WO2011095924A1

WO2011095924A1 - Apparatus and method for detecting magnetic particles

Info

Publication number: WO2011095924A1
Application number: PCT/IB2011/050410
Authority: WO
Inventors: Bernhard Gleich; Juergen Weizenecker
Original assignee: Koninklijke Philips Electronics N.V.; Philips Intellectual Property & Standards Gmbh
Priority date: 2010-02-08
Filing date: 2011-01-31
Publication date: 2011-08-11
Also published as: JP2013518658A; RU2012138332A

Abstract

The present invention relates to an apparatus and a method for detecting magnetic particles in a field of view (28). More specifically, the present invention relates to the field of magnetic particle imaging (MPI). The method and arrangement according to the present invention use an acoustic MPI detection technique which detects acoustic emissions of a magnetic tracer material in an MPI setup. The apparatus according to the present invention therefore comprises an acoustic signal receiver (160) for acquiring acoustic detection signals, which detection signals depend on the magnetization in the field of view (28), which magnetization is influenced by the change in the position in space of the first and second sub-zone (52,54).

Description

Apparatus and method for detecting magnetic particles

FIELD OF THE INVENTION

The present invention relates to an apparatus and a method for 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. Future versions will be three-dimensional (3D). A time-dependent, or 4D, 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 field free point (FFP) at the isocenter of the scanner. 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; if the object is an animal or a patient, a contrast agent containing such particles is administered to the animal or patient prior to the scan. During the data acquisition, the MPI scanner steers the FFP along a deliberately chosen trajectory that traces out 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.

The above introduced MPI technology has so far lead to the ability to image e.g. iron oxide particles of several ten nanometers in diameter. Even though this has been a great effort in the field of medical imaging using MPI, there is still a need for higher resolutions. Especially the detection of soft tissue properties requires a very high resolution. However, the resolution of current MPI techniques has so far not been sufficient to detect properties of tissue, especially in the case of soft tissue, in which the magnetic particles were embedded.

SUMMARY OF THE INVENTION

It is therefore an object of the present invention to provide an improved apparatus and method for detecting magnetic particles in a field of view using MPI, which enables, compared to known MPI techniques, a higher resolution and allows for a more reliable and more efficient detection.

In a first aspect of the present invention an apparatus for detecting magnetic particles in a field of view is presented comprising:

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 and a second sub-zone having a higher magnetic field strength are formed in the field of view, - drive means comprising drive field signal generator units and drive field 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, an acoustic signal receiver for acquiring acoustic detection signals, which detection signals depend on the magnetization in the field of view, which magnetization is influenced by the change in the position in space of the first and second sub-zone, and

control means for controlling said signal generator units to generate selection currents and drive currents for causing the selection field elements and the drive field coils to generate the magnetic selection field and the magnetic drive field.

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

In still a further aspect of the present invention a computer program is presented comprising program code means for causing a computer to control the apparatus according to the present invention to carry out the steps of the method 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. It has been recognized by the inventors that instead of detecting a change in magnetization of the magnetic particles by measuring an induction signal, as has been done in known MPI arrangements, it is also possible to detect a local soundwave which is generated due to a change in force in the magnetic material respectively in the magnetic particles. In other words, it has been found that, instead of magnetically detecting MPI signals, it is also possible to acoustically detect MPI signals.

Hence, it is one idea of the present invention to use parts of a known MPI apparatus and method for generating the required magnetic fields, such as the selection field and the drive field, and, since it now has been shown that also reliable acoustic signals can be detected within an adapted MPI arrangement, to replace the magnetic detection means (e.g. magnetic detection coils) by an acoustic signal receiver for acquiring acoustic detection signals.

The physical principle works as follows. The magnetic gradient field

(selection field) generated by the selection means imposes a force on the magnetic particles that is directed away from the first sub-zone (FFP) having a low magnetic field strength. If the FFP is, due to the drive field, moved over the field of view, the direction of the force which is imposed on the magnetic particles changes. It has now been shown that this change in force in a material generates a soundwave which is large enough to be detected using an acoustic signal receiver. Hence, due to the movement of the FFP a changing force on the magnetic particles within the field of view occurs which can be measured as a soundwave.

