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EP1622649A2 - Apparatus and method for examining an object by means of elastically scattered x-ray radiation and contrast agent - Google Patents

Apparatus and method for examining an object by means of elastically scattered x-ray radiation and contrast agent

Info

Publication number
EP1622649A2
EP1622649A2 EP04731078A EP04731078A EP1622649A2 EP 1622649 A2 EP1622649 A2 EP 1622649A2 EP 04731078 A EP04731078 A EP 04731078A EP 04731078 A EP04731078 A EP 04731078A EP 1622649 A2 EP1622649 A2 EP 1622649A2
Authority
EP
European Patent Office
Prior art keywords
contrast agent
scattering particles
examination area
scattering
ray radiation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP04731078A
Other languages
German (de)
French (fr)
Inventor
J.-P. Philips I.P. & Standards GmbH SCHLOMKA
G. Philips I.P. & Standards GmbH HARDING
G. Philips I.P. & Standards GmbH MARTENS
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Philips Intellectual Property and Standards GmbH
Koninklijke Philips NV
Original Assignee
Philips Intellectual Property and Standards GmbH
Koninklijke Philips Electronics NV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Philips Intellectual Property and Standards GmbH, Koninklijke Philips Electronics NV filed Critical Philips Intellectual Property and Standards GmbH
Priority to EP04731078A priority Critical patent/EP1622649A2/en
Publication of EP1622649A2 publication Critical patent/EP1622649A2/en
Withdrawn legal-status Critical Current

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B6/00—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment
    • A61B6/48—Diagnostic techniques
    • A61B6/481—Diagnostic techniques involving the use of contrast agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B6/00—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment
    • A61B6/48—Diagnostic techniques
    • A61B6/483—Diagnostic techniques involving scattered radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B6/00—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment
    • A61B6/50—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment specially adapted for specific body parts; specially adapted for specific clinical applications
    • A61B6/504—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment specially adapted for specific body parts; specially adapted for specific clinical applications for diagnosis of blood vessels, e.g. by angiography
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B6/00—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment
    • A61B6/50—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment specially adapted for specific body parts; specially adapted for specific clinical applications
    • A61B6/508—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment specially adapted for specific body parts; specially adapted for specific clinical applications for non-human patients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/04—X-ray contrast preparations
    • A61K49/0409—Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is not a halogenated organic compound
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/04—X-ray contrast preparations
    • A61K49/0409—Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is not a halogenated organic compound
    • A61K49/0414—Particles, beads, capsules or spheres
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/04—X-ray contrast preparations
    • A61K49/0409—Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is not a halogenated organic compound
    • A61K49/0414—Particles, beads, capsules or spheres
    • A61K49/0423—Nanoparticles, nanobeads, nanospheres, nanocapsules, i.e. having a size or diameter smaller than 1 micrometer
    • A61K49/0428—Surface-modified nanoparticles, e.g. immuno-nanoparticles

Definitions

  • the invention relates to the field of X-ray examinations using elastically scattered X-ray radiation.
  • Elastically scattered X-ray radiation which is also referred to as coherently scattered X-ray radiation, arises when irradiated X-ray quanta do not lose any energy at the scattering object during the scattering process.
  • the form of X-ray scattering associated with an energy loss is referred to as Compton scattering.
  • Elastic scattering dominates in the case of small scattering angles, whereas Compton scattering is predominant in the case of larger scattering angles.
  • the detection of elastically scattered X-rays allows characterization of the molecular structure of the scattering object onto which the X-rays are irradiated.
  • Coherently scattered X-ray radiation also comprises small angle scattering, detection and evaluation of which can be used for a rough estimation of the size of smaller ( ⁇ 100 nm) scattering particles.
  • X-ray contrast agents which absorb the X-ray radiation to a weaker or greater extent than a surrounding body tissue
  • X-ray contrast agents which absorb the X-ray radiation to a weaker or greater extent than a surrounding body tissue
  • Such X-ray contrast agents are therefore used in X-ray diagnosis to make organs and vessels visible on an X-ray film or an X-ray screen and/or to make it possible for them to be recorded photographically.
  • the X-ray contrast agents may be administered orally or parenterally in order to show the organ that is to be examined or the vessel that is to be examined.
  • the effect of the known X-ray contrast agents is based on the weaker or greater absorption of the irradiated X-ray radiation, compared to the surrounding tissue
  • the vessels or organs that are filled with the X-ray contrast agent therefore have an improved visibility in an X-ray image.
  • the degree of visibility improvement depends on the absorption properties of the X-ray contrast agent. The larger the absorption difference is between organs or vessels filled with X-ray contrast agent and the surrounding tissue, the larger the improvement in visibility. It is an object of the invention to improve the possibilities for examination using X-ray radiation and also to expand the application possibilities of the latter.
