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PubMed2004

Cure of Fisher rats bearing radioresistant F98 glioma treated with cis-platinum and irradiated with monochromatic synchrotron X-rays.

High-grade gliomas are usually of poor prognosis, and conventional radiotherapy, even combined with chemotherapy, still fails to improve the survival of patients. Here, we propose an innovative therapeutic approach combining synchrotron radiation with cis-diamminedichloroplatinum (II) (CDDP). As suggested previously, monochromatic synchrotron irradiation of CDDP at 78.8 keV, just above the 78.4 keV platinum absorption K-edge, leads to an enhanced photoelectric effect and an increased local toxicity. To select a particular radiation energy that could provide supra-additive effect, we used pulsed-field gel electrophoresis to assess yields of DNA double-strand breaks induced in rat F98 glioma cells after CDDP treatment combined with synchrotron X-rays. Thereafter, intracerebral CDDP injection combined with synchrotron X-rays was applied to Fisher rats bearing F98 glioma. CDDP concentrations were mapped by synchrotron X-ray microfluorescence. An extra number of more slowly repaired double strand breaks were observed when irradiating CDDP-treated F98 cells at 78.8 keV. In vivo treatments were then performed with different radiation doses and CDDP concentrations. All cell inoculations in rat brain resulted in tumor development, and tumor presence was controlled by computed tomography. Among all of the conditions tested, the combination of 3 micro g of CDDP with 15 Gy resulted in the largest median survival time (206 days). After 1 year, about 34% of treated rats were still alive. This preclinical finding, validated by molecular analysis, represents the most protracted survival reported with this radioresistant glioma model and demonstrates the interest in powerful monochromatic X-ray sources as new tools for cancer treatments.

Animals↗

PubMed1996

Intravenous coronary angiography with dichromography using synchrotron radiation.

Dichromography represents a digital subtraction angiography mode based on energy substraction which allows imaging of fast moving subjects like the heart. For logarithmic subtraction 2 images with X-rays just below and above the iodine K-edge (33.17 keV) are simultaneously obtained in a line scan mode. Monochromatic X-rays of sufficient intensity to visualize coronary arteries of 1 mm diameter with extremely low iodine concentrations (1 mg/cm2) after venous injection is only provided by synchrotron radiation. The system NIKOS (non-invasive coronary arteriography with synchrotron radiation) at the Deutsches Elektronen Synchrotron (DESY) consists of 6 components: a wiggler, a monochromator, a safety system, a scanning device, a detector and a computer system. After experimental studies in dogs patients are imaged since 1990. Initial results demonstrate feasibility and safety of synchrotron radiation coronary angiography. Large scale studies are designed to further evaluate sensitivity and specificity. When compact synchrotron radiation sources become available, this technique could be used for follow-up studies and for evaluation of certain high coronary risk populations.

Angiography, Digital Subtraction↗

PubMed1991

Synchrotron-produced ultrasoft X-rays: a tool for testing biophysical models of radiation action.

Ultrasoft X-rays are useful for mechanistic studies of ionizing radiation damage in living cells due to the localized nature of their energy depositions. To date radiobiology experiments in this energy region have relied on characteristic X-rays (mainly Alk and Ck) from X-ray tubes. However, limitations in the photon intensity and the available energies from X-ray tube sources prevent a definitive characterization of the relationship between photon energy and biological damage. Synchrotron radiation has the potential to avoid these limitations, since it produces X-rays with high intensity over a continuous spectrum. We have established a synchrotron-based system for radiation biology studies using the ES-0 exposure station of the Center for X-ray Lithography at the University of Wisconsin Synchrotron Radiation Center storage ring, Aladdin. A characterization of the system including spectral and intensity properties of the photon beam is presented. The first mammalian cell survival curve for synchrotron-produced ultrasoft X-rays was generated and is presented. Cell survival curves of C3H/10T 1/2 cells using synchrotron radiation of 1.48 keV agree with previous data using Alk X-rays (1.49 keV). An RBE of 1.47 +/- 0.30 at the 10% survival level was measured with reference to 250 kVp X-rays.

Animals↗

PubMed1998

Application of synchrotron radiation to ultrafast spectroscopy.

A novel application of synchrotron radiation to ultrafast optical spectroscopy is demonstrated. The application is based on the short coherence time of broadband synchrotron radiation and employs a conventional interferometer. From a detailed study of the coherence of synchrotron radiation, it is shown that the coherent interference between two synchrotron radiation beams, split from a single beam, can provide ultimate time resolution down to a few femtoseconds. Experimental results of ultrafast spectroscopy using broadband synchrotron radiation are presented; these include free-induction decay and photon echoes in the visible and ultraviolet regions.

