Sensitivity to local dipole fields in the CRAZED experiment: An approach to bright spot MRI

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Abstract

Local dipole fields such as those created by small iron-oxide particles are used to produce regions of low intensity (dark contrast) in many molecular magnetic resonance imaging applications. We have investigated, with computer simulations and experiments at 17.6 T, how the COSY revamped with asymmetric z-gradient echo detection (CRAZED) experiment that selects intermolecular double-quantum coherences can also be used to visualize such local dipole fields. Application of the coherence-selection gradient pulses parallel to the main magnetic field produced similar, dark contrast as conventional gradient echo imaging. Application of the gradient along the magic angle leads to total loss of signal intensity in homogeneous samples. In the presence of local dipole fields, the contrast was inverted and bright signals from the dipoles were observed over a very low background. Both simulations and experiments showed that the signal strongly decreased when a phase-cycle suppressing single-quantum coherences was employed. Therefore, we conclude that most of the signal comes from directly refocused magnetization or intermolecular single-quantum coherences. Finally, we demonstrate that bright contrast from local dipole fields can also be obtained, when the pair of coherence-selection gradient pulses is deliberately mismatched. Both methods allowed visualization of local dipole fields in phantoms in experimental times of about 3 min.

Introduction

Since, applications of molecular imaging have become feasible in magnetic resonance imaging (MRI), considerable interest has been dedicated to local dipole fields. The most common strategy for visualizing cellular populations or molecular targets is to label them with small paramagnetic iron-oxide particles (SPIOs). The dipole field originating from the SPIOs locally changes the contrast in imaging experiments. In particular in gradient echo experiments magnetization is dephased in a surrounding area large compared to the actual size of the SPIO. Thus, micrometer-sized particles can be visualized even at moderate magnetic field strengths and spatial resolution, as used for example in clinical MRI systems [1], [2]. The disadvantage of this approach in molecular imaging is that negative contrast is created so that in experiments where SNR is low or other sources of strong signal attenuation are present, the effects of the structure of interest may well be obscured. A variety of methods have been proposed to allow inversion of the negative contrast so as to produce bright signal at the sites of interest. This has been, for example, achieved by deliberately mismatching gradient pulse pairs [3], [4], or by using off-resonance refocusing pulses to exploit the frequency shift caused by the SPIOs [5]. In an alternative approach the CRAZED (COSY revamped with asymmetric z-gradient echo detection) experiment [6] has been shown to enhance the effects of magnetic nanoparticles and produce excellent contrast in tissue [7].

Here, we describe how the CRAZED sequence can be used to visualize local dipole fields and how positive contrast can thus be obtained.

Section snippets

Theoretical background

Every NMR experiment makes use of an equilibrium nuclear magnetization M0 created by a polarizing field B0, generally applied along the z-direction. This magnetization gives rise to a long range dipolar magnetic field BDDF (DDF, for distant dipolar field) which, if B0  μ0M0, is given by [8]BDDF(r)=μ04πd3r1-3cos2θ2|r-r|33Mz(r)zˆ-M(r),where zˆ is the unit vector in the direction of B0 and θ is the angle between zˆ and, (r-r), while M(r) characterises the spatial distribution of

Computer simulations

All simulations were carried out with the program package MATLAB (The MathWorks Inc., Natick, MA) on conventional personal computers. Signal evolution as described by Eq. (2) was calculated for the CRAZED sequence shown in Fig. 1. BDDF and MDiff, describing changes in magnetization originating from diffusion, were calculated after Fourier-transformation in k-space, following the strategy proposed by Enss et al. [31]. Calculations with matrices of up to 128 × 128 × 64 in size were performed.

Negative contrast from local dipole fields

To demonstrate the influence of Bdip on the evolution of the magnetization we have simulated a CRAZED experiment without gradient-imposed modulation. Figs. 2a and b show contour plots of the longitudinal magnetization, Mz, in the central yz-plane of the simulation grid, immediately after the second rf-pulse for t1 = 2 ms (Fig. 2a) and t1 = 10 ms (Fig. 2b). Mz is modulated in a typical dipolar pattern with strong modulation along the z-axis and in the transverse plane, but zero modulation along the

Discussion

CRAZED imaging can be used to visualize local dipole fields. In the normal CRAZED experiment, areas of reduced signal near the source of the dipole field are observed, similar to the effects manifested in gradient echo imaging experiments. While it was recently shown that CRAZED produces superior contrast in tissue with larger amounts of embedded nanoparticles [7], the effects of single sources of dipole fields are not more pronounced in the CRAZED experiment. Taking into account the fact that

Conclusion

We have shown that CRAZED imaging can be used to visualize local dipole fields. With gradient modulation applied along the magic angle or mismatched coherence-selection gradients, positive contrast from local dipole fields can be created. Excellent suppression of the background and sufficient signal from the dipoles can be achieved in short experimental times. Although no exact solution for signal evolution was found, the method may be a valuable tool for the investigation of experimentally

Acknowledgments

This work was supported by Grants from the Deutsche Forschungsgemeinschaft (DFG, Fa474/1), DAAD (PPP/ARC program), and a Senior Mansfield Fellowship. The 750 MHz spectrometer was funded by the DFG (Ha1232/13).

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