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Biomedical subjects

G Margaritondo

Publications and source records attributed to G Margaritondo.

At least 19 recordsLinked to original sources

Phase contrast radiography of Lewy bodies in Parkinson disease.

Parkinson's disease (PD), defined as a neurodegenerative disorder, is characterized by the loss of dopaminergic neurons and the presence of Lewy bodies in neurons. Morphological study of Lewy bodies is important to identify the causes and the processes of PD. Here, we investigate a possibility of phase contrast radiography using coherent synchrotron X-rays to explore the microscopic details of Lewy bodies in thick (approximately 3 mm) midbrain tissues. Autopsied midbrain tissues of a PD patient were sliced in 3 mm thickness and then examined using synchrotron X-rays from the 7B2 beamline of the Pohang Light Source. Refraction-enhanced phase contrast radiography and microtomography were adopted to identify dark core and dim edge of Lewy bodies in neurons. The morphology of Lewy bodies was clearly revealed by the phase contrast radiography in very thick (3 mm) midbrain tissues without any staining treatment. Three-dimensional volume rendered microtomography of the autopsied midbrain tissues demonstrates striking evidence that several Lewy bodies are agglomerated by dim edges in a neuron. We suggest that the phase contrast radiography could be a useful tool to morphologically investigate the causes or the processes in PD.

Dopamine↗

Imaging cells and tissues with refractive index radiology.

Can individual cells, including live cells, be imaged using hard x rays? Common wisdom until now required sophisticated staining techniques for this task. We show instead that individual cells and cell details can be detected in culture solution and tissues with no staining and no other contrast-enhancing preparation. The sample examined can be much thicker than for many other microscopy techniques without sacrificing the capability to resolve cells. The key factor in our approach is the use of a coherent synchrotron source and of contrast mechanisms based on the refractive index. The first successful tests were conducted on a variety of cell systems including skin and internal leaf cells, mouse neurons, rabbit fibroblast cells, and human tumor cells.

Animals↗

Manifestation of the magnetic resonance mode in the nodal quasiparticle lifetime of the superconducting cuprates.

Studying the nodal quasiparticles in superconducting cuprates by photoemission with highly improved momentum resolution, we show that a new "kink" feature in the scattering rate is a key to uncover the nature of electron correlations in these compounds. Our data provide evidence that the main doping independent contribution to the scattering can be well understood in terms of the conventional Fermi liquid model, while the additional doping dependent contribution has a magnetic origin. This sheds doubt on applicability of a phonon-mediated pairing mechanism to high-temperature superconductors.

Journal Article↗

Synchrotron microangiography with no contrast agent.

Coherent x-rays from synchrotron sources are increasingly used in non-conventional radiological techniques ('phase-contrast' radiology). Our experiments demonstrate that by using white (unmonochromatic) radiation and a time-resolving system, it is possible to image microscopic details of moving blood vessels in different live animals without using any contrast agent. The images have excellent contrast plus unprecedented spatial resolution for microangiography (< 10 microm). This result is likely to impact many different areas of biological and medical research and of diagnostic radiology.

Angiography↗

Synchrotron radiation in radiology: novel X-ray sources.

X-rays, the key ingredient of radiology, are still primarily produced with the mechanism discovered by Röntgen over one century ago. A different approach, however, is becoming increasingly important: the use of synchrotron sources based on fast-moving electrons and on their relativistic properties. We discuss the elements of this new strategy, its practical implementation, and some new types of synchrotron sources under development. The present and potential impact on radiology of different classes of synchrotron sources is briefly and realistically analyzed.

Humans↗

Strain and high temperature superconductivity: unexpected results from direct electronic structure measurements in thin films.

