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Biomedical subjects

Joseph A Izatt

Publications and source records attributed to Joseph A Izatt.

At least 19 recordsLinked to original sources
PubMed2006

Real-time quadrature projection complex conjugate resolved Fourier domain optical coherence tomography.

We present a novel algorithm for full-range imaging by suppression of the complex conjugate artifact in phase-shifting Fourier domain optical coherence tomography. This technique utilizes the projection of multiple phase-shifted interferograms onto an orthogonal basis set to reconstruct the complex interferogram. Full-range imaging with >30 dB suppression of the symmetric artifact is demonstrated using a 3 x 3 fiber coupler swept source OCT system, providing a depth range of 6.6mm with -8 dB roll-off in sensitivity at the depth boundaries relative to DC. Real-time display of full-range images of the anterior segment of the human eye acquired in vivo at a line rate of 6.67 kHz are presented.

Algorithms↗
PubMed2006

Full-field swept-source phase microscopy.

We present a full-field phase microscopy technique for quantitative nanoscale surface profiling of samples in reflection. This technique utilizes swept-source optical coherence tomography in a full-field common path interferometer for phase-stable cross-sectional acquisition without scanning. Subwavelength variations in surface sample features are measured without interference from spurious reflections by processing the interferometric phase at a selected depth plane, providing a 1.3 nm stability for high signal-to-noise ratio surface features. Nanoscale imaging was demonstrated by measuring the location of receptor sites on a DNA assay biochip and the surface topography of erythrocytes in a blood smear.

Cells, Cultured↗
PubMed2006

Drosophila as a model for the identification of genes causing adult human heart disease.

Drosophila melanogaster genetics provides the advantage of molecularly defined P-element insertions and deletions that span the entire genome. Although Drosophila has been extensively used as a model system to study heart development, it has not been used to dissect the genetics of adult human heart disease because of an inability to phenotype the adult fly heart in vivo. Here we report the development of a strategy to measure cardiac function in awake adult Drosophila that opens the field of Drosophila genetics to the study of human dilated cardiomyopathies. Through the application of optical coherence tomography, we accurately distinguish between normal and abnormal cardiac function based on measurements of internal cardiac chamber dimensions in vivo. Normal Drosophila have a fractional shortening of 87 +/- 4%, whereas cardiomyopathic flies that contain a mutation in troponin I or tropomyosin show severe impairment of systolic function. To determine whether the fly can be used as a model system to recapitulate human dilated cardiomyopathy, we generated transgenic Drosophila with inducible cardiac expression of a mutant of human delta-sarcoglycan (deltasg(S151A)), which has previously been associated with familial dilated cardiomyopathy. Compared to transgenic flies overexpressing wild-type deltasg, or the standard laboratory strain w(1118), Drosophila expressing deltasg(S151A) developed marked impairment of systolic function and significantly enlarged cardiac chambers. These data illustrate the utility of Drosophila as a model system to study dilated cardiomyopathy and the applicability of the vast genetic resources available in Drosophila to systematically study the genetic mechanisms responsible for human cardiac disease.

Animals↗
PubMed2005

Spectral domain second-harmonic optical coherence tomography.

Optical coherence tomography (OCT) provides micrometer-scale structural imaging by coherent detection of backscattered light. Molecular contrast in OCT has been demonstrated using transient absorption, coherent anti-Stokes Raman scattering, and second-harmonic (SH) generation. The sensitivity of molecular contrast signals can be enhanced by use of Fourier domain techniques. We have constructed a spectrometer-based Fourier domain SH-OCT system for simultaneous acquisition of the fundamental and SH signals. We report a >30 dB increase in SH sensitivity over a similar time domain SH-OCT system and demonstrate contrast between cartilage and bone using collagen as the contrast agent.

Equipment Design↗
PubMed2005

Spectral-domain phase microscopy.

