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Biomedical subjects

A G Yodh

Publications and source records attributed to A G Yodh.

16 recordsLinked to original sources

Angle-resolved second-harmonic light scattering from colloidal particles.

We report angle-resolved second-harmonic generation (SHG) measurements from suspensions of centrosymmetric micron-size polystyrene spheres with surface-adsorbed dye (malachite green). The second-harmonic scattering profiles differ qualitatively from linear light scattering profiles of the same particles. We investigated these radiation patterns using several polarization configurations and particle diameters. We introduce a simple Rayleigh-Gans-Debye model to account for the SHG scattering anisotropy. The model compares favorably with our experimental data. Our measurements suggest scattering anisotropy may be used to isolate particle nonlinear optics from other bulk nonlinear optical effects in suspension.

Anisotropy↗

Colloidal interactions in suspensions of rods.

We report direct measurements of entropic interactions of colloidal spheres in suspensions of rodlike fd bacteriophage. We investigate the influence of sphere size, rod concentration, and ionic strength on these interactions. Although the results compare favorably with a recent calculation, small discrepancies reveal entropic effects due to rod flexibility. At high salt concentrations, the potential turns repulsive as a result of viral adsorption on the spheres and viral bridging between the spheres.

Biophysical Phenomena↗

Measurement of long-range steric repulsions between microspheres due to an adsorbed polymer.

We have measured the interparticle potential between pairs of micron-sized silica spheres induced by adsorbed polyethylene oxide polymer using a line-scanned optical tweezer. We found this long-range steric repulsion to be exponential over the range of energies (0.1k(B)T-5k(B)T) and polymer molecular weights (452,000-1,580,000) studied, and that the potential scaled with the polymer's radius of gyration R(G). The potential's exponential decay length was about 0.6R(G) and its range was about 4R(G), although both parameters varied significantly from one pair of spheres to another. The potential's exponential prefactor was greater than mean-field predictions.

Adsorption↗

In vivo cerebrovascular measurement combining diffuse near-infrared absorption and correlation spectroscopies.

We combine two near-infrared diffuse optical techniques to study variations of blood flow, haemoglobin concentration, and blood oxygen saturation in the functioning rat brain. Diffuse correlation spectroscopy (or flowmetry) monitors changes in the cerebral blood flow, without the use of the principles of tracer clearance, by measuring the optical phase-shifts caused by moving blood cells. Near-infrared absorption spectroscopy concurrently measures tissue absorption at two wavelengths to determine haemoglobin concentration and blood oxygen saturation in this same tissue volume. This optical probe is non-invasive and was employed through the intact skull. The utility of the technique is demonstrated in vivo by measuring the temporal changes in the regional vascular dynamics of rat brain during hypercapnia. Temporal and spatial variations of cerebral blood flow, haemoglobin concentration and blood oxygen saturation during hypercapnia are compared with other measurements in the literature, and a quantitative analysis demonstrating the self-consistency of our combined observations of vascular response is presented.

Animals↗

Diffuse optical tomography of highly heterogeneous media.

We investigate the performance of diffuse optical tomography to image highly heterogeneous media, such as breast tissue, as a function of background heterogeneity. To model the background heterogeneity, we have employed the functional information derived from Gadolinium-enhanced magnetic resonance images of the breast. We demonstrate that overall image quality and quantification accuracy worsens as the background heterogeneity increases. Furthermore we confirm the appearance of characteristic artifacts at the boundaries that scale with background heterogeneity. These artifacts are very similar to the ones seen in clinical examinations and can be misinterpreted as actual objects if not accounted for. To eliminate the artifacts and improve the overall image reconstruction, we apply a data-correction algorithm that yields superior reconstruction results and is virtually independent of the degree of the background heterogeneity.

Algorithms↗

Recovery of optical parameters in multiple-layered diffusive media: theory and experiments.

