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WO2019219832A1 - Dispositif pour libérer localement une substance active par tomographie par résonance magnétique - Google Patents

Dispositif pour libérer localement une substance active par tomographie par résonance magnétique Download PDF

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Publication number
WO2019219832A1
WO2019219832A1 PCT/EP2019/062654 EP2019062654W WO2019219832A1 WO 2019219832 A1 WO2019219832 A1 WO 2019219832A1 EP 2019062654 W EP2019062654 W EP 2019062654W WO 2019219832 A1 WO2019219832 A1 WO 2019219832A1
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WO
WIPO (PCT)
Prior art keywords
active substance
magnetic resonance
carrier
excitation
substance
Prior art date
Application number
PCT/EP2019/062654
Other languages
German (de)
English (en)
Inventor
Markus May
Boris Keil
Original Assignee
Technische Hochschule Mittelhessen
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Filing date
Publication date
Application filed by Technische Hochschule Mittelhessen filed Critical Technische Hochschule Mittelhessen
Publication of WO2019219832A1 publication Critical patent/WO2019219832A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/40—Applying electric fields by inductive or capacitive coupling ; Applying radio-frequency signals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0033—Features or image-related aspects of imaging apparatus, e.g. for MRI, optical tomography or impedance tomography apparatus; Arrangements of imaging apparatus in a room
    • A61B5/0036—Features or image-related aspects of imaging apparatus, e.g. for MRI, optical tomography or impedance tomography apparatus; Arrangements of imaging apparatus in a room including treatment, e.g., using an implantable medical device, ablating, ventilating
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
    • A61B5/055—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00—Arrangements or instruments for measuring magnetic variables
    • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/48—NMR imaging systems
    • G01R33/483—NMR imaging systems with selection of signals or spectra from particular regions of the volume, e.g. in vivo spectroscopy
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00—Arrangements or instruments for measuring magnetic variables
    • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/48—NMR imaging systems
    • G01R33/54—Signal processing systems, e.g. using pulse sequences ; Generation or control of pulse sequences; Operator console
    • G01R33/543—Control of the operation of the MR system, e.g. setting of acquisition parameters prior to or during MR data acquisition, dynamic shimming, use of one or more scout images for scan plane prescription

Definitions

  • the invention relates to a method and a device for the local release of an active substance (for example agents for chemotherapy) by means of magnetic resonance tomography (MRT).
  • an active substance for example agents for chemotherapy
  • MRT magnetic resonance tomography
  • Magnetic resonance imaging is a procedure commonly used for imaging, which is used primarily in medical diagnostics for the representation of structure and function of the tissues and organs in the body. It is physically based on the principles of nuclear magnetic resonance (NMR), in particular field gradient NMR, and is therefore also referred to as magnetic resonance imaging (MRI).
  • NMR nuclear magnetic resonance
  • MRI magnetic resonance imaging
  • sectional images of the human (or animal) tissue can be generated, which allow an assessment of the organs and many pathological organ changes.
  • the method is based on the fact that the atomic nuclei in the examined tissue are excited in a phase-synchronous manner to a certain movement by means of a combination of static and high-frequency magnetic fields (by means of one or more transmitting coil (s)) and then deliver a measurable signal in the form of an alternating voltage until the movement has subsided. This signal is measured by means of one or more receiver coils and used for image reconstruction.
  • This movement of the atoms is called the lar- more precession and is mechanically analogous to a toy gyroscope when its axis of rotation is not vertical but precesses around the vertical.
  • the frequency for the Larmor precession is defined by:
  • B is the magnetic field strength in Tesla and g is the gyromagnetic ratio.
  • MRI since the object to be observed itself is excited, MRI is not subject to the physical law of resolving power of optical instruments, according to which the wavelength of the used radiation must be smaller, the higher the required resolution.
  • MRI with sub-millimeter wavelengths in the meter range (low-energy radio waves), object points in the submillimeter range can be resolved.
