Imaging through scattering media by the use of an analytical model of perturbation amplitudes in the time domain

A method of generating images through highly scattering media is presented that involves comparing measurements of the time-dependent intensity of transmitted light with an analytical model describing the sensitivity of that intensity on localized changes in optical properties. A least-squares fitting procedure is employed to derive the amplitudes of the measurement perturbations caused by embedded absorbers and scatterers located along a line of sight between the source and detector. Images are presented of a highly scattering, solid plastic phantom with optical properties closely matched to those of human breast tissue at near-infrared wavelengths. The phantom is a 54-mm-thick slab, containing four small cylinders of contrasting scatter and absorption. Results show that embedded absorbers can be distinguished from embedded scatterers, and that the diffusion perturbation amplitude provides inherently greater spatial resolution than the absorption perturbation amplitude.     

Development of a web-based CT dose calculator: WAZA-ARI

A web-based computed tomography (CT) dose calculation system (WAZA-ARI) is being developed based on the modern techniques for the radiation transport simulation and for software implementation. Dose coefficients were calculated in a voxel-type Japanese adult male phantom (JM phantom), using the Particle and Heavy Ion Transport code System. In the Monte Carlo simulation, the phantom was irradiated with a 5-mm-thick, fan-shaped photon beam rotating in a plane normal to the body axis. The dose coefficients were integrated into the system, which runs as Java servlets within Apache Tomcat. Output of WAZA-ARI for GE LightSpeed 16 was compared with the dose values calculated similarly using MIRD and ICRP Adult Male phantoms. There are some differences due to the phantom configuration, demonstrating the significance of the dose calculation with appropriate phantoms. While the dose coefficients are currently available only for limited CT scanner models and scanning options, WAZA-ARI will be a useful tool in clinical practice when development is finalised.     

Method for recovering quantitative broadband diffuse optical spectra from layered media

We report the recovery of broadband (650-1000 nm) diffuse optical absorption and reduced scattering spectra stratified by layer in a two-layer phantom. The broadband optical properties of the phantom featured top and bottom layers designed to simulate adipose and muscle, respectively. The absolute value and dynamic variation of chromophore concentrations in both layers (top layer thickness greater than 5 mm) were calculated with an average 10% error and 3% error, respectively. In addition to spectra, the algorithm recovers the top layer thickness up to 12 mm within 10% error. It is insensitive to initial guesses of both layers' optical properties as long as the layer thickness initial guess is within +/-2 mm.     

Absorption and scattering images of heterogeneous scattering media can be simultaneously reconstructed by use of dc data

We present a carefully designed phantom experimental study aimed to provide solid evidence that both absorption and scattering images of heterogeneous scattering media can be reconstructed independently from dc data. We also study the important absorption-scattering cross-talk issue. In this regard, we develop a simple normalizing scheme that is incorporated into our nonlinear finite-element-based reconstruction algorithm. Our results from the controlled phantom experiments show that the cross talk of an absorption object appearing in scattering images can be eliminated and that the cross talk of a scattering object appearing in absorption images can be reduced considerably. In addition, these carefully designed phantom experiments clearly suggest that both absorption and scattering images can be simultaneously recovered and quantitatively separated in highly scattering media by use of dc measurements. Finally, we discuss our results in light of recent theoretical findings on nonuniqueness for dc image reconstruction.     

Radiation protection of staff in 111In radionuclide therapy--is the lead apron shielding effective?

(111)In (Eγ = 171-245 keV, t1/2 = 2.83 d) is used for targeted therapies of endocrine tumours. An average activity of 6.3 GBq is injected into the liver by catheterisation of the hepatic artery. This procedure is time-consuming (4-5 min) and as a result, both the physicians and the technical staff involved are subjected to radiation exposure. In this research, the efficiency of the use of lead apron has been studied as far as the radiation protection of the working staff is concerned. A solution of (111)In in a cylindrical scattering phantom was used as a source. Close to the scattering phantom, an anthropomorphic male Alderson RANDO phantom was positioned. Thermoluminescent dosemeters were located in triplets on the front surface, in the exit and in various depths in the 26th slice of the RANDO phantom. The experiment was repeated by covering the RANDO phantom by a lead apron 0.25 mm Pb equivalent. The unshielded dose rates and the shielded photon dose rates were measured. Calculations of dose rates by Monte Carlo N-particle transport code were compared with this study's measurements. A significant reduction of 65 % on surface dose was observed when using lead apron. A decrease of 30 % in the mean absorbed dose among the different depths of the 26th slice of the RANDO phantom has also been noticed. An accurate correlation of the experimental results with Monte Carlo simulation has been achieved.     

