WO2006106507A2 - Dispositif et procede de detection de pathologies - Google Patents

Dispositif et procede de detection de pathologies Download PDF

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Publication number
WO2006106507A2
WO2006106507A2 PCT/IL2006/000422 IL2006000422W WO2006106507A2 WO 2006106507 A2 WO2006106507 A2 WO 2006106507A2 IL 2006000422 W IL2006000422 W IL 2006000422W WO 2006106507 A2 WO2006106507 A2 WO 2006106507A2
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Prior art keywords
particles
nano
magnetic field
water molecules
pathology
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PCT/IL2006/000422
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WO2006106507A3 (fr
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Elisha Rabinovitz
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Given Imaging Ltd
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Given Imaging Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
    • A61K49/1818—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Definitions

  • the present invention relates to the detection of pathologies such as cancer, for example in the gastrointestinal tract.
  • Diagnosis may include imaging by, for example, endoscopy, computed tomography (CT), magnetic resonance imaging (MRI), or other suitable imaging systems.
  • CT computed tomography
  • MRI magnetic resonance imaging
  • Such processes may include if the gastrointestinal tract (GI) is being diagnosed cleaning the colon of residuals of food or other contents and inflating the colon, for example, with air, gas or water.
  • Colorectal endoscopy may involve inserting endoscopes, for example, from the rectum through the colon until the cecum. Complications may occur during such invasive and uncomfortable procedures.
  • CT or MRI systems may use magnetic or X-ray fields to highlight or detect damaged areas of the body. These systems may be bulky or power costly. For example the weight of an MRI system may reach over 10 tons and consume 125 ampere (480V). The need for high resolution imaging for detection of pathologies as small as few millimeters may necessitate diagnostic tools, such as CT or MRI systems, to be bulky and to consume much power. For example, CT or MRI systems may be room-sized machines. Tests that use these CT or MRI systems may be costly.
  • MRI imaging relates to the absorption and emission of energy in the radio frequency range of the electromagnetic spectrum, by nuclei having unpaired spins, mainly hydrogen protons.
  • an MRI scanner operates at 1.5 Tesla in order to achieve a sufficient excitation level of the proton.
  • the hardware components associated with an MRI imager may include a primary magnet, for generating a magnetic field, gradient coils for producing a gradient in the magnetic field, an RF coil, for producing an additional magnetic field or modifying the magnetic field, which may be necessary to rotate the spins by 90 or 180 degrees and may be used for detecting MRI signals, and a workstation, for controlling the components of the MRI imager.
  • the magnet is a large horizontal bore superconducting magnet, which provides a homogeneous or substantially constant magnetic field in an internal region within the magnet.
  • a patient may be positioned in the homogeneous field region located in the central air gap for imaging.
  • a coil system may include gradient coils such as antihelmholtz coils.
  • An antihelmholtz coil may include two parallel ring shaped coils. Current in each of the two coils may flow in opposite directions, which may produce a magnetic field gradient between the two coils.
  • the coil system may include RP coils, which may produce an additional magnetic field or modify the magnetic field, which may rotate the net magnetization in a pulse sequence.
  • Gradient or RF coils may include transmission or reception coils.
  • Internal imaging for example, imaging body cavities, may include positioning the patient in a conventional large MRI magnet and using catheters with RF coils. This may produce deficient images because the various orientations of the RF coil. For example, the transverse colon, may not be positioned collinearly with the RF excitation field. This problem has been discussed in U.S. Pat. No. 5,572,132, to Pulyer, et al. entitled, "MRI probe for external imaging", the disclosure of which is incorporated herein by reference.
  • Gastrointestinal diagnosis or examination may include a colon clearing preparation procedure and insertion of a probe into the colon with close proximity to the tissue to be examined.
  • nano-particles made of ferromagnetic materials such as iron oxide.
  • a few pure metals like iron, nickel and cobalt maintain their ferromagnetic properties even at nano-size particles.
  • generating a magnetic field that alternates on a nano-scale may cause particles to exhibit superparamagnetic behavior, magnetizing strongly under an applied field, but retaining no magnetism once the field is removed.
