WO2003038395A2 - Remote nmr/mri detection of laser polarized gases - Google Patents
Remote nmr/mri detection of laser polarized gases Download PDFInfo
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- WO2003038395A2 WO2003038395A2 PCT/US2002/032471 US0232471W WO03038395A2 WO 2003038395 A2 WO2003038395 A2 WO 2003038395A2 US 0232471 W US0232471 W US 0232471W WO 03038395 A2 WO03038395 A2 WO 03038395A2
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Definitions
- This invention pertains generally to nuclear magnetic resonance spectroscopy, and more particularly to an apparatus and method for NMR spectroscopy by spatially and temporally remote signal detection or optical detection.
- Nuclear magnetic resonance (NMR) has developed into a very versatile analytical tool for the study of molecular structures and surface features.
- NMR is a relatively insensitive detection method compared to others since the NMR signal depends on the population difference between two spin states.
- a number of approaches have been taken to increase the spatial, temporal and spectral resolution of NMR devices.
- One approach to increasing sensitivity is increasing magnetic field strengths since NMR sensitivity increases as the 7/4 th power of the strength of the magnetic field.
- NMR and MRI signals could be enhanced through the use of hyperpolarized Noble gases.
- Xenon and other Noble gases that are members of the zero group of the periodic table of elements, exhibit NMR characteristics that are highly sensitive to the chemical environment surrounding the atoms.
- the characteristic and highly sensitive chemical shift of 129 Xe, and other noble gases has been widely used to probe the structure of molecules, microporous solids, such as zeolites and clathrates, and the surface features of membranes and other biological and non-biological materials.
- Recent improvements in the methods for producing hyperpolarized Noble gases have lead to many innovative NMR and MRI applications including medical imaging of the lungs and other parts of the body.
- the technique typically used to produce hyperpolarized Noble gases involves the indirect transfer of angular momentum from optical photons to the nuclei of the noble gas molecules called "optical pumping and spin exchange.”
- Optical pumping uses an alkali metal intermediary such as Rb, K, or Cs with a valence electron carrying the spin polarization to polarize the Noble gas.
- An intermediary is used because the polarization of photons cannot be directly transferred to the nuclear spins of the Noble gas atoms.
- an alkali metal such as rubidium is vaporized and mixed with a Noble gas.
- the mixture is irradiated with circularly polarized laser light at the wavelength of the first principal resonance (i.e. its principal electric-dipole transition).
- the wavelength is 795nm, for example.
- the alkali metal vapor absorbs a photon and the valence electron transitions from a ground state to an excited state.
- Hyperpolarized Noble gas atoms can also transfer spin polarization to the nuclei of atoms in sample molecules exposed to the gas.
- spin polarization There are two primary techniques for the transfer of enhanced spin polarization from laser-polarized Noble gases to other nuclei such as protons that have been developed: (1) cross relaxation (SPINOE) and (2) cross polarization (CP).
- SPINOE cross relaxation
- CP cross polarization
- SPINOE spin-polarization-induced nuclear Overhauser effect
- Cross polarization requires a static magnetic dipole interaction between the xenon spins and the nuclei that is the target of the transfer. With cross polarization, the xenon and the target nuclei are locked with simultaneous electromagnetic fields at two separate frequencies creating a quantum transition that allows the polarization to be transferred from the xenon to the target nucleus.
- Hyperpolarized xenon and other noble gases can also be combined with a gas or fluid carrier that is chemically, biologically or materially compatible with the sample to be analyzed.
- SQUID superconducting quantum interference devices
- the AC or rf SQUID and the DC SQUID are the two main types of SQUID devices that have been developed.
- the SQUID device may be considered a flux to voltage converter consisting of a superconducting ring interrupted by one or more junctions called Josephson junctions and a large area flux antenna. Magnetic flux modulates the current passing through the Josephson junction.
- SQUID devices exhibit instability in the presence of the pulsed magnetic fields that are necessary to prepare (encode) nuclear magnetization for detection. Consequently, these devices may be limited in their utility because of this instability.
- the present invention is directed to an apparatus and method for Nuclear Magnetic Resonance or Magnetic Resonance Imaging that provides optimized NMR/MRI encoding coil geometries and conditions and optimized detecting methods and conditions through the spatial and temporal separation of the encoding and detecting steps and by the use of signal carrying sensors.
- the invention comprises an encoder having a sample analysis vessel or chamber; a supply of polarized signal carrier atoms or molecules configured to discharge signal carrier sensors into the sample analysis vessel; and a detector configured to receive encoded signal sensors from the sample analysis vessel.
