WO2005119286A1

WO2005119286A1 - Heating apparatus for selectively heating material by spin resonance

Info

Publication number: WO2005119286A1
Application number: PCT/EP2004/005947
Authority: WO
Inventors: Yousef Hassan Al-Subaiha
Original assignee: Terramark Markencreation Gmbh
Priority date: 2004-06-02
Filing date: 2004-06-02
Publication date: 2005-12-15

Abstract

The present invention relates to a heating apparatus for selectively heating material by spin resonance. The heating apparatus comprises a RF-generator, a main magnetic flux generator and means for generating a spatial flux for selecting a target area. The present invention further relates to a heating apparatus for selectively heating material by spin resonance having a magnetic flux generator, which generates an inhomogeneous flux distribution with a fixed maximum in a target region. The present invention further relates to a method for modifying an imaging spin resonance apparatus to a combined hyperthermia and imaging apparatus. The heating apparatus can also be combined with an imaging apparatus.

Description

Heating apparatus for selectively heating material by spin resonance

The invention relates to magnetic resonance hyperthermia, in particular to a heating apparatus for selectively heating a body by magnetic resonance, an imaging and hyperthermia apparatus, a method for modifying an imaging spin resonance apparatus and to a method for selectively applying heat.

Heat treatments are applications of heat to a body. Two common types of heat treatments are superficial heat treatments, which apply heat to the outside of the material to be heated, e.g. a body, and deep heat treatments that direct heat toward specific inner tissues through ultrasound or by electric current.

In Oncology, however, Hyperthermia therapy involves raising the body's internal temperature as a method for eradicating tumors. H3φerthermia can involve the whole body, or just an affected local region. In Physical Therapy and Physiotherapy, heat treatments target specific body regions experiencing injury or dysfunction. The general purpose is to increase the extensibility of soft tissues, remove toxins from cells, enhance blood flow, increase function of the tissue cells, encourage muscle relaxation, and help relieve pain. Adding the potent effects of hyperthermia in treating tumors can however prove far more deadly to cancer than traditional therapies alone.

In the state of the art, different methods used for heat treatment are known. The commonly used tools for heat treatment are : hot packs, paraffin, hydrotherapy, fluidotherapy and ultrasound. In diathermy, high frequency excitation used to produce heat. In shortwave diathermy, the body part to be treated is placed between two capacitor plates, whereby heat is generated as the high frequency waves travel through the body tissues between the plates. In microwave diathermy, radar waves are used to heat tissue. This form is the easiest to use, but the microwaves cannot penetrate deep muscles. In the state of the art it is known to use the patient's data provided by a MR-imaging system to direct and align several RF-beams in the frequency range of microwaves to a certain region in the patient's body for selectively applying heat. The hybrid system is composed of a MR-imaging system combined with a microwave heating system.

However, hyperthermia devices using RF-radiation only, in particular microwave, can not focus the RF-power on small regions without significantly heating the surrounding tissue. Also, in case of the treatment of a region inside the patient's body, the tissue along the direction of the RF-beam absorbs the RF-energy and consequently is heated. For treating tumors having a size significantly smaller than the wavelength, the RF-energy can not be concentrated to avoid a substantial heating of the surrounding tissue. However, if short wavelengths are used to improve the resolution, the RF-energy is absorbed at the surface, regions inside the body can not be treated.

The document US 2003/0069464 Al describes a device for treatment with magnetic fields, the device including a magnet for producing an inhomogeneous magnetic field and a coil system for producing an alternating field. The coil system is adapted to produce spin resonance with a broad RF frequency distribution to reach all body parts. The RF energy is pulsed according to the spin-lattice relaxation time. A broad RF-frequency distribution is used to cause a uniform spreading of the spin resonance effect throughout the complete body.

It is an object of the invention to provide a heating apparatus for selectively heating matter, which in particular provides an improved separation between regions which are to be heated and the surrounding regions which should not be affected by the heating process.

Another object of the invention is to provide a combined imaging and heating apparatus for providing a controlled heating process.

Further, it is an object to provide a simple method to provide a heating apparatus for selectively heating matter starting from a common device.

These objects are fulfilled by the heating apparatus of claim 1 and claim 8, by the imaging and hyperthermia apparatus of claim 9, by the use of an imaging apparatus of claim 13 and by the method for modifying an imaging spin resonance apparatus of claim 15. Further, these objects are fulfilled by a use of a method for selectively applying heat according to claim 21.

A heating apparatus for selectively heating matter, preferably biological matter, preferably a body or a part of a body, e.g. a body region comprising a tumor, by magnetic spin resonance according to the invention comprises a RF-generator capable of generating RF radiation; a magnetic flux generator generating a main magnetic flux; generating means for generating a spatial flux distribution at least in said main magnetic flux, the generating means being capable of controlling said spatial flux distribution resulting in a combined flux comprising said spatial flux distribution and said main magnetic flux, said combined flux and said RF-radiation providing spin resonance condition only in a, preferably adjustable, 3 -dimensional target region of said material, thereby heating said material essentially only in said 3 -dimensional target region.

With this apparatus, a predefined temperature can be produced inside a predefined region of the material, preferably a patient's body. The resolution for the heating region is improved with regard to a heating apparatus based on microwave absorption and independent from the wavelength respectively the frequency of the RF-radiation. As the resolution is limited by the spatial flux distribution only, the frequency of the RF- transmitters is not limited on microwave frequencies. Any frequencies corresponding to the magnetic flux in the heating region that constitute a spin resonance condition can be used. As parts of the architecture of the apparatus according to the invention correspond to known imaging spin resonance apparatus, standard parts can be used in the manufacturing process.