Journal Article↗

PubMed1998

Medical applications with synchrotron radiation in Japan.

In Japan, various medical applications of synchrotron X-ray imaging, such as angiography, monochromatic X-ray computed tomography (CT), radiography and radiation therapy, are being developed. In particular, coronary arteriography (CAG) is quite an important clinical application of synchrotron radiation. Using a two-dimensional imaging method, the first human intravenous CAG was carried out at KEK in May 1996; however, further improvements of image quality are required in clinical practice. On the other hand, two-dimensional aortographic CAG revealed canine coronary arteries as clearly as those on selective CAG, and coronary arteries less than 0.2 mm in diameter. Among applications of synchrotron radiation to X-ray CT, phase-contrast X-ray CT and fluorescent X-ray CT are expected to be very interesting future applications of synchrotron radiation. For actual clinical applications of synchrotron radiation, a medical beamline and a laboratory are now being constructed at SPring-8 in Harima.

Journal Article↗

PubMed2004

Thermal residual stresses near the interface between plasma-sprayed hydroxyapatite coating and titanium substrate: finite element analysis and synchrotron radiation measurements.

Plasma-sprayed hydroxyapatite (HA) coatings on titanium alloy are often used in prosthetic implants. The metallic substrate gives the implant good mechanical strength which is combined with good biocompatibility and osteointegration of the ceramic coating. However, the interface between the HA coating and titanium alloy substrate is an area of critical weakness when compared with the interlamellar cohesive strength of the HA coating structure. Knowledge of the stresses in materials near the interface seems to be an important step in understanding why failure occurs. Synchrotron radiation, using Beamline BM16 at the European Synchrotron Radiation Facility (Grenoble, France), has been used to determine local stresses near the interface, down to 10 microm in resolution, between a plasma-sprayed HA coating and a titanium alloy substrate. This experimental determination of residual stresses is compared with the results found by a finite element analysis modeling the thermal effects of the plasma-spraying process. Residual stresses have been found in deposited ceramic near the interface due to a thermal properties mismatch of the materials. If the plane stress state is assumed, meaning the perpendicular component of residual stress is ignored (sigma(z) = 0), then the synchrotron residual stress measurements should be interpreted as mainly compressive in the ceramic coating. This is in contradiction with the coefficient of thermal expansion mismatch; therefore, the simplified plane stresses assumption seems to be inappropriate for the deposited morphology characterized by pores and a network of microcracks. The detailed finite element analysis model, taking into account the real morphology of the coating and the real three-dimensional stress field distribution, allowed the estimation of sigma(z), leading to a more accurate interpretation of synchrotron measurements, which is validated by the experimental results.

Algorithms↗

PubMed1997

Time-resolved synchrotron X-ray "footprinting", a new approach to the study of nucleic acid structure and function: application to protein-DNA interactions and RNA folding.

Hydroxyl radicals (.OH) can cleave the phosphodiester backbone of nucleic acids and are valuable reagents in the study of nucleic acid structure and protein-nucleic acid interactions. Irradiation of solutions by high flux "white light" X-ray beams based on bending magnet beamlines at the National Synchrotron Light Source (NSLS) yields sufficient concentrations of .OH so that quantitative nuclease protection ("footprinting") studies of DNA and RNA can be conducted with a duration of exposure in the range of 50 to 100 ms. The sensitivity of DNA and RNA to X-ray mediated .OH cleavage is equivalent. Both nucleic acids are completely protected from synchrotron X-ray induced cleavage by the presence of thiourea in the sample solution, demonstrating that cleavage is suppressed by a free radical scavenger. The utility of this time-dependent approach to footprinting is demonstrated with a synchrotron X-ray footprint of a protein-DNA complex and by a time-resolved footprinting analysis of the Mg(2+)-dependent folding of the Tetrahymena thermophilia L-21 ScaI ribozyme RNA. Equilibrium titrations reveal differences among the ribozyme domains in the cooperativity of Mg(2+)-dependent .OH protection. RNA .OH protection progress curves were obtained for several regions of the ribozyme over timescales of 30 seconds to several minutes. Progress curves ranging from > or = 3.5 to 0.4 min-1 were obtained for the P4-P6 and P5 sub-domains and the P3-P7 domain, respectively. The .OH protection progress curves have been correlated with the available biochemical, structural and modeling data to generate a model of the ribozyme folding pathway. Rate differences observed for specific regions within domains provide evidence for steps in the folding pathway not previously observed. Synchrotron X-ray footprinting is a new approach of general applicability for the study of time-resolved structural changes of nucleic acid conformation and protein-nucleic acid complexes.

