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Imaging changes in blood volume and oxygenation in the newborn infant brain using three-dimensional optical tomography.

Induced haemodynamic and blood oxygenation changes occurring within the brain of a ventilated newborn infant have been imaged in three dimensions using optical tomography. Noninvasive measurements of the flight times of transmitted light were acquired during illumination of the brain by laser pulses at wavelengths of 780 nm and 815 nm. The oxygen and carbon dioxide partial pressures were adjusted through alterations to the ventilator settings, resulting in changes to the cerebral blood volume and oxygenation. Three-dimensional images were generated using the physiologically associated differences in the measured data, obviating the need for data calibration using a separate reference measurement. The results exhibit large changes in absorption coefficient at both wavelengths. Images corresponding to differences in concentrations of oxy- and deoxyhaemoglobin are in qualitative agreement with known physiological data.

Blood Flow Velocity↗

Gauss-Newton method for image reconstruction in diffuse optical tomography.

We present a regularized Gauss-Newton method for solving the inverse problem of parameter reconstruction from boundary data in frequency-domain diffuse optical tomography. To avoid the explicit formation and inversion of the Hessian which is often prohibitively expensive in terms of memory resources and runtime for large-scale problems, we propose to solve the normal equation at each Newton step by means of an iterative Krylov method, which accesses the Hessian only in the form of matrix-vector products. This allows us to represent the Hessian implicitly by the Jacobian and regularization term. Further we introduce transformation strategies for data and parameter space to improve the reconstruction performance. We present simultaneous reconstructions of absorption and scattering distributions using this method for a simulated test case and experimental phantom data.

Algorithms↗

Optimal linear inverse solution with multiple priors in diffuse optical tomography.

A general framework for incorporating single and multiple priors in diffuse optical tomography is described. We explore the use of this framework for simultaneously utilizing spatial and spectral priors in the context of imaging breast cancer. The utilization of magnetic resonance images of water and lipid content as a statistical spatial prior for the diffuse optical image reconstructions is also discussed. Simulations are performed to demonstrate the significant improvement in image quality afforded by combining spatial and spectral priors.

Algorithms↗

Feasibility of three-dimensional optical coherence tomography and optical Doppler tomography of malignancy in hamster cheek pouches.

OBJECTIVE: Hamster cheek pouches (HCP) with various degrees of 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced dysplasia and malignancies were imaged with OCT/ODT in vivo and in vitro to assess the potential for three-dimensional high-resolution optical localization of airway malignancy. BACKGROUND DATA: Optical coherence tomography (OCT)/optical doppler tomography (ODT) provide potential capability for real-time in vivo high-resolution (2-20 microm) cross-sectional imaging of tissues and spatially resolved blood flow in microvasculature for pathology diagnostics. METHODS: DMBA was applied to the right side of the cheek pouch (HCP), and mineral oil (control) to the left side three times weekly for 10-18 weeks in Syrian Golden Hamsters using a standard protocol for malignancy induction. HCP were imaged in vivo with OCT/ODT as well as in vitro post-excision, using a prototype 1310-nm broadband superluminescent diode-based OCT/ODT device constructed in our laboratory. Three-dimensional images were constructed, and compared to standard and three-dimensional histology hematoxylin and eosin staining. RESULTS AND CONCLUSION: OCT imaging offered exceptional resolution of the HCP to depths of 1-2 mm and confirmed ability to detect dysplasia and malignancy. Three-dimensional OCT images were readily constructed, allowing visualization of extent and localization of tumor margins. ODT demonstrated increased vascularity in the area of neoplasia. OCT/ODT is a promising new technology for oral airway diagnostics.

Animals↗

Measurement of particle-size distribution and concentration in heterogeneous turbid media with multispectral diffuse optical tomography.