  • nano-particles may have diameters ranging from, for example, 300 to 5nm; other sizes may be used.
  • Ultra-small superparamagnetic particles for example, ferromagnetic materials with a diameter under 50 micron may penetrate the walls of blood vessels to reach the tissue cells.
  • Utra-small superparamagnetic particles for example, with diameters ranging from 5nm to lOnm, may be sufficiently small to reach intracellular locations.
  • SUMMARY A method and system may provide detection of pathologies and/or target molecules, for example, the detection of cancer in, for example, the gastrointestinal tract utilizing for example magnetically susceptible nano-particles.
  • Ultrasound imaging, MRI technology or other suitable techniques may be used in conjunction to localize detected pathologies.
  • FIG. 1 is a schematic illustration of a magnetically susceptible nano-particle, in accordance with an embodiment of the present invention
  • Fig. 2 A, Fig. 2B and Fig. 2C are schematic illustrations of diagnostic systems, in accordance with embodiments of the present invention
  • Fig. 3 is a schematic illustration of sensing coils used in a diagnostic system, in accordance with an embodiment of the present invention
  • Fig. 4 is a graph that shows the response of the sense coils, in accordance with an embodiment of the present invention.
  • Fig. 5A and Fig. 5B are flowcharts of methods for detecting target molecules according to embodiments of the present invention.
  • Embodiments of the present invention provide a method and system for the detection of target substances or pathologies in human and/or animal bodies. For example, tissue diagnosis within the GI tract may be performed that may not require colon cleaning prior to testing.
  • a device including for example a magnetic probe may be operative to perform diagnostic detection by measuring changes or disturbances in magnetic fields made by magnetic particles attracted to target in-vivo substances or particles.
  • Embodiments of the present invention may provide a method and system for detection of pathologies in human and/or animal bodies.
  • One embodiment may include monitoring relaxation times of particles such as magnetically susceptible nano-particles or water molecules attached to or combined with magnetically susceptible nano-particles.
  • the nano-particles may bond or attach to substances of interest, for example, disordered cells or tissues, or other substances associated with pathologies.
  • An accumulation of magnetically susceptible nano- particles in a patient's body that are bonded to certain cells or tissues may indicate the presence of a pathology. Changes in an induced alternating magnetic field may be monitored to detect accumulated nano-particles.
  • One embodiment may include monitoring changes in an induced constant or alternating magnetic field due to the presence of water or other molecules attached or adsorbed onto magnetically susceptible nano-particles that may accumulate near disordered cells or tissues and/or bond to target molecules.
  • Fig. 1 schematically illustrates a magnetically susceptible nano-particle, in accordance with an embodiment of the present invention.
  • the detection of substances, antigens or pathologies may involve detecting nano-particles 50 that may bond to, or attach to the substances.
  • Nano-particles 50 have a core 51 which is a nano-particles made of ferromagnetic materials like iron cobalt and any other magnetically susceptible nano- particles with superparamagnetic properties, that may be conjugated with a ligand 53 that may include an antigen, receptor, expression on cell, for example anti-target monoclonal antibodies, or an active part of an antibody, a "hotspot" of an antibody or a protein (e.g., minimal functional domains involved in protein-to-protein interactions and sufficient to induce a biological or chemical response) glycoproteins, glycolipids or "glycocalyx” or bacterial poly-saccharides that can either covalently or non-covalently be attached to specific receptors or antigen or to a antigenic expressed on target sites (e.g., GI tract tissue) optionally: coated with layer 52.
  • a ligand 53 may include an antigen, receptor, expression on cell, for example anti-target monoclonal antibodies, or an active part of an antibody, a "
  • Protective layer 52 may coat at least a portion of a surface of nano-particle 50.
  • Protective layer 52 may be, for example, a thin gold layer, to prevent aggregation of the nano-particles in storage or during administration into blood. Other protective layers may be used.
  • protective layer 52 may be used to reduce toxicity.