Angle-resolved photoemission spectroscopy reveals very surprising strain-induced effects on the electronic band dispersion of epitaxial La(2-x)Sr(x)CuO(4-delta) thin films. In strained films we measure a band that crosses the Fermi level (E(F)) well before the Brillouin zone boundary. This is in contrast to the flat band reported in unstrained single crystals and in our unstrained films, as well as in contrast to the band flattening predicted by band structure calculations for in-plane compressive strain. In spite of the density of states reduction near E(F), the critical temperature increases in strained films with respect to unstrained samples. These results require a radical departure from commonly accepted notions about strain effects on high temperature superconductors, with possible general repercussions on superconductivity theory.

Journal Article↗

Electrochemistry: building on bubbles in metal electrodeposition.

In the electrodeposition of metals, a widely used industrial technique, bubbles of gas generated near the cathode can adversely affect the quality of the metal coating. Here we use phase-contrast radiology with synchrotron radiation to witness directly and in real time the accumulation of zinc on hydrogen bubbles. This process explains the origin of the bubble-shaped defects that are common in electrodeposited coatings.

Journal Article↗

Spectroscopic indications of polaronic carriers in the quasi-one-dimensional conductor (TaSe4)2I.

Angle-resolved photoemission (ARPES) on the quasi-one-dimensional conductor (TaSe4)2I shows a hidden Fermi-surface crossing in its metallic state and the opening of a Peierls gap at low temperatures. The underlying quasiparticles have vanishing spectral weight and extremely short coherence lengths. They are interpreted as polarons in the strong-coupling adiabatic limit, and almost all their ARPES weight is incoherent. These observations suggest a scenario where the long-standing contradictions between ARPES and other experiments on Peierls materials could be resolved.

Journal Article↗

Spectroscopic scanning near-field optical microscopy with a free electron laser: CH2 bond imaging in diamond films.

Hydrogen chemistry in thin films and biological systems is one of the most difficult experimental problems in today's science and technology. We successfully tested a novel solution, based on the spectroscopic version of scanning near-field optical microscopy (SNOM). The tunable infrared radiation of the Vanderbilt free electron laser enabled us to reveal clearly hydrogen-decorated grain boundaries on nominally hydrogen-free diamond films. The images were obtained by SNOM detection of reflected 3.5 microm photons, corresponding to the C-H stretch absorption, and reached a lateral resolution of 0.2 microm, well below the lambda/2 (lambda = wavelength) limit of classical microscopy.

Journal Article↗

Electronic structure of solids with competing periodic potentials.

When electrons are subject to a potential with two incommensurate periods, translational invariance is lost, and no periodic band structure is expected. However, model calculations based on nearly free one-dimensional electrons and experimental results from high-resolution photoemission spectroscopy on a quasi-one-dimensional material do show dispersing band states with signatures of both periodicities. Apparent band structures are generated by the nonuniform distribution of electronic spectral weight over the complex eigenvalue spectrum.

Journal Article↗

UV-ozone ashing of cells and tissues for spatially resolved trace element analysis.

UV/ozone ashing of thin tissue sections and cell cultures is a simple technique to enhance relative elemental concentrations, while maintaining their spatial location at the sub-micron level. This approach may enhance the capability of spatially resolved analysis techniques to detect the distribution of trace elements in biological matrices. We present results from light microscopy and x-ray spectromicroscopy studies of tissues and cells demonstrating that the micro-structure is very well conserved. We show the signal enhancement resulting from the removal of carbon, which allows otherwise undetectable gadolinium to be mapped in cancer tissue for a novel neutron capture therapy.

Carbon↗

Charging phenomena in PEEM imaging and spectroscopy.

