Effect of magnetic field alignment of cellulose nanocrystals in starch nanocomposites: Physicochemical and mechanical properties.

The magnetic field (MF) induced alignment of cellulose nanocrystals (CNC) within a starch matrix is investigated and its effect on the physicochemical and mechanical properties of the nanocomposites are discussed in the paper. Two different kinds of CNC i.e. plant-CNC and tunicate-CNC and its hybrid combination are studied to understand the effect of aspect ratio of CNC on the properties of nanocomposite. Nanocomposites with tunicate sourced CNC showed higher tensile strength and modulus, and lower water vapor permeability as compared to plant sourced CNC. These properties are higher for nanocomposites prepared under MF. The modulus of starch nanocomposites increased from 0.26 GPa and 0.32 GPa to 0.38 GPa and 0.44 GPa, respectively for plant-CNC and tunicate-CNC when exposed to MF. The improved orientation and alignment of CNC in presence of MF is further supported by Raman and scanning electron micrographs studies.

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.

Optoacoustic characterization of prostate cancer in an in vivo transgenic murine model.

Optoacoustic (OA) imaging was employed to distinguish normal from neoplastic tissues in a transgenic murine model of prostate cancer. OA images of five tumor-bearing mice and five age-matched controls across a 14 mm × 14 mm region of interest (ROI) on the lower abdomen were acquired using a reverse-mode OA imaging system (Seno Medical Instruments Inc., San Antonio, Texas). Neoplastic prostate tissue was identified based on the OA signal amplitude in combination with spectral analysis of the OA radio frequency (RF) data. Integration of the signal amplitude images was performed to construct two-dimensional images of the ROI. The prostate tumors generated higher amplitude signals than those of the surrounding tissues, with contrast ratios ranging from 31 to 36 dB. The RF spectrum analysis showed significant differences between the tumor and the control mice. The midband fit was higher by 5 dB (62%), the intercept higher by 4 dB (57%) and the spectral slope higher by 0.4 dB/MHz (50%) for neoplastic prostate tissue compared to normal tissues in the control mice. The results demonstrate that OA offers high contrast imaging of prostate cancer in vivo.

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.

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.

Optical absorption and scattering properties of bulk porcine muscle phantoms from interstitial radiance measurements in 650-900 nm range.

We demonstrated the application of relative radiance-based continuous wave (cw) measurements for recovering absorption and scattering properties (the effective attenuation coefficient, the diffusion coefficient, the absorption coefficient and the reduced scattering coefficient) of bulk porcine muscle phantoms in the 650-900 nm spectral range. Both the side-firing fiber (the detector) and the fiber with a spherical diffuser at the end (the source) were inserted interstitially at predetermined locations in the phantom. The porcine phantoms were prostate-shaped with ∼4 cm in diameter and ∼3 cm thickness and made from porcine loin or tenderloin muscles. The described method was previously validated using the diffusion approximation on simulated and experimental radiance data obtained for homogenous Intralipid-1% liquid phantom. The approach required performing measurements in two locations in the tissue with different distances to the source. Measurements were performed on 21 porcine phantoms. Spectral dependences of the effective attenuation and absorption coefficients for the loin phantom deviated from corresponding dependences for the tenderloin phantom for wavelengths <750 nm. The diffusion constant and the reduced scattering coefficient were very close for both phantom types. To quantify chromophore presence, the plot for the absorption coefficient was matched with a synthetic absorption spectrum constructed from deoxyhemoglobin, oxyhemoglobin and water. The closest match for the porcine loin spectrum was obtained with the following concentrations: 15.5 µM (±30% s.d.) Hb, 21 µM (±30% s.d.) HbO2 and 0.3 (±30% s.d.) fractional volume of water. The tenderloin absorption spectrum was best described by 30 µM Hb (±30% s.d), 19 µM (±30% s.d.) HbO2 and 0.3 (±30% s.d.) fractional volume of water. The higher concentration of Hb in tenderloin was consistent with a dark-red appearance of the tenderloin phantom. The method can be applied to a number of biological tissues and organs for interstitial optical interrogation.

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

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.

Tagging photons with gold nanoparticles as localized absorbers in optical measurements in turbid media.