Preferably the apparatus is arranged such that the material inside said 3 -dimensional target region is heated with a rate between 0.1 °C/min. and 10 °C/min., or more preferable between 1 °C/min. and 5 °C/min.

Preferably, the apparatus is designed such that the material outside the 3 -dimensional target region is not heated at all, or at least less than 0.01 °C/min. or less than 0.1 °C/min.

In another embodiment, the apparatus is arranged such that in said material within said 3- dimensional target region radiation energy between 7 mW/cm³ and 0.7 W/cm³ is transformed to heat. Preferably, the apparatus is designed such that outside the 3 -dimensional target region no radiation energy is absorbed and/or transformed into heating energy, or at least a maximum of 0.7 W/cm³ or a maximum of 7 mW/cm³ is transformed into heating energy.

Preferably, the generating means of the heating apparatus comprises a first gradient flux generator generating a first gradient field being variable along the first axis, a second gradient flux generator generating a second gradient field being variable along a second axis different to the first axis and a third gradient flux generator generating a third gradient field being variable along a third axis different to the first and different to the second axis, whereby said main magnetic flux, said first gradient field, said second gradient field, said third gradient field and said RF radiation at least are partly overlapping in said 3- dimensional target region and said main magnetic flux, said first gradient field, said second gradient field and said third gradient field combine together to said spatial flux distribution.

The first, second and third gradient flux generator allow a simple selection of the region which is to be heated according to the first, second and third axes. To select or to define a region which is to be heated, a common orientation based on three coordinates can be used. Further, the three flux generators can provide one coil each, allowing for a relatively simple coil structure.

In one embodiment, the 3 -dimensional target region comprises a location and a volume which are provided by the spatial flux distribution and/or by a frequency distribution of said RF-radiation emitted by said RF-generator.

This allows to adjust the region which is to be heated according to the features of the RF- generator and according to the features of the gradient flux generators. The region which is to be heated can be selected by adjusting the frequency distribution only, while the spatial flux distribution is fixed. Vice versa, the frequency distribution can be fixed and the spatial flux distribution can be changed. In the latter case, the frequency distribution can have only one frequency, which can be generated easily by an oscillator having a constant frequency, while location and size are selected by the gradient flux generators. In this way, the apparatus can alternatively be based on a fixed gradient flux which is more easily to provide than an adjustable gradient flux distribution. Advantageously, the first, second and third gradient flux generator generate fluxes aligned with said first direction.

As tlie main magnetic flux is aligned with said first direction, too, the total magnetic flux is the sum of the amount of the fluxes and thus can be calculated easily. Further, the spin resonance is homogeneous, if the total flux has only one direction and thus can easier be controlled and the heating effects can be pre-calculated easier and more exactly. On the other hand, as the phase orientation is only relevant for imaging spin resonance devices and is not relevant for the present heating apparatus, the first, second and third gradient fluxes can alternatively be not parallel to each other. In this way constraints related to the alignment parallel are obviated.

The first gradient field can continuously increase along the first axis, the second gradient field can provide a local apse along the second axis and the third gradient field can provide a local apse along said third axis.

With this arrangement, the region to be heated can be selected along the first axis slide by slide, while the location of the region can be adjusted by second and third gradient field on a plane perpendicular to the first axis. This allows to use a simple Cartesian orientation, which can be reduced to a 2-dimensional slide-by-slide orientation, if once the location of a slide at the first axis is selected. Further, for a magnetic flux distribution having one apse, coils can be used having a very simple structure. Also, continuously increasing gradient fields can be provided by coils having a simple structure.

Preferably, the second gradient field provides a local minimum along the second axis and the third gradient field provides a local minimum along the third axis.

As all gradient fields sum up, the contribution of the first and second gradient field at the selected region equals the sum of both minima, allowing for an easy calculation and selection of the region, especially, if the gradient field at the minima is zero. In this way, the frequency yielding a spin resonance condition can be set according to the main magnetic field, which can be constant, and the first gradient field. In this case, the resonance condition occurs in the region, in which the minima join or meet, whereby the RF-frequency is depending only on one variable, i.e. the first gradient field. Thus, the control of the RF-generator can be simplified.

Advantageously, the first, second and third axes are perpendicular to each other.

The resulting Cartesian system allows to control the 3 -dimensional location of the volume without having a mutual dependency among the axes. With a Cartesian system, the import of data related to imaging or heating distribution is standardized and can be input from other systems, e.g. imaging systems or therapy plans or a combination thereof.

An imaging and hyperthermia apparatus using magnetic spin resonance advantageously comprises an imaging unit providing imaging data of said material, whereby the imaging and hyperthermia apparatus provides the above described heating apparatus.

An imaging and hyperthermia apparatus allows for a control of the heating in the patients body and also provides a control of the heated location. By the combination of the imaging and the hyperthermia functions in one device, a relocation of the body is obviated. This results in a better precision and a device, which is less costly, as at least some parts can be used for both functions.

Preferably, the imaging and hyperthermia apparatus has a control unit controlling the heating apparatus to heat said material in said target region, which is related to said imaging data.

In this way, the heating can be performed in an automated process, in which data produced by imaging can be used for defining and redefining the target region. The control unit can also perform other tasks, e.g. a security task to avoid the heating of a region which is not identical with the targeted region. The control unit can control the flux generation as well as the RF-generator or only parts thereof.

The control unit can additionally control the imaging unit, thus reducing the number of necessary components. Also, the same data for both processes can be shared more easily. In common imaging units, a control is already provided, which could e.g. be reprogrammed to perform the tasks for both imaging and heating processes.

