WO2008125680A1

WO2008125680A1 - Method and device for the radiation therapy treatment of tissue by means of an x-ray/ct system or a diagnostic or orthovoltage x-ray system

Info

Publication number: WO2008125680A1
Application number: PCT/EP2008/054577
Authority: WO
Inventors: Vladimir Arkadiev; Daniel Fratzscher; Johannes Rabe; Reiner Wedell; Hanns-Joachim Weinmann; Rüdiger LAWACZECK; Hubertus Pietsch; Sven Golfier; Gregor Jost; Peter Wust; Lutz LÜDEMANN; Norbert Langhoff; Michael Haschke; Michael Krumrey; Martin Gerlach; Levent Cibik
Original assignee: Institut Für Angewandte Photonik E.V.; Bayer Schering Pharma Ag; Charité - Universitätsmedizin Berlin; Ifg - Institute For Scientific Instruments Gmbh; Physikalisch-Technische Bundesanstalt
Priority date: 2007-04-16
Filing date: 2008-04-16
Publication date: 2008-10-23
Also published as: DE102007018102B4; CL2008001064A1; UY31025A1; DE102007018102A1; PE20090134A1; TW200920437A

Abstract

The invention proposes modifying an X-ray diagnostic device such that the diagnostic functions are preserved, but radiation therapy of tumors is possible as well. As is conventional in X-ray diagnostics, X-ray contrast media are used to improve diagnostics. Contrast media containing one or more atoms of heavy elements are also used for dose amplification in radiation therapy mode. The dosage increase is based on the photoelectric effect. The tumor is only irradiated as long as a target concentration of the contrast medium is exceeded in the tumor. Preferred diagnostic X-ray devices are computer tomography devices equipped with high-performance X-ray tubes and operated with high voltage in the range of up to 140 kV or more. Modifications for the transition from the diagnostic mode to the therapy mode relate to the additional modules, the X-ray concentrator 3 and the fluorescence detector unit 6. Using the X-ray concentrator 3, which is pushed into the beam path in a mechanical or computer-controlled manner, the X-ray beam is monochromatized with optimal energies for the dose increase of the contrast medium and focused on the target area. The fluorescence detector 6 measures the concentration of the contrast medium in the tumor 11 in an online fashion during irradiation. Alternately, the concentration must be determined from the diagnostic image by a rapid switch to the diagnostic mode.

Description

Method and device for the radiotherapeutic treatment of tissue by means of an X-ray CT system or a diagnostic or Orthovolt X-ray system

description

The invention relates to a method and a device for the radiotherapeutic treatment of tissue, that is to say tumors, by means of an X-ray CT system or of tumors or other diseases by means of a diagnostic or orthovolt X-ray system, each having at least one X-ray source, an X-ray optical module, consisting of an energy-dispersive X-ray concentrator and a diaphragm system, an imaging unit and a measuring device for determining the radiation dose.

A medical focus for the use of the method is seen in the treatment of malignant brain tumors, because these types of tumors are relatively well accessible due to the skull dimensions with the aforementioned X-rays and have with conventional therapies an extremely poor prognosis.

The successful radiotherapeutic treatment of tumors requires their early diagnosis and localization. Success depends on how targeted the absorbed dose required to kill the tumor can be concentrated on the tumor without damaging healthy tissue. In radiation therapy today the use of linear accelerators or more recently particle accelerators with energies in the megavolt range is common. The investment costs for such a system are approximately € 5 million, due in part to the high level of structural protection measures. Thus, only a few centers are able to offer state-of-the-art radiotherapy. The high costs and the problems of radiation prevent a widespread use of this technology even in countries whose economic power is below that of the rich industrialized countries.

In addition, radiation therapy using a linear accelerator sometimes requires uncomfortable immobilization techniques (facial mask, stereotactic fixation) for the patient during the therapy sessions.

In addition to the established radiotherapy, there are more complex techniques such as the irradiation with neutrons, protons or heavy particles, which are located because of the high investment effort in the majority of cases at major research centers and have not found the way into the routine application. The only exception is the proton irradiation of eye tumors, which is successfully operated at a few centers.

External radiation therapy (teletherapy) is supported by interstitial forms of application in which radioactive implants are permanently or temporarily placed in the target volume (brachytherapy) and thus achieve a particularly high dose in the tumor. On an experimental basis, pelt radioisotopes of targeting substances and can also link imaging and therapy. However, the selectivity is far from sufficient so far, so that radiation exposure, and in particular the burden of the excretory organs liver and kidney, are limiting.

An alternative to X-ray therapy is to use an intensive synchrotron radiation instead of the X-ray tube, which can advantageously be set to the energy maximum of the X-ray absorption. However, this synchrotron radiation with medical application is only available at a few research centers worldwide. The studies with synchrotron radiation have so far been regarded as experimental studies or pioneering work.

