FIELD OF THE INVENTION

The present invention relates to an apparatus and a method for influencing and/or detecting magnetic particles in a field of view. Further, the present invention relates to a computer program for implementing said method on a computer and for controlling such an apparatus. The present invention relates particularly to the field of Magnetic Particle

Imaging.

BACKGROUND OF THE INVENTION

Magnetic Particle Imaging (MPI) is an emerging medical imaging modality.

The first versions of MPI were two-dimensional in that they produced two-dimensional images. Newer versions are three-dimensional (3D). A four-dimensional image of a non- static object can be created by combining a temporal sequence of 3D images to a movie, provided the object does not significantly change during the data acquisition for a single 3D image.

MPI is a reconstructive imaging method, like Computed Tomography (CT) or Magnetic Resonance Imaging (MRI). Accordingly, an MP image of an object's volume of interest is generated in two steps. The first step, referred to as data acquisition, is performed using an MPI scanner. The MPI scanner has means to generate a static magnetic gradient field, called the "selection field", which has a (single or more) field- free point(s) (FFP(s)) or a field- free line (FFL) at the isocenter of the scanner (in the following reference is mostly made to the field- free point, which shall however include the option of using a field- free line instead). Moreover, this FFP (or the FFL; mentioning "FFP" in the following shall generally be understood as meaning FFP or FFL) is surrounded by a first sub-zone with a low magnetic field strength, which is in turn surrounded by a second sub-zone with a higher magnetic field strength. In addition, the scanner has means to generate a time-dependent, spatially nearly homogeneous magnetic field. Actually, this field is obtained by superposing a rapidly changing field with a small amplitude, called the "drive field", and a slowly varying field with a large amplitude, called the "focus field". By adding the time-dependent drive and focus fields to the static selection field, the FFP may be moved along a predetermined FFP trajectory throughout a "volume of scanning" surrounding the isocenter. The scanner also has an arrangement of one or more, e.g. three, receive coils and can record any voltages induced in these coils. For the data acquisition, the object to be imaged is placed in the scanner such that the object's volume of interest is enclosed by the scanner's field of view, which is a subset of the volume of scanning.

The object must contain magnetic nanoparticles or other magnetic non-linear materials; if the object is an animal or a patient, a tracer containing such particles is administered to the animal or patient prior to the scan. During the data acquisition, the MPI scanner moves the FFP along a deliberately chosen trajectory that traces out / covers the volume of scanning, or at least the field of view. The magnetic nanoparticles within the object experience a changing magnetic field and respond by changing their magnetization. The changing magnetization of the nanoparticles induces a time-dependent voltage in each of the receive coils. This voltage is sampled in a receiver associated with the receive coil. The samples output by the receivers are recorded and constitute the acquired data. The parameters that control the details of the data acquisition make up the "scan protocol".

In the second step of the image generation, referred to as image reconstruction, the image is computed, or reconstructed, from the data acquired in the first step. The image is a discrete 3D array of data that represents a sampled approximation to the position-dependent concentration of the magnetic nanoparticles in the field of view. The reconstruction is generally performed by a computer, which executes a suitable computer program. Computer and computer program realize a reconstruction algorithm. The reconstruction algorithm is based on a mathematical model of the data acquisition. As with all reconstructive imaging methods, this model can be formulated as an integral operator that acts on the acquired data; the reconstruction algorithm tries to undo, to the extent possible, the action of the model.

Such an MPI apparatus and method have the advantage that they can be used to examine arbitrary examination objects - e. g. human bodies - in a non-destructive manner and with a high spatial resolution, both close to the surface and remote from the surface of the examination object. Such an apparatus and method are generally known and have been first described in DE 101 51 778 Al and in Gleich, B. and Weizenecker, J. (2005),

"Tomographic imaging using the nonlinear response of magnetic particles" in Nature, vol. 435, pp. 1214-1217, in which also the reconstruction principle is generally described. The apparatus and method for magnetic particle imaging (MPI) described in that publication take advantage of the non-linear magnetization curve of small magnetic particles.

An MPI apparatus and method are based on a new physical principle (i.e. the principle referred to as MPI) that is different from other known conventional medical imaging techniques, as for example nuclear magnetic resonance (NMR). In particular, this MPI-principle, does, in contrast to NMR, not exploit the influence of the material on the magnetic resonance characteristics of protons, but rather directly detects the magnetization of the magnetic material by exploiting the non-linearity of the magnetization characteristic curve. In particular, the MPI-technique exploits the higher harmonics of the generated magnetic signals which result from the non-linearity of the magnetization characteristic curve in the area where the magnetization changes from the non-saturated to the saturated state.

Particularly for fast imaging, the conventionally available time-dependent, spatially nearly homogeneous magnetic fields, i.e. the drive field and the focus field, may not be sufficient. Thus, there is a need for improvement of the known apparatus and method to enable fast imaging.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide an apparatus and a method for influencing and/or detecting magnetic particles in a field of view that enable the influencing and/or detecting of magnetic particles in a fast way, in particular that enable fast imaging by use of such an apparatus and method.