Diffuse photon density waves have lately been used both to characterize diffusive media and to locate and characterize hidden objects, such as tumors, in soft tissue. In practice, most biological media of medical interest consist of various layers with different optical properties, such as the fat layer in the breast or the different layers present in the skin. Also, most experimental setups consist of a multilayered system, where the medium to be characterized (i.e., the patient's organ) is usually bounded by optically diffusive plates. Incorrect modeling of interfaces may induce errors comparable to the weak signals obtained from tumors embedded deep in highly heterogeneous tissue and lead to significant reconstruction artifacts. To provide a means to analyze the data acquired in these configurations, the basic expressions for the reflection and transmission coefficients for diffusive-diffusive and diffusive-nondiffusive interfaces are presented. A comparison is made between a diffusive slab and an ordinary dielectric slab, thus establishing the limiting distance between the two interfaces of the slab for multiple reflections between them to be considered important. A rigorous formulation for multiple-layered (M-layered) diffusive media is put forward, and a method for solving any M-layered medium is shown. The theory presented is used to characterize a two-layered medium from transmission measurements, showing that the coefficients of scattering, mu'(s) , and absorption, mu(a) , are retrieved with great accuracy. Finally, we demonstrate the simultaneous retrieval of both mu;(s) and mu(a).

Diffusion↗

Two-point microrheology of inhomogeneous soft materials.

We demonstrate a novel method for measuring the microrheology of soft viscoelastic media, based on cross correlating the thermal motion of pairs of embedded tracer particles. The method does not depend on the exact nature of the coupling between the tracers and the medium, and yields accurate rheological data for highly inhomogeneous materials. We demonstrate the accuracy of this method with a guar solution, for which other microscopic methods fail due to the polymer's mesoscopic inhomogeneity. Measurements in an F-actin solution suggest conventional microrheology measurements may not reflect the true bulk behavior.

Actins↗

Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement.

We present quantitative optical images of human breast in vivo. The images were obtained by using near-infrared diffuse optical tomography (DOT) after the administration of indocyanine green (ICG) for contrast enhancement. The optical examination was performed concurrently with a magnetic resonance imaging (MRI) exam on patients scheduled for excisional biopsy or surgery so that accurate image coregistration and histopathological information of the suspicious lesions was available. The ICG-enhanced optical images coregistered accurately with Gadolinium-enhanced magnetic resonance images validating the ability of DOT to image breast tissue. In contrast to simple transillumination, we found that DOT provides for localization and quantification of exogenous tissue chromophore concentrations. Additionally our use of ICG, an albumin bound absorbing dye in plasma, demonstrates the potential to differentiate disease based on the quantified enhancement of suspicious lesions.

Aged↗

Comparison between isotropic and nonisotropic dosimetry systems during intraperitoneal photodynamic therapy.

BACKGROUND AND OBJECTIVE: On-line monitoring of light fluence during intraperitoneal photodynamic therapy (IP PDT) is crucial for safe light delivery. A flat photodiode-based dosimetry system is compared with an isotropic detector-based system in patients undergoing IP PDT. STUDY DESIGN/MATERIALS AND METHODS: Flat photodiodes and spherical detectors were placed side by side in the abdomen, for simultaneous light dosimetry in 19 patients. Tissue phantom experiments were performed to provide a preliminary estimate of the tissue optical properties of the peritoneum. RESULTS: The conversion factor between systems for 630-nm light was found to be 1.7 +/- 0.12. The mu(eff) of the tissues in the abdomen is estimated to vary between 0.5 cm(-1) to 1.4 cm(-1) assuming a mu(s)' = 7 cm(-1). CONCLUSIONS: The measured conversion factor should allow for comparison of light fluences with future clinical protocols that use an isotropic-based detector system. Differences in the optical properties of the underlying tissues may contribute to the variability in light measurements.

Clinical Protocols↗

Near-field diffraction tomography with diffuse photon density waves.

An angular spectrum algorithm is presented for fast, near-field diffraction tomographic imaging with diffuse photon density waves in highly scattering media. A general relation in K space is derived that connects the spatial variations of the optical properties of heterogeneities to the spatial spectra of the measured scattered diffuse photon density waves. The theory is verified experimentally for situations when boundary effects can be neglected. We further describe how to reconstruct absorption and scattering properties simultaneously, and how to incorporate boundary conditions into this angular spectrum algorithm for a turbid medium of finite size (e.g., the slab medium). Limitations and potential improvements of the near-field diffraction tomography are also discussed.

Algorithms↗

Three-dimensional diffuse optical mammography with ultrasound localization in a human subject.

