Medical imaging applied to heritage.

The use of imaging has transformed the study of cultural heritage artefacts in the same way that medical imaging has transformed medicine. X-ray-based techniques are common in both medical and heritage imaging. Optical imaging, including scientific photography and spectral imaging techniques, is also common in both domains. Some common medical imaging methods such as ultrasound and MRI have not yet found routine application in heritage, whereas other methods such as imaging with charged and uncharged particles and 3D surface imaging are more common in heritage. Here, we review the field of heritage imaging from the point of view of medical imaging and include some classic challenges of heritage imaging such as reading the text on burnt scrolls, identifying underdrawings in paintings, and CT scanning of mummies, an ancient calculating device and sealed documents. We show how hyperspectral imaging can offer insight into the drawing techniques of Leonardo da Vinci and explain how laparoscopy has identified the method of construction of a 500-year-old pop-up anatomical text book.

Cambrian edrioasteroid reveals new mechanism for secondary reduction of the skeleton in echinoderms.

Echinoderms are characterized by a distinctive high-magnesium calcite endoskeleton as adults, but elements of this have been drastically reduced in some groups. Herein, we describe a new pentaradial echinoderm, Yorkicystis haefneri n. gen. n. sp., which provides, to our knowledge, the oldest evidence of secondary non-mineralization of the echinoderm skeleton. This material was collected from the Cambrian Kinzers Formation in York (Pennsylvania, USA) and is dated as ca 510 Ma. Detailed morphological observations demonstrate that the ambulacra (i.e. axial region) are composed of flooring and cover plates, but the rest of the body (i.e. extraxial region) is preserved as a dark film and lacks any evidence of skeletal plating. Moreover, X-ray fluorescence analysis reveals that the axial region is elevated in iron. Based on our morphological and chemical data and on taphonomic comparisons with other fossils from the Kinzers Formation, we infer that the axial region was originally calcified, while the extraxial region was non-mineralized. Phylogenetic analyses recover Yorkicystis as an edrioasteroid, indicating that this partial absence of skeleton resulted from a secondary reduction. We hypothesize that skeletal reduction resulted from lack of expression of the skeletogenic gene regulatory network in the extraxial body wall during development. Secondary reduction of the skeleton in Yorkicystis might have allowed for greater flexibility of the body wall.

Diffuse optical tomography for the detection of perinatal stroke at the cot side: a pilot study.

BACKGROUND: Perinatal stroke is a potentially debilitating injury, often under-diagnosed in the neonatal period. We conducted a pilot study investigating the role of the portable, non-invasive brain monitoring technique, diffuse optical tomography (DOT), as an early detection tool for infants with perinatal stroke. METHODS: Four stroke-affected infants were scanned with a DOT system within the first 3 days of life and compared to four healthy control subjects. Spectral power, correlation, and phase lag between interhemispheric low frequency (0.0055-0.3 Hz) hemoglobin signals were assessed. Optical data analyses were conducted with and without magnetic resonance imaging (MRI)-guided stroke localization to assess the efficacy of DOT when used without stroke anatomical information. RESULTS: Interhemispheric correlations of both oxyhemoglobin and deoxyhemoglobin concentration were significantly reduced in the stroke-affected group within the very low (0.0055-0.0095 Hz) and resting state (0.01-0.08 Hz) frequencies (p < 0.003). There were no interhemispheric differences for spectral power. These results were observed even without MRI stroke localization. CONCLUSION: This suggests that DOT and correlation-based analyses in the low-frequency range can potentially aid the early detection of perinatal stroke, prior to MRI acquisition. Additional methodological advances are required to increase the sensitivity and specificity of this technique.

Image reconstruction of oxidized cerebral cytochrome C oxidase changes from broadband near-infrared spectroscopy data.

In diffuse optical tomography (DOT), overlapping and multidistance measurements are required to reconstruct depth-resolved images of oxy- ([Formula: see text]) and deoxy- (HHb) hemoglobin concentration changes occurring in the brain. These can be considered an indirect measure of brain activity, under the assumption of intact neurovascular coupling. Broadband systems also allow changes in the redox state of cytochrome c oxidase (oxCCO) to be measured, which can be an important biomarker when neurovascular coupling is impaired. We used DOT to reconstruct images of [Formula: see text], [Formula: see text], and [Formula: see text] from data acquired with a broadband system. Four healthy volunteers were measured while performing a visual stimulation task (4-Hz inverting checkerboard). The broadband system was configured to allow multidistance and overlapping measurements of the participants' visual cortex with 32 channels. A multispectral approach was employed to reconstruct changes in concentration of the three chromophores during the visual stimulation. A clear and focused activation was reconstructed in the left occipital cortex of all participants. The difference between the residuals of the three-chromophore model and of the two-chromophore model (recovering only [Formula: see text] and [Formula: see text]) exhibits a spectrum similar to that of oxCCO. These results form a basis for further studies aimed to further optimize image reconstruction of [Formula: see text].

Evaluating real-time image reconstruction in diffuse optical tomography using physiologically realistic test data.

