Modular microfluidic system as a model of cystic fibrosis airways.

A modular microfluidic airways model system that can simulate the changes in oxygen tension in different compartments of the cystic fibrosis (CF) airways was designed, developed, and tested. The fully reconfigurable system composed of modules with different functionalities: multichannel peristaltic pumps, bubble traps, gas exchange chip, and cell culture chambers. We have successfully applied this system for studying the antibiotic therapy of Pseudomonas aeruginosa, the bacteria mainly responsible for morbidity and mortality in cystic fibrosis, in different oxygen environments. Furthermore, we have mimicked the bacterial reinoculation of the aerobic compartments (lower respiratory tract) from the anaerobic compartments (cystic fibrosis sinuses) following an antibiotic treatment. This effect is hypothesised as the one on the main reasons for recurrent lung infections in cystic fibrosis patients.

Imaging ex vivo healthy and pathological human brain tissue with ultra-high-resolution optical coherence tomography.

The ability of ultra-high-resolution optical coherence tomography (UHR OCT) to discriminate between healthy and pathological human brain tissue is examined by imaging ex vivo tissue morphology of various brain biopsies. Micrometer-scale OCT resolution (0.9x2 microm, axialxlateral) is achieved in biological tissue by interfacing a state-of-the-art Ti:Al2O3 laser (lambda(c)=800 nm, delta lambda=260 nm, and P(out)=120 mW exfiber) to a free-space OCT system utilizing dynamic focusing. UHR OCT images are acquired from both healthy brain tissue and various types of brain tumors including fibrous, athypical, and transitional meningioma and ganglioglioma. A comparison of the tomograms with standard hematoxylin and eosin (H&E) stained histological sections of the imaged biopsies demonstrates the ability of UHR OCT to visualize and identify morphological features such as microcalcifications (>20 microm), enlarged nuclei of tumor cells (approximately 8 to 15 microm), small cysts, and blood vessels, which are characteristic of neuropathologies and normally absent in healthy brain tissue.

Adaptive-optics ultrahigh-resolution optical coherence tomography.

Merging of ultrahigh-resolution optical coherence tomography (UHR OCT) and adaptive optics (AO), resulting in high axial (3 microm) and improved transverse resolution (5-10 microm) is demonstrated for the first time to our knowledge in in vivo retinal imaging. A compact (300 mm x 300 mm) closed-loop AO system, based on a real-time Hartmann-Shack wave-front sensor operating at 30 Hz and a 37-actuator membrane deformable mirror, is interfaced to an UHR OCT system, based on a commercial OCT instrument, employing a compact Ti:sapphire laser with 130-nm bandwidth. Closed-loop correction of both ocular and system aberrations results in a residual uncorrected wave-front rms of 0.1 microm for a 3.68-mm pupil diameter. When this level of correction is achieved, OCT images are obtained under a static mirror configuration. By use of AO, an improvement of the transverse resolution of two to three times, compared with UHR OCT systems used so far, is obtained. A significant signal-to-noise ratio improvement of up to 9 dB in corrected compared with uncorrected OCT tomograms is also achieved.

Precision of extracting absorption profiles from weakly scattering media with spectroscopic time-domain optical coherence tomography.

The feasibility of spectroscopic optical coherence tomography (SOCT) to quantify spatially localized absorption profiles of chromophores embedded in weakly scattering media with a single measurement over the full spectral bandwidth of the light source was investigated by using a state-of-the-art ultra-broad bandwidth Ti:Al(2)O(3) laser (lambdac = 800 nm, Deltalambda = 260 nm, P(out) = 120 mW ex-fiber). The precision of the method as a function of the chromophore absorption, the sample thickness, and different parameters related to the measurement procedure was evaluated both theoretically and experimentally in single and multilayered phantoms. It is demonstrated that in weakly scattering media SOCT is able to extract mua(lambda) as small as 0.5 mm-1 from 450 mum thick phantoms with a precision of ~2% in the central and ~8% at the edges of the used wavelength region. As expected, in phantoms with the same absorption properties and thickness ~180 mum the precision of SOCT decreases to >10% in the central wavelength region.