One of the major advantages of the new acoustic MPI arrangement, respectively method is the very high resolution which is, compared to the prior art magnetic MPI technique, more than doubled. Since the local sound velocity is very material- specific, especially in the case of soft tissue examination, a very good contrast may be provided with the proposed arrangement.

A further advantage is the immunity of the detection principle to electromagnetic disturbances. Furthermore, it is advantageous that due to the immunity to electromagnetic disturbances, the proposed arrangement can also be used in an unshielded environment and the MPI send chain (selection, drive and focus means) may be greatly simplified.

It has to be noted that in practice this new acoustic MPI principle may be either used separately or in combination to the known magnetic MPI detection principle. For example, in an imaging application combining the acoustic and magnetic detection principle, the additional sound information may be used to add additional contrast to the concentration image in an MPI imaging system.

According to a preferred embodiment, the acoustic signal receiver comprises one or more microphones and a spectrum analyzer. These microphones, which are preferably broadband microphones, are either arranged around the examination object or directly attached to the examination object, i.e. attached to the body of the patient. Since the pressure respectively strength of the acoustic waves decreases very fast with the distance from the FFP, the microphones are preferably installed in close proximity to the object under examination or directly attached to it. In case the microphones are arranged around the examination object, it is preferable to measure the movement of the examination object with respect to the imaging system, i.e. using laser interferometry as done in conventional ultrasound systems. This allows for error corrections due to movement of the examination object. The microphones may of course also be mounted on a robot arm in order to move them to their desired position. The electrical output of the microphones is preferably connected to a spectrum analyzer which is used to examine the spectral composition of the acoustic information, e.g. by a discrete Fourier transformation.

According to another embodiment, the control means is adapted for controlling said signal generator units to generate selection currents and drive currents for causing the selection field elements and the drive field coils to generate a magnetic selection field and a magnetic drive field by which the first sub-zone is moved with a velocity that is faster than the local sound velocity. This embodiment is especially advantageous in case the proposed MPI apparatus is used for tissue examination. In such cases, the detected signals are rather low, as the pressure decreases rapidly with the distance from the FFP. This is comparable to a loudspeaker without box, where the positive pressure and negative pressure interfere destructively. It has now been shown that this effect may be circumvented if the FFP moves with a higher speed than local sound velocity. This effect may be compared to the Cerenkov effect for charged particles moving faster than light in the medium.

According to a further preferred embodiment, the selection field elements comprise permanent magnets or selection field coils. Both, permanent magnets or selection field coils can optionally be used. The advantage of electromagnetic coils is that the magnetic gradient field strength can, compared to permanent magnets, easily be adapted to the physical properties of the object under examination.

Still further, in an embodiment the apparatus comprises signal processing means for processing the acquired acoustic detection signals and for reconstructing an image, in particular a soft tissue contrast image, of the area from which acoustic detection signals have been acquired. This embodiment mainly focuses on an imaging application where the additional sound information is used to add additional contrast to the concentration image in MPI. The signal processing means is thereby adapted for processing said received acoustic signals in order to reconstruct a soft tissue contrast image of the area of interest by use of a mathematical model. It has been found that the system function components behave similarly to the system function found for the magnetic detection, even though they are not exactly the Chebyshev polynomials as found for the magnetic detection.

Using this imaging technique based on acoustic signal detection according to the present invention, it is particularly preferred that the signal processing means are adapted for reconstructing an image of the mechanical tissue properties, in particular the sound velocity and attenuation. In such an application, the occurring soundwave, which is emitted and travels through the tissue to the detector, is attenuated, scattered and delayed during its propagation through the tissue. Using the proposed signal processing means, it is possible to image the local mechanical tissue properties, like sound velocity and attenuation.

Compressibility and density may also be used as additional model parameters within the image reconstruction. Another model parameter which can additionally or separately be used is the thermal expansion, since the magnetic material is heated during the change of magnetization (i.e. due to the change of direction of the magnetic drive field) and thereby also contributes to the generated respectively detected sound signal (soundwave). With the proposed imaging technique, which generates, compared to prior art MPI imaging techniques, additional signals (sound signals) and complementary information to the tissue parameters, very good results have been shown for medical tissue examination.