In a first aspect of the present invention an apparatus for influencing and/or detecting magnetic particles in a field of view is presented, which apparatus comprises:

selection means comprising a selection field signal generator unit and selection field elements for generating a magnetic selection field having a pattern in space of its magnetic field strength such that a first sub-zone having a low magnetic field strength where the magnetization of the magnetic particles is not saturated and a second sub-zone having a higher magnetic field strength where the magnetization of the magnetic particles is saturated are formed in the field of view,

- drive and focus means comprising a drive field signal generator unit, a focus field signal generator unit, drive-focus-coils for changing the position in space of the two sub-zones in the field of view by means of a magnetic drive field so that the magnetization of the magnetic material changes locally and a magnetic focus field having a lower frequency than the magnetic drive field, and coupling coils coupled between said focus field signal generator unit and said drive-focus-coils,

wherein said drive-focus-coils each have at least two drive-focus-coil windings,

wherein said coupling coils each have at least two coupling coil windings, and

wherein one or more drive-focus-coil windings and one or more coupling coil windings are alternately electrically coupled in series to form a closed loop DC path coupled to the focus field signal generator unit.

In a further aspect of the present invention a corresponding method is presented.

In yet a further aspect of the present invention a computer program is presented comprising program code means for causing a computer to control an apparatus as according to the present invention to carry out the steps of the method proposed according to the present invention when said computer program is carried out on the computer.

Preferred embodiments of the invention are defined in the dependent claims. It shall be understood that the claimed method and the claimed computer program have similar and/or identical preferred embodiments as the claimed apparatus and as defined in the dependent claims.

As explained above, an MPI apparatus uses several static and dynamic magnetic fields. The gradient type field (selection field) is responsible for the spatial resolution, while drive field and ("normal") focus field move the field free point. It has been recognized that it is advantageous to have two different focus fields, i.e. the "normal"

(known) focus field and an additional (new) "fast" focus field, as fast imaging requires fast focus field changes. At the same time of realizing a short image acquisition time, it has been shown necessary to remain within certain safety limits of the patient. In principle a fast focus field can fulfill this. Due to physiological limitations, the focus field (i.e. the "normal" focus field plus the "fast" focus field) requires low amplitude high frequency components and high amplitude low frequency components (to cover the complete patient). Due to technical limitations (coil voltage and amplifier reactive power) it is not or at least not easily possible to generate the two focus fields using the same coils, and also the reactive power of the amplifier will be unacceptably high. But it has been found that it is possible to combine the fast focus field and the drive field by using "drive-focus-coils" and additional coupling coils to insulate the drive field from the fast focus field (also called near DC focus field, in comparison with the drive field), both being generated by the drive-focus-coils. The drive- focus-coils can thus generate a comparably small magnetic field, but with a high frequency. By use of a suitably intertwined trajectory of the field- free point (i.e. the first sub-zone) the aim of a fast imaging of a comparably large volume can be achieved.

One problem with the approach to use additional coupling coils is the very high current strength needed. To avoid self-resonance problems in the drive-focus-coils, the number of windings of the coupling coils has to be very low. This means, the currents to generate fast focus fields with high enough amplitude are in the order of several thousand Ampere. This is not very feasible in terms of e.g. used cable diameters.

Hence, it is further proposed according to the present invention to wind the respective drive-focus-coils and the respective coupling coils using several (preferably parallel) windings (also called strands) or an electrically equivalent set-up. The strands are connected in such a way that a common closed loop is formed with the current always changing between a strand in the drive-focus-coil and an associated coupling coil.

In an embodiment said closed loop DC path starts and ends with one or more coupling coil windings, preferably with the same number or an integer multiple of coupling coil windings. This provides that the current for generating the (HF) drive field and the current for generating the (LF) fast focus field are equally split over the conductors which minimizes the losses. Preferably, the arrangement of the coupling coil winding and the drive-focus-coil windings along the closed loop DC path is symmetrical. This is the easiest way to make sure that the current for generating the (HF) drive field and the current for generating the (LF) fast focus field are equally split over the conductors which minimizes the losses.

Preferably, the direction of the current for generating the (HF) drive field and the direction of the current for generating the (LF) fast focus field in each strand are equal at one point in time, the drive- focus coil thus generates the two fields with equal and maximum efficiency. A (near) DC source is connected in series to the closed loop DC path preferably at a symmetric position in the DC coupling coil.

In another embodiment a DC blocking capacitor is coupled to each coupling point between a coupling coil winding and a drive-focus-coil winding, i.e. at both ends of each drive-focus-coil winding a DC blocking capacitor is placed. Both the drive-field coils and the coupling coils are thus connected to the drive field signal generator unit with the drive-field-coil strands being individually insulated by capacitors at both ends. This prevents that DC current provided by the focus field signal generator unit flows into the drive field signal generator unit.

In an embodiment said coupling coil and/or said drive-focus coil windings are mechanically arranged in parallel. This provides a space-saving arrangement and an inductive coupling of the adjacent coupling coil windings and/or drive-focus coil windings, thus forming a common coil.

Preferably, the coupling coil windings of a coupling coil are arranged such that the current direction of a DC current provided by the focus field signal generator unit is identical in all coupling coil windings. Hence, all coupling coils commonly generate an almost stationary magnetic field.

