Serge Grabtchak

Separation of absorption and scattering properties of turbid media using relative spectrally resolved cw radiance measurements

We present a new method for extracting the effective attenuation coefficient and the diffusion coefficient from relative spectrally resolved cw radiance measurements using the diffusion approximation. The method is validated on both simulated and experimental radiance data sets using Intralipid-1% as a test platform. The effective attenuation coefficient is determined from a simple algebraic expression constructed from a ratio of two radiance measurements at two different source–detector separations and the same 90° angle. The diffusion coefficient is determined from another ratio constructed from two radiance measurements at two angles (0° and 180°) and the same source–detector separation. The conditions of the validity of the method as well as possible practical applications are discussed.

Detection of localized inclusions of gold nanoparticles in Intralipid-1% by point-radiance spectroscopy

Interstitial fiber-optic-based approaches used in both diagnostic and therapeutic applications rely on localized light-tissue interactions. We present an optical technique to identify spectrally and spatially specific exogenous chromophores in highly scattering turbid media. Point radiance spectroscopy is based on directional light collection at a single point with a side-firing fiber that can be rotated up to 360 deg. A side firing fiber accepts light within a well-defined, solid angle, thus potentially providing an improved spatial resolution. Measurements were performed using an 800-μm diameter isotropic spherical diffuser coupled to a halogen light source and a 600 μm, ∼43 deg cleaved fiber (i.e., radiance detector). The background liquid-based scattering phantom was fabricated using 1% Intralipid. Light was collected with 1 deg increments through 360 deg-segment. Gold nanoparticles , placed into a 3.5-mm diameter capillary tube were used as localized scatterers and absorbers introduced into the liquid phantom both on- and off-axis between source and detector. The localized optical inhomogeneity was detectable as an angular-resolved variation in the radiance polar plots. This technique is being investigated as a potential noninvasive optical modality for prostate cancer monitoring.

Optical detection of gold nanoparticles in a prostate-shaped porcine phantom

Abstract. Gold nanoparticles can be used as molecular contrast agents binding specifically to cancer sites and thus delineating tumor regions. Imaging gold nanoparticles deeply embedded in tissues with optical techniques possesses significant challenges due to multiple scattering of optical photons that blur the obtained images. Both diagnostic and therapeutic applications can benefit from a minimally invasive technique that can identify, localize, and quantify the payloads of gold nanoparticles deeply embedded in biological tissues. An optical radiance technique is applied to map localized inclusions of gold nanorods in 650- to 900-nm spectral range in a porcine phantom that mimics prostate geometry. Optical radiance defines a variation in the angular density of photons impinging on a selected point in the tissue from various directions. The inclusions are formed by immersing a capillary filled with gold nanorods in the phantom at increasing distances from the detecting fiber. The technique allows the isolation of the spectroscopic signatures of the inclusions from the background and identification of inclusion locations in the angular domain. Detection of ∼4×1010 gold nanoparticles or 0.04  mg Au/mL (detector–inclusion separation 10 mm, source–detector separation 15 mm) in the porcine tissue is demonstrated. The encouraging results indicate a promising potential of radiance spectroscopy in early prostate cancer diagnostics with gold nanoparticles.

Experimental spectro-angular mapping of light distribution in turbid media

We present a new approach to the analysis of radiance in turbid media. The approach combines data from spectral, angular and spatial domains in a form of spectro-angular maps. Mapping provides a unique way to visualize details of light distribution in turbid media and allows tracking changes with distance. Information content of experimental spectro-angular maps is verified by a direct comparison with simulated data when an analytical solution of the radiative transfer equation is used. The findings deepen our understanding of the light distribution in a homogenous turbid medium and provide a first step toward applying the spectro-angular mapping as a diagnostic tool for tissue characterization.

Radiance detection of non-scattering inclusions in turbid media

Detection of non-scattering domains (voids) is an area of active research in biomedical optics. To avoid complexities of image reconstruction algorithms and requirements of a priori knowledge of void locations inherent to diffuse optical tomography (DOT), it would be useful to establish specific experimental signatures of voids that would help identify and detect them by other means. To address this, we present a radiance-based spectro-angular mapping approach that identifies void locations in the angular domain and establishes their spectral features. Using water-filled capillaries in scattering Intralipid as a test platform, we demonstrate perturbations in the directional photon density distribution produced by individual voids.

Feasibility of interstitial near-infrared radiance spectroscopy platform for ex vivo canine prostate studies: optical properties extraction, hemoglobin and water concentration, and gold nanoparticles detection

Abstract. The canine prostate is a close match for the human prostate and is used in research of prostate cancers. Determining accurately optical absorption and scattering properties of the gland in a wide spectral range (preferably in a minimally invasive way), linking optical properties to concentrations of major endogenous chromophores, and detecting the presence of localized optical inhomogeneities like inclusions of gold nanoparticles for therapeutic and diagnostic purposes, are among the major challenges for researchers. The goal of the article is to demonstrate a feasibility of the multifunctional radiance spectroscopy platform in providing the required information. For ex vivo canine prostate, extraction of the effective attenuation and diffusion coefficients using relative cw radiance measurements was demonstrated in the 650- to 900-nm range. The derived absorption coefficient was decomposed to contributions from 9.0 μM HbO2, 29.6 μM Hb, and 0.47 fractional volume of H2O. Detection of a localized inclusion containing ∼1.5·1010 gold nanorods (0.8 μg Au) at 10 mm distance from the urethra was achieved with the detector in the urethra and the light source in a virtual rectum position. The platform offers the framework for a systematic study of various chromophores in the prostate that can be used as comprehensive diagnostic markers.