  • Some atomic nuclei such as the hydrogen nuclei in the molecules of the tissue to be examined have an intrinsic angular momentum (Kemspin) and are therefore magnetic. These cores produce a small longitudinal magnetization in the direction of the static field (paramagnetism) after aligning a strong static magnetic field. Due to a short-term applied high-frequency alternating field in the radio frequency range through the transmitter coil / n, this magnetization can be deflected (tilted) from the direction of the static field, ie convert partially or completely (saturation) into a transverse magnetization. The transverse magnetization immediately begins to precess around the field direction of the static magnetic field, ie the direction of magnetization rotates.
  • Kemspin intrinsic angular momentum
  • This precession movement of the tissue magnetization induces an electrical voltage in the receiving coil (s) and can thus be detected. Their amplitude is proportional to the transverse magnetization. After switching off the high-frequency alternating field, the transversal magnetization decreases (again), so the spins align themselves again parallel to the static magnetic field. For this relaxation they need a characteristic cooldown. This depends on the chemical compound and the molecular environment in which the precessing hydrogen nucleus is located. Therefore, the different types of tissue characteristically differ in their signal, resulting in different signal strengths (brightnesses) in the resulting image.
  • DE102009024589A1 describes a device for local heating of body tissue. In addition to a radiation source for heating, this also includes an MRI. This is used here only for imaging and should not be used for heating. Furthermore, DE102009024589A1 does not disclose that active substances should be released by heating.
  • thermolabile liposomes having a controlled release temperature for the liposome content, in particular a liposome stable at 37 ° C. in serum with a controlled release temperature between 40 and 80 ° C.
  • thermolabile liposomes are excellently suited for use in various fields, but especially in the context of regional deep hyperthermia.
  • the regional deep hyperthermia in combination with systemic Chemotherapy is used at specialized clinical centers, as a technique for the tumor-specific liposomal transport and the subsequent release of a drug from the liposomal envelope. There are indications for an increased cytotoxic effect of cytostatics as well as an immune modulation by regional deep hyperthermia.
  • the drug release from the liposomes but always done with a local hyperthermia. It is not possible to achieve drug release without heating the surrounding tissue to the same extent.
  • Object of the present invention is to provide a method for a targeted local release of an active substance in a body region by means of magnetic resonance imaging, which allows an active substance release but also independent of heating of the surrounding tissue.
  • At least one carrier substance is required. This is designed such that it can be excited by the magnetic resonance tomograph and thereby heated, thereby releasing at least one active substance which is bound to the carrier substance or contained in it.
  • exemplary carrier substance are thermolabile liposomes.
  • the material composition may vary to achieve a different Larmorfrequenz than that of the surrounding tissue.
  • Various or several carrier substances are possible in principle. Liposomes are well known to those skilled in the art. These are colloidal particles which form spontaneously when phospholipids are mixed with an aqueous medium.
  • a particularly advantageous feature for the medical use of such liposomes is that the phospholipids organize themselves in the formation of the liposomes in the form of a membrane, which is very similar to the natural membrane of cells and cell organelles. At the same time, some of the aqueous solution is encapsulated inside the liposomes. Liposomes can therefore be used both as carrier for fat-soluble - stored in the membrane - as well as carriers for water-soluble - stored in the encapsulated aqueous solution - therapeutic agents.
  • the preferred composition of the liposomes used as a carrier can be adapted for different temperature ranges by the choice of components with the respectively suitable main conversion temperature.
  • FIG. 1 An exemplary group of liposomes are phosphatidylcholines.
  • Figure 2 shows the main transition temperatures (TM) of phosphatidylcholines whose main transition temperatures are in the range of 0 to 80 ° C.
  • Active substances may be, for example, agents for chemotherapy or analgesics.
  • the use of other active substances is possible in principle.
  • the method according to the invention comprises the following steps:
  • step E introducing one or more carrier substances with one or more active substances into a body. This must be done no later than step E, the implementation of the suggestion.
  • Body is to be understood biologically.
  • a body is the materially appearing form of a living being, with which it is set apart from its environment, regardless of whether it lives or not.
  • a input of the body region or body regions of the body to be treated in which at least one active substance is to be released with an input means (60) and transmission of the position data to an evaluation means (30). Simultaneous entry of the location coordinates of the region and the temperature to be treated with hyperthermia.