Ultrahigh resolution Fourier domain optical coherence tomography.

We present, for the first time, in vivo ultrahigh resolution (~2.5 microm in tissue), high speed (10000 A-scans/second equivalent acquisition rate sustained over 160 A-scans) retinal imaging obtained with Fourier domain (FD) OCT employing a commercially available, compact (500x260mm), broad bandwidth (120 nm at full-width-at-half-maximum centered at 800 nm) Titanium:sapphire laser (Femtosource Integral OCT, Femtolasers Produktions GmbH). Resolution and sampling requirements, dispersion compensation as well as dynamic range for ultrahigh resolution FD OCT are carefully analyzed. In vivo OCT sensitivity performance achieved by ultrahigh resolution FD OCT was similar to that of ultrahigh resolution time domain OCT, although employing only 2-3 times less optical power (~300 microW). Visualization of intra-retinal layers, especially the inner and outer segment of the photoreceptor layer, obtained by FDOCT was comparable to that, accomplished by ultrahigh resolution time domain OCT, despite an at least 40 times higher data acquisition speed of FD OCT.

Enhanced visualization of choroidal vessels using ultrahigh resolution ophthalmic OCT at 1050 nm.

In this article the ability of ultrahigh resolution ophthalmic optical coherence tomography (OCT) to image small choroidal blood vessels below the highly reflective and absorbing retinal pigment epithelium is demonstrated for the first time. A new light source (lambdac= 1050 nm, Deltalambda = 165 nm, Pout= 10 mW), based on a photonic crystal fiber pumped by a compact, self-starting Ti:Al2O3 laser has therefore been developed. Ex-vivo ultrahigh resolution OCT images of freshly excised pig retinas acquired with this light source demonstrate enhanced penetration into the choroid and better visualization of choroidal vessels as compared to tomograms acquired with a state-of-the art Ti:Al2O3 laser (Femtolasers Compact Pro, lc= 780 nm, Deltalambda= 160 nm, Pout= 400 mW), normally used in clinical studies for in vivo ultrahigh resolution ophthalmic OCT imaging. These results were also compared with retinal tomograms acquired with a novel, spectrally broadened fiber laser (MenloSystems, lambdac= 1350 nm, Deltalambda= 470 nm, Pout = 4 mW) permitting even greater penetration in the choroid. Due to high water absorption at longer wavelengths retinal OCT imaging at ~1300 nm may find applications in animal ophthalmic studies. Detection and follow-up of choroidal neovascularization improves early diagnosis of many retinal pathologies, e.g. age-related macular degeneration or diabetic retinopathy and can aid development of novel therapy approaches.

Real-time assessment of retinal blood flow with ultrafast acquisition by color Doppler Fourier domain optical coherence tomography.

We interfaced color Doppler Fourier domain optical coherence tomography (CD-FDOCT) with a commercial OCT system to perform in vivo studies of human retinal blood flow in real time. FDOCT does not need reference arm scanning and records one full depth and Doppler profile in parallel. The system operates with an equivalent A-scan rate of 25 kHz and allows real time imaging of the color encoded Doppler information together with the tissue morphology at a rate of 2-4 tomograms (40 x 512 pixel) per second. The recording time of a single tomogram (160 x 512 data points) is only 6,4ms. Despite the high detection speed we achieve a system sensitivity of 86dB using a beam power of 500microW at the cornea. The fundus camera allows simultaneous view for selection of the region of interest. We observe bi-directional blood flow and pulsatility of blood velocity in retinal vessels with a Doppler detection bandwidth of 12.5 kHz and a longitudinal velocity sensitivity in tissue of 200microm/s.

Full range complex spectral optical coherence tomography technique in eye imaging.

