W Thomlinson

Medical applications of synchrotron radiation

The medical imaging and therapeutic technologies that are based on the use of radiation are reviewed briefly, with special emphasis on the recent developments of synchrotron radiation (SR) methods. New results have been achieved in all of these areas since the last comprehensive reviews were written in this field. This topical review is intended to make the latest possible results and complete set of references available. The different contrast mechanisms in imaging by x-rays are described. The applications range from whole-body imaging to studies of atomic and molecular structures. The SR imaging applications include coronary angiography, bronchography, mammography, computed tomography, x-ray microscopy and imaging by scattering. The therapy applications include photon activation therapy and microbeam radiation therapy.

Weanling piglet cerebellum: a surrogate for tolerance to MRT (microbeam radiation therapy) in pediatric neuro-oncology

The cerebellum of the weanling piglet (Yorkshire) was used as a surrogate for the radiosensitive human infant cerebellum in a Swiss-led program of experimental microbeam radiation therapy (MRT) at the ESRF. Five weanlings in a 47 day old litter of seven, and eight weanlings in a 40 day old litter of eleven were irradiated in November, 1999 and June, 2000, respectively. A 1.5 cm-wide x 1.5 xm-high array of equally space approximately equals 20-30 micrometers wide, upright microbeams spaced at 210 micrometers intervals was propagated horizontally, left to right, through the cerebella of the prone, anesthetized piglets. Skin-entrance intra-microbeam peak adsorbed doses were uniform, either 150, 300, 425, or 600 gray (Gy). Peak and inter-microbeam (valley) absorbed doses in the cerebellum were computed with the PSI version of the Monte Carlo code GEANT and benchmarked using Gafchromic and radiochromic film microdosimetry. For approximately equals 66 weeks [first litter; until euthanasia], or approximately equals 57 weeks [second litter; until July 30, 2001] after irradiation, the littermates were developmentally, behaviorally, neurologically and radiologically normal as observed and tested by experienced farmers and veterinary scientists unaware of which piglets were irradiated or sham-irradiated. Morever, MRT implemented at the ESRF with a similar array of microbeams and a uniform skin-entrance peak dose of 625 Gy, followed by immunoprophylaxis, was shown to be palliative or curative in young adult rats bearing intracerebral gliosarcomas. These observations give further credence to MRTs potential as an adjunct therapy for brain tumors in infancy, when seamless therapeutic irradiation of the brain is hazardous.

A method to extract quantitative information in analyzer-based x-ray phase contrast imaging

Analyzer-based imaging is a powerful phase-sensitive technique that generates improved contrast compared to standard absorption radiography. Combining numerically two images taken on either side at ±1/2 of the full width at half-maximum (FWHM) of the rocking curve provides images of “pure refraction” and of “apparent absorption.” In this study, a similar approach is made by combining symmetrical images with respect to the peak of the analyzer rocking curve but at general positions, ±α⋅FWHM. These two approaches do not consider the ultrasmall angle scattering produced by the object independently, which can lead to inconsistent results. An accurate way to separately retrieve the quantitative information intrinsic to the object is proposed. It is based on a statistical analysis of the local rocking curve, and allows one to overcome the problems encountered using the previous approaches.

Imaging lobular breast carcinoma: comparison of synchrotron radiation DEI-CT technique with clinical CT, mammography and histology.

Different modalities for imaging cancer-bearing breast tissue samples are described and compared. The images include clinical mammograms and computed tomography (CT) images, CT images with partly coherent synchrotron radiation (SR), and CT and radiography images taken with SR using the diffraction enhanced imaging (DEI) method. The images are evaluated by a radiologist and compared with histopathological examination of the samples. Two cases of lobular carcinoma are studied in detail. The indications of cancer are very weak or invisible in the conventional images, but the morphological changes due to invasion of cancer become pronounced in the images taken by the DEI method. The strands penetrating adipose tissue are seen clearly in the DEI-CT images, and the histopathology confirms that some strands contain the so-called Indian file formations of cancer cells. The radiation dose is carefully measured for each of the imaging modalities. The mean glandular dose (MGD) for 50% glandular breast tissue is about 1 mGy in conventional mammography and less than 0.25 mGy in projection DEI, while in the clinical CT imaging the MGD is very high, about 45 mGy. The entrance dose of 95 mGy in DEI-CT imaging gives rise to an MGD of 40 mGy, but the dose may be reduced by an order of magnitude, because the contrast is very large in most images.

