Sensitivity of MRI resonance frequency to the orientation of brain tissue microstructure

Abstract

Recent advances in high-field (>or=7 T) MRI have made it possible to study the fine structure of the human brain at the level of fiber bundles and cortical layers. In particular, techniques aimed at detecting MRI resonance frequency shifts originating from local variation in magnetic susceptibility and other sources have greatly improved the visualization of these structures. A recent theoretical study [He X, Yablonskiy DA (2009) Proc Natl Acad Sci USA 106:13558-13563] suggests that MRI resonance frequency may report not only on tissue composition, but also on microscopic compartmentalization of susceptibility inclusions and their orientation relative to the magnetic field. The proposed sensitivity to tissue structure may greatly expand the information available with conventional MRI techniques. To investigate this possibility, we studied postmortem tissue samples from human corpus callosum with an experimental design that allowed separation of microstructural effects from confounding macrostructural effects. The results show that MRI resonance frequency does depend on microstructural orientation. Furthermore, the spatial distribution of the resonance frequency shift suggests an origin related to anisotropic susceptibility effects rather than microscopic compartmentalization. This anisotropy, which has been shown to depend on molecular ordering, may provide valuable information about tissue molecular structure.

Fig. 1.

High-resolution (250 × 250-μm in-plane, 2 mm slice thickness, axial slices) GRE frequency images at 7 T (f₀ = 298.095 MHz) in vivo. Strong contrast is seen in association with the major white matter fiber bundles: (1) corpus callosum body; (2) corona radiata; (3) corpus callosum splenium; (4) optic radiation. Frequency was zeroed in areas with low or absent NMR signal (e.g. outside the brain).

Fig. 2.

Selection of white matter sections for postmortem MRI. (A) Five square cylindrical pieces of fixed tissue were sectioned along the primary fiber orientation in the corpus callosum (coronal view). (B) The tissues were placed in a groove at the bottom of a disk-shaped container. (C and D) Representations of condition A (C) and condition B (D) showing fiber orientations. The zoomed images show the detailed tissue structure.

Fig. 3.

Results of MRI frequency measurement at the original (condition A: A, C, and E) and rotated positions of fiber bundle segments C2 and C4 (condition B: B, D, and F). (A and B) DTI confirmation of microstructure orientation of segments, with red representing parallel orientations and blue representing perpendicular (through-plane) orientations relative to B₀. (C and D) Magnitude images. (E and F) Frequency images. In F, rotation leads to a positive frequency shift within and near the lateral edges of the rotated segments. A slightly negative frequency shift is observed in unrotated segments. A few small dipole field patterns, likely originating from air bubbles, are also seen in E. The images are from coronal scans in which the slice selection was along the physical y-axis, the readout gradient was along the physical z-axis, and the phase encoding was along the physical x-axis. B₀ was along the z-axis.

Fig. 4.

Averaged cross-sectional profile of the frequency difference image (condition B − condition A). The rotated segments (C2 and C4) show positive frequency shifts compared with the unrotated segments (C1, C3, and C5). Error bars represent SE. The scanner frequency was 300.390 MHz.

Fig. 5.

Simulation results for anisotropic susceptibility. (A) simulation result for condition B. (B) Cross-sectional profile of the best-fit susceptibility model (solid line) and the simulated frequency (dashed line). The simulated frequency image in A shows a strong similarity to the experimental results shown in Fig. 3F. The average cross-sectional profile (dashed in B) also agrees well with the experimental results (Fig. 4).

Fig. 6.

Cross-sectional profile of the calculated magnetic susceptibility. Note that the relative susceptibility of C1, C3, and C5 is not 0, because the result was obtained from the frequency difference images. Error bars represent SE.