Zewu Chen

The pathology of superficial siderosis of the central nervous system.

Chronic or intermittent extravasations of blood into the subarachnoid space, and dissemination of heme by circulating cerebrospinal fluid, are the only established causes of superficial siderosis of the central nervous system (CNS). We studied the autopsy tissues of nine patients by iron histochemistry, immunocytochemistry, single- and double-label immunofluorescence, electron microscopy of ferritin, and high-definition X-ray fluorescence. In one case, frozen brain tissue was available for quantitative assay of total iron and ferritin. Siderotic tissues showed extensive deposits of iron and ferritin, and infiltration of the cerebellar cortex was especially severe. In addition to perivascular collections of hemosiderin-laden macrophages, affected tissues displayed iron-positive anuclear foamy structures in the neuropil that resembled axonal spheroids. They were especially abundant in eighth cranial nerves and spinal cord. Double-label immunofluorescence of the foamy structures showed co-localization of neurofilament protein and ferritin but comparable merged images of myelin-basic protein and ferritin, and ultrastructural visualization of ferritin, did not allow the conclusion that axonopathy was simply due to dilatation and rupture of fibers. Heme-oxygenase-1 (HO-1) immunoreactivity persisted in macrophages of siderotic cerebellar folia. Siderosis caused a large increase in total CNS iron but high-definition X-ray fluorescence of embedded tissue blocks excluded the accumulation of other metals. Holoferritin levels greatly exceeded the degree of iron accumulation. The susceptibility of the cerebellar cortex is likely due to Bergmann glia that serve as conduits for heme; and the abundance of microglia. Both cell types biosynthesize HO-1 and ferritin in response to heme. The eighth cranial nerves are susceptible because they consist of CNS axons, myelin, and neuroglial tissue along their subarachnoid course. The persistence of HO-1 protein implies continuous exposure of CNS to free heme or an excessively sensitive transcriptional response of the HO-1 gene. The conversion of heme iron to hemosiderin probably involves both translational and transcriptional activation of ferritin biosynthesis.

Doubly curved crystal (DCC) X-ray optics and applications

Doubly curved crystal (DCC) X-ray optics provide an enabling technology for new portable, remote, and in situ applications of monochromatic X-rays for composition and structure analysis of amorphous, polycrystalline, and crystalline solids. Femtogram sensitivity for surface contamination, parts-per-billion (ppb) impurity levels for solids, and composition, structure and uniformity of thin films with compact, low power (20–50 W) source optic combinations are possible.

Measurement of the microdistribution of strontium and lead in bone via benchtop monochromatic microbeam X-ray fluorescence with a low power source

Determination of the microdistribution of trace elements in bone at low concentrations has previously been performed with proton induced X-ray emission (PIXE), high-energy synchrotron source X-ray fluorescence (XRF) and laser ablation - inductively coupled plasma mass spectrometry (LA-ICP-MS). Several commercial benchtop XRF systems with micrometer-scale resolution are currently available. While providing convenient, non-destructive mapping capability, they appear to lack the sensitivity required for detection of trace elements in biological tissues such as bone. We investigated the application of a prototype benchtop XRF system for the measurement of strontium and lead at physiological levels in bone. Detection of several elements of interest, including Sr and Pb was achieved with an experimental set up based on focused monochromatic microbeam X-ray fluorescence (Mµ-XRF) instrumentation with a low power source (45 W molybdenum tube) coupled to doubly curved crystal (DCC) optics. A cross-section of bone about 5 mm × 8 mm size was mapped with 80-µm resolution showing heterogeneous distribution of Sr and Pb. The data showed that Mµ-XRF coupled to DCC is powerful method for measurement of the spatial distribution of trace elements in bone.