Competing therapies are:

a) Ablation Method Such techniques are based on the introduction of probes into the tumor area to be ablated. The tumor is overheated, undercooled or irradiated with high doses. Depending on the physical method, a distinction is made e.g. radio ablation, radio frequency ablation, laser ablation or cryoablation. Ethanolinjections are also applied to the tumor for local therapy. In extensive processes, embolization techniques are used to occlude the vessels supplying the tumor. All of these methods disadvantageously require intratumoral administration and are thus invasive.

b) Chemotherapy / Radiosensitizer Individual cytostatics are already used by default for local enhancement of radiotherapy. However, there remains a need for action in the applications (malignant brain tumors) targeted by the present method. The classical radiosensitizers, which are intended to prevent the recombination of Radiolyseprodukte by their high electron affinity, have not yet achieved clinical importance.

c) other experimental techniques

Among the bi-modal techniques are: i. Neutron capture therapy in which high-capture substances (e.g., boron or gadolinium compound) for thermal neutrons are delivered to the tumor and then activated in the neutron beam. The fission and emission products lead to local cell killing. The therapy is physically very expensive. A breakthrough has not been achieved even after several clinical trials.

ii. The magnetic field hyperthermia. In this case, magnetic nanoparticles are applied to the tumor, which are then heated by an external magnetic field and thus can lead to overheating of the tumor. Initial clinical studies on this form of therapy are promising, although this form of therapy has so far required intratumoral application of the nanoparticles. Magnetic resonance imaging is no longer possible after application of nanoparticles.

For physical reasons, different X-ray energies are used for CT imaging and radiotherapy. CT remains in the range up to a maximum of 140 keV, whereas the lower energies in therapy only begin at 1 MeV, that is, the X-ray energies for imaging and radiation differ by an order of magnitude. As a result, it is precisely the modern irradiation units that are not suitable for high-resolution imaging. Conversely, X-ray systems with acceleration voltages up to 140 kV, which are excellently suited for imaging, have been replaced in conventional radiotherapy because of the low penetration depth, thus high surface doses, first by Telekobalt and then by the high-voltage linear accelerators.

So-called tomotherapy units, ie systems that can be used equally for imaging as for radiation therapy, are currently being considered. For example, WO 2005081842 and DE 698 39 480 T2 disclose proposals according to which an X-ray system used for irradiation therapy is combined with a magnetic resonance imaging system. The systems must be arranged so that the coil systems of the magnetic resonance system can not be disturbed by the treatment beam of the X-ray system. Such a plant would have enormous costs. In addition, the open design of the MRI system results in a lower spatial resolution compared to the closed high-field variants and CT imaging. Furthermore, the acquisition times are within 10 minutes or more, so that no real simultaneous diagnosis and therapy is possible.

The invention has for its object to provide a method and a device that get along with the same principle device technology as the diagnostics to allow a targeted and gentle radiotherapy. The goal is the coupling of diagnosis and therapy in the fight against cancer. According to the invention the object is achieved by features that are mentioned in the main claims 1 and 9. Advantageous embodiments are the subject of the dependent claims.

The invention is the instrumental extension of a conventional CT device (or a simplified version of a diagnostic or Orthovolt X-ray system, as will be shown later) such that the CT device for diagnostics hardware remains unmodified, for therapy, an X-ray optical concentrator the beam path is pushed and an additional emission detector is attached. Both additional elements can be easily replaced and ultimately be electromechanically swung out of the control console or into the beam, so that the radiation risk for the operating personnel is kept as low as possible. With the X-ray concentrator, a quasi-monochromatic X-radiation is selected from the divergent and polychromatic X-radiation emitted by the conventional high-performance tube and focused specifically on the target, the tumor. This physical measure of X-ray optics alone achieves a considerable increase in intensity in the target. In addition to this X-ray optical focusing, a monochromatization and a further dose increase in the target area are effected by previously introduced absorber elements. The dose increase is based on the photoelectric effect, which increases approximately with the third power of the atomic number (Z) of the elements, so that, for example, the elements iodine (Z = 53) and gadolinium (Z = 64), which in X-ray or MR - Contain contrast agents, leading to a remarkable dose increase. This dose increase should be registered on-line (ie without time delay) via the radiated X-ray fluorescence with a second detector. The monochromatization of the X-ray beam allows optimal energy adaptation of X-ray excitation and absorber element. By detecting the X-ray fluorescence, the Streuanteil can be suppressed by means of an energy-dispersive detector or by a fine optics.