Broadband interferometry is an attractive technique for the detection of cellular motions because it provides depth-resolved phase information via coherence gating. We present a phase-sensitive technique called spectral-domain phase microscopy (SDPM). SDPM is a functional extension of spectral-domain optical coherence tomography that allows for the detection of nanometer-scale motions in living cells. The sensitivity of the technique is demonstrated, and its calibration is verified. A shot-noise limit to the displacement sensitivity of this technique is derived. Measurement of cellular dynamics was performed on spontaneously beating cardiomyocytes isolated from chick embryos.

Animals↗
PubMed2005

Comparison of optical coherence tomography and ultrasound biomicroscopy for detection of narrow anterior chamber angles.

OBJECTIVE: To assess the accuracy of classification of narrow anterior chamber (AC) angles using quantitative imaging by optical coherence tomography (OCT) and ultrasound biomicroscopy (UBM). DESIGN: Observational comparative study. METHODS: A high-speed (4000 axial scans/s) anterior segment OCT prototype was developed using a 1.3-microm light source. Seventeen normal subjects (17 eyes) and 7 subjects (14 eyes) with narrow angle glaucoma were enrolled. All subjects underwent gonioscopy, OCT, and UBM. Quantitative AC angle parameters (angle opening distance, angle recess area, and the trabecular-iris space area [a new parameter we have defined]) were measured from OCT and UBM images using proprietary processing software. MAIN OUTCOME MEASURES: Specificity and sensitivity in identifying narrow angles with image-derived AC angle parameters. RESULTS: Eight of 31 eyes were classified as having narrow angles (Shaffer grade < or =1 in all quadrants). The AC angle parameters measured by both OCT and UBM had similar mean values, reproducibility, and sensitivity-specificity profiles. Both OCT and UBM showed excellent performance in identifying eyes with narrow angles. Areas under the receiver operating characteristic curves for these parameters were all in the range of 0.96 to 0.98. CONCLUSIONS: Optical coherence tomography was similar to UBM in quantitative AC angle measurement and detection of narrow angles. In addition, it was easier to use and did not require contact with the eye. Optical coherence tomography is a promising method for screening individuals at risk for narrow angle glaucoma.

Adult↗
PubMed2005

High-speed optical coherence tomography of laser iridotomy.

PURPOSE: To describe high-speed (4000 axial scans/s) optical coherence tomography (OCT) findings in a patient with narrow angles. DESIGN: Interventional case report. METHODS: A 56-year-old woman was found to have occludable narrow angles on OCT screening. This was confirmed by gonioscopy. Bilateral iridotomy was performed. Imaging of the angles was performed with a high-speed OCT prototype before and after iridotomy. RESULTS: OCT showed narrow angle bilaterally. Cornea, sclera, scleral spur, trabecula, iris, and iris recess were visualized. After iridotomy, the OCT showed reduction of iris concavity and patent iridotomies. Quantitative measurements of trabecula-iris space area on the OCT images showed widening of the angles to nonoccludable values. CONCLUSIONS: A 1.3-microm wavelength OCT allows noncontact quantitative assessment of the angle and may be useful in the management of narrow-angle glaucoma.

Diagnostic Techniques, Ophthalmological↗
PubMed2005

Anterior chamber width measurement by high-speed optical coherence tomography.