  • protective layer 52 may provide a surface for attaching one or more receptor molecules 53 (e.g. antibodies) to nano-particles 50. Once in the body, water molecules 54 from the biological environment may adsorb onto, attach or coat the surface of the magnetically susceptible nano-particles 50.
  • the nano-particles may be introduced by swallowing.
  • conjugated nano-particles may for example be encapsulated in a pill and released only when the relevant organ of the GI tract may have been reached.
  • the conjugated nano-particles may be, for example controllably released in the colon e.g. the nano-particles are contained in a pill that may be coated with a pH sensitive coating that may degraded at pH greater than 7 .
  • the pill may be administered to a subject and once it may reach the colon the pill or other housing or container may decompose and release the nano- particles.
  • a high concentration of nano-particles may be attached to the cancerous tumor with the targeted antibody.
  • a syringe or an intravenous injection or any other suitable delivery mechanisms may be used to administer nano-particles 50, for example, into the blood stream.
  • nano-particles 50 may be introduced into a body they may diffuse in the blood stream or other lumen. If pathologies exist that express antigens, such as polyps or cancerous tumors, nano-particles 50 may react with the antigen or targeted agent and accumulate in or in close vicinity to the disorder. According to one embodiment, nano-particles 50 may be introduced to the body being examined, for example, by injecting the subject with a suspension of nano-particles 50. Some time later, such as a few minutes later, for example, when at least some nano-particles 50 have had sufficient time to travel through the blood stream where they may bond or attach to antigens present in the body, the body may be screened.
  • nano-particles 50 may include paramagnetic nano-particles 51. Unlike superparamagnetic particles, paramagnetic particles typically retain their magnetization once an external magnetic field is withdrawn. Nano-particles 51 may be made from magnetically susceptible substances, for example, pure transition metals, such as Fe, Ni and Co. Paramagnetic nano-particles typically have a larger magnetic moment than superparamagnetic nano-particles of similar size. Thus, in an alternating magnetic field, the field distortion due to the accumulation of paramagnetic nano-particles is typically larger than super-paramagnetic particles of similar size.
  • system 100 may detect magnetically susceptible nano-particles 50, for example, as described in Fig. 1, for example, with receptor molecules 53 that may include antibodies that may typically attach or bond to substances of interest, for example, pathological or disordered biological structures.
  • Systems 110 and/or 120 may detect water molecules 54 that attach, adsorb or are attracted and/or bond to nano-particles 50.
  • Systems 100, 110 and 120 may include a table or bed 20, a belt 30, one or more magnets 11 and/or 13, one or more coils 60, a base 10, a workstation 40 and an imaging and/or location probe 80, e.g. an ultrasound probe 80.
  • Bed 20 may support a patient's body.
  • Belt 30 may be cylindrically shaped and may be positioned on bed 20 that may be closed around the body of a subject, such that the body may be positioned substantially within the range of the generated alternating magnetic field 12. Other suitable components may be used.
  • Systems 100, 110 and 120 may generate a magnetic field 12 which may be for example alternating or constant. Different elements of systems 100, 110 and 120 may be supported by base 10.
  • a workstation 40 may be used for controlling the components of systems 100, 110 or 120 and presenting the resulting detection data and/or image data.
  • Workstation 40 may include a data processor that may analyze the data received and may be in communication with storage e.g., transferring data to and from storage units. The data processor may provide the analyzed data to monitor 18, where a user (e.g., a physician) may view or otherwise use the data.
  • data processor and/or workstation 40 may be configured and/or may be implemented using a hand-held device.
  • Monitor 18 may additionally be used to display one or more images or a stream of images e.g., images of the GI tract or of other imaged body lumen or cavity as provided from an MRI or from ultrasound or x-ray machine and may display the data relating to the location or position data of the concentration of the covalently bonded nano-particles 50, which may indicate a location of a pathology.
  • images or a stream of images e.g., images of the GI tract or of other imaged body lumen or cavity as provided from an MRI or from ultrasound or x-ray machine and may display the data relating to the location or position data of the concentration of the covalently bonded nano-particles 50, which may indicate a location of a pathology.