On the basis of the collected data (tumor geometry and X-ray absorption from the coordinates and image units of the CT image, registration of the X-ray fluorescence for on-line measurement of the dose increase) an optimal control of the tumor irradiation is possible up to the additional dose of the contrast medium or the termination of the session when falling below predetermined irradiation parameters.

Although similar approaches have already been described in the scientific literature and in patents, they have not been so far as yet. For example, the working group headed by A. Norman (University of California, Los Angeles) has spent a long time studying the dose increase of iodine and gadolinium-containing contrast agents.

Literature on papers by A. Norman et al. :

Solberg TD, Iwamoto KS, Norman A.

Calculation of radiation enhancement factors for dose enhancement therapy of brain tumors. Phys Med Biol. 1992 Feb; 37 (2): 439-43.

Norman A, Ingram M, Skillen RG, Freshwater DB, Iwamoto KS, Solberg T. X-ray phototherapy for canine brain masses. Radiat Oncol Investig. 1997; 5 (1): 8-14.

Mesa AV, Norman A, Solberg TD, Demarco JJ, Smathers JB. Can distributions using kilovoltage x-rays and can enhancement from iodine contrast agents. Phys Med Biol. 1999 Aug; 44 (8): 1955-68.

Rose JH, Norman A, Ingram M, Aoki C, Solberg T, Mesa A. First radiotherapy of human metastatic brain tumors delivered by a computerized tomography scanner (CTRx). Int J Radiat Oncol Biol Phys. 1999 Dec 1; 45 (5): 1127-32.

The investigations of Norman et al. whose essential results are cited in the literature cited above span a wide range from initial dose-escalation calculations to initial clinical trials on a CT scanner, in which the normal fan beam was narrowed by blending on a pencil beam Neither energy-dispersive X-ray optics nor on-line dose registration were available, so the dose increase was verified but more extensive studies failed.

The patents US 6,782,073 B2, US 6,853,704 B2, US 2004/0006254 Al have the work of A. Norman or the like as a starting point and improve them by the type of contrast agent application and by improving the Strahlrahlgeometrie.

According to US Pat. No. 6,853,704 B2, a CT apparatus is to be used for radiotherapeutic treatment, with a plurality of radiation sources being used. are used, whose divergent rays are focused with a concentrator. In addition, an aperture system is provided in each case. The measurement of the radiation dose should be made on the diaphragm system.

Although the present in the CT device imaging system is addressed, this is obviously not used during the treatment for the reasons described above. On the contrary, as shown by US Pat. No. 6,782,073 B2, prior to radiotherapy treatment, a CT scan is provided with a second device exclusively for imaging for treatment planning. As contrast agents Photoelectric Radiation Enhancer (PRE) are used, which are already known for example from US 2004/0006254 Al.

All modifications and instrumental extensions are carried out according to the present method on common for CT diagnostics devices. The use of high-performance x-ray tubes is advantageous.

The computational tomograph generates the representation of patient anatomy and topography for the exact determination of the tumor extent and the determination of the target volume in three-dimensional imaging, usually with the help of contrast agents. The spatial resolution of such devices is now in the submillimeter range and represents anatomical conditions in high detail accuracy.

The basic device is extended by two additional functions. The imaging software needs to be a new one

Enhanced or rewrote diagnostic therapy software which should also contain the therapy planning mode. The additional modules will be described in more detail below.

The two device components (energy-dispersive X-ray concentrator and fluorescence detection unit) can be individually introduced manually or, controlled by the control panel, in the beam path or be removed again. This conversion from diagnostics to therapy (and possibly back again) can be done while the patient is placed on the couch. Advantageously, you will first perform a contrast-enhanced CT scan, save the target coordinates and X-ray attenuations and then move the patient bed so that then the target area (tumor) is located in the isocenter of the gantry. At the same time, the two additional functions can be retracted. These conversions are done in a short time so that the target coordinates have not changed practically due to motion artifacts. The measurement of the dose increase with the fluorescence detection module allows an exact control of the irradiation of the target area.

Modern high-performance tubes allow the application of therapeutically common radiation doses in the minute range, so that normally a target coordinate changes only minimally fails. A readjustment is possible at any time by switching to the diagnostic mode of the CT device. Ultimately, switching to the diagnostic mode at the press of a button can be done so quickly that motion artifacts and the pharmacokinetics of the contrast agents can be detected and adapted to the radiation.

