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Terahertz (THz) imaging and optical coherence tomography (OCT) provide complementary information with similar length scales. In addition to OCT’s extensive use in ophthalmology, both methods have shown some promise for other medical applications and non-destructive testing. In this paper, we present an iterative algorithm that combines the information from OCT and THz imaging at two different measurement locations within an object to determine both the depth of the reflecting layers at the two locations and the unknown refractive index of the medium for both the OCT wavelengths and THz frequencies. We validate this algorithm using a silicone test object with embedded layers and show that the depths and refractive index values obtained from the algorithm agreed with the measured values to within 3.3%. We further demonstrate for the first time that OCT and THz images can be co-registered and aligned using unsupervised image registration. Hence we show that a combined OCT/THz system can provide unique information beyond the capability of the separate modalities alone, with possible applications in the medical, industrial and pharmaceutical sectors.

Gold nanoparticles (GNPs) may be used as a contrast agent to identify tumour location and can be modified to target and image specific tumour biological parameters. There are currently no imaging systems in the literature that have sufficient sensitivity to GNP concentration and distribution measurement at sufficient tissue depth for use in in vivo and in vitro studies. We have demonstrated that high detecting sensitivity of GNPs can be achieved using x-ray fluorescence; furthermore this technique enables greater depth imaging in comparison to optical modalities. Two x-ray fluorescence systems were developed and used to image a range of GNP imaging phantoms. The first system consisted of a 10 mm(2) silicon drift detector coupled to a slightly focusing polycapillary optic which allowed 2D energy resolved imaging in step and scan mode. The system has sensitivity to GNP concentrations as low as 1 ppm. GNP concentrations different by a factor of 5 could be resolved, offering potential to distinguish tumour from non-tumour. The second system was designed to avoid slow step and scan image acquisition; the feasibility of excitation of the whole specimen with a wide beam and detection of the fluorescent x-rays with a pixellated controlled drift energy resolving detector without scanning was investigated. A parallel polycapillary optic coupled to the detector was successfully used to ascertain the position where fluorescence was emitted. The tissue penetration of the technique was demonstrated to be sufficient for near-surface small-animal studies, and for imaging 3D in vitro cellular constructs. Previous work demonstrates strong potential for both imaging systems to form quantitative images of GNP concentration.

This paper presents a new numerical method for optical tomography: the combined boundary element/finite element method (BEM-FEM), designed to tackle reconstructions in layered turbid media. The BEM-FEM focuses on the region of interest by creating a volume mesh and reconstructing in this region only. All other regions are treated as piecewise constant in a surface-integral approach. We validate the model in concentric spheres, with different positions of the volume-integral treated area and found it compared well with an analytical result. We then performed functional imaging of the neonate's motor cortex in vivo, in a reconstruction restricted to the brain, both with FEM and BEM-FEM. These results show the effectiveness of the BEM-FEM in situations where the organ of interest is surrounded by superficial layers.

The use of THz radiation as a potential tool for medical imaging is of increasing interest. In this paper three methods of analysis of THz spectroscopic information for diagnosis of tissue pathologies at THz frequencies are presented. The frequency-dependent absorption coefficients, refractive indices and Debye relaxation times of pure water and pure lipids were measured and used as prior knowledge in the different theoretical methods for the determination of concentration. Three concentration analysis methods were investigated: (a) linear spectral decomposition, (b) spectrally averaged dielectric coefficient method and (c) the Debye relaxation coefficient method. These methods were validated on water and lipid emulsions by determining the concentrations of phantom chromophores and comparing to the known composition. The accuracy and resolution of each method were determined to assess the potential of each method as a tool for medical diagnosis at THz frequencies.

The development of diffuse optical tomography as a functional imaging modality has relied largely on the use of model-based image reconstruction. The recovery of optical parameters from boundary measurements of light propagation within tissue is inherently a difficult one, because the problem is nonlinear, ill-posed and ill-conditioned. Additionally, although the measured near-infrared signals of light transmission through tissue provide high imaging contrast, the reconstructed images suffer from poor spatial resolution due to the diffuse propagation of light in biological tissue. The application of model-based image reconstruction is reviewed in this paper, together with a numerical modelling approach to light propagation in tissue as well as generalized image reconstruction using boundary data. A comprehensive review and details of the basis for using spatial and structural prior information are also discussed, whereby the use of spectral and dual-modality systems can improve contrast and spatial resolution.

