M. J. Farquharson's research while affiliated with University of Tuebingen and other places

Publications (83)

Article
Full-text available
Iron is an essential element vital for growth and development. The severe effects on the body due to iron deficiency or overload have prompted sustained research into accurate in vivo iron measurement techniques for the past several decades. X-ray fluorescence (XRF) analysis of iron in the body has been investigated in this work because of the non-...
Article
BACKGROUND Contrast agents (CA) are administered in magnetic resonance imaging (MRI) clinical exams to measure tissue perfusion, enhance image contrast between adjacent tissues, or provide additional biochemical information in molecular MRI. The efficacy of a CA is determined by the tissue distribution of the agent and its concentration in the extr...
Article
Prostatic zinc content is a known biomarker for discriminating normal healthy tissue from benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Given that zinc content is not readily measured without a tissue biopsy, we have been exploring noninvasive imaging methods to detect these diagnostic differences using a zinc-responsive MRI contras...
Article
Previous studies have shown that the combination of X‐ray fluorescence and X‐ray diffraction data can be used as a histopathological characterization tool for breast tissue. Recent advances in energy‐dispersive X‐ray fluorescence techniques have allowed for benchtop systems to produce useful results in a reasonable time frame, allowing for clinical...
Article
The present study was implemented using two X-ray detection systems; a monochromatic X-ray system for X-ray Fluorescence (XRF) and Angular Dispersive X-ray Diffraction (ADXRD) techniques, and a combined Polarized Energy Dispersive X-ray Fluorescence (PEDXRF) and Energy Dispersive X-ray Diffraction (EDXRD) system. As both of these systems involve di...
Article
Chromium (III) is a trace mineral that plays an important role in glucose and lipid metabolism in the body, in addition to being used in clinical formulations for the treatment of hypoglycemia. Chromium (Cr) deficiency in humans is known to cause insulin resistance and diabetes, however, effects of over exposure are not well studied or understood....
Article
There exists a need for accurate, non-invasive point-of-care tests to detect body iron burden. This study investigated the use of x-ray fluorescence (XRF) measurements of skin iron as a marker for organ iron content in rats. This study also evaluated a novel application of a commercial XRF device, commonly used in mining and construction, as a rapi...
Article
Full-text available
Purpose: One of the major problems in breast cancer surgery is defining surgical margins and establishing complete tumor excision within a single surgical procedure. The goal of this work is to establish instrumentation that can differentiate between tumor and normal breast tissue with the potential to be implemented in vivo during a surgical proc...
Article
The cuprizone model of demyelination is well established in the mouse as a tool for the study of the mechanisms of both demyelination and remyelination. It is often desirable, however, to have a larger model, such as the rat, especially for imaging-based studies, yet initial work has failed to show demyelination in cuprizone-fed rats. Several recen...
Article
Tube-based-polarized energy-dispersive X-ray fluorescence (EDXRF) is a powerful adaptation on traditional EDXRF, requiring very specific geometry and a scattering target to generate polarized X-rays. This secondary target is typically chosen to be a metallic foil, allowing for the polarization of the incident X-ray beam, and the addition of the sec...
Conference Paper
Transition metal concentrations in the central nervous system (CNS) are altered in neurodegenerative diseases such as Alzheimer’s, Parkinson’s and multiple sclerosis. A common symptom of these diseases is demyelination, which is the degradation of the myelin sheath that encapsulates the neurons in vertebrates. Transition metal concentrations were m...
Article
A model of dysmyelination, the Long Evans Shaker (les) rat, was used to study the contribution of myelin to MR tissue properties in white matter. A large region of white matter was identified in the deep cerebellum and was used for measurements of the MR relaxation rate constants, R1 = 1/T1 and R2 = 1/T2 , at 7 T. In this study, R1 of the les deep...
Article
In the cuprizone model of demyelination, the neurotoxin cuprizone is fed to mice to induce a reproducible pattern of demyelination in the brain. Cuprizone is a copper chelator and it has been hypothesized that it induces a copper deficiency in the brain which leads to demyelination. To test this hypothesis and investigate the possible role of other...
Article
Routine tissue sample preparation using chemical fixatives is known to preserve the morphology of the tissue being studied. A competitive method, cryofixation followed by freeze drying, involves no chemical agents and maintains the biological function of the tissue. The possible effects of both sample preparation techniques in terms of the distribu...
