The impact of force, time, and rotation on the transfer of ammonium nitrate: A reductionist approach to understanding evidence dynamics.

Empirical studies evaluating the conditions under which the transfer of forensic materials occurs can provide contextual information and offer insight into how that material may have been transferred in a given scenario. Here, a reductionist approach was taken to assess the impact of force, time, and rotation on the transfer of an explosive compound. An Instron ElectroPuls E3000 material testing instrument was used to bring porous and non-porous surfaces adulterated with an ammonium nitrate into direct contact with a human skin analogue, controlling for the force of contact, duration of contact, and rotation applied during contact. Quantifiable amounts of ammonium nitrate were recovered from all of the recipient surfaces demonstrating that ammonium nitrate is readily transferred from one surface to another, even when contact occurs for a short duration with a relatively low force. More particulates were transferred from non-porous surfaces onto the human skin analogue, but the amount of ammonium nitrate transferred did not depend upon the force of contact, duration of contact, or the amount of rotation applied. However, when contact occurred and involved rotation, a greater transfer of ammonium nitrate was observed, compared to those contacts occurring without rotation being applied. This approach complements more commonly-used holistic experiments that test multiple interacting variables in a realistic setting by isolating these variables, allowing them to be examined individually. This can be utilised to better understand the individual impact that specific variables have on the transfer of trace evidence in relevant crime reconstruction contexts.

Trace evidence dynamics of cocaine on banknotes: A comparison study of paper and polymer banknotes.

It is well established that a large proportion of paper banknotes in circulation contain traces of cocaine. Being able to discriminate between the innocent transfer of illicit drug particles acquired through everyday interactions with surfaces such as banknotes, as opposed to transfer resulting from criminal activities can provide valuable intelligence that can inform an investigation. With many countries adopting polymer banknotes as legal tender, it is important to consider the transfer of cocaine from these surfaces as well as the retention of these particulates on polymer banknotes for evaluative interpretation in crime reconstruction. This comparison study assessed three contact variables (force, time, and rotation) on the transfer of cocaine particulates from paper and polymer banknotes onto a human skin proxy. The persistence of cocaine particulates was assessed through a realistic scenario which mimicked a cash transaction. Quantifiable amounts of cocaine were transferred onto the human skin proxy across all of the contacts assessed, with a greater transfer observed with contacts involving polymer banknotes and those contacts which involved rotation. Following extensive handling, cocaine persisted on both banknote types, with paper banknotes retaining larger amounts of cocaine than polymer banknotes. These findings show that cocaine can persist on both paper and polymer banknotes for extended periods of time following handling and is therefore available for transfer. This transfer then readily occurs, even when contact is brief and involves relatively small forces. A key distinction between the banknote types was that cocaine particulates are more likely to transfer from polymer banknotes due to the lower retention rate of particulates on this surface. Such insights can aid in evaluating the relevance of illicit drug particles identified on items or persons of interest in crime reconstruction approaches.

Sampling of explosive residues: The use of a gelatine-based medium for the recovery of ammonium nitrate.

Forensic scientists must be able to recover traces of any original explosive materials not consumed in the detonation, in a careful controlled manner to aid a crime reconstruction. In current sampling techniques, the collection efficiency of post-blast residue is highly variable and often dependent on the swabbing materials and solvent systems used. To address these method limitations, this study presents a gelatine-based sampling medium and assesses its capabilities for the collection of ammonium nitrate. Common surfaces were spotted with a known concentration of ammonium nitrate, the unset gel applied, allowed to set, and then peeled from the surface. The gel was dissolved, and solid phase extraction employed to isolate the target explosive compound and remove the constituents of the gel. The eluate was concentrated and subsequently analysed and quantified. Overall, the gel formulation was able to collect ammonium nitrate from all of the test surfaces, with recoveries ranging from 0.1% to 61.7%. This study presents a gelatine-based formulation that has the potential to become a valuable asset in the forensic tool kit for the collection of explosive traces. A key attribute of the gel is that it offers an alternative recovery tool to conventional swabbing and solvent extraction methods.

Co-registered combined OCT and THz imaging to extract depth and refractive index of a tissue-equivalent test object.

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.

The physics of Cerenkov light production during proton therapy.

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.

An x-ray fluorescence imaging system for gold nanoparticle detection.

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.

The reproducibility of optical mammography in healthy volunteers.

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.

A quantitative x-ray detection system for gold nanoparticle tumour biomarkers.

X-ray fluorescence techniques have proven beneficial for identifying and quantifying trace elements in biological tissues. A novel approach is being developed that employs x-ray fluorescence with an aim to locate heavy nanoparticles, such as gold, which are embedded into tissues. Such nanoparticles can be functionalized to act as markers for tumour characteristics to map the disease state, with the future aim of imaging them to inform cancer therapy regimes. The uptake of functionalized nanoparticles by cancer cells will also enable detection of small clusters of infiltrating cancer cells which are currently missed by commonly used imaging modalities. The novel system, consisting of an energy-resolving silicon drift detector with high spectral resolution, shows potential in both quantification of and sensitivity to nanoparticle concentrations typically found in tumours. A series of synchrotron measurements are presented; a linear relationship between fluorescence intensity and gold nanoparticle (GNP) concentration was found down to 0.005 mgAu ml(-1), the detection limit of the system. Successful use of a bench-top source, suitable for possible future clinical use, is also demonstrated, and found not to degrade the detection limit or accuracy of the GNP concentration measurement. The achieved system sensitivity suggests possible future clinical usefulness in measuring tumour uptake in vivo, particularly in shallow tumour sites and small animals, in ex vivo tissue and in 3D in vitro research samples.