- the preferred signal carriers are hyperpolarized Noble gases, particularly xenon. Although xenon is preferred, essentially any gas or liquid that has a long polarization relaxation time can be used. A continuous source of laser polarized xenon through spin exchange with an alkali-metal such as rubidium in a low magnetic field is preferred.
- the source of the supply of signal carriers, the sample analysis vessel in the encoder and the detector chamber are operably interconnected with a continuous circulatory system including a pump.
- the circulatory system includes a number of flow shut off valves allowing the control of the flow of signal carrier molecules between each of the system components.
- the encoded signal carrier from the encoder can be enclosed in a tube or vessel and physically carried from one location to another.
- the signal carriers may be mixed with a liquid or gas that assists in the transportation or movement of the carrier molecules from the source of supply to the encoder and then to the detector.
- the transportation liquid is preferably chemically and biologically compatible with the sample or humans.
- the spatial and temporal separation of the encoding and detecting steps allows the conditions of each step to be optimized depending on the subject of investigation.
- the encoding can take place in a low magnetic field and the detecting step can be conducted in a high magnetic field NMR detector.
- the encoding takes place in a high magnetic field coil and the detection takes place in a high magnetic field NMR detector. While high and low magnetic field encoding coils and detection coils are shown for illustration, it will be understood that essentially any combination of magnetic field strengths can be used in the encoding coil and detector coil embodiment of the invention.
- the encoding takes place in a high or low magnetic field and detection is performed by a Superconducting Quantum Interference Device that directly measures magnetic flux.
- the detector is an optical detector that probes the build-up of spin polarization due to spin exchange between the encoded noble gas and an initially unpolarized alkali metal, such as rubidium, in the gas phase, which is exposed to the encoded noble gas.
- Optical detection using a magnetometer with nonlinear Faraday rotation is used in another embodiment of the invention.
- the pulse sequences that are typically needed can be split between the encoder and detector. The preferred sequence includes a period of time for the signal carriers to associate with the sample before a first 90° pulse in the encoding coil.
- a second 90° pulse in the encoding coil is applied after a dwell time.
- a third 90° pulse with an FID is applied in the detecting coil after a travel time during which the encoded signal carriers have been transferred to the detector coil in one embodiment.
- the invention also includes a method for remote NMR/MRI that generally comprises exposing a sample to a supply of polarized signal carriers and encoding NMR signals and then transferring the encoded carriers to a detector and detecting the encoded signals and analyzing the resulting spectra.
- the method of the invention may also include concentrating the encoded signal carriers in the detection analysis vessel or chamber by physical compression or thermal condensation, for example. Concentration of the encoded signal carriers increases the signal to noise ratios and provides a higher spin density.
- the coil geometry of the field coil in one embodiment of the detector is configured to maximize the filling factor. It is preferred that the greatest number of spins be provided within in the volume enclosed by the detector coil. A good filling factor is important in achieving the signal enhancement.
- an optical detector in one embodiment provides a more sensitive method of detection effectively amplifying the noble gas MNR/MRI signal thereby allowing detection of smaller sample sizes and the use of micro-devices.
- An object of the invention is to provide an apparatus and method that allows the spatial and temporal separation of the NMR signal preparation and detection steps. Another object of the invention is to provide an apparatus and method that allows the optimization of the conditions of the encoding and detection steps independently of each other.
- Another object of the invention is to provide an apparatus and method for imaging in the presence of susceptibility gradients using low magnetic fields and low frequency signals and detecting the signals at high magnetic field strengths.
- Another object of the invention is to provide an NMR/MRI imaging apparatus that can be used in the presence of diamagnetic, paramagnetic and ferromagnetic materials and implants at low magnetic field strengths.
- Yet another object of the invention is to provide a sensitive apparatus and method for NMR or MRI imaging that uses optical detection.
- Another object of the invention is to provide a remote detection apparatus and method for NMR or MRI imaging that uses Superconducting Quantum Interference Devices for detection.
- Still another object of the invention is to provide an apparatus and method for NMR spectroscopy that can functionally amplify signals from small sample quantities and accurately detect chemical shifts.
- a further object of the invention is to take images as well as determine the travel time, flow and diffusion information over long distances.
- Another object of the invention is to provide an apparatus and method that can provide remote NMR with detection magnets with poor field homogeneity.