We analyze a role of a localized inclusion as a probe for spatial distributions of migrating photons in turbid media. We present new experimental data and two-dimensional analysis of radiance detection of a localized absorptive inclusion formed by gold nanoparticles in Intralipid-1% when the target is translated along the line connecting the light source and detector. Data are analyzed using the novel analytical expression for the relative angular photon distribution function for radiance developed by extending the perturbation approach for fluence. Obtained photon maps allow predicting conditions for detectability of inclusions for which proximity to the detector is essential.

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.

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.

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.

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.

Study of laser-induced thermoelastic deformation of native and coagulated ex-vivo bovine liver tissues for estimating their optical and thermomechanical properties.

Several studies have explored the potential of optoacoustic imaging for monitoring thermal therapies, yet the origin of the contrast in the images is not well understood. A technique is required to measure the changes in the optical and thermomechanical properties of tissues upon coagulation to better understand this contrast. An interferometric method is presented for measuring simultaneously the optical and thermomechanical properties of native and coagulated ex-vivo bovine tissue samples based on analysis of the surface displacement of irradiated samples. Surface displacements are measured after irradiation by short laser pulses at 750 nm. A 51% decrease in the optical attenuation depth is observed for coagulated liver samples compared to native samples. No significant differences in the Grüneisen coefficient are measured in the native and coagulated tissue samples. A mean value of 0.12 for the Grüneisen coefficient is measured for both native and coagulated liver tissues. The displacement profiles exhibit consistent differences between the two tissue types. To assess the changes in the sample mechanical properties, the experimental data also are compared to numerical solutions of the equation for thermoelastic deformation. The results demonstrate that differences in the tissue expansion dynamics arise from higher values of elastic modulus for coagulated liver samples compared to native ones.

Assessment of thermal coagulation in ex-vivo tissues using Raman spectroscopy.

Raman spectroscopy is used to study the effects of heating on specific molecular bonds present in albumen-based coagulation phantoms and ex-vivo tissues. Thermal coagulation is induced by submerging albumen-based phantoms in a 75°C water bath to achieve target temperatures of 45, 55, 65, and 75°C. Laser photocoagulation is performed on ex-vivo bovine muscle samples, yielding induced temperatures between 46 and 90°C, as reported by implanted microthermocouples. All phantoms and tissue samples are cooled to room temperature, and Raman spectra are acquired at the microthermocouple locations. Shifts in major Raman bands are observed with laser heating in bovine muscle, specifically from the amide-1 α-helix group (∼1655 cm(-1)), the CH(2)/CH(3) group (∼1446 cm(-1)), the Cα-H stretch group (∼1312 cm(-1)), and the CN stretch group (∼1121cm(-1)). Raman bands at 1334 cm(-1) (tryptophan), 1317 cm(-1) [ν(Cα-H)], and 1655 cm(-1) (amide-1 α-helix) also show a decrease in intensity following heating. The results suggest that Raman band locations and relative intensities are affected by thermal denaturation of proteins, and hence, may be a useful tool for monitoring the onset and progression of coagulation during thermal therapies.

Frequency domain photothermoacoustic signal amplitude dependence on the optical properties of water: turbid polyvinyl chloride-plastisol system.

Photoacoustic (more precisely, photothermoacoustic) signals generated by the absorption of photons can be related to the incident laser fluence rate. The dependence of frequency domain photoacoustic (FD-PA) signals on the optical absorption coefficient (micro(a)) and the effective attenuation coefficient (micro(eff)) of a turbid medium [polyvinyl chloride-plastisol (PVCP)] with tissuelike optical properties was measured, and empirical relationships between these optical properties and the photoacoustic (PA) signal amplitude and the laser fluence rate were derived for the water (PVCP system with and without optical scatterers). The measured relationships between these sample optical properties and the PA signal amplitude were found to be linear, consistent with FD-PA theory: micro(a)=a(A/Phi)-b and micro(eff)=c(A/Phi)+d, where Phi is the laser fluence, A is the FD-PA amplitude, and a, ...,d are empirical coefficients determined from the experiment using linear frequency-swept modulation and a lock-in heterodyne detection technique. This quantitative technique can easily be used to measure the optical properties of general turbid media using FD-PAs.

