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Cutaneous T-cell Lymphoma (CTCL) is a rare form of non-Hodgkin lymphoma characterized by skin lesions, which can negatively impact the quality of life of both patients and their caregivers. The Decision Support Unit (DSU) at the National Institute for Health and Care Excellence (NICE) in the UK recently outlined a rationale for the inclusion of caregiver burden in economic evaluations. This study aimed to estimate utilities for health states associated with being a caregiver for an individual with CTCL at different stages of treatment.A targeted literature review and interviews with CTCL specialists informed the development of health state vignettes describing the experience caring for an individual with CTCL. The vignettes were evaluated in interviews with the UK general population using a visual analogue scale (VAS), the time trade-off (TTO) method and the EQ-5D-5L.Four vignettes were developed describing the caregiver experience for an individual with CTCL on i) second line treatment, ii) third line treatment, iii) end of life care, iv) a post-patient death. One hundred interviews were conducted to evaluate the health state vignettes. The pattern of results was similar across the evaluation methods: second line treatment (VAS: 39.2, TTO = 0.52, EQ-5D-5L: 0.56), third line treatment (VAS: 31.1, TTO = 0.39, EQ-5D-5L: 0.37), end of life care (VAS: 28.2, TTO = 0.37, EQ-5D-5L: 0.31) and post-patient death (VAS: 41.2, TTO = 0.63, EQ-5D-5L: 0.59).

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.

With the number of new proton centers increasing rapidly, there is a need for an assessment of the available proton treatment planning systems (TPSs). This study compares the dose distributions of complex meningioma plans produced by three proton TPSs: Eclipse, Pinnacle3, and XiO. All three systems were commissioned with the same beam data and, as best as possible, matched configuration settings. Proton treatment plans for ten patients were produced on each system with a pencil beam scanning, single‐field uniform dose approach, using a fixed horizontal beamline. All 30 plans were subjected to identical dose constraints, both for the target coverage and organ at risk (OAR) sparing, with a consistent order of priority. Beam geometry, lateral field margins, and lateral spot resolutions were made consistent across all systems. Few statistically significant differences were found between the target coverage and OAR sparing of each system, with all optimizers managing to produce plans within clinical tolerances (D295%, D99>90%, and OAR maximum doses) despite strict constraints and overlapping structures. PACS number: 87.55.D‐

Ethnopharmacological relevance/Introduction In Canada, all natural health products (NHPs) are regulated by Health Canada (HC) under the Food and Drugs Act and the Natural Health Product Regulations. All authorized products undergo pre-market assessment for safety, efficacy and quality and the degree of pre-market oversight varies depending on the risk of the product. Overview In Canada, over 70,000 products have been authorized for sale and over 2000 sites have been licensed to produce NHPs. In the management of NHPs on the Canadian market, HC employs a number of active and collaborative methods to address the most common issues such as contamination, adulteration and deceptive or misleading advertising practices. HC is currently evolving its approaches to NHPs to recognize them as part of the larger group of health products available without a prescription. As such, the regulatory responsibility for all over-the-counter (OTC) drugs, including non-prescription drugs and NHPs, has been transferred to a single federal division. Conclusion As a result of this transition a number of benefits are being realized with respect to government efficiency, clarity for industry, support for new innovations and consolidated government interactions with the Canadian market.

SUMMARY Aim: Information regarding the characteristics and breast cancer risk factors of British women in the standard population attending breast cancer screening is limited. Such information could be useful in personalizing screening and care, and informing and educating women about their risk. Materials & methods: Information about various breast cancer risk factors was obtained from 355 women aged between 46 and 74 years at a UK inner-city breast cancer screening clinic using questionnaires. The risk of breast cancer was calculated using the modified Gail model and analyzed using descriptive and regression statistics. Results: There were 26 women recalled for further assessment and two cases confirmed as invasive breast cancer. Forty-seven women reported first-degree relatives with breast cancer. A total of 58% of our sample was overweight or obese, although 84% reported meeting the recommended target of ≥150 min of exercise per week. A total of 44% were smokers and 23% reported consuming alcohol on a regular basis. The mean lifetime risk score was 9.0% and the mean 5-year risk score was 1.5%. Various non-Gail model risk factors were found to be correlated with risk scores, but the only factor that was significantly different between women recalled for further assessment and those who were not was age of menarche. Conclusion: The results suggest that determining risk factor data in a standard screening population could be useful both to the women, who may have modifiable lifestyle factors that can be changed to improve their risk, and to the clinics, which can identify women at a higher risk who may be unaware and not present themselves as candidates for risk assessment.