Conventionally, the patient is displaced in the z direction on the couch during CT scans. During the Lungsmodus is thought to move the patient bed additionally in the x and y directions. Furthermore, the gantry can be tilted and the beam intensity can be modulated during the circulation, so that even larger tumors can be scanned specifically with the focused and monochromatized X-ray beam and the X-radiation introduced from the outside into the area of the dose increase

Description of instrumental accessories

1. X-ray concentrator

The X-ray tubes used in medical practice emit a divergent beam in a broad energy spectrum. The possibilities for modulating X-rays in the range of 20-140 keV in X-ray optical elements are limited. The use of a glare system alone does not represent a solution to the problem at hand. This method has no possibility of problem-matching and thus energetically modifying the beam quality. However, convergent and quasi-monochromatic radiation (that is, defined energies) are required for effective treatment with minimal side effects. The diaphragm system (in the Z plane), which is already present on CT, is therefore used together with an X-ray concentrator for focusing and monochromatization. For example, graphite-based X-ray concentrators may be used to form convergent quasi-monochromatic beams. In this case, even when the X-ray tube is rotating, the beam is precisely focused on the tumor and its intensity is increased substantially precisely in the spectral range in which the activatable sensitizers (PREs below) are most effective. The goal of the concentrator is to form a convergent or quasiparallel and quasi-monochromatic beam from a fan-shaped and spectrally wide beam of a CT device. The concentrator is a two-layered closed surface with a beam stop. The inner layer is made of an energy-dispersive material, preferably graphite crystals. The outer layer is made of a highly absorbent material so that the direct jet can not penetrate the wall of the concentrator. The concentrator may also contain multiple closed or non-closed surfaces. In the simplest case, the concentrator is a hollow cylinder with a HOPG layer on its inner wall. The layer thickness must be adapted to the photon energies, so that an effective reflection is realized. The diameter and length of the concentrator can vary between 1 to 5 cm for the diameter and 1 to 15 cm for the length. Preferred values are about 2 cm for the diameter and about 8 cm for the length. The concentrator is located at a distance of about 20 to 30 cm from the focal spot of the anode and is mounted on a plate with an adjusting device which is constructed similar to the usual CT CT collimator, so a replacement is easily and quickly possible. In addition to the hollow cylinder with constant diameter over the length of other shapes are preferred in which the diameter over the length of elliptical or in the form of a logarithmic spiral is varied, but also any other forms are advantageously possible.

The reflection on the HOPG crystal is due to the Bragg relationship, whereby the closed shape with its focusing geometry helps to optimally illuminate the target area and thus to increase the intensity in the target area. So that the primary beam does not interfere with the X-ray optics. can happen, a beam stop is attached. Position and shape of the beam stop adapt to the shape of the X-ray optics. Only the Beamstop guarantees that only Bragg-reflected X-rays with defined energy are focused on the target area. For example, the X-ray optics are designed so that the focus coincides with the isocenter of the gantry. For the total blockage of the direct jet, the wall of the concentrator is also decisive. The wall material and the wall thickness must be optimized in terms of energy, so that the direct beam and its scattering are totally shaded.

The building block X-ray concentrator can alternatively be provided with a device for measuring the radiation intensity.

2. X-ray fluorescence detection

The determination of the radiation dose is carried out by measuring the X-ray fluorescence of the contrast agent, as described in DE 102005 026940 Al. For this purpose, a detection system arranged in the vicinity of the tumor is provided, which is preferably attached to the patient couch. For the measurement of the X-ray fluorescence either a sensitive energy dissolving detector, eg a CdTe detector, is used or a dosimeter in combination with an optical system. This optical system is similar in construction to the concentrator described above. The X-ray fluorescence is focused on the measuring probe of the dosimeter, without the Streuanteil significant importance. Instead of the dosimeter, a photon counter can also be used. Photons activatable substances

The use of special activatable substances (Photoelectric Radiation Enhancer (PRE)) as a contrast agent simultaneously enhances the effect on the previously localized tumor and allows follow-up monitoring via diagnostic imaging. That is, the PREs provide on the one hand for an improved representation of the anatomy or the pathological changes of the patient, on the other hand for a reinforcing effect during the radiotherapy treatment.

In clinical X-ray diagnostics only substances are used which represent the target area (tumor) in a passive manner. The localization in the target area comes about because the tumor physiology differs from the normal tissue and so the residence times of the diagnostic agents in the tumor and normal tissue are different. In Anglo-Saxon, this phenomenon is referred to as "enhanced permeation and retention (EPR)." This is especially noticeable in malignant brain tumors, where in most cases the blood-brain barrier is open "Blood-brain barrier into the tumor, but can not leave the bloodstream with an intact blood-brain barrier and so does not pass into the surrounding healthy brain tissue. As a result, the tumor stands out clearly from the normal tissue.

In order for substances to absorb X-rays through the photoelectric effect, they must contain atoms of high atomic number

(Absorption behavior ~ Z ³ ). This is iodine (element 53) of

Case, but also in magnetic resonance contrast media. gadolinium (element 64) is suitable for this purpose. In both cases, due to the photoelectric effect, increased absorption and, as a consequence, a local radiation dose increase occur.