  • both an image, and its position or location e.g., relative to the body lumen being imaged
  • the position of bonded nano-particles 50 or water molecules 54 bonded to nano- particles 5O 5 indicating a substance indicating a pathology may be superimposed on those
  • system 100 may be for example a magnetometer system that may be capable of inducing an alternating magnetic field and measuring changes in the induced magnetic field
  • system 100 may only detect nano-particles 50 that are attached or bonded to biological structures, through for example ligand 53.
  • components of system 100 may provide or generate an alternating magnetic field 12, across portions of the body being examined.
  • the alternating magnetic field 12 may cause nano-particles 50 to vibrate, move or rotate.
  • Dipole moments of magnetically susceptible nano-particles 50 may spontaneously rotate to align toward a field direction.
  • the anisotropy energy barrier of the particle, E which is proportional to its volume, may inhibit the dipole moment from rotating, but may be overcome with sufficient thermal energy, k ⁇ T, where T is the temperature and k ⁇ is the Boltzmann's constant.
  • nano-particles in suspension may undergo Brownian rotation, which may randomize the orientation of the dipole moments.
  • ⁇ B may depend linearly on nano-particle 50, for example, a 20-nm magnetite nano-particle 50, for an ideal ⁇ N ⁇ 1 s and ⁇ B ⁇ 1 ⁇ s.
  • the time for the effective relaxation process may be the faster of the two times, ⁇ N and ⁇ B .
  • the free or unbound magnetically susceptible nano-particles 50 may randomize by Brownian rotation in a few microseconds.
  • the bound magnetically susceptible nano-particles 50 typically do not rotate and relax by the Neel mechanism for a period of time, for example, several second, after the field is turned off.
  • magnetically susceptible nano-particles 50 may
  • substantially slow responding magnetic probe 60 may detect substantially only decaying magnetic fields 12 discrepancies produced by bound magnetically susceptible nano-particles 50.
  • System 100 may include various components and configurations of components that may be used to generate an alternating magnetic field 12 created for example by magnets 11 and 13 and measure discrepancies in the alternating magnetic field 12.
  • alternating magnetic field 12 may be of a frequency in a range to measure only those magnetically susceptible nano-particles 50 that are bonded to a substance or target molecule indicating a pathology. The frequency range may depend on particle size and the bonding energy between particles and the target molecule or particle.
  • these bonded magnetic nano-particles 50 since these bonded magnetic nano-particles 50 typically do not substantially orient themselves with the alternating magnetic field, they may cause a disturbance in the magnetic field.
  • Magnetic probe 60 for example, a coil vibrating magnetometer, hall- effect magnetometer or GMT based magnetometer may be used to measure disturbances in the applied, alternating magnetic field at different locations throughout a body. Such disturbances may indicate the presence of or an accumulation of attached or bonded nano-particles 50 with ligand 53, and thus the presence of the corresponding antigens, pathologies or substance indicating a pathology.
  • Magnets 11 and/or 13 (e.g., constant or alternating magnets) of system 100 may produce alternating magnetic field 12.
  • Fig. 3 schematically illustrates the magnetometer 60 based on spiral coils used in diagnostic system 100, in accordance with an embodiment of the present invention.
  • system 100 described with reference to Fig. 2A, may include spiral coils 60.
  • Spiral coils 60 may be arranged in a symmetrical gradiometer configuration and installed in for example pairs with symmetry to the short axis of bed 20. Other numbers of coils and other positions may be used.
  • coil 60 may include two spiraled coils that may be arranged in perpendicular configurations.
  • coil 60 may produce current in equal and opposite directions. Thus the current contribution from each of the two spiraled coils may cancel and the overall current of coil 60 may be zero.
  • Coil 60 e.g., contained in belt 30
  • Coil 60 may scan magnetic fields 12 along the patient's body and pass over an area that contains bonded nano-particles 50 that produce a local discrepancy in magnetic fields 12. Typically, only one of the two spiraled coils may pass over such areas at a time. If there is a discrepancy in the magnetic field of the one spiraled coil, there will be a discrepancy in the current of that spiraled coil.