Diffuse optical imaging and spectroscopy have been extensively used to detect, diagnose and monitor cancer. This paper is a review not of cancer in general, but of the biological changes that occur that can provide contrast for near infrared (NIR) techniques. Cancer is defined by characteristics such as the development of new blood vessels, changes in metabolism and the ability to invade surrounding tissue. The sensitivity of NIR techniques to haemoglobin, water and lipid concentrations, tissue oxygen saturation and cell density means that the pathological changes that occur in malignant tissues can provide contrast between healthy and pathological tissue. Each of these contrast mechanisms are discussed in turn, with a short introduction to the physiological changes that occur, and then a review of the NIR techniques that can be used to investigate these changes and findings from published papers. The role of exogenous contrast agents with NIR techniques in cancer diagnosis and assessment are also discussed. By understanding the characteristics of cancer and the changes that occur, we can interpret our results from NIR with greater confidence and accuracy and develop new techniques that target these characteristics. Information on angiogenesis or hypoxia can be clinically useful, especially when planning treatment (hypoxia) or predicting outcome to chemotherapy (haemoglobin concentration can be used as a measure of vessel density). By understanding the characteristics of cancer and the changes that occur, we can interpret our results from NIR with greater confidence and accuracy and develop new techniques that target these characteristics.

We describe a series of novel simultaneous EEG and diffuse optical imaging studies of newborn infants. These experiments provide evidence of large, transient haemodynamic events which occur repeatedly and consistently within and across several infants with neurological damage, all of whom were diagnosed with seizures. A simple but independent process of rejecting artifacts and identifying events within diffuse optical imaging data is described, and this process is applied to data from 4 neurologically damaged neonates and from 19 healthy, age-matched controls. This method results in the consistent identification of events in three out of four of the neurologically damaged infant group which are dominated by a slow (> 30 s) and significant increase in oxyhaemoglobin concentration, followed by a rapid and significant decrease before a slow return to baseline. No comparable events are found in any of our control data sets. The importance and physiological implications of our findings are discussed, as is the suitability of a combined EEG and diffuse optical imaging approach to the study and monitoring of neonatal brain injury.

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.

We have developed a novel phantom material: a solution of polyvinyl alcohol (PVAL) in ethanol and water, freeze-thawed to produce a solid yet elastically compressible gel. The x-ray attenuation and mechanical properties of these gels are compared with published measurements of breast tissue. Gels with PVAL concentrations from 5 to 20% w/v were produced. The linear x-ray attenuation coefficients of these gels range from 0.76 to 0.86 cm(-1) at 17.5 keV, increasing with PVAL concentration. These values are very similar to the published values of breast tissue at this energy, 0.8-0.9 cm(-1). Under compression cancerous breast tissue is approximately ten times stiffer than healthy breast tissue. The Young's moduli of the gels increase with PVAL concentration. Varying the PVAL concentration from 7.5 to 20% w/v produces gels with Young's moduli from 20 to 220 kPa at 15% strain. These values are characteristic of normal and cancerous breast tissue, respectively.

Diffuse optical imaging is a medical imaging technique that is beginning to move from the laboratory to the hospital. It is a natural extension of near-infrared spectroscopy (NIRS), which is now used in certain niche applications clinically and particularly for physiological and psychological research. Optical imaging uses sophisticated image reconstruction techniques to generate images from multiple NIRS measurements. The two main clinical applications—functional brain imaging and imaging for breast cancer—are reviewed in some detail, followed by a discussion of other issues such as imaging small animals and multimodality imaging. We aim to review the state of the art of optical imaging.

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.

