WO2008091712A2 - Imagerie à résonance paramagnétique électronique en champ de faible intensité - Google Patents

Imagerie à résonance paramagnétique électronique en champ de faible intensité Download PDF

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Publication number
WO2008091712A2
WO2008091712A2 PCT/US2008/001136 US2008001136W WO2008091712A2 WO 2008091712 A2 WO2008091712 A2 WO 2008091712A2 US 2008001136 W US2008001136 W US 2008001136W WO 2008091712 A2 WO2008091712 A2 WO 2008091712A2
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WO
WIPO (PCT)
Prior art keywords
squid
set forth
coil
processing system
circuit
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Application number
PCT/US2008/001136
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English (en)
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WO2008091712A3 (fr
Inventor
Inseob Hanh
Peter Day
Konstantin I. Penanen
Byeong H. Eom
Mark S. Cohen
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California Institute Of Technology
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Publication of WO2008091712A2 publication Critical patent/WO2008091712A2/fr
Publication of WO2008091712A3 publication Critical patent/WO2008091712A3/fr
Priority to US12/359,576 priority Critical patent/US8179135B2/en

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Classifications

    • 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
    • G01R33/28—Details of apparatus provided for in groups G01R33/44 - G01R33/64
    • G01R33/32—Excitation or detection systems, e.g. using radio frequency signals
    • G01R33/323—Detection of MR without the use of RF or microwaves, e.g. force-detected MR, thermally detected MR, MR detection via electrical conductivity, optically detected MR
    • G01R33/326—Detection of MR without the use of RF or microwaves, e.g. force-detected MR, thermally detected MR, MR detection via electrical conductivity, optically detected MR involving a SQUID
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N24/00—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects
    • G01N24/10—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects by using electron paramagnetic resonance
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00—Arrangements or instruments for measuring magnetic variables
    • G01R33/02—Measuring direction or magnitude of magnetic fields or magnetic flux
    • G01R33/035—Measuring direction or magnitude of magnetic fields or magnetic flux using superconductive devices
    • G01R33/0354—SQUIDS
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00—Arrangements or instruments for measuring magnetic variables
    • G01R33/02—Measuring direction or magnitude of magnetic fields or magnetic flux
    • G01R33/035—Measuring direction or magnitude of magnetic fields or magnetic flux using superconductive devices
    • G01R33/0354—SQUIDS
    • G01R33/0358—SQUIDS coupling the flux to the SQUID
    • 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]
    • G01R33/445—MR involving a non-standard magnetic field B0, e.g. of low magnitude as in the earth's magnetic field or in nanoTesla spectroscopy, comprising a polarizing magnetic field for pre-polarisation, B0 with a temporal variation of its magnitude or direction such as field cycling of B0 or rotation of the direction of B0, or spatially inhomogeneous B0 like in fringe-field MR or in stray-field imaging