  • step E Performing the excitation from the excitation plan of step C and the setting of the magnetic resonance tomograph from step D and thereby releasing the active substance (s) from the carrier substance (s) in the stimulated body region and / or simultaneously or subsequently performing the hyperthermia in possibly different ones regions.
  • step 0 one or more carrier substances with one or more active substances must be introduced into a body. Injection can be done, for example, via an infusion, oral, pulmonary. This must be done no later than step E, the implementation of the suggestion.
  • step A Input of the position of the body region to be treated
  • the position of the body region or body regions to be treated is input to which an active substance introduced into the body in step 0 is to be released with an input means (60) and transmission of the position data to an evaluation means (30).
  • the body region (s) to be treated is / are usually also the regions which are stimulated.
  • an offset region is a region of the body in which the excitation of the carrier but no release of the active substance takes place.
  • the input may include data from prior or simultaneous diagnostic imaging (e.g., MRI data, X-ray images, ultrasound images).
  • prior or simultaneous diagnostic imaging e.g., MRI data, X-ray images, ultrasound images.
  • the position data are stored in a database and are transferred from this database to an evaluation means (30) for further processing.
  • Another possibility is that the position data already stored in a database are used. This is particularly advantageous to allow for rapid treatment.
  • the position data includes the data about the geometry and the structure of the body region to be treated.
  • the surface and the temperature of the body region to be treated are detected simultaneously with a detection means (50). If it is a position on the body surface, it is possible to detect this position on the surface with a detection means (50, for example a camera) and then transmit the image data to an evaluation means (30) for further processing.
  • a detection means for example a camera
  • the temperature is determined in this embodiment of the method according to the invention from the received signal and its intensity.
  • step B input of the amount and type of active substance to be released and the carrier substance used for the active substance and transmission to an evaluation means (30)
  • step B the amount and type of active substance to be released and the carrier substance used for the active substance and the transmission of this data to an evaluation means (30) are entered.
  • a first possibility is to input the data via an input means (60) and to transmit it to an evaluation means (30) for further processing.
  • the second option would be to regulate the dose automatically by feeding back the MRI data.
  • step C the calculation of an excitation plan from the position data from step A and the data from step B.
  • the release of the active substance from the carrier substance with the necessary temperature profile is first calculated by the evaluation means (30).
  • the evaluation means (30) calculates how the magnetic resonance tomograph must be controlled.
  • excitation plan This includes the data about which period t, with which intensity I and at which frequency f the excitation region is to be excited. These data form the operating parameters of the magnetic resonance tomograph.
  • the resolution of magnetic resonance tomographs is usually limited by technical conditions, in particular the field strength.
  • the excitation frequency f is chosen so that the carrier substance is excited by the magnetic resonance tomograph, is heated and the active substance is released from the carrier substance.
  • the carrier is designed so that it can release at least one active substance when heated.
  • the carrier substance can be designed such that it also has a different Larmor frequency than that having surrounding tissue. In this case, at a certain frequency f, which corresponds to the Larmor frequency of the carrier substance, only the carrier substance is excited, whereby it heats up, but the surrounding tissue does not.
  • the stimulation of the surrounding tissue can be carried out additionally.
  • the carrier substance is designed such that its Larmor frequency is the same as the Larmor frequency of the surrounding tissue.
  • the carrier substance for example liposomes
  • a different frequency must be used for excitation.
  • the frequency depends on the gyromagnetic ratio as well as the magnetic field strength.
  • the gyromagnetic ratio is 42.576MHz / T / 2p and thus the frequency is at a magnetic field strength of 7T
  • the non-toxic black or red phosphor has a gyromagnetic ratio of 17.235 MHZ / T / 2TT, and thus the Larmor frequency at 7T is 120.645 MHz.
  • the Larmor frequency will be adjusted.
  • the composition of the carrier substance must be matched to the respective active substance.
  • the material composition of the carriers may be varied to achieve a different Larmor frequency and temperature for activation in MRI.
  • the intensity I and the time t determine how strongly the carrier substance heats up.
  • the excitation time and thus the temperature can be increased or decreased. Subsequently, the transmission of the excitation plan from step C to a control means (40).