Suitable for radiation dose increase are substances containing one or more, even different atoms of atomic numbers 38-42, 44-53, 56-83 elements. Technetium (Tc, Z = 43) is radioactive and can only be used as an admixture. The heavy alkaline elements are difficult to formulate specifically for parenteral administration and are thus only available for oral or topical applications. Lighter elements from about manganese (Mn, Z = 25) can be advantageously used for the secondary absorption of the emitted X-ray fluorescence of heavy elements in combination with these.

In addition to the clinically used iodine-containing X-ray contrast agents are also compounds MR contrast agents in question, such as Gd-DTPA or Gd-DOTA. The aim is to achieve a higher concentration in the tumor than in the surrounding tissue in order to further increase the selectivity of radiotherapy in addition to the radiation guidance. This can be further increased by using tumor-affine compounds or nanoparticles. Also interesting are combinations with chemotherapeutic agents (for example cis-platinum) or other modern metal complexes which have already found their way into tumor therapy and act intracellularly. The dose increase by radiation-absorbing substances is based on the photoelectric effect. The incoming X-ray photon, upon sufficient energy and collision with an atom, strikes an electron from an inner shell. Large cross-sections have atoms of high atomic numbers with their K electrons. For iodine, the K-edge is 33.2 keV, for gadolinium it is 50.2 keV. The energetic gap is closed by the emission of X-ray fluorescence and / or a cascade of Auger electrons, the X-ray fluorescence increasing with the atomic number and the Auger cascade decreasing with the ordinal number. The photoelectrons and Auger electrons have short ranges, so that the energy is deposited near the absorption site. A local dose increase is observed, which depends on the concentration of the absorber molecule.

Software and control

The Photoelectric Radiation Enhancer (PRE) is first applied. The images then generated in the imaging mode are used for anatomical localization and thus for defining the areas to be irradiated. After further PRE application and the achievement of the target or necessary for the photoelectric dose increase effect concentration in the tumor is switched from the imaging mode in the therapy mode and started with the irradiation. The software can calculate the coordinates for an exact positioning of the irradiation from the measuring signals and take over the control of the CT device. Within the feedback loops, it is ensured that if the concentration falls below a threshold concentration in the tumor, a message is issued and a subsequent dosing of the PRE can be carried out. Is this for the sake of acute Tolerability is no longer possible, the radiation can be stopped and a new meeting can be scheduled.

The temporal course of the concentration and the degradation of the X-ray marker in the tissue forces to device and control technical solutions, which must be done practically in real time. This relates to the measurement of the actual dose recording, the use of these results to control and continuous recalculation of the radiation still to be introduced, the adaptation of the CT control to the realization of these requirements and the correct switching and interval sequence for switching between diagnosis and therapy.

With the method according to the invention, the irradiation planning can be carried out daily in the shortest time before each radiotherapy in accordance with the contrast agent-based CT image. This considerably increases the accuracy of radiation therapy, as deviations in patient positioning and changes in the target volume (for example, tumor regression or organ mobility) are immediately taken into account during radiotherapy without interruption.

logistics

Diagnostics, treatment planning and therapy can be fused in one device. This is a significant financial and logistical advantage over currently established technologies. It is not insignificant that systems operating according to the method according to the invention can be installed at any hospital (even in emerging countries) without great safeguards (radiation protection), since ortho- Protect volt photons against megavolt photons by minor constructional measures or do not incur additional costs with existing CT devices.

Variant in a simplified version

In a simplified embodiment, especially in the treatment of near-surface malignant tumors or in the treatment of benign tumors and arthritis-like diseases, CT high technology is not critical and one can also use the X-ray concentrator with conventional C-arms and other diagnostic X-ray units combine. Although in this simplified version, the complete 3D imaging is not possible or only to a limited extent, it is still possible to advantageously combine diagnostics and therapy. In principle, the tumor can also be irradiated in this variant from all 3D directions. The same applies to interventional applications or Orthovolt irradiation devices.

As in the CT embodiment described above, the x-ray concentrator is pushed into the x-ray beam prior to the beam exit of the x-ray tube for the therapy mode. X-ray energy and beam focus are adjusted to the target area. Also in this case, the irradiation can be computer-controlled from all spatial directions focused on the tumor. The energy profile can be adjusted so that the main dose is deposited in the near-surface target areas. For the above-mentioned dose enhancement, the range of described photon activatable substances (PREs) can be extended to those which are known or can be formulated directly in the form of ointments, solutions, creams, emulsions from dermatological applications. Examples are povidone-iodine (poly (1-vinyl-2-pyrrolidone) -iodo-complex) containing solutions or ointments such as Betaisodona®.