  • a contrast agent for application to an examination area of an object that is to be examined, in particular a patient, for an X-ray examination of the examination area by means of X-ray radiation, is provided, characterized in that the contrast agent comprises scattering particles.
  • the object is achieved by a method of examining an object, in particular a patient, by means of elastically scattered X-ray radiation as claimed in claim 9, a method of producing a contrast agent as claimed in claim 12, and an apparatus for examining an object by means of elastically scattered X-ray radiation as claimed in claim 15.
  • the invention comprises, as essential concept, a contrast agent comprising scattering particles for examinations, in which elastically scattered X-ray radiation is used for analysis.
  • a contrast agent comprising scattering particles for examinations, in which elastically scattered X-ray radiation is used for analysis.
  • the scattering particles to which the present application refers have characteristic scattering properties which differ from the scattering properties of the tissue composition of the object that is to be examined in the examination area. These characteristic scattering properties lead to a defined angular distribution of the elastically scattered X-ray radiation coming from the contrast agent that comprises the scattering particles.
  • the scattering particles may be provided in the form of crystalline scattering particles.
  • the angular distribution of the elastically scattered X-ray radiation at scattering particles of the contrast agent has a characteristic profile.
  • this characteristic elastic scattering profile leads to a contrast difference between examination areas where contrast agent is present and areas where no contrast agent is present. If the contrast agent comprising scattering particles is utilized in a coherent scatter computed tomography examination (see e.g. US patent document 6,470,067 Bl), the characteristic scattering profiles of the scattering particles lead to contrast differences in the reconstructed images that show the spectrally resolved scattering properties in the examination area.
  • the contrast agent comprising the scattering particles may be applied to the examination area in any desired manner, in particular orally or parenterally.
  • An expedient feature of the invention may provide that the scattering particles comprise crystalline scattering particles.
  • Such scattering particles have scattering properties that differ from the scattering behavior of various tissue types in human and non-human organs and vessels in a characteristic manner, which makes it easier to visualize the examination area.
  • the contrast agent comprises small angle scattering particles.
  • a rough size estimate from the detected X-ray scattering measurements is made possible in that the applied scattering particles comprise small angle scattering particles and small angle X-rays scattered at the small angle scattering particles are detected.
  • the contrast agent comprises small angle scattering particles having a diameter of about ⁇ 100 nm and > about 1 nm. If the size (diameter) of the scattering particles is about ⁇ 100 nm or less, small angle scattering occurs. Small angle scattering can also be used to produce a contrast if no other particles of similar size are present in the examination area. Small angle scattering occurs in the case of both crystalline and non-crystalline particles. Preferably, the size distribution of the small angle scattering particles is very small or the size of the small angle scattering particles is essentially constant so that the characteristics of the small angle scattering is not blurred in the angular dimension.
  • the contrast agent comprises crystalline scattering particles, which are embedded in an interior of a shield.
  • crystalline particles which are soluble for example in the surrounding matter (notably comprising any body liquids in which the crystalline particles would be soluble) that is to be examined. This solubility would prevent the applied scattering particles from being able to perform their function during elastic scattering of the irradiated X-ray radiation as the regular structure of the crystal responsible for the characteristic elastic scattering properties would be dissolved.
  • the scattering function of the scattering particles is retained for a period given by the stability of the shield, which could be adapted to the duration of the X-ray examination.
  • the scattering particles could be poisonous for the matter in the examination area, for which reason between the matter and the scattering particles any direct contact has to be prevented; this is possible by embedding them in the shield.
  • the shield is formed by an envelope of phospholipids.
  • use may be made for example of the known microbubbles which are formed by phospholipids and are used in conjunction with the ultrasound examination technique.
  • the microbubbles are filled with a gas.
  • the scattering particles may be embedded using microbubbles.
  • the shield is broken up to release the scattering particles. This means, for example, that the scattering particles dissolve following release into the surrounding matter and are thus decomposed.
  • the contrast agent comprises the scattering particles which comprise sodium chloride particles.
  • a contrast agent can be produced in a simple manner and that is essentially harmless to human and non-human organs and vessels.
  • the scattering particles are chemically coupled to a function-specific compound.
  • the function-specific compound can be an element or a compound which on account of its chemical/physical/biological properties couples to elements of the matter that is to be examined.
  • the contrast agent comprising the particles may be applied in the region of matter that is to be examined.
  • a function-specific compound for coupling to the - scattering particles may be selected as a function of the matter or the body function that is to be examined.
  • Fig. 1 shows a schematic diagram of a measuring arrangement for carrying out an examination by means of elastically scattered X-ray radiation.