  • step D the setting of a magnetic resonance tomograph for the execution of the excitation plan from step C.
  • step E the excitation is carried out starting from the excitation plan from step C and the setting of the magnetic resonance tomograph from step D.
  • the release of the at least one active substance (s) from at least one carrier substance (s) occurs, for example. thermally labile liposomes introduced into the body in step 0.
  • the tissue of the excited body region is excited and thus heated. This can be used, for example, for local hyperthermia and / or improved drug absorption in the stimulated body region.
  • the excitation of an offset region is effected by the magnetic resonance tomograph.
  • a body region is excited with the carrier substance, which differs from the Body region in which the active substance is released from the carrier, differs.
  • This is achieved by using a carrier substance whose release of active substance is delayed in time for excitation.
  • the carrier substances or the carrier substance need a certain amount of time to release the active ingredient. Since the carrier substance (s) in the body moves or moves or grows, so a certain offset time can be realized and the active substance are released exactly in the target area.
  • a simultaneous measurement of the MRI signal of the carrier substance and / or active substance takes place simultaneously for excitation. This can be used to monitor whether the carrier substance has heated up sufficiently to release the active substance. Furthermore, it can be determined from the MRT signal of the active substance whether it is still bound to the carrier substance or has already been released.
  • the excitation of the body region can also be individually changed and controlled by the modulation of amplitudes and phases of the individual transmission channels.
  • a measurement of the MRT and of the received signal intensity takes place at the same time for excitation, monitoring the temperature of the excited body region in step E.
  • a target temperature of the excited body region is additionally input in step B, and during the execution of the excitation, this setpoint temperature is compared with the actual temperature.
  • the evaluation means (30) generates iterative adjustments of the excitation plan during step E and sends them to the control means (40) so that the control means adjusts the operating parameters of the magnetic resonance tomograph accordingly to a target temperature in the excited body region to realize the magnetic resonance tomograph.
  • the various alternative embodiments of the method according to the invention can be combined.
  • the method of the invention is applicable to all clinical and experimental MRI.
  • the carrier substance comprises tracers for displaying the distribution and the position of the carrier substances with or without active substance in the body during image generation by the MRI.
  • T racers are contrast agents. Among other things, all substances that are used in angiography are suitable.
  • the T racer is mixed with the active substance and liposomes so that liposomes with entrapped tracer and active substance are formed.
  • Liposomes may preferably cross the blood-brain barrier, so that regions in the head of a body can be stimulated by the method according to the invention.
  • the device 10 according to the invention for the local release of an active substance from a carrier substance in a body region 110 of a body 100 comprises various components.
  • the device 10 according to the invention comprises a magnetic resonance tomograph 20.
  • This magnetic resonance tomograph 20 comprises at least one transmitting coil for excitation of the carrier substance.
  • the magnetic resonance tomograph 20 comprises a plurality of parallel anatomically adapted transmitting coils (pTx: parallel transmitters) 23, 24, which are designed so that different types of tissue or regions can be excited with a high accuracy of aiming.
  • the second transmission coil 24 preferably has a different resonance frequency than the first transmission coil 23.
  • the individual transmitting coils are formed geometrically, inductively and / or capacitively separated from each other electrically.
  • the latter has in each case at least one first transmitting coil for exciting the carrier substance and at least one second transmitting coil for exciting the surrounding tissue.
  • the at least one first transmitting coil and the at least one second transmitting coil are arranged separately from one another.
  • the arrangement of the two transmitting coils with different resonant frequency can be arranged both one above the other and in each other.
  • the possibility of overlapping these transmission systems is possible because they have a different resonance frequency and therefore do not disturb or interact with each other.
  • the device 10 comprises an input means 60.
  • the input means 60 serves to input the position data in method step A and the data for method step B and to transmit them to the evaluation means 30 for further processing.
  • the input means 60 may be a keyboard or a graphic user interface or graphical user interface (GUI).
  • the device 10 comprises an evaluation means 30. This serves to receive and (temporarily) store the position data from step A of the method according to the invention and the data from step B of the method according to the invention. Furthermore, the evaluation means 30 serves to generate an excitation plan from these data in the context of step C and to send this to a control unit 40.