Definitions

  • the present invention relates to electron paramagnetic resonance imaging.
  • Electron paramagnetic resonance (EPR) imaging has been recently recognized as an important tool for non-invasive imaging of free radicals and REDOX (reduction/oxidization) metabolism.
  • EPR Electron paramagnetic resonance
  • Electron paramagnetic resonance may be observed at frequencies of a few MHz in magnetic fields of a few Gauss, up to the microwave region in a magnetic field of a few thousand Gauss.
  • the latter frequency region is often chosen because the signal-to-noise ratio is usually much improved with the use of relatively high magnetic fields, which implies a relatively high Lamour frequency.
  • microwave radiation e.g., in the 1 GHz to 60 GHz region
  • a resonance cavity that is not suitable for non-invasive imaging of a large size living animal, such as a human.
  • the motion of an animal in a resonance cavity such as motion due to respiration or a beating heart, may cause changes in the resonance frequency of the cavity.
  • the skin depth decreases as the frequency of the electromagnetic radiation increases, which may preclude imaging within regions of interest in a human for EPR imaging systems operating in the 1 GHz to 60 GHz region.
  • high magnetic fields often pose a safety hazard.
  • FIG. 1 illustrates an EPR SQUID detection system according to an embodiment.
  • FIG. 2 illustrates a coil system according to the embodiment of Fig. 1.
  • FIG. 3 illustrates a microwave EPR SQUID detection system according to an embodiment.
  • Fig. 1 is a schematic illustrating EPR detection with a SQUID
  • Object 102 is the specimen (e.g., human) to be imaged.
  • Coil systemlO4 comprises various coils to apply to object 102 a magnetic field having a spatial gradient, and to provide pulses of electromagnetic excitation to object 102 so that electron spin echo pulses may be detected.
  • the Lamour frequency of an electron spin echo pulse depends on magnetic field strength, so that spectral analysis applied to the received electron spin echo pulses yields imaging information.
  • the various components making up coil system 104 are not shown in Fig. 1 , but are described later with respect to Fig. 2.
  • the remaining components in the detector of Fig. 1 are kept at a low temperature during operation so that they operate in their superconducting state.
  • the temperature is about 4.2 Kelvin, although for some embodiments, high-temperature superconductors may be used.
  • the EPR imaging embodiment of Fig. 1 comprises a second order gradiometer within dashed rectangle 108 to receive the electron spin echo pulses from object 102.
  • the gradiometer comprises two turns (108A), four turns (108B), and two turns (108C) of 80 ⁇ m diameter Nb (Niobium) wire wound on a MACOR® former grooved for the wire.
  • MACOR is a registered trademark of Corning Glass Works Corporation, Houghton Park, Corning, New York.
  • the gradiometer baseline is 55 mm and the loop diameter is 25.4 mm.
  • the inductance of the gradiometer is 1.02 ⁇ H.
  • the total effective sensing area of the gradiometer is about 6.5 mm 2 .
  • the average distance from the gradiometer to object 102 is about 15 mm.
  • the EPR imaging system of Fig. 1 is not sensitive to homogeneous magnetic fields, such as unwanted magnetic fields from far away sources that are essentially homogenous over the scale of the gradiometer.
  • Other embodiments other than that described with reference to Fig. 1 may utilize other types of pickup coils sensitive to electron spin echo pulses.
  • Coil 110 is electrically connected to the gradiometer and is magnetically coupled to SQUID 1 12.
  • SQUID 112 comprises SQUID loop 112A and Joshepson junctions 1 12B, and for the embodiment of Fig. 1 is a DC (Direct Current) SQUID.
  • Magnetic flux from coil 110 links SQUID loop 112A.
  • the combination of coil 110 and the gradiometer serves as a flux transformer.
  • the physical dimension of SQUID 1 12 is on the order of microns, whereas the gradiometer is on the order of centimeters.
  • the operation frequency may be significantly lowered when compared to prior art systems.
  • the operating frequency may be 1.4 MHz at the Earth's magnetic field of 0.5 Gauss.
  • the electron spin echo pulses may be detected by use of a gradiometer without the need for a cavity
  • Fig. 1 also makes use of a SQUID array amplifier, comprising a plurality of coils coupled to the output of SQUID 1 12, and a plurality of
  • SQUIDs in a SQUID array amplifier In the simplified SQUID array amplifier of Fig. 1, coils 114A, 1 15 A, 116A, and 117A are connected in series with each other, and connected to the output of SQUID ,112 by way of resistor 1 18. SQUIDs 114B, 115B,
  • SQUID 114B is magnetically coupled to coil 114A
  • SQUID 115B is magnetically coupled to coil 115A
  • SQUID 116B is magnetically coupled to coil 1 16A
  • SQUID 1 17B is magnetically coupled to coil 1 17A.
  • the SQUID array amplifier is expected to have a bandwidth of about 1 MHz using commercially available
  • Fig. 2 is a schematic illustration of a coil system for generating magnetic fields so that unpaired electrons in object 102 give off electron spin echo pulses.
  • Fig. 2 illustrates a coil system comprising square Helmholtz coil 202 to provide a homogenous static magnetic field, square Maxwell coil 204 to provide a z-gradient in the applied magnetic field, x-gradient coil 206 to provide an x-gradient in the applied magnetic field, and y-gradient coil 208 to provide a y-gradient in the applied magnetic field.
  • the x-y-z directions are indicated by the coordinate system displayed in Fig. 2.
  • Fig. 2 further illustrates pre-polarizing coil 210 to increase the magnetization of object 102, and excitation coil 212 to provide an oscillating magnetic
  • excitation pulses generated by excitation coil 212 provide the ⁇ /2 and ⁇ magnetic pulses that are often described semi-classically as tipping the magnetization vectors in object 102 so that electron spin echo pulses are generated.
  • Fig. 2 also illustrates a portion of a Dewar (106) to contain the flux transformer and the SQUID detector components illustrated in Fig. 1.
  • Fig. 2 like Fig. 1, is a schematic, so that relative sizes are not implied.
  • the coils illustrated in Fig. 2 are simplified, so that electrical connections and individual turns are not shown, but rather, the coils are schematically illustrated as simple rectangles, or simple cylinders (to represent solenoids, to be discussed later) in the case of pre-polarization coil 210.
  • the measurement sequence includes a pre-polarization interval, followed by encoding and acquisition.
  • Pre-polarization coil 210 polarizes object 102 in a higher magnetic field than the homogeneous static magnetic field provided by Helmholtz coil 202, and this pre-polarization technique uses a fast ramping-down of the pre-polarizing field.
  • pre-polarizing coil 210 comprises two identical short and thick solenoids, and has a symmetric design so that it does not induce an appreciable magnetic flux to the gradiometer. In this way, a current-limiting device is not necessarily needed in the gradiometer to protect SQUID 1 12 from an excessive current that may be induced by a fast change (about 10 T/s) of the pre-polarizing field.