  • the other spiraled coil typically does not pass over the area with the local discrepancy in magnetic fields 12 the coil will not have discrepancies in its current.
  • the two spiraled coils may have different currents and the overall current of coil 60 will not be zero.
  • Fig. 4 schematically illustrates a graph that shows the response of a spiral coil against the position of the spiral coil according to an embodiment of the present invention.
  • the response of spiral coil 60 (Fig. 3) may be for example measured in volts or other suitable units.
  • Curve 405 may indicate the electric current of coil 60 as it passes over an area of the body with no local discrepancies in magnetic fields 12. The current contribution from each of the two spiraled coils may cancel and the overall current of coil 60 may be zero.
  • Curve 410 may indicate the current of coil 60 as a first spiraled coil of coil 60 passes over an area of the body with a local discrepancy in magnetic fields 12. The two spiraled coils have different currents and the overall current of coil 60 will not be zero.
  • Curve 420 may indicate the current of coil 60 as the other or second spiraled coil of coil 60 passes over the same area with a local discrepancy in magnetic fields 12. Due to the inverse or mirrored configuration of the second spiraled coil with respect to the first, discrepancies in its current of the second spiraled coil may be of equal amplitude and opposite direction, as indicated by curve 420. Curve 425 may indicate the current of coil 60 in a position away from local discrepancies in magnetic fields 12. In such a position, there is typically no substantial discrepancies in the current of either of the spiraled coils and the overall current of coil 60 may return to zero.
  • magnetometers e.g. hall-effect or GMR devices arranged in a Wheatstone bridge arrangement may scan magnetic fields 12 along the patient's body and pass over an area that contains bonded nano- particles 50 that produce a local discrepancy in magnetic fields 12.
  • hall-effect or GMR devices arranged in a Wheatstone bridge arrangement may scan magnetic fields 12 along the patient's body and pass over an area that contains bonded nano- particles 50 that produce a local discrepancy in magnetic fields 12.
  • system 100 may include additional localization devices.
  • Localization devices 80 for example may include a hand held ultrasound transing system.
  • transducers 72 for example, piezoelectric transducers, that may be arranged in direct contact with a patient's body.
  • a signal sent by transducer 72 may reflect, for example, off the walls of the patient's body, for example, near the gastrointestinal tract, and may be received by transducers 72.
  • a minimum of three transducers 72 may be used.
  • a plurality of transducers 72 may be arranged in belt 30 separated by a predetermined distance. Cross correlating signals from transducers 72 may be processed, for example, by workstation 40 to produce localization data relating to magnetic field measurements of the examined body.
  • transducers 72 may operate in combination, where at least three receivers 71 may be used.
  • receivers may function as transducers.
  • the receivers 71 may be arranged at different locations, for example, in direct contact with a body.
  • a signal, sent by transducer 72 may be received by receiver 71, and may then be sent to workstation 40.
  • Localization data relating to magnetic field measurements of the examined body may be produced based on the distance between transducers 72 and receivers 71 and the differences in the amplitudes of the signals receivers 71 receive.
  • system 110 may be an MRI based system, e.g. a low power MRI system and/or system based on MRI technology.
  • System 110 may be used to detect pathologies in human and/or animal bodies by detecting resonance effect in water molecules 54 that may be attracted, or adsorbed onto the surface of magnetically susceptible nano-particles 50 that bond to target substances. The presence of an accumulation of such adsorbed water molecules 54 may indicate a presence of the target substances.
  • the excited water molecules may start to relax due to two main processes: intra-molecular interactions between protons and associated electrons in the same molecule and intermolecular interactions due to diffusion and molecular rotation. In pure or unbound water those interactions may be weak and relaxation time may be relatively long, e.g., about 4 seconds. Water molecule adsorbed to magnetically susceptible nano-particles 50 may still rotate under the effect of RF energy as a result of Brownian rotation of the particle itself. Since nano-particles 50 are typically small, the effect of unbounded magnetically susceptible nano-particles 50 on the relaxation time may be relatively small.