In one embodiment, the control unit alternatingly controls the heating apparatus and said imaging unit to alternatingly heat said material in said target region and provide said imaging data.

With only one control, the number of necessary parts is reduced, while the temperature distribution and the location of the heated region can repeatedly controlled and adjusted. If some devices are used by the heating apparatus and by the imaging unit, the same control unit can be used in a time-shared manner, e.g. by alternatingly switching between two respective subroutines, one corresponding to the heating apparatus and one corresponding to the imaging unit.

Preferably, the heating apparatus for heating a target region is used with an imaging apparatus.

The imaging apparatus can provide imaging data to identify the target region which is heated subsequently by the heating apparatus.

In one embodiment, the imaging apparatus is a spin resonance imaging apparatus.

In this embodiment, one or more parts of the imaging and the heating apparatus can be shared as the same physical principle is used.

According to another aspect of the invention, a method for modifying an imaging spin resonance apparatus to a combined hyperthermia and imaging apparatus is provided, whereby the imaging spin resonance apparatus is capable of providing spin resonance to a 3 -dimensional target region by a RF-generator, the method including a step of modifying the RF-energy of said RF-generator and absorbed by said spin resonance producing a preset heating distribution predominantly in said 3 -dimensional target region, or preferably, only. With this method, a standard spin resonance imaging apparatus providing a 3-d resolution can be modified easily. A customary spin resonance imaging apparatus is controlled by software running in a control unit and therefore this method can be performed by a software update only.

In a preferred embodiment, the method for modifying an imaging spin resonance apparatus includes the step of modifying a scanning pattern which is defined by the adjusting of said 3 -dimensional region according to said heating distribution and depending on the RF- power of said generator.

Conventional imaging devices scan or sample the complete space or body inside the device. By concentrating the scanning process on the region which is to be heated while the temperature increase equals the absorbed RF-power, which can be adjusted according to the preset temperature distribution, the temperature distribution can exactly defined and concentrated on the target region. Further, the step of modifying can be accomplished by changing the scanning pattern only, maintaining the RF-power. This is preferable, if the RF-power has a fixed value.

In one embodiment, the method for modifying an imaging spin resonance apparatus also includes modifying the RF-power of the RF transmitter of the imaging apparatus according to the preset heating distribution and, preferably, depending on said modified scanning pattern.

As the RF systems of imaging devices have a high slew rate, the desired volume which is to be heated, can be defined precisely. In this embodiment, the conditions concerning the rate of change of the gradient field are less restrictive, while the spatial precision of the heating distribution can be maintained. Preferably, the RF-power also depends on the modified scanning pattern, allowing a flexible control of the temperature distribution. By controlling both, the RF-power and the modified scanning pattern, the highest resolution and exactness of the heating distribution can be achieved. In particular, step of modifying said scanning pattern can comprise concentrating and/or limiting the scanning pattern on a target heating region, ' defined by said preset heating distribution.

By concentrating the scanning pattern on the region which is to be heated, unnecessary scanning of regions, which are not to be heated, can be avoided. Preferably, the heating region is repeatedly scanned depending on said heating distribution. In this way, the temperature and the temperature distribution can be controlled by the number of performed scanning repetitions allowing for a simple modification step of MRT control (MRT - Magnetic Resonance Therapy).

The method for modifying an imaging spin resonance apparatus advantageously comprises the steps of repeatedly interrupting a step of heating using said modified imaging spin resonance apparatus by steps of imaging using said imaging spin resonance apparatus unmodified and introducing a step of readjusting said preset heating distribution after at least one of said steps of imaging.

By a repeated imaging process, the heating can be controlled, e.g. automatically, and can be readjusted accordingly, which is also preferably done automatically. If a patient body is treated, which moves or shifts, the heating distribution and/or the target region can follow this movement based on new imaging data by readjusting the RF-distribution/-frequency and/or the spatial magnetic flux distribution which influence the spin resonance and the RF-energy absorption. Further, if threshold values related to given maximum temperatures are used, the heating treatment can be stopped to avoid injuries. The imaging steps and the imaging devices can also be used to measure and output the actual temperature distribution. Methods for determining a temperature by spin resonance measurements are already known. Further, anatomical changes to tlie target volume compared to images taken in former imaging steps can be detected, which are caused by the increasing temperature and thus are correlated with the temperature.

The present invention further relates to a method for selectively heating material, preferably biological material, e.g. a patient's body, in particular a tumor or a part thereof, by providing a spatial magnetic flux distribution and heating by applying RF-radiation at least over a 3 -dimensional region. Preferably, the RF-radiation and the spatial magnetic field distribution provide substantial spin resonance only, or substantially only, in said 3- dimensional region.

This method allows for heating only certain parts of a body, while other parts are not affected, irrespective of the depth in which the region is located which is to be heated. In this way, heat can be applied very concentrated on a body, while the heating effect adjacent to the heated region is neglectable. Especially in view of a cancer therapy using hyperthermia, very small tumors can be treated, while the not infested tissue surrounding the tumor does not substantially suffer from the heating.

Alternatively, the spectrum of the RF-radiation and / or the spatial magnetic field distribution in this method is matched to the 3 -dimensional region yielding a spin resonance condition.

By adjusting the RF-spectrum or by changing the spatial magnetic field distribution, the 3- dimensional region can easily by selected by providing a resonance condition in the region. The resonance condition is given, if the RF-frequency matches the magnetic field strength considering the gyromagnetic ratio of the concerned material. This is the case, if the energy of the emitted RF-photons equals the energy difference given by the two spin energy states produced by the applied magnetic field.