Article
Full-text available
Breast cancer is the most common cancer and ovarian cancer is the 8th most common cancer affecting women worldwide. This study highlights the changes of trace element levels accompanied by the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) of the breast, using micro probe Synchrotron Radiation X-ray Fluorescence...
Article
Worldwide, about 1.3 million women are diagnosed with breast cancer annually with an estimated 465,000 deaths. Accordingly, there is a need for high accuracy and speed in diagnosis of lesions suspected of being cancerous. This study assesses the interaction data collected from low energy x-rays within breast tissue samples. Trace element concentrat...
Article
Full-text available
Drinking water aquifers in many areas of the world have naturally elevated levels of inorganic arsenic exceeding the World Health Organization limit. Arsenic concentrations in human nail clippings are commonly used as a biomarker of exposure to this toxic element. However, the chemical form of arsenic accumulated in nail tissues is not well determi...
Article
X‐ray interaction data, including measuring bio‐metal levels and scattering characteristics, are being shown to be a possible discriminating variable in the classification of human tissues. However, a major concern when using X‐ray interaction data in breast cancer material is that the samples are rarely 100% tumour because of the invasive nature o...
Article
Full-text available
Arsenic (As) distribution in nail clippings from three healthy human subjects was investigated using the microbeam experimental setup of the hard x-ray micro-analysis (HXMA) beamline from the Canadian Light Source (CLS) synchrotron. A pair of toenail and fingernail clippings was collected from each of three subjects (one contributed two fingernail...
Article
Worldwide, breast cancer is the most frequently diagnosed cancer in women and the leading cause of cancer death among women. The concentrations of bio‐metals are crucial for the homeostasis of human health and are being shown to have significantly different concentrations when comparing human cancer tissue and normal tissue. This is the first study...
Article
In vivo monitoring of trace and biometals in skin is normally quantified using phantoms that assume a constant elemental distribution within the skin. Layered calibration skin phantoms could potentially improve the reliability of in vivo calibration skin phantoms by better representing the actual in vivo distribution. This work investigates the mic...
Article
In manganese-enhanced magnetic resonance imaging (MEMRI), the paramagnetic divalent ion of manganese (Mn(2+)) is injected into animals to generate tissue contrast, typically at much higher exposures than have been previously used in studies of Mn toxicity. Here we investigate the effect of these injections on the homeostasis of the transition metal...
Article
Secondary colorectal liver cancer is the most widespread malignancy in patients with colorectal cancer. The aim of this study is to identify and differentiate between normal liver tissue and malignant secondary colorectal liver cancer tissue using X-ray scattering and X-ray fluorescence spectroscopy to investigate the best combination of data that...
Article
Micro-Proton Induced X-ray Emission (μ-PIXE) and Proton Induced Gamma-ray Emission (PIGE) techniques were employed in the investigation of trace and essential elements distribution in normal and diseased human femoral head sections affected by osteoarthritis (OA). PIGE was exploited in the determination of elements of low atomic number z15 viz Ca,...
Article
In the past decade, energy-dispersive X-ray diffraction (EDXRD) has been used to identify the nature of tissues. However, these systems have limited clinical use because of problems such as the long measurement times. In this study, the relation between various setup parameters and some performance specifications such as sensitivity, spatial resolu...
Article
Trace elements are involved in many key pathways involving cell cycle control. The influence of zinc and zinc chelator (TPEN) on transcription levels of the main zinc transporters (ZnT1 and ZIP1) in the HT-29 colorectal cell line has not been reported. Proliferation of HT-29 cells was measured using the methylene blue assay after exposure to zinc (...
Article
X-ray absorption near-edge structure (XANES) spectroscopy was used to examine the oxidation state of Zn, Fe and Cu in 22 normal and 23 tumour regions spread over 30 formalin-fixed, paraffin-embedded tissue samples of human primary invasive breast cancer. A micro-mapping analysis of the metal distribution in the tissue was performed prior to the XAN...
Conference Paper
The divalent cations Ca, P and Zn have been reported to play an important role in the normal growth and remodelling of articular cartilage and subchondral bone and in the degenerative and inflammatory processes associated with osteoarthritis (OA). In particular, they act as co-factors of a class of enzymes known as metalloproteinases, believed to b...
Article
The aim of this work was to investigate the differences in composition between malignant and non-malignant breast tissue. 38 invasive ductal carcinomas and 45 non-malignant breast tissues were measured, each being mounted in cylindrical sample holders of volume 25 mm2. The experiments were performed at the European Synchrotron Radiation Facility (E...