  • an evaluation means 30 a device for electronic data processing is used, for example. a programmable microprocessor integrated into the device.
  • the evaluation means 30 is furthermore designed such that it can evaluate the results of a detection means 50 and / or an input means 60 and transmit the results to a control means 40.
  • the position data are stored in an internal buffer of the evaluation means 30 or are obtained by a data exchange with an external database, for example via a network or by a data exchange with a detection means 50.
  • the evaluation means 30 preferably has an interface for electronic data interchange (EDI).
  • the data transmission can take place via a fixed data line or wirelessly, for example via a radio link
  • the data from method steps A and B are stored in an internal database of the evaluation means 30 or are obtained by a data exchange with an external database, for example via a network or by a data exchange with an input means 60.
  • the device 10 according to the invention comprises a control means 40 for controlling the magnetic resonance tomograph 20.
  • the control means 40 may comprise, for example, one or more magnets for shaping the magnetic field of the magnetic resonance tomograph and / or one or more motors for moving the magnetic resonance tomograph.
  • the use of alternative components is possible.
  • the device 10 further comprises a detection means 50.
  • the detection means 50 serves the surface of the treated body region, e.g. to capture with a camera and then transmit the position data of this body region to the evaluation means 30 for further processing.
  • a first application example of active substances of the inventive method is the cancer treatment of metastases.
  • metastases are marked manually or by an algorithm by the imaging of the MRT, and then an activation with an MRT is carried out at these marked locations so that the carrier substances, such as e.g. There, liposomes release their active ingredient to treat the cancer.
  • This method therefore offers the possibility of developing new active substances which, if taken globally, would have side effects (for example because they have a detrimental effect on certain body sites or some organs) that do not occur in the case of local release (since they are not released in the relevant region) do not concern these).
  • ThermoDox® An exemplary chemotherapeutic agent which is suitable in principle for the method according to the invention would be ThermoDox®. It is a drug candidate in the US with thermolabile liposomes as a carrier substance. It is based on lysolipids that release the encapsulated drug doxorubicin by heat.
  • this chemotherapy drug is generally compromising, so that all fast-growing cells are affected. This affects especially tumor cells but also the hair. If the chemotherapeutic agent is released by the method according to the invention, the release takes place only at the relevant region or regions or at the metastases which were determined before the treatment. Side effects such as hair loss on the head can thus be minimized.
  • a second example of application of active substances of the inventive method are diuretics.
  • these medicines are used to treat heart, kidney and liver failure to eliminate excess water. Adverse effects of these drugs occur, e.g. when these drugs enter the ear region. In all diuretics, hearing damage in the high frequencies to deafness can occur due to inhibition of the sodium-potassium-chloride symporter. With the method according to the invention, these and other side effects can be minimized.
  • a third example of application of active substances of the process according to the invention are antibiotics. These are used successfully for a variety of diseases, but also have side effects on organs, which are not the target of the actual treatment.
  • a side effect is the diarrhea caused by the killing of intestinal bacteria by the antibiotic. Patients who have damaged the intestine in a particular way can cause serious permanent damage.
  • the antibiotic can be released as an active substance only at the site or region of the operation by the inventive method. Possible side effects in the intestine can be minimized.
  • the method according to the invention offers the possibility of optimizing the release of many further medicaments and of limiting or eliminating their side effects.
  • This procedure involves a variety of medications with side effects on local body regions.
  • the optimization potential for existing drugs as well as for future developing drugs is far reaching.
  • TM 1008 In a manufacturing process for providing a carrier substance exemplified here, first at least one phospholipid is dissolved in a solvent mixture (eg from chloroform and methanol).
  • a solvent mixture eg from chloroform and methanol.
  • the solvent mixture is then removed above the phase transition temperature of the phospholipid or lipid mixture, e.g. with the help of a rotary evaporator. This gives a thin lipid film, which is then dried. Active ingredients and dyes are dissolved in buffer e.g. PBS buffer solved. This solution is heated, e.g. to 65 ° C and added to the lipid film, so that an encapsulation of the drug or dye takes place. Centrifugation separates loaded liposomes and excess dye. The pellet with the loaded liposomes is taken up again in buffer and can be administered to the patient.