The 3 -dimensional region can be selected based on data provided by a magnetic spin resonance imaging device. In this way, regions inside a body can be precisely located non- invasively. The heating process can be effectively controlled providing an exactly limited heating effect.

Advantageously, the spatial magnetic field distribution and/or the RF-radiation is provided by this magnetic spin resonance imaging device. Using the same apparatus reduces the costs and obviated the need for a relocation. Further, errors introduced by relocating e.g. a body are obviated, too. The data provided by the magnetic spin resonance imaging device can be used for providing a spatial temperature distribution. With this information, the heating effects during application of the heating method can be watched.

Alternatively, the RF-radiation and / or the spatial magnetic field distribution is adjusted according to minimize a difference between said spatial temperature distribution and a predefined temperature distribution.

This allows for regulating a yielded spatial temperature distribution or can be used for a controlling step. Also, security steps can be provided, e.g. shutting down the RF-generator, if a maximum temperature is reached. Further, certain desired heat distributions can be effected and controlled during the complete duration of the application.

Preferably, the described methods can be used for treating tumors by hyperthermia in a body alone or in combination with other tumor therapy methods.

In this way, the potent effects of hyperthermia in combination with other therapies, e.g. chemotherapy, can add together. Further, hyperthermia can be combined with radiotherapy to enhance the effectiveness of the therapy. Since hyperthermia enhances blood flow in tumor tissues, it increases the uptake of chemotherapy drugs that depend on blood transport for delivery. In case of bulky tumors, hyperthermia is able to attack cells in blood-deficient regions of the tumor while the chemotherapy drug permeates tissues with higher blood flow nearer the surface (thermochemotherapy).

The invention will become more apparent by way of the following description which refers to the appended drawings.

The drawings show in detail :

Fig. la and Fig. lb are diagrams showing the relationship between absorbed energy, RF- frequency and magnetic field strength, providing the conditions for spin resonance according to the invention. Fig. 2 is a perspective illustration showing one embodiment of an apparatus according to the present invention and the orientation of the axes as well as the applied magnetic field with regard to a patient' s body

Fig. 3 is a perspective illustration of applied magnetic gradient fields used in the present invention.

Fig. 4a- 4e show different embodiments of the gradient field distribution in different embodiments of the present invention.

Fig. 5 shows an example of a pulse pattern, which can alternatively be used in a combined imaging and heating apparatus for heating and imaging the target area at the same time.

In the following, a short introduction into magnetic spin resonance in accordance with the invention is given with regard to Figures la and lb. The angular momentum of a nucleus is determined by the spin of the unpaired neutrons and protons and by the orbital angular momentum of the neutrons and protons. The nuclear spin is either zero or multiples of ^l . The nuclear spin of hydrogen is Vi. If a magnetic field B is applied, the magnetic dipole momentum resulting from the spin can have different orientations relative to the magnetic field B. The energy difference ΔE between the energies of the two opposite orientations corresponds to the RF-frequency that can be absorbed. The energy difference ΔE is proportional to the strength of the applied magnetic field B. In Fig. la, the increasing line indicates the energy state of a nucleus having a magnetic dipole momentum antiparallel to the applied magnetic field. The decreasing line indicates the relationship between the applied magnetic field B and a nucleus having a magnetic dipole momentum in parallel to the applied magnetic field B. At a certain magnetic field Bres, the difference between the two energy states at the opposite orientations of the magnetic dipole momentum is ΔE. RF- radiation having a frequency f corresponding to that energy (i.e. ΔE = h-f holds, h being Planck's constant) yields spin resonance, and therefore, the RF-energy is absorbed. Figure lb shows the dependency between the absorbed energy Eabsorb and the applied RF- frequency f for a certain magnetic field strength Bres corresponding to a certain energy gap ΔE. In Fig. 2, an embodiment of a magnetic spin resonance apparatus according to the invention is shown. In a tube 10, a magnetic field Bz,main is applied to a patient's body 12 lying in the tube 10. The magnetic field Bz,main is in line with the longitudinal axes of the body 12. The magnetic field distribution is composed of the static main magnetic field Bz,main and three variable gradient fields.

Figure 3 shows the gradient field distribution in a preferred embodiment of the invention. All three variable gradient fields Bz,x-gradient, Bz,_y-gradient, Bz,z-gradient are parallel and are in the direction of the main magnetic field Bz,main. The Bz,x-gradient gradient field varies along the x- axis and decreases continuously beginning with a field component parallel to the z-axis at a far end, having a point of zero field generation and ending with an anti-parallel field component at the nearer end. The decrease is shown as linear decrease, but can have any other continuously decreasing shape. The Bz,y-gradient gradient field varies along the y-axis and decreases continuously beginning with a field component parallel to the z-axis at an upper end, having a point of zero field generation and ending with an anti -parallel field component at a lower end. The decrease can have any other continuously decreased shape. The Bz,z-gradient gradient field varies along the z-axis and decreases continuously beginning with a field component parallel to the z-axis at a left end, having a point of zero field generation and ending with an anti-parallel field component at a right end. Also this gradient field can have any continuously decreasing shape. All gradient fields add together, but cancel to zero at the location, at which all points zero field generation meet. The total magnetic field strength at this point is Bz,mam. If the RF-frequency matches Bz,main, spin resonance is generated only at this point. By varying the distribution shape of the gradient fields, this point can be selected. Alternatively, the orientation of the gradient fields can be changed, e.g. rotated.