Article
A microbeam synchrotron X-ray fluorescence (mu SRXRF) technique has been used to determine the localization and the relative concentrations of Zn, Cu, Fe and Ca in primary colorectal cancer and secondary colorectal liver metastases. 24 colon and 23 liver samples were examined, all of which were formalin fixed tissues arranged as microarrays of 1.0...
Article
Micro-proton-induced X-ray emission (μ-PIXE) analysis has been employed in investigating the presence of number of essential anions and cations in thin sections of diseased human articular cartilage affected by osteoarthritis (OA). Distribution maps for Ca, P, K and S in diseased sections show marked alterations in the concentrations of these at th...
Article
X-ray scattering techniques allow uncovering the nanostructure of human hard and soft tissues. They provide not only the presence of nanostructures but also their orientation and texture. The combination of these techniques with highly intense, focused X-ray, highly efficient and fast detection systems as well as scanning possibilities results in s...
Article
Full-text available
Determination of the dynamics of specific cell populations in vivo is essential for the development of cell-based therapies. For cell tracking by magnetic resonance imaging (MRI), cells need to internalize, or be surface labeled with a MRI contrast agent, such as superparamagnetic iron oxide nanoparticles (SPIOs): SPIOs give rise to signal loss by...
Article
The investigations reported herein link tissue structure and elemental presence with issues of environmental health and disease, exemplified by uptake and storage of potentially toxic elements in the body, the osteoarthritic condition and malignancy in the breast and other soft tissues. Focus is placed on application of state-of-the-art ionizing ra...
Article
Synovial joints articulate in a lubricating environment, the system providing for smooth articulation. The articular cartilage overlying the bone consists of a network of collagen fibres. This network is essential to cartilage integrity, suffering damage in degenerative joint disease such as osteoarthritis. At Surrey and also in work conducted by t...
Article
Micro Proton Induced X-ray Emission (micro-PIXE) analysis has been employed herein in investigating and quantifying the distribution of a number of essential elements in thin human diseased articular cartilage sections affected by osteoarthritis (OA). Various cations Ca, P and Zn have been reported to play an important role both in the normal growt...
Article
The motivation behind this study is to assess whether angular dispersive x-ray diffraction (ADXRD) data, processed using multivariate analysis techniques, can be used for classifying secondary colorectal liver cancer tissue and normal surrounding liver tissue in human liver biopsy samples. The ADXRD profiles from a total of 60 samples of normal liv...
Article
Zinc is known to play an important role in many cellular processes, and the levels of zinc are controlled by specific transporters from the ZIP (SLC39A) influx transporter group and the ZnT (SLC30A) efflux transporter group. The distribution of zinc was measured in 59 samples of invasive ductal carcinoma of breast using synchrotron radiation micro...
Article
An x-ray fluorescence (XRF) system utilising a synchrotron radiation source was used to quantify the levels of Fe, Cu, Zn and K in colorectal liver metastases and surrounding normal liver tissue as a possible mechanism for detecting cancer in a tissue biopsy. Sixty samples were measured and a lower level of all four elements was found in the cancer...
Article
BMD is commonly obtained with DXA, but this is confounded by the length and composition of tissues that the X-ray must traverse. Subpixel enhancement of nonuniform tissue (SPENT) is a novel MRI technique that can provide (direction specific) information based on the subvoxel structural uniformity of a sample. We hypothesized that the SPENT signal w...
Article
There is a growing interest being shown in the changes occurring in elemental distribution at the bone-cartilage interface, the changes either being a result of mechanical damage or disease. In particular, such investigations have tended to concern the elemental alterations associated with the osteoarthritic wear and tear damage occurring to the ca...
Article
Trace elements are involved in many key pathways involving cell cycle control. The levels of trace metals such as iron, copper, and zinc in colorectal liver metastases have not previously been assessed. The trace element content in snap-frozen cancerous liver tissue from patients who underwent liver resection for colorectal liver metastases was com...
Article
A micro beam synchrotron x-ray fluorescence (muSRXRF) technique has been used to determine the localization of metals in primary invasive ductal carcinoma of breast. Nine samples were examined, all of which were formalin fixed tissues arranged as micro arrays of 1.0 mm diameter and 10 microm thickness. Cu was the particular interest in this study a...
Article
This topical review is intended to describe the x-ray techniques used for human soft tissue analysis. X-ray techniques have been applied to human soft tissue characterization and interesting results have been presented over the last few decades. The motivation behind such studies is to provide improved patient outcome by using the data obtained to...