- FIG. 1 is a flow diagram of the method of remote NMR detection according to the present invention.
- FIG. 2 is a schematic diagram of one embodiment of the apparatus of the present invention with a high magnetic field NMR encoder and a remote high field detector in a closed system.
- FIG. 3 is a schematic diagram of one embodiment of the apparatus of the present invention with a low magnetic field NMR encoder and a remote high field detector in a closed system.
- FIG. 4 is a schematic diagram of one embodiment of the apparatus of the present invention with a low magnetic field NMR encoder and an alternative optical detector in a closed system.
- FIG. 5 is a two dimensional graph of the remote detection of chemical shift of xenon.
- FIG. 6 is a pulse sequence for a low magnetic field encoding and high magnetic field detection shown in FIG. 3 according to the present invention.
- FIG. 1 through FIG. 6 the apparatus generally shown in FIG. 1 through FIG. 6. It will be appreciated that the apparatus may vary as to configuration and as to details of the parts, and that the method may vary as to the specific steps and sequence, without departing from the basic concepts as disclosed herein.
- the remote detection apparatus allows the NMR signals from a sample to be encoded and detected in separate locations, environments, and times through the use of signal carrying sensors (signal carriers), an encoding coil and a remote detector.
- the NMR signals from a subject or sample can be amplified if the detection field is higher than the encoding field, the filling factor is more favorable, or the encoded carrier molecules are concentrated in the detection coil.
- the NMR signals may also be qualitatively amplified by using detection devices that are more sensitive than conventional high field NMR or MRI detectors.
- One obvious advantage to separate encoding and detection steps is that the conditions of the sample and encoding can be manipulated independently from those conditions for detection allowing the optimal conditions for each to be chosen.
- the resolution of the encoded NMR signal is determined by the characteristics of the encoding magnet, the characteristics of the encoding apparatus including the magnetic field and coil geometries can be optimized. For example, the resolution of imaging information can be improved by removing high field susceptibility artifacts from the image by lowering the encoding field. Since susceptibility differences in a sample scale with the static field, resolution can be improved by imaging at lower fields. However, there is also a cost in signal to noise.
- Low fields typically range from approximately 0 Tesla to approximately 1 Tesla. Likewise, the detection efficiency scales linearly with the detection frequency indicating that a higher field for detection is optimum.
- High fields refer to a magnetic field that is greater than approximately 1 Tesla.
- a detector that is remote from the encoder allows a susceptibility related resolution gain by imaging at a lower field with no cost in signal to noise because the signal is still detected at high field.
- the detection magnetic field could be inhomogeneous and still yield the resolution determined by the encoding field. This could be especially useful for settings in which the high field signal is unsteady such as in a high field magnet laboratory or simply an inexpensive un-shimmed magnet is all that is available.
- high magnetic fields can be used around the sample to resolve small chemical shift differences during encoding and then directly detected with either high or low magnetic fields. Accordingly, it can be seen that the coil geometries and sampling conditions in encoding coil and detector can be optimized with remote detection.
- Remote detection may also be advantageous in certain medical applications such as imaging of the lungs.
- a patient may be given a quantity of laser polarized xenon by inhalation which is adsorbed on to the lung tissue. It would be difficult to detect the adsorbed xenon signal with conventional MRI because the filling factor of the huge coil wrapped around the body would be so poor.
- the remote detection scheme of the present invention the xenon chemical shift and location would first be encoded by rf pulses and magnetic field gradients around the body and then exhaled and transported to an optimized detector where the signal could be detected.
- the S/N could be much improved. Accordingly, the filling factor can easily be improved for void space NMR and MRI with the spatial and temporal separation of the encoding and detection steps.
- a patient would inhale a volume of xenon while in a conventional MRI apparatus and a sample could be encoded.
- the path of the encoded blood can be traced non-invasively.
- the circulation of blood in parts of the body may be tracked through vascular restrictions and the like with polarized Xe dissolved in a compatible liquid and introduced through a catheter for example.
- low field encoding will allow imaging in the presence of diamagnetic, paramagnetic or ferromagnetic materials.
- patients with medical implants made from magnetic materials risk the movement of such implants when exposed to strong magnetic fields. Consequently, these patients are presently deprived of the benefits of conventional MRI imaging.
- the separation of the encoding and detecting steps allows encoding at very low fields while detection is performed at high fields.
- S/N signal to noise
- Alternative methods of detection may also be employed by the use of spatially separated encoding and detection steps.