Optical systems could be valuable tools for assessing cerebral function at the cotside The newborn brain is vulnerable to a variety of insults with potentially lifelong consequences. As our understanding of the mechanism of brain injury improves and new therapies are developed to prevent or minimise brain injury, new non-invasive methods are required to assess cerebral function at the cotside. The application of near-infrared spectroscopy (NIRS) for continuous monitoring of cerebral haemodynamics and oxygenation non-invasively was first reported by Jobsis in 1977.1 Since that time NIRS has become an effective research tool for studying infant cerebral haemodynamics and oxygenation.2,3 NIRS exploits the relative transparency of biological tissue to near-infrared light (700–1000 nm), and the wavelength-dependent absorption characteristics of haemoglobin, which vary with oxygenation. By monitoring the intensity of light passing through brain tissue at two or more wavelengths, observed changes in attenuation can be converted into changes in the cerebral concentrations of oxyhaemoglobin and deoxyhaemoglobin. An obvious application of NIRS is the investigation of localised changes in oxyhaemoglobin and deoxyhaemoglobin resulting from functional activation of the cerebral cortex. Increases in local cerebral blood flow (CBF) are manifested by a rise in oxyhaemoglobin and a fall in deoxyhaemoglobin whereas oxygen consumption during activation results in a decrease in oxyhaemoglobin and an increase in deoxyhaemoglobin. The balance between local perfusion and consumption can be investigated with NIRS. The first functional studies in the newborn with optical techniques used conventional single source-detector systems to measure overall changes in oxygenation over a particular area of the head. Meek et al reported that, in response to a visual stimulus, there was an increase in both oxyhaemoglobin and deoxyhaemoglobin over the occipital lobe.4 This finding was consistent with those of studies in infants using functional MRI and contrasted with the response in …

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.

Optical methods provide a means of monitoring cerebral oxygenation in newborn infants at risk of brain injury. A 32-channel optical imaging system has been developed with the aim of reconstructing three-dimensional images of regional blood volume and oxygenation. Full image data sets were acquired from 14 out of 24 infants studied; successful images have been reconstructed in 8 of these infants. Regional variations in cerebral blood volume and tissue oxygen saturation are present in healthy preterm infants. In an infant with a large unilateral intraventricular haemorrhage, a corresponding region of low oxygen saturation was detected. These results suggest that optical tomography may provide an appropriate technique for investigating regional cerebral haemodynamics and oxygenation at the cotside.

A time-resolved optical tomography system has been used to generate cross-sectional images of the human breast. Images are reconstructed using an iterative, nonlinear algorithm and measurements of mean photon flight time relative to those acquired on a homogeneous reference phantom. Thirty-eight studies have been performed on three healthy volunteers and 21 patients with a variety of breast lesions including cancer. We have successfully detected 17 out of 19 lesions, and shown that optical images of the healthy breast of the same volunteer display a heterogeneity which is repeatable over a period of months. However, results also indicate that the lack of accurate quantitation of optical parameters and limited morphological information limits the ability to characterize different types of lesions and distinguish benign from malignant tissues. Drawbacks of our current methodology and plans for overcoming them are discussed.

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 ...

Diffuse optical tomography (DOT) is a novel functional imaging modality for visualizing and continuously monitoring tissue and blood oxygenation levels, which is useful for brain imaging and tumor detection. Because of the nonlinearity of infrared light propagation in tissue, developing fast and robust reconstruction methods is the main challenge in making DOT a viable tool for clinical diagnostics.

There is increasing interest in using Cerenkov emissions for quality assurance and in vivo dosimetry in photon and electron therapy. Here, we investigate the production of Cerenkov light during proton therapy and its potential applications in proton therapy. A primary proton beam does not have sufficient energy to generate Cerenkov emissions directly, but we have demonstrated two mechanisms by which such emissions may occur indirectly: (1) a fast component from fast electrons liberated by prompt gamma (99.13%) and neutron (0.87%) emission; and (2) a slow component from the decay of radioactive positron emitters. The fast component is linear with dose and doserate but carries little spatial information; the slow component is non-linear but may be localised. The properties of the two types of emission are explored using Monte Carlo modelling in GEANT4 with some experimental verification. We propose that Cerenkov emissions could contribute to the visual sensation reported by some patients undergoing proton therapy of the eye and we discuss the feasibility of some potential applications of Cerenkov imaging in proton therapy.