  • water molecules 54 adsorbed to the particle surface that is covalently bonded typically are not free to rotate and may relax only by the Neel mechanism of the particles itself.
  • its relaxation time is very short.
  • intermediate ranges of relaxation times may also be detected, for example, relaxation times that correspond neither to bound water molecules 54 nor free water molecules.
  • magnetically susceptible nano-particles 50 may get into a cell or macrophage. The nano-particles' 50 ability to move is limited which may lead to an intermediate range of relaxation times.
  • the size of magnetically susceptible nano-particles 50 may be chosen according to the desired relaxation time.
  • system 110 may generate a constant magnetic field 15, for example with magnets 11 and 13.
  • system 110 may include one or more components to excite water molecules, for example, RF coils 60 that may generate RF pulses in the presence of magnetic field 15, which may for example, resonate water molecules 54.
  • Adsorbed water molecules 54 typically have shorter relaxation times than free, unadsorbed or unbound water molecules. Thus, by detecting water molecules 54 bound to nano- particles 50 that may bond to substances indicating a pathology, system 110 may detect the pathological structures.
  • the relaxation time or behavior of water molecules may be measured, for example, using low intensity MRI devices with modified hardware and software to analyze relaxation time of each Vauxhall
  • RF coils 60 may emit RF pulses that in the presence of constant magnetic field 15 may resonate water molecules throughout the body.
  • the excited molecules typically relax or realign with the conformation and/or orientation of the nano-particles.
  • the relaxation time of water molecules 54 that are adsorbed to a covalently bonded particle is faster than the relaxation time of water molecules that are not bonded.
  • Embodiments of the present invention may use the difference in the relaxation behavior of water molecules 54 bonded to nano-particles 50, bonded to other particles and not bonded, to detect or isolate water molecules 54 bonded to nano-particles 50.
  • Introducing magnetically susceptible nano-particles 50 into a patient's body may significantly affect the relaxation time and behavior of water molecules in the body, for example, due to local magnetic fields created by the magnetically susceptible nano- particles 50.
  • an RF pulse may be emitted (e.g., by RF coils 60) at the resonance frequency of the water molecules 54.
  • System 110 may include additional coils 60 and additional for example, gradient coils, may create a gradient magnetic field 15 along the Z-axis, for example, perpendicular to the surface of bed 20. There may be a magnetic amplitude and direction associated with each position along a gradient magnetic field 15. The amplitude of the gradient magnetic field may allow nano-particle MRI imaging. The direction of the gradient magnetic field 15 associated with the amplitude of gradient magnetic field 15 may provide localization data for those nano- particles 50. Workstation 40 may process and present data to a viewer, for example, magnetic field measurements, images or image data, etc. Referring to Fig. 2C, in one embodiment of the present invention, system 120 may include a bed or platform 140, which may be used to position the patient.
  • System 120 may include methods, components and/or configurations used in systems 100 and/or 110 for example either an MRI based system and/or a magnetometer based system.
  • system 120 may generate a constant magnetic field 15 and/or an alternating magnetic field 12.
  • System 120 may produce and magnetic fields and measure discrepancies in those fields, according to embodiments described with reference to Fig. 2A and Fig. 2B.
  • Bed 140 may move and/or rotate in order to refine or change the body's location during the diagnostic test period. Bed 140 may move relative to a device that generates or scans magnetic fields 12 or 15 (e.g., measures magnetic field discrepancies), which may include magnets 11 and/or 13 and coils 60.
  • the location of discrepancies in magnetic fields, and thus of nano-particles 50 or water molecules 54 bonded to nano-particles 50 that produce the discrepancies, may be determined by the location of the magnetic field scanning device relative to bed 140 or the body at the time of detection.
  • magnet 11 may be positioned above bed 140 and may move along an upper track, magnet 11 may be located in or adjacent to base 10 and bed 140 may be moved on base 10 to allow magnetic field 12 or 15 to surround the patient's body.
  • systems 110 and 120 may generate low intensity constant magnetic fields 15, for example, with intensities of 0.04 - 0.2 Tesla.