  • Fig. 2 shows a schematic diagram of a measuring arrangement for carrying out an examination by means of coherent scatter computer tomography.
  • Figs. 3 A, 3B show part of the measuring arrangement of Fig. 2 comprising radiation source, examination area and an angle selection device, in front and side view respectively.
  • Fig. 4 shows a schematic sectional diagram of a microbubble consisting of phospholipids.
  • Fig. 5 shows a graph of the scattering function for sodium chloride (NaCl).
  • Fig. 1 shows a schematic diagram of a measuring arrangement for examining an object 1 with the aid of elastically scattered X-rays.
  • a radiation source 2 generates X-rays 3 which are directed onto the object 1. Some of the generated X-rays 3 pass as transmitted X- ray radiation 4 through the object 1 without any interaction. Other generated X-rays 3 are elastically scattered at non-crystalline or crystalline scattering particles 5, 6 in the object 1 that is to be examined, resulting in scattered X-ray radiation 7.
  • the transmitted X-ray radiation 4 and the scattered X-ray radiation 7 are detected by means of a two-dimensional detector 8. This may be an X-ray detector or an X-ray film.
  • the respective diameter of the scattering rings 9, 10 is a measure of the distance between the detector 8 and the respective scattering particle 5, 6, since when using monochromatic X-ray radiation the angle at which the generated X-rays 3 are scattered at the particles 5, 6 is predetermined.
  • the width (sharpness) of the scattering rings 9, 10 depends on the size of the particles and on their scattering characteristics.
  • a crystalline scattering particle 9, 10 may generate sharp scattering rings 9, 10 but the scattering rings are blurred when the size of the crystalline scattering particles is small or when the crystalline scattering particles have a certain size distribution.
  • the contrast agent may be applied both orally and parenterally.
  • the contrast agent may be injected using a needle.
  • the specific form of application of the contrast agent comprising the crystalline scattering particles is not critical to the invention.
  • the contrast agent comprising scattering particles may be produced as a non-specific contrast agent, which means that the contrast agent does not have any means for the specific deposition of the particles on specific parts of organs or vessels.
  • the particles may be embedded in a shielding cover in order for example to prevent dissolution of the crystalline particles following application of the contrast agent and prior to carrying out of the examination by means of elastically scattered X-rays.
  • Particles which are harmful, in particular poisonous, to the object, for example an organ or a vessel, that is to be examined may also be applied with the aid of a shielding cover.
  • Fig. 1 shows the basic design of a measuring arrangement for examining by means of elastically scattered X-ray radiation. Any desired methods may be used here, for example using fan-like X-ray radiation or computer tomography technology, as described for example in the document DE 100 09 285.
  • Fig. 2 shows a schematic diagram of a computer tomography scanner comprising a gantry 100 which can rotate about an axis of rotation 140.
  • the gantry 100 is driven by a motor 200.
  • a radiation source S for example an X-ray radiator, is fixed on the gantry 100.
  • the beam used for the examination is determined by a first screen arrangement 310 and/or a second screen arrangement 320. If the first screen arrangement 310 is active, the beam fan is produced (shown in unbroken lines) which runs perpendicular to the axis of rotation 140 and in the direction thereof has small dimensions (for example 1 mm).
  • the beam cone 420 is produced (shown in dashed line) which in a plane perpendicular to the axis of rotation 140 has the same shape as the beam fan 410 but in the direction of the axis of rotation 140 has significantly larger dimensions.
  • a beam 410 or 420 passes through a cylindrical examination area 130 in which there may be for example a patient on a patient table (neither of which are shown in any more detail) or else a technical object. After it has passed through the examination area 130, the beam 410 or 420 impinges on a two-dimensional detector arrangement 160 that is fixed on the gantry 100, said detector arrangement comprising a large number of detector elements arranged in the form of a matrix.
  • the detector elements are arranged in rows and columns.
  • the detector columns run parallel to the axis of rotation; the detector rows may be located in planes perpendicular to the axis of rotation, for example in an arc of a circle about the radiation source S.
  • the detector rows usually comprise significantly more detector elements, for example 1000, than the detector columns (for example 16).
  • An angle selection device 260 is mounted in front of the detector arrangement 160, which angle selection device comprises a collimator 260a and an angle selector 260b.
  • the collimator 260a and the angle selector 260b may be designed to be combined with one another as one component.
  • Figs. 3 A and 3B show part of the measuring arrangement of Fig. 2 comprising radiation source S, examination area 130 and the angle selection device 260 in front and side views respectively.
  • the screening effect can be used to select a predefined part of the beam 410 or 420 at a scattering angle ⁇ following scattering in the examination area 130.