Monitoring the response to primary medical therapy for breast cancer using three- dimensional time-resolved optical mammography.

Primary medical therapy is used to reduce tumour size prior to surgery in women with locally advanced breast cancer. Optical tomography is a functional imaging technique using near- infrared light to produce three-dimensional breast images of tissue oxygen saturation and haemoglobin concentration. Its advantages include the ability to display quantitative physiological information, and to allow repeated scans without the hazards associated with exposure to ionising radiation. There is a need for a non-invasive functional imaging tool to evaluate response to treatment, so that non-responders can be given the opportunity to change their treatment regimen. Here, we evaluate the use of optical tomography for this purpose. Four women with newly diagnosed breast cancer who were about to undergo primary medical therapy gave informed and voluntary consent to take part in the study. Changes in physiological and optical properties within the tumour were evaluated during the course of neoadjuvant chemotherapy. Optical imaging was performed prior to treatment, after the first cycle of chemotherapy, halfway through, and on completion of chemotherapy. Images of light absorption and scatter at two wavelengths were produced, from which images of total haemoglobin concentration and oxygen saturation were derived. All patients that showed a good or complete response to treatment on MRI showed a corresponding recovery in the haemoglobin concentration images. Changes in mean tumour total haemoglobin concentration could be seen four weeks into treatment. The tumour oxygen saturation was low compared to background in three out of four patients, and also showed a return to baseline over treatment. Optical imaging of the breast is feasible during primary medical therapy and can be used to assess response to treatment over six months.

Transient haemodynamic events in neurologically compromised infants: a simultaneous EEG and diffuse optical imaging study.

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 (>30s) 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.

An elastically compressible phantom material with mechanical and x-ray attenuation properties equivalent to breast tissue.

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.

A tissue equivalent phantom for simultaneous near-infrared optical tomography and EEG.

We describe a phantom which enables EEG and near-infrared optical tomography to be performed simultaneously over the same volume. The phantom provides a surface electrical contact impedance comparable to that of the human scalp, whilst also possessing an optical scattering coefficient and electrical conductivity equivalent to that of brain tissue. The construction of the phantom is described, as is the resulting simultaneous EEG and near infrared optical tomography experiment, which, to our knowledge, is the first performed on a scale comparable to that of the infant human brain. This imaging experiment successfully shows the suitability of this phantom construction for the assessment of simultaneous EEG and near infrared optical tomography systems.

Design and evaluation of a probe for simultaneous EEG and near-infrared imaging of cortical activation.

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'.

Assessing the validity of modulation transfer function evaluation techniques with application to small area and scanned digital detectors.

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.

Investigation of depth dependent changes in cerebral haemodynamics during face perception in infants.

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.

Three dimensional optical imaging of blood volume and oxygenation in the neonatal brain.

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.

Three-dimensional whole-head optical tomography of passive motor evoked responses in the neonate.

Optical tomography has been used to reconstruct three-dimensional images of the entire neonatal head during motor evoked responses. Data were successfully acquired during passive movement of each arm on four out of six infants examined, from which eight sets of bilateral images of hemodynamic parameters were reconstructed. Six out of the eight images showed the largest change in total hemoglobin in the region of the contralateral motor cortex. The mean distance between the peak response in the image and the estimated position of the contralateral motor cortex was 10.8 mm. These results suggest that optical tomography may provide an appropriate technique for non-invasive cot-side imaging of brain function.

Recent advances in diffuse optical imaging.

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.

A method for generating patient-specific finite element meshes for head modelling.

Finite element modelling of fields within the body, whether electrical or optical, requires knowledge of the geometry of the object being examined. It can be clinically impractical to obtain accurate surface information for individual patients, although a limited set of measurements such as the locations of sensors attached to the body, can be acquired more readily. In this paper, we describe how a generic surface taken from an adult head is warped to fit points measured on a neonatal head surface to provide a new, individual surface from which a finite element mesh was generated. Simulations show that data generated from this mesh and from the original neonatal head surface are similar to within experimental errors. However, data generated from a mesh of the best fit sphere were significantly different from data generated from the original neonatal head surface.

Endothelial dysfunction induced by oxidized low-density lipoproteins in isolated mouse aorta: a comparison with apolipoprotein-E deficient mice.

We characterized the acute effects of oxidized low-density lipoproteins (oxidized-LDL) on vascular reactivity in isolated aorta from wild-type C57BL/6J mice, and compared these with the chronic alterations in vascular function observed in apolipoprotein-E gene knockout [ApoE(-/-)] mice fed a high-fat diet, which results in hyperlipidemia and atherosclerosis. In the abdominal (but not thoracic) aorta, oxidized-LDL (100 microg/ml) reduced relaxations induced by acetylcholine (10(-9) M-10(-5) M), which are mediated entirely by nitric oxide (NO). The relaxations induced by the NO donor S-nitroso-N-acetylpenicillamine (SNAP, 10(-8) M-10(-4) M), the cyclic GMP analogue 8-bromo cyclic GMP (100 microM) and the nonspecific vasodilator papaverine (100 microM) were not changed by oxidized-LDL. Native LDL had no effect on vasorelaxations. The attenuation of endothelium-dependent relaxations caused by oxidized-LDL mimicked the endothelial dysfunction found in ApoE(-/-) mice. These results are consistent with the suggestion that oxidized-LDL has an important role in the pathogenesis of endothelial NO dysfunction associated with hyperlipidemia and atherosclerosis in these mice.