A solid dynamic phantom with tissue-like optical properties is presented, which contains seven discrete targets impregnated with thermochromic pigment located at different depths from the surface. Changes in absorption are obtained in response to localized heating of the targets, simulating haemodynamic changes occurring in the brain and other tissues. The depth sensitivity of a continuous wave optical topography system was assessed successfully using the phantom. Images of the targets have been reconstructed using a spatially variant regularization, and the determined spatial localization in the depth direction is shown to be accurate within an uncertainty of about 3 mm down to a depth of about 30 mm.

An electrically-activated phantom for evaluating diffuse optical imaging systems has been designed based on an array of semiconductor diodes which are used to heat a thermochromic dye embedded in a solidified polyester resin with tissue-like optical properties. The array allows individual diodes to be addressed sequentially, thus simulating the movement of a small volume of contrasting optical absorption. Two designs of diode-array phantom are described and results of imaging experiments are presented.

Through application of spatio-temporal regularisation techniques, we demonstrate the real-time three-dimensional dynamic reconstruction of the optical properties of a hemispherical infant head phantom, with moving absorption and scattering targets.

A novel design of solid dynamic phantom with tissue-like optical properties is presented, which contains variable regions of contrast which are activated electrically. Reversible changes in absorption are produced by localized heating of targets impregnated with thermochromic pigment. A portable, battery-operated prototype has been constructed, and its optical and temporal characteristics have been investigated. The phantom has been developed as a means of assessing the performance of diffuse optical imaging systems, such as those used to monitor haemodynamic changes in the brain and other tissues. Images of the phantom have been reconstructed using data acquired with a continuous wave optical topography system.

A recipe is presented for the manufacture of highly compressible phantoms for diffuse optical tomography. The recipe is based on polyvinyl alcohol (PVA) slime, a viscoelastic fluid which readily deforms under moderate pressure. Scattering particles and absorbing compounds can be added to provide a uniform material with stable and reproducible optical properties. A linear relationship between the concentration of scattering particles (either titanium dioxide or microspheres) and the transport scatter coefficient is demonstrated. Phantoms of an arbitrary size and shape may be produced by containing the slime within a thin latex shell, and a stability over a period of at least 3 months has been established. The deformable phantoms may be used to test and calibrate optical tomography systems designed for use on patients with irregular or variable geometries.

A portable topographic near-infrared spectroscopic (NIRS) imaging system has been developed to provide real-time temporal and spatial information about the cortical response to stimulation in unrestrained infants. The optical sensing array is lightweight, flexible, and easy to apply to infants ranging from premature babies in intensive care to children in a normal environment. The sensor pad consists of a flexible double-sided circuit board onto which are mounted multiple sources (light-emitting diodes) and multiple detectors (p-i-n photodiodes), all electrically encapsulated in silicone rubber. The control electronics are housed in a box with a medical grade isolated power supply and linked to a PC fitted with a data acquisition card, the signal acquisition and analysis being performed using LABVIEW™. The signal output is displayed as an image of oxy- and deoxyhemoglobin concentration ([HbO2], [Hb]) changes at a frame rate of 3 Hz. Experiments have been conducted on phantoms to determine the sensitivity ...

We present a method for acquiring whole-head images of changes in blood volume and oxygenation from the infant brain at cot-side using time-resolved diffuse optical tomography (TR-DOT). At UCL, we have built a portable TR-DOT device, known as MONSTIR II, which is capable of obtaining a whole-head (1024 channels) image sequence in 75 seconds. Datatypes extracted from the temporal point spread functions acquired by the system allow us to determine changes in absorption and reduced scattering coefficients within the interrogated tissue. This information can then be used to define clinically relevant measures, such as oxygen saturation, as well as to reconstruct images of relative changes in tissue chromophore concentration, notably those of oxy- and deoxyhaemoglobin. Additionally, the effective temporal resolution of our system is improved with spatio-temporal regularisation implemented through a Kalman filtering approach, allowing us to image transient haemodynamic changes. By using this filtering technique with intensity and mean time-of-flight datatypes, we have reconstructed images of changes in absorption and reduced scattering coefficients in a dynamic 2D phantom. These results demonstrate that MONSTIR II is capable of resolving slow changes in tissue optical properties within volumes that are comparable to the preterm head. Following this verification study, we are progressing to imaging a 3D dynamic phantom as well as the neonatal brain at cot-side. Our current study involves scanning healthy babies to demonstrate the quality of recordings we are able to achieve in this challenging patient population, with the eventual goal of imaging functional activation and seizures.