Radiance spectroscopy tool box for characterizing Au Nanoparticles in tissue mimicking phantoms as applied to prostate

Background: We have developed a new approach to map localized inclusions of gold nanoparticles in the Intralipid-1% liquid phantom. Our goal was to show that combined spectroscopic and angular snapshots of liquid phantoms and phantoms with inclusions allow obtaining information relevant for prostate cancer diagnostics and treatment. Methods: A combination of the point radiance spectroscopy and white light spectroscopy was used to measure angular resolved light distribution in 450-900 nm spectral range in Intralipid-1% liquid phantoms with and without localized inclusions of gold nanoparticles. Results: Characteristic spectro-angular snapshots of the liquid phantom alone and with the localized inclusion of gold nanoparticles were obtained. For liquid phantoms without inclusions, the snapshots demonstrate wavelength dependent light distribution inside the turbid medium, visualize the transparency window and provide a quantification of angular spread of different wavelengths of light. For liquid phantoms with gold inclusions, the approach allows to isolate the spectroscopic signatures of the inclusions from the background, identify locations of the inclusions in the angular domain and quantify the detection limits in terms of the contrast value attainable for the selected quantity of gold nanoparticles located at the specific depth in tissue. A detection of 3x10 13 particles up to 25 mm deep in Intralipid-1% was demonstrated. Conclusions: The encouraging results indicate a promising potential of radiance spectroscopy in prostate treatment and diagnostics with gold nanoparticles.

Two-step lateral taper spot-size converter for efficient fiber coupling to InP-based photonic integrated circuits

Spot-size converters (SSC) are an important building block of InP-based photonic integrated circuits since it allows a standard single-mode fiber with a large and symmetric mode spot to be efficiently coupled with large displacement tolerance to a semiconductor waveguide with a small and asymmetric mode spot. Having an on-chip SSC is practically advantageous since such an element greatly simplifies the packaging process while increasing its reliability. In this paper, a SSC utilizing two-step lateral tapering is proposed for converting the semiconductor waveguide device mode into that suitable for fiber coupling without compromising the designs of the device and coupling waveguides. This is achieved by inserting a transient taper between the device and coupling waveguide as an impedance matcher. This paper describes the design principles and characterization results for such a two-step SSC, compatible with earlier reported InP-based photonic integrated circuits for WDM. Transmission and photoresponsivity measurements (the last - by using an on-chip waveguide photodetector monolithically integrated with the SSC) show excellent performance of the two-step SSC. In good agreement with simulations, it was experimentally demonstrated that using this integrated component for fiber coupling can reduce the coupling loss to below 1dB and the alignment tolerances are improved by two and three times on the horizontal and vertical directions, respectively.

Spatially-resolved probing of biological phantoms by point-radiance spectroscopy

Interstitial fiber-optic based strategies for therapy monitoring and assessment rely on detecting treatment-induced changes in the light distribution in biological tissues. We present an optical technique to identify spectrally and spatially specific tissue chromophores in highly scattering turbid media. Typical optical sensors measure non-directional light intensity (i.e. fluence) and require fiber translation (i.e. 3-5 positions), which is difficult to implement clinically. Point radiance spectroscopy is based on directional light collection (i.e. radiance) at a single point with a side-firing fiber that can be rotated up to 360°. A side firing fiber accepts light within a well-defined solid angle thus potentially providing an improved spatial resolution. Experimental measurements were performed using an 800-μm diameter isotropic spherical diffuser coupled to a halogen light source and a 600 μm, ~43° cleaved fiber (i.e. radiance detector). The background liquid-based scattering phantom was fabricated using 1% Intralipid (i.e. scattering medium). Light was collected at 1-5° increments through 360°-segment. Gold nanoparticles, placed into a 3.5 mm diameter capillary tube were used as localized scatterers and absorbers introduced into the liquid phantom both on- and off-axis between source and detector. The localized optical inhomogeneity was detectable as an angular-resolved variation in the radiance polar plots. This technique is being investigated as a non-invasive optical modality for prostate cancer monitoring.

Interstitial diffuse radiance spectroscopy of gold nanocages and nanorods in bulk muscle tissues

Radiance spectroscopy was applied to the interstitial detection of localized inclusions containing Au nanocages or nanorods with various concentrations embedded in porcine muscle phantoms. The radiance was quantified using a perturbation approach, which enabled the separation of contributions from the porcine phantom and the localized inclusion, with the inclusion serving as a perturbation probe of photon distributions in the turbid medium. Positioning the inclusion at various places in the phantom allowed for tracking of photons that originated from a light source, passed through the inclusion’s location, and reached a detector. The inclusions with high extinction coefficients were able to absorb nearly all photons in the range of 650–900 nm, leading to a spectrally flat radiance signal. This signal could be converted to the relative density of photons incident on the inclusion. Finally, the experimentally measured quantities were expressed via the relative perturbation and arranged into the classical Beer–Lambert law that allowed one to extract the extinction coefficients of various types of Au nanoparticles in both the transmission and back reflection geometries. It was shown that the spatial variation of perturbation could be described as 1/r dependence, where r is the distance between the inclusion and the detector. Due to a larger absorption cross section, Au nanocages produced greater perturbations than Au nanorods of equal particle concentration, indicating a better suitability of Au nanocages as contrast agents for optical measurements in turbid media. Individual measurements from different inclusions were combined into detectability maps.