The drive-focus-coil windings of a drive-focus-coil are preferably arranged such that the current direction of a DC current provided by the focus field signal generator unit is identical in all drive-focus-coil windings. Hence, all drive-focus-coils commonly generate the desired magnetic field.

In another embodiment the apparatus further comprises a coupling network, in particular an inductive coupling network, between the drive field signal generator unit and the drive-focus-coils. This provides for a good coupling of the signals between the drive field signal generator unit and the drive-focus-coils.

Still further, the apparatus may comprise receiving means, in particular a receiving coil, and a signal receiving unit for receiving signals detected by said receiving means and processing means for processing the received signals. This enables e.g. the reconstruction of images from the signals detected by the receiving means as is generally known in the field of MPI.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other aspects of the invention will be apparent from and elucidated with reference to the embodiment(s) described hereinafter. In the following drawings

Fig. 1 shows a first embodiment of an MPI apparatus,

Fig. 2 shows an example of the selection field pattern produced by an apparatus as shown in Fig. 1,

Fig. 3 shows a second embodiment of an MPI apparatus,

Fig. 4 shows a third and a fourth embodiment of an MPI apparatus,

Fig. 5 shows a block diagram of an MPI apparatus according to the present invention,

Fig. 6 shows an embodiment of a circuit diagram of the drive and focus means according to the present invention, and

Fig. 7 shows an embodiment of the mechanical arrangement of the drive and focus means according to the present invention.

DETAILED DESCRIPTION OF THE INVENTION

Before the details of the present invention shall be explained, basics of magnetic particle imaging shall be explained in detail with reference to Figs. 1 to 4. In particular, four embodiments of an MPI scanner for medical diagnostics will be described. An informal description of the data acquisition will also be given. The similarities and differences between the different embodiments will be pointed out. Generally, the present invention can be used in all these different embodiments of an MPI apparatus.

The first embodiment 10 of an MPI scanner shown in Fig. 1 has three pairs 12, 14, 16 of coaxial parallel circular coils, these coil pairs being arranged as illustrated in Fig. 1. These coil pairs 12, 14, 16 serve to generate the selection field as well as the drive and focus fields. The axes 18, 20, 22 of the three coil pairs 12, 14, 16 are mutually orthogonal and meet in a single point, designated the isocenter 24 of the MPI scanner 10. In addition, these axes 18, 20, 22 serve as the axes of a 3D Cartesian x-y-z coordinate system attached to the isocenter 24. The vertical axis 20 is nominated the y-axis, so that the x- and z-axes are horizontal. The coil pairs 12, 14, 16 are named after their axes. For example, the y-coil pair 14 is formed by the coils at the top and the bottom of the scanner. Moreover, the coil with the positive (negative) y-coordinate is called the y -coil (y -coil), and similarly for the remaining coils. When more convenient, the coordinate axes and the coils shall be labelled with x _{l s} x ₂ , and x ₃ , rather than with x, y, and z.

The scanner 10 can be set to direct a predetermined, time-dependent electric current through each of these coils 12, 14, 16, and in either direction. If the current flows clockwise around a coil when seen along this coil's axis, it will be taken as positive, otherwise as negative. To generate the static selection field, a constant positive current I ^s is made to flow through the z ⁺ -coil, and the current -I ^s is made to flow through the z -coil. The z-coil pair 16 then acts as an anti-parallel circular coil pair.

It should be noted here that the arrangement of the axes and the nomenclature given to the axes in this embodiment is just an example and might also be different in other embodiments. For instance, in practical embodiments the vertical axis is often considered as the z-axis rather than the y-axis as in the present embodiment. This, however, does not generally change the function and operation of the device and the effect of the present invention.

The magnetic selection field, which is generally a magnetic gradient field, is represented in Fig. 2 by the field lines 50. It has a substantially constant gradient in the direction of the (e.g. horizontal) z-axis 22 of the z-coil pair 16 generating the selection field and reaches the value zero in the isocenter 24 on this axis 22. Starting from this field- free point (not individually shown in Fig. 2), the field strength of the magnetic selection field 50 increases in all three spatial directions as the distance increases from the field-free point. In a first sub-zone or region 52 which is denoted by a dashed line around the isocenter 24 the field strength is so small that the magnetization of particles present in that first sub-zone 52 is not saturated, whereas the magnetization of particles present in a second sub-zone 54 (outside the region 52) is in a state of saturation. In the second sub-zone 54 (i.e. in the residual part of the scanner's field of view 28 outside of the first sub-zone 52) the magnetic field strength of the selection field is sufficiently strong to keep the magnetic particles in a state of saturation.

By changing the position of the two sub-zones 52, 54 (including the field- free point) within the field of view 28 the (overall) magnetization in the field of view 28 changes. By determining the magnetization in the field of view 28 or physical parameters influenced by the magnetization, information about the spatial distribution of the magnetic particles in the field of view 28 can be obtained. In order to change the relative spatial position of the two sub-zones 52, 54 (including the field-free point) in the field of view 28, further magnetic fields, i.e. the magnetic drive field, and, if applicable, the magnetic focus field, are superposed to the selection field 50.