A new potential quality assurance (QA) method is explored (including assessment of depth dose, dose linearity, dose rate linearity and beam profile) for clinical electron beams based on imaging Cerenkov light. The potential of using a standard commercial camera to image Cerenkov light generated from electrons in water for fast QA measurement of a clinical electron beam was explored and compared to ionization chamber measurements. The new method was found to be linear with dose and independent of dose rate (to within 3%). The uncorrected practical range measured in Cerenkov images was found to overestimate the actual value by 3 mm in the worst case. The field size measurements underestimated the dose at the edges by 5% without applying any correction factor. Still, the measured field size could be used to monitor relative changes in the beam profile. Finally, the beam-direction profile measurements were independent of the field size within 2%. A simulation was also performed of the deposited energy and of Cerenkov production in water using GEANT4. Monte Carlo simulation was used to predict the measured light distribution around the water phantom, to reproduce Cerenkov images and to find the relation between deposited energy and Cerenkov production. The camera was modelled as a pinhole camera in GEANT4, to attempt to reproduce Cerenkov images. Simulations of the deposited energy and the Cerenkov light production agreed with each other for a pencil beam of electrons, while for a realistic field size, Cerenkov production in the build-up region overestimated the dose by +8%.

Accurate imaging of impedance changes in the brain with EIT using scalp electrodes ideally requires an algorithm designed for a 3D hemispherical object that is capable of imaging through the skull. A 2D algorithm is presented, intended as the first step towards a full 3D version. It is based on a sensitivity matrix approach and allows images to be reconstructed from any electrode positions. Its performance was assessed using a 2D circular tank with a simulated skull. The findings suggested the following: if polar current drive was used with no explicit skull compensation, a feature in the image would be placed 25% closer to the center and would be around one-third the amplitude of an identical perturbation in a homogeneous medium.

We present simulations and measurements of Cerenkov optical radiation in electron and proton radiotherapy. Photographs of Cerenkov emission from electrons can predict the range to ±1.5mm, but underestimate superficial dose.

We propose a method for combining multiparameter data to inform a model of microstructure and validate it with data acquired from tissue-like mayonnaise. Quantitative recovery of microstructural parameters is improved using the combined model.

The present contribution lies in the framework of a research effort aimed at identifying the most suitable imaging techniques able to map the distribution of functionalized nanoparticles acting as biological markers taken up by specific cellular receptors in healthy and pathological biological tissues and to give a map of cellular radio-sensitivity across the tumor volume, in order to guide radiation dose prescription in intensity modulated radiotherapy (IMRT). To this aim we conceived and developed a custom compact spectroscopic module which accommodates a 10 mm2 Silicon Drift Detector as well as a thermoelectric Peltier cooler and the front-end electronics. A slightly focusing polycapillary optics coupled to the detector allows performing 2D mapping in step and scan mode. We present the results obtained during a beam time in DIAMOND synchrotron source at beamline B16. Different Perspex phantoms have been measured: both single holes and two-holes in a donut configuration filled with different concentrations of gold nanoparticles (starting from 8 mg/ml down to 0.005 mg/ml).

A method is presented to select the optimal wavelengths for multispectral optical topography, which not only gives good separation between chromophores, absorption, and scattering, but also minimizes the differences between interrogated volumes. This method uses the sum of squared differences to compare photon measurement density functions, which were generated for wavelengths in the near-infrared (NIR) range for a suitable model of tissue optical properties. It is found that including this condition significantly influences the range of optimal wavelengths. However, for the adult human head, the differences between interrogated volumes at NIR wavelengths are very small and image reconstruction is only slightly improved when measurements with overlapping sensitivities are used.