In diffuse optical tomography (DOT), real-time image reconstruction of oxy- and deoxy-haemoglobin changes occurring in the brain could give valuable information in clinical care settings. Although non-linear reconstruction techniques could provide more accurate results, their computational burden makes them unsuitable for real-time applications. Linear techniques can be employed under the assumption that the expected change in absorption is small. Several approaches exist, differing primarily in their handling of regularization and the noise statistics. In real experiments, it is impossible to compute the true noise statistics, because of the presence of physiological oscillations in the measured data. This is even more critical in real-time applications, where no off-line filtering and averaging can be performed to reduce the noise level. Therefore, many studies substitute the noise covariance matrix with the identity matrix. In this paper, we examined two questions: does using the noise model with realistic, imperfect data yield an improvement in image quality compared to using the identity matrix; and what is the difference in quality between online and offline reconstructions. Bespoke test data were created using a novel process through which simulated changes in absorption were added to real resting-state DOT data. A realistic multi-layer head model was used as the geometry for the reconstruction. Results validated our assumptions, highlighting the validity of computing the noise statistics from the measured data for online image reconstruction, which was performed at 2 Hz. Our results can be directly extended to a real application where real-time imaging is required.

Data-driven approach to optimum wavelength selection for diffuse optical imaging.

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.

A 3D in vitro cancer model as a platform for nanoparticle uptake and imaging investigations.

In order to maximize the potential of nanoparticles (NPs) in cancer imaging and therapy, their mechanisms of interaction with host tissue need to be fully understood. NP uptake is known to be dramatically influenced by the tumor microenvironment, and an imaging platform that could replicate in vivo cellular conditions would make big strides in NP uptake studies. Here, a novel NP uptake platform consisting of a tissue-engineered 3D in vitro cancer model (tumoroid), which mimics the microarchitecture of a solid cancer mass and stroma, is presented. As the tumoroid exhibits fundamental characteristics of solid cancer tissue and its cellular and biochemical parameters are controllable, it provides a real alternative to animal models. Furthermore, an X-ray fluorescence imaging system is developed to demonstrate 3D imaging of GNPs and to determine uptake efficiency within the tumoroid. This platform has implications for optimizing the targeted delivery of NPs to cells to benefit cancer diagnostics and therapy.

MONSTIR II: a 32-channel, multispectral, time-resolved optical tomography system for neonatal brain imaging.

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.

Multimodality characterization of microstructure by the combination of diffusion NMR and time-domain diffuse optical data.

Combining datasets with a model of the underlying physics prior to mapping of tissue provides a novel approach improving the estimation of parameters. We demonstrate this approach by merging near infrared diffuse optical signal data with diffusion NMR data to inform a model describing the microstructure of a sample. The study is conducted on a homogeneous emulsion of oil in a dispersion medium of water and proteins. The use of a protein based background, rich in collagen, introduces a similarity to real tissues compared to other models such as intralipids. The sample is investigated with the two modalities separately. Then, the two datasets are used to inform a combined model, and to estimate the size of the microstructural elements and the volume fraction. The combined model fits the microstructural properties by minimizing the difference between experimental and modelled data. The experimental results are validated with confocal laser scanning microscopy. The final results demonstrate that the combined model provides improved estimates of microstructural parameters compared to either individual model alone.

Terahertz time-domain spectroscopy of human blood.

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.

A systematic review of computer-assisted diagnosis in diagnostic cancer imaging.

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.

Recommendations for research design and reporting in computer-assisted diagnosis to facilitate meta-analysis.

Computer-assisted diagnosis (CAD) describes a diverse, heterogeneous range of applications rather than a single entity. The aims and functions of CAD systems vary considerably and comparing studies and systems is challenging due to methodological and design differences. In addition, poor study quality and reporting can reduce the value of some publications. Meta-analyses of CAD are therefore difficult and may not provide reliable conclusions. Aiming to determine the major sources of heterogeneity and thereby what CAD researchers could change to allow this sort of assessment, this study reviews a sample of 147 papers concerning CAD used with imaging for cancer diagnosis. It discusses sources of variability, including the goal of the CAD system, learning methodology, study population, design, outcome measures, inclusion of radiologists, and study quality. Based upon this evidence, recommendations are made to help researchers optimize the quality and comparability of their trial design and reporting.

Terahertz pulsed imaging of freshly excised human colonic tissues.

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.

Accuracy and resolution of THz reflection spectroscopy for medical imaging.

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.

A quantitative assessment of the depth sensitivity of an optical topography system using a solid dynamic tissue-phantom.

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.

Optical tomography of breast cancer-monitoring response to primary medical therapy.

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.

Information theoretic regularization in diffuse optical tomography.

Diffuse optical tomography (DOT) retrieves the spatially distributed optical characteristics of a medium from external measurements. Recovering the parameters of interest involves solving a nonlinear and highly ill-posed inverse problem. This paper examines the possibility of regularizing DOT via the introduction of a priori information from alternative high-resolution anatomical modalities, using the information theory concepts of mutual information (MI) and joint entropy (JE). Such functionals evaluate the similarity between the reconstructed optical image and the prior image while bypassing the multimodality barrier manifested as the incommensurate relation between the gray value representations of corresponding anatomical features in the two modalities. By introducing structural information, we aim to improve the spatial resolution and quantitative accuracy of the solution. We provide a thorough explanation of the theory from an imaging perspective, accompanied by preliminary results using numerical simulations. In addition we compare the performance of MI and JE. Finally, we have adopted a method for fast marginal entropy evaluation and optimization by modifying the objective function and extending it to the JE case. We demonstrate its use on an image reconstruction framework and show significant computational savings.

A dynamic optical imaging phantom based on an array of semiconductor diodes.

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.

An electrically-activated dynamic tissue-equivalent phantom for assessment of diffuse optical imaging systems.

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.

Three-dimensional time-resolved optical mammography of the uncompressed breast.

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.