In the continuing development of terahertz technology to enable the determination of tissue pathologies in real-time during surgical procedures, it is important to distinguish the measured terahertz signal from biomaterials and fluids, such as blood, which may mask the signal from tissues of interest. In this paper, we present the frequency-dependent absorption coefficients, refractive indices, and Debye relaxation times of whole blood, red blood cells, plasma, and a thrombus.

Previous work has demonstrated that electrical impedance tomography can be used to image human brain activity during evoked responses, but two-thirds of the reconstructed images fail to localize an impedance change to the expected stimulated cortical area. The localization failure may be caused by modelling the head as a homogenous sphere in the reconstruction algorithm. This assumption may lead to errors when used to reconstruct data obtained from the human head. In this study a 3D reconstruction algorithm, based on a model of the head as a homogenous sphere, was characterized by simulating the algorithm model, the head shape and the presence of the skull in saline-filled tanks. EIT images of a sponge, 14 cm3 volume with a resistivity contrast of 12%, were acquired in three different positions in tanks filled with 0.2% saline. In a hemispherical tank, 19 cm in diameter, the sponge was localized to within 3.4-10.7% of the tank diameter. In a head-shaped tank, the errors were between 3.1 and 13.3% without a skull and between 10.3 and 18.7% when a real human skull was present. A significant increase in localization error therefore occurs if an algorithm based on a homogeneous sphere is used on data acquired from a head-shaped tank. The increased error is due to the presence of the skull, as no significant increase in error occurred if a head-shaped tank was used without the skull present, compared to the localization error within the hemispherical tank. The error due to the skull significantly shifted the impedance change within the skull towards the centre of the image. Although the increased localization error due to the skull is not sufficient to explain the localization errors of up to 50% of the image diameter present in the images of some human subjects, the future use of a realistic head model in the reconstruction algorithm is likely to reduce the localization error in the human images due to the presence of the skull.

Previously, electrical impedance tomography (EIT) has been used to image impedance decreases in the exposed cortex of rabbits during brain activity. These are due to increased blood volume at the site of the stimulated cortex; as blood has a lower impedance than brain, the impedance decreases. During human brain activity similar blood flow changes have been detected using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). If blood volume also changes then the impedance of human cortex will change during brain activity; this could theoretically be imaged with EIT. EIT data were recorded from a ring of 16 scalp electrodes in 34 recordings in 19 adult volunteers before, during and after stimulation with (1) a visual stimulus produced by an 8 Hz oscillating checkerboard pattern or (2) sensory stimulation of the median nerve at the wrist by a 3 Hz electrical square wave stimulus. Reproducible impedance changes, with a similar timecourse to the stimulus, were seen in all experiments. Significant impedance changes were seen in 21 ± 5% (n = 16, mean ± SEM) and 19 ± 3% (n = 18) of the electrode measurements for visual and somatosensory paradigms respectively. The reconstructed 2D EIT images showed reproducible impedance changes in the approximate region of the stimulated cortex in 7/16 visual and 5/18 somatosensory experiments. This demonstrates that reproducible impedance changes can be measured during human brain activity. The final images contained spatial noise; the reasons for this and strategies to reduce this in future are discussed.

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.

This study was designed to determine the reproducibility of optical mammography. Eight healthy pre-menopausal volunteers were scanned at different time intervals (minutes, weeks and months apart) to investigate the effects of within-subject variation, between-subject variation and systematic variations on both the raw data and images. The study shows that the greatest source of variation in optical mammography raw data and images is between different subjects, and scans of the same subject are very reproducible. The averaged total haemoglobin concentration from the eight volunteers was (24 ± 10) µM, and the average tissue oxygen saturation was (70 ± 10)%, which is comparable with other data in the literature. The average absorption coefficient at 780 nm was (0.0048 ± 0.0017) mm(-1) and the average reduced scatter coefficient at 780 nm was (0.80 ± 0.12) mm(-1). Again, this is comparable with published values. When our data are combined with the published values, the weighted average total haemoglobin concentration and tissue oxygen saturation for pre-menopausal breasts are (29 ± 8) µM and (73 ± 3)%, respectively. The results of our study show that we can be reassured that any changes within the tumour region seen during neoadjuvant therapy are likely to be due to a real physiological response to treatment, as the physiological properties of the breast remain relatively constant. However, in this study, we cannot distinguish between a tumour response to treatment and systemic changes in the healthy breast.