Quantitative functional lung imaging with synchrotron radiation using inhaled xenon as contrast agent

Small airways play a key role in the distribution of ventilation and in the matching of ventilation to perfusion. The purpose of this study was to introduce an imaging method that allows measurement of regional lung ventilation and evaluation of the function of airways with a small diameter. The experiments were performed at the Medical Beamline of the European Synchrotron Radiation Facility. Monochromatic synchrotron radiation beams were used to obtain quantitative respiration-gated images of lungs and airways in two anaesthetized and mechanically ventilated rabbits using inhaled stable xenon (Xe) gas as a contrast agent. Two simultaneous images were acquired at two different energies, above and below the K-edge of Xe. Logarithmic subtraction of the two images yields absolute Xe concentrations. This technique is known as K-edge subtraction (KES) radiography. Two-dimensional planar and CT images were obtained showing spatial distribution of Xe concentrations within the airspaces, as well as the dynamics of filling with Xe. Bronchi down to 1 mm in diameter were visible both in the subtraction radiographs and in tomographic images. Absolute concentrations of Xe gas were calculated within the tube carrying the inhaled gas mixture, small and large bronchi, and lung tissue. Local time constants of ventilation with Xe were obtained by following the evolution of gas concentration in sequential computed tomography images. The results of this first animal study indicate that KES imaging of lungs with Xe gas as a contrast agent has great potential in studies of the distribution of ventilation within the lungs and of airway function, including airways with a small diameter.

Small-angle x-ray scattering studies of human breast tissue samples

Small-angle x-ray scattering (SAXS) patterns are recorded from thin breast tissue samples containing healthy and cancerous regions. The SAXS patterns are compared with histo-pathological observations. The information available from SAXS is reviewed, and a model for scattering from collagen is presented. Scattering patterns of collagen at regions far from the tumours are essentially different from those at tumours. The axial period of collagen fibrils is 65.0 +/- 0.1 nm in healthy regions, and 0.3 nm larger in cancer-invaded regions. The average intensity of scattering from cancerous regions is an order of magnitude higher than the intensity from healthy regions. This is interpreted to arise from an increase of the specific surface area of the scatterers, which is due to a disruption of the molecular and supra-molecular structures in cancerous regions and invasion of new types of cells. The differences of the SAXS patterns are large and distinctive enough to suggest that these phenomena may be utilized in mammography.

First human transvenous coronary angiography at the European Synchrotron Radiation Facility

The first operation of the European Synchrotron Radiation Facility (ESRF) medical beamline is reported in this paper. The goal of the angiography project is to develop a reduced risk imaging technique, which can be used to follow up patients after coronary intervention. After the intravenous injection of a contrast agent (iodine) two images are produced with monochromatic beams, bracketing the iodine K-edge. The logarithmic subtraction of the two measurements results in an iodine enhanced image, which can be precisely quantified. A research protocol has been designed to evaluate the performances of this method in comparison with the conventional technique. Patients included in the protocol have previously undergone angioplasty. If a re-stenosis is suspected, the patient is imaged both at the ESRF and at the hospital with the conventional technique, within the next few days. This paper reports the results obtained with the first patients. To date, eight patients have been imaged and excellent image quality was obtained.