Both x-ray diffraction and x-ray fluorescence techniques have proven beneficial for identifying and characterizing biological tissues. X-ray diffraction analysis uses the elemental composition of the sample to discriminate between tissue types, and can provide a considerable enhancement in contrast over conventional x-ray imaging. X-ray fluorescence, in this case, is being used to locate the presence of nanoparticles, such as gold, which are embedded into tissues as biomarkers to map the disease state. A novel system is being developed which combines these two techniques in order to locate tumours and provide information on the tumour characteristics. A series of preliminary fluorescence and diffraction measurements were made over a range of gold nanoparticle concentrations using the SYRMEP beamline at the Elettra synchrotron, Italy. The novel system, consisting of an energy resolving silicon drift detector with high spectral resolution and a polycapillary optic angular collimator, showed potential in both quantification of and sensitivity to nanoparticle concentrations typically found in tumours. The signal from each technique was found to be linear with nanoparticle concentration down to the minimum detectable limit. We found a linear relationship between fluorescence intensity and concentration down to 3.2 ppm by weight. Such system sensitivity suggests usefulness in measuring tumour uptake in vivo. However, both the x-ray fluorescence and diffraction signals are small, and will benefit from an increase in counting statistics and a reduction of the noise.

Medical imaging equipment is routinely characterised and tested using tissue equivalent phantoms. Combined x-ray and optical mammography could provide increased screening specificity over either system alone. The ongoing evaluation of this approach depends upon the development of phantoms with simultaneously breast tissue equivalent optical and x-ray properties. Furthermore deformation models used in the registration of optical and x-ray images, which are acquired at differing levels of breast compression, require validation through phantoms which are also mechanically tissue equivalent. As well as static imaging, dynamic optical imaging of blood flow whilst breast compression is applied has been proposed as a method of enhancing screening specificity. The effect of changes in blood flow and volume on optical tomography still need to be established. A novel phantom material created by freezing and thawing a solution of polyvinyl alcohol (PVAL) in ethanol to create a solid yet elastically compressible gel is described. These gels have x-ray attenuation coefficients equivalent to those of breast tissues whilst their optical and mechanical properties are readily modified. Titanium dioxide is added to the optically non-scattering and colourless gels to obtain the transport scattering coefficient required. Cancerous tissues are often many times stiffer than healthy. Similar differences in stiffness are achieved between gels by varying PVAL concentration. The first x-ray and optical images of an anthropomorphically shaped breast phantom made from this gel are presented. This contains a lesion filled with blood equivalent dye whose volume changes upon compression of the phantom.

Investigators have previously attempted to determine the optimal wavelengths to employ for Near-Infrared Spectroscopy (NIRS) which yield the best separation between absorption and scatter and the least influence of noise. Although these are important criteria it is also important that the volume of tissue sampled at each of the wavelengths is the same. In our study we have generated spatial sensitivity profiles at multiple wavelengths for a suitable model of tissue optical properties, and studied the spatial sensitivity overlap for different combinations of wavelengths. It is found that including this condition significantly influences the range of optimal wavelengths.

The quality of phase and amplitude data from two medical optical tomography systems were compared. The two systems are a 32-channel time-domain system developed at University College London (UCL) and a 16-channel frequency-domain system developed at Helsinki University of Technology (HUT). Difference data measured from an inhomogeneous and a homogeneous phantom were compared with a finite-element method (diffusion equation) and images of scattering and absorption were reconstructed based on it. The measurements were performed at measurement times between 1 and 30 s per source. The mean rms errors in the data measured by the HUT system were 3.4% for amplitude and 0.51 deg for phase, while the corresponding values for the UCL data were 6.0% and 0.46 deg, respectively. The reproducibility of the data measured with the two systems was tested with a measurement time of 5 s per source. It was 0.4% in amplitude for the HUT system and 4% for the UCL system, and 0.08 deg in phase for both systems. The image quality of the reconstructions from the data measured with the two systems were compared with several quantitative criteria. In general a higher contrast was observed in the images calculated from the HUT data.

Novel probes have been developed for optical tomography (whole-brain imaging) and optical topography (cortical mapping) of the newborn brain. These have been evaluated on a range of infants at rest and during functional stimulation.

Most research in optical imaging incorrectly assumes that light transport in nonscattering regions in the head may be modeled by use of the diffusion approximation. The effect of this assumption is examined in a series of experiments on tissue-equivalent phantoms. Images from cylindrical and head-shaped phantoms with and without clear regions [simulating the cerebrospinal fluid (CSF) filled ventricles] and a clear layer (simulating the CSF layer surrounding the brain) are reconstructed with linear and nonlinear reconstruction techniques. The results suggest that absorbing and scattering perturbations can be identified reliably with nonlinear reconstruction methods when the clear regions are also present in the reference data but that the quality of the image degrades considerably if the reference data does not contain these features. Linear reconstruction performs similarly to nonlinear reconstruction, provided the clear regions are present in the reference data, but otherwise linear reconstruction fails. This study supports the use of linear reconstruction for dynamic imaging but suggests that, in all cases, image quality is likely to improve if the clear regions are modeled correctly.

