P. Berkvens

Instrumentation of the ESRF medical imaging facility

Abstract At the European Synchrotron Radiation Facility (ESRF) a beamport has been instrumented for medical research programs. Two facilities have been constructed for alternative operation. The first one is devoted to medical imaging and is focused on intravenous coronary angiography and computed tomography (CT). The second facility is dedicated to pre-clinical microbeam radiotherapy (MRT). This paper describes the instrumentation for the imaging facility. Two monochromators have been designed, both are based on bent silicon crystals in the Laue geometry. A versatile scanning device has been built for pre-alignment and scanning of the patient through the X-ray beam in radiography or CT modes. An intrinsic germanium detector is used together with large dynamic range electronics (16 bits) to acquire the data. The beamline is now at the end of its commissioning phase; intravenous coronary angiography is intended to start in 1999 with patients and the CT pre-clinical program is underway on small animals. The first in vivo images obtained on animals in angiography and CT modes are presented to illustrate the performances of these devices.

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.

Dosimetry protocol for the forthcoming clinical trials in synchrotron stereotactic radiation therapy (SSRT)

PURPOSE An adequate dosimetry protocol for synchrotron radiation and the specific features of the ID17 Biomedical Beamline at the European Synchrotron Radiation Facility are essential for the preparation of the forthcoming clinical trials in the synchrotron stereotactic radiation therapy (SSRT). The main aim of this work is the definition of a suitable protocol based on standards of dose absorbed to water. It must allow measuring the absolute dose with an uncertainty within the recommended limits for patient treatment of 2%-5%. METHODS Absolute dosimetry is performed with a thimble ionization chamber (PTW semiflex 31002) whose center is positioned at 2 g cm(-2) equivalent depth in water. Since the available synchrotron beam at the ESRF Biomedical Beamline has a maximum height of 3 mm, a scanning method was employed to mimic a uniform exposition of the ionization chamber. The scanning method has been shown to be equivalent to a broad beam irradiation. Different correction factors have been assessed by using Monte Carlo simulations. RESULTS The absolute dose absorbed to water at 80 keV was measured in reference conditions with a 2% global uncertainty, within the recommended limits. The dose rate was determined to be in the range between 14 and 18 Gy/min, that is to say, a factor two to three times higher than the 6 Gy/min achievable in RapidArc or VMAT machines. The dose absorbed to water was also measured in a RW3 solid water phantom. This phantom is suitable for quality assurance purposes since less than 2% average difference with respect to the water phantom measurements was found. In addition, output factors were assessed for different field sizes. CONCLUSIONS A dosimetry protocol adequate for the specific features of the SSRT technique has been developed. This protocol allows measuring the absolute dose absorbed to water with an accuracy of 2%. It is therefore satisfactory for patient treatment.

Potential high resolution dosimeters for MRT

Microbeam Radiation Therapy (MRT) uses highly collimated, quasi‐parallel arrays of X‐ray microbeams of 50–600 keV, produced by 2nd and 3rd generation synchrotron sources, such as the National Synchrotron Light Source (NSLS) in the U.S., and the European Synchrotron Radiation Facility (ESRF) in France, respectively. High dose rates are necessary to deliver therapeutic doses in microscopic volumes, to avoid spreading of the microbeams by cardiosynchronous movement of the tissues. A small beam divergence and a filtered white beam spectrum in the energy range between 30 and 250 keV results in the advantage of steep dose gradients with a sharper penumbra than that produced in conventional radiotherapy. MRT research over the past 20 years has allowed a vast number of results from preclinical trials on different animal models, including mice, rats, piglets and rabbits. Microbeams in the range between 10 and 100 micron width show an unprecedented sparing of normal radiosensitive tissues as well as preferential damage to malignant tumor tissues. Typically, MRT uses arrays of narrow (∼25–100 micron‐wide) microplanar beams separated by wider (100–400 microns centre‐to‐centre, c‐t‐c) microplanar spaces. We note that thicker microbeams of 0.1–0.68 mm used by investigators at the NSLS are still called microbeams, although some invesigators in the community prefer to call them minibeams. This report, however, limits it discussion to 25–100 μm microbeams. Peak entrance doses of several hundreds of Gy are surprisingly well tolerated by normal tissues. High resolution dosimetry has been developed over the last two decades, but typical dose ranges are adapted to dose delivery in conventional Radiation Therapy (RT). Spatial resolution in the sub‐millimetric range has been achieved, which is currently required for quality assurance measurements in Gamma‐knife RT. Most typical commercially available detectors are not suitable for MRT applications at a dose rate of 16000 Gy/s, micron resolution and a dose range over several orders of magnitude. This paper will give an overview of all dosimeters tested in the past at the ESRF with their advantages and drawbacks. These detectors comprise: Ionization chambers, Alanine Dosimeters, MOSFET detectors, Gafchromic® films, Radiochromic polymers, TLDs, Polymer gels, Fluorescent Nuclear Track Detectors (Al2O3:C, Mg single crystal detectors), OSL detectors and Floating Gate‐based dosimetry system. The aim of such a comparison shall help with a decision on which of these approaches is most suitable for high resolution dose measurements in MRT. The principle of these detectors will be presented including a comparison for some dosimeters exposed with the same irradiation geometry, namely a 1×1 cm5 field size with microbeam exposures at the surface, 0.1 cm and 1 cm in depth of a PMMA phantom. For these test exposures, the most relevant irradiation parameters for future clinical trials have been chosen: 50 micron FWHM and 400 micron c‐t‐c distance. The experimental data are compared with Monte Carlo calculations.Microbeam Radiation Therapy (MRT) uses highly collimated, quasi‐parallel arrays of X‐ray microbeams of 50–600 keV, produced by 2nd and 3rd generation synchrotron sources, such as the National Synchrotron Light Source (NSLS) in the U.S., and the European Synchrotron Radiation Facility (ESRF) in France, respectively. High dose rates are necessary to deliver therapeutic doses in microscopic volumes, to avoid spreading of the microbeams by cardiosynchronous movement of the tissues. A small beam divergence and a filtered white beam spectrum in the energy range between 30 and 250 keV results in the advantage of steep dose gradients with a sharper penumbra than that produced in conventional radiotherapy. MRT research over the past 20 years has allowed a vast number of results from preclinical trials on different animal models, including mice, rats, piglets and rabbits. Microbeams in the range between 10 and 100 micron width show an unprecedented sparing of normal radiosensitive tissues as well as preferential da...

