MAGNETIC STRUCTURES

Abstract

The present invention relates to a contrast agent for magnetic resonance imaging, in which the contrast agent comprises: a plurality of magnetic nanoparticles, wherein each magnetic nanoparticle comprises a core covered at least in part with a layer of metal, wherein the core and the layer of metal are comprised of different materials; and one or more pharmaceutically acceptable carriers.

Claims

1. A contrast agent for magnetic resonance imaging, the contrast agent comprising: a plurality of magnetic nanoparticles, each of the plurality of magnetic nanoparticle comprising a core covered at least in part with a layer of metal, wherein the core and the layer of metal are comprised of different materials; and one or more pharmaceutically acceptable carriers.

2. The contrast agent of claim 1, further comprising a matrix, wherein the plurality of magnetic nanoparticles are embedded in the matrix, and wherein at least one of the matrix or the core comprises a ferromagnetic material.

3. The contrast agent of claim 2, wherein the core comprises a ferromagnetic material.

4. The contrast agent of claim 2, wherein the matrix comprises a transition metal or a rare earth metal.

5. The contrast agent of claim 4, wherein the transition metal is a ferromagnetic transition metal selected from Fe, Co, Ni, or a diamagnetic transition metal selected from Ag or Au.

6. The contrast agent of claim 4, wherein the rare earth metal is selected from Dy or Ho.

7. The contrast agent of claim 2, wherein the matrix and the layer of metal are comprised of the same material.

8. The contrast agent of claim 2, wherein the core comprises a transition metal, wherein the layer of metal comprises an antiferromagnetic material, and wherein the matrix material comprises a rare earth metal.

9. The contrast agent of claim 8, wherein the layer of metal comprises an antiferromagnetic transition metal and the core comprises a ferromagnetic transition metal.

10. The contrast agent of claim 9, wherein the ferromagnetic transition metal is selected from Fe, Co, or Ni.

11. The contrast agent of claim 9, wherein the antiferromagnetic transition metal is selected from Cr or Mn.

12. (canceled)

13. The contrast agent of claim 8, further comprising a second layer which covers the layer of metal at least in part, the second layer being formed from a rare earth metal.

14. The contrast agent of claim 2, wherein the core comprises a ferromagnetic transition metal, and the layer of metal comprises a ferromagnetic transition metal or a diamagnetic transition metal.

15. (canceled)

16. The contrast agent of claim 1, wherein each magnetic nanoparticle is of a diameter of no more than one of 10 nm.

17. (canceled)

18. (canceled)

19. (canceled)

20. (canceled)

21. (canceled)

22. (canceled)

23. (canceled)

24. (canceled)

25. (canceled)

26. (canceled)

27. A magnetic resonance imaging apparatus for simultaneously or subsequently diagnosing and treating an illness or condition of a patient to whom the contrast agent of claim 1 has been administered, the apparatus comprising: a source of a radio frequency pulse operable to expose a patient located within the apparatus to a radio frequency pulse; and a controller operable to vary the field amplitude of the radio frequency pulse.

28. The apparatus of claims 15, wherein the controller is operable to vary the field amplitude between a plurality of amplitudes.

29. The apparatus of claim 16, wherein the controller is operable to vary the field amplitude of the radio frequency pulse between a first low field amplitude and a second high field amplitude.

30. The apparatus of claim 17, wherein the first low field amplitude is sufficient to generate an image or series of images of a body part of a user, and wherein the second high field amplitude is sufficient to cause the magnetic nanoparticles to generate or emit heat.

31. (canceled)

32. (canceled)

33. (canceled)

34. A nanoparticle for use in diagnosis or therapy, comprising: a core covered at least in part with a layer of metal, in which the core and the layer of metal are comprised of different materials.

35. (canceled)

36. The nanoparticle according to claim 19, for use in the diagnosis or treatment of cancer, viruses, bacterial infections, inflammatory conditions, or any combination thereof.