We present a multi-dimensional TCSPC technique that combines multi-detector and multiplexing capability, and records fast and virtually unlimited sequences of time-of-flight distributions. The system consists of four fully parallel TCSPC channels. Each channel records simultaneously in up to eight detection channels. Up to four lasers and 32 source positions can be multiplexed. The total count rate is up to 4 x 10 7 photons per second. Time-of-flight sequences can be recorded with a resolution of 50 to 100 ms per curve. The system is operated within a single personal computer.

We review the current state-of-the-art of diffuse optical imaging, which is an emerging technique for functional imaging of biological tissue. It involves generating images using measurements of visible or near-infrared light scattered across large (greater than several centimetres) thicknesses of tissue. We discuss recent advances in experimental methods and instrumentation, and examine new theoretical techniques applied to modelling and image reconstruction. We review recent work on in vivo applications including imaging the breast and brain, and examine future challenges.

We have developed a novel near-infrared optical topography system that can acquire images of functional activation in the human brain at 10 frames per second using 32 detectors. The image acquisition rate is inversely proportional to the number of detectors, so the maximum acquisition rate using four detectors is 80Hz. 16 laser diode sources (8 at 785 and 8 at 850nm) are illuminated simultaneously, and each of 8 avalanche photodiode detectors records light from several sources at the same time. The contribution from each source is demultiplexed in software using fast Fourier transforms. This allows for a more flexible, smaller, and less complex system than is achievable using traditional hardware demodulation techniques, such as lock-in amplifiers. The system will eventually incorporate a total of 64 sources and 32 detectors, enabling the entire adult cortex to be imaged. The system is designed to be as flexible as possible, and to be applicable to a wide variety of experimental and clinical needs. To thi...

We propose a computational calibration method for optical tomography. The model of the calibration scheme is based on the rotation symmetry of source and detector positions in the measurement setup. The relative amplitude losses and phase shifts at the optic fibers are modeled by complex-valued coupling coefficients. The coupling coefficients can be estimated when optical tomography data from a homogeneous and isotropic object are given. Once these coupling coefficients have been estimated, any data measured with the same measurement setup can be corrected for the relative variation in the data due to source and detector losses. The final calibration of the data for the source and detector losses and the source calibration between the data and the forward model are obtained as part of the initial estimation for reconstruction. The calibration method was tested with simulations and measurements. The results show that the coupling coefficients of the sources and detectors can be estimated with good accuracy. Furthermore, the results show that the method can significantly improve the quality of reconstructed images.

Studies on volunteers are being performed to evaluate three-dimensional time-resolved optical tomography as a means of detecting and specifying breast disease. Two acquisition geometries have been assessed and the images obtained are presented.

We have developed a novel near-infrared optical topography system that can acquire images at 10 frames per second. It uses frequency multiplexed sources, and FFT detection.

Optical tomography is being developed at UCL as a tool for understanding the mechanisms of haemorrhagic and hypoxic-ischaemic brain injury and assessing the effectiveness of novel neural rescue therapies in the newborn infant. Our 32-channel time-resolved optical imaging system measures photon flight times between multiple pairs of points on the surface of the head, and images sensitive to local variation in tissue absorption and scattering properties are reconstructed using non-linear algorithms. Several studies have been performed on premature infants using custom-built helmets, which hold up to 32 sources and detectors in contact with the head. Simulations have revealed that combining data with reference measurements acquired on a homogeneous object using the same fibre locations can significantly reduce errors in reconstructions due to uncertainty in the location of the sources and detectors. To provide the reference data, a homogeneous phantom based on a balloon filled with a scattering fluid of precisely known optical properties was made and inserted into the helmet immediately following each infant scan. In this paper, we evaluate the effectiveness of this approach by acquiring data on a realistically head-shaped phantom containing a small perturbation, and reconstructing it using the homogeneous head-shaped phantom and the fluid-filled balloon.