Figures 4a - 4e show different embodiments of the gradient field distribution. The shown distributions relate to the Bz,x-gradient, to the Bz,y-gradient and/or Bz,z-gradient gradient field. The location is given on tlie abscissa of the diagrams and relates to a location along the x-, y- or z-axes, respectively. Accordingly, the axes of ordinate show the strength of the corresponding gradient field. A negative value corresponds to a decreased field strength when added to the magnetic main field Bz,main and a positive value corresponds to an increased field strength when added to the magnetic main field Bz,main. Figure 4a shows a field distribution having a minimum equal zero at a certain point at the abscissa. From this point, the field strength increases linearly. The distribution is only schematic, also approximated distributions are possible. For a small heating region, the interval in which the gradient field equals zero must be as small as possible. Figure 4b shows another gradient field distribution having a minimum equal zero. In contrast to Fig. 4a, the distribution has no linear dependency but a real dependency which appears with real coils.

If only gradient field distributions with a small minimum are used, there is only one small 3-dimensional region, in which the gradient fields sum up to zero. Thus, in this case, the total magnetic field equals Bz,main only at a point, in which the minima meet, whereas at any other point, the total magnetic field is higher. If the RF-frequency corresponds to, only this region is heated. Figure 4c shows a realistic distribution produced by coils, e.g. a Gaussian distribution. Further, the gradient field of figure 4c has an offset. Thus, if gradient fields with one or more offsets are used, the resonance condition is given, if the RF-frequency corresponds to Bz,main plus the sum of all offsets, heating the point (region), at which all minima gradients cross. Fig. 4d shows two curves having a maximum. The maximum of the lower curve equals zero, whereas the maximum of the upper curve has an offset. Figure 4e shows a curve similar to curve 4b. However, the curve of Figure 4e has a minimum including a wide interval. By adjusting the width of this interval, the width of the heated 3- dimensional region can be set, e.g. for applications, in which the heating distribution should cover a large space. Also, the RF-frequency distribution can be used to widen the region in which spin resonance occurs. For a RF-distribution only having one discrete frequency, only a small region (depending on the gradient field) can be heated. If the RF- distribution covers a range of RF-frequencies, the resonance condition is given for a wider region, even if gradient fields with small minima are used.

In figure 4f, a field distribution is shown having a maximum at a certain point at the abscissa. From this point, the field strength decreases linearly. Similar to figure 4a, the field has a linear dependency on the distance. In contrast to fig. 4a, the apse is a local maximum, at which the field is not equal zero.

In the following, a preferred embodiment of the invention is described as non limiting example. A magnetic flux generator generating the main magnetic flux comprises a cylindrical coil which has compensation windings. As the windings of cylindrical coil are uniformly distributed, the flux in the middle of the coil is higher than the flux introduced at the ends. Therefore, the compensation windings provide a compensational flux, which adds to the flux of the cylindrical coil and produces a homogeneous main magnetic flux. In the preferred example, the main magnetic flux is 1.5 Tesla, but can also provide a flux in the preferred range between 0.1 Tesla and 25 Tesla, but at least in a range between 0.002 Tesla ' and 8 Tesla. Also, higher magnetic fluxes can be used, whereby the costs for a magnetic flux generator increase with the maximum field strength. Preferably, superconducting coils are used.

Alternatively, the cylindrical coil can consist of a winding, which is not uniformly distributed, e.g. having a density of windings at the outer ends which are higher than a density at the center, generating a constant magnetic flux. Also, a Helmholtz coil pair could be used.

In the preferred embodiment of the invention, a spatial flux distribution is used to set spin resonant conditions for a certain target region, while no spin resonant conditions are met outside said region. Such a spatial flux distribution is preferably provided by three separated gradient flux generators produce three different gradient fields. The gradient fields vary along three different directions, whereby one gradient field only varies along one of the three directions and provides a constant field along the other directions. One of the three gradient fields linearly decreases along the axis of the cylindrical coil, while each of the two other gradient fields provide a distribution having a minimum. The two gradient fields providing a minimum can be in order to define the target region. The linearly decreasing gradient field has an adjustable offset wliich can be used to adjust the location of the target region along the axis of the cylindrical coil. Preferably, the decreasing gradient field provides a zero-crossing at the location at which the target region is located. Advantageously, the minima of each of the two other gradient fields is zero. In this case, the flux produced by the gradient field generators in target region equals zero, whereby the total flux is equal to the main magnetic flux. An RF-generator provides RF-radiation having a resonant frequency to provide spin resonance of a hydrogen nucleus. The total magnetic flux at the target region and the spin resonant frequency f_res_onant meet the relationship : γ = fresonant / B_totai , whereby γ is the gyromagnetic ratio of a hydrogen nucleus ( 42.58 MHz/Tesla ), f_resonant is the resonant frequency and B_totai is the total magnetic flux in the target region.