Animals↗

PubMed2002

A biologist's guide to synchrotron facilities: the BioSync web resource.

Research at synchrotron radiation facilities, once the domain of high energy physics, now has a major impact on fields as diverse as immunology, neurobiology, physiology, molecular biology, medicine and biotechnology. This article describes the development of a comprehensive synchrotron portal and informational website (http://www.biosync.sdsc.edu) for biologists engaged in research at synchrotrons. The site automatically provides timely and accurate information in a unified format by gathering technical descriptions of synchrotron beamlines using modern information management practices.

Internet↗

PubMed2004

Using synchrotron-based FTIR microspectroscopy to reveal chemical features of feather protein secondary structure: comparison with other feed protein sources.

Studying the secondary structure of proteins leads to an understanding of the components that make up a whole protein. An understanding of the structure of the whole protein is often vital to understanding its digestive behavior in animals and nutritive quality. Usually protein secondary structures include alpha-helix and beta-sheet. The percentages of these two structures in protein secondary structures may influence feed protein quality and digestive behavior. Feathers are widely available as a potential protein supplement. They are very high in protein (84%), but the digestibility of the protein is very low (5%). The objective of this study was to use synchrotron-based Fourier transform infrared (FTIR) microspectroscopy to reveal chemical features of feather protein secondary structure within amide I at ultraspatial resolution (pixel size = 10 x 10 microm), in comparison with other protein sources from easily digested feeds such as barley, oat, and wheat tissue at endosperm regions (without destruction of their inherent structure). This experiment was performed at beamline U2B of the Albert Einstein Center for Synchrotron Biosciences at the National Synchrotron Light Source (NSLS) in Brookhaven National Laboratory (BNL), U.S. Dept of Energy (NSLS-BNL, Upton, NY). The results showed that ultraspatially resolved chemical imaging of feed protein secondary structure in terms of beta-sheet to alpha-helix peak height ratio by stepping in pixel-sized increments was obtained. Using synchrotron FTIR microspectroscopy can distinguish structures of protein amide I among the different feed protein sources. The results show that the secondary structure of feather protein differed from those of other feed protein sources in terms of the line-shape and position of amide I. The feather protein amide I peaked at approximately 1630 cm(-1). However, other feed protein sources showed a peak at approximately 1650 cm(-1). By using multicomponent peak modeling, the relatively quantitative amounts of alpha-helix and beta-sheet in protein secondary structure were obtained, which showed that feather contains 88% beta-sheet and 4% alpha-helix, barley contains 17% beta-sheet and 71% alpha-helix, oat contains 2% beta-sheet and 92% alpha-helix, and wheat contains 42% beta-sheet and 50% alpha-helix. The difference in percentage of protein secondary structure may be part of the reason for different feed protein digestive behaviors. These results demonstrate the potential of highly spatially resolved infrared microspectroscopy to reveal feed protein secondary structure. Information from this study by the infrared probing of feed protein secondary structure may be valuable as a guide for feed breeders to improve and maintain protein quality for animal use.

Amides↗

PubMed2005

Applications of hierarchical cluster analysis (CLA) and principal component analysis (PCA) in feed structure and feed molecular chemistry research, using synchrotron-based Fourier transform infrared (FTIR) microspectroscopy.

Synchrotron technology based Fourier transform infrared microspectroscopy (S-FTIR) is a recently emerging bioanalytical microprobe capable of exploring the molecular chemistry within microstructures of feed tissues at a cellular or subcellular level. To date there has been very little application of hierarchical cluster analysis (CLA) and principal component analysis (PCA) to the study of feed inherent microstructures and feed molecular chemistry between feeds and/or between different structures within a feed, in relation to feed quality and nutrient availability using S-FTIR. In this paper, multivariate statistical methods--CLA and PCA--were used to analyze synchrotron-based FTIR individual spectra obtained from feed inherent microstructures within intact tissues by using the S-FTIR as a novel approach. The S-FTIR spectral data of three feed inherent structures (strucutre 1, feed pericarp; structure 2, feed aleurone; structure 3, feed endosperm) and different varieties of feeds within cellular dimensions were collected at the National Synchrotron Light Source (NSLS) at Brookhaven National Laboratory (BNL), U.S. Department of Energy (NSLS-BNL, New York). Both PCA and CLA methods gave satisfactory analytical results and are conclusive in showing that they can discriminate and classify inherent structures and molecular chemistry between and among the feed tissues. They also can be used to identify whether differences exist between the varieties. These statistical analyses place synchrotron-based FTIR microspectroscopy at the forefront of those new potential techniques that could be used in rapid, nondestructive, and noninvasive screening of feed intrinsic microstructures and feed molecular chemistry in relation to the quality and nutritive value of feeds.

