Microbeam radiation therapy.

It is proposed to carry out radiotherapy and radiosurgery for brain lesions by crossfiring an array of parallel, closely spaced microbeams of synchrotron-generated x rays several times through an isocentric target, each microbeam in the array having an approximately 25-microns-wide adjustable-height rectangular cross section. The following inferences from the known tissue sparing of 22-MeV deuteron microbeams in the mouse brain and the following exemplary Monte Carlo computations indicate that endothelial cells in the brain that are lethally irradiated by any microbeam in an array of adequately spaced microbeams outside an isocentric target will be replaced by endothelial cells regenerated from microscopically contiguous, minimally irradiated endothelium in intermicrobeam segments of brain vasculature. Endothelial regeneration will prevent necrosis of the nontargeted parenchymal tissue. However, neoplastic and/or nonneoplastic targeted tissues at the isocenter will be so severely depleted of potentially mitotic endothelial and parenchymal cells by multiple overlapping microbeams that necrosis will ensue. The Monte Carlo computations simulate microbeam irradiations of a 16-cm diameter, 16-cm-long cylindrical human head phantom using 50-, 100-, and 150-keV monochromatic x rays.

A synchrotron radiation microtomography system for the analysis of trabecular bone samples.

X-ray computed microtomography is particularly well suited for studying trabecular bone architecture, which requires three-dimensional (3-D) images with high spatial resolution. For this purpose, we describe a three-dimensional computed microtomography (microCT) system using synchrotron radiation, developed at ESRF. Since synchrotron radiation provides a monochromatic and high photon flux x-ray beam, it allows high resolution and a high signal-to-noise ratio imaging. The principle of the system is based on truly three-dimensional parallel tomographic acquisition. It uses a two-dimensional (2-D) CCD-based detector to record 2-D radiographs of the transmitted beam through the sample under different angles of view. The 3-D tomographic reconstruction, performed by an exact 3-D filtered backprojection algorithm, yields 3-D images with cubic voxels. The spatial resolution of the detector was experimentally measured. For the application to bone investigation, the voxel size was set to 6.65 microm, and the experimental spatial resolution was found to be 11 microm. The reconstructed linear attenuation coefficient was calibrated from hydroxyapatite phantoms. Image processing tools are being developed to extract structural parameters quantifying trabecular bone architecture from the 3-D microCT images. First results on human trabecular bone samples are presented.

Tissue lesions caused by microplanar beams of synchrotron-generated X-rays in Drosophila melanogaster.

PURPOSE: To examine tissue lesions caused by microplanar beams of synchrotron-generated X-rays in Drosophila melanogaster using stereomicroscopy, light and electron microscopy. MATERIALS AND METHODS: Pupae were irradiated by 25-microm wide, 1.175 mm-high parallel microplanes at 100 microm on-centre intervals, at 20, 24, 32, 36, 48 or 72 h of development, with absorbed doses per microplane between 75 and 3,000 Gy. RESULTS: Transverse or longitudinal irradiation with in-slice absorbed doses of 75 or 375 Gy caused no recognizable effects. All pupae irradiated at or after 48 h developed normally. Conversely, the development to adulthood was delayed in 90% of pupae irradiated at 24h with doses of 750 Gy. However, neither those pupae nor adults that hatched after pupal irradiation at 48 and 72 h displayed morphological changes. Pupae exposed at 48 h of development to 3,000 Gy developed into adults with sharply delimited lesions in the irradiated microplanes of the compound eye or the cuticle of wings and abdomen. CONCLUSIONS: Post-mitotic eukaryotic cells can survive radiation doses of 3,000 Gy largely undamaged, even at the beginning of the terminal morphogenesis. The extremely sharp delimitation between damaged tissue microplanes and adjacent intact tissues may be relevant for future perspectives of radiosurgery.

The influence of the single-event energy-deposition distribution on the signal-to-noise ratio in x-ray images in the presence of scattered radiation.