To generate the drive field, a time dependent current I°i is made to flow through both x-coils 12, a time dependent current I ^D ₂ through both y-coils 14, and a time dependent current I°3 through both z-coils 16. Thus, each of the three coil pairs acts as a parallel circular coil pair. Similarly, to generate the focus field, a time dependent current I ^F i is made to flow through both x-coils 12, a current I ^F ₂ through both y-coils 14, and a current I ^F 3 through both z-coils 16.

It should be noted that the z-coil pair 16 is special: It generates not only its share of the drive and focus fields, but also the selection field (of course, in other

embodiments, separate coils may be provided). The current flowing through the z ^± -coil is I°3 + I ^F ₃ ± I ^s . The current flowing through the remaining two coil pairs 12, 14 is I° _k + I ^F _k , k = 1, 2. Because of their geometry and symmetry, the three coil pairs 12, 14, 16 are well decoupled. This is wanted.

Being generated by an anti-parallel circular coil pair, the selection field is rotationally symmetric about the z-axis, and its z-component is nearly linear in z and independent of x and y in a sizeable volume around the isocenter 24. In particular, the selection field has a single field- free point (FFP) at the isocenter. In contrast, the

contributions to the drive and focus fields, which are generated by parallel circular coil pairs, are spatially nearly homogeneous in a sizeable volume around the isocenter 24 and parallel to the axis of the respective coil pair. The drive and focus fields jointly generated by all three parallel circular coil pairs are spatially nearly homogeneous and can be given any direction and strength, up to some maximum strength. The drive and focus fields are also time- dependent. The difference between the focus field and the drive field is that the focus field varies slowly in time and may have a large amplitude, while the drive field varies rapidly and has a small amplitude. There are physical and biomedical reasons to treat these fields differently. A rapidly varying field with a large amplitude would be difficult to generate and potentially hazardous to a patient.

In a practical embodiment the FFP can be considered as a mathematical point, at which the magnetic field is assumed to be zero. The magnetic field strength increases with increasing distance from the FFP, wherein the increase rate might be different for different directions (depending e.g. on the particular layout of the device). As long as the magnetic field strength is below the field strength required for bringing magnetic particles into the state of saturation, the particle actively contributes to the signal generation of the signal measured by the device; otherwise, the particles are saturated and do not generate any signal.

The embodiment 10 of the MPI scanner has at least one further pair, preferably three further pairs, of parallel circular coils, again oriented along the x-, y-, and z- axes. These coil pairs, which are not shown in Fig. 1, serve as receive coils. As with the coil pairs 12, 14, 16 for the drive and focus fields, the magnetic field generated by a constant current flowing through one of these receive coil pairs is spatially nearly homogeneous within the field of view and parallel to the axis of the respective coil pair. The receive coils are supposed to be well decoupled. The time-dependent voltage induced in a receive coil is amplified and sampled by a receiver attached to this coil. More precisely, to cope with the enormous dynamic range of this signal, the receiver samples the difference between the received signal and a reference signal. The transfer function of the receiver is non-zero from zero Hertz ("DC") up to the frequency where the expected signal level drops below the noise level. Alternatively, the MPI scanner has no dedicated receive coils. Instead the drive field transmit coils may be used as receive coils as is the case according one embodiment according to the present invention using combined drive-receiving coils.

The embodiment 10 of the MPI scanner shown in Fig. 1 has a cylindrical bore 26 along the z-axis 22, i.e. along the axis of the selection field. All coils are placed outside this bore 26. For the data acquisition, the patient (or object) to be imaged is placed in the bore 26 such that the patient's volume of interest - that volume of the patient (or object) that shall be imaged - is enclosed by the scanner's field of view 28 - that volume of the scanner whose contents the scanner can image. The patient (or object) is, for instance, placed on a patient table. The field of view 28 is a geometrically simple, isocentric volume in the interior of the bore 26, such as a cube, a ball, a cylinder or an arbitrary shape. A cubical field of view 28 is illustrated in Fig. 1.

The size of the first sub-zone 52 is dependent on the strength of the gradient of the magnetic selection field and on the field strength of the magnetic field required for saturation, which in turn depends on the magnetic particles. For a sufficient saturation of typical magnetic particles at a magnetic field strength of 80 A/m and a gradient (in a given space direction) of the field strength of the magnetic selection field amounting to 50xl0 ³ A/m ² , the first sub-zone 52 in which the magnetization of the particles is not saturated has dimensions of about 1 mm (in the given space direction).

The patient's volume of interest is supposed to contain magnetic nanoparticles. Prior to the diagnostic imaging of, for example, a tumor, the magnetic particles are brought to the volume of interest, e.g. by means of a liquid comprising the magnetic particles which is injected into the body of the patient (object) or otherwise administered, e.g. orally, to the patient.