OBJECTIVE: To measure anterior chamber (AC) width and other dimensions relevant to the sizing of phakic intraocular lenses (IOLs) with a high-speed optical coherence tomography (OCT) system. DESIGN: Cross-sectional observational study. PARTICIPANTS: Both eyes of 20 normal volunteers. METHODS: A novel high-speed (4000 axial scans/second) OCT prototype was developed for anterior segment scanning. The system uses long wavelength (1310 nm) for deeper angle penetration, rectangular scanning for undistorted imaging, and short image acquisition time (0.125 seconds) to reduce motion error. Three horizontal cross-sectional OCT images (15.5 mm wide and 6 mm deep) of the anterior segment were obtained from each eye with real-time image display to guide centration on the corneal apex. Image processing software was developed to correct for image warping resulting from index transitions. Anterior chamber dimensions were measured using computer calipers by 3 expert raters (ophthalmologists). Analysis of variance was used to determine interrater, interimage, right versus left eye, and intersubject standard deviation (SD) of OCT measurements. MAIN OUTCOME MEASURES: Anterior chamber width (recess to recess), AC depth, and crystalline lens vault as measured by OCT; external white-to-white (WTW) corneal diameter (CD) as measured by Holladay-Godwin gauge. RESULTS: The mean AC width was 12.53+/-0.47 mm (intereye SD), and the mean corneal diameter was 11.78+/-0.57 mm. Optical coherence tomography measurement of AC width has good repeatability from image to image (SD, 0.134 mm), but there was significant difference between raters (SD, 0.215 mm). Estimation of AC width from WTW CD by linear regression was relatively inaccurate (residual SD, 0.41 mm). The mean AC depth was 2.99+/-0.323 mm (intereye SD), with repeatability of less than 0.001 mm (interimage SD), and the mean crystalline lens vault was 0.39+/-0.27 mm with 0.023 mm repeatability. CONCLUSIONS: Reproducible OCT AC biometry was demonstrated using a high-speed OCT prototype. Further improvement in reproducibility may be achieved by automating the measurements with a computer. Direct OCT AC width measurement may improve sizing of angle-supported AC IOLs over conventional estimation by WTW CD. The measurement of AC depth and lens vault also may be useful for other types of phakic AC IOLs.

Adult↗
PubMed2005

Correlation of endoscopic optical coherence tomography with histology in the lower-GI tract.

BACKGROUND: Optical coherence tomography (OCT), a noninvasive optical imaging technique, provides high-resolution cross-sectional images of tissue microstructure. We developed a system for real-time endoscopic OCT (EOCT) of the human GI tract. During clinical trials, the structure of mucosa and submucosa, glands, blood vessels, pits, villi, and crypts was observed in a range of GI organs. Although EOCT images are thought to accurately depict actual histologic features, there are few data to support this assumption. Therefore, the present study correlated images acquired with an EOCT imaging system in vitro to corresponding histologic sections. METHODS: EOCT images were obtained of fresh specimens of ileum, colon, and rectum that then were fixed in formalin and were processed for microscopic evaluation by using standard methods. The thickness of mucosa and of submucosa was determined for both EOCT images and histologic slides. RESULTS: The first hyper-reflective layer in the EOCT images was identified as mucosa. A close correlation (R 2=0.84) was observed between EOCT and histology. Furthermore, the submucosa and the muscularis propria could be identified as the next deepest hyporeflective band and a hyper-reflective layer, respectively, in EOCT images. The submucosa was found to be more compressible than mucosa, and its EOCT appearance was dependent on its content of adipose tissue. CONCLUSIONS: EOCT provides images that precisely correlate with the histologic structure of the mucosa and the submucosa of the GI tract.

Colon↗
PubMed2004

Polarization-resolved second-harmonic-generation optical coherence tomography in collagen.

We describe a novel imaging technique, second-harmonic-generation optical coherence tomography (SHOCT). This technique combines the spatial resolution and depth penetration of optical coherence tomography (OCT) with the molecular sensitivity of second-harmonic-generation spectroscopy. As a consequence of the coherent detection required for OCT, polarization-resolved images arise naturally. We demonstrate this new technique on a skin sample from the belly of Icelandic salmon, acquiring polarization-resolved SHOCT and OCT images simultaneously.

Animals↗
PubMed2004

Spectral triangulation molecular contrast optical coherence tomography with indocyanine green as the contrast agent.

We report a new molecular contrast optical coherence tomography (MCOCT) implementation that profiles the contrast agent distribution in a sample by measuring the agent's spectral differential absorption. The method, spectra triangulation MCOCT, can effectively suppress contributions from spectrally dependent scatterings from the sample without a priori knowledge of the scattering properties. We demonstrate molecular imaging with this new MCOCT modality by mapping the distribution of indocyanine green, a FDA-approved infrared red dye, within a stage 54 Xenopus laevis.