Sound velocity and attenuation of the tissue is not even directly accessible by ultrasound imaging. Therefore, the tissue properties, measured with the apparatus/method according to the present invention are therefore also useful in combination with ultrasound imaging. In a further embodiment it is therefore preferred that the apparatus comprises signal processing means for processing the acquired acoustic detection signals for using them to guide a focused ultrasound beam. The major advantage of combining the proposed acoustic MPI imaging technique with ultrasound imaging is that the image quality can be significantly improved since e.g. multi- scattering artefacts, often occurring in ultrasound imaging, can be illuminated. The signal-to-noise ratio can also be increased. The proposed acoustic MPI detection and imaging technique has therefore shown to be an efficient medical examination method, especially in the field of soft tissue examination. 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 block diagram of an exemplary known MPI apparatus, Fig. 5 shows a block diagram of a first embodiment of an MPI apparatus according to the present invention,

Fig. 6 shows a block diagram of a second embodiment of the MPI apparatus according to the present invention,

Fig. 7 shows an exemplary test-measurement set-up of the MPI apparatus according to the present invention in a schematic way,

Fig. 8 shows a diagram illustrating the physical principle of the MPI technique according to the present invention,

Fig. 9 shows a diagram comparing the resolution determining terms of magnetic and the proposed acoustic MPI, and

Fig. 10 shows a simulation of an acoustic MPI system function according to the present invention in the frequency space.

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, two 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 two embodiments will be pointed out.

The first embodiment 10 of an MPI scanner shown in Fig. 1 has three prominent pairs 12, 14, 16 of coaxial parallel circular coils, each pair 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 xi, x₂, and x₃, rather than 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 is made to flow through the z -coil, and the current -I is made to flow through the z -coil. The z-coil pair 16 then acts as an anti-parallel circular coil pair.

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 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 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^D 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 i is made to flow through both x-coils 12, a current I ₂ through both y-coils 14, and a current p

I 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. The current flowing through

D S

the z^"-coil is I ₃ + I ₃ ± I . The current flowing through the remaining two coil pairs 12, 14 is

D F

I k + I 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 has 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 hazardous to the patient.

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 DC up to the point where the expected signal level drops below the noise level. 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 (or treated) 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 (or treated) - 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, or a cylinder. A cubical field of view 28 is illustrated in Fig. 1.

The size of the first sub-zone 52 is dependent on the one hand on the strength of the gradient of the magnetic selection field and on the other hand on the field strength of the magnetic field required for saturation. For a sufficient saturation of the 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 50x10 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. Especially prior to a therapeutic and/or diagnostic treatment of, for example, a tumor, the magnetic particles are positioned in 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.

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, 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. Magnetic particles that can generally be used are available on the market under the trade name Resovist.

For further details of the generally usable magnetic particles and particle compositions, the corresponding parts of EP 1304542, 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.

The data acquisition starts at time t_s and ends at time t_e. 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 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 receive coil pair along the Xk-axis. The associated receiver converts this voltage to a signal S_k, which it samples and outputs.

It is advantageous to receive or to detect signals from the magnetic particles located in the first sub-zone 52 in another frequency band (shifted to higher frequencies) than the frequency band of the magnetic drive field variations. This is possible because frequency components of higher harmonics of the magnetic drive field frequency occur due to a change in magnetization of the magnetic particles in the scanner' s field of view 28 as a result of the non-linearity of the magnetization characteristics.

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. The signals picked up by the receive coils are sent through a high-pass filter that suppresses the contribution caused by the applied field.

To give a few typical parameters of such an embodiment: The z-gradient of the selection field, G, has a strength of G/^» o = 2.5 T/m, where · o is the vacuum permeability. The selection field generated does either not vary at all over the time or the variation is comparably slow, preferably between approximately 1 Hz and approximately 100 Hz. The temporal frequency spectrum of the drive field is concentrated in a narrow band around 25 kHz (up to approximately 100 kHz). The useful frequency spectrum of the received signals lies between 50 kHz and 1 MHz (eventually up to approximately 10 MHz). The bore has a diameter of 120 mm. The biggest cube 28 that fits into the bore 46 has an edge length of 120