Analysis of Variance↗

PubMed2004

Imaging capabilities of synchrotron infrared microspectroscopy.

It has become increasingly clear that synchrotron infrared micro-spectroscopy is an extremely valuable analysis tool when determining the chemical composition of biological and biomedical samples, at the diffraction-limited spatial resolution. Highly resolved infrared micro-spectroscopy, together with the high signal-to-noise level of the recorded spectra, is essential in generating chemical and statistical (multivariate) images. This is illustrated in the case of individual cell and hair section studies. Unprecedented chemical images of lipid distribution and secondary structure relative concentration have been achieved using the synchrotron source. A comparison with a Focal plane Array imaging system, on the same hair section, shows that, despite the fast imaging processing and improved quality achieved with the focal plane array detectors, spectral quality is markedly superior in the case of the synchrotron source. It is clear that the two approaches could be very complementary if combined on the same sample area, in a synchrotron facility.

Algorithms↗

PubMed2001

Synchrotron protein footprinting: a technique to investigate protein-protein interactions.

Traditional approaches for macromolecular structure elucidation, including NMR, crystallography and cryo-EM have made significant progress in defining the structures of protein-protein complexes. A substantial number of macromolecular structures, however, have not been examined with atomic detail due to sample size and heterogeneity, or resolution limitations of the technique; therefore, the general applicability of each method is greatly reduced. Synchrotron footprinting attempts to bridge the gap in these methods by monitoring changes in accessible surface areas of discrete macromolecular moieties. As evidenced by our previous studies on RNA folding and DNA-protein interactions, the three-dimensional structure is probed by examining the reactions of these moieties with hydroxyl radicals generated by synchrotron X-rays. Here we report the application of synchrotron footprinting to the investigation of protein- protein interactions, as the novel technique has been utilized to successfully map the contact sites of gelsolin segment-1 in the gelsolin segment 1/actin complex. Footprinting results demonstrate that phenylalanine 104, located on the actin binding helix of gelsolin segment 1, is protected from hydroxyl radical modification in the presence of actin. This change in reactivity results from the specific protection of gelsolin segment-1, consistent with the substantial decrease in solvent accessibility of F104 upon actin binding, as calculated from the crystal structural of the gelsolin segment 1/actin complex. The results presented here establish synchrotron footprinting as a broadly applicable method to probe structural features of macromolecular complexes that are not amenable to conventional approaches.

Actins↗

PubMed1998

A microangiographic technique using synchrotron radiation to visualize dermal circulation in vivo.

Conventional angiography cannot resolve dermal small vessels with a diameter of 200 microm or less. In vitro microangiography is currently characterized by better spatial resolution than conventional angiography but does not allow visualization of the blood stream in dermal vessels in vivo. In this study, we introduce a novel synchrotron radiation microangiographic system for visualizing the structure of and blood flow in dermal microvessels in vivo repeatedly. We used monochromatic synchrotron radiation with an energy just above the k-edge of iodine (33.3 keV) as an x-ray and a high-definition television camera system with a high-sensitivity image pick-up tube for detection. The 33.3-keV monochromatic synchrotron radiation allows detection of a small amount of iodine, and the high-definition television camera system can resolve small vessels with high-spatial resolution and no loss of sensitivity. We performed synchrotron radiation angiography of superficial inferior epigastric arteries and their branches in nine rats, and of the caudal artery in 14 rats, and compared angiographic images taken by the current system with those taken by a conventional angiographic system in seven rats. With this new microangiographic technique, we could visualize small dermal vessels with a diameter as low as 50 microm. In addition, repeated angiograms at baseline and under increasing body temperature could be obtained. This new microangiographic approach is expected to be very useful for the assessment of dermal circulation in patients.

Angiography↗

PubMed2002

Synchrotron infrared spectromicroscopy as a novel bioanalytical microprobe for individual living cells: cytotoxicity considerations.

