Black Dipole or White Dipole: Using Susceptibility Phase Imaging to Differentiate Cerebral Microbleeds from Intracranial Calcifications

DISCUSSION

Our study indicated that the border phase patterns had higher interobserver reliability than the central phase patterns. The border phase patterns were homogeneous, whereas the central phase patterns were relatively heterogeneous and variable. The border phase patterns had higher diagnostic accuracy in differentiating calcifications and CMBs than the central phase patterns, particularly for lesions of >2.5 mm in diameter. Moreover, the border phase patterns had the same diagnostic accuracy as QSM in differentiating calcifications and CMBs.

The phase pattern of a GRE dark spot is determined by its susceptibility. The local magnetic field change (ΔB), caused by a spheric paramagnetic/diamagnetic lesion at an arbitrary point (r) from the center of the lesion, is described in Equation 1 for within the lesion and Equation 2 for outside the lesion:¹⁹ 1) 2)where Δχ is the relative susceptibility of the lesion compared with water, D is the diameter of the lesion, B₀ is the main magnetic field, and θ is the angle between r and B₀. Furthermore, the local phase shift caused by a lesion in GRE phase images is proportional to the local magnetic field change multiplied by the gyromagnetic ratio then multiplied by the TE.⁸ In the 2D phase imaging simulation, a paramagnetic lesion induced an increased local phase shift parallel to the main magnetic field on the superior and inferior sides and antiparallel on the lateral side (Fig 6A), whereas a diamagnetic lesion caused the opposite change (Fig 6B).⁸ Because the direction of the main magnetic field in clinical MR imaging examinations is parallel to the body axis, the coronal phase image more favorably represented the susceptibility effect of a lesion than the axial phase image. A paramagnetic CMB appeared as a black dipole with a pair of bright wings, whereas a diamagnetic calcification appeared as a white dipole with black wings.

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Fig 6.

2D simulation of the local phase shift around lesions smaller and larger than 2.5 mm in diameter. The simulation was based on Equations 1 and 2. The phase shift is represented in the radians, and phase aliasing occurs when the phase shift exceeds +π or –π radians. The parameters are the same as those in our clinical setting: B₀, 3T; TE, 25 ms; and gyromagnetic ratio, 42.58 × 10⁶ Hz/T. The relative susceptibility (Δχ) and diameter (D) of the lesion are the mean values of the lesions in each group in our study. In lesions <2.5 mm in diameter, the simulated phase image reveals a black dipole with white side wings in the paramagnetic lesion (A) and a white dipole with black side wings in the diamagnetic lesion (B). In lesions >2.5 mm in diameter, the relative susceptibility is higher and the diameter is larger, which causes a larger phase shift that exceeds the aliasing threshold within the lesion. This results in a black dipole with a white core from phase aliasing, the white side wings in the paramagnetic lesion (C), and a white dipole with a black core and black side wings in the diamagnetic lesion (D).

The strong correlation between the size and susceptibility of CMBs and calcifications suggested that large lesions cause high phase shifts. If the positive phase shift caused by a large paramagnetic lesion exceeds π radians, it aliases to −π radians and appears to be bright rather than dark in the phase image.²⁰ Phase aliasing is most likely to occur in the center of a lesion because the local phase shift is most severe inside lesions and decreases with the cube of the distance from the center of the lesion to outside the lesion (Equations 1 and 2). Therefore, a small white core caused by phase aliasing could be observed in the center of the black dipole in the 2D phase simulation of a large paramagnetic lesion with high susceptibility (Fig 6C). Notably, we observed the same pattern in the coronal reformation of the phase images in paramagnetic CMBs of >2.5 mm in diameter (Fig 7B). A small black core caused by phase aliasing was observed in the center of a white dipole in the 2D phase simulation of a large diamagnetic lesion with high susceptibility (Fig 6D) and in our clinical coronal phase images when the calcifications were >2.5 mm (Fig 7A). Furthermore, when a lesion had even higher susceptibility, the local phase shift could be large enough to alias twice, which resulted in an alternating white and black core and led to a more heterogeneous phase pattern in the central section (Fig 7C). Other factors may have also led to heterogeneity in the phase pattern, including the noise of T2*-weighted GRE imaging, high-pass filtering (particularly for large lesions), and the heterogeneous density of calcification and hemosiderin deposition in CMBs.^8,10,11,21 Therefore, in this study, central phase patterns were more heterogeneous and variable, particularly for lesions of >2.5 mm in diameter, and were unreliable in determining the susceptibility of the lesions.