  • a region in which the scattered radiation of the scattering particles is expected can be selected with the aid of the angle selection device 260, so that other fractions of the scattered radiation can be screened out and as a result not detected by the detector arrangement 160, which makes it easier to measure scattered radiation having a smaller amplitude with the aid of the measuring arrangement.
  • the angle selection device 260 may be moved into the region between the detector arrangement 160 and the examination area 130 if measurement is to be carried out contrast-agent-selectively in an optimized manner, wherein measurement in conjunction with the contrast agent comprising scattering particles would be possible even without using the angle selection device 260. If the intention is to use another type of measurement, the angle selection device 260 can be moved out of the region between the detector arrangement 160 and the examination area 130. For this purpose, the angle selection device 260 is integrated in the measuring arrangement in a manner such that it can be moved.
  • the detector arrangement 160 are adapted to one another.
  • the dimensions of this beam fan 410 or of the beam cone 420 are selected such that the examination area 130 is completely irradiated, and the length of the rows of the detector arrangement is dimensioned such that the beams 410 or 420 can be completely detected.
  • the beam cone 420 is selected according to the length of the detector columns so that the beam cone can be completely detected by the detector arrangement 160. If only the beam fan 410 irradiates the examination area, it impinges on the central detector row(s). If the object concerned is a technical object rather than a patient, the object may be rotated during an examination, whereas the radiation source S and the detector arrangement 160 remain stationary.
  • the object may also be moved parallel to the axis of rotation 140 by means of a motor. If the motors 500 and 200 are operating at the same time, this results in a helix-like scanning movement of the radiation source S and detector arrangement 160.
  • the motors 500 and 200 are coupled to a control device 700.
  • Fig. 4 shows a schematic diagram of a microbubble 20 in cross section.
  • the microbubble is formed by a number of phospholipids 21 in which a hydrophobic tail 21a is directed inward and a hydrophilic head 21b is directed outward.
  • Such microbubbles 20 are used in conjunction with ultrasound analyses.
  • a crystalline or non-crystalline particle 23 is embedded in the interior 22 of the microbubble 20.
  • crystalline particles embedded in this way can be brought into the area that is to be examined.
  • the microbubble 20 is broken up using another technique, for example an ultrasound pulse, which results in the particle 23 being released and dissolving for example.
  • the contrast agent may be designed as a specific or functional contrast agent.
  • the scattering particles are coupled to a chemical compound or component which are specific with regard to an interaction with parts of the object that is to be examined, for example specific vessels or parts of vessels.
  • contrast agents can be produced which can be used in an organ- or tissue-specific manner.
  • One cost-effectively available contrast agent comprising crystalline scattering particles which is harmless to human and non-human organs/vessels may be produced on the basis of sodium chloride.
  • Sodium chloride has no toxic effect at all and when used in conjunction with a microbubble 20, as shown in Fig. 4, can dissolve following the break-up of the microbubble 20, for example by means of ultrasound.
  • the contrast effect of sodium chloride-based, crystalline scattering particles is in this case based on the characteristic scattering behavior in respect of X-ray radiation, as shown in Fig. 5.
  • a pronounced maximum 30 makes it possible to make examination areas of the object that is to be examined visible compared to areas in which the sodium chloride-based scattering particles are not present.

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Abstract

The invention relates to A contrast agent for application to an examination area of an object that is to be examined, in particular a patient, for an X-ray examination of the examination area by means of X-ray radiation, characterized that the contrast agent comprises scattering particles to form elastically scattered X-rays. By means of the scattering particles, the examination area can be made visible in the detected signal compared to surrounding areas. Furthermore, the invention relates to a method of examining an object, in particular a patient, by means of elastically scattered X-ray radiation as claimed in claim 9, a method of producing a contrast agent as claimed in claim 12, and an apparatus for examining an object by means of elastically scattered x-ray radiation as claimed in claim 15.

Description

Apparatus and method for examining an object by means of elastically scattered X-ray radiation and contrast agent
The invention relates to the field of X-ray examinations using elastically scattered X-ray radiation.
Elastically scattered X-ray radiation, which is also referred to as coherently scattered X-ray radiation, arises when irradiated X-ray quanta do not lose any energy at the scattering object during the scattering process. By contrast, the form of X-ray scattering associated with an energy loss is referred to as Compton scattering. Elastic scattering dominates in the case of small scattering angles, whereas Compton scattering is predominant in the case of larger scattering angles. The detection of elastically scattered X-rays allows characterization of the molecular structure of the scattering object onto which the X-rays are irradiated. Coherently scattered X-ray radiation also comprises small angle scattering, detection and evaluation of which can be used for a rough estimation of the size of smaller (<100 nm) scattering particles.