37. (canceled)

38. (canceled)

39. (canceled)

40. (canceled)

Description

BRIEF DESCRIPTION OF DRAWINGS

[0122] The present invention will now be described by way of example only with reference to the following Figures, of which:

[0123] FIG. 1A illustrates the formation of a known magnetic structure;

[0124] FIG. 1B contains a graph of magnetic moment per atom as a function of the Fe volume fraction for magnetic structures having Fe nanoparticles in a Co matrix and Co nanoparticles in an Fe matrix;

[0125] FIG. 2A shows in block diagram form apparatus for forming a magnetic structure according to the present invention;

[0126] FIG. 2B shows apparatus for coating a core of a nanoparticle;

[0127] FIG. 3 illustrates the method of simultaneously or subsequently diagnosing and treating an illness or condition of a patient in a single operation of an apparatus according to one embodiment of the present invention;

[0128] FIG. 4 illustrates the relationship between the power dissipated in the tissue by a radio frequency pulse having a field frequency f and amplitude H.sub.0, conductivity of tissue (Sm-1) , and magnetic susceptibility of the tissue

DESCRIPTION OF EMBODIMENTS

[0129] Apparatus for and a process of forming a known magnetic structure comprising a matrix with embedded particles formed from a ferromagnetic transition metal have been described above with reference to FIGS. 1A and 1B.

[0130] According to one embodiment of the present invention, the contrast agent of the present invention comprises a plurality of magnetic nanoparticles. Each magnetic nanoparticle comprises a core covered at least in part by a layer of metal. The core is composed of ferromagnetic material. The layer of metal and the core are composed of different materials.

[0131] According to a further embodiment, the contrast agent comprises a plurality of magnetic nanoparticles. Each magnetic nanoparticle comprises a core covered at least in part with a layer of metal; and a matrix. The magnetic nanoparticles are embedded in the matrix. At least one of the matrix and the core is composed of ferromagnetic material. The core and the layer of metal are composed of different materials.

[0132] FIG. 2A shows in block diagram form apparatus 30 for producing the contrast agent of the present invention. The apparatus 30 comprises an MBE source 32, a thermal gas aggregation source 34, a first thermal evaporator 36, a second thermal evaporator 38 and a venturi 40. The apparatus 30 further comprises refrigeration apparatus 42 which is operative with liquid nitrogen in certain examples to refrigerate a substrate 44 and its environs. The thermal gas aggregation source 34 and the first and second thermal evaporators 36, 38 are operative in the same vacuum. As is described further below the MBE source 32 is operative to generate an atomic beam of matrix material and the thermal gas aggregation source 34 is operative at the same time to generate a beam of nanoparticles. The two beams are deposited simultaneously on the substrate 44 to form a magnetic structure in the form of a thin film matrix formed from deposited matrix material with nanoparticles distributed through and embedded in the matrix. The substrate 44 constitutes a component forming part or to form part of a product. According to one application example the substrate 44 is constituted by part of a roll of material in reel to reel coating apparatus.

[0133] According to another application example the substrate 44 forms part or will form part of the like of an electric motor or mobile telephone. According to a further application example the substrate 44 is constituted by one of several strategic locations on a critical magnetic component in electro-mechanical apparatus or the like. In use the magnetic structure is operative to amplify the magnetic field of the magnetic component.