An optical imaging system has been developed which uses measurements of diffusely reflected near-infrared light to produce maps of changes in blood flow and oxygenation occurring within the cerebral cortex. Optical sources and detectors are coupled to the head via an array of optical fibers, on a probe held in contact with the scalp, and data is collected at a rate of 10 Hz. A clinical electroencephalography (EEG) system has been integrated with the optical system to enable simultaneous observation of electrical and hemodynamic activity in the cortex of neurologically compromised newborn infants diagnosed with seizures. Studies have made a potentially critically important discovery of previously unknown transient hemodynamic events in infants treated with anticonvulsant medication. We observed repeated episodes of small increases in cortical oxyhemoglobin concentration followed by a profound decrease in 3 of 4 infants studied, each with cerebral injury who presented with neonatal seizures. This was not accompanied by clinical or EEG seizure activity and was not present in nineteen matched controls. The underlying cause of these changes is currently unknown. We tentatively suggest that our results may be associated with a phenomenon known as cortical spreading depolarization, not previously observed in the infant brain.

Diffuse optical imaging has been developed at University College London (UCL) as a new method of assessing cerebral function and pathology in the newborn infant brain. The technique exploits the relative transparency of biological tissue to near-infrared light (700–1000nm) and the wavelength dependent absorption characteristics of hemoglobin, which vary with oxygenation. Methods have been developed to localize rapid hemodynamic changes resulting from functional activation of the cerebral cortex, and to generate three-dimensional images representing the spatial variation in cerebral blood volume and oxygenation. Previous studies have also been made of the brains of infants with intraventricular hemorrhage, hypoxic-ischemic injury, and epileptic seizures. This paper summarizes preliminary measurements performed with a new time-resolved system.

The use of optical tomography to monitor changes in the uncompressed breast in response to neoadjuvant treatment of breast cancer. An investigation of the reproducibility of data and images from healthy volunteers was also conducted.

We present the results from a feasibility study which measures properties in the terahertz frequency range of excised cancerous, dysplastic and healthy colonic tissues from 30 patients. We compare their absorption and refractive index spectra to identify trends which may enable different tissue types to be distinguished. In addition, we present statistical models based on variations between up to 17 parameters calculated from the reflected time and frequency domain signals of all the measured tissues. These models produce a sensitivity of 82% and a specificity of 77% in distinguishing between healthy and all diseased tissues and a sensitivity of 89% and a specificity of 71% in distinguishing between dysplastic and healthy tissues. The contrast between the tissue types was supported by histological staining studies which showed an increased vascularity in regions of increased terahertz absorption.

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.

Objectives This study reviews the evidence for the effectiveness of computer-assisted diagnosis (CAD) in cancer imaging. Diagnostic applications were studied to estimate the impact of CAD on radiologists’ detection and diagnosis of cancer lesions. Methods Online databases were searched and 48 studies from 1992 to 2010 were included: 16 with radiologists using CAD to detect lesions (CADe) and 32 with radiologists using CAD to classify or diagnose lesions (CADx). Weighted means, statistics, summary receiver operating characteristics (SROC) curves, and related measures were used for analysis. Results There is evidence that CADx significantly improves diagnosis in mammography and breast ultrasound. In contrast, studies of CADx applied to lung CT and dermatologic imaging show an adverse impact on diagnosis. Overall, there is no evidence of a benefit due to the use of CADe. The area under the SROC curves was not significantly increased for radiologists using either CADe or CADx. Conclusions From this analysis it seems CADx can offer some benefit to radiologists in specific imaging applications for breast cancer diagnosis. There is no evidence of a beneficial effect in other applications of CAD and some evidence of a detrimental one.

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.

We describe a study of neurovascular coupling in the visual cortex of neonates using simultaneous, co-located EEG and near-infrared imaging. We also discuss the application of this technology to the study of neonatal seizure.