Slow light for deep tissue imaging with ultrasound modulation

Slow light has been extensively studied for applications ranging from optical delay lines to single photon quantum storage. Here, we show that the time delay of slow-light significantly improves the performance of the narrowband spectral filters needed to optically detect ultrasound from deep inside highly scattering tissue. We demonstrate this capability with a 9?cm thick tissue phantom, having 10?cm(-1) reduced scattering coefficient, and achieve an unprecedented background-free signal. Based on the data, we project real time imaging at video rates in even thicker phantoms and possibly deep enough into real tissue for clinical applications like early cancer detection.     

Combined ultrasound and near infrared diffused light imaging in a test object

We have investigated the use of combining near infrared (NIR) diffuse light and ultrasound imaging methods to increase the detection sensitivity and to reduce the false alarm rate in small target detection. A line-of-sight optical projection through a test object is identified from an amplitude null and a sharp phase transition produced by diffusive waves originating from two in-phase (initial phase 0 degrees ) and out-of-phase (initial phase 180 degrees ) light emitting diode sources. This line-of-sight is scanned across a scattering phantom. A complete ultrasound B-scan image is recorded at each projected line in the optical scan. Each acoustic image plane is bisected by the optical beam path and lies in the optical scan plane. The scattering phantom simulates acoustic and optical properties of homogeneous tissue. A single small cylinder-like object simulating some acoustic and optical breast tumor properties is inserted at various places in the scattering phantom. With this single object, the optical scanning identifies the line-of-sight passing through the simulated tumor quite well. Most of these simulated tumors were at or below the threshold for acoustic detection and were not seen consistently with unguided ultrasound. For tests in which a target was apparently detected optically, the selected line-of-sight was indicated in each of three adjacent ultrasound images. Two radiologist observers were statistically more accurate (83%) in identifying the target location on the optically-selected ultrasound images than in the unmarked images (52%). That is, in these single-targets of homogeneous scattering background, the optical technique usually provided the correct line-of-sight, and ultrasound generally showed the location along that line.     

Fabrication and characterization of a solid polyurethane phantom for optical imaging through scattering media

A phantom based on a polyurethane system that replicates the optical properties of tissue for use in near-infrared imaging is described. The absorption properties of tissue are simulated by a dye that absorbs in the near infrared, and the scattering properties are simulated by TiO2 particles. The scattering and absorption coefficients of the plastic were measured with a new technique based on time-resolved transmission through two slabs of materials that have different thicknesses. An image of a representative phantom was obtained from time-gated transmission.     

Estimation of scatterer size from backscattered ultrasound: a simulation study

The reliability of the estimation of the size of scattering structures is assessed by realistic simulations and phantom experiments. The acoustic tissue model used in the simulation studies comprised a constant sound speed, homogeneous attenuation, and isotropic scattering. The scattering models considered were a discrete (spherical) model and two inhomogeneous-continuum models. The latter were characterized by an exponential and a Gaussian autocorrelation function, respectively. The backscattering spectra were, over the range from 5 to 10 MHz, fitted to linear, power, and autocorrelation functions of the three scattering models. The effects of the fitting function, the attenuation-either in an intervening layer or within the region of interest (ROI)-of the transmission pulse, and a spread in the scatterer sizes on the accuracy and the precision of the size estimates were assessed. The attenuation in the intervening tissue layer(s) as well as in the ROI itself has a significant effect on the accuracy of the size estimates and needs to be corrected. When performing the attenuation correction the inaccuracy of the attenuation estimate of the intervening layer leads to a large bias in the estimated scatterer size. Experimental results support the conclusion that scatterer size is a feasible tissue characterization parameter.     