Article
The levels of iron (Fe), copper (Cu), zinc (Zn) and potassium (K) have been measured in normal and malignant liver and kidney tissue using X-ray fluorescence. Zn was reduced in liver and kidney tumours by 63% and 26%, respectively. Fe, Cu and K were increased in kidney tumours by 150%, 8% and 90%, and reduced in liver tumours by 76%, 29% and 43%. A...
Article
A microbeam synchrotron x-ray fluorescence (µ-SXRF) technique has been employed in investigating the localisation of metals in two biological systems, soft and calcified tissue. Breast carcinoma is the focus of the former investigations, and osteoarthritis, that of the latter. Copper has been the metal of particular interest in breast tissue work,...
Article
This study utilized two radiation scatter interactions in order to differentiate malignant from non-malignant breast tissue. These two interactions were Compton scatter, used to measure the electron density of the tissues, and coherent scatter to obtain a measure of structure. Measurements of these parameters were made using a laboratory experiment...
Article
Trace elements have critical roles in cancer biology. The quantity and distribution of the elements Cl, Ca, K, P, S, Ti, Fe, Cu and Zn in samples of primary breast cancer have been assessed. The samples were formalin fixed tissue specimens formatted as microarrays of cores 1.0 mm diameter and 10 microm thick each. The data were obtained using a syn...
Article
Full-text available
Hydrophilic copolymers which consist of a combination of hydrophobic monomers (methyl methacrylate, MMA) and hydrophilic monomers (vinyl pyrolidone, VP) have all the required major elements such as hydrogen, carbon, nitrogen and oxygen, found in tissues. They have the potential to be used as breast phantom materials since they can be made to have s...
Article
This study describes a technique for measuring the electron density of breast tissue utilizing Compton scattered photons. The Kalpha2 line from a tungsten target industrial x-ray tube (57.97 keV) was used and the scattered x-rays collected at an angle of 30 degrees . At this angle the Compton and coherent photon peaks can be resolved using an energ...
Article
The concentrations of K, Fe, Cu and Zn were measured in 77 breast tissue samples (38 classified as normal and 39 classified as diseased) using x-ray fluorescence (XRF) techniques. The coherent scattering profiles were also measured using energy-dispersive x-ray diffraction (EDXRD), from which the proportions of adipose and fibrous tissue in the sam...
Article
This paper presents improvements on a previously reported method for the measurement of elements in breast tissue specimens (Geraki et al 2002 Phys. Med. Biol. 47 2327-39). A synchrotron-based system was used for the detection of the x-ray fluorescence (XRF) emitted from iron, copper, zinc and potassium in breast tissue specimens, healthy and cance...
Article
Full-text available
A synchrotron X-ray fluorescence system was employed to quantify the levels of iron, copper, zinc and potassium in 80 healthy and cancerous breast tissue samples. The statistical analysis of the sample concentrations reveals a trend of elevated levels in the cancerous tissue. The elevation is most pronounced for potassium and least for iron.
Article
An x-ray fluorescence system with a synchrotron radiation source was used to quantify the levels of iron, copper and zinc in breast tissue specimens. Healthy tissue and breast carcinomas were investigated as an aid to understanding the mechanisms of breast cancer and as a possible complementary diagnostic tool. Eighty samples were measured in total...
Article
X-ray fluorescence analysis was used to determine the concentrations of iron, copper and zinc in skin phantoms. The system used consisted of a high-output tungsten target x-ray tube and a germanium secondary target, the fluorescence from which was used to excite the elements in the sample. Calibration models were constructed in order to allow quant...
Article
Within the context of developing techniques to aid the diagnosis of breast cancer, the elemental composition of healthy and pathological breast tissue was investigated. In this study the identification of the trace elements present in breast tissue was accomplished using the detection of X-ray fluorescence (XRF) emitted from the elements when irrad...
Article
X-ray fluorescence, using Cu K alpha and K beta radiation, has been used to measure the Fe content of skin of two groups of rats, one Fe overloaded and one control group. These skin Fe levels were compared to the liver and heart Fe levels measured using colorimetry. Correlation coefficients of 0.86 and 0.88 respectively were found indicating that s...
Article
In the clinical environment, the most common method of assessing bone mineral density (BMD) loss is dual energy X-ray absorptiometry (DEXA), which relies on the transmission of X-ray photons through the volume of interest. Energy dispersive X-ray diffraction (EDXRD), which utilises coherent X-ray scattering, potentially is a more accurate method. A...