The Liquid Argon calorimeter (LAr) is one of the main sub-detectors in the ATLAS experiment at the LHC. It provides precision measurements of electrons, photons, jets and missing transverse energy produced in the LHC pp collisions. The LAr calorimeter has been installed in the ATLAS cavern and filled with liquid argon since 2006. The electronic calibration of the readout system, a critical system for precision measurements, has been continuously exercised in the commissioning phase, resulting in a fully commissioned calorimeter with its readout and a small number of problematic channels. A total of only 0.02% of the read out channels are dead beyond repair and 0.4% need special treatment for calibration. Throughout the last two years a large amount of calibration data has been collected. Cosmic muon data, first triggered via specially developed trigger boards on the LVL1 output of the Tile calorimeter and later with the standard ATLAS LVL1 calorimeter trigger, have been recorded at various stages of commissioning. In Sept 2008, with the first single beams circulating in the LHC ring and a near full readout of the calorimeter, events resulting from beam-gas interactions and beam-collimator splashes were recorded. We present here the LAr electronic calibration scheme, the measured stability of the pedestal, the pulse shape and the gain, and the expected calibration procedure for LHC running. We also present the calorimeter perfor mance study based on the cosmic muon and LHC beam events. With the reconstructed muon minimum ionizing signal in the calorimeter, the uniformity of the barrel electromagnetic calorimeter can be checked. The timing alignment as measured from the data can be compared to the expectation. The high energy depositions in the calorimeter readout cells, either from catastrophic energy loss of the cosmic muons or from beam interactions, are used to validate the signal shape of calorimeter response derived from the calibration pulse.

Diffuse optical tomography (DOT) is a functional imaging modality which aims to retrieve the optical characteristics of the probed tissue, namely light absorption and diffusion. The accurate retrieval of the spatial distribution for each optical characteristic involves the solution of a highly-ill posed, non-linear inverse problem, thus employing a regularization is essential. In this work, we propose an entropic regularization scheme for DOT reconstruction that uses a priori structural information through mutual information (MI) and joint entropy (JE).We compare MI and JE through simulations that illustrate their behavior when the reference and DOT images are not identical in structure. We propose an efficient implementation of these regularizers based on fast Fourier transforms. The method is tested through numerical simulations.

Diffuse optical imaging and spectroscopy use near-infrared light to derive physiological parameters such as total hemoglobin concentration and tissue oxygen saturation. Numerous clinical studies have been carried out, either using stand-alone optical methods or in combination with alternative imaging techniques. Studies have demonstrated that diffuse optical imaging and spectroscopy are able to distinguish malignant lesions from benign tissues. Breast cancer is characterized by an increase in total hemoglobin and a decrease in tissue oxygen saturation. Benign lesions such as cysts and fibroadenomas have also been studied, with less conclusive results. As diffuse optical imaging and spectroscopy do not use ionizing radiation, they are a suitable technique for performing repeated scans, such as for monitoring treatment response. This provides a unique functional and dynamic imaging method that reflects changes in tumor angiogenesis and hypoxia. When breast cancers are treated with primary medical therapy, this can result in a selective antiangiogenic effect that could help predict response to treatment earlier than by assessment of tumor size. Diffuse optical imaging and spectroscopy have been used to scan women at several points prior to and during their neoadjuvant chemotherapy treatment, with images and data showing physiological changes in the tumor in response to treatment. In the women who respond to therapy, the total hemoglobin concentration decreases and the level of oxygenation increases in the tumor over the course of the treatment. It is possible to predict a response to treatment as little as 4 days after the start of treatment. These findings demonstrate that optical techniques could play a role in the monitoring of changes in angiogenesis, apoptosis and hypoxia due to neoadjuvant chemotherapy.

We present a novel probe design which enables simultaneous electroencephalography (EEG) and near-infrared (NIR) optical imaging to be performed in a manner which is easy to apply, allows for optimum co-registration of the two forms of data and maximizes the number of sensors which can be applied to a given area. Our probe design is evaluated using a dual-modality, tissue-mimicking phantom and by performing a simple functional activation study of the human motor cortex. We successfully acquired NIR optical and EEG data simultaneously for both our phantom and our human motor cortex experiments, clearly demonstrating the effectiveness and suitability of our 'opto-electrode'.

Optical tomography is being developed to detect and specify disease in the female breast.Assessors were trained to interpret optical images, then presented with images from further patients.The sensitivity was 85.8% and the specificity 66.8%.

We report findings of a study aiming to improve research process and outcomes by eliciting detailed feedback on their experience from patient-volunteers taking part in early clinical evaluation of an optical breast imaging system.

