technique for Doppler optical coherence tomography.

We propose and demonstrate a novel detection technique, based on a modified electronic phase-locked loop, for Doppler optical coherence tomography. The technique permits real-time simultaneous reflectivity and continuous, bidirectional velocity mapping in turbid media over a wide velocity range with minimal sensitivity penalty compared with conventional optical coherence tomography, which is a major advance over current postprocessing and discrete parallel detection techniques.

Noise in coherence-multiplexed optical fiber systems.

We present measurements, in good agreement with theory, of the noise power spectral density at the outputs of a coherence-multiplexed system employing a low-coherence source. We investigate correlations in the noise between outputs and confirm that differential detection can be used to improve the signal-to-noise ratio of sensor and communication systems based on coherence multiplexing.

High bandwidth, optical fiber delay line multichannel digital correlator.

We present an implementation of a multichannel digital correlator based on passive optical fiber delay lines capable of achieving higher real-time bandwidths than current-generation, purely electronic instruments. Theoretical limits are shown to be in the 10(3) channels and tens of gigahertz range. Digital correlation is demonstrated with instruments based on laser diodes and optoelectronic single-bit AND multipliers consisting of eight channels at a 100-MHz sample rate and four channels at 500 MHz. Low-cost optoelectronics operating at 800 nm are shown likely to be suitable for up to 1-GHz sample rates. Applications for which high bandwidth correlation is necessary or advantageous are considered, and future, more compact, and all-optical architectures are suggested.

Experimental realization of a fiber-optic-based multichannel digital correlator.

An experimental demonstration of a new realization of a multichannel digital correlator is presented. It uses optical fiber networks based on a tree topology to implement the required passive delay lines and intensity addition followed by electronic thresholding to perform the multiplication function. Application of this device to laser light scattering and spectroscopy in radio astronomy and the potential for operating at higher bandwidths are discussed.

Coherent optical fiber communications system using all-optical correlation processing.

We propose a point-to-point or single-ended communications technique based on single-mode optical fibers that uses all-optical pulse multiplexing at the transmitter and coherent optical correlation at the receiver. This technique shows potential for application to secure untappable communications, fiber local-area networks, and optical ranging in the presence of a strong white-light background. The system can employ a low-coherence source, is insensitive to source phase noise and polarization-state rotation in the fiber link, and uses simple electronic threshold detection. Coherent correlation and anticorrelation are demonstrated experimentally, and practical requirements are examined.

Recalcitrant nodulocystic acne in black Americans: treatment with isotretinoin.

The beneficial effects of isotretinoin (Accutane) on severe nodulocystic acne and significant clinical improvement with prolonged remission are well documented in the literature; however, the subjects in these clinical studies are invariably white. The purpose of this study was to evaluate the response of black patients with recalcitrant nodulocystic acne to isotretinoin treatment. Ten black patients, ranging in age from 17 to 34 years, were treated for nodulocystic acne with 1 mg/kg/d of isotretinoin for 20 weeks and followed for an additional six months. Of the ten patients, eight adhered to the treatment regimen and were still in remission six months after completion of isotretinoin therapy. The differences and similarities seen between black patients and white patients with nodulocystic acne are discussed.

Intraepidermal epithelioma of Jadassohn.

Intraepidermal epithelioma of Jadassohn is a rare cutaneous neoplasm characterized by a solitary scaly verrucous plaque. Histologic examination of these plaques reveals intraepidermal nests of basaloid cells. To our knowledge this is the first case reported in a black person.