We demonstrate a new implementation of complex spectral optical coherence tomography (OCT) in biomedical imaging. By reconstruction of both amplitude and phase we are able to use the negative and positive optical path differences to get images of objects of considerable thickness. An accompanying reduction of coherent noise improves the quality of the images. The property of the complex spectral OCT that permits the measurement range to be increased and permits the simultaneous use of phase and amplitude in spectral systems was not described previously. To show the potential of this technique we measured an anterior chamber of a porcine eye in vitro.

Submicrometer axial resolution optical coherence tomography.

Optical coherence tomography (OCT) with unprecedented submicrometer axial resolution achieved by use of a photonic crystal fiber in combination with a compact sub-10-fs Ti:sapphire laser (Femtolasers Produktions) is demonstrated for what the authors believe is the first time. The emission spectrum ranges from 550 to 950 nm (lambda(c)=725 nm , P(out)=27 mW) , resulting in a free-space axial OCT resolution of ~0.75 mum , corresponding to ~0.5 mum in biological tissue. Submicrometer-resolution OCT is demonstrated in vitro on human colorectal adenocarcinoma cells HT-29. This novel light source has great potential for development of spectroscopic OCT because its spectrum covers the absorption bands of several biological chromophores.

Halo size under distance and near conditions in refractive multifocal intraocular lenses.

AIMS: To calculate the diameter of halos perceived by patients with multifocal intraocular lenses (IOLs) and to stimulate halos in patients with refractive multifocal IOLs in a clinical experiment. METHODS: Calculations were done to show the diameter of halos in the case of the bifocal intraocular lens. 24 patients with a refractive multifocal IOLs and five patients with a monofocal IOL were asked about their subjective observation of halos and were included in a clinical experiment using a computer program (Glare & Halo, FW Fitzke and C Lohmann, Tomey AG) which simulates a light source of 0.15 square degrees (sq deg) in order to stimulate and measure halos. Halo testing took place monoculary, under mesopic conditions through the distance and the near focus of the multifocal lens and through the focus of the monofocal lens. RESULTS: The halo diameter depends on the pupil diameter, the refractive power of the cornea, and distance focus of the multifocal IOL as well as the additional lens power for the near focus. 23 out of 24 patients with a refractive multifocal IOL described halos at night when looking at a bright light source. Only one patient was disturbed by the appearance of halos. Under test conditions, halos were detected in all patients with a refractive multifocal IOL. The halo area testing through the distance focus was 1.05 sq deg +/- 0.41, through the near focus 1.07 sq deg +/- 0.49 and in the monofocal lens 0.26 sq deg +/- 0.13. CONCLUSIONS: Under high contrast conditions halos can be stimulated in all patients with multifocal intraocular lenses. The halo size using the distance or the near focus is identical.

Improved prediction of intraocular lens power using partial coherence interferometry.

PURPOSE: To evaluate the feasibility of using a new optical biometry technique, dual-beam partial coherence interferometry (PCI), to improve intraocular lens (IOL) power prediction in cataract surgery. SETTING: Department of Ophthalmology, Vienna General Hospital, and Institute of Medical Physics, University of Vienna, Vienna, Austria. METHODS: Preoperative axial length (AL) data obtained with PCI biometry and applanation ultrasound (US) biometry in 77 eyes of 51 patients was applied to 4 commonly used IOL power formulas. The refractive outcome and the mean absolute error (MAE) were calculated for each formula using both biometry methods. A linear multiple-regression model based on preoperative PCI biometry data was derived to predict the postoperative anterior chamber depth (ACD). The predictive power of this regression model was assessed by adding the predicted ACD to the SRK/T formula. Predicted residuals were calculated to evaluate the feasibility and stability of this modified IOL power formula. RESULTS: Using PCI instead of US biometry significantly improved the refractive outcome with all 4 IOL power formulas. The Holladay I and SRK/T formulas yielded an MAE of 0.44 diopter (D) using PCI AL data and 0.56 D and 0.57 D, respectively, using US biometry data. The SRK/T formula combined with the PCI regression model for postoperative ACD prediction performed slightly better (MAE 0.42 D) than the conventional SRK/T formula alone. Predicted residuals revealed an MAE of 0.46 D, proving the predictive performance of the new formula. CONCLUSIONS: Partial coherence interferometry biometry applied to several widely used IOL power formulas yielded significantly better IOL power prediction and therefore refractive outcome in cataract surgery than US biometry. Further improvement can be achieved by applying PCI to a modified SRK/T formula that predicts the postoperative ACD using PCI biometry data.