As shown in the above embodiments the various magnetic fields can be generated by coils of the same coils pairs and by providing these coils with appropriately generated currents. However, and especially for the purpose of a signal interpretation with a higher signal to noise ratio, it may be advantageous when the temporally constant (or quasi constant) selection field and the temporally variable drive field and focus field are generated by separate coil pairs. Generally, coil pairs of the Helmholtz type can be used for these coils, which are generally known, e.g. from the field of magnetic resonance apparatus with open magnets (open MRI) in which a radio frequency (RF) coil pair is situated above and below the region of interest, said RF coil pair being capable of generating a temporally variable magnetic field. Therefore, the construction of such coils 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 a general block diagram of an exemplary prior art MPI apparatus 100. The general principles of magnetic particle imaging and of magnetic resonance imaging explained above are valid and applicable to this embodiment as well, unless otherwise specified. The embodiment of the apparatus 100 shown in Fig. 4 comprises a set of various coils for generating the desired magnetic fields. First, the coils and their functions in a MPI mode shall be explained.

For generating the magnetic (gradient) selection field explained above, selection means are provided comprising a set of selection field (SF) coils 116, preferably comprising at least one pair of coil elements. The selection means further comprises a selection field signal generator unit 110. Preferably, a separate generator subunit is provided for each coil element (or each pair of coil elements) of the set 116 of selection field coils. Said selection field signal generator unit 110 comprises a controllable selection field current source 112 (generally including an amplifier) and a filter unit 114 which provide the respective section field coil element with the selection field current to individually set the gradient strength of the selection field in the desired direction. Preferably, a DC current is provided. If the selection field coil elements are arranged as opposed coils, e.g. on opposite sides of the field of view, the selection field currents of opposed coils are preferably oppositely oriented.

The selection field signal generator unit 110 is controlled by a control unit 150, which preferably controls the selection field current generation 110 such that the sum of the field strength and the sum of the gradient strength of all spatial fractions of the selection field is maintained at a predefined level.

For generation of a magnetic focus field the apparatus 100 further comprises focus means comprising a set of focus field (FF) coils, preferably comprising three pairs 126a, 126b, 126c of oppositely arranged focus field coil elements. Said magnetic focus field is generally used for changing the position in space of the region of action. The focus field coils are controlled by a focus field signal generator unit 120, preferably comprising a separate focus field signal generation subunit for each coil element (or at least each pair of coil elements) of said set of focus field coils. Said focus field signal generator unit 120 comprises a focus field current source 122 (preferably comprising a current amplifier) and a filter unit 124 for providing a focus field current to the respective coil of said subset of coils 126a, 126b, 126c which shall be used for generating the magnetic focus field. The focus field current unit 120 is also controlled by the control unit 150.

For generation of the magnetic drive field the apparatus 100 further comprises drive means comprising a subset of drive field (DF) coils, preferably comprising three pairs 136a, 136b, 136c of oppositely arranged drive field coil elements. The drive field coils are controlled by a drive field signal generator unit 130, preferably comprising a separate drive field signal generation subunit for each coil element (or at least each pair of coil elements) of said set of drive field coils. Said drive field signal generator unit 130 comprises a drive field current source 132 (preferably including a current amplifier) and a filter unit 134 for providing a drive field current to the respective drive field coil. The drive field current source 132 is adapted for generating an AC current and is also controlled by the control unit 150.

For signal detection receiving means 148, in particular a receiving coil, and a signal receiving unit 140, which receives signals detected by said receiving means 148, are provided. Said signal receiving unit 140 comprises la filter unit 142 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. 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 receiving coil 148 is 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 to an analog/digital converter 146 (ADC). The digitalized 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.

Further, an input unit 158 is provided, for example a keyboard. A user is therefore 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.

Now referring to the MPI apparatus according to the present invention, a general block diagram of a first embodiment of this new apparatus 200 is shown in Fig. 5. This new MPI apparatus 200, which is based on acoustic signal detection, has a similar structure as the known and above-described MPI apparatus (which is based on magnetic signal detection). It also includes the above-described selection means comprising the selection field signal generator unit 110 as well as the set of selection field coils 116. For the generation of the magnetic drive field, the drive field means including the drive field signal generator unit 130 and the drive field coil elements 136a, 136b, 136c are also necessary in the MPI apparatus according to the present invention. The focus field generation means (not shown in Fig. 5) do not necessarily have to be included into the MPI apparatus according to the present invention. However, it has to be noted that, for specific applications, the focus field generation means can also be included in the apparatus according to the present invention.