Synchrotron radiation-based Fourier transform infrared spectromicroscopy is a newly emerging analytical tool capable of monitoring the biochemistry within an individual living mammalian cell in real time. This unique technique provides infrared (IR) spectra, hence chemical information, with high signal to noise at spatial resolutions as fine as 3-10 microm. Mid-IR photons are too low in energy (0.05-0.5 eV) to either break bonds or to cause ionization, and the synchrotron IR beam has been shown to produce minimal sample heating. However, an important question remains, "Does the intense synchrotron beam induce any cytotoxic effects in living cells?" In this work, we present the results from a series of standard biological assays to evaluate any short- and/or long-term effects on cells exposed to the synchrotron radiation-based infrared (SR-IR) beam. Cell viability was tested using alcian blue dye exclusion and colony formation assays. Cell-cycle progression was tested with bromodeoxyuridine (BrdU) uptake during DNA synthesis. Cell metabolism was tested using a 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. All control, 5, 10, and 20 min SR-IR exposure tests (267 total and over 1000 controls) show no evidence of cytotoxic effects. Concurrent infrared spectra obtained with each experiment confirm no detectable biochemical changes between control and exposed cells.

Adenosine Triphosphate↗

PubMed2000

Research at the European Synchrotron Radiation Facility medical beamline.

The application of synchrotron radiation in medical research has become a mature field of research at synchrotron facilities worldwide. In the relatively short time that synchrotrons have been available to the scientific community, their characteristic beams of UV and X-ray radiation have been applied to virtually all areas of medical science which use ionizing radiation. The ability to tune intense monochromatic beams over wide energy ranges differentiates these sources from standard clinical and research tools. At the European Synchrotron Radiation Facility (Grenoble, France), a major research facility is operational on an advanced wiggler radiation beamport, ID17. The beamport is designed to carry out a broad range of research ranging from cell radiation biology to in vivo human studies. Medical imaging programs at ID17 include transvenous coronary angiography, computed tomography, mammography and bronchography. In addition, a major research program on microbeam radiation therapy is progressing. This paper will present a very brief overview of the beamline and the imaging and therapy programs.

Animals↗

PubMed2000

In vivo K-edge imaging with synchrotron radiation.

We present in this paper two imaging techniques using contrast agents assessed with in vivo experiments. Both methods are based on the same physical principle, and were implemented at the European Synchrotron Radiation Facility medical beamline. The first one is intravenous coronary angiography using synchrotron radiation X-rays. This imaging technique has been planned for human studies in the near future. We describe the first experiments that were carried out with pigs at the ESRF. The second imaging mode is computed tomography using synchrotron radiation on rats bearing brain tumors. Owing to synchrotron radiation physical properties, these new imaging methods provide additional information compared to conventional techniques. After infusion of the contrast agent, it is possible to derive from the images the concentration of the contrast agent in the tumor area for the computed tomography and in any visible vessel for the angiography method.

Animals↗

PubMed1992

[Synchrotron radiation: a new source in x-ray mammography].

This work was aimed at evaluating the image quality obtainable in X-ray mammography using synchrotron radiation monochromatic lines. After a short review of the current mammographic techniques, the main features of synchroton radiation in the X-ray field are analyzed, especially of that emitted by the Adone storage ring. Its features are then compared with the radiation emitted by a Coolidge tube. The experimental unit used in this study, including beamline, monochromator and mammograph, is then described together with the experimental method for carrying out a series of experiments in the mammographic field employing both monochromatic lines (E = 17 keV) and white radiation from conventional sources. The first series of experiments is described, which employed standard phantoms: the dependence of resolution and contrast on both wavelength and thickness of breast specimens is reported. Several mammograms of neoplastic breast specimens were obtained after mastectomy: they were acquired using both synchrotron monochromatic lines and radiation emitted by a conventional tube and employing the same acquisition system. The comparison of the two series of images shows that synchrotron radiation can demonstrate a high number of anatomopathologic details with high definition, contrast and resolution which cannot be obtained by means of a conventional source. Our results appear very promising and suggest synchrotron radiation as the major tool in the early diagnosis of neoplastic breast lesions.

Breast Neoplasms↗

PubMed1997

The synchrotron beam, a new dimension for contrast media research?

Synchrotron sources can provide intense, collimated and tunable X-ray beams suitable for medical imaging and research, allowing the use of monochromatic X-rays for human examinations. At the European Synchrotron Radiation Facility (ESRF), a beam line dedicated to medical research is under commissioning. Two imaging programs are being developed, for coronary angiography and cerebral CT. The new monochromatic imaging systems should improve image contrast and provide better image quantification. The properties of synchrotron radiation are described, as well as the instrumentation of the medical beam line and its 2 imaging programs. The new possibilities offered by synchrotron radiation for contrast media research are discussed, the improvement on concentration measurement precision achievable is underlined.

Academies and Institutes↗