Perturbative diffusion theory formalism for interpreting temporal light intensity changes during laser interstitial thermal therapy.

In an effort to understand dynamic optical changes during laser interstitial thermal therapy (LITT), we utilize the perturbative solution of the diffusion equation in heterogeneous media to formulate scattering weight functions for cylindrical line sources. The analysis explicitly shows how changes in detected interstitial light intensity are associated with the extent and location of the volume of thermal coagulation during treatment. Explanations for previously reported increases in optical intensity observed early during laser heating are clarified using the model and demonstrated with experimental measurements in ex vivo bovine liver tissue. This work provides an improved understanding of interstitial optical signal changes during LITT and indicates the sensitivity and potential of interstitial optical monitoring of thermal damage.

Determination of the optical properties of turbid media using relative interstitial radiance measurements: Monte Carlo study, experimental validation, and sensitivity analysis.

Interstitial quantification of the optical properties of tissue is important in biomedicine for both treatment planning of minimally invasive laser therapies and optical spectroscopic characterization of tissues, for example, prostate cancer. In a previous study, we analyzed a method first demonstrated by Dickey et al., [Phys. Med. Biol. 46, 2359 (2001)] to utilize relative interstitial steady-state radiance measurements for recovering the optical properties of turbid media. The uniqueness of point radiance measurements were demonstrated in a forward sense, and strategies were suggested for improving performance under noisy experimental conditions. In this work, we test our previous conclusions by fitting the P3 approximation for radiance to Monte Carlo predictions and experimental data in tissue-simulating phantoms. Fits are performed at: 1. a single sensor position (0.5 or 1 cm), 2. two sensor positions (0.5 and 1 cm), and 3. a single sensor position (0.5 or 1 cm) with input knowledge of the sample's effective attenuation coefficient. The results demonstrate that single sensor radiance measurements can be used to retrieve optical properties to within approximately 20%, provided the transport albedo is greater than approximately 0.9. Furthermore, compared to the single sensor fits, employing radiance data at two sensor positions did not significantly improve the accuracy of recovered optical properties. However, with knowledge of the effective attenuation coefficient of the medium, optical properties can be retrieved experimentally to within approximately 10% for an albedo greater or equal to 0.5.

Information content of point radiance measurements in turbid media: implications for interstitial optical property quantification.

Motivated by a recent report by Dickey et al. [Phys. Med. Biol. 46, 2359 (2001)], who demonstrated optical property retrieval by using relative radiance measurements at a single position, we investigate the uniqueness of relative radiance measurements for quantifying the optical properties of turbid media by studying the solutions of the diffusion and P3 approximations of the Boltzmann transfer equation for a point source. Using the P3 approximation, we investigate the potential of radiance measurements for optical property recovery by examining the optical property response surface for point radiance information. We further derive first-order similarity relations for relative point radiance measurements and use these expressions to examine analytically the effects of noise on optical property retrieval over a wide range of optical properties typical of biological tissue. Finally, optimal experimental configurations are studied and explicit conditions for uniqueness derived that suggest potential strategies for improving optical property recovery. It is expected that point radiance measurements will prove valuable for both on-line treatment planning of minimally invasive laser therapies and optical characterization of tissues.

Laser photothermoacoustic heterodyned lock-in depth profilometry in turbid tissue phantoms.

Frequency-domain correlation and spectral analysis photothermoacoustic (FD-PTA) imaging is a promising new technique, which is being developed to detect tumor masses in turbid biological tissue. Unlike conventional biomedical photoacoustics which uses time-of-flight acoustic information induced by a pulsed laser to indicate the tumor size and location, in this research, a new FD-PTA instrument featuring frequency sweep (chirp) and heterodyne modulation and lock-in detection of a continuous-wave laser source at wavelength is constructed and tested for its depth profilometric capabilities with regard to turbid media imaging. Owing to the linear relationship between the depth of acoustic signal generation and the delay time of signal arrival to the transducer, information specific to a particular depth can be associated with a particular frequency in the chirp signal. Scanning laser-fluence modulation frequencies with a linear frequency sweep method preserves the depth-to-delay time linearity and recovers FD-PTA signals from a range of depths. Combining with the depth information carried by the back-propagated acoustic chirp signal at each scanning position, one could rapidly generate subsurface three-dimensional images of the scanning area at optimal signal-to-noise ratios and low laser fluences, a combination of tasks that is difficult or impossible by use of pulsed photoacoustic detection. In this paper, results of PTA scans performed on tissue mimicking control phantoms with various optical, acoustical, and geometrical properties are presented. A mathematical model is developed to study the laser-induced photothermoacoustic waves in turbid media. The model includes both the scattering and absorption properties of the turbid medium. A good agreement is obtained between the experimental and numerical results. It is concluded that frequency domain photothermoacoustics using a linear frequency sweep method and heterodyne lock-in detection has the potential to be a reliable tool for biomedical depth-profilometric imaging.