Alternatively, the gyromagnetic ratio of atoms can be used, which are contained in the target region, which is to be heated. Also, electron spin resonance could be used, with γ being the gyromagnetic ratio of an electron. The used RF-frequency typically lies between 100 kHz and 1 GHz. Preferably, frequencies between 100 kHz and 85.16 MHz or between 21.29 and 340.64 MHz are used. If the total magnetic flux is e.g. between 0.1 T and 2 Tesla, frequencies between 4.258 MHz and 85.16 MHz are used. For a low resonant frequency between 100 kHz and 21.29 MHz, magnetic fluxes between 2.349 mT and 500 mT are used. For the range between 21.29 MHz and 340.64 MHz, the required magnetic flux is between 0.5 Tesla and 8 Tesla. The generation of magnetic fluxes of 8 Tesla or higher is relatively costly. In the preferred embodiment, a main magnetic flux of 1.5 Tesla is used. The gradient fields provide a zero crossing or a minimum of 0 Tesla at the target region. Thus, the required resonant frequency is 63.87 MHz. If the gradient fields provide a gradient of 0.3 mT/cm in all directions, and the target region is approximately spherical having a radius of 0.5 cm, e.g. the node of a breast cancer, a certain frequency spectrum instead of a fixed resonant frequency is used. Such a frequency spectrum lies between 63.87 MHz and 63.88 MHz, whereby 63.87 MHz is the resonant frequency in the center of the target region with a flux of 1.5 Tesla and 63.88 MHz is the resonant frequency at the limits of the target region, at which the total flux equals (0.5cm x 0.3mT/cm) + 1.5 Tesla = 1.50015 Tesla. The frequency spectrum can be achieved by sweeping the frequency in the limits of the desired frequency interval or by using a non-sinusoidal waveform, e.g. a Gaussian impulse, a saw-tooth signal or a signal corresponding to a raised cosine frequency distribution. Preferably, the signal is sinusoidal having a frequency that is sweeped in the interval, e.g. slowly in the center of the interval and rapidly at the outer ends of the interval for providing a high heating effect in tlie center of the target region and a decaying heating effect at the outer limits of the target region. The RF-power of the RF-transmitter can reach up to 25 kW, which are applied in pulses by. one or more RF-antennas. In the present invention, any duty cycle ratio can be used. In one embodiment, the RF-transmitter emits the RF-power with a duty cycle, allowing for an imaging or a detection process, in which the flip angle of the resonant matter is detected. Also, the flip angle may be considered, when the characteristics of the RF-radiation transmitted to the target region are selected, in particular with regard to the polarization of the emitted RF-radiation.

Alternatively, the RF-power is applied to the target region in a substantially continuous way.

However, only a small part of the RF-power transmitted by the RF-generator is absorbed in the target region by spin resonance. Preferably, the anticipated power in the target region is between 0.01 and 1000 W. For small tumors, the power should be in a range of 0.01 and 1 W, whereas for large tumors, the anticipated power should be between 1 W and 100 W. For an adequate temperature slew rate, the anticipated power can be in the range of 0.1 W and 100 W. For maintaining a high temperature, only the leaked heat has to be compensated by the anticipated RF-power, which can be in the range of 0.01 W to 50 W, depending on the size, surface, type of target tissue, type of surrounding tissues and blood circulation.

As an example, the preferred embodiment is used to heat a tumor of 33.5 g, corresponding to a sphere with a radius of 2 cm assuming tissue with the density of water. An appropriate heating with a slew rate of 5°C / min would require the anticipation of 11.5 Watts, neglecting the temperature loss introduced by thermal conductivity. Thus, the intensity of the RF-power at the location of the tumor is equal to 11.5W / 1.257 x 10^"3 m² = 9149 W/m². Assuming an efficiency of 50 %, an RF-intensity of approx. 18.3 kW/m² is required. The RF-intensity decreasing with the distance to the RF-transmitter antenna and is typically decreasing with the square of the distance between target region an RF- transmitter antenna. Alternatively, the form of the target region is not spherical, but can have an ovoid or cylindrical form. Any other form can be approximated to yield a maximum heating distribution in the treated tissue and a minimum heating distribution outside the treated tissue (e.g. a tumor), especially to avoid substantial heating of the surrounding tissue. Also, a tumor region of any form can be isolated using imaging data, whereby the target region is matched to the tumor region.

In general, the RF-power produced by the RF-generator is not only absorbed in the target region by spin resonance. In regions of the body, in which no spin resonance condition is given, some RF-power is absorbed, too. This RF-power also leads to a heating effect, which is substantially smaller than the absorption rate induced by the spin resonance. As an example, the absorption rate in regions with no spin resonance condition, the heating effect is only 0.1 to 10 % of the absorption rate in the target region. Depending on the used RF-frequency, this heating effect can be in the range of 0.1 % to 90 %. For high RF- frequencies, e.g. 340.64 - 1 Ghz, this heating effect can be in the range of 10 to 50 %; and for low RF-frequencies, e.g. 100 kHz - 21.29 MHz, this effect can be in the range of approx. 0.1 % to 10 %. Preferably, the RF-energy is focused on the target region, in which spin resonance occurs, to avoid heating effects in regions outside the target region. This can be accomplished by using directional antennas, e.g. array antennas or other shaped beam antennas, to apply the RF-power mainly to the target region. Also, several beam antennas can be used, which are focused on the target region.

A second side effect, which can lead to a heating effect outside the target region is based on thermal conduction. If the target region is surrounded by tissue, this surrounding tissue is also heated, depending on the thermal conduction between the target region and the surrounding tissue. This side effect can result in a heating distribution which is not limited on the target region. However, depending on the blood circulation, this effect only occurs adjacent to the target region. The resulting heat gradient can be in the range of 1 °C/cm to 5 °C/cm, depending in the thermal conduction between target region and surrounding region. For a low thermal conduction, this heat gradient can be in the range of 5°C/cm to 50°C/cm. For a high thermal conduction, e.g. if the target region and the surrounding region are in an aqueous tissue, the heat gradient can be in the range of 0.5°C/cm to 1 °C/cm. In the latter case, only the center of a tumor should be the target region which is heated by spin resonance, in order to avoid substantial heating effects in tissue that surrounds the tumor which is to be treated. If the target region is near the surface of the body, cooling means can be used which are applied from outside.