The single-event energy-deposition distribution has been included in the signal-to-noise ratio for the detection of low-contrast detail in x-ray projection imaging. Calculations for an ideal detector show that this results in a higher signal-to-noise ratio for energy proportional detection than for the counting technique when scattered radiation is present, in contradiction to what has previously been assumed. The difference is less than 20% for photon spectra typical of medical radiography. If scattered radiation is reduced, the difference between energy proportional detection and counting diminishes. For very efficient scatter reduction, counting is slightly better than energy proportional detection.

X-ray energy optimisation in computed microtomography.

Expressions describing the absorbed dose and the number of incident photons necessary for the detection of a contrasting detail in x-ray transmission CT imaging of a circular phantom are derived as functions of the linear attenuation coefficients of the materials comprising the object and the detail. A shell of a different material can be included to allow simulation of CT imaging of the skulls of small laboratory animals. The equations are used to estimate the optimum photon energy in x-ray transmission computed microtomography. The optimum energy depends on whether the number of incident photons or the absorbed dose at a point in the object is minimised. For a water object of 300 mm diameter the two optimisation criteria yield optimum photon energies differing by an order of magnitude.

Feasibility study of x-ray diffraction computed tomography for medical imaging.

A feasibility study of soft-tissue imaging based on x-ray wide-angle diffraction contrast has been performed at the medical beamline of the European Synchrotron Radiation Facility (ESRF). The technique employs computed-tomography algorithms to reconstruct from one data set the spatial distribution of several tissues differentiated by their diffraction properties. Radial diffraction profiles are measured in parallel projections from the sample and decomposed into material-selective weighting factors, which form the sinograms for the reconstructions. Attenuation effects--inherent in imaging techniques using scattered radiation--are efficiently corrected for by a ray-tracing method applied to the corresponding absorption image. Images of 7 cm diameter samples composed of fat, bone and muscle were generated at 60 and 80 keV x-ray energy. The highest surface-absorbed dose was 24 mGy, but substantial contrast could still be obtained at 7 mGy, indicating potential applicability in medical imaging. The dominant noise contribution in the images stems from the detection system, pointing to a possible decrease in the surface-absorbed dose for an optimized system of more than a factor of 2.

In-line holography and phase-contrast microtomography with high energy x-rays.

Holography with high energy x-rays is now feasible due to the coherence properties of third generation synchrotron sources. Simple in-line holographic techniques can be used to generate edge-enhanced images which for many samples can be interpreted without direct phase retrieval. The coherence properties of such sources and their exploitation for phase-contrast microimaging are demonstrated. The technique can easily be combined with computed microtomography (CMT) data collection and reconstruction strategies for three-dimensional imaging. A dramatically improved image contrast, as compared with absorption CMT, was obtained when imaging a wet human coronary artery specimen. In the tomograms, previously invisible detail could be visualized with absorbed doses below the level where radiation damage impedes the imaging. The results indicate the considerable potential of the in-line holographic CMT method in three-dimensional biomedical microscopy.

Grain reconstruction of porous media: application to a low-porosity Fontainebleau sandstone.

The fundamental issue of reconstructing a porous medium is examined anew in this paper, thanks to a sample of low-porosity Fontainebleau sandstone that has been analyzed by computed microtomography. Various geometric properties are determined on the experimental sample. A statistical property, namely, the probability density of the covering radius, is determined. This is used in order to reconstruct a porous medium by means of a Poissonian generation of polydisperse spheres. In a second part, the properties of the real experimental sample and of the reconstructed one are compared. The most important success of the present reconstruction technique is the fact that the numerical sample percolates despite its low porosity. Moreover, other geometrical features and conductivity are found to be in good agreement.

[A new X-ray source for medical imaging and radiotherapy research: synchrotron radiation]. / Une nouvelle source de rayons X pour la recherche en imagerie médicale et en radiothérapie: le rayonnement synchrotron.