- the limitations experienced by SQUID devices in the presence of pulsed magnetic fields can be overcome by removing the detector from proximity to the NMR encoding coils or other sources of interfering magnetic fields.
- the pulses required to encode the spins from the subject sample are sufficiently removed from the detector so that the sensitive SQUID detector can be used.
- optical detection methods via Rb-Xe spin exchange or an optical magnetometer using nonlinear Faraday rotation may also be used in the alternative to traditional NMR coil detection. These methods detect magnetization directly so that the field requirements are greatly reduced.
- remote detection may allow one to gain spatial or spectroscopic information from signals that were previously too small to be measured and now become accessible.
- Ultra-low field encoded samples, biological tissue and low concentration sites in materials may now be susceptible to spectroscopy with remote detection.
- performing NMR or MRI at ultra-low magnetic fields will minimize the effects of susceptibility gradients in a sample. Therefore, spectroscopy and imaging of highly heterogeneous samples or samples in the presence of metals may now be possible.
- FIG. 1 a flow diagram of one embodiment of the method 10 according to the present invention is generally shown.
- a supply of signal carriers preferably hyperpolarized xenon, is provided at block 12.
- the signal carriers are directed to a chamber containing a sample in an encoder and NMR signals are encoded at block 14.
- the encoded-signal-carrying atoms or molecules are then transferred from the encoder to a remote detector at block 16 where the signal carriers can be concentrated and detected using any method capable of detecting the encoded signal at block 18.
- FIG. 2 FIG. 3 and FIG. 4, alternative embodiments of a closed flow system of the apparatus can be seen.
- the supply of signal carriers is produced in a hyperpolarizer 20 that is connected with suitable tubing 26 to a sample chamber 22 that preferably resides in an encoder 24.
- the system of tubing preferably has one or more valves 28 that will allow the selective flow of signal carriers through the various components in the system.
- the system in the embodiment shown in FIG. 2, FIG. 3 and FIG. 4 has a pump 30 that will provide a continuous flow of signal carriers and will also create pressure in the system. While a closed system is preferred, it will be understood that an open system using a batch method is also contemplated. In an open system embodiment, the signal carrier atoms are transported in a batch from the hyperpolarizer 20 to the encoder 24 and finally to the decoder 32. Another open system embodiment uses continuous flow from the pumping cell through the encoding and detection coils and then out to the atmosphere.
- a signal carrier is defined herein as a magnetically active-nucleus containing species atom or molecule that preferably has the capability of polarization transfer with a sufficiently long relaxation time as well as the capability of associating with protons and other atoms in a sample.
- the signal carrier is preferably chemically inert but may be chemically or biologically compatible with the sample to be analyzed.
- Hyperpolarized noble gases are the preferred signal carrying sensors in the present invention. Noble gases such as 129 Xe are particularly useful in NMR because the Xe nucleus has a spin of 1 2.
- the signal carriers may be gaseous or liquid although gaseous carrier atoms are preferred. Additionally, gaseous signal carriers may be dissolved or mixed with liquids or other gases. These liquids or gases preferably facilitate the transfer through the encoder to the decoder through the system. For example, it has been shown that hyperpolarized 129 Xe gas can be mixed with liquids or gases and maintain the polarization for several hours. Such liquids may include, but are not limited to water, saline solution, isotonic buffers, lipid emulsions, organic solvents, fluorocarbon blood substitutes including aqueous perfluorocarbon emulsions and other medically safe media.
- any liquid or gas that does not substantially interfere with the polarization of the signal carrier molecules may serve as a transportation media.
- Liquids that are capable of dissolving large quantities of xenon and other noble gases are especially preferred.
- the typical and preferred method for producing hyperpolarized gas is the optical pumping spin exchange method using an alkali-metal intermediary to polarize the preferred noble gas.
- the sample chamber 22 is preferably located in an encoder 24.
- the preferred encoder 24 comprises a high resolution NMR spectrometer providing a homogeneous magnetic field.
- magnetic field gradient and radio frequency pulses are preferably used to encode spatial or spectroscopic information and prepare the signal carrier molecule spins for detection.
- the flow of signal carrier molecules is preferably stopped during encoding and detection steps with valves 28.
- the spatial separation of the encoding apparatus from the detecting apparatus allows optimal conditions for encoding and detection to be selected including coil geometries and magnetic field strengths. For example, the encoding takes place in a high magnetic field and detection takes place in a high magnetic field in the embodiment seen in FIG. 2 and shown in Example 1.