The advantage of the method over the photodynamic therapy results from the fact that the location of the irradiation focus can be arbitrarily variable even in the centimeter range below the skin surface. Furthermore, in contrast to the X-ray diagnosis, which has a very high spatial and temporal resolution, the diagnostics in the optical range is limited by the strong absorption and the high scattered radiation background.

The invention will be explained in more detail below with reference to exemplary embodiments. In the accompanying drawings show

1 is a schematic representation of the device according to the invention in two views,

2 is a schematic diagram of a working according to the invention CT system, 3 is a schematic diagram of the function of the X-ray concentrator,

4 shows a photograph of the X-ray concentrator mounted on a base plate of a CT collimator,

5 shows a photograph of the X-ray concentrator after installation in a CT system,

FIG. 6 shows the intensity distribution in focus (identical to the gantry rotation center) of the energy range concentrator of the W-KCC line. FIG.

Fig. 7 shows the energy spectrum in focus and

8 shows the excitation conditions for iodine and gadolinium, the calculated dose increase as a function of the photon energy.

The operation of the device system is outlined in Fig. 1. An X-ray-optical module consisting of a diaphragm system 2 and an X-ray concentrator 3, which focuses or collimates the X-rays onto a tumor 4, is attached to the output of an X-ray tube 1. For this purpose, a CT system is used (see FIG. 2). X-ray tube 1 and X-ray optical module rotate about the tumor 11 and can specifically irradiate the localized tumor 11, wherein adjacent, healthy tissue is spared maximum. Before radiotherapy, the tumor 11 is sensitized by the application of PREs for the X-radiation. Radiation and PREs must be coordinated. Using modern diagnostic methods, the effect of the therapy is followed in order to simulate the treatment planning in a feedback step. It should be noted that the marker function is time-dependent. The marker substances in the blood circulation are removed, ie the markers do not encase themselves in the cancer cells.

The core of the irradiation unit is a modern CT scanner with a movable patient table 5. It can be a standard product, as it is used by any radiotherapeutic device for radiation diagnosis. The range of application of such a CT device must be extended by therapy tasks. Such an image therapy CT (IT-CT) can then be operated in diagnostic and therapy mode. This results in hardly any additional spatial requirements, which increases the acceptance and significantly reduces the financial expenses for the users.

In addition to the beam shaping, the positioning of the tumor 11 plays the decisive role. Since the localization of the tumor 11 can be controlled by the imaging, automation of the positioning of the tumor 11 in the rotation of the X-ray tube 1, tilting the gantry and advancing the patient table 5 is possible, so that the highest possible precision in the irradiation are ensured can. An advantageous effect is the detection system 6 for determining the registered tumor dose (by photoelectric effect) on the basis of the measured X-ray fluorescence 7. The induced by the photoelectric effect X-ray fluorescence 7 increases sigmoid with the atomic number, so that for this example, iodine and gadolinium are suitable elements , From these measurement data, the effective radiation dose deposited in the tumor 11 or the dose-increasing effect in the tumor 11 can be determined. This provides the radiation therapist criteria for further individualized, therapeutic approach. Since photons from linear accelerators interact with matter via the Compton effect, which has a comparably low dependence on the atomic number of the elements and does not lead to the release of photons from inner electron shells, the above-described high-energy fluorine detection of the linear accelerators is not possible.

By changing the dimensions and the shape of the collimator 2 in combination with the concentrator 3 during the irradiation, tumors 11 of complicated shape can be effectively irradiated and, at the same time, the surrounding healthy tissue preserved as far as possible. Therefore, a controlled diaphragm system 2 is preferably provided for the device according to the invention.

The shutter system 2 alone would significantly reduce the irradiation intensity and have no possibility of modifying the emission spectrum. This can be achieved with the aid of the aperture system 2 and X-ray concentrator 3 existing X-ray optics. The concentrator 3 is a two-layered closed surface with a Beamstop 8 (Figure 3). The inner layer 14 is made of an energy dispersive material. For physical reasons, a graphite layer (HOPG - Highly Oriented Pyrolytic Graphite) is favored. The outer layer 13 is made of a highly absorbent material, so that the direct beam can not penetrate the wall of the X-ray concentrator 3. The X-ray concentrator 3 may also contain a plurality of closed or non-closed surfaces. In the simplest case, the X-ray concentrator 3 is a hollow cylinder with a HOPG layer on its inner wall.

The X-ray concentrator 3 should be adjusted to an energy of about 60 keV (this corresponds approximately to the W KCC line of the anode material): In this case, a quasi-monochromatic X-ray having a bandwidth of about ΔE ~ 15 keV (ΔE / E ~ 20 %) expected. To block the direct beam a Beamstop 8 is provided.