Compared to a known prior art MPI apparatus, the MPI apparatus according to the present invention mainly differs in the physical principle of the signal detection, which is now based on an acoustic signal detection technique. The magnetic gradient field (selection field) generated by the selection means 110 imposes a force on the magnetic particles that is directed away from the first sub-zone 52 (FFP) having a low magnetic field strength. If the FFP is, due to the drive field, moved over the field of view 28, the direction of the force which is imposed on the magnetic particles changes. It has now been shown that this change in force in a material generates a soundwave which is large enough to be detected using an acoustic signal receiver. In other words, this means that, due to the movement of the FFP, a changing force on the magnetic particles occurs within the field of view 28 which can be measured as a soundwave.

Therefore, the apparatus 200 comprises an acoustic signal receiver 160 for acquiring acoustic detection signals. The detected signals depend on the magnetization in the field of view 28, which magnetization is influenced by the change in the position in space of the first and second sub-zone 52, 54. The acoustic signal receiver 160 further comprises one or more microphones 162 which are connected to a spectrum analyzer 164. These

microphones 162 are arranged around the examination object, preferably in close proximity to the area under examination. In order to receive a rather large spectrum of acoustic signals, preferably broadband microphones are used. The acoustic signals which are detected by the one or more microphones 162 are transferred to the spectrum analyzer 164 which then examines the spectral composition of the detected acoustic signals, for example by a discrete Fourier transformation.

In case of an image reconstruction, these data are then transferred to a signal processing means 152 which is adapted for processing the acquired acoustic detection signals and for reconstructing an image, in particular a soft tissue contrast image, of the area from which acoustic detection signals have been acquired. Similar as in the case of prior art MPI arrangements based on magnetic detection, the reconstructed image information is finally transmitted via the control means 150 to a computer 154, which displays it on a monitor 156.

It has to be noted that an image reconstruction is not needed in every application. For specific applications, the signal processing means 152 can be omitted. In this case, the spectrum analyzer 164 is directly connected to the control means 150. Similar to the case of magnetic detection, the acoustic signal receiver 160 may also comprise a filter unit, an amplifier unit as well as an analogue/digital converter.

The acoustic detection technique and signal processing introduced above can be either used as a separate detection and imaging technique (see Fig. 5) or according to a second embodiment of the present invention it may be combined with the known MPI detection based on magnetic detection signals. This second embodiment is shown in Fig. 6. Here, magnetic and acoustic detection signals are detected in parallel and fed to the signal processing means 152. In an image application the additional sound information is then used to add additional contrast to the concentration image in MPI.

Fig. 7 shows an exemplary experimental test-set-up 300 of the apparatus according to the present invention in a schematic way. The selection field is hereby generated by two opposing permanent magnet 302. A single torus-shaped permanent magnet 302 could be used instead. FeNdB can exemplarily be used as magnetic material. The drive field is generated by a drive field coil 304 which could for example be realized as a single layer solenoid which is connected to an audio amplifier (not shown here) and resonantly matched. The sample 306 (the examination object) is in this simplified experimental set-up glued to a flexible cling film membrane 308 which is again attached to a tube 310. At the end of the tube 310, one or more microphones 312 are attached. The electrical output of the

microphones 312 is connected to a spectrum analyzer (not shown here). In order to be able to move the sample in vertical direction during examination, the tube 310 with the test sample 306 and the one or more microphones 312 may also be attached to a robot arm (indicated by an arrow 314). In an exemplary measurement procedure, the sample 306 may be positioned such that the recorded signal in the fundamental frequency is maximized. Then it may be stepwise moved upwards and downwards. At each step, the amplitude, e.g. the first three harmonics, may be recorded using the spectrum analyzer.

It is pointed out that the experimental set-up shown in Fig. 7 is only a simplified test-set-up. In practical medical applications, the apparatus 200 would have to be modified. Instead of a test sample 306, the tissue or object of interest could be examined in vivo.