- the encoding takes place in a low magnetic field and detection takes place in a high magnetic field.
- the encoding takes place in a high magnetic field and the detection takes place in a low magnetic field.
- a high and low field encoding and high and low field detection embodiments are shown for illustration, it will be understood that the encoding fields and detecting fields may be provided at essentially any field strength.
- encoding is preferred within a homogeneous magnetic field, it will be understood that encoding may take place in inhomogeneous fields under some circumstances.
- a portable apparatus may be used where the signal was encoded by inhomogeneous surface coils out in the field, such as with porous materials containing oil or the like, and then detected with a better filling factor to enhance signal to noise that one would get with a surface coil.
- the preferred encoding step comprises a series of two 90° pulses divided by a variable dwell time N*dw2.
- the first pulse begins precession in the x-y plane and the second stores the magnetization in the +/- z direction. Since a phase difference develops between the rotating magnetization and the carrier frequency, the amplitude of the magnetization rotated into the +/- z direction varies as a function of the phase difference. It will be understood that different pulse schemes may be used for the high field and low field encoding. For example, at high field, normal rotating frame pulses may be applied. In this embodiment, the amplitude of the signal stored by the second encoding pulse is proportional to the development of phase with respect to the rotating frame carrier frequency. Since the magnetization of the carrier molecules from the encoder 24 is stored as an amplitude, there is no phase information stored and therefore no quadrature.
- the second low field pulse is alternated between sin and cos in the rotating frame, quadrature may reconstructed by acquiring the real and imaginary FID's separately during detection.
- all of the pulses in the encoding coil 24 begin and end with x-direction zero phase in the lab frame.
- the time between pulses may be set arbitrarily, meaning that the second pulse stores an amplitude proportional to the development of phase with respect to the x-direction in the lab frame. In this case the actual precession of the magnetization is mapped out in the lab frame.
- the dwell time is too long to meet the Nyquist condition an apparent frequency is recorded.
- the encoded signal carrier molecules are transferred in a traveling time T t from the encoder 24 to the detector 32 with a detection chamber 34 as shown in FIG. 2.
- the encoded magnetization reaches the detector over a time period Tt +n*Td.
- Tt is defined as the shortest time in which the magnetization shows variation
- T d is the time between detections.
- T d is preferably chosen to be long enough so that the gas in the detection coil exchanges by greater than 95%.
- the time between encoding and detection steps may typically range between milliseconds to several hours or until the signal carrier sample has been fully saturated or longitudinally relaxed.
- the encoded signal carriers are collected in a container and transported to detector 32. It can be seen that simply removing the carrier molecule before detection allows physical compression or thermal compensation which can concentrate the encoded signal carrier molecules up to three orders of magnitude in the detector, yielding a higher spin density and coil filling factor leading to greatly improved signal to noise ratios.
- the amplitude of the signal detected after a 90° pulse at the detector 32 is constant if the encoding step at encoder 24 is excluded. Additionally, a single 90° pulse at encoder 24 causes the magnetization to precess and in the case of hyperpolarized 129 Xe also destroys the high polarization.
- the travel time T t between locations may be experimentally determined by inverting the magnetization in the encoding coil 24 using an adiabatic sweep pulse or a hard 180° pulse. The inverted magnetization mixes with un-encoded 129 Xe as it flows through sealed tubing 26.
- the amplitude of the encoded magnetization is preferably detected using a third 90° pulse in the embodiment shown.
- the length of N*dw2 at the encoder 24 determines the amplitude of the z- direction magnetization when it is detected as a FID at detector 32.
- the amplitude variation due to changing dw2 is the signal encoded at the encoder 24.
- the variation of N*dw2 at the encoding coil indirectly maps out the encoded FID as part of a 2D experiment.
- a series of acquisitions are preferably made then in the detection coil at detector 32 in the embodiment shown in FIG. 2.
- the data is preferably two dimensional and taken point by point as seen in FIG. 5, for example.
- An amplitude is stored for each encoding step, and, after traveling to the detection coil 32, is acquired as a single point in the indirectly encoded spectrum.
- the polarization resulting from a given series of encoding pulses and evolution times is stored along the z-axis for its intensity to be detected in the detector 32.
- Signal intensity may be measured for each pulse strength and evolution time, allowing the effect of the pulses and evolution to be recorded multi-dimensionally.
- the use of a point-by-point detection scheme will produce a remotely detected spectrum will have one more dimension of data than the equivalent directly detected spectrum.