The application of the X-ray concentrator 3 allows:

• the suppression of all low-energy photons with

E <40 keV;

• the suppression of all high-energy photons with E> 80 keV;

The substantial increase in the beam intensity in the region of the highest absorption of the contrast agent (60 ± 10 keV for Gd); • the local irradiation of small tumors and metastases;

• in case of extensive tumors (focal spot <tumor) the

Focal spot 4 guided over the tumor 11 targeted.

The X-ray concentrator 3 is positioned immediately in front of the exit window of the X-ray tube 1. The radiation leaving the X-ray concentrator 3 consists of a reflected radiation component 9 and a direct beam 10 (FIG. 1). The X-ray concentrator 3 is equipped with a beam stop 8 for blocking the direct jet 10. In this way, only the reflected radiation portion 9 is focused on the tumor 11, whereby a high intensity quasi-monochromatic radiation in the focal spot 4 is generated.

4 shows a photograph of a practical embodiment of the X-ray concentrator 3 prior to installation on the collimator plate of the CT device. In Fig. 5, the X-ray concentrator 3 can be seen in the installed state. For installation, the plastic cover of the CT device must be removed.

6 gives an impression of the intensity distribution in the focus. For this purpose, an x-ray detector was displaced millimeter by millimeter in the horizontal direction (x-direction) and the intensity was measured. One sees a concise increase in intensity in focus.

FIG. 7 shows the energy spectrum measured with an energy-dispersive detector. The measurement was made on the basis of the scattered radiation on a Kapton foil and recalculation of the Compton shift. It can clearly be seen that the energy is concentrated in the range around 60 keV. In addition, the spectrum of the X-ray beam without X-ray concentrator 3 is shown. It can be seen clearly that the X-ray concentrator 3 leads, in addition to the monochromatization of the radiation, to a marked increase in intensity in the center.

Because of the higher surface doses in the case of X-rays in the range up to a few 10 keV, the local increase in dose due to radiation-absorbing substances is an advantageous element for the therapy. Thus, the desired dose distribution or the dose drop from the target volume to the environment can be generated.

Iodine- or lanthanide-containing PRE examples should accumulate in the tumor area in relation to the surrounding tissue or show high tumor tissue concentration quotients. They are very compatible at the same time.

FIG. 8 reflects the dependence of the dose increase of iodine and gadolinium as a function of the X-ray photon energy and shows that the maximum of the dose increase of iodine and gadolinium in the energy range is about 60 keV. This energy range is currently well covered by the X-ray optics (see FIG. 7). Because the Gd K edge is at about 50 keV, photons with energies of about 50-70 keV are most suitable for the excitation of Gd K lines. These optimum conditions are provided with a tungsten tube as X-ray tube 1 which emits a strong W-KCC line at 59.3 keV. The use of the X-ray concentrator 3 increases the intensity of the primary radiation in the energy range 50-70 keV essential. In addition, in this case, all high-energy photons (> 80 keV) are suppressed, whereby the scattered radiation background can be reduced.

The determination of the absorbed dose, which is registered on-line during the irradiation, is based on the measurement of the X-ray fluorescence signal of the registered contrast agent (for example Gd) by a detection system 6. The underlying finding is that the X-radiation used for the therapy stimulates characteristic lines of the contrast agent. These fluorescence lines can be registered by means of at least one detector. With known contrast medium concentration, the measured intensity of the secondary radiation is a measure of the absorbed dose. The detection system 6 is located on the patient couch 5. Because the active area of these detectors of the detection system 6 is relatively small, multiple detectors can be assembled into arrays to increase the capture angle for registration of fluorescence radiation. If necessary, it would also be possible to use a secondary concentrator for effective trapping of the emitted characteristic line of the contrast agent and the suppression of stray radiation as far as possible.

Suitable detectors are CdTe detectors with good efficiency and acceptable energy resolution at high energies.

In a practical embodiment, an X-ray tube 1 with the following operating data was used: U = 140 kV, I = 0.2 A. The Gd concentration was 10 mg / g. For a detection angle Ω = 0.01 sr and an excited volume of about 1 cm ³ , one then finds about 70 000 ph / s.

In contrast to conventional X-ray fluorescence analysis (RFA), which uses characteristic L-lines to detect heavy elements, the present method has a number of features:

High energies of fluorescence photons (heavy element K-lines);

• large excitation volume;

• large entrance depth of the primary radiation;

Large exit depth and associated absorption of fluorescence photons;

• a high scattered radiation background.

