Magnetic Relaxometry with an Atomic Magnetometer and SQUID Sensors on Targeted Cancer Cells

Magnetic relaxometry methods have been shown to be very sensitive in detecting cancer cells and other targeted diseases. Superconducting Quantum Interference Device (SQUID) sensors are one of the primary sensor systems used in this methodology because of their high sensitivity with demonstrated capabilities of detecting fewer than 100,000 magnetically-labeled cancer cells. The emerging technology of atomic magnetometers (AM) represents a new detection method for magnetic relaxometry with high sensitivity and without the requirement for cryogens. We report here on a study of magnetic relaxometry using both AM and SQUID sensors to detect cancer cells that are coated with superparamagnetic nanoparticles through antibody targeting. The AM studies conform closely to SQUID sensor results in the measurement of the magnetic decay characteristics following a magnetization pulse. The AM and SQUID sensor data are well described theoretically for superparamagnetic particles bound to cells and the results can be used to determine the number of cells in a cell culture or tumor. The observed fields and magnetic moments of cancer cells are linear with the number of cells over a very large range. The AM sensor demonstrates very high sensitivity for detecting magnetically labeled cells does not require cryogenic cooling and is relatively inexpensive.     

Capacitor-based detection of nuclear magnetization: nuclear quadrupole resonance of surfaces

We demonstrate excitation and detection of nuclear magnetization in a nuclear quadrupole resonance (NQR) experiment with a parallel plate capacitor, where the sample is located between the two capacitor plates and not in a coil as usually. While the sensitivity of this capacitor-based detection is found lower compared to an optimal coil-based detection of the same amount of sample, it becomes comparable in the case of very thin samples and even advantageous in the proximity of conducting bodies. This capacitor-based setup may find its application in acquisition of NQR signals from the surface layers on conducting bodies or in a portable tightly integrated nuclear magnetic resonance sensor.     

High contrast atomic magnetometer based on coherent population trapping

We present an experimental and theoretical investigation of the coherent population trapping （CPT） resonance excited on the D1 line of 87Rb atoms by bichromatic linearly polarized laser light. The experimental results show that a lin｜｜lin tran- sition scheme is a promising alternative to the conventional circular-circular transition scheme for an atomic magnetometer. Compared with the circular light transition scheme, linear light accounts for high-contrast transmission resonances, which makes this excitation scheme promising for high-sensitivity magnetometers. We also use linear light and circular light to detect changes of a standard magnetic field, separately.     

1H and 129Xe NMR absorption line shapes in the presence of highly polarized and concentrated xenon solutions in high magnetic field

The presence of highly concentrated dissolved laser-polarized xenon (approximately 1mol/L, polarization up to 0.2) induces numerous effects on proton and xenon NMR spectra. We show that the proton signal enhancements due to (129)Xe-(1)H cross-relaxation (SPINOE) and overall shifts of the proton resonances due to the average dipolar shift created by the intense xenon magnetization are correlated. Protons behave as very useful sensors of the xenon magnetization. Indeed the xenon resonances exhibit many features such as superimposition of narrow lines on the main resonance due to clustering effects, or such as a polarization-dependent line broadening that is tentatively assigned to the effects of temperature fluctuations that decorrelate some distant dipolar field effects from local interactions, transforming xenon spins from "like" to "unlike" spins. These spectral features make difficult the determination of the average dipolar field by means of the xenon resonance but have interesting consequences on the heteronuclear polarization transfer experiment in Hartmann-Hahn conditions (SPIDER).     

NMR detection using laser-polarized xenon as a dipolar sensor

Hyperpolarized (129)Xe can be used as a sensor to indirectly detect NMR spectra of heteronuclei that are neither covalently bound nor necessarily in direct contact with the Xe atoms, but coupled through long-range intermolecular dipole-dipole interactions. To reintroduce long-range dipolar couplings the sample symmetry has to be broken. This can be done either by using an asymmetric sample arrangement, or by breaking the symmetry of the spin magnetization with field gradient pulses. Experiments are performed where only a small fraction of the available (129)Xe magnetization is used for each point, so that a single batch of xenon suffices for the point-by-point acquisition of a heteronuclear NMR spectrum. Examples with (1)H as the analyte nucleus show that these methods have the potential to obtain spectra with a resolution that is high enough to determine homonuclear J couplings. The applicability of this technique with remote detection is discussed.     