Generally, various ways for bringing the magnetic particles into the field of view exist. In particular, in case of a patient into whose body the magnetic particles are to be introduced, the magnetic particles can be administered by use of surgical and non-surgical methods, and there are both methods which require an expert (like a medical practitioner) and methods which do not require an expert, e.g. can be carried out by laypersons or persons of ordinary skill or the patient himself / herself. Among the surgical methods there are potentially non-risky and/or safe routine interventions, e.g. involving an invasive step like an injection of a tracer into a blood vessel (if such an injection is at all to be considered as a surgical method), i.e. interventions which do not require considerable professional medical expertise to be carried out and which do not involve serious health risks. Further, nonsurgical methods like swallowing or inhalation can be applied.

Generally, the magnetic particles are pre-delivered or pre-administered before the actual steps of data acquisition are carried out. In embodiments, it is, however, also possible that further magnetic particles are delivered / administered into the field of view.

An embodiment of magnetic particles comprises, for example, a spherical substrate, for example, of glass which is provided with a soft-magnetic layer which has a thickness of, for example, 5 nm and consists, for example, of an iron-nickel alloy (for example, Permalloy). This layer may be covered, for example, by means of a coating layer which protects the particle against chemically and/or physically aggressive environments, e.g. acids. The magnetic field strength of the magnetic selection field 50 required for the saturation of the magnetization of such particles is dependent on various parameters, e.g. the diameter of the particles, the used magnetic material for the magnetic layer and other parameters.

In the case of e.g. a diameter of 10 μιη with such magnetic particles, a magnetic field of approximately 800 A/m (corresponding approximately to a flux density of 1 mT) is then required, whereas in the case of a diameter of 100 μιη a magnetic field of 80 A/m suffices. Even smaller values are obtained when a coating of a material having a lower saturation magnetization is chosen or when the thickness of the layer is reduced.

In practice, magnetic particles commercially available under the trade name Resovist (or similar magnetic particles) are often used, which have a core of magnetic material or are formed as a massive sphere and which have a diameter in the range of nanometers, e.g. 40 or 60 nm.

For further details of the generally usable magnetic particles and particle compositions, the corresponding parts of EP 1224542, WO 2004/091386, WO 2004/091390, WO 2004/091394, WO 2004/091395, WO 2004/091396, WO 2004/091397, WO

2004/091398, WO 2004/091408 are herewith referred to, which are herein incorporated by reference. In these documents more details of the MPI method in general can be found as well.

During the data acquisition, the x-, y-, and z-coil pairs 12, 14, 16 generate a position- and time-dependent magnetic field, the applied field. This is achieved by directing suitable currents through the field generating coils. In effect, the drive and focus fields push the selection field around such that the FFP moves along a preselected FFP trajectory that traces out the volume of scanning - a superset of the field of view. The applied field orientates the magnetic nanoparticles in the patient. As the applied field changes, the resulting magnetization changes too, though it responds nonlinearly to the applied field. The sum of the changing applied field and the changing magnetization induces a time-dependent voltage V _k across the terminals of the receive coil pair along the Xk-axis. The associated receiver converts this voltage to a signal S _k , which it processes further.

Like the first embodiment 10 shown in Fig. 1 , the second embodiment 30 of the MPI scanner shown in Fig. 3 has three circular and mutually orthogonal coil pairs 32, 34, 36, but these coil pairs 32, 34, 36 generate the selection field and the focus field only. The z- coils 36, which again generate the selection field, are filled with ferromagnetic material 37. The z-axis 42 of this embodiment 30 is oriented vertically, while the x- and y-axes 38, 40 are oriented horizontally. The bore 46 of the scanner is parallel to the x-axis 38 and, thus, perpendicular to the axis 42 of the selection field. The drive field is generated by a solenoid (not shown) along the x-axis 38 and by pairs of saddle coils (not shown) along the two remaining axes 40, 42. These coils are wound around a tube which forms the bore. The drive field coils also serve as receive coils.

To give a few typical parameters of such an embodiment: The z-gradient of the selection field, G, has a strength of G/μο = 2.5 T/m, where μο is the vacuum permeability. The temporal frequency spectrum of the drive field is concentrated in a narrow band around 25 kHz (up to approximately 250 kHz). The useful frequency spectrum of the received signals lies between 50 kHz and 1 MHz (eventually up to approximately 15 MHz). The bore has a diameter of 120 mm. The biggest cube 28 that fits into the bore 46 has an edge length

Since the construction of field generating coils is generally known in the art, e.g. from the field of magnetic resonance imaging, this subject need not be further elaborated herein.

In an alternative embodiment for the generation of the selection field, permanent magnets (not shown) can be used. In the space between two poles of such

(opposing) permanent magnets (not shown) there is formed a magnetic field which is similar to that shown in Fig. 2, that is, when the opposing poles have the same polarity. In another alternative embodiment, the selection field can be generated by a mixture of at least one permanent magnet and at least one coil.

Fig. 4 shows two embodiments of the general outer layout of an MPI apparatus 200, 300. Fig. 4A shows an embodiment of the proposed MPI apparatus 200 comprising two selection-and- focus field coil units 210, 220 which are basically identical and arranged on opposite sides of the examination area 230 formed between them. Further, a drive field coil unit 240 is arranged between the selection-and- focus field coil units 210, 220, which are placed around the area of interest of the patient (not shown). The selection-and- focus field coil units 210, 220 comprise several selection-and- focus field coils for generating a combined magnetic field representing the above-explained magnetic selection field and magnetic focus field. In particular, each selection-and- focus field coil unit 210, 220 comprises a, preferably identical, set of selection-and-focus field coils. Details of said selection-and-focus field coils will be explained below.