[0134] The first and second thermal evaporators 36, 38 of FIG. 2A are of the same form and function. FIG. 2B provides a detailed view of the first and second thermal evaporators 50. The thermal evaporator 50 is of generally tubular form such that it defines a bore through which a beam of nanoparticles may pass. The thermal evaporator 50 comprises a tube of pure material 52 which is to be deposited as a layer on each of the nanoparticles passing through the thermal evaporator. The thermal evaporator 50 further comprises a tubular heater 54 which surrounds and is adjacent the tube of pure material 52. A water cooled heat shield 56 surrounds the outwardly directed surface of the tubular heater 54 and the end faces of the tubular heater 54 and the tube of pure material 52. In use the thermal evaporator 50 is operative to vaporise the pure material 52 with the material vapour being present in the bore of the thermal evaporator. A beam of uncoated nanoparticles 58 is received at one end of the bore of the thermal evaporator 50 and on passing through the material vapour in the bore the nanoparticles are coated with a layer of the material. The coated nanoparticles 60 then leave the other end of the bore of the thermal evaporator. In forms of the apparatus 30 nanoparticles are coated with only one layer of material. According to such forms the second thermal evaporator 38 of the apparatus of FIG. 2A is either absent or inoperative. In other forms of the apparatus 30 nanoparticles are coated with first and second layers of the same or different material. According to such forms the first thermal evaporator 36, 50 comprises a tube of a first material 52 and the second thermal evaporator 38, 50 comprises a tube of the first material or a second different material 52. In further forms of the apparatus 30 nanoparticles are coated with third and further layers of the same or different material. According to such further forms the apparatus 30 comprises thermal evaporators which correspond in number to the number of layers to be deposited on the nanoparticles with the plural thermal evaporators disposed in line such that the beam of nanoparticles can pass in turn through the bore of each of the thermal evaporators. A first example of a process of forming a magnetic structure on the substrate will now be described with reference to FIGS. 2A and 2B.

[0135] According to the first example only one layer of material is deposited on the nanoparticles. As stated above the second thermal evaporator 38 of FIG. 2A is therefore either absent or inoperative. The thermal gas aggregation source 34 is operative to generate a beam of Fe nanoparticles of diameters in the range of 1 nm to 5 nm. The diameter of the Fe nanoparticles is determined by controlling the power level and the gas pressure of the thermal gas aggregation source 34. The beam of Fe nanoparticles passes through the bore of the first thermal evaporator 36 which comprises a tube 52 of either Co or Ag. Each Fe nanoparticle is therefore coated with a layer of either Co or Ag to a thickness of between 1 and 10 atomic layers. The operative temperature of the first thermal evaporator 36 is determined by the material to be deposited. The operative temperature for Ag is about 800 C. As mentioned above the thickness of the layer depends on the velocity of the nanoparticles, which cannot be controlled, and the temperature. If it is desired to increase the thickness of the layer the operative temperature need only be increased slight because the vapour pressure is very sensitive to temperature. For example, to double the thickness of an Ag layer it is only necessary to increase the temperature by about 50 C. In such composite nanoparticles Fe constitutes the core of the nanoparticles. The MBE source 32 is operative at the same time as the thermal gas aggregation source 34 to generate an atomic beam of either Co or Ag such that the atomic beam is of the same material as the coating on the Fe nanoparticles. The atomic beam and the beam of nanoparticles are deposited simultaneously on the substrate 44 to form a magnetic structure comprising a matrix formed by the atomic beam in which nanoparticles are embedded. The layer of material on the Fe core decreases the likelihood of the Fe cores coming into contact with one another. By way of example and to provide a comparison with the performance of uncoated cores as described above with reference to FIG. 1B, if the Fe cores have a diameter of 5 nm and the coating is of a single atomic layer of 0.2 nm the volume fraction of the core can be increased to 66% without agglomeration compared to about 20% if uncoated Fe nanoparticles are used. A second example of process of forming a magnetic structure on the substrate will now be described with reference to FIGS. 2A and 2B.