Whether for diagnosis or therapeutic purposes, X-rays have many applications in medicine. Synchrotron Radiation sources open new perspectives. This has already been the case for a number of years in molecular and cellular biology where the scope of absorption and diffraction work has been greatly extended. This could also be the case for medical imaging and radiotherapy where the characteristics of the beam (collimation, stability, flux) allow new approaches in the energy range of radiological X-rays, namely between 30 keV and 100 keV. Such a source exists today in Grenoble, with the European Synchrotron Radiation Facility (ESRF). The opening of a beamline dedicated to medical research for whole European scientific community is planned for the end of 1996. This beamline, coupled with the "microbeam" beamlines, will cover medical imaging (angiography, tomodensitometry, microtomography, X-ray microscopy) as well as radiotherapy.

Prospects for microcomputerized-tomography using synchrotron radiation.

A microversion of a computerized tomograph (CT) is described, in which the object is subjected to a successive series of translations with rotation by a small angle in between. The spatial resolution is determined by collimators and translation step lengths and is today, with clinical X-ray tube, of the order of 100 µm. The use of synchrotron radiation instead of X-ray tubes offers the advantages of much higher fluence rates, which can be used to diminish the exposure times from days to minutes or to increase the spatial resolution from 100 µm to about 1 µm. The possibility to receive monoenergetic photons of selectable energy makes it possible to avoid spectral hardening image artifacts, as well as to optimize the information sampling with regard to average absorbed dose or exposure time. Selectable photon energies are valuable also for tomochemistry applications.

An X-ray microprobe facility using synchrotron radiation.

An X-ray microprobe for trace elemental analysis at micrometer spatial resolutions, using synchrotron radiation (SR), is under development. The facility consists of two beamlines, one including a 1:1 focusing mirror and the other an 8:1 ellipsoidal mirror. At present, "white light" is used for excitation of the characteristic X-ray fluorescence lines. Sensitivities in thin biological samples are in the range of 2-20 fg in 100 microns2 areas in 5 min irradiation times. Scanning techniques, as well as microtomography and chemical speciation, are discussed. Application to a specific biomedical study is included.

Dosimetry at 28 keV synchrotron radiation for cell irradiations.

Accurate dosimetry is a prerequisite for reliable comparisons between radiobiological irradiation experiments. Parameters affecting the determination of absorbed dose to cells in the shape of a small cell pellet in a centrifuge tube, irradiated by 28 keV mono-energetic photons from a synchrotron, were investigated. Thermoluminescent dosimeter (TLD), diode and ion chambers were utilized to monitor the irradiations. The distribution of the absorbed dose and such parameters as scatter, attenuation and interface dosimetry in the target, which influence the dose, were studied. A method for inter-calibrations of two different calibration sources by using TLD and TLD readers is given. Characteristics of the TLD, that is, fading, supralinearity, energy response, self-attenuation and mini-dosimetry were considered for the dosimetry. A method for correcting photon fluence attenuation in cylindrical TLDs is presented. The study shows that the absorbed dose to cells irradiated at low photon energy at a synchrotron irradiation facility can, using accurate dosimetry protocol, be correctly and reproducibly determined.

Radiation exposure to personnel in departments of gynaecologic oncology in Sweden.

Radium-226 and cesium-137 are used at six departments of gynaecologic oncology in Sweden. A survey of radiation exposure (dose equivalents) to the personnel is reported. The measurements were performed with TL dosemeters. From dose distribution measurements, the dose equivalents in different parts of the body, related to different working procedures, were determined. Effective dose equivalents and collective dose equivalents were also estimated. The estimated collective dose equivalent for this category of personnel in Sweden was 1.3 manSv. The effective dose equivalent was less than the dose equivalent measured with dosemeters worn on the chest, and was less than half the annual limit set by ICRP.

Electron microscopy and computed microtomography studies of in vivo implanted mini-TL dosimeters.