For imaging during a therapy session, a CT detector 12, which is present in any case in the CT system, is used for imaging purposes. The concentrator 3 is swiveled out of the beam path of the x-ray tube 1 and thus rendered ineffective. In this way, high-contrast, high-resolution images can be obtained. The images can be used directly to design the further therapy. They also serve to control the current concentration of the contrast agent (PRE). List of reference numbers

I X-ray tube 2 aperture system

3 X-ray concentrator

4 focal spot

5 patient table

6 Detection System 7 X-ray fluorescence

8 beam stop

9 reflected radiation component

10 direct beam

II tumor 12 CT detector

13 Outer layer

14 inner layer

Claims

claims

1. A method for the radiotherapeutic treatment of tissue by means of an X-ray CT system or by means of a diagnostic or Orthovolt X-ray system with at least one X-ray source, an X-ray optical module consisting of an energy dispersive X-ray concentrator and a diaphragm system, an imaging unit and a

Measuring device for determining the radiation dose,

characterized in that

a. the X-ray concentrator is removed from the beam path for imaging and introduced into the beam path of the X-ray source for radiotherapeutic treatment,

b. the X-ray concentrator based on the Bragg reflection on a HOPG crystal in combination with a beam stop for the non-reflected beam is geometrically designed to focus a quasi-mono-energetic X-ray beam on the tumor,

c. in or on the tissue a photoelectrically activatable contrast agent is applied or applied,

d. the determination of the radiation dose / dose increase by measurement of the X-ray fluorescence takes place.

2. The method according to claim 1, characterized in that the selectively transmitted through the X-ray concentrator energy is between 20 and 140 keV, preferably between 30 and 100 keV and more preferably between 40 and 80 keV.

3. The method according to claim 1 or 2, characterized in that the X-ray concentrator is adapted to the energy of the emission line of the X-ray anode, preferably at Wolframanoden on the energy of the tungsten KCC line with 59.3 keV.

4. The method according to any one of the preceding claims, characterized in that

the energy bandwidth is kept in the range of +/- 15%.

5. The method according to any one of the preceding claims, characterized in that

as contrast agent substances are used which contain at least one atom from the elements of atomic numbers 25-35, 38-42, 44-53, 56-83.

6. The method according to claim 5, characterized in that

iodine-containing photoelectric radiation enhancers (PRE) can be used as the contrast agent.

7. The method according to claim 5, characterized in that

as a contrast agent lanthanide-containing Photoelectric Radiation Enhancer (PRE) can be used.

8. The method according to claim 5, characterized in that

as contrast agent gadolinium-containing photoelectric radiation enhancer (PRE) can be used.

9. Device for the radiotherapeutic treatment of provided with a photoelectrically activatable contrast agent tissue by means of an X-ray CT system or by means of a diagnostic or Orthovolt X-ray system with at least one X-ray source (1), an X-ray optical module consisting of a diaphragm system (2 ) and X-ray concentrator (3), an imaging unit (12) and a measuring device for determining the radiation dose,

characterized in that

a. the X-ray concentrator (3) contains an energy-dispersive element in combination with a beam stop (8) for suppressing the non-reflected primary beam,

b. the X-ray concentrator (3) can be removed from the beam path of the X-ray source (1)

c. a detection system (6) arranged in the vicinity of the tumor (4) for measuring the X-ray fluorescence of the contrast agent is provided for determining the radiation dose.

10. Device according to claim 9, characterized in that

the detection system (6) consists of a plurality of detectors joined in an array.

11. Device according to claim 9 or 10, characterized in that

the detector (s) are CdTe detectors.

12. Device according to claim 9 or 10, characterized in that

the detector includes an optical module for energy selection in combination with an energy independent photon counter.

13. Device according to one of claims 9 to 10, characterized in that

the detector or detectors on the patient table (5) of the X-ray system are arranged.

14. Device according to one of claims 9 to 13, characterized in that

the X-ray source (1) is a tungsten X-ray tube.

15. Device according to one of claims 9 to 14, characterized in that

the X-ray concentrator (2) is a graphite-based X-ray mirror (HOPG).

16. Device according to one of claims 9 to 15, characterized in that

the detection system (6) is fed back to the emission of the photon radiation enhancer (PRE) element.

17. Device according to one of claims 9 to 16, characterized in that

the X-ray concentrator (3) is a graphite-based X-ray mirror (HOPG), which contains a beam stop and which is designed so that the primary beam is absorbed and only the monoenergetic part is transmitted.

18. Device according to one of claims 9 to 17, characterized in that

the energy transmitted through the X-ray concentrator (3) is set to the excitation optimum of the photoelectric beam amplifiers.

19. Device according to one of claims 9 to 18, characterized in that

for tumor diagnostics and tumor therapy one and the same basic unit is used, which can be switched over from one mode to the other in a short time sequence.