We have successfully performed optical tomography of the uncompressed breast on 52 volunteers with breast lesions. We describe a new method for image reconstruction which draws prior information from the optical image itself.

The new Editor-in-Chief and new Deputy Editor share their introductory message.

Near-infrared spectroscopy has been used to record oxygenation changes in the visual cortex of 4 month old infants. Our in-house topography system, with 30 channels and 3 different source–detector separations, recorded changes in the concentration of oxy-, deoxy- and total haemoglobin (HbO2, HHb and HbT) in response to visual stimuli (face, scrambled visual noise and cartoons as rest). The aim of this work was to demonstrate the capability of the system to spatially localize functional activation and study the possibility of depth discrimination in the haemodynamic response. The group data show both face stimulation and visual noise stimulation induced significant increases in HbO2 from rest, but the increase in HbO2 with face stimulation was not significantly different from that seen with visual noise stimulation. The face stimuli induced increases in HbO2 were spread across a greater area across all depths than visual noise induced changes. In results from a single subject there was a significant increase of HbO2 in the inferior area of the visual cortex in response to both types of stimuli, and a larger number of channels (source–detector pairs) showed HbO2 increase to face stimuli, especially at the greatest depth. Activation maps were obtained using 3D reconstruction methods on multi source–detector separation optical topography data. (Some figures in this article are in colour only in the electronic version)

In this study, tissue mimicking phantoms for the THz regime were developed to aid the current understanding of contrast mechanisms of tissue with THz pulsed imaging (TPI). The phantoms, compromising mixtures of water and protein, mimic biological tissue in both spatial and spectroscopic regimes. THz spectroscopy of the individual phantom constituents was compared with reflection measurements of phantoms of varying compositions. Phantom composition was varied enabling the emulation of specific tissue properties, thus allowing the analysis of parameters such as the error with which discreet components can be identified; 7.5% for low gelatin concentration gels and 17% for higher concentration gels. Identifying this uncertainty is important when imaging tissues that have surface features not obvious to other techniques such as visible imaging of dysplasia.

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.

Screening X-ray mammography is limited by false positives and negatives leading to unnecessary physical and psychological morbidity. Diffuse Optical Imaging using harmless near infra red light, provides lesion detection based on functional abnormalities and represents a novel diagnostic arm that could complement traditional mammography. Reviews of optical breast imaging have not been systematic, are focused mainly on technological developments, and have become superseded by rapid technological advancement. The aim of this study is to review clinically orientated studies involving approximately 2,000 women in whom optical mammography has been used to evaluate the healthy or diseased breast. The results suggest that approximately 85% of breast lesions are detectable on optical mammography. Spectroscopic resolution of tissue haemoglobin composition and oxygen saturation may improve the detectability of breast diseases. Results suggest that breast lesions contain approximately twice the haemoglobin concentration of background tissue. Current evidence suggests that it is not possible to distinguish benign from malignant disease using optical imaging techniques in isolation. Methods to improve the performance of Diffuse Optical Imaging, such as better spectral coverage with additional wavelengths, improved modelling of light transport in tissues and the use of extrinsic dyes may augment lesion detection and characterisation. Future research should involve large clinical trials to determine the overall sensitivity and specificity of optical imaging techniques as well as to establish patient satisfaction and economic viability.

We have added new TCSPC electronics to our 3D time-resolved imaging system. This will allow 3D functional images of the neonatal brain. We report on preliminary validation of the electronics.

We present our latest 3D optical tomography images of the neonatal brain, and discuss new image reconstruction techniques which incorporate prior anatomical information from MRI.

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.

We present initial results from a new approach to optical mammography in which the patient lies with her uncompressed breast suspended in a cup filled with a tissue-equivalent liquid. Data are acquired using a 32 channel time-resolved optical tomography system, from which images of blood volume and oxygenation are reconstructed. To date, we have imaged twelve patients with lesions (eight malignant, four benign). In eight cases the lesion was the dominant feature in the image, and in three of the remaining four patients the lesion was clearly identifiable. Initial results confirm that malignant tumors commonly appear as regions of anomalously high absorption, and sometimes of higher than average scatter. These encouraging results suggest that optical mammography of the uncompressed breast may provide a practical alternative to other approaches which is clinically acceptable and provides full 3D localization.