High-resolution NMR of static samples by rotation of the magnetic field

Mechanical rotation of a sample at 54.7 degrees with respect to the static magnetic field, so-called magic-angle spinning (MAS), is currently a routine procedure in nuclear magnetic resonance (NMR). The technique enhances the spectral resolution by averaging away anisotropic spin interactions thereby producing isotropic-like spectra with resolved chemical shifts and scalar couplings. It should be possible to induce similar effects in a static sample if the direction of the magnetic field is varied, e.g., magic-angle rotation of the B0 field (B0-MAS). Here, this principle is experimentally demonstrated in a static sample of solid hyperpolarized xenon at approximately 3.4 mT. By extension to moderately high fields, it is possible to foresee interesting applications in situations where physical manipulation of the sample is inconvenient or impossible. Such situations are expected to arise in many cases from materials to biomedicine and are particularly relevant to the novel approach of ex situ NMR spectroscopy and imaging.     

Imaging of laser-polarized solid xenon

The enhanced spin polarization produced by optical pumping of gaseous rubidium/xenon samples has made possible a number of recent experiments in nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI). Here we report MRI of laser-polarized xenon in the solid phase at low temperature. Due to the high xenon density in the solid phase and the enhanced spin polarization, it is possible to achieve high intensity and spatial resolution of the image. Signals were observed from xenon films solidified onto the glass container walls and not from an enclosed chili pepper.     

The Frequency Shifts of the Nuclear Magnetic Momenta Larmor Precession in the Mixture of Two Noble Gases

The dynamics of nuclear magnetization in the mixture of two noble gases with different gyromagnetic ratios of the nuclei is studied theoretically. The nuclear magnetization is induced by the radiofrequency electromagnetic radiation, which causes the nuclear magnetic resonance in both types of noble gases in the mixture. Frequency shifts of the nuclear magnetic resonance appeared due to an interaction between different types of the noble gases is analytically predicted. The specifics of these shifts are such that they cannot be compensated by means of the external magnetic field. The nature of the magnetic field distortion in the cell caused by the nuclear magnetization is also discussed.     

170 nm nuclear magnetic resonance imaging using magnetic resonance force microscopy

We demonstrate one-dimensional nuclear magnetic resonance imaging of the semiconductor GaAs with 170 nm slice separation and resolve two regions of reduced nuclear spin polarization density separated by only 500 nm. This was achieved by force detection of the magnetic resonance, magnetic resonance force microscopy (MRFM), in combination with optical pumping to increase the nuclear spin polarization. Optical pumping of the GaAs created spin polarization up to 12 times larger than the thermal nuclear spin polarization at 5K and 4T. The experiment was sensitive to sample volumes of 50 microm(3) containing approximately 4 x 10(11)71 Ga/Hz. These results demonstrate the ability of force-detected magnetic resonance to apply magnetic resonance imaging to semiconductor devices and other nanostructures.     

Time resolved spectroscopic NMR imaging using hyperpolarized 129Xe

We have visualized the melting and dissolution processes of xenon (Xe) ice into different solvents using the methods of nuclear magnetic resonance (NMR) spectroscopy, imaging, and time resolved spectroscopic imaging by means of hyperpolarized 129Xe. Starting from the initial condition of a hyperpolarized solid Xe layer frozen on top of an ethanol (ethanol/water) ice block we measured the Xe phase transitions as a function of time and temperature. In the pure ethanol sample, pieces of Xe ice first fall through the viscous ethanol to the bottom of the sample tube and then form a thin layer of liquid Xe/ethanol. The xenon atoms are trapped in this liquid layer up to room temperature and keep their magnetization over a time period of 11 min. In the ethanol/water mixture (80 vol%/20%), most of the polarized Xe liquid first stays on top of the ethanol/water ice block and then starts to penetrate into the pores and cracks of the ethanol/water ice block. In the final stage, nearly all the Xe polarization is in the gas phase above the liquid and trapped inside the pores. NMR spectra of homogeneous samples of pure ethanol containing thermally polarized Xe and the spectroscopic images of the melting process show that very high concentrations of hyperpolarized Xe (about half of the density of liquid Xe) can be stored or delivered in pure ethanol.     