  • low intensity constant magnetic fields 15 produce poor quality MRI images of body tissues, and thus, are not used in conventional MRI procedures.
  • the low intensity constant magnetic field 15 and/or low detection times may enable detection of particles, for example, water molecules 54 (bound or unbound) and their location relative to a given space.
  • systems 100, 110 or 120 may include an additional imaging or detection device or mechanism that may be used to scan, map or image the patient's body, for example, organs and/or tissues.
  • systems 100, 110 or 120 may include an imaging device that may include an imager and a localization tool, which may provide information relating to location, for example, of a substance indicating a pathology, the imaging device or an element thereof, magnetically susceptible nano-particles 50, water molecules 54 bonded or adsorbed onto magnetically susceptible nano-particles 50, anatomical structures and/or other related objects or devices.
  • Additional imaging mechanisms may include, for example, ultrasound screening, MRI, X ray screening, CT, or any other suitable method.
  • the results of the magnetic field measurement may be combined with additional image data to provide both detection and localization of the antigens or pathologies.
  • Systems 100, 110 and 120 may localize detected substances or pathologies with respect to components of the systems 100, 110 and 120 (e.g., bed 20 or 140) or with respect to another reference such as a position along a gradient magnetic field 15 (e.g., which may also be associated with the positions of components of the systemslOO, 110 and 120).
  • Image data may provide localization of organs with respect to the positions of components of the systems 100, 110 and 120.
  • systems 100, 110 and 120 may provide both detection and localization of the antigens or pathologies.
  • data from the low intensity magnetic probe 80 and the additional imaging results may be combined to localize detected magnetically susceptible nano-particles 50 to a specific body part, such as an organ or tissue, thus providing detection of, for example, a pathology location.
  • Combining data that may be collected by separate mechanisms may involve normalizing a coordinate systems and/or superimposing data and/or results as is known.
  • workstation 40 may combine data.
  • systems 100, 110 or 120 may provide data relating to antigens or the concentrations of substances indicating a pathology.
  • systems 100, 110 or 120 may provide data relating to concentrations of magnetically susceptible nano-particles 50, water molecules 54 bonded or adsorbed onto magnetically susceptible nano-particles 50, the decay of such particle concentrations and/or other pathology detection data.
  • Fig. 5 A is a flowchart of a method for detecting target substances according to one embodiment of the present invention.
  • magnetically susceptible nano-particles may be introduced into a patient's body by, for example, injecting or swallowing nano-particles (e.g., in suspension).
  • the nano-particles may be conjugated or coated with one or more receptor molecules.
  • receptor molecules may include antibodies, which are attracted to and may typically accumulate near a target substance.
  • the conjugated nano-particles, via the receptor molecules, may be more concentrated near corresponding antigens than throughout a body.
  • the body may be exposed to an alternating magnetic field.
  • the alternating magnetic field around the body may excite the magnetic nano-particles inside the body.
  • operation 510 may be executed some time after operation 500, for example, a few minutes after, so that at least some of the introduced nano-particles have substantially sufficient time to diffuse or travel through the blood stream where they may accumulate near a target substance.
  • disturbances in the alternating magnetic field may be detected.
  • one or more devices may be used, for example, portable magnetic probe sensors such as magnetometers.
  • the device may scan the body or the area substantially surrounding the body and may generate data relating to the magnetic field, for example, over a period of time, of the body or of the surrounding area.
  • the device may process data relating to the magnetic field surrounding the body.
  • a magnetometer may substantially only detect disturbances in the alternating magnetic field surrounding the body.
  • the nano-particles introduced in operation 500 that have bonded or attached to a biological substance typically do not align or align less with the produced alternating magnetic field. Since these bonded or attached magnetically susceptible nano-particles typically do not substantially align with the produced alternating magnetic field, they cause disturbances in the alternating magnetic field that is detected by the magnetometer indicating a pathology.
  • a localization device may localize discrepancies in the magnetic field for example detected in operation 520, for example, by an array of transducers and receivers creating an ultrasound image, or an hand held ultrasound or by by MRI images.