Quantitative differential phase measurement and imaging in transparent and turbid media by optical coherence tomography.

Differential phase-contrast optical coherence tomography allows one to measure the path-length differences of two transversally separated beams in the nanometer range. We calculate these path-length differences from the phase functions of the interferometric signals. Pure phase objects consisting of chromium layers containing steps of approximately 100-200-nm height were imaged. Phase differences can be measured with a precision of +/-2 degrees , corresponding to a path-difference resolution of 2-3 nm. To investigate the influence of scattering, we imaged the phase objects through scattering layers with increasing scattering coefficients. The limit of phase imaging through these layers was at approximately 8-9 mean free path lengths thick (single pass).

Differential phase measurements in low-coherence interferometry without 2pi ambiguity.

Quantitative phase measurements by low-coherence interferometry and optical coherence tomography are restricted by the well-known 2pi ambiguity to path-length differences smaller than lambda/2 . We present a method that overcomes this ambiguity. Introducing a slight dispersion imbalance between reference and sample arms of the interferometer causes the short and long wavelengths of the source spectrum to separate within the interferometric signal. This causes the phase slope to vary within the signal. The phase-difference function between two adjacent sample beam components is calculated by subtraction of their phase functions obtained from phase-sensitive interferometric signal recording. Because of the dispersive effect, the phase difference varies across the interferometric signal. The slope of that phase difference is proportional to the optical path difference, without 2pi ambiguity.

Numerical dispersion compensation for Partial Coherence Interferometry and Optical Coherence Tomography.

Dispersive samples introduce a wavelength dependent phase distortion to the probe beam. This leads to a noticeable loss of depth resolution in high resolution OCT using broadband light sources. The standard technique to avoid this consequence is to balance the dispersion of the sample byarrangingadispersive materialinthereference arm. However, the impact of dispersion is depth dependent. A corresponding depth dependent dispersion balancing technique is diffcult to implement. Here we present a numerical dispersion compensation technique for Partial Coherence Interferometry (PCI) and Optical Coherence Tomography (OCT) based on numerical correlation of the depth scan signal with a depth variant kernel. It can be used a posteriori and provides depth dependent dispersion compensation. Examples of dispersion compensated depth scan signals obtained from microscope cover glasses are presented.

Measurement and imaging of birefringence and optic axis orientation by phase resolved polarization sensitive optical coherence tomography.

We present an improved method of polarization sensitive optical coherence tomography that enables measurement and imaging of backscattered intensity, birefringence, and fast optic axis orientation simultaneously with only one single A-scan per transverse measurement location. While intensity and birefringence data are obtained in a conventional way, the optic axis orientation is determined from the phase difference recorded in two orthogonal polarization channels. We report on accuracy and precision of the method by measuring birefringence and optic axis orientation of well defined polarization states in a technical object and present maps of birefringence and, what we believe for the first time, of optic axis orientation in biological tissue.

Resolution-improved dual-beam and standard optical coherence tomography: a comparison.