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Fig 7.

Serial changes in the axial phase pattern in paramagnetic and diamagnetic dipoles. A, A diamagnetic dipole, which represents a pineal calcification, is displayed in the coronal phase image (left) and magnified image (middle). The white dipole with a black core and side wings in the coronal phase image explains serial changes in the axial phase patterns (right upper images) in the corresponding 5 levels: 1, totally white; 2, white circle with black core; 3, heterogeneously black (epicenter); 4, white circle with black core; and 5, totally white (lower border). The phase shift diagram (right lower images) crossing the center of the lesion reveals that when the positive phase shift is large enough to exceed π radians, it aliases toward −π radians and appears to be partially dark in the phase images near the central slices (2, 3, and 4 of the right lower images). B, A paramagnetic black dipole, which represents a microbleed in the white matter of the right cerebral hemisphere, presents the opposite pattern in the coronal and axial phase images and phase shift diagrams. C, A paramagnetic black dipole larger than that in B shows an alternating “black in white” core in the coronal phase (middle) and axial phase images (2, 3, and 4 of the right upper images). The phase shift diagram indicates that when the negative phase shift is large enough to exceed −π radians, it aliases toward +π radians (2 and 4 of the right lower images), and if the phase shift exceeds +π radians after the first aliasing, it aliases backward by −π radians (3 of the right lower images), which causes the alternating black in white core pattern in the center of the black dipole.

The border phase patterns achieved the same sensitivity and specificity for identifying calcifications as QSM. The border section was far from the center of the lesion and, by definition, presented the smallest perceptible phase shift. Therefore, the border phase patterns were not affected by aliasing and were always homogeneous and accurate in reflecting the susceptibility of the lesions. Chen et al⁸ reported that QSM has higher sensitivity and specificity than GRE phase imaging for differentiating calcifications and hemorrhages; however, in their study, the location and orientation of GRE phase images were not precisely defined. Examples of heterogeneous GRE phase images leading to the misinterpretation of the susceptibility of lesions in their study were correctly interpreted using our method. In addition to the border phase pattern, we could identify the susceptibility of lesions from the phase shift in the peripheral rim of the lesion in the axial central phase image, which revealed the opposite phase change to the susceptibility of the lesion.¹² However, in our clinical experience, phase changes in the peripheral rim are weaker and less easy to interpret than the dipole itself, particularly in large lesions that have phase aliasing in the axial central phase images. They could also be affected by the local susceptibility change of the surrounding tissue, such as nearby veins.

The only lesion that was misinterpreted as a CMB based on its border phase pattern was a choroid plexus calcification at the foramen of Luschka. Calcifications could reveal paramagnetic susceptibility with extra depositions of paramagnetic substances, such as hemosiderin and ferrous or other metal components. This is a common finding in calcifications within the deep nucleus, particularly in the globus pallidum; however, this is rarely reported in calcifications outside the deep nucleus.^8,9

Our study has several limitations. First, our method focused on only the phase patterns of GRE dark spots that are small (<10 mm in diameter) and round or oval. The phase patterns may become heterogeneous in large lesions because of increased phase aliasing from high susceptibility effects and high-pass filtering. In addition, the dipole pattern caused by the susceptibility effect can differ in linear, tubular, and irregular lesions. However, the phase shift in the border section is less affected by the size and shape of the lesion. We observed that border phase patterns could be used to correctly identify the susceptibility of large and irregular lesions; however, additional studies should be conducted to confirm this finding. Second, the susceptibility of lesions with mixed hemorrhagic and calcified components cannot be precisely evaluated from the phase pattern because the phase image can only reveal the susceptibility of the dominant component, and this problem cannot be completely overcome through QSM. Third, if a calcification is accompanied by the deposition of paramagnetic substances, such as those in the deep nucleus or our false-negative case, this feature may be interpreted as a CMB from the phase pattern. However, this is also a limitation of QSM. In this situation, CT is still needed for the final diagnosis. Finally, it is important to know MR imaging vendors’ phase presenting system (right-handed or left-handed system) to avoid making a wrong interpretation.