  • the detection data may be localized with respect to system position. Additional image data may provide the location of organs or biological structured with respect to system position.
  • the detection data may be combined with the image, for example, to provide both detection and localization of the pathologies.
  • An imaging device may generate image data that relates to the body. Magnetic field detection measurement may be combined with image data to provide both detection and localization of the antigens or pathologies.
  • the fused data of the disorder location and image location may be displayed.
  • the monitor may be part of a workstation that a healthcare professional may view.
  • the monitor may display data relating to the magnetic field surrounding the body, disturbances in that field, localization data, image data or any combination, derivation or superimposition of these data.
  • FIG. 5B is a flowchart of a method for detecting target substances according to one embodiment of the present invention.
  • 60O 5 magnetically susceptible nano-particles may be introduced into a body.
  • the body may be exposed to a magnetic field.
  • the magnetic field may include a constant or alternating magnetic field.
  • electromagnetic radiation such as, for example, a series of RF pulses or signals may be applied and the response may be detected and measured.
  • the patient's body may be positioned within the range of the magnetic field.
  • the RF pulses may be substantially at the resonance frequency of water molecules. Unbound water molecules may resonate with relatively long relaxation times.
  • Bound water molecules typically may have short relaxation times, which may depend on the particles to which the water molecule may bond and/or the type of bond. Water molecules
  • substantially bonded or adsorbed onto the nano-particles may have a specific relaxation time, which may depend on the size and/or concentration of the nano-particles.
  • operation 610 may be executed some time after operation 600, for example, a few minutes after, so that at least some of the introduced nano-particles have substantially sufficient time to adsorb water molecules and to travel through the blood stream where they may accumulate and bond or attach, for example, around antigens or pathologies.
  • imaging e.g., MRI using RF and gradient coils or ultrasound may be used, hi operation 630, pathologies may be detected.
  • the results of the magnetic field detection measurement may be combined with additional image data, for example, recorded by an imaging device, to provide both detection and localization of the antigens or pathologies, hi operation 640, the fused data may be displayed. Other operations or series of operations may be used.

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Abstract

L'invention concerne un procédé et un système pouvant permettre la détection de pathologies, par exemple, la détection du cancer dans, par exemple, le tractus gastro-intestinal, à l'aide, par exemple, de nanoparticules sensibles au magnétisme. L'imagerie ultrasonore, la technologie IRM ou d'autres techniques appropriées peuvent être utilisées conjointement afin de localiser des pathologies détectées.
PCT/IL2006/000422 2005-04-04 2006-04-04 Dispositif et procede de detection de pathologies Ceased WO2006106507A2 (fr)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012063186A1 (fr) * 2010-11-11 2012-05-18 Koninklijke Philips Electronics N.V. Examen du côlon par imagerie à particules magnétiques
GB2567132A (en) * 2017-08-10 2019-04-10 Hipermag Ltd Magnetic structures
CN112823765A (zh) * 2019-11-21 2021-05-21 上海市第六人民医院 超声可视化纳米磁调控装置

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4117782C2 (de) * 1991-05-28 1997-07-17 Diagnostikforschung Inst Nanokristalline magnetische Eisenoxid-Partikel, Verfahren zu ihrer Herstellung sowie diagnostische und/oder therapeutische Mittel
US20020177769A1 (en) * 2001-04-23 2002-11-28 The Regents Of The University Of California Method and apparatus for locating cells in the body by measuring magnetic moments

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012063186A1 (fr) * 2010-11-11 2012-05-18 Koninklijke Philips Electronics N.V. Examen du côlon par imagerie à particules magnétiques
US9820672B2 (en) 2010-11-11 2017-11-21 Koninklijke Philips N.V. Colon screening by using magnetic particle imaging
GB2567132A (en) * 2017-08-10 2019-04-10 Hipermag Ltd Magnetic structures
CN112823765A (zh) * 2019-11-21 2021-05-21 上海市第六人民医院 超声可视化纳米磁调控装置

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