- Amplification of the signal in the detection coil by concentration or by detecting at a high field will also permit longer transportation and procedure times as well as allow signal averaging.
- a selective pulse centered about the functionalized-xenon resonances is used to allow signal averaging of the functionalized-xenon peaks. Between saturations the mixing time ( ⁇ m j X ) allows for the replenishment of functionalized-xenon signal by exchanging saturated spins with excessive polarized xenon that has been dissolved in water.
- One preferred pulse is an EBURP1 pulse designed to selectively saturate magnetization.
- SQUIDs Superconducting Quantum Interference Devices
- SQUIDs are very sensitive detectors of magnetic fields that generally comprise a superconducting loop with a plurality of Josephson junctions that are typically formed by a very thin insulating barrier through which electron pairs can tunnel.
- an optical detector 36 and similar methods can be used in the alternative of a high field NMR detector or a SQUID device. In the embodiment shown in FIG.
- an optical detection apparatus 36 generally includes a detection chamber that receives polarized and encoded signal carriers from the encoder 24 and contains a volume of a vaporized alkali metal, preferably rubidium.
- the signal carriers preferably xenon, create a rapid spin-exchange with the rubidium perturbing the polarization of the rubidium.
- the resulting rubidium polarization indirectly reports the 129 Xe polarization and can be directly detected optically. Since optical detection is many orders of magnitude more sensitive than the NMR signal, especially for low 129 Xe concentrations, a large amplification of the Xe NMR/MRI signal is obtained.
- an optical magnetometer using nonlinear Faraday rotation may also be used.
- a multi-dimensional procedure need not be conducted. Since the magnetization is measured directly, a 90° pulse does not need to be applied and there is no FID to detect in the direct dimension. Instead, the amplitude of the magnetization is measured directly and supplies one point in the point-by-point encoded spectrum. Likewise, a SQUID could be used as a magnetometer, also measuring only one data point in the encoded spectrum corresponding to the z component of the magnetization. However, essentially any magnetometer could measure the z-magnetization and supply one point in the encoded signal, simplifying the data to a 1-D experiment although still preferably taken point by point.
- the amplified signal scheme provides a modality for measuring miniscule NMR signals arising from small subject samples, in-vivo cells, and micro-devices like microfluidic chips. It would also allow the detection of small SPINOE effects in materials, which may be crucial in revealing solvent-solute interactions, surface properties in solid materials, and local structures like hydrophobic pockets in proteins and other complex molecules.
- this embodiment provides for measurement of Xe chemical shifts in samples at ultra-low fields for use as contrast agent in imaging and spectroscopy.
- the monitoring of diffusion, exchange, and imaging of Xe in the tissues surrounding the lung could be conducted by encoding in the lung and detecting outside of the body.
- this embodiment provides for analysis of noble gas-sample interactions that may provide selective imaging of samples.
- the enhanced signal may also allow the study of fundamental physics in isolated and single spin systems.
- the embodiment shown in FIG. 4 with optically detected NMR/MRI signals provides a method of amplifying the Xe signal from samples over what is typically detected using a conventional NMR detection apparatus.
- the present invention may be more particularly described in the following examples that are intended for illustrative purposes only, since numerous modifications, adaptations and variations to the apparatus and methods will be apparent to those skilled in the art.
- Example 1 Example 1
- a preliminary test of the concept of remote detection used an apparatus in which both an encoding coil and detection coil were controlled within the same NMR spectrometer with the same magnetic field and had a minimal travel distance between the encoding and detection coils.
- the high field encoding probe that was used contains two coils that are separated by 2 cm, center to center, and by a copper sheet, which serves as an //shield.
- the encoding and detection coils were each controlled by a separate x-channel of a Varian Infinity Plus spectrometer tuned to 83.25 MHz.
- Hyperpolarized 129 Xe polarized to 1-5%, was produced using a commercial polarizer from MITI. After the polarized 129 Xe gas was produced, the flow was directed through the encoding and detecting coils sequentially and was later lost into the laboratory atmosphere or was alternatively returned to the polarizer. Gas flow rate was controlled using a pressure differential through a silver coated needle valve and an on-board flow meter. The gas was stopped during the pulse sequence using a TTL driven home built gas flow valve. The subject sample in the lower or encoding coil was a packed layer of Aerogel crystals. Aerogel is a low density silicate that allows 129 Xe to freely pass through its lattice and also produces a chemical shift of about 25 ppm corresponding to bound 129 Xe.