Tomographic imaging of ratiometric fluorescence resonance energy transfer in scattering media

A method to visualize and quantify fluorescence resonance energy transfer (FRET) in scattering media is proposed. It combines the ratiometric FRET method with fluorescence molecular tomography (FMT) in continuous wave (CW) mode. To evaluate the performance of the proposed method, experiments on a tissue-mimicking phantom are carried out. The results demonstrate that the proposed approach is capable of visualizing and quantifying the FRET distribution in scattering media, which implies the further application of the ratiometric assay in in vivo studies.     

Gold nanocages: bioconjugation and their potential use as optical imaging contrast agents

Gold nanocages of <40 nm in dimension have been synthesized using the galvanic replacement reaction between Ag nanocubes and HAuCl4 in an aqueous solution. By controlling the molar ratio between Ag and HAuCl4, the gold nanocages could be tuned to display surface plasmon resonance peaks around 800 nm, a wavelength commonly used in optical coherence tomography (OCT) imaging. OCT measurements on phantom samples indicate that these gold nanocages have a moderate scattering cross-section of approximately 8.10 x 10(-16) m2 but a very large absorption cross-section of approximately 7.26 x 10(-15) m2, suggesting their potential use as a new class of contrast agents for optical imaging. When bioconjugated with antibodies, the gold nanocages have also been demonstrated for specific targeting of breast cancer cells.     

Holographic characteristics of a 1-mm-thick photopolymer to be used in holographic memories

Poly(vinyl alcohol-acrylamide) photopolymers are materials of interest in the field of digital information storage (holographic memories). We analyzed the behavior of a 1-mm-thick photopolymer. Using a standard holographic setup, we recorded unslanted diffraction gratings. The material has high angular selectivity (0.4 degrees), good sensitivity (88 mJ/cm2), and small losses caused by absorption and scattering of light. It also has a high maximum diffraction efficiency (70%). A significant induction period was seen in the material. The authors hypothesize that, during most of this induction period, polymerization does in fact take place but is not reflected in the appearance of the diffracted light until a certain threshold value of exposure is reached.     

In vivo breast imaging with diffuse optical tomography based on higher-order diffusion equations

We report on in vivo absorption and scattering imaging of a human breast cyst and implant, using a reconstruction algorithm based on our third-order diffusion equations. To validate these in vivo images, a series of phantom experiments were conducted, in which we used low-absorbing and low-scattering heterogeneities to mimic a breast cyst or implant. These heterogeneities or targets were composed of pure water or a mixture of water and very dilute Intralipid (0.05% and 0.1%). The phantom experiment confirmed the quantitative imaging capability of our improved algorithm for reconstructing heterogeneities where the conventional diffusion approximation is inadequate. Pilot clinical results from female volunteers indicate that enhanced diffuse optical tomography can quantitatively image findings such as breast cysts or implants in which the absorption and scattering coefficients are usually low.     

Quantitative microspectrophotometry in turbid media

We present a new technique to determine the scattering coefficient, the absorption coefficient, and the anisotropy factor in turbid media on a microscopic level. To this end, a microspectrophotometer was used to obtain transmission measurements at different solid angles. To extract the optical properties from phantom materials (liquid and solid) and biological tissue (bovine liver) an inverse Monte Carlo algorithm was used. The results obtained with the new microspectrophotometric technique agreed within one standard deviation with the values from Mie theory and within less than 10% with the data derived from conventional spectroscopic measurements. The results suggest that this new method is a valid tool to determine the optical properties of turbid media on a microscopic level.     