The need for direct methods of measuring the absorbed dose in vivo increases for systemic radiation therapy, and in more sophisticated methodologies developed for radioimmunotherapy. One method suggested is the use of mini-thermoluminescent dosimeters (TLD). Recent reports indicate a marked loss of signal when the dosimeters are used in vivo. We investigated the exterior surface of the dosimeters with scanning electron microscopy and the interior dosimeter volume with computed microtomography. The results show that the dosimeters initially have crystals uniformly embedded in the teflon matrix, with some of them directly exposed to the environment. After incubation in gel, holes appear in the dosimeter matrix where the crystals should have been. The computed microtomographic images show that crystals remain in the interior of the matrix, producing the remaining signal. We conclude that these dosimeters should be very carefully handled, and for practical use of mini-TLDs in vivo the dosimeters should be calibrated in equivalent milieus. An alternative solution to the problem of decreased TL efficiency, would be to coat the dosimeters with a thin layer, of Teflon, or other suitable material.

Cell survival after Auger electron emission from stable intracellular indium exposed to monochromatic synchrotron radiation.

The biological effect of Auger electrons emitted from indium in V79 cells was investigated. K-shell vacancies were induced by synchrotron x-rays. Two energies, 100 eV above and below the K-edge of indium, were used. The cell survival for controls was similar to that which has been reported by others, with D37 = 4.4 Gy. Indium-oxine-labelled cells exhibited a survival clearly below that of the controls, D37 = 3.2 Gy, but no significant difference in survival between irradiations above and below the K-edge could be observed. The explanation is, inter alia, that the number of photons interacting with indium atoms incorporated into the cell, is small compared with the number of photons interacting with other atoms in the cell. The toxicity of indium oxine made it impossible to incorporate a sufficient number of indium atoms into the cells to observe a difference in this study. However, monoenergetic irradiation above and below the K-edge, provides a technique for the investigation of basic biological effects of Auger processes.

Subacute neuropathological effects of microplanar beams of x-rays from a synchrotron wiggler.

Microplanar beam radiation therapy has been proposed to treat brain tumors by using a series of rapid exposures to an array of parallel x-ray beams, each beam having uniform microscopic thickness and macroscopic breadth (i.e., microplanar). Thirty-six rats were exposed head-on either to an upright 4-mm-high, 20- or 37-microns-wide beam or to a horizontal 7-mm-wide, 42-microns-high beam of mostly 32- to 126-keV, minimally divergent x-rays from the X17 wiggler at the National Synchrotron Light Source at Brookhaven National Laboratory. Parallel slices of the head, separated at either 75 or 200 microns on center, were exposed sequentially at 310-650 grays (Gy) per second until each skin-entrance absorbed dose reached 312, 625, 1250, 2500, 5000, or 10,000 Gy. The rats were euthanized 2 weeks or 1 month later. Two rats with 10,000-Gy-entrance slices developed brain tissue necrosis. All the other 10,000- and 5000-Gy-entrance slices and some of the 2500- and 1250-Gy-entrance slices showed loss of neuronal and astrocytic nuclei and their perikarya. No other kind of brain damage was evident histologically in any rat with entrance absorbed doses < or = 5000 Gy. Brain tissues in and between all the 312- and 625-Gy-entrance slices appeared normal. This unusual resistance to necrosis is central to the rationale of microplanar beam radiation therapy for brain tumors.

In vivo animal models of body composition in aging.

We developed several techniques that provide data on body elemental composition from in vivo measurements in rats. These methods include total body potassium by whole-body counting of endogenous 40K; total body calcium (TBCa), sodium and chloride by in vivo neutron activation analysis and total body phosphorus (TBP) and nitrogen (TBN) by photon activation analysis. These elements provide information on total body fat, total body protein and skeletal mass. Measurements were made in 6-, 12- and 24-month-old rats. TBN increased slightly between 6 and 12 months but was significantly lower by 24 months, indicating a substantial loss in total body protein. Working at the National Synchrotron Light Source, we studied rat femurs by computed microtomography (CMT), and the elemental profile of the femur cortex by synchrotron-radiation induced X-ray emission (SRIXE). Although there were no significant changes in TBCa and TBP, indices of skeletal mass, CMT revealed a marked increase in the size and number of cavities in the endosteal region of the femur cortex with increasing age. The SRIXE analysis of this cortical bone revealed a parallel decrease in the endosteal Ca/P ratio. Thus, there are major alterations in bone morphology and regional elemental composition despite only modest changes in total skeletal mass.