For diagnostic purposes in the medical sector, use is made during X-ray examinations of X-ray contrast agents which absorb the X-ray radiation to a weaker or greater extent than a surrounding body tissue (cf. O.-A. Neumύller: Rδmpps Chemie-Lexikon [Rδmpp's Chemistry Lexicon], page 3606-3607, Franckische Verlagshandlung, 8th edition, 1987). Such X-ray contrast agents are therefore used in X-ray diagnosis to make organs and vessels visible on an X-ray film or an X-ray screen and/or to make it possible for them to be recorded photographically. The X-ray contrast agents may be administered orally or parenterally in order to show the organ that is to be examined or the vessel that is to be examined. The effect of the known X-ray contrast agents is based on the weaker or greater absorption of the irradiated X-ray radiation, compared to the surrounding tissue The vessels or organs that are filled with the X-ray contrast agent therefore have an improved visibility in an X-ray image. The degree of visibility improvement depends on the absorption properties of the X-ray contrast agent. The larger the absorption difference is between organs or vessels filled with X-ray contrast agent and the surrounding tissue, the larger the improvement in visibility. It is an object of the invention to improve the possibilities for examination using X-ray radiation and also to expand the application possibilities of the latter.
This object is achieved according to the invention by a contrast agent as taught in Claim 1 of the present invention. Accordingly, a contrast agent for application to an examination area of an object that is to be examined, in particular a patient, for an X-ray examination of the examination area by means of X-ray radiation, is provided, characterized in that the contrast agent comprises scattering particles.
Furthermore, the object is achieved by a method of examining an object, in particular a patient, by means of elastically scattered X-ray radiation as claimed in claim 9, a method of producing a contrast agent as claimed in claim 12, and an apparatus for examining an object by means of elastically scattered X-ray radiation as claimed in claim 15.
The invention comprises, as essential concept, a contrast agent comprising scattering particles for examinations, in which elastically scattered X-ray radiation is used for analysis. Compared to the amorphous structure of various tissue types in human and non- human organs and vessels which are usually examined in diagnostic methods in the medical sector, the scattering particles to which the present application refers have characteristic scattering properties which differ from the scattering properties of the tissue composition of the object that is to be examined in the examination area. These characteristic scattering properties lead to a defined angular distribution of the elastically scattered X-ray radiation coming from the contrast agent that comprises the scattering particles. Particularly, the scattering particles may be provided in the form of crystalline scattering particles. The angular distribution of the elastically scattered X-ray radiation at scattering particles of the contrast agent has a characteristic profile. In an X-ray examination in which the elastically scattered X-rays are analyzed, this characteristic elastic scattering profile leads to a contrast difference between examination areas where contrast agent is present and areas where no contrast agent is present. If the contrast agent comprising scattering particles is utilized in a coherent scatter computed tomography examination (see e.g. US patent document 6,470,067 Bl), the characteristic scattering profiles of the scattering particles lead to contrast differences in the reconstructed images that show the spectrally resolved scattering properties in the examination area.
The contrast agent comprising the scattering particles may be applied to the examination area in any desired manner, in particular orally or parenterally. An expedient feature of the invention may provide that the scattering particles comprise crystalline scattering particles. Such scattering particles have scattering properties that differ from the scattering behavior of various tissue types in human and non-human organs and vessels in a characteristic manner, which makes it easier to visualize the examination area.
According to a further preferred embodiment of the present invention, the contrast agent comprises small angle scattering particles. In one embodiment of the invention, a rough size estimate from the detected X-ray scattering measurements is made possible in that the applied scattering particles comprise small angle scattering particles and small angle X-rays scattered at the small angle scattering particles are detected.
According to a further preferred embodiment of the present invention, the contrast agent comprises small angle scattering particles having a diameter of about < 100 nm and > about 1 nm. If the size (diameter) of the scattering particles is about < 100 nm or less, small angle scattering occurs. Small angle scattering can also be used to produce a contrast if no other particles of similar size are present in the examination area. Small angle scattering occurs in the case of both crystalline and non-crystalline particles. Preferably, the size distribution of the small angle scattering particles is very small or the size of the small angle scattering particles is essentially constant so that the characteristics of the small angle scattering is not blurred in the angular dimension.