  • pre-polarization coil 210 may be sufficiently corrected by moving Dewar 106 with respect to pre-polarization coil 210 while observing the SQUID voltage response to a low-frequency AC (Alternating Current) magnetic field induced in pre-polarization coil 210.
  • the polarization provided by pre-polarization coil 210 may not be required for the EPR detection if the signal strength is large enough.
  • the 210 may be chosen for easy construction, convenient imaging volume access, and based upon the tentative sample size of object 102.
  • the thickness and the diameter of the wire for pre-polarization coil 210 were determined to maximize the field strength at the center at fixed power. Once the shape and the size are determined, the ratio of the field strength to the applied power is independent of the wire diameter and the number of windings.
  • pre-polarization coil 210 it was found that if the two solenoids forming pre-polarization coil 210 were aligned coaxially, then the close proximity of the massive copper coils to the gradiometer induced significant thermal noise. To reduce the noise and to increase the magnetic field with the distance from the gradiometer, the solenoids were aligned in a V shape so that the separation is larger at the top end near the gradiometer. This arrangement was found to partially compensate the sensitivity profile of the gradiometer.
  • Fig. 2 may be described as follows.
  • pre-polarization coil 210 two solenoids were used, each with an outer diameter of 204 mm, an inner diameter of 38 mm, a thickness of 35 mm, with a top separation of 149 mm and a bottom separation of 19 mm.
  • the windings comprised 398 turns in 6 parallel groups, to provide a magnetic field of 2.4 mT/A.
  • Helmholtz coil 202 is a square shaped coil with a 1 108 mm side and a separation of 603 mm.
  • the windings comprised 30 turns to provide 44 ⁇ T/A.
  • Maxwell coil 204 is a square shaped coil with a 1 108 mm side, with windings comprising 15 turns in two parallel groups, to provide a magnetic field gradient of 32 ⁇ Tm 'A '1 .
  • X-gradient coil 206 and y-gradient coil 208 are each a bi-planar coil, each with a long side of 1087 mm, a short side of 188 mm, having a plane separation of 1 108 mm and an in-plane separation of 647 mm. Each has windings comprising 15 turns in two parallel groups, to provide a magnetic field gradient of 12 ⁇ TnV'A "1 .
  • Excitation coil 212 comprised a pair of rectangular coils, each with a long side of 400 mm, a short side of 319 mm, with a separation of 183 mm, with each winding comprising 2 turns to provide a magnetic field of 9.5 ⁇ T/A.
  • Fig. 3 is a schematic illustrating a microwave SQUID detector system according to another embodiment. Again, only a portion of Dewar 106 is shown, where system components 302, 304, 306, 308, 310, and 312, are electronic systems that need not be cooled, or at least not cooled to the same low temperature as the rest of the system
  • Components 316 and 318 are co-planar waveguides with connections to frequency up-converter 302 and high electron mobility transistor (HEMT) amplifier 314. Their frequency of operation for some embodiments may be about 10 GHz.
  • Co-planar waveguide 324 may comprise a meandering half-wavelength line (one-half the wavelength of the carrier provided by frequency up-converter 302). The combination of waveguide 324 and capacitors 320 and 322 form a resonator loaded by SQUID 326.
  • SQUID 326 is a DC (Direct Current) SQUID that may be biased by a direct current, indicated by bias port 328.
  • bias port 328 is optional, and the bias may be provided by the microwave current by way of co-planar waveguides 316 and 318.
  • another coil, modulation coil 330 is magnetically coupled to SQUID 326 and is driven by oscillator 312 at some specified frequency.
  • Dashed line 332 indicates that for some embodiments the components within dashed line 332 may be fabricated on a single chip.
  • Fig. 3 may operate SQUID 326 in a non-flux-locked mode. Based on prior art systems, it might be expected that operation in a non-flux-locked mode might be hampered by the periodic nature of the SQUID response function, which limits the dynamic range and may lead to the possibility that stray magnetic fields bias the SQUID at a point of degraded sensitivity. However, in the embodiment of Fig.
  • this problem is mitigated by applying a high frequency modulation to SQUID 326 by use of modulation coil 330, and by implementing what might be termed a / and 2/ modulation scheme, where / is the modulation frequency provided by oscillator 312.
  • the output of SQUID chip 332 is lock- in detected both at the frequencies / and 2/ to provide output signals
  • phase locked loop technology may be utilized to generate the sinusoids sin ⁇ t and cos 2 ⁇ t.
  • the time average ( > may be performed in the analog domain by a mixer followed by a low pass filter. These techniques are well known in the art of communication technology.
  • a phase angle may be defined by
  • the modulation frequency / may be about 100
  • the carrier frequency provided by frequency up-converter 302 may be about 10 GHz, and the bandwidth of the system may be about 10 MHz.
  • the microwave signal provided over waveguide 318 was amplified with a 4 to 12 GHz HEMT amplifier with a noise temperature of 5K, and a mixer was used to demodulate the microwave signal to recover the 10 MHz SQUID signal. A second demodulator mixed this signal down to baseband.
  • the time average may be performed by low pass filtering the output of the mixer.
  • Analog-to-digital conversion is applied, followed by digital signal processing to provide the phase angle ⁇ ( ⁇ ).
  • Processing system 306 includes the digital signal processing, and includes other control functions for operating frequency up- converter 302 by way of digital-to-analog converter 304. Some or all of the control and processing represented by processing system 306 may be implemented by special
  • waveguides 316 and 318 may be shared by a plurality of resonators, each loaded by a SQUID with its own modulation coil and gradiometer. Each resonator is tuned to a different carrier frequency. A comb of microwave frequencies is used to simultaneously excite all of the resonators of the array. Standard frequency de-multiplexing techniques may be employed to separate out the SQUID responses, followed by the / and 2/ modulation scheme as described earlier.
  • each SQUID may be biased by the microwave carrier amplitude, and the modulation coils may be connected in series. As a result, such embodiments may utilize thousands of detectors, where the warm signal connections comprise only two pairs of wires for the modulation coils, and a single microwave coaxial cable.
  • a mathematical relationship or mathematical transformation may express a relationship by which a quantity is derived from one or more other quantities by way of various mathematical operations, such as addition, subtraction, multiplication, division, etc.
  • a mathematical relationship may indicate that a quantity is larger, smaller, or equal to another quantity.