Spectromicroscopy with the imaging technique of X-ray photoelectron emission microscopy (X-PEEM) is a microchemical analytical tool installed in many synchrotron radiation laboratories, and which is finding application in diverse fields of research. The method of sample analysis, X-ray absorption spectroscopy, does not encounter the same problems as X-ray photoemission spectroscopy when sample charging occurs, hence even good insulators may often be analyzed without any apparent artifacts in images or spectra. We show, however, that charging effects cannot be neglected. We model the effect of surface charge formation on the secondary electron yield from uniform samples to demonstrate that surface charge primarily reduces the yield of electrons which may contribute to the detected signal. We illustrate that on non-uniform insulating samples, localized centers of charge may substantially affect microscope imaging and resolution as the electrostatic field close to the surface is distorted. Finally, in certain circumstances non-uniform surface charge may lead to unexpected lineshapes in X-ray absorption spectra causing, in some extreme cases, negative spectra. These negative spectra are explained, and several strategies are reviewed to minimize the impact of sample charging when analyzing poorly conducting samples of any nature.

Artifacts↗

Spectromicroscopy of boron in human glioblastomas following administration of Na2B12H11SH.

Boron neutron capture therapy (BNCT) is an experimental, binary treatment for brain cancer which requires as the first step that tumor tissue is targeted with a boron-10 containing compound. Subsequent exposure to a thermal neutron flux results in destructive, short range nuclear reaction within 10 microm of the boron compound. The success of the therapy requires than the BNCT agents be well localized in tumor, rather than healthy tissue. The MEPHISTO spectromicroscope, which performs microchemical analysis by x-ray absorption near edge structure (XANES) spectroscopy from microscopic areas, has been used to study the distribution of trace quantities of boron in human brain cancer tissues surgically removed from patients first administered with the compound Na2B12H11SH (BSH). The interpretation of XANES spectra is complicated by interference from physiologically present sulfur and phosphorus, which contribute structure in the same energy range as boron. We addressed this problem with the present extensive set of spectra from S, B, and P in relevant compounds. We demonstrate that a linear combination of sulfate, phosphate and BSH XANES can be used to reproduce the spectra acquired on boron-treated human brain tumor tissues. We analyzed human glioblastoma tissue from two patients administered and one not administered with BSH. As well as weak signals attributed to BSH, x-ray absorption spectra acquired from tissue samples detected boron in a reduced chemical state with respect to boron in BSH. This chemical state was characterized by a sharp absorption peak at 188.3 eV. Complementary studies on BSH reference samples were not able to reproduce this chemical state of boron, indicating that it is not an artifact produced during sample preparation or x-ray exposure. These data demonstrate that the chemical state of BSH may be altered by in vivo metabolism.

Borohydrides↗

Cell ashing for trace element analysis: A new approach based on ultraviolet/ozone.

We studied a new approach to cell ashing based on illuminating the specimens with a low-pressure mercury discharge lamp. We analyzed with synchrotron spectromicroscopy its effects on different physiological elements in neurobiological specimens. Our results demonstrate that carbon is removed, whereas phosphorus, calcium, potassium, and sulfur are retained and their relative concentrations are enhanced. Applied to trace elements, this technique will enhance their practical detectability.

Animals↗

High sensitivity quantitative analysis of cobalt uptake in rat cerebellar granule cells with and without excitatory amino acids.

We quantified the effect of the excitatory amino acids kainate and glutamate on the uptake of cobalt in primary rat cerebellar granule neurons, by using inductively coupled plasma-atomic emission spectroscopy (ICP-AES). We quantitatively demonstrated that Co2+ uptake, although enhanced by glutamate and kainate also takes place in the absence of excitatory amino acids. We also found that cobalt uptake is not significantly altered by the presence of glutamate receptor competitive or noncompetitive antagonists, indicating that cobalt uptake in granule neurons does not require glutamate receptor stimulation. Our results suggest, therefore, that Co2+ may enter the cell by passive diffusion through the plasma membrane.

Animals↗

The effect of ashing on cells: spectromicroscopy of physiological elements.

We analyzed the effects of cold oxygen plasma ashing of neurobiological specimens on different elements with synchrotron spectromicroscopy. Our results demonstrate that while carbon is almost completely removed, phosphorus, calcium, potassium, sulfur, and, to some extent, nitrogen are retained and their relative concentration is enhanced.

Animals↗