We describe an approach that combines clinical ultrasound and photon migration techniques to enhance the sensitivity and information content of diffuse optical tomography. Measurements were performed on a postmenopausal woman with a single 1.8 x 0.9 cm malignant ductal carcinoma in situ approximately 7.4 mm beneath the skin surface (UCI IRB protocol 95-563). The ultrasound-derived information about tumor geometry enabled us to segment the breast tissue into tumor and background regions. Optical data was obtained with a multifrequency, multiwavelength hand-held frequency-domain photon migration backscattering probe. The optical properties of the tumor and background were then computed using the ultrasound-derived geometrical constraints. An iterative perturbative approach, using parallel processing, provided quantitative information about scattering and absorption simultaneously with the ability to incorporate and resolve complex boundary conditions and geometries. A three to four fold increase in the tumor absorption coefficient and nearly 50% reduction in scattering coefficient relative to background was observed (lambda = 674, 782, 803, and 849 nm). Calculations of the mean physiological parameters reveal fourfold greater tumor total hemoglobin concentration [Hbtot] than normal breast (67 microM vs 16 microM) and tumor hemoglobin oxygen saturation (SOx) values of 63% (vs 73% and 68% in the region surrounding the tumor and the opposite normal tissue, respectively). Comparison of semi-infinite to heterogeneous models shows superior tumor/background contrast for the latter in both absorption and scattering. Sensitivity studies assessing the impact of tumor size and refractive index assumptions, as well as scan direction, demonstrate modest effects on recovered properties.

Absorption↗

Regional imager for low-resolution functional imaging of the brain with diffusing near-infrared light.

We have developed a near-infrared spectroscopy system for low-resolution regional imaging of the brain. Our regional imager employs two intensity-modulated (frequency-domain) diode lasers operating at 779 and 834 nm, respectively, in order to produce macroscopic waves of diffusing photons. The interaction of these diffusive waves with tissue depends on laser modulation frequency, laser wavelength and the optical properties of the sample tissue volume. The lasers can be modulated over a range of frequencies from 50 to 400 MHz. Light is coupled to and from the head using a pad that has 12 source and 4 detector positions within an area of approximately 40 cm2. The pad can be moved to different positions on the head. Measurements from different source-detector combinations enable reconstruction of low-resolution images of the tissue volume beneath the pad. For example, we have made two-dimensional back-projection images of model systems in order to demonstrate the capabilities of the regional imager. We also present preliminary results from initial clinical studies at the Children's Hospital of Philadelphia.

Brain↗

Does the photon-diffusion coefficient depend on absorption?

We investigate the controversy over the precise form of the photon diffusion coefficient and suggest that it is largely independent of absorption, i.e., Do = v/3mu(s)'. After presentation of the general theoretical arguments underlying this assertion, Monte Carlo simulations are performed and explicitly reveal that the absorption independent diffusion coefficient gives better agreement with theory than the traditionally accepted photon diffusion coefficient, D(mu)a = v/3(mu(s) + mu(a)). The importance of resolving this controversy for the proper characterization of the material optical properties is discussed.

Absorption↗

Determination of optical properties and blood oxygenation in tissue using continuous NIR light.

In this article, we introduce a simple method to characterize optical properties and blood oxygenation in tissue using spatially resolved, steady-state reflectance. The method considers multiple source-detector separations larger than 2 cm, i.e. 20 times the optical mean free path in tissue, and makes an approximation to linearize the relationship between the separation and reflectance. Simulation results show that errors of the algorithm due to the approximation are less than 10%. Using a calibration sample, we calculate from the slope and intercept the absorption and reduced scattering coefficients, mu a and mu's, of a tissue-like solution, and experimental results confirm the usefulness of the method for quantitation of haemoglobin saturation in tissue.

Algorithms↗

Scattering of diffuse photon density waves by spherical inhomogeneities within turbid media: analytic solution and applications.

We present an analytic solution for the scattering of diffuse photon density waves by spherical inhomogeneities within turbid media. The analytic result is compared to experimental measurements. Close agreement between theory and experiment permits the use of the theory to determine the properties of unknown sphere-like objects embedded in turbid media. The analytic solution is extended to encompass several problems of practical interest in imaging, including the influence of multiple sources, multiple objects, and boundaries on the characterization of spherical inhomogeneities. We also extend the solution to encompass time-domain measurements.

Algorithms↗