According to a further preferred embodiment of the present invention, the contrast agent comprises crystalline scattering particles, which are embedded in an interior of a shield. As a result, it is possible to use, in the contrast agent, crystalline particles which are soluble for example in the surrounding matter (notably comprising any body liquids in which the crystalline particles would be soluble) that is to be examined. This solubility would prevent the applied scattering particles from being able to perform their function during elastic scattering of the irradiated X-ray radiation as the regular structure of the crystal responsible for the characteristic elastic scattering properties would be dissolved. By embedding the scattering particles in the shield, the scattering function of the scattering particles is retained for a period given by the stability of the shield, which could be adapted to the duration of the X-ray examination. In another case, the scattering particles could be poisonous for the matter in the examination area, for which reason between the matter and the scattering particles any direct contact has to be prevented; this is possible by embedding them in the shield. One preferred embodiment of the invention provides that the shield is formed by an envelope of phospholipids. Here, use may be made for example of the known microbubbles which are formed by phospholipids and are used in conjunction with the ultrasound examination technique. When using ultrasound examinations, the microbubbles are filled with a gas. For use in the contrast agent for elastically scattered X-ray radiation, the scattering particles may be embedded using microbubbles.
It may advantageously be provided that after the object has been examined by means of elastically scattered X-ray radiation the shield is broken up to release the scattering particles. This means, for example, that the scattering particles dissolve following release into the surrounding matter and are thus decomposed.
According to a further preferred embodiment of the present invention, the contrast agent comprises the scattering particles which comprise sodium chloride particles. By doing so, a contrast agent can be produced in a simple manner and that is essentially harmless to human and non-human organs and vessels. In order to ensure that the contrast agent is applied to the specific examination area, for example a specific organ or vessel, a preferred embodiment of the invention provides that the scattering particles are chemically coupled to a function-specific compound. The function-specific compound can be an element or a compound which on account of its chemical/physical/biological properties couples to elements of the matter that is to be examined. As a result, the contrast agent comprising the particles may be applied in the region of matter that is to be examined. A function-specific compound for coupling to the - scattering particles may be selected as a function of the matter or the body function that is to be examined.
The invention will be further described with reference to examples of embodiments shown in the drawings to which, however, the invention is not restricted.
Fig. 1 shows a schematic diagram of a measuring arrangement for carrying out an examination by means of elastically scattered X-ray radiation. Fig. 2 shows a schematic diagram of a measuring arrangement for carrying out an examination by means of coherent scatter computer tomography. Figs. 3 A, 3B show part of the measuring arrangement of Fig. 2 comprising radiation source, examination area and an angle selection device, in front and side view respectively.
Fig. 4 shows a schematic sectional diagram of a microbubble consisting of phospholipids.
Fig. 5 shows a graph of the scattering function for sodium chloride (NaCl).
Fig. 1 shows a schematic diagram of a measuring arrangement for examining an object 1 with the aid of elastically scattered X-rays. A radiation source 2 generates X-rays 3 which are directed onto the object 1. Some of the generated X-rays 3 pass as transmitted X- ray radiation 4 through the object 1 without any interaction. Other generated X-rays 3 are elastically scattered at non-crystalline or crystalline scattering particles 5, 6 in the object 1 that is to be examined, resulting in scattered X-ray radiation 7. The transmitted X-ray radiation 4 and the scattered X-ray radiation 7 are detected by means of a two-dimensional detector 8. This may be an X-ray detector or an X-ray film. As a result of the elastic scattering of the generated X-rays 3 at the scattering particles 5, 6, scattering rings 9, 10 are produced on the two-dimensional detector 8. The respective diameter of the scattering rings 9, 10 is a measure of the distance between the detector 8 and the respective scattering particle 5, 6, since when using monochromatic X-ray radiation the angle at which the generated X-rays 3 are scattered at the particles 5, 6 is predetermined. The width (sharpness) of the scattering rings 9, 10 depends on the size of the particles and on their scattering characteristics. A crystalline scattering particle 9, 10 may generate sharp scattering rings 9, 10 but the scattering rings are blurred when the size of the crystalline scattering particles is small or when the crystalline scattering particles have a certain size distribution.
Independently of the measurement principle selected in each case for examining the object 1 by means of elastically scattered X-ray radiation, during the examination a characteristic scattering behavior through the scattering particles 5, 6, which are applied with the aid of a contrast agent to the object 1 that is to be examined, is produced which allows regions in which the particles 5, 6 are located as a result of the contrast agent application to appear on the detector in a manner such that they can be distinguished from other regions or allows them to become visible in a tomographic reconstruction. When examining an organ or a vessel of a human or non-human living thing, the contrast agent may be applied both orally and parenterally. By way of example, the contrast agent may be injected using a needle. The specific form of application of the contrast agent comprising the crystalline scattering particles is not critical to the invention.
The contrast agent comprising scattering particles may be produced as a non-specific contrast agent, which means that the contrast agent does not have any means for the specific deposition of the particles on specific parts of organs or vessels. In this case, the particles may be embedded in a shielding cover in order for example to prevent dissolution of the crystalline particles following application of the contrast agent and prior to carrying out of the examination by means of elastically scattered X-rays. Particles which are harmful, in particular poisonous, to the object, for example an organ or a vessel, that is to be examined may also be applied with the aid of a shielding cover.