Formation of quantum-degenerate sodium molecules

Ultracold sodium molecules were produced from an atomic Bose-Einstein condensate by ramping an applied magnetic field across a Feshbach resonance. More than 10(5) molecules were generated with a conversion efficiency of approximately 4%. Using laser light resonant with an atomic transition, the remaining atoms could be selectively removed, preventing fast collisional relaxation of the molecules. Time-of-flight analysis of the pure molecular sample yielded an instantaneous phase-space density greater than 20.     

Magnetic structure of MnO at 10 K from total neutron scattering data

Total neutron scattering data from a powdered sample of MnO collected at 10 K have been analyzed using the reverse Monte Carlo method to refine the nuclear and magnetic structure. The results give the first unambiguous assignment of the average magnetic structure. The magnetic moments are aligned ferromagnetically within (111) sheets with the magnetization vectors of alternate sheets along axes parallel and antiparallel to the <112> directions, albeit with a small modulated out-of-plane component. Small displacements of Mn and O (modulated with the same periodicity) accompany the magnetic ordering and both atomic and magnetic structures may be described in the monoclinic space group C2.     

Time resolved spectroscopic NMR imaging using hyperpolarized Xe

We have visualized the melting and dissolution processes of xenon (Xe) ice into different solvents using the methods of nuclear magnetic resonance (NMR) spectroscopy, imaging, and time resolved spectroscopic imaging by means of hyperpolarized ¹²⁹Xe. Starting from the initial condition of a hyperpolarized solid Xe layer frozen on top of an ethanol (ethanol/water) ice block we measured the Xe phase transitions as a function of time and temperature. In the pure ethanol sample, pieces of Xe ice first fall through the viscous ethanol to the bottom of the sample tube and then form a thin layer of liquid Xe/ethanol. The xenon atoms are trapped in this liquid layer up to room temperature and keep their magnetization over a time period of 11 min. In the ethanol/water mixture (80 vol%/20%), most of the polarized Xe liquid first stays on top of the ethanol/water ice block and then starts to penetrate into the pores and cracks of the ethanol/water ice block. In the final stage, nearly all the Xe polarization is in the gas phase above the liquid and trapped inside the pores. NMR spectra of homogeneous samples of pure ethanol containing thermally polarized Xe and the spectroscopic images of the melting process show that very high concentrations of hyperpolarized Xe (about half of the density of liquid Xe) can be stored or delivered in pure ethanol.     

Optically detected nuclear magnetic resonance at the sub-micron scale

Nuclear magnetic resonance is arguably one of the most powerful techniques available today to characterize diverse systems. However, the low sensitivity of the standard detection method constrains the applicability of this technique to samples having effective dimensions not less than a few microns. Here, we propose a novel scheme and device for the indirect detection of the nuclear spin signal at a submicroscopic scale. This approach--for which the name Dipolar Field Microscopy is suggested--is based on the manipulation of the long-range nuclear dipolar interaction created between the sample and a semiconductor tip located close to its surface. After a preparation interval, the local magnetization of the sample is used to modulate the nuclear magnetization in the semiconductor tip, which, in turn is determined by an optical inspection. Based on results previously reported, it is shown that, in principle, images and/or localized high-resolution spectra of the sample can be retrieved with spatial resolution proportional to the size of the tip.     

Fast-field-cycling NMR study of magnetomechanically induced relaxation enhancement in ferrogelatine

We describe a field-cycling magnetic resonance experiment aimed to study the nuclear spinlattice relaxation in the simultaneous presence of an oscillating magnetic field and a magnetomechanically induced perturbation across the sample volume. The studied system is a gelatine doped with surfacted nanosize ferromagnetic particles. The spin system relaxes in coexistence with the magnetic interaction between the dopants and a weak external alternating magnetic field. Due to the interaction between the alternating field and the high magnetic moment of the dopants, a mechanical shaking of the particles becomes effective at low evolution fields. In this way, the particles act as local sonic sources, thus transmitting the vibrations to the gelic matrix where they are trapped. The impact produced on the molecular dynamics is observed through a magnetic resonance relaxation experiment. Saturation of the proton magnetization produced by the alternating magnetic field is also discussed. Results are compared with the direct effects produced by a pure sonic perturbation at the same frequency, introduced by coupling a piezoelectric transducer in direct contact with the sample.     