BACKGROUND: The purpose of the study was to demonstrate the improved axial resolution and longitudinal stability of dual-beam optical coherence tomography (OCT) in comparison to conventional OCT setups used in commercially available OCT instruments. METHODS: The conventional OCT technique is based on an interferometric setup that is rather sensitive to axial eye motions. We have developed a special dual-beam OCT technique which eliminates the influence of axial eye motions. This is achieved by using the anterior corneal surface as the reference surface for the interferometric ranging. To improve the signal quality, the different wavefront curvatures of beams reflected at cornea and retina are matched by a diffractive optical element. To improve the axial resolution, a broadband synthesized light source with an effective bandwidth of 50 nm is used, and the group dispersion of the ocular media is compensated. Tomographic images were recorded in the fovea and the optic nerve head of healthy volunteers. For comparison purposes, approximately the same locations in the same eyes were imaged by a commercially available OCT instrument. RESULTS: Compared to the standard OCT technique, the dual-beam OCT images show considerably improved axial resolution. Especially in tomograms recorded at the fovea, dual-beam OCT resolves microstructural details that are not visible in the standard OCT images. Furthermore, the axial stability of dual-beam OCT enables the recording of exact geometrical contours of fundus layers. CONCLUSIONS: Dual-beam OCT is able to provide structural information on the ocular fundus that is not obtained with standard OCT. The long recording times of our instrument limit the transverse resolution to 100-150 microm at present.

Polarization-sensitive optical coherence tomography of dental structures.

Optical coherence tomography (OCT) has been developed during the last 10 years as a new noninvasive imaging tool and has been applied to diagnose different ocular and skin diseases. This technique has been modified for cross-sectional imaging of dental structures. In this first preliminary study the technique was applied to obtain tomographic images of extracted sound and decayed human teeth in order to evaluate its possible diagnostic potential for dental applications. Classical OCT images based on reflectivity measurements and phase retardation images using polarization-sensitive OCT were recorded. It was demonstrated that polarization-sensitive OCT can provide additional information which is probably related to the mineralization status and/or the scattering properties of the dental material. One of the attractive features of OCT is that it uses near-infrared light instead of ionizing radiation. Furthermore, high transversal and depth resolution on the order of 10 microm can be obtained. Present limitations, e.g. the limited penetration depth, and possible solutions are discussed.

Spectral measurement of absorption by spectroscopic frequency-domain optical coherence tomography.

A new method of measurement that essentially combines Fourier-domain optical coherence tomography with spectroscopy is introduced. By use of a windowed Fourier transform it is possible to obtain, in addition to the object structure, spectroscopic information such as the absorption properties of materials. The feasibility of this new method for performing depth-resolved spectroscopy is demonstrated with a glass filter plate. The results are compared with theoretically calculated spectra by use of the well-known spectral characteristics of the light source and the filter plate.

Changes in intraocular lens position after neodymium: YAG capsulotomy.

PURPOSE: To quantify changes in intraocular lens (IOL) position caused by neodymium: YAG (Nd:YAG) capsulotomy with 3 IOL styles. SETTING: Department of Ophthalmology, University of Vienna, Austria. METHODS: In a prospective study, anterior chamber depth (ACD) was measured by dualbeam partial coherence interferometry (PCI) in 32 pseudophakic eyes of 32 patients with posterior capsule opacification before and immediately after planned capsulotomy under mydriasis. Patients were divided into 3 groups with the following IOL styles: 1-piece poly(methyl methacrylate) (PMMA), 3-piece foldable, and plate haptic. RESULTS: The capsulotomy induced a backward IOL movement in all 32 eyes (mean 25 microns; range 9 to 55 microns). It was more pronounced in eyes with plate-haptic IOLs than in those with the other styles. Precision of ACD measurement by PCI was 4 microns. Changes in ACD correlated significantly with capsulotomy size but not with preoperative lens-capsule distance. CONCLUSION: Capsulotomy caused a backward movement of the IOL, which was more pronounced with plate-haptic IOLs than with 1-piece PMMA and 3-piece foldable IOLs. Since the magnitude of IOL movement in this study population was small, a hyperopic shift in refraction after capsulotomy will usually be small and not clinically relevant.