Fig. 1 shows the basic design of a measuring arrangement for examining by means of elastically scattered X-ray radiation. Any desired methods may be used here, for example using fan-like X-ray radiation or computer tomography technology, as described for example in the document DE 100 09 285.
Fig. 2 shows a schematic diagram of a computer tomography scanner comprising a gantry 100 which can rotate about an axis of rotation 140. For this purpose, the gantry 100 is driven by a motor 200. A radiation source S, for example an X-ray radiator, is fixed on the gantry 100. The beam used for the examination is determined by a first screen arrangement 310 and/or a second screen arrangement 320. If the first screen arrangement 310 is active, the beam fan is produced (shown in unbroken lines) which runs perpendicular to the axis of rotation 140 and in the direction thereof has small dimensions (for example 1 mm). If, on the other hand, only the second screen arrangement 320 is active in the beam path, then the beam cone 420 is produced (shown in dashed line) which in a plane perpendicular to the axis of rotation 140 has the same shape as the beam fan 410 but in the direction of the axis of rotation 140 has significantly larger dimensions.
A beam 410 or 420 passes through a cylindrical examination area 130 in which there may be for example a patient on a patient table (neither of which are shown in any more detail) or else a technical object. After it has passed through the examination area 130, the beam 410 or 420 impinges on a two-dimensional detector arrangement 160 that is fixed on the gantry 100, said detector arrangement comprising a large number of detector elements arranged in the form of a matrix. The detector elements are arranged in rows and columns. The detector columns run parallel to the axis of rotation; the detector rows may be located in planes perpendicular to the axis of rotation, for example in an arc of a circle about the radiation source S. The detector rows usually comprise significantly more detector elements, for example 1000, than the detector columns (for example 16).
An angle selection device 260 is mounted in front of the detector arrangement 160, which angle selection device comprises a collimator 260a and an angle selector 260b. The collimator 260a and the angle selector 260b may be designed to be combined with one another as one component. For the purpose of further explanation, Figs. 3 A and 3B show part of the measuring arrangement of Fig. 2 comprising radiation source S, examination area 130 and the angle selection device 260 in front and side views respectively. With the aid of the angle selector 260b, the screening effect can be used to select a predefined part of the beam 410 or 420 at a scattering angle α following scattering in the examination area 130. When using a contrast agent comprising scattering particles for which a characteristic scattering angle is known, a region in which the scattered radiation of the scattering particles is expected can be selected with the aid of the angle selection device 260, so that other fractions of the scattered radiation can be screened out and as a result not detected by the detector arrangement 160, which makes it easier to measure scattered radiation having a smaller amplitude with the aid of the measuring arrangement.
The angle selection device 260 may be moved into the region between the detector arrangement 160 and the examination area 130 if measurement is to be carried out contrast-agent-selectively in an optimized manner, wherein measurement in conjunction with the contrast agent comprising scattering particles would be possible even without using the angle selection device 260. If the intention is to use another type of measurement, the angle selection device 260 can be moved out of the region between the detector arrangement 160 and the examination area 130. For this purpose, the angle selection device 260 is integrated in the measuring arrangement in a manner such that it can be moved. The beams 410 and 420, the examination area 130, the angle selection device
260 and the detector arrangement 160 are adapted to one another. In a plane 140 perpendicular to the axis of rotation, the dimensions of this beam fan 410 or of the beam cone 420 are selected such that the examination area 130 is completely irradiated, and the length of the rows of the detector arrangement is dimensioned such that the beams 410 or 420 can be completely detected. The beam cone 420 is selected according to the length of the detector columns so that the beam cone can be completely detected by the detector arrangement 160. If only the beam fan 410 irradiates the examination area, it impinges on the central detector row(s). If the object concerned is a technical object rather than a patient, the object may be rotated during an examination, whereas the radiation source S and the detector arrangement 160 remain stationary. The object may also be moved parallel to the axis of rotation 140 by means of a motor. If the motors 500 and 200 are operating at the same time, this results in a helix-like scanning movement of the radiation source S and detector arrangement 160. The motors 500 and 200 are coupled to a control device 700.