Furthermore, in order to further deepen the physical background of the acoustic detection technique, Fig. 8 shows a diagram illustrating the physical principle of the MPI technique according to the present invention. The diagram shows the magnetization within the field of view in dependence of the location of the FFP. It can be seen that the magnetically and acoustically detected MPI signal formation is similar. At time to, the drive field is zero and therefore the total field H_tot is the selection field Hs. For a magnetic material with step response, the magnetization M points in different directions left and right from the FFP. At ti, the drive field Ho(ti) has moved the FFP and therefore changed the magnetization M. This change in magnetization was detected in previous MPI experiments by measuring an induction signal.

However, as the selection field exerts a force on the magnetic particle, the change in magnetization is also accompanied with a change in force F. As the magnetization of the magnetic particles points in field direction, the force will be directed away from the FFP. If the FFP is left of the magnetic particles, the particles are forced to the right. If at a later point in time (ti) the FFP passes to the right side, the force F points to the left. This change in force F in a material generates a soundwave, which can be detected as explained above (e.g. using a broadband microphone).

Assuming a Langevin behavior for the magnetic nano particles, the force on the magnetic material reads:

Here Mo is the saturation magnetization of the material were the magnetic particles are dispersed, L is the Langevin function, μ is the magnetic moment of the particles and 1¾T the thermal energy. If the particles are in saturation, which is fulfilled if the FFP is

F = M₀ ( B )

sufficiently away, the above formula can be simplified to . So the force points in the direction of the strongest change of the magnitude. In the case of one dimensional signal generation Equation (1) simplifies to:

Here a is an abbreviation for μ/ΙίβΤ and B magnitude of the field, solely pointing in x-direction. G_x is dB_x/dx, i.e. the gradient of the B_x component, which is assumed to be constant for the region of investigation. From Equation (2) it can be deduced that magnetically and acoustically detected MPI differ in terms of resolution. In magnetically detected MPI the flux through the receiving coil is proportional to the magnetization i.e.

L(a£)+ B ^- L((aB )) L(ccB). For the force detection however, the corresponding term is ^at>

This sum has the double initial steepness than the L(ccB) alone. As for large B the limit of the sum is the limit of L(ccB) i.e. 1, the shape of the sum is similar to L(ccB), but the initial steepness is doubled as seen in Fig. 9, which shows a diagram comparing the resolution determining terms of magnetic MPI technique and the acoustic MPI according to the present invention. So for given particle properties a, the resolution obtained in acoustically detected MPI is twice the resolution one would obtain in the magnetically detected case.

In the acoustical case as proposed according to the present invention, it is possible to define a system function in analogy to the magnetically detected MPI. This function describes the measured signal as a function of the position of a small sample in the measuring device. A signal of an unknown object can be decomposed into a superposition of the system function. The weight coefficients represent the image of the object.

Mathematically, the system function can be obtained by replacing B_x in Formula 2 by G_xx+Asin((Oot). The amplitude A and the frequency θΰο are the parameters defining the drive field. Fig. 10 shows a simulation of an acoustic MPI system function according to the present invention in the frequency space. In figure 10, the magnitudes of the first three harmonics of the Fourier-transformed system functions are plotted. It can be seen that the system function components behave similarly to the system function found for the magnetic detection, but they are not exactly the Chebyshev-polynomials as found for the magnetic MPI detection.

To explore the sensitivity theoretically, the generated pressure has to be compared to a noise pressure. The lowest possible noise pressure is the one generated by thermal fluctuations. It can be expressed as:

4k_sTft(2)Af

where A is the detector area and Δ the bandwidth. 9 (Z) is the real part of the sound impedance which is in good approximation the product of density and sound speed as long as the damping is negligible.

In an exemplary test set-up, the following specifications were chosen:

For a square millimeter detector and material properties of water at 310 K, the noise pressure is 160 μPa/ Hz . For the signal part, a cube of 1 mm³ filled with 0.5 mol(Fe)/l as magnetite has been assumed. In this dilution the saturation magnetization became about 4.4 ιηΤμο^"1. In a gradient field of 5 Τμο^_1/ιη this translates to a force of 18 μΝ or a pressure of 18 Pa. So a signal to noise of l. lxl 0⁵ at a measuring time of 1 second has been expected. On the other hand a concentration of 4.4 μι ο1(Ρ6)/1 should be detectable within 1 second. For

comparison, a typical dosage in MRI is 8 to 40 μι ο1(Ρ6)/1 with a detectable local

concentration of about 50 μι ο1(Ρ6)/1.