Optical and acoustic properties at 1064 nm of polyvinyl chloride-plastisol for use as a tissue phantom in biomedical optoacoustics.

A novel optoacoustic phantom made of polyvinyl chloride-plastisol (PVCP) for optoacoustic studies is described. The optical and acoustic properties of PVCP were measured. Titanium dioxide (TiO2) powder and black plastic colour (BPC) were used to introduce scattering and absorption, respectively, in the phantoms. The optical absorption coefficient (mua) at 1064 nm was determined using an optoacoustic method, while diffuse reflectance measurements were used to obtain the optical reduced scattering coefficient (mu's). These optical properties were calculated to be mua = (12.818 +/- 0.001)ABPC cm(-1) and mu's = (2.6 +/- 0.2)S(TiO2) + (1.4 +/- 0.1) cm(-1), where ABPC is the BPC per cent volume concentration, and S(TiO2) is the TiO2 volume concentration (mg mL(-1)). The speed of sound in PVCP was measured to be (1.40 +/- 0.02) x 10(3) m s(-1) using the pulse echo transmit receive method, with an acoustic attenuation of (0.56 +/- 1.01) f(1.51+/-0.06)MHz (dB cm(-1)) in the frequency range of 0.61-1.25 MHz, and a density, calculated by measuring the displacement of water, of 1.00 +/- 0.04 g cm(-3). The speed of sound and density of PVCP are similar to tissue, and together with the user-adjustable optical properties, make this material well suited for developing tissue-equivalent phantoms for biomedical optoacoustics.

Characterization of measurement artefacts in fluoroptic temperature sensors: implications for laser thermal therapy at 810 nm.

BACKGROUND AND OBJECTIVES: Fluoroptic sensors are used to measure interstitial temperatures but their utility for monitoring laser interstitial thermal therapy (LITT) is unclear because these sensors exhibit a measurement artefact when exposed to the near-infrared (NIR) treatment light. This study investigates the cause of the artefact to determine whether fluoroptic sensors can provide reliable temperature measurements during LITT. STUDY DESIGN/MATERIALS AND METHODS: The temperature rise measured by a fluoroptic sensor irradiated in non-absorbing media (air and water) was considered an artefact. Temperature rise was measured as a function of distance from a laser source. Two different sensor designs and several laser powers were investigated. A relationship between fluence rate and measurement artefact in water was determined and coupled with a numerical simulation of LITT in liver to estimate the error in temperature measurements made by fluoroptic sensors in tissue in proximity to the laser source. The effect of ambient light on the performance of sensors capped with a transparent material ("clear-capped sensors") was also investigated. RESULTS: The temperature rise recorded in air by both clear- and black-capped fluoroptic sensors decreased with distance from a laser source in a manner similar to fluence rate. Sensor cap material, laser power, and the thermal properties of the surrounding medium affected the magnitude of the artefact. Numerical simulations indicated that the accuracy of a clear-capped fluoroptic sensor used to monitor a typical LITT treatment in liver is > 1 degrees C provided the sensor is further than approximately 3 mm from the source. It was also shown that clear-capped fluoroptic sensors are affected by ambient light. CONCLUSIONS: The measurement artefact experienced by both black-capped and clear-capped fluoroptic sensors irradiated by NIR light scales with fluence rate and is due to direct absorption of the laser light, which results in sensor self-heating. Clear-capped fluoroptic sensors can be used to accurately monitor LITT in tissue but should be shielded from ambient light.