Synchrotron Radiation Therapy from a Medical Physics point of view

Synchrotron radiation (SR) therapy is a promising alternative to treat brain tumors, whose management is limited due to the high morbidity of the surrounding healthy tissues. Several approaches are being explored by using SR at the European Synchrotron Radiation Facility (ESRF), where three techniques are under development Synchrotron Stereotactic Radiation Therapy (SSRT), Microbeam Radiation Therapy (MRT) and Minibeam Radiation Therapy (MBRT).The sucess of the preclinical studies on SSRT and MRT has paved the way to clinical trials currently in preparation at the ESRF. With this aim, different dosimetric aspects from both theoretical and experimental points of view have been assessed. In particular, the definition of safe irradiation protocols, the beam energy providing the best balance between tumor treatment and healthy tissue sparing in MRT and MBRT, the special dosimetric considerations for small field dosimetry, etc will be described. In addition, for the clinical trials, the definition of appropiat...

Radiation Therapy Using Synchrotron Radiation: Preclinical Studies Toward Clinical Trials

After decades of intensive research, high-grade gliomas are still resistant to therapies, including surgery, chemotherapy, and radiotherapy or a combination thereof. The most important advance in the treatment of these tumors has been the introduction of a new chemotherapy drug called temozolomide, in combination with external beam photon irradiation [1]. One of the goals of the association of the CHU/UJF/INSERM and ESRF teams has been to develop research on synchrotron radiotherapy up to clinics.

Highly robust, high intensity white synchrotron beam monitor

Microbeam Radiation Therapy (MRT) uses highly collimated, quasi-parallel arrays of X-ray microbeams of 50-600 keV, produced by 3rd generation synchrotron sources. Among the MRT instrument components, the IC0 white X-ray beam monitor serves to measure the dose rate in the white synchrotron beam during the MRT irradiation. This device is essential for MRT clinical application. We constructed an extremely robust yet simple and reliable beam monitor. The device is based on a vacuum isolated Compton diode and is naturally UHV vacuum compatible. The device was subjected to a series of rigorous acceptance and characterization test. These tests are very promising and predetermining the device as an IC0 monitor for the future clinical MRT application.

SU‐E‐T‐335: Contrast‐Enhanced Stereotactic Synchrotron Radiation Therapy Clinical Trials: A Dry Run Report

Purpose: Contrast‐enhanced stereotactic synchrotron radiation therapy (SSRT) is an innovative technique based on localized dose‐enhancement effects obtained by reinforced photoelectric absorption in the target. Medium energy monochromatic x‐rays (50 –100 keV) are used for irradiating tumors previously loaded with high‐Z elements. SSRT clinical trials are being prepared at the European Synchrotron Radiation Facility (ESRF). The first patients (scheduled in summer–autumn 2011) should be treated at 80 keV, with 10 conformational beams. A dry run has been performed using an anthropomorphic radiosurgery human head phantom (Computerized Imaging Reference Systems, Norfolk, VA, USA). Methods: The phantom was scanned on a dedicated CT‐scanner, with and without a 3 cm diameter latex balloon filled with 3 mg/ml of iodine located in the supratentorial brain area. The PTV as well as the OAR were then contoured. The fisrt patient should receive 5 Gy at the ESRF in one fraction followed by a 6 Gy fraction and two 11 Gy fractions at the university hospital under stereotactic conditions (6 MV). The treatment will be followed by a whole brain irradiation (30 Gy, 10 fractions of 3 Gy, 6 MV). The treatment plan for the conventional stereotactic and whole brain irradiations were performed respectively on the Brainlab‐IPlan system, and on the Varian‐Eclipse TPS. The contrast enhanced SSRT treatment plan is performed on the ESRF dedicated version of Isogray (Dosisoft, Cachan, France) that has been developed for our irradiation technique.Results: The treatment plan was then successfully evaluated (Isodoses, DVHs and ICRU points). The full treatment was then realized on the phantom. Dose verifications were performed using gafchromic films and nPaG polymergeldosimetry as well as in vivo dosimetry. Conclusions: This contrast enhanced SSRT clinical trial “dry run” was the last step before the phase I/II trial and shows the feasibility and readiness of the whole treatment chain.