The drive field coil unit 240 comprises a number of drive field coils for generating a magnetic drive field. These drive field coils may comprise several pairs of drive field coils, in particular one pair of drive field coils for generating a magnetic field in each of the three directions in space. In an embodiment the drive field coil unit 240 comprises two pairs of saddle coils for two different directions in space and one solenoid coil for generating a magnetic field in the longitudinal axis of the patient.

The selection-and-focus field coil units 210, 220 are generally mounted to a holding unit (not shown) or the wall of room. Preferably, in case the selection-and-focus field coil units 210, 220 comprise pole shoes for carrying the respective coils, the holding unit does not only mechanically hold the selection-and-focus field coil unit 210, 220 but also provides a path for the magnetic flux that connects the pole shoes of the two selection-and- focus field coil units 210, 220.

As shown in Fig. 4a, the two selection-and-focus field coil units 210, 220 each include a shielding layer 211, 221 for shielding the selection-and-focus field coils from magnetic fields generated by the drive field coils of the drive field coil unit 240.

In the embodiment of the MPI apparatus 201 shown in Fig. 4B only a single selection-and-focus field coil unit 220 is provided as well as the drive field coil unit 240. Generally, a single selection-and-focus field coil unit is sufficient for generating the required combined magnetic selection and focus field. Said single selection-and-focus field coil unit 220 may thus be integrated into a (not shown) patient table on which a patient is placed for the examination. Preferably, the drive field coils of the drive field coil unit 240 may be arranged around the patient's body already in advance, e.g. as flexible coil elements. In another implementation, the drive field coil unit 240 can be opened, e.g. separable into two subunits 241, 242 as indicated by the separation lines 243, 244 shown in Fig. 4b in axial direction, so that the patient can be placed in between and the drive field coil subunits 241, 242 can then be coupled together.

In still further embodiments of the MPI apparatus, even more selection-and- focus field coil units may be provided which are preferably arranged according to a uniform distribution around the examination area 230. However, the more selection-and-focus field coil units are used, the more will the accessibility of the examination area for placing a patient therein and for accessing the patient itself during an examination by medical assistance or doctors be limited.

Fig. 5 shows a general block diagram of an MPI apparatus 100 according to the present invention. The general principles of magnetic particle imaging explained above are valid and applicable to this embodiment as well, unless otherwise specified.

The embodiment of the apparatus 100 shown in Fig. 5 comprises various coils for generating the desired magnetic fields. First, the coils and their functions in MPI shall be explained. For generating the combined magnetic selection-and- focus field, selection- and- focus means 110 are provided. The magnetic selection-and- focus field has a pattern in space of its magnetic field strength such that the first sub-zone (52 in Fig. 2) having a low magnetic field strength where the magnetization of the magnetic particles is not saturated and a second sub-zone (54 in Fig. 4) having a higher magnetic field strength where the magnetization of the magnetic particles is saturated are formed in the field of view 28, which is a small part of the examination area 230, which is conventionally achieved by use of the magnetic selection field. Further, by use of the magnetic selection-and- focus field the position in space of the field of view 28 within the examination area 230 can be changed, as conventionally done by use of the magnetic focus field.

The selection-and- focus means 110 comprises at least one set of selection-and- focus field coils 114 and a selection-and- focus field generator unit 112 for generating selection-and- focus field currents to be provided to said at least one set of selection-and- focus field coils 114 (representing one of the selection-and- focus field coil units 210, 220 shown in Figs. 4A, 4B) for controlling the generation of said magnetic selection-and- focus field. Preferably, a separate generator subunit is provided for each coil element (or each pair of coil elements) of the at least one set of selection-and-focus field coils 114. Said selection- and- focus field generator unit 112 comprises a controllable current source (generally including an amplifier) and a filter unit which provide the respective coil element with the field current to individually set the gradient strength and field strength of the contribution of each coil to the magnetic selection-and-focus field. It shall be noted that the filter unit 114 can also be omitted. Further, separate focus and selection means are provided in other embodiments.

For generating the magnetic drive field and an additional "fast" magnetic focus field the apparatus 100 further comprises drive and focus means 120 comprising a drive field signal generator unit 122, a focus field signal generator unit 132 and a set of drive- focus-coils 124 (representing the drive coil unit 240 shown in Figs. 4A, 4B, but additionally providing the function of generating an additional fast focus field) for changing the position in space and/or size of the two sub-zones in the field of view by means of a magnetic drive field and a fast magnetic focus field so that the magnetization of the magnetic material changes locally. The drive-focus-coils 124 preferably comprise two pairs 125, 126 of oppositely arranged saddle coils and one solenoid coil 127. Other implementations, e.g. three pairs of coil elements, are also possible. The fast focus field has a larger dB/dt but a smaller amplitude than the drive field, e.g. by a factor in the range of 10 (e.g. by a factor between 5 and 50).