The production of accurate and independent images of the changes in concentration of oxyhemoglobin and deoxyhemoglobin by diffuse optical imaging is heavily dependent on which wavelengths of near-infrared light are chosen to interrogate the target tissue. Although wavelengths can be selected by theoretical methods, in practice the accuracy of reconstructed images will be affected by wavelength-specific and system-specific factors such as laser source power and detector sensitivity. We describe the application of a data-driven approach to optimum wavelength selection for the second generation of University College London's multichannel, time-domain optical tomography system (MONSTIR II). By performing a functional activation experiment using 12 different wavelengths between 690 and 870 nm, we were able to identify the combinations of 2, 3, and 4 wavelengths which most accurately reproduced the results obtained using all 12 wavelengths via an imaging approach. Our results show that the set of 2, 3, and 4 wavelengths which produce the most accurate images of functional activation are [770, 810], [770, 790, 850], and [730, 770, 810, 850] respectively, but also that the system is relatively robust to wavelength selection within certain limits. Although these results are specific to MONSTIR II, the approach we developed can be applied to other multispectral near-infrared spectroscopy and optical imaging systems.

For the first time, three-dimensional images of the newborn infant brain have been generated using measurements of transmitted light. A 32-channel time-resolved imaging system was employed, and data were acquired using custom-made helmets which couple source fibres and detector bundles to the infant head. Images have been reconstructed using measurements of mean flight time relative to those acquired on a homogeneous reference phantom, and using a head-shaped 3D finite-element-based forward model with an external boundary constrained to match the measured positions of the sources and detectors. Results are presented for a premature infant with a cerebral haemorrhage predominantly located within the left ventricle. Images representing the distribution of absorption at 780 nm and 815 nm reveal an asymmetry consistent with the haemorrhage, and corresponding maps of blood volume and fractional oxygen saturation are generally within expected physiological values.

A 32-channel time-resolved imaging system has been used to acquire three-dimensional (3D) optical tomography data on newborn infants for the first time. Multiple sources and detectors were coupled to the infant head using a custom-designed helmet. Temporal distributions of transmitted light were recorded during illumination by picosecond pulses of light at 780 nm and 815 nm in order to generate 3D images of the brain.

Optical tomography images have been reconstructed from data generated using a head-shaped finite element model. The images were significantly improved when a priori information was included. Further results will be presented from a realistic phantom.

We detail the design, construction and performance of the second generation UCL time-resolved optical tomography system, known as MONSTIR II. Intended primarily for the study of the newborn brain, the system employs 32 source fibres that sequentially transmit picosecond pulses of light at any four wavelengths between 650 and 900 nm. The 32 detector channels each contain an independent photo-multiplier tube and temporally correlated photon-counting electronics that allow the photon transit time between each source and each detector position to be measured with high temporal resolution. The system's response time, temporal stability, cross-talk, and spectral characteristics are reported. The efficacy of MONSTIR II is demonstrated by performing multi-spectral imaging of a simple phantom.

Cortical mapping, also called optical topography is a new medical imaging modality which allows the non-invasive investigation of the outer layers of the cortex. This technique is challenging and the geometry of the subject is very often over-simplified. We aim here to localize activated regions of an anatomically accurate brain. A Boundary Element Method is used for the forward model. The reconstruction of perturbations in the absorption coefficient is demonstrated in a geometrically realistic simulation and in vivo. These results show that diffuse optical imaging of the head can provide reliable activity maps when anatomical data is available.

A novel prototype step and shoot x-ray system, the intelligent imaging system (I-Imas), has been developed in the UCL Radiation Physics laboratories. The system uses collimators to split the beam into two: the first, "scout" beam, strongly attenuated, identifies regions of interest in the image. This information is then fed back to the system so that the intensity of the second beam is modulated to optimize the dose distribution--i.e., "interesting" regions of the sample receive a higher dose, whereas other regions receive a lower one. Such systems may be capable of improved diagnostic capability at the same overall patient dose levels as typical when using large area digital plates. This acquisition mode means that large overall images are obtained by aligning many smaller images. This paper investigates the effects that this acquisition modality has on the overall spatial resolution of the system. We review different modulation transfer function (MTF) evaluation techniques and those shown to be optimal are used in the investigation of two considerations key to such a system: (i) whether there is a minimum size sensor whose MTF can accurately be determined using these techniques and (ii) whether the MTF of the large overall image differs significantly from those of the many constituent images. As the use of step and shoot systems is becoming more and more widespread, both are important considerations. We found that, for a fixed pixel pitch, the MTF is determined marginally less accurately the smaller the sensor area, with the perceived resolution varying by up to 0.1 lp/mm. It was also found that use of such a step and shoot technique does cause a very small overall degradation in resolution. The resolution of overall images was calculated to be 0.1 lp/mm lower than that of the individual images acquired.