A method for improved standardization of in vivo calcaneal time-domain speed-of-sound measurements

Although calcaneal speed of sound (SOS) is an effective predictor of osteoporotic fracture risk, clinical SOS measurements exhibit a high degree of inter-system variability. Calcaneal SOS is usually computed from time-of-flight measurements of broadband ultrasound pulses that propagate through the foot. In order to minimize the effects of multi-path interference, many investigators measure time-of-flight from markers near the leading edge of the pulse. The calcaneus is a highly attenuating, highly inhomogeneous bone that distorts propagating ultrasound pulses via frequency-dependent attenuation, reverberation, dispersion, multiple scattering, and refraction. This pulse distortion can produce errors in leading-edge transit-time marker-based SOS measurements. In this paper, an equation to predict dependence of time-domain SOS measurements on system parameters (center frequency and bandwidth), transit-time marker location, and bone properties (attenuation coefficient and thickness) is validated with through-transmission measurements in a bone-mimicking phantom and in 73 women in vivo, using a clinical bone sonometer. In order to test the utility of the formula for suppressing system dependence of SOS measurements, a wideband laboratory data acquisition system was used to make a second set of through-transmission measurements on the phantom. The compensation formula reduced system-dependent leading-edge transit-time marker-based SOS measurements in the phantom from 41 m/s to 5 m/s and reduced average transit-time marker-related SOS variability in 73 women from 40 m/s to 10 m/s. The compensation formula can be used to improve standardization in bone sonometry.     

Time-gated transillumination of biological tissues and tissuelike phantoms

The applicability and limits of time-resolved transillumination to determine the internal details of biological tissues are investigated by phantom experiments. By means of line scans across a sharp edge, the spatial resolution (Δx) and its dependence on the time-gate width (Δt) can be determined. Additionally, measurements of completely absorbing bead pairs embedded in a turbid medium demonstrate the physical resolution in a more realistic case. The benefit of time resolution is especially high for a turbid medium with a comparatively small reduced scattering coefficient of approximately μ(s)' = 0.12 mm(-1). Investigations with partially absorbing beads and filled plastic tubes demonstrate the high sensitivity of time-resolving techniques with respect to spatial variations in scattering or absorption coefficients that are due to the embedded disturber. In particular, it is shown that time gating is sensitive to variations in scattering coefficients.     

Three-dimensional time-resolved optical tomography of a conical breast phantom

A 32-channel time-resolved imaging device for medical optical tomography has been employed to evaluate a scheme for imaging the human female breast. The fully automated instrument and the reconstruction procedure have been tested on a conical phantom with tissue-equivalent optical properties. The imaging protocol has been designed to obviate compression of the breast and the need for coupling fluids. Images are generated from experimental data with an iterative reconstruction algorithm that employs a three-dimensional (3D) finite-element diffusion-based forward model. Embedded regions with twice the background optical properties are revealed in separate 3D absorption and scattering images of the phantom. The implications for 3D time-resolved optical tomography of the breast are discussed.     

Calculation of the properties of digital mammograms using a computer simulation

A Monte Carlo computer model of mammography has been developed to study and optimise the performance of digital mammographic systems. The program uses high-resolution voxel phantoms to model the breast, which simulate the adipose and fibroglandular tissues, Cooper's ligaments, ducts and skin in three dimensions. The model calculates the dose to each tissue, and also the quantities such as energy imparted to image pixels, noise per image pixel and scatter-to-primary (S/P) ratios. It allows studies of the dependence of image properties on breast structure and on position within the image. The program has been calibrated by calculating and measuring the pixel values and noise for a digital mammographic system. The thicknesses of two components of this system were unknown, and were adjusted to obtain a good agreement between measurement and calculation. The utility of the program is demonstrated with the calculations of the variation of the S/P ratio with and without a grid, and of the image contrast across the image of a 50-mm-thick breast phantom.     

Quantification of fluorophore concentration in tissue-simulating media by fluorescence measurements with a single optical fiber

Quantifying fluorescent compounds in turbid media such as tissue is made difficult by the effects of multiple scattering and absorption of the excitation and emission light. The approach that we used was to measure fluorescence using a single 200-microm optical fiber as both the illumination source and the detector. Fluorescence of aluminum phthalocyanine tetrasulfonate (AlPcS4) was measured over a wide range of fluorophore concentrations and optical properties in tissue-simulating phantoms. A root-mean-square accuracy of 10.6% in AlPcS4 concentration was attainable when fluorescence was measured either interstitially or at the phantom surface. The individual effects of scattering, absorption, and the scattering phase function on the fluorescence signal were also studied by experiments and Monte Carlo simulations.