  • buffer e.g. PBS buffer solved.
  • This solution is heated, e.g. to 65 ° C and added to the lipid film, so that an encapsulation of the drug or dye takes place. Centrifugation separates loaded liposomes and excess dye.
  • the pellet with the loaded liposomes is taken up again in buffer and can be administered to the patient.
  • FIG. 1 shows a schematic representation of the device 10 according to the invention for the local release of an active substance from a carrier substance in an excited body region 110.
  • the detection means 50 shown here is optional.
  • Fig. 2 shows a table with the main conversion temperatures of various phosphatidylcholines.

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Abstract

La présente invention concerne un dispositif pour réaliser un procédé afin de libérer localement une substance active dans une région corporelle par tomographie par résonance magnétique. Celui-ci comprend les étapes suivantes consistant à : - 0. introduire dans le corps au moins un excipient avec au moins une substance active ; - A. entrer, grâce à un moyen de saisie (60), la position de la région corporelle à traiter dans laquelle la ou les substances actives doivent être libérées et communiquer les données de position à un moyen d'évaluation ; - B. entrer la quantité et le type de substance active à libérer et d'excipient utilisé pour la ou les substances actives et communiquer ces données à un moyen d'évaluation ; - C. calculer un plan de stimulation à l'aide d'un moyen d'évaluation à partir des données de position de l'étape A et des données de l'étape B et communiquer le plan de stimulation à un moyen de commande (40) ; - D. régler un tomographe à résonance magnétique (20) avec le moyen de commande (40) afin de réaliser le plan de stimulation de l'étape C ; - E. réaliser la stimulation basée sur le plan de stimulation de l'étape C et régler le tomographe par résonance magnétique de l'étape D et ainsi libérer dans la région corporelle à traiter au moins une substance active à partir d'au moins un excipient.
PCT/EP2019/062654 2018-05-17 2019-05-16 Dispositif pour libérer localement une substance active par tomographie par résonance magnétique WO2019219832A1 (fr)

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DE102009024589A1 (de) 2009-06-10 2010-12-23 Siemens Aktiengesellschaft Thermotherapievorrichtung und Verfahren zum Durchführen einer Thermotherapie
US20120101363A1 (en) * 2010-10-13 2012-04-26 Gordon Andrew C Methods and apparatus for patient treatment using magnetic medical hardware
EP1536770B1 (fr) 2002-09-12 2015-07-29 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Liposome thermolabile a temperature de liberation regulee
US20150273230A1 (en) * 2014-03-26 2015-10-01 Bastien Guerin System and Method For Hyperthermia Treatment Using Radiofrequency Phased Arrays
US20170209579A1 (en) * 2014-07-24 2017-07-27 Baylor College Of Medicine Non-invasive radiofrequency field treatment for cancer therapy
WO2017181182A1 (fr) * 2016-04-15 2017-10-19 Kansas State University Research Foundation Système pour administrer des traitements de l'hyperthermie

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1536770B1 (fr) 2002-09-12 2015-07-29 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Liposome thermolabile a temperature de liberation regulee
US20090192383A1 (en) * 2006-08-22 2009-07-30 Koninklijke Philips Electronics N. V. Method and device for obtaining information about a mammalian body
DE102009024589A1 (de) 2009-06-10 2010-12-23 Siemens Aktiengesellschaft Thermotherapievorrichtung und Verfahren zum Durchführen einer Thermotherapie
US20120101363A1 (en) * 2010-10-13 2012-04-26 Gordon Andrew C Methods and apparatus for patient treatment using magnetic medical hardware
US20150273230A1 (en) * 2014-03-26 2015-10-01 Bastien Guerin System and Method For Hyperthermia Treatment Using Radiofrequency Phased Arrays
US20170209579A1 (en) * 2014-07-24 2017-07-27 Baylor College Of Medicine Non-invasive radiofrequency field treatment for cancer therapy
WO2017181182A1 (fr) * 2016-04-15 2017-10-19 Kansas State University Research Foundation Système pour administrer des traitements de l'hyperthermie

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