- the gas is preferably temporarily stopped during the encoding step in order to avoid a signal loss due to flow through gradient. Redirecting the flow to a bypass loop effectively stopped the polarized gas in the magnet loop.
- the polarizing gas mixture of Xe/N2/He was mixed with ratio 1/2/3 and a total pressure of 7atm. The other details of the polarization process have been described previously.
- the encoding magnet and probe were both home built.
- the magnet provided a homogeneous field of 70.1 Gauss with a current of 8.19 A applied.
- the probe was tuned correspondingly to a frequency of 83.3 kHz and its impedance matched to 50 ohms with a standard tank circuit.
- the pulses were gated and generated from a Hewlett Packard 3314A frequency generator and amplified to up to 20 V p-P by an Amplifier Research 75-Watt unity gain amplifier. With an 8 V p-P pulse, the experimental 90° time was about 48 ⁇ s.
- the three dimensional gradient coils were fixed on the outside of the magnet bore. This allowed the probe to be moved independently from the gradients magnets.
- the high field detection magnet was a 4.23T super wide bore with a 129 Xe frequency of 49.782 MHz.
- the home built imaging probe was controlled from the x-channel of a Chem Magnetics spectrometer.
- the high field encoding and high field detecting apparatus generally shown in FIG. 2 described above was used to obtain a spectrum for comparison with a spectrum obtained from a direct measurement of the same sample and shown in FIG. 5. It was shown that the remote signal could be amplified by concentrating the xenon sample in the detection coil 32. It can be seen from the comparison in the high field experiment that a spectrum obtained point by point in a remote detector is essentially identical to the spectrum that is directly detected in the encoding NMR coils.
- the sample in the encoding coil 24 was an Aerogel sample with ⁇ 25ppm chemical shift with respect to the Xe gas peak.
- the direct spectrum was recorded from the encoding coil 24 for comparison and had an absorbed peak signal to noise
- the remote spectrum had three peaks corresponding to the Xe gas peak, the absorbed phase peak and a DC offset peak that comes from 129 Xe, which was not encoded in the encoding coil 24.
- the signal to noise ratio (S/N) of the absorbed peak in the remotely detected spectrum was found to be -20:1.
- the amplification of signal between the two spectra can be attributed to an increased density of spins within the detection coil of the remote experiment. This was achieved by using a coil with a 10x improved filling ratio.
- the S/N of the remote spectrum was superior to the directly detected spectrum.
- the improvement in S/N can be attributed to the improvement in filling factor in the detection coil.
- the same volume of gas was encoded in each experiment but the filling factor was better in the remote detection because the gas fills the coil volume more completely.
- This principle can be used to improve the signal of any remotely detected signal in which the spin density of encoded gas is low.
- the signal can be amplified by increasing the density of spins in the detection coil 32.
- Example 2 Using an apparatus shown generally in FIG. 3, a low field encoding and high field detecting procedure was performed. In this procedure, two dimensional images were obtained from a sample and Xe gas that was encoded at 0.008 T and detected at 4T. The experimental apparatus and pulse sequence were identical to that in Example 1 with the exception that frequency encoding gradients were added between the two encoding 90° pulses. The travel time was set to 10 seconds corresponding to a flow rate of ⁇ 0.6ml/s. In order for a remote image to be properly reconstructed in the detection coil, preferably all of the encoded gas will be detected in the detection coil. The processes of diffusion and flow allow the encoded sample to mix with un-encoded gas and to spatially spread out along the length of tubing. The total distance traveled is approximately 5m, but the movement of the encoded sample is better measured in terms of travel time.
- the traveling time Tt is preferably determined by inverting the magnetization at the encoder 24 using an adiabatic sweep pulse and then measuring the time required for the inverted sample to flow to the detection coil 32.
- a longer T t allows more diffusion and mixing leading to lesser modulation of the amplitude and greater temporal spread of the encoded sample.
- the Tt of the gas sample being imaged in this example was between 10 seconds and 12.7 seconds.
- a single 90° pulse was applied to the gas flowing in the detection coil and an FID that represented the amplitude of the signal in a volume that resides for -0.15s in the detection coil was taken. This is called the detection time T d .
- the resolution of the image is improved by acquiring the entire encoded sample, but the S/N is improved by averaging only those T d that are strongly modulated.