We present a method that is capable of extracting particle-size distribution (PSD) and concentration in heterogeneous turbid media by use of multispectral diffuse optical tomography (MSDOT). After the spectroscopic scattering images of the heterogeneous turbid media are obtained with MSDOT, the morphologic information of particles in the heterogeneities is recovered with an iterative regularized reconstruction algorithm based on Mie scattering theory when a particular form of PSD is assumed (Gaussian distribution is used in this study). The method described is tested and evaluated with both simulated and experimental data. The simulations are intended to test the sensitivity of the overall approach to noise effect. A series of phantom experiments are conducted with our newly developed ten-wavelength MSDOT system. Polystyrene microsphere suspensions contain particles of varying size from 2 to 6 microm as targets are embedded in a scattering background medium in these experiments. To achieve optimized results from experimental data, we developed a data preprocessing method for MSDOT as well as a scheme for calibrating scattering spectra. The results from both simulations and experiments show that the particle mean size and concentration can be reconstructed with acceptable accuracy, whereas the recovery of the standard deviation is sensitive to noise effect and can be as large as 86% from the experimental data.

Algorithms↗

Design and implementation of a multifrequency near-infrared diffuse optical tomography system.

The design and implementation of a multifrequency and multispectral diffuse optical tomography system is described. Four wavelengths are utilized: 665, 785, 808, and 830 nm. The system is based on a network analyzer, which provides rf modulation signals for the laser diodes, as well as measures the amplitude and the phase of the detected signals. Six different modulation frequencies ranging from 110 to 280 MHz are used. The details of instrumentation, calibration, data acquisition, and performance of the system are given. A finite element algorithm is used to solve the diffusion equation, and an inverse solver based on this forward solver is implemented to calculate the absorption and scattering maps from the acquired data. Data acquisition for one wavelength is completed in less than 2.5 min for a single modulation frequency. The measurement repeatability is 0.5% in ac intensity and 0.2 deg in phase. The performance of the system is evaluated with phantom studies. A multifrequency reconstruction algorithm is used, in which a single absorption and scattering image pair is obtained using the whole dataset obtained at different modulation frequencies. It is shown that the multifrequency reconstruction approach provides superior image quality compared to the single frequency counterpart.

Equipment Design↗

Imaging growth dynamics of tumour spheroids using optical coherence tomography.

Optical coherence tomography (OCT) was used to monitor the dynamics of tumour spheroid formation by the hanging drop method. In contrast to microscopy, the estimates obtained using OCT for the volume of the spheroid, were consistent with the measured changes in cell number as a function of time. The OCT images also revealed heterogeneous structures in the spheroids of approximately 200 microm diameter. These corresponded to the necrotic regions identified by fluorescence of propidium iodide stained cells.

Cell Count↗

Possible histopathologic correlates of dermoscopic features in pigmented melanocytic lesions identified by means of optical coherence tomography.

Optical coherence tomography (OCT) is a novel non-invasive imaging technique for in vivo histologic characterization of tissues. Besides pure morphology, additional functional parameters of the tissue investigated can be evaluated at the same time, such as the refractive index and the scattering coefficient. The purpose of our study is to correlate in vivo the dermoscopic structures that first appear in the melanocytic pigmented lesion (pigment network and brown globules) using this new method, with the histopathologic correlates, in order to improve their characterization and achieve easier recognition and inter-observer reproducibility. We concentrated in particular on the pigment network and the brown globules, as these are dermoscopic parameters of great diagnostic importance in melanocytic lesions. Moreover, as these parameters are the histopathologic equivalents of structures located at the level of the dermo-epidermal junction, they enable a correct evaluation to be made using OCT, that at present has only a few millimetres penetration power. The results of our trial, performed using the histopathological preparation as an evaluation gold standard, show that in selected cases OCT allows an in vivo correlation to be made between surface dermoscopic parameters and histopathologic correlates, in particular the pigment network and brown globules. The resolution is not high enough to reveal the morphology of the single cells, but it is possible to evaluate the architecture of a lesion.

Adult↗

New method for evaluation of in vivo scattering and refractive index properties obtained with optical coherence tomography.