Chapter
This chapter focuses on various x-ray techniques that can be applied to the examination of archaeological bones. A brief explanation of the anatomy and physiology of bone is given and the basic radiation physics that is needed to understand the technique described is outlined. The study of BMD has also been important for archaeozoology and a range...
Article
Full-text available
A system based on the detection of K-shell x-ray fluorescence (XRF) has been used to investigate whether a correlation exists between the concentration of iron in the skin and the concentration of iron in the liver, as the degree of iron loading increases. The motivation behind this work is to develop a non-invasive method of determining the extent...
Article
We are seeking to extend the capabilities of an in vivo XRF system which was originally designed for the exclusive detection of Fe in skin. Our interest concerns development of a more versatile in vivo XRF diagnostic facility for measurement of Fe and Zn. Elevations of these two elements have been noted to occur in a number of skin disorders and ai...
Article
Elastic scattering of x-ray photons can provide information in a number of areas of tissue analysis in medicine. This paper describes measurements made of two types of tissue to demonstrate three different areas of application:•Data are presented on the differential linear coherent scattering coefficients for healthy and diseased breast tissue with...
Article
X-ray fluorescence (XRF) is rapidly becoming established as a powerful tool in the in vivo study of body composition. One particular area of interest concerns occupational health and the monitoring of heavy metal exposure. Another concerns monitoring of the efficacy of chelation of Fe in those suffering from the hereditary blood disorder β-thalassa...
Article
X-ray fluorescence (XRF) is rapidly becoming established as a powerful tool in the in vivo study of body composition. One particular area of interest concerns occupational health and the monitoring of heavy metal exposure. Another concerns monitoring of the efficacy of chelation of Fe in those suffering from the hereditary blood disorder β-thalassa...
Article
An x-ray fluorescence (XRF) system designed for monitoring of skin Fe concentrations has been performance tested for use on patients treated for beta-thalassaemia. The essentials of the system are: a collimated x-ray tube operated at 20 kV and 20 mA; energy selection of the x-ray beam by means of a Cu K-edge filter; use of skin phantoms containing...
Article
Crosslinked hydrophilic copolymers have the potential to be used as breast phantom materials because they can be made to have similar elemental composition to that of body soft tissues. The copolymer, which consists of a combination of hydrophobic monomers (methyl methacrylate [MMA]) and hydrophilic monomers (vinylpyrolidone [VP]), have all the req...
Article
A measurement of trabecular bone density is conducted utilizing energy dispersive X-ray diffraction method. The results obtained are compared to the computed tomography scans. A correlation coefficient was computed to be 0.95 significant at the 0.1% level.
Article
Energy dispersive x-ray diffraction (EDXRD) has been developed as a tool for the detection of explosives in passenger baggage. The measured spectra result from the combined diffraction from each of the materials within a scattering volume. Multivariate regression was used to identify known components within very noisy data, permitting the rapid det...
Article
Phantoms have been constructed to simulate trabecular bone mineral loss and cortical bone thinning which consist of a mixture of hydroxylapatite powder and animal fat in various quantities, surrounded by a varying thickness of dural sleeve. Energy dispersive X-ray diffraction (EDXRD) spectra have been recorded, and multivariate calibration has been...
Article
Measurement of trabecular bone mineral density might play an important role in the determination of levels of osteoporosis in a sample population of archaeological bones. Low angle X-ray scattering (LAXS) is a technique that can be configured to measure trabecular bone density only. LAXS measurements were made on 30 femora and 25 fourth lumbar vert...
Article
The use of multivariate calibration for the real time analysis of energy dispersive x-ray scatter profiles is being investigated. The requirements of a practical baggage scanner necessitate rapid interrogation and an analysis procedure is required that can differentiate between spectral structure in diffraction profiles in very noisy data. Multivar...
Article
The object of the study was to measure the linear attenuation coefficients of hydrophilic materials with the aim of investigating their suitability as tissue equivalent materials. Hydrophilic materials are used in the ophthalmic industry for the manufacture of soft contact lenses. Hydrophilic materials have the trade name "Biogel" and are commonly...
Article
Rapid, quantative assessment of x-radiation source intensity distributions would be useful in several areas of radiation physics. A simple x-ray sensitive CCD based camera for the measurement of focal spot and radiation beam intensity profiles has been constructed. Focal spot images recorded with the CCD camera and radiographic emulsion are compare...