[0136] According to the second example two layers of material are deposited in turn on the nanoparticles. As stated above the second thermal evaporator 38 of FIG. 2A is therefore operative. The thermal gas aggregation source 34 is operative to generate a beam of Co nanoparticles of diameters in the range of 1 nm to 5 nm. The diameter of the Co nanoparticles is determined by controlling the power level and the gas pressure of the thermal gas aggregation source 34. The beam of Co nanoparticles passes through the bore of the first thermal evaporator 36 which comprises a tube 52 of an anti-ferromagnetic material such as Cr or Mn. Each Co nanoparticle is therefore coated with a layer of either Cr or Mn to a thickness of between 1 and 10 atomic layers. Then the nanoparticles pass through the bore of the second thermal evaporator 38 which in one form comprises a tube 52 of a rare earth metal such as Ho or Dy. Each nanoparticle is therefore coated with a second layer of either Ho or Dy to a thickness of between 1 and 10 atomic layers. In another form the nanoparticles pass through the bore of the second thermal evaporator 38 which comprises a tube 52 of the same anti-ferromagnetic material as the first thermal evaporator 36. The operative temperatures of the first and second thermal evaporators 36, 38 are determined by the material to be deposited. FIG. 3 shows a perspective view of a Co core coated with a layer of each of Cr and a rare earth metal (i.e. Ho or Dy). FIG. 3 shows a section through a coated nanoparticle 70 with Co forming the core 72, Cr forming a layer immediately over the Co core and either Ho or Dy forming an exterior layer immediately over the Cr layer. FIG. 3 further shows a beam of nanoparticles 78 after deposition of the Cr layer and Ho or Dy layer. The MBE source 32 is operative at the same time as the thermal gas aggregation source 34 to generate an atomic beam of either Ho or Dy such that the atomic beam is of the same material as the outer coating on the Co nanoparticles. The atomic beam and the beam of nanoparticles are deposited simultaneously on the substrate 44 to form a magnetic structure comprising a matrix formed by the atomic beam in which nanoparticles are embedded.

[0137] A third example of process of forming a magnetic structure on the substrate will now be described with reference to FIGS. 2A and 2B. According to the third example only one layer of material is deposited on the nanoparticles. As stated above the second thermal evaporator 38 of FIG. 2A is therefore either absent or inoperative. The thermal gas aggregation source 34 is operative to generate a beam of Fe nanoparticles of diameters in the range of 1 nm to 5 nm. The beam of Fe nanoparticles passes through the bore of the first thermal evaporator 36 which comprises a tube 52 of either Au or Ag. Each Fe nanoparticle is therefore coated with a layer of either Au or Ag to a thickness of between 1 and 10 atomic layers. The operative temperature of the first thermal evaporator 36 is determined by the material to be deposited. A thermal evaporator is employed in the apparatus of FIG. 2 instead of the MBE source 32. The thermal evaporator is operative on a body of water to direct water vapour such that it impinges upon the substrate 44. The substrate is refrigerated by the refrigeration apparatus 42 whereby the impinging water vapour is deposited as ice on the substrate 44. The ice and the nanoparticles are deposited simultaneously on the substrate 44 to form a magnetic structure comprising an ice matrix in which nanoparticles are embedded. When the magnetic structure is formed the temperature is raised to room temperature to provide a liquid containing the nanoparticles. The liquid is then sprayed onto a desired surface to deposit the nanoparticles upon the surface.

[0138] With reference to the FIG. 3, the apparatus is a magnetic resonance imaging machine 1 comprising a central cavity dimensioned to receive at least one body part, and in some instances the entire body of a patient. The magnetic resonance imaging machine 1 comprises a source of a radio frequency pulse (not shown) operable to expose a patient located within the central cavity of the apparatus to a radio frequency pulse. The magnetic resonance imaging machine 1 comprises a controller (not shown) operable to vary the field amplitude of the radio frequency pulse.

[0139] A contrast agent of the present invention as described herein is administered, preferably intravenously, to the patient. It is however to be understood that the contrast agent may be administered by any suitable means. Furthermore, the contrast agent may become concentrated within the region of affected tissue by direct injection in the localised region, due to enhanced permeability retention effect of the affect tissue, and/or by application of an external magnetic field.