Optical coherence tomography (OCT) provides more parameters than pure morphology does. In a recent paper [A. Knuettel and M. Boehlau-Godau, J. Biomed. Opt. 5(1) 83-92 (2000)] we have shown that the refractive index (RI) can be evaluated in a localized manner in skin tissue under in vivo conditions. Based on a theory, originally developed for light detecting and ranging applications [L. Thrane et al., J. Opt. Soc. Am. A 17(3) 484-490 (2000)], the parameter mean scattering angle (MSA) could be derived in addition to RI. The effects of hydration on MSA and RI have been evaluated in vitro in pigskin and in vivo in human skin with our OCT scanner SkinDex 300. These parameters may have a viable impact in (cosmetic) skin research and clinical diagnoses. To the best of our knowledge, this is the first time that (multiple) scattering of light has been quantified through the observation of a new scattering parameter under in vivo conditions.

Adult↗

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↗

Visualization of neointima formation by optical coherence tomography.

Optical coherence tomography (OCT) has recently been proposed as a high-resolution imaging method. Our male patient, who had been treated with a coronary stent, died due to acute leukemia. Coronary artery images using intravascular ultrasound (IVUS) and OCT were obtained postmortem. We also compared the image of neointima formation after stent implantation evaluated by histopathological examination with that evaluated by IVUS and OCT. OCT visualized well-apposed stent struts and neointima formation, which could not be visualized completely by IVUS. OCT may be useful for monitoring structural changes after stent implantation.

Coronary Stenosis↗

Complete-angle projection diffuse optical tomography by use of early photons.

We present the first, to our knowledge, experimental images of complex-shaped phantoms embedded in diffuse media by use of optical tomography. Imaging is based on a complete-angle projection tomographic technique that utilizes transmitted early photons. Results are contrasted with measurements obtained at later gates as well as pseudocontinuous-wave data. The scanning system developed employs noncontact illumination and detection technologies that allow for high spatial sampling of transmitted photons. Combining this system with complete-angle illumination is found to be an important strategy toward improved imaging performance, resulting in a better-posed inversion problem. The appropriateness of reconstruction algorithms similar to those employed in x-ray computed tomography are showcased, and suggestions for model improvements are provided.

Algorithms↗

Signal dependence and noise source in ultrasound-modulated optical tomography.

A Monte Carlo modeling technique was used to simulate ultrasound-modulated optical tomography in inhomogeneous scattering media. The contributions from two different modulation mechanisms were included in the simulation. Results indicate that ultrasound-modulated optical signals are much more sensitive to small embedded objects than unmodulated intensity signals. The differences between embedded absorption and scattering objects in the ultrasound-modulated optical signals were compared. The effects of neighboring inhomogeneity and background optical properties on the ultrasound-modulated optical signals were also studied. We analyzed the signal-to-noise ratio in the experiment and found that the major noise source is the speckle noise caused by small particle movement within the biological tissue sample. We studied this effect by incorporating a Brownian motion factor in the simulation.

Animals↗

Measurement and imaging of birefringent properties of the human cornea with phase-resolved, polarization-sensitive optical coherence tomography.

Optical coherence tomography (OCT) is an emerging technology for high-resolution, noncontact imaging of transparent and scattering media. Polarization-sensitive optical coherence tomography (PS-OCT) is a functional extension of OCT that can image birefringent properties of a biological sample. PS-OCT was used to measure and image retardation and birefringent axis orientation of in vitro human cornea. We used a two-channel PS-OCT system employing a phase-sensitive recording of the interferometric signals in two orthogonal polarization channels. Using an algorithm based on a Hilbert transform, it is possible to calculate the retardation and the slow axis orientation of the sample with only a single A-scan per transversal measurement location. While the retardation information is encoded in the amplitude ratio of the two interferometric signals, the axis orientation is encoded entirely in their phase difference. We present maps of retardation and the distribution of slow axis orientation of the human cornea in longitudinal cross-sections and en face images obtained at the back surface of the cornea. The retardation increases in a radial direction and with depth; the slow axis varies in the transversal direction. Knowledge of the retardation and the slow axis distribution of the cornea might improve nerve fiber polarimetry for glaucoma diagnostics and could be useful for diagnosing different types of pathologies of the cornea.