In summary, a new method and arrangement using an acoustic detection technique in MPI are herewith provided. The inventors have found a technique to detect acoustic emissions of a magnetic tracer material in a MPI setup. A theoretical model predicts the spatial distribution of the signal. In an imaging application the additional sound information may be used to add additional contrast to the concentration image in MPI. The resolution of the presented apparatus/method has shown to be even higher than twice the resolution of known MPI systems. The presented method is therefore especially

advantageous in applications in the field of soft tissue examination. With the proposed method it is possible to image the local mechanical tissue properties, like sound velocity and attenuation. Since these quantities are not directly accessible by ultrasound imaging, the measured tissue properties may can be used in combination with ultrasound imaging in order to improve the image quality by eliminating e.g. multi- scattering artefacts. Hence, the apparatus and method according to the present invention can therefore be used to guide a focused ultrasound beam in therapeutical applications. Due to the immunity of the detection principle to electromagnetic disturbances, the proposed apparatus can also be used in an unshielded environment and the MPI send chain can also greatly be simplified.

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 measured cannot be used to advantage.

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

Claims

CLAIMS:

1. An apparatus (200) for detecting magnetic particles in a field of view (28), which apparatus comprises:

selection means comprising a selection field signal generator unit (110) and selection field elements (116) for generating a magnetic selection field (50) having a pattern in space of its magnetic field strength such that a first sub-zone (52) having a low magnetic field strength and a second sub-zone (54) having a higher magnetic field strength are formed in the field of view (28),

drive means comprising drive field signal generator units (130) and drive field coils (136a, 136b, 136c) for changing the position in space of the two sub-zones (52, 54) in the field of view (28) by means of a magnetic drive field so that the magnetization of the magnetic material changes locally,

an acoustic signal receiver (160) for acquiring acoustic detection signals, which detection signals depend on the magnetization in the field of view (28), which magnetization is influenced by the change in the position in space of the first and second sub- zone (52, 54), and

control means (150) for controlling said signal generator units (110, 130) to generate selection currents and drive currents for causing the selection field elements and the drive field coils to generate the magnetic selection field and the magnetic drive field.

2. An apparatus (200) as claimed in claim 1,

wherein said acoustic signal receiver (160) comprises one or more microphones (162) and a spectrum analyzer (164).

3. An apparatus (200) as claimed in claim 1,

wherein said control means (150) is adapted for controlling said signal generator units (110, 130) to generate selection currents and drive currents for causing the selection field elements and the drive field coils to generate a magnetic selection field and a magnetic drive field by which the first sub-zone (52) is moved with a velocity that is faster than the local sound velocity.

4. An apparatus (200) as claimed in claim 1,

wherein said selection field elements comprise permanent magnets (302) or selection field coils.

5. An apparatus (200) as claimed in claim 1,

further comprising signal processing means (152) for processing the acquired acoustic detection signals and for reconstructing an image, in particular a soft tissue contrast image, of the area from which acoustic detection signals have been acquired.

6. An apparatus (200) as claimed in claim 5,

wherein the signal processing means (152) are further adapted for reconstructing an image of the mechanical tissue properties, in particular the sound velocity and attenuation, of the area from which acoustic detection signals have been acquired.

7. An apparatus (200) as claimed in claim 1,

further comprising signal processing means (152) for processing the acquired acoustic detection signals for using them to guide a focused ultrasound beam.

8. A method for detecting magnetic particles in a field of view (28), which method comprises the steps of:

generating a magnetic selection field (50) having a pattern in space of its magnetic field strength such that a first sub-zone (52) having a low magnetic field strength and a second sub-zone (54) having a higher magnetic field strength are formed in the field of view (28),

changing the position in space of the two sub-zones (52, 54) in the field of view (28) by means of a magnetic drive field so that the magnetization of the magnetic material changes locally,

acquiring acoustic detection signals, which detection signals depend on the magnetization in the field of view (28), which magnetization is influenced by the change in the position in space of the first and second sub-zone (52, 54), and

controlling said signal generation to generate selection currents and drive currents for causing the generation of the magnetic selection field and the magnetic drive field.

9. Computer program comprising program code means for causing a computer to control an apparatus as claimed in claim 1 to carry out the steps of the method as claimed in claim 7 when said computer program is carried out on the computer.