Spin-lattice relaxation and a fast T1-map acquisition method in MRI with transient-state magnetization

The magnetization under the spin-lattice relaxation and the nuclear magnetic resonance radiofrequency (RF) pulses is calculated for a signal RF pulse train and for a sequence of multiple RF pulse-trains. It is assumed that the transverse magnetization is zero when each RF pulse is applied. The result expressions can be grouped into two terms: a decay term, which is proportional to the initial magnetization M0, and a recovery term, which has no M0 dependence but strongly depends on the spin-lattice relaxation and the equilibrium magnetization Meq. In magnetic resonance pulse sequences using magnetization in transient state, the recovery term produces artifacts and can seriously degrade the function of the preparation sequence for slice selection, contrast weighting, phase encoding, etc. This work shows that the detrimental effect can be removed by signal averaging in an eliminative fashion. A novel fast data acquisition method for constructing the spin-lattice relaxation (T1) map is introduced. The method has two features: (i) By using eliminative averaging, the curve to fit the T1 value is a decay exponential function rather than a recovery one as in conventional techniques; therefore, the measurement of Meq is not required and the result is less susceptible to the accuracy of the inversion RF pulse. (ii) The decay exponential curve is sampled by using a sequence of multiple pulse-trains. An image is reconstructed from each train and represents a sample point of the curve. Hence a single imaging sequence can yield multiple sample points needed for fitting the T1 value in contrast to conventional techniques that require repeating the imaging sequence for various delay values but obtain only one sample point from each repetition.     

Effective gyromagnetic ratios in a mixture of noble gases with artificial nuclear magnetization

The precession of nuclear magnetic moments for a noble gas in an external magnetic field upon the laser pumping of nuclear magnetization is considered. A shift of the nuclear magnetic resonance for a mixture of noble gases with different gyromagnetic ratios of nuclei is observed.     

129Xe NMR – highly polarized thin films

We studied the macroscopic effects of nuclear magnetization. Highly polarized xenon is often used to increase the sensitivity in NMR investigations of porous media, diluted liquids or for imaging in the gas phase. In the condensed phase, however, highly nuclear spin polarized xenon also possesses a sizable magnetization due to the nuclear spin density. This results in an additional magnetic field, that is used to measure the polarization of the sample, when only the particle density is known. Here we find P_z≈0.8 corresponding to a spin temperature of 0.5 mK. We use isotopically enriched xenon with a ¹²⁹Xe abundance of 0.71. At high abundance of ¹²⁹Xe and high nuclear polarization the dipolar linewidth is considerably reduced. We find for small angle excitation a reduction from 650 Hz to 400 Hz. We investigate this using a thin film geometry. The susceptibility effects of the substrate and the Xe film are treated. The macroscopic angle between the normal of the film and the external field strongly changes the polarization induced line shift and line width. The first follows an expected cos²θ dependence with an understood amplitude the latter however is not understood up to now. Relaxation of ¹²⁹Xe in the condensed film is observed to be T₁=15±1.8 min, much faster than expected. To cite this article: P. Gerhard et al., C. R. Physique 5 (2004).     

Optical magnetometer array for fetal magnetocardiography

We describe an array of spin-exchange-relaxation-free optical magnetometers designed for detection of fetal magnetocardiography (fMCG). The individual magnetometers are configured with a small volume with intense optical pumping, surrounded by a large pump-free region. Spin-polarized atoms that diffuse out of the optical pumping region precess in the ambient magnetic field and are detected by a probe laser. Four such magnetometers, at the corners of a 7 cm square, are configured for gradiometry by feeding back the output of one magnetometer to a field coil to null uniform magnetic field noise at frequencies up to 200 Hz. We present the first measurements of fMCG signals using an atomic magnetometer.     

铁磁共振实验中值得注意的几个问题

与顺磁样品相比铁磁样品的磁共振信号不仅是强得多,铁磁样品的许多特点都会在铁磁共振(FMR)谱中反映出来.诸如,起始磁化过程的FMR谱线与有剩余磁化强度Mr的FMR谱是不同的,起始磁化过程中的巴克豪森跳跃也会在FMR谱中反映出来.样品的磁晶各向异性、形状各向异性,铁磁高温顺磁的磁性相变等等都能用FMR方法加以研究.