Various temperature slew rates can be used, which are typically in the range of 0.1 °C/min to 10°C / min, depending on the sensitivity of the targeted tissue. Preferably, a range between 1°C / min and 5°C / min is used. The yielded temperature can be slightly above 37 °C for the treating of human tumors, and can reach up to 50°C. Preferably, a temperature range between 39°C and 45 °C is used. In the preferred embodiment, the yielded temperature is 42°C. A first slew rate corresponding to a first RF-power is used, e.g. a slew rate of 5°C / min which is achieved by a RF-power of 25 kW. After reaching the yielded temperature of 42°C, the RF-power is reduced to a level, in which the yielded temperature is maintained. Starting from 37°C, the yielded temperature is reached after approx. 1 min. As an example, the reduced RF-power level is 2.5 kW, which is depending e.g. on the blood circulation and surface of the target region. Reducing the level of RF-power to a fifth can be accomplished by reducing the peak RF-power to a fifth of the start level. In the preferred embodiment, the duty cycle of the pulses of the RF-radiation is reduced to a fifth, e.g. from 40 % to 8 %. A duty cycle of 8 % corresponds to an impulse, which has a power level of 100% for 8% of a time period and which has a power level of 0% during 92% of a time period. In this document, the power anticipated in the target region corresponds to the averaged anticipated power.

The invention can be implemented in common MRT-imaging devices providing spin resonance in limited 3-dimensional regions, e.g. by repeatedly scanning the same region. In one embodiment, the RF-power is emitted as a pulse allowing for an imaging process as well as leading to an increase of temperature in the target region. In Fig. 5, an example of such a pulse is shown as function of the gradient fields Gx, Gy, Gz over the course of time. Further, the emitted pulse of RF-power is shown (20a, 22a, 24a). The RF-pulse comprises a first part related to a flip angle of 90° followed by a second part 22a, which is related to a flip angle of 180°. This sequence is repeated, whereby Fig. 5 only shows the repetition of the first part 24a. For imaging, a sequence of gradient pulses 20b, 22b, 24b; 20c, 24c; and 22c of the gradient fields Gx, Gy and Gz is applied. These gradient pulses in combination with the RF-pulse 20a, 22a, 24a lead to a resonance echo 40, which can be received and processed in an imaging process, providing imaging data. In order to achieve an improved heating effect in parallel (i.e. synchronously with the imaging pulses), additional pulses of the gradient field can be superposed to the imaging pulses of the gradient fields, for example as depicted in Fig.5 as dashed fields. In Fig.5, the pulses 30a, 32a, 34a of the Gy- gradient field and the pulses 30b, 32b, 34b of the Gz-gradient field generate a heating effect in the target area. In general, the gradient fields Gy, Gx are switched ON, whenever Gz is ON. Thus, the target which is to be heated, can be selected by these additional gradient field pulses. In other words, the target is "shot" with a known amount of energy, while, at the same time, the flip angle of the resonant region is tracked for generating data used in a subsequent imaging process. It is apparent that in the example shown in Fig.5, the duty cycle ratio is essential to the generation of imaging while heating the target region and can not be selected arbitrarily. In one embodiment of a combined heating and imaging method, only the target region, which is heated, is imaged. In this embodiment, preferably a combined gradient pulse as described with reference to Fig. 5 is used.

Alternatively, the limits of the region can be selected by adjusting the RF-frequency, the strength, orientation or the shape of the gradient fields. The absorbed heating power can be adjusted by adjusting the heating region and/or by selecting an appropriate RF-power. The heating process and the target region can be controlled and readjusted by repeatedly switching between a standard imaging mode and the heating mode provided by the invention. Common spin resonance devices are based on spin resonance of a hydrogen- nucleus. However, also electron resonance or nucleus resonance of other elements can used for a heating apparatus or method according to the invention. Also, the nucleus of other elements than hydrogen can be used, e.g. for yielding resonance in a certain RF-frequency, magnetic flux range or to concentrate the resonance on other elements than hydrogen.

A heating apparatus for selectively heating a body can alternatively comprise a field generator generating a high magnetic flux using a magnet in the form of a ring comprising an inhomogeneous field distribution and a maximum flux in its center. Further, the heating apparatus comprises an RF-generator generating an RF-radiation providing, together with the maximum flux of the ring, a spin resonance condition only at the center of the magnet. A tumor in a patient's body can be heated selectively by locating the patient's body such that the tumor is located in the center of the magnet. As the fluxes in magnet in form of rings are highly inhomogeneous, the region, in which a spin resonance condition is met, can be very small allowing for a high resolution of the heating effect produced by the spin resonance in combination with the RF-radiation of the RF-generator. The form and diameter of the region of the body, in which the spin resonance condition is yielded, can be selected by moving the patient's body. Alternatively, the RF-frequency can be sweeped in a small frequency range corresponding to the inhomogeneous flux distribution in the center in order to yield a spin resonance condition in the center of the magnet as well as in a small region surrounding the center of the magnet. Further an additional magnetic field can be applied to shift the spin resonance condition away from the center. For this purpose, fixed or moveable permanent magnets or coils can be used. Alternatively, additionally gradient field generating means can be used.

Claims

Heating apparatus for selectively heating material by spin resonanceClaims

1. Heating apparatus for selectively heating material by magnetic spin resonance having a RF-generator capable of generating RF radiation; a magnetic flux generator generating a main magnetic flux; generating means for generating a spatial flux distribution at least in said main magnetic flux, the generating means being capable of controlling said spatial flux distribution resulting in a combined flux comprising said spatial flux distribution and said main magnetic flux, said combined flux and said RF-radiation providing a spin resonance condition only in a 3 -dimensional target region of said material, thereby heating said material essentially only in said 3 -dimensional target region.

