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.
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 ∼4×10 10 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.
We have applied an optical radiance technique to map localized inclusions of gold nanoparticles in a porcine phantom. Our goal was to show that combined spectroscopic and angular snapshots of phantoms allow the obtaining of information that is relevant for prostate cancer diagnostics. A combination of the radiance spectroscopy and white light spectroscopy was used to measure angular resolved light distribution in 600-900 nm spectral range inside the 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. To obtain radiance data, a specially constructed optical probe with a well-defined angular detection window must be rotated along its axis. Characteristic spectro-angular snapshots of the phantom alone and with the localized inclusion of gold nanoparticles were obtained. The inclusions were formed by immersing a capillary filled with gold nanoparticles into selected locations in the phantom. For phantoms with gold inclusions, this approach allows the isolation of the spectroscopic signatures of the inclusions from the background and identification of inclusion locations in the angular domain. Detection of ~1010 gold nanoparticles (detector-inclusion separation 10 mm, source-detector separation 15 mm) in the porcine tissue was demonstrated. These encouraging results indicate a promising potential of radiance spectroscopy in early prostate cancer diagnostics with gold nanoparticles.
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.
We have applied an interstitial radiance-based technique based on a spectro-angular mapping approach to the
identification and angular localization of 250-nm and 5-nm Au nanoparticle-based inclusions and non-scattering (water
only) inclusions in the Intralipid-1% liquid phantom. 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% with
and without localized inclusions. Characteristic spectro-angular snapshots of the liquid phantom alone and with the
localized inclusions were obtained. For liquid phantoms without inclusions, the snapshots demonstrate wavelength
dependent light distribution inside the turbid medium. 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 show how a presence of water in the inclusion affects spectral identification and angular localization
of the target. For liquid phantoms with water-based inclusions, an ability of the inclusion to enhance photon density
above reference values and angular dependent signatures were demonstrated. The technique is seen as a potential tool in
prostate treatment and diagnostics with gold nanoparticles.
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.
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.
Spot-size converter (SSC) is 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 high displacement tolerance to a semiconductor waveguide with a small and asymmetric mode spot. Having an on-chip SSC integrated with a semiconductor waveguide 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, Fabry-Perot fringes 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, which includes the taper radiation loss of ~0.2 dB.
In WDM optical networks, signals have to be manipulated and monitored on a per wavelength basis. This requires that (de)multiplexing and wavelength processing functions are combined in the same optical component. The most efficient solution from a footprint size, cost and reliability point of view would be a combination of both functions in one photonic integrated circuit (PIC), fabricated by photolithography. Given that processing / detecting of individual wavelengths is an active function, in S, C and L communication bands naturally realized by InP and related semiconductor materials, InP-based PICs are widely agreed to be the superior choice.
This paper reports a practical design of such InP-based PICs. It is based on a building block approach, which allows a large variety of WDM optical components to be built from relatively few monolithically integrable elements, by using standard semiconductor fabrication technologies. These include: (i) (de)multiplexer based on a planar echelle diffractive grating with polarization compensation in the slab waveguide region; (ii) single-mode vertically integrated waveguide active devices with detecting, attenuating, amplifying and switching features, inserted in every (in)output waveguide channel of a planar (de)multiplexer, and (iii) passive waveguide circuitry required for coupling the light to and directing it through the InP-based photonic chip. Design and characterization examples of the building blocks and PICs for channel monitoring, variable attenuation / equalization and spatial switching are presented.
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