- Each projection has a 1.23 mT/m gradient oriented along a proscribed angle and a 64 point FID, yielding a resolution of 1.2mm. Images consisting of sixteen, sixty-four point 1 D projections separated by 11.25° were obtained. The projection angles were formed by physically rotating the low field probe by integer multiples of 11.25°. All of the obtained image projections were zero-filled to 256 points and multiplied by a suitable apodization filter. In addition the projections were corrected for low field magnet drift by centering each projection using a Lorenzian fit.
- this invention is an apparatus and method providing a sensitive technique for NMR/MRI imaging of polarized signal carrier molecules and allowing the spatial and temporal separation of signal encoding and detection steps permitting the conditions of each step to be optimized.
- Imaging in the presence of susceptibility gradients can be performed using low Bo fields and low frequency signals and the encoded signal carriers can be moved to another location and detected in high fields.
- Signal to noise ratios can also be optimized by the physical compression or thermal condensation of signal carrier atoms producing a higher spin density and coil filling factor.
- Remote optical detection may also provide an amplification of the signal over conventional tuning coils.
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EP02782147A EP1590647A2 (en) | 2001-10-31 | 2002-10-09 | Remote nmr/mri detection of laser polarized gases |
JP2003540616A JP2005515406A (en) | 2001-10-31 | 2002-10-09 | Remote NMR / MRI detection of laser polarized gas |
AU2002348428A AU2002348428A1 (en) | 2001-10-31 | 2002-10-09 | Remote nmr/mri detection of laser polarized gases |
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US60/335,240 | 2001-10-31 | ||
US39904102P | 2002-07-25 | 2002-07-25 | |
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PCT/US2002/032481 WO2003038396A2 (en) | 2001-10-31 | 2002-10-09 | Method for detecting macromolecular conformational change and binding information |
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Cited By (3)
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EP1555538A1 (en) * | 2004-01-15 | 2005-07-20 | Bruker BioSpin MRI GmbH | Method of fast multidimensional NMR spectroscopy |
FR2881226A1 (en) * | 2005-01-27 | 2006-07-28 | Commissariat Energie Atomique | Liquid solution`s nuclear magnetic resonance analyzing method, involves realizing Hartmann-Hahn type polarization transfer of xenon spins of polarizing source to proton spins of solution by coherent coupling due to dipolar field of xenons |
JP2006322802A (en) * | 2005-05-18 | 2006-11-30 | National Institute Of Advanced Industrial & Technology | Hyperpolarized rare gas production apparatus, nuclear magnetic resonance spectrometer using hyperpolarized rare gas, and magnetic resonance imaging apparatus |
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US7359059B2 (en) * | 2006-05-18 | 2008-04-15 | Honeywell International Inc. | Chip scale atomic gyroscope |
JP5424578B2 (en) * | 2007-06-05 | 2014-02-26 | キヤノン株式会社 | Magnetic sensing method, atomic magnetic sensor, and magnetic resonance imaging apparatus |
CN114207127B (en) * | 2019-08-09 | 2024-11-29 | 国立研究开发法人产业技术综合研究所 | Artificial gene and gene mutation method |
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US6426058B1 (en) * | 1996-03-29 | 2002-07-30 | The Regents Of The University Of California | Enhancement of NMR and MRI in the presence of hyperpolarized noble gases |
US6591128B1 (en) * | 2000-11-09 | 2003-07-08 | Koninklijke Philips Electronics, N.V. | MRI RF coil systems having detachable, relocatable, and or interchangeable sections and MRI imaging systems and methods employing the same |
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Publication number | Priority date | Publication date | Assignee | Title |
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EP1555538A1 (en) * | 2004-01-15 | 2005-07-20 | Bruker BioSpin MRI GmbH | Method of fast multidimensional NMR spectroscopy |
FR2881226A1 (en) * | 2005-01-27 | 2006-07-28 | Commissariat Energie Atomique | Liquid solution`s nuclear magnetic resonance analyzing method, involves realizing Hartmann-Hahn type polarization transfer of xenon spins of polarizing source to proton spins of solution by coherent coupling due to dipolar field of xenons |
WO2006079702A3 (en) * | 2005-01-27 | 2007-05-03 | Commissariat Energie Atomique | Method for enhancing the nmr signal of a liquid solution using the long-range dipolar field |
JP2006322802A (en) * | 2005-05-18 | 2006-11-30 | National Institute Of Advanced Industrial & Technology | Hyperpolarized rare gas production apparatus, nuclear magnetic resonance spectrometer using hyperpolarized rare gas, and magnetic resonance imaging apparatus |
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WO2003038395A3 (en) | 2008-10-16 |
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