Detected measured values are forwarded to an image-processing computer 600 by means of which various image processing operations can be carried out. Processed image data can be output via a monitor 610. Fig. 4 shows a schematic diagram of a microbubble 20 in cross section. The microbubble is formed by a number of phospholipids 21 in which a hydrophobic tail 21a is directed inward and a hydrophilic head 21b is directed outward. Such microbubbles 20 are used in conjunction with ultrasound analyses. Unlike in this known use, in which the microbubbles are filled with gas, a crystalline or non-crystalline particle 23 is embedded in the interior 22 of the microbubble 20. When a contrast agent comprising a large number of microbubbles formed like the microbubble 20 is applied, crystalline particles embedded in this way can be brought into the area that is to be examined. In such an examination method, it may be provided that, following the X-ray scattering measurement, the microbubble 20 is broken up using another technique, for example an ultrasound pulse, which results in the particle 23 being released and dissolving for example.
Alternatively, the contrast agent may be designed as a specific or functional contrast agent. In this case, the scattering particles are coupled to a chemical compound or component which are specific with regard to an interaction with parts of the object that is to be examined, for example specific vessels or parts of vessels. In this way, contrast agents can be produced which can be used in an organ- or tissue-specific manner.
One cost-effectively available contrast agent comprising crystalline scattering particles which is harmless to human and non-human organs/vessels may be produced on the basis of sodium chloride. Sodium chloride has no toxic effect at all and when used in conjunction with a microbubble 20, as shown in Fig. 4, can dissolve following the break-up of the microbubble 20, for example by means of ultrasound. The contrast effect of sodium chloride-based, crystalline scattering particles is in this case based on the characteristic scattering behavior in respect of X-ray radiation, as shown in Fig. 5. A pronounced maximum 30 makes it possible to make examination areas of the object that is to be examined visible compared to areas in which the sodium chloride-based scattering particles are not present.

Claims

1. A contrast agent for application to an examination area of an object (1) that is to be examined, in particular a patient, for an X-ray examination of the examination area by means of X-ray radiation, characterized in that the contrast agent comprises scattering particles.
2. A contrast agent as claimed in claim 1 , characterized in that the scattering particles comprise crystalline scattering particles.
3. A contrast agent as claimed in Claim 1 or 2, characterized in that the scattering particles comprise small angle scattering particles
4. A contrast agent as claimed in any of the claims 1 to 3, characterized in that the small angle scattering particles have a diameter of about < 100 nm.
5. A contrast agent as claimed in any of the claims 1 to 4, characterized in that the scattering particles are embedded in an interior (22) of a shield (20).
6. A contrast agent as claimed in any of the claims 1 to 5, characterized in that the shield (20) is formed by an envelope of phospholipids (21).
7. A contrast agent as claimed in any of the claims 1 to 6, characterized in that the crystalline scattering particles comprise sodium chloride particles.
8. A contrast agent as claimed in any of the claims 1 to 7, characterized in that the scattering particles are coupled to a function-specific compound.
9. A method of examining an object (1), in particular a patient, in which X-rays (3) are irradiated onto an examination area of the object (1), characterized in that a contrast agent according to any of the claims 1 to 8 is applied to the examination area and X-rays (4) which are elastically scattered at the scattering particles are detected in the examination area.
10 A method as claimed in claim 9, characterized in that after the object has been exarnined by means of elastically scattered X-ray radiation the shield (20) is broken up to release the crystalline scattering particles.
11. The use of a method as claimed in any one of claims 9 to 10 in conjunction with Coherent Scatter Computer Tomography (CSCT).
12. A method of producing a contrast agent for application to an examination area of an object (1) that is to be examined, in particular a patient, during X-ray examination of the examination area, characterized in that scattering particles are added for the elastic scattering of X-ray radiation.
13. A method as claimed in claim 12, characterized in that crystalline scattering particles are added.
14. A method as claimed in claim 12 or 13, characterized in that small angle scattering particles are added, at which small angle X-rays are formed upon irradiation of
X-rays (4).
15. An apparatus for examining an object, in particular a patient, in which a contrast agent according to any of the claims 1 to 8 can be applied to an examination area, said apparatus comprising a radiation source (S) for generating X-ray radiation that is to be irradiated onto the examination area (130) and a detector arrangement (160) for detecting X-ray radiation scattered in the examination area (130), characterized in that an angle selection device (260) for selecting X-ray radiation scattered at the scattering particles of the contrast agent is arranged in a region between the examination area (130) and the detector arrangement (160).
16. An apparatus as claimed in claim 15, characterized in that the angle selection device (260) comprises a collimator (260a) and an angle selector (260b).
17. An apparatus as claimed in claim 15 or 16, characterized in that the angle selection device (260) can be moved in and out in order to be placed in/removed from the region between the examination area (130) and the detector arrangement (160).
EP04731078A 2003-05-06 2004-05-04 Apparatus and method for examining an object by means of elastically scattered x-ray radiation and contrast agent Withdrawn EP1622649A2 (en)

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