Optical tomography is being developed as a means of detecting and specifying disease in the adult female breast. We present a series of clinical three-dimensional optical images obtained with a 32-channel time-resolved system and a liquid-coupled interface. Patients place their breasts in a hemispherical cup to which sources and detectors are coupled, and the remaining space is filled with a highly scattering fluid. A cohort of 38 patients has been scanned, with a variety of benign and malignant lesions. Images show that hypervascularization associated with tumors provides very high contrast due to increased absorption by hemoglobin. Only half of the fibroadenomas scanned could be observed, but of those that could be detected, all but one revealed an apparent increase in blood volume and a decrease in scatter and oxygen saturation.

Results are presented of a study to monitor the changes in the optical properties of breast tissue over a 12-month period after interstitial laser photocoagulation treatment of a fibroadenoma. The study involved generating cross-sectional images of the breast with a multichannel time-resolved imaging system and a nonlinear image reconstruction algorithm. Images of the internal absorbing and scattering properties revealed the expected initial inflammatory response, followed by the development of low-scattering cysts consistent with corresponding ultrasound examinations. Although results indicate that purely qualitative images can potentially provide clinically valuable data, means of enhancing diagnostic information by overcoming present limitations of the approach are discussed.

A method has been devised for generating three-dimensional optical images of the breast using a 32-channel time-resolved system and a liquid-coupled interface. The breast is placed in a hemispherical cup surrounded by sources and detectors, and the remaining space is filled with a fluid with tissue-like optical properties. This approach has three significant benefits. First, cups can accommodate a large range of breast sizes, enabling the entire volume of the breast to be sampled. Second, the coupling of the source and detector optics at the surface is constant and independent of the subject, enabling intensity measurements to be employed in the image reconstruction. Third, the external geometry of the reconstructed volume is known exactly. Images of isolated targets with contrasting absorbing and scattering properties have been acquired, and the performance of the system has been evaluated in terms of the contrast, spatial resolution, and localization accuracy. These parameters were strongly dependent on the location of the targets within the imaged volume. Preliminary images of a healthy human subject are also presented, which reveal subtle heterogeneity, particularly in the distribution of scatter. The ability to detect an absorbing target adjacent to the breast is also demonstrated.

We have begun clinical trials of optical tomography of the neonatal brain. To validate this research, we have built and imaged an anatomically realistic, tissue-equivalent neonatal head phantom that is hollow, allowing contrasting objects to be placed inside it. Images were reconstructed by use of two finite-element meshes, one generated from a computed tomography image of the phantom and the other spherical. The phantom was filled with a liquid of the same optical properties as the outer region, and two perturbations were placed inside. These were successfully imaged with good separation between the absorption and scatter coefficients. The phantom was then refilled with a liquid of increased absorption compared with the background to simulate the brain, and the absolute properties of the two regions were found. These were used as a priori information for the complete reconstruction. Both perturbations were visible, superimposed on the increased absorption of the central region. The head-shaped mesh performed slightly better than the spherical mesh, particularly when the absorption of the central region of the phantom was increased.

A 32-channel time-resolved optical imaging device is de- veloped at University College London to produce functional images of the neonatal brain and the female breast. Reconstruction of images using time-resolved measurements of transmitted light requires careful calibration of the temporal characteristics of the measurement system. Since they can often vary over a period of time, it is desirable to evaluate these characteristics immediately after, or prior to, the acqui- sition of image data. A calibration technique is investigated that is based on the measurement of light back-reflected from the surface of the object being imaged. This is facilitated by coupling each detector channel with an individual source fiber. A Monte Carlo model is em- ployed to investigate the influence of the optical properties of the object on the back-reflected signal. The results of simulations indicate that their influence may be small enough to be ignored in some cases, or could be largely accounted for by a small adjustment to the cali- brated data. The effectiveness of the method is briefly demonstrated by imaging a solid object with tissue-equivalent optical properties.