Evaluation of portable XRF instrumentation for assessing potential environmental exposure to toxic elements

ABSTRACT Portable instruments based on X-Ray Fluorescence Spectrometry (XRF) have the potential to assist in field-based studies, provided that the data produced are reliable. In this study, we evaluate the performance of two different types of XRF instrument (XOS prototype and Thermo Niton XL3t). These two XRF analysers were evaluated in a laboratory setting, and data were reported for 17 elements (As, Ba, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Se, Sn, Sr, Ti, V, and Zn). Samples analysed (n = 38) included ethnic herbal medicine products (HMPs), ethnic spices (ES), and cosmetic products (CPs). Comparison analyses were carried out using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). In general, results reported for Cd, Cu, and Pb by the XOS prototype analyser, using the non-metal mode, were negatively biased (5–95%) as compared to ICP-OES. In contrast, results reported for Pb, As, Cd, Cu and Zn by the Niton, using the soil mode, were positively biased, in some instances (Cd) by up to four orders of magnitude. While the sensitivity of both instruments was insufficient for reliably ‘quantifying’ toxic elements below 15 mg/kg, XRF was still capable of positively ‘detecting’ many elements at the low single-digit mg/kg levels. For semi-quantification estimates of contaminants at higher levels, and with limited sample preparation, both XRF instruments were deemed fit for the purpose. This study demonstrates that modern XRF instrumentation is valuable for characterising the elemental content of food, cosmetic, and medicinal products. The technology is particularly useful for rapidly screening large numbers of products (100’s per day) in the field, and quickly identifying those that may contain potentially hazardous levels of toxic elements. Toxic elements can be confirmed by examining the raw spectrum, and the limitations of factory-based calibration are generally manageable for field-based studies.

Evaluation of a Prototype Point-of-care Instrument Based on Monochromatic X-Ray Fluorescence Spectrometry: Potential for Monitoring Trace Element Status of Subjects with Neurodegenerative Disease

Assessment of trace elements such as Cu, Zn, and Se in patients with neurodegenerative disease, such as Alzheimers (AD) and Parkinsons disease (PD), may be useful in etiologic studies and in assessing the risk of developing these conditions. A prototype point-of-care (POC) instrument based on monochromatic x-ray fluorescence (M-XRF) was assembled and evaluated for the determination of Cu, Zn, and Se in whole blood, plasma, and urine. The prototype instrument was validated using certified reference materials for Cu and Zn in serum/plasma, and the reported bias and relative imprecision were <10%. The M-XRF prototype performance was further assessed using human specimens collected from AD and PD subjects, and was found to be satisfactory (<20% bias) for monitoring Cu and Zn levels in plasma and whole blood. However, the prototype M-XRF sensitivity was not sufficient for quantifying Cu, Zn, or Se in urine. Nonetheless, while validating the prototype instrument, body fluids (whole blood, plasma, and urine) were collected from 19 AD patients, 23 PD patients, and 24 controls specifically for trace element analysis using well-validated methods based on inductively coupled plasma mass spectrometry (ICP-MS). This limited biomonitoring study provided robust data for up to 16 elements including Sb, As, Ba, Cd, Cs, Co, Cr, Cu, Hg, Pb, Mo, Se, Tl, Sn, Zn, and U in plasma, whole blood, and urine. The results did not indicate any significant differences in most trace elements studied between AD or PD patients compared to controls, although the sample size is limited. A statistically significant increase in plasma Se was identified for PD patients relative to AD patients, but this could be due to age differences.

High-Definition X-Ray Fluorescence: Applications

Energy dispersive X-ray fluorescence (EDXRF) is a well-established and powerful tool for nondestructive elemental analysis of virtually any material. It is widely used for environmental, industrial, pharmaceutical, forensic, and scientific research applications to measure the concentration of elemental constituents or contaminants. The fluorescing atoms can be excited by energetic electrons, ions, or photons. A particular EDXRF method, monochromatic microbeam X-ray fluorescence (M μ EDXRF), has proven to be remarkably powerful in measurement of trace element concentrations and distributions in a large variety of important medical, environmental, and industrial applications. When used with state-of-the-art doubly curved crystal (DCC) X-ray optics, this technique enables high-sensitivity, compact, low-power, safe, reliable, and rugged analyzers for insitu, online measurements in industrial process, clinical, and field settings. This new optic-enabled M μ EDXRF technique is known as high-definition X-Ray fluorescence (HD XRF). Selected applications of HD XRF are described in this paper including air particulate analysis, analysis of body fluid contamination at ppb levels, elemental mapping of brain tissue and bone samples, as well as analysis of toxins in toys and other consumer products.