Comparison between a position sensitive germanium detector and a taper optics CCD FRELON camera for diffraction enhanced imaging

Abstract Diffraction Enhanced Imaging (DEI) can significantly improve the expressiveness of radiology. The contrast mechanism of DEI, in addition to absorption contrast, exploits the differences in X-ray refraction properties, which are sensed by a perfect crystal placed between the sample and the detector. DEI needs a monochromatic collimated X-ray source, which is available for instance from synchrotrons. The X-ray beam is laminar and the sample is vertically scanned for projection imaging or is rotated for CT. Detectors should match the beam characteristics and should also accomplish the other two main requirements for DEI mammography: high spatial resolution and high Detective Quantum Efficiency (DQE) in a large energy range (20–60xa0keV). The first permit to exploit the edge contrast enhancement obtained with the DEI technique, for example the improved visualization of microcalcifications in mammographic imaging. The second allows minimizing the dose needed for a radiograph without sacrificing spatial resolution. Apart from this, a dynamic range as good as possible is required (typically from 14 to 16 bits) as well as a high readout speed, which is particularly important for CT. These specifications are difficult to be all condensed in a single detector. At the medical beamline of the ESRF two devices have been utilized for DEI radiography: a linear germanium detector (432 pixels, 350 microns pitch), which had been developed for angiography and cerebral CT and a 2048×2048 CCD camera with taper optics which has been built at the ESRF. The first detector shows an excellent DQE at zero frequency in a large energy range (∼90% from 20xa0keV up to 50xa0keV) but limited spatial resolution. In the latter a better compromise for DEI in the 20–30xa0keV range has been realized: a pixel size of 47xa0μm and a DQE(0) from 0.5 to 0.6 has been achieved. The performances of the two detectors will be presented here in detail and discussed.

Fixed-exit monochromator for computed tomography with synchrotron radiation at energies 18–90 keV

A fixed-exit monochromator has been constructed for computed tomography (CT) studies at the Medical Beamline of the European Synchrotron Radiation Facility. A non-dispersive pair of bent Laue-type crystals is used, and the first crystal is water-cooled. The monochromator operates at energies from 18 to 90 keV, and the maximum width of the beam is 150 mm. The performance of the monochromator is studied with respect to the beam intensity and energy distributions, and a close agreement is found between the calculated and experimental results. The intensity is between 10(9) and 10(10) photons s(-1) mm(-2) under typical operating conditions. The harmonic content of a 25 keV beam is about 30% at the minimum wiggler gap of 25 mm (field 1.57 T) and decreases by an order of magnitude when the gap is increased to 60 mm (field 0.62 T). The experimental set-up for CT studies includes dose monitors, goniometers and translation stages for positioning and scanning the object, and a 432-element linear-array Ge detector. Examples from phantom studies and in vivo animal experiments are shown to illustrate the spatial resolution and contrast of the reconstructed images.

A white-beam fast-shutter for microbeam radiation therapy at the ESRF

Abstract The ID17 Medical Beamline port at the European Synchrotron Radiation Facility (ESRF) delivers white beam generated by a 1.4xa0T wiggler. It is devoted to medical applications of synchrotron radiation. One major program of the beamline is called Microbeam Radiation Therapy (MRT). In this radiotherapy technique, still under development, the white beam fan is divided into several microbeams before reaching the target which is a tumoral brain. The maximum skin-entrance absorbed dose can reach extremely high values (over 1000xa0Gy) before causing tissue necrosis, while causing tumor necrosis. One of the key parameters for the success of the MRT is the accurate control of the radiation dose delivered to the target, as well as its location with respect to the tumor, to prevent unnecessary damage to normal tissues. Therefore, the opening and closing positions of the shutter while the target is moving vertically at a constant speed reaching 150xa0mm/s must be carefully controlled. Shutter opening times as short as 5±0.5xa0ms must be achieved. The total power of the white beam generated by the wiggler may reach 14.5xa0kW. It is essential to maintain vacuum continuity in the entire beamline and therefore the shutter had to be built to be vacuum compatible to a level of 10 −8 xa0mbar. This paper describes the fast shutter mechanics and its associated electronics.