Animals↗
PubMed2004

Protein-based molecular contrast optical coherence tomography with phytochrome as the contrast agent.

We report the use of phytochrome A (phyA), a plant protein that can reversibly switch between two states with different absorption maxima (at 660 and 730 nm), as a contrast agent for molecular contrast optical coherence tomography (MCOCT). Our MCOCT scheme builds up a difference image revealing the distribution of phyA within a target sample from pairs of consecutive OCT A-scans acquired at a probe wavelength of 750 nm, both with and without additional illumination of the target sample with 660-nm light. We demonstrate molecular imaging with this new MCOCT modality in a target sample containing a mixture of 0.2% Intralipid and 83 microM of phyA.

Contrast Media↗
PubMed2004

Group index of the human cornea at 1.3-microm wavelength obtained in vitro by optical coherence domain reflectometry.

The group index of the cornea, rather than the phase refractive index, is required for thickness calculations with optical coherence tomography. Recent advances with high-speed optical coherence tomography at 1.3 microm make index measurement at this wavelength of great interest. Group indices of three human corneas from an eye bank were measured in vitro with optical coherence domain reflectometry. Measurements were made in a calibrated cuvette filled with a preservation medium to maintain proper corneal hydration. Group indices were calculated from the optical path lengths measured. The corneal group index was 1.389 +/- 0.004 (average +/- standard deviation). The average group index of a balanced salt solution, an approximation to aqueous humor, was 1.343 +/- 0.001.

Chondroitin Sulfates↗
PubMed2003

Instantaneous quadrature low-coherence interferometry with 3 x 3 fiber-optic couplers.

We describe fiber-based quadrature low-coherence interferometers that exploit the inherent phase shifts of 3 x 3 and higher-order fiber-optic couplers. We present a framework based on conservation of energy to account for the interferometric shifts in 3 x 3 interferometers, and we demonstrate that the resulting interferometers provide the entire complex interferometric signal instantaneously in homodyne and heterodyne systems. In heterodyne detection we demonstrate the capability for extraction of the magnitude and sign of Doppler shifts from the complex data. In homodyne detection we show the detection of subwavelength sample motion. N x N (N > 2) low-coherence interferometer topologies will be useful in Doppler optical coherence tomography (OCT), optical coherence microscopy, Fourier-domain OCT, optical frequency domain reflectometry, and phase-referenced interferometry.

Equipment Design↗
PubMed2003

Fourier-domain low-coherence interferometry for light-scattering spectroscopy.

We present a novel method for obtaining depth-resolved spectra for determining scatterer size through elastic-scattering properties. Depth resolution is achieved with a white-light source in a Michelson interferometer with the mixed signal and reference fields dispersed by a spectrograph. The spectrum is Fourier transformed to yield the axial spatial cross correlation between the signal and reference fields with near 1-microm depth resolution. Spectral information is obtained by windowing to yield the scattering amplitude as a function of wave number. The technique is demonstrated by determination of the size of polystyrene microspheres in a subsurface layer with subwavelength accuracy. Application of the technique to probing the size of cell nuclei in living epithelial tissues is discussed.

Fourier Analysis↗
PubMed2003

Molecular contrast in optical coherence tomography by use of a pump-probe technique.

We describe a novel technique for contrast enhancement in optical coherence tomography (OCT) that makes possible molecular-specific imaging for what is believed to be the first time. A pump-probe technique is employed in which a pulsed pump laser is tuned to ground-state absorption in a molecule of interest. The location of the target molecule population is derived from the resulting transient absorption of OCT sample-arm light acting as probe light. A signal processing technique for three-dimensional localization of the transient absorption signal is described, and preliminary results exhibiting OCT contrast from methylene blue dye in multilayer and scattering phantoms are presented.

Contrast Media↗