[0140] The controller is set to produce a first low field amplitude radio frequency pulse having a first low field frequency. The radio frequency pulse (low field amplitude and low frequency) causes the magnetic nanoparticles of the contrast agent to alter their magnetization alignment relative to the field. In response to the force bringing them back to their equilibrium orientation, the magnetic nanoparticles undergo a rotating motion (precession). These changes in magnetization alignment cause a changing magnetic flux, which yields a changing voltage in receiver coils to give the signal. The frequency at which the magnetic nanoparticles of the contrast agent resonate depends on the strength of the local magnetic field around the magnetic nanoparticles. By applying additional magnetic fields (gradients) that vary linearly over space, specific slices to be imaged can be selected, and an image is obtained by taking the 2-D Fourier transform of the spatial frequencies of the signal (a.k.a., k-space).

[0141] Application of the radio frequency pulse at the first low field amplitude and frequency generates a first image or series of images of a desired body portion or entire body of the patient. The location of diseased tissue, such as tumours, can be detected because the magnetic nanoparticles within the contrast agent adjacent or in different tissues return to their equilibrium state at different rates (i.e., they have different relaxation times). By changing the parameters on the scanner this effect is used to create contrast between different types of body tissue.

[0142] An illness or condition of the patient may therefore be diagnosed during application of the radiofrequency pulse at the first low field amplitude. Once the illness or condition has been diagnosed and accurately located, the controller is operated to generate a radio frequency pulse at a second high field amplitude and second high field frequency directed selectively towards the target area or areas of the body for treatment.

[0143] The second high field amplitude radio frequency pulse causes the magnetic nanoparticles to generate a hot spot of localised heat within the targeted region of the body. The radio frequency pulse is rastered, moved back and forth repeatedly across the target region, creating a localised heat spot which also moves back and forth repeatedly across the target region. The raster effect causes a selective localised heat treatment in the target area of illness, condition or disease. The apparatus of the present invention is therefore able to selectively target diseased body areas or tissue of a patient enabling selective treatment.

[0144] The apparatus of the present invention enables the identification of diseased tissue within a body of a patient followed by subsequent selective and localised treatment of the diseased tissue during a single operation of the apparatus.

[0145] Once the contrast agent has emitted heat selectively at the desired location of a user's body, the damaged tissue undergoes apoptosis with reduced damage to surrounding healthy tissue. Once the treatment has been completed, the controller may be further operated to once again generate a radio frequency pulse at the first low field amplitude and first frequency to generate a further series of images of the diseased body part or tissue to determine whether the treatment has been successful or whether further rounds of exposure to a radio frequency pulse at a second high field amplitude are required. The further images are assessed and if necessary further treatment is provided by once again operating the controller to generate a radio frequency pulse at the second high field amplitude and second frequency.

[0146] FIG. 4 demonstrates the relationship between the power dissipated by the heat spot in the localised tissue by the radio frequency pulse having a frequency f and amplitude H.sub.0.

x E=B/t

P=.sup.2(.sup.2.sub.0.sup.2/2)f.sup.2H.sub.0.sup.2r.sup.2

[0147] It can be seen from the equation and the Figure that the critical parameter is the product of the frequency (f) and the amplitude (H.sub.0) of the pulse. The safe zone for providing direct heating to tissue is indicated in the Figure.

[0148] The present invention provides an apparatus and a method for simultaneously or subsequently diagnosing and treating an illness or condition of a patient during a single operation of the apparatus. The present invention provides an apparatus and a method for accurately identifying, diagnosing and locating an illness or condition of a patient while simultaneously or subsequently accurately locating and treating the illness or condition of a patient. The present invention provides an apparatus and a method with improved selectivity for treating an illness or condition of a patient. The apparatus and method of the present invention therefore enables an illness or condition of a patient to be identified and treated, either simultaneously or subsequently, during a single operation of the apparatus and as such reduces the number of hospital appointments required by the patient and reduces the attendance time of a medical practitioner. As a result of the improved selectivity of the apparatus and method of the present invention for treating an illness or condition of a patient, the recovery time of a patient is significantly reduced.