Birefringence↗

Three-dimensional optical tomography: resolution in small-object imaging.

Near-infrared (NIR) optical tomography provide estimates of the internal distribution of optical absorption and transport scattering from boundary measurement of light propagation within biological tissue. Although this is a truly three-dimensional (3D) imaging problem, most research to date has concentrated on two-dimensional modeling and image reconstruction. More recently, 3D imaging algorithms are demonstrating better estimation of the light propagation within the imaging region and are providing the basis of more accurate image construction algorithms. As 3D methods emerge, it will become increasingly important to evaluate their resolution, contrast, and localization of optical property heterogeneity. We present a concise study of 3D reconstructed resolution of a small, low-contrast, absorbing and scattering anomaly as it is placed in different locations within a cylindrical phantom. The object is an 8-mm-diameter cylinder, which represents a typical small target that needs to be resolved in NIR mammographic imaging. The best resolution and contrast is observed when the object is located near the periphery of the imaging region (12-22 mm from the edge) and is also positioned within the multiple measurement planes, with the most accurate results seen for the scatter image when the anomaly is at 17 mm from the edge. Furthermore, the accuracy of quantitative imaging is increased to almost 100% of the target values when a priori information regarding the internal structure of imaging domain is utilized.

Breast Neoplasms↗

Iterative total least-squares image reconstruction algorithm for optical tomography by the conjugate gradient method.

We present an iterative total least-squares algorithm for computing images of the interior structure of highly scattering media by using the conjugate gradient method. For imaging the dense scattering media in optical tomography, a perturbation approach has been described previously [Y. Wang et al., Proc. SPIE 1641, 58 (1992); R. L. Barbour et al., in Medical Optical Tomography: Functional Imaging and Monitoring (Society of Photo-Optical Instrumentation Engineers, Bellingham, Wash., 1993), pp. 87-120], which solves a perturbation equation of the form W delta x = delta I. In order to solve this equation, least-squares or regularized least-squares solvers have been used in the past to determine best fits to the measurement data delta I while assuming that the operator matrix W is accurate. In practice, errors also occur in the operator matrix. Here we propose an iterative total least-squares (ITLS) method that minimizes the errors in both weights and detector readings. Theoretically, the total least-squares (TLS) solution is given by the singular vector of the matrix [W/ delta I] associated with the smallest singular value. The proposed ITLS method obtains this solution by using a conjugate gradient method that is particularly suitable for very large matrices. Simulation results have shown that the TLS method can yield a significantly more accurate result than the least-squares method.

Algorithms↗

Optical projection tomography.

Optical projection tomography is a new approach for three-dimensional (3-D) imaging of small biological specimens. It fills an imaging gap between MRI and confocal microscopy, being most suited to specimens that are from 1 to 10 mm across. The tomographic principles of optical projection tomography (OPT) are explained, its most important applications in biomedical research explored, and comparisons drawn of its pros and cons compared to a number of alternative imaging technologies.

Animals↗

Macular hole: improved understanding of pathogenesis, staging, and management based on optical coherence tomography.

Optical coherence tomography (OCT) has improved the understanding and management of idiopathic macular hole. Images of precursor lesions and their progression demonstrate that antero-posterior as well as tangential traction are involved in macular hole formation. The staging of macular holes with biomicroscopic examination can be paralleled by optical coherence tomography staging with some modification. OCT is useful in differentiating simulating lesions and in allowing better counseling of patients regarding their disorder. Finally, OCT findings are prognostic of surgical success and can assist in evaluating the results of surgery.

Diagnosis, Differential↗