In an exemplary practical implementation the fast focus field may use changes of the field strength of up to 20 T/s and an amplitude in the range of 20 mT. For a complete cycle approx. 4 ms are required, i.e. at maximum 250 Hz (with full amplitude). With smaller amplitudes the frequency will be higher proportionally. Much smaller amplitudes than 1 mT will most likely not be used, i.e. the frequency will likely be smaller than 5 kHz. There might generally not be a lower limit for the frequency, unless there are other advantages such as a better amplifier (if available in the future).

The drive and focus means 120 further comprises a set of coupling coils 134 comprising one or more, in this embodiment three, coupling coils 135, 136, 137 that are electrically coupled between the focus field signal generator unit 132 and the set of drive- focus-coils 124 to insulate the drive field from the fast focus field. Preferably, one coupling coil is provided per drive-focus-coil. An embodiment of the particular arrangement and construction of the drive-focus-coils 124 and the coupling coils 134 will be explained in more detail below.

The drive field signal generator unit 122 preferably comprises a separate drive field signal generation subunit for each coil element (or at least each pair of coil elements) of said set of drive-focus-coils 124. Said drive field signal generator unit 122 preferably comprises a drive field current source (preferably including a power amplifier) and a filter unit for providing a time-dependent drive field current to the respective drive-focus-coil.

The focus field signal generator unit 132 preferably comprises a separate focus field signal generation subunit for each coil element (or at least each pair of coil elements) of said set of drive-focus-coils 124. Said focus field signal generator unit 132 preferably comprises a focus field current source (preferably including a power amplifier) and a filter unit for providing a time-dependent focus field current to the respective drive-focus-coil.

This focus field signal generator unit 132 provides a near DC current to the drive-focus-coils to generate a fast focus field, which is a homogeneous magnetic field having a much lower frequency than the drive field.

The selection-and- focus field signal generator unit 112, the drive field signal generator unit 122 and the focus field signal generator unit 132 are preferably controlled by a control unit 150, which preferably controls the selection-and- focus field signal generator unit 112 such that the sum of the field strengths and the sum of the gradient strengths of all spatial points of the selection field is set at a predefined level. For this purpose the control unit 150 can also be provided with control instructions by a user according to the desired application of the MPI apparatus, which, however, is preferably omitted according to the present invention.

For using the MPI apparatus 100 for determining the spatial distribution of the magnetic particles in the examination area (or a region of interest in the examination area), particularly to obtain images of said region of interest, signal detection receiving means 148, in particular a receiving coil, and a signal receiving unit 140, which receives signals detected by said receiving means, are provided. One to three separate receiving coils 148 are provided in an MPI apparatus as receiving means.

According to other embodiments of the present invention, however, one to three of said drive-focus-coils 124 (or drive-focus-coil pairs) act (simultaneously or alternately) as receiving coils for receiving detection signals, wherein these drive-focus-coils are then called "drive- focus-receiving coils" herein. The generation of magnetic drive fields and fast focus fields and the detection of detection signals may then be performed

simultaneously or alternately. Preferably, all three drive- focus-receiving coils (or coil pairs) may then act as receiving coils.

One to three receiving units 140 - one per receiving coil (or coil pair) - are provided in practice, but more than three receiving coils and receiving units can be also used, in which case the acquired detection signals are not 3 -dimensional but K-dimensional, with K being the number of receiving coils.

Said signal receiving unit 140 comprises a filter unit 142 (also called Rx filter) for filtering the received detection signals. The aim of this filtering is to separate measured values, which are caused by the magnetization in the examination area which is influenced by the change in position of the two part-regions (52, 54), from other, interfering signals (in particular crosstalk of the fundamental frequency). To this end, the filter unit 142 may be designed for example such that signals which have temporal frequencies that are smaller than the temporal frequencies with which the drive-focus-coil(s) is (are) operated, or smaller than twice these temporal frequencies, do not pass the filter unit 142. The signals are then transmitted via an amplifier unit 144 (also called LNA, Low-Noise- Amplifier) to an analog/digital converter 146 (ADC).

The digitized signals produced by the analog/digital converter 146 are fed to an image processing unit (also called reconstruction means) 152, which reconstructs the spatial distribution of the magnetic particles from these signals and the respective position which the first part-region 52 of the first magnetic field in the examination area assumed during receipt of the respective signal and which the image processing unit 152 obtains from the control unit 150. The reconstructed spatial distribution of the magnetic particles is finally transmitted via the control means 150 to a computer 154, which displays it on a monitor 156. Thus, an image can be displayed showing the distribution of magnetic particles in the field of view of the examination area.

In other applications of the MPI apparatus 100, e.g. for influencing the magnetic particles (for instance for a hyperthermia treatment) or for moving the magnetic particles (e.g. attached to a catheter for moving the catheter or attached to a medicament for moving the medicament to a certain location) the receiving means may also be omitted or simply not used.