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  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Condensed Matter Physics & Semiconductors (AREA)
  • High Energy & Nuclear Physics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Measuring Magnetic Variables (AREA)
  • Magnetic Resonance Imaging Apparatus (AREA)

Abstract

Selon un mode de réalisation de l'invention parmi d'autres, un transformateur de flux est couplé magnétiquement à un SQUID, et une pluralité de SQUID, montés en série, sont couplés magnétiquement à la sortie dudit SQUID.
PCT/US2008/001136 2007-01-25 2008-01-28 Imagerie à résonance paramagnétique électronique en champ de faible intensité WO2008091712A2 (fr)

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US12/359,576 US8179135B2 (en) 2008-01-28 2009-01-26 Low field electron paramagnetic resonance imaging with SQUID detection

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US60/897,356 2007-01-25

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WO2013074068A1 (fr) * 2011-11-14 2013-05-23 Neocera, Llc Procédé et système de localisation de défauts ouverts dans des dispositifs électroniques ayant un magnétomètre radiofréquence (rf) basé sur dispositif supraconducteur à interférence quantique (squid) cc

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US5885215A (en) * 1989-07-06 1999-03-23 U.S. Philips Corporation Method of reconstructing the spatial current distribution in a biological object, and device for performing the method

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Title
CHUI T ET AL: "High-resolution displacement sensor using SQUID array amplifier" NUCLEAR PHYSICS B. PROCEEDINGS SUPPLEMENT, NORTH-HOLLAND, AMSTERDAM, NL, vol. 134, 1 September 2004 (2004-09-01), pages 214-216, XP004573801 ISSN: 0920-5632 *
MCDERMOTT R ET AL: "SQUID-Detected Magnetic Resonance Imaging in Microtesla Magnetic Fields" JOURNAL OF LOW TEMPERATURE PHYSICS, KLUWER ACADEMIC PUBLISHERS-CONSULTANTS BUREAU, NE, vol. 135, no. 5-6, 1 June 2004 (2004-06-01), pages 793-821, XP019282681 ISSN: 1573-7357 *
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013074068A1 (fr) * 2011-11-14 2013-05-23 Neocera, Llc Procédé et système de localisation de défauts ouverts dans des dispositifs électroniques ayant un magnétomètre radiofréquence (rf) basé sur dispositif supraconducteur à interférence quantique (squid) cc
US20140253111A1 (en) * 2011-11-14 2014-09-11 Antonio Orozco Method and system for localization of open defects in electronic devices with a dc squid based rf magnetometer
US9529035B2 (en) * 2011-11-14 2016-12-27 Neocera, Llc Method and system for localization of open defects in electronic devices with a DC squid based RF magnetometer

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