2. The heating apparatus of claim 1, in which said generating means comprise a first gradient flux generator generating a first gradient field being variable along a first axis, a second gradient flux generator generating a second gradient field being variable along a second axis different to the first axis and a third gradient flux generator generating a third gradient field being variable along a third axis different to the first and different to the second axis; said main magnetic flux, said first gradient field, said second gradient field, said third gradient field and said RF radiation at least being partly overlapping in said 3- dimensional target region, said main magnetic flux, said first gradient field, said second gradient field and said third gradient field combining together to said spatial flux distribution.

3. The heating apparatus of one of the preceding claims, whereby said 3 -dimensional target region comprises a location and a volume which are provided by the spatial flux distribution and/or by a frequency distribution of said RF-radiation emitted by said RF-generator.

4. The heating apparatus of one of the claims 2 - 3, whereby said first, said second and said third gradient flux generator generate fluxes aligned with said first direction.

5. The heating apparatus according to the claims 2 - 4, whereby said first gradient field is continuously increasing along said first axis, said second gradient field provides a local apse along said second axis and said third gradient field provides a local apse along said third axis.

6. The heating apparatus according to the claim 5, whereby said second gradient field provides a local minimum along said second axis and said third gradient field provides a local minimum along said third axis.

7. The heating apparatus according to one of the preceding claims, said first, second and third axes being perpendicular to each other.

8. Heating apparatus for selectively heating material by magnetic spin resonance comprising : a magnetic flux generator generating an inhomogeneous magnetic flux distribution having a fixed maximum in a target region and a RF-generator generating RF-radiation which is applied to said target region, said RF- radiation having a frequency distribution being matched to the magnetic flux in said target region and providing, together with the magnetic flux, spin resonance only in said target region.

9. Imaging and hyperthermia apparatus using magnetic spin resonance having an imaging unit providing imaging data of said material, wherein s_aid imaging and hyperthermia apparatus provides the heating apparatus of one of the preceding claims.

10. The imaging and hyperthermia apparatus of claim 9 having a control unit controlling the heating apparatus of one of the claim 1 - 8 to heat said material in said target region, which is related to said imaging data.

11. The imaging and hyperthermia apparatus of claim 10, whereby said control unit further controls said imaging unit.

12. The imaging and hyperthermia apparatus of one of claims 10 - 11, whereby said control unit alternatingly controls said heating apparatus and said imaging unit to alternatingly heating said material in said target region and providing said imaging data.

13. Use of an imaging apparatus with a heating apparatus according to one of the claims 1 to 8 for selectively heating material by magnetic spin resonance.

14. The use of an imaging apparatus with a heating apparatus according to claim 13, the imaging apparatus being a spin resonance imaging apparatus.

15. Method for modifying an imaging spin resonance apparatus to a combined hyperthermia and imaging apparatus, the imaging spin resonance apparatus being capable of providing spin resonance only in a 3 -dimensional target region by a RF-generator, the method comprising : - modifying a RF-radiation emitted by said RF-generator and absorbed by said spin resonance producing a preset heating distribution in said 3-dimensional target region only.

16. The method of claim 15 whereby said step of modifying comprises : - modifying a scanning pattern by adjusting said 3-dimensional target region according to said preset heating distribution and depending on the RF-radiation of said generator.

17. The method of one of claims 15 or 16 whereby said step of modifying comprises : - modifying the power of said RF-radiation according to said preset heating distribution and depending on said modified scanning pattern.

18. The method of claim 16, whereby said step of modifying said scanning pattern comprises : - concentrating or limiting said scanning pattern on a target heating region defined by said preset heating distribution.

19. The method of claim 18, whereby said step of concentrating or limiting said scanning pattern comprises : - repeatedly scanning said heating region defined by said preset heating distribution.

20. The method for modifying an imaging spin resonance apparatus of one of claims 12 - 19, further comprising the steps of : repeatedly interrupting the step of heating using said modified imaging spin resonance apparatus by steps of imaging using said imaging spin resonance apparatus in an unmodified mode and introducing a step of readjusting said preset heating distribution after at least one of said steps of imaging.

21. Method for selectively heating material comprising the steps of : - providing a spatial magnetic flux distribution, generating heat by applying RF-radiation to a 3-dimensional target region, said RF-radiation and said spatial magnetic flux distribution substantially providing spin resonance only in said 3-dimensional target region.

22. Method for selectively heating material of claim 21 , wherein a frequency distribution of said RF-radiation and / or said spatial magnetic flux distribution matches said 3- dimensional target region to provide a spin resonance condition.

23. Method for selectively heating material of claim 21 or 22, wherein said 3-dimensional target region is selected based on imaging data provided by a magnetic spin resonance imaging device.

24. Method for selectively heating material of claim 23, wherein said spatial magnetic flux distribution and/or said RF-radiation is provided by said magnetic spin resonance imaging device.

25. Method for selectively heating material of claim 23 or 24 including the step of providing a spatial heating distribution based on said imaging data.

26. Method for selectively heating material of claim 25, wherein said RF-radiation and / or said spatial magnetic flux distribution is adjusted to minimize a difference between said spatial heating distribution and a predefined heating distribution.

27. Method for selectively applying heat of one of claims 21 to 26, said method being used for treating tumors by hyperthermia in a body alone or in combination with other tumor therapy methods.