Further, an input unit 158 may optionally be provided, for example a keyboard. A user may therefore be able to set the desired direction of the highest resolution and in turn receives the respective image of the region of action on the monitor 156. If the critical direction, in which the highest resolution is needed, deviates from the direction set first by the user, the user can still vary the direction manually in order to produce a further image with an improved imaging resolution. This resolution improvement process can also be operated automatically by the control unit 150 and the computer 154. The control unit 150 in this embodiment sets the gradient field in a first direction which is automatically estimated or set as start value by the user. The direction of the gradient field is then varied stepwise until the resolution of the thereby received images, which are compared by the computer 154, is maximal, respectively not improved anymore. The most critical direction can therefore be found respectively adapted automatically in order to receive the highest possible resolution.

Fig. 6 shows an embodiment of a circuit diagram of the drive and focus means 120 according to the present invention. In particular, the electrical arrangement of one drive- focus-coil 125 comprising three drive-focus-coil windings 125a, 125b, 125c in this embodiment and one coupling coil 135 comprising four coupling coil windings 135a, 135b, 135c, 135d (with the first and last windings 135a, 135d being only half windings) is shown. Following the electrical DC path from the focus field signal generator unit 132 a (near) DC current provided by it subsequently flows through the first coupling coil winding 135a, the first drive-focus-coil winding 125a, the second coupling coil winding 135b, the second drive- focus-coil winding 125b, the third coupling coil winding 135c, the third drive-focus-coil winding 125c and the fourth coupling coil winding 135d before it enters the focus field signal generator unit 132. Hence, this DC path forms a closed loop. DC blocking capacitors 161, 162, 163, 164, 165, 166 are coupled to each coupling point 171, 172, 173, 174, 175, 176 between a coupling coil winding and a drive-focus-coil winding, i.e. at both ends of each drive-focus-coil winding 125a, 125b, 125c a DC blocking capacitor is provided to block the DC current from flowing in the direction of the drive field signal generator unit 122. Further DC blocking capacitors 190, 191 are preferably coupled to the terminals of the focus field signal generator unit 132 for filtering noise or other disturbances.

In shall be noted that the coupling coil windings 135a-d are coupled to the output of the focus field signal generator unit 132 in series to provide a high impedance for all frequencies (not only the drive field frequency, but also their harmonics and frequency conversion products. If the focus field signal generator unit 132 were directly coupled to the drive-focus-coil windings 125a-c, it would not be possible to apply the high RF frequency to the drive field coil to drive the drive field current since the amplifier has a lower impedance at the output so that the complete current would flow through it. This is prevented by the coupling coil windings 135a-d.

The drive field signal generator unit 122 is preferably coupled to the drive- focus-coil 125 by a coupling network 180. In this exemplary embodiment an inductive coupling by use of inductive coupling elements 181, 182 is provided followed by a capacitive bridge of four bridge capacitors 184, 185, 186, 187. The capacitive bridge further includes a low noise amplifier (LNA) 183 arranged as diagonal element in the bridge. These elements enable the receiving of detection signals simultaneously to the generation of drive and focus fields. The LNA 183 amplifies the received detection signal. The coil 125 converts the current into a voltage which is amplified by the LNA 183. The bridge capacitors 184-187 lead to a resonance on the drive field frequency and to a smaller voltage at the LNA 183so that it is not saturated by the large drive field amplitude.

Fig. 7 shows an embodiment of the mechanical arrangement of the drive and focus means 120 according to the present invention. Particularly the arrangement of the three drive-focus-coil windings 125a, 125b, 125c and the four coupling coil windings 135a, 135b, 135c, 135d is shown. The arrow indicates the direction of a DC current provided by the focus field signal generator unit 132.

All the drive-focus-coil windings 125a, 125b, 125c are preferably mechanically arranged in parallel, and the DC current direction through all the drive-focus- coil windings 125a, 125b, 125c is identical as indicated by the arrows. Further, all the coupling coil windings 135a, 135b, 135c, 135d are preferably mechanically arranged in parallel, and the DC current direction through all the coupling coil windings 135a, 135b, 135c, 135d is identical, he arrangement of the coupling coil winding 135a, 135b, 135c, 135d and the drive-focus-coil windings 125a, 125b, 125c along the closed loop DC path is preferably symmetrical as shown in Fig. 7.

In another electrically equivalent embodiment the coils are not wound as shown in Fig. 7, but separate (partial) coils are provided, i.e. each winding is replaced by a set of windings, each set forming a (partial) coil. For the drive-focus-coils the (partial) coils are preferably arranged adjacent to each other, for the coupling coils the (partial) coils can be arranged adjacent to each other or at a larger (arbitrary) distance.

It should be noted that the proposed arrangement may be applied for special applications, e.g. for implementing in a head scanner. "Normal" focus fields may be obsolete in such an application, but only the proposed fast focus field and the drive field may be sufficient, which reduces the number of coils needed.

While the invention has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive; the invention is not limited to the disclosed embodiments. Other variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing the claimed invention, from a study of the drawings, the disclosure, and the appended claims.

In the claims, the word "comprising" does not exclude other elements or steps, and the indefinite article "a" or "an" does not exclude a plurality. A single element or other unit may fulfill the functions of several items recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage.

Any reference signs in the claims should not be construed as limiting the scope.