Inversion Recovery Susceptibility Weighted Imaging With Enhanced T2 Weighting at 3 T Improves Visualization of Subpial Cortical Multiple Sclerosis Lesions

Abstract

Objectives: Cortical demyelination is common in multiple sclerosis (MS) and can be extensive. Cortical lesions contribute to disability independently from white matter lesions and may form via a distinct mechanism. However, current magnetic resonance imaging methods at 3 T are insensitive to cortical, and especially subpial cortical, lesions. Subpial lesions are well seen on T2*-weighted imaging at 7 T, but T2*-weighted methods on 3 T scanners are limited by poor lesion-to-cortex and cerebrospinal fluid-to-lesion contrast. We aimed to develop and evaluate a cerebrospinal fluid-suppressed, T2*-weighted sequence optimized for subpial cortical lesion visualization.

Materials and methods: We developed a new magnetic resonance imaging sequence, inversion recovery susceptibility weighted imaging with enhanced T2 weighting (IR-SWIET; 0.8 mm × 0.8 mm in plane, 0.64 mm slice thickness with whole brain coverage, acquisition time ~5 minutes). We compared cortical lesion visualization independently on IR-SWIET (median signal from 4 acquisitions), magnetization-prepared 2 rapid acquisition gradient echoes (MP2RAGE), double inversion recovery (DIR), T2*-weighted segmented echo-planar imaging, and phase-sensitive inversion recovery images for 10 adults with MS. We also identified cortical lesions with a multicontrast reading of IR-SWIET (median of 2 acquisitions), MP2RAGE, and fluid-attenuated inversion recovery (FLAIR) images for each case. Lesions identified on 3 T images were verified on "gold standard" 7 T T2* and MP2RAGE images.

Results: Cortical, and particularly subpial, lesions appeared much more conspicuous on IR-SWIET compared with other 3 T methods. A total of 101 true-positive subpial lesions were identified on IR-SWIET (average per-participant sensitivity vs 7 T, 29% ± 8%) versus 36 on MP2RAGE (5% ± 2%; comparison to IR-SWIET sensitivity, P = 0.07), 17 on FLAIR (2% ± 1%; P < 0.05), 28 on DIR (6% ± 2%; P < 0.05), 42 on T2*-weighted segmented echo-planar imaging (11% ± 5%; P < 0.05), and 13 on phase-sensitive inversion recovery (4% ± 2%; P < 0.05). When a combination of IR-SWIET, MP2RAGE, and FLAIR images was used, a total of 147 subpial lesions (30% ± 5%) were identified versus 83 (16% ± 3%, P < 0.01) on a combination of DIR, MP2RAGE, and FLAIR. More cases had at least 1 subpial lesion on IR-SWIET, and IR-SWIET improved cortical lesion subtyping accuracy and correlation with 7 T subpial lesion number.

Conclusions: Subpial lesions are better visualized on IR-SWIET compared with other 3 T methods. A 3 T protocol combining IR-SWIET with MP2RAGE, in which leukocortical lesions are well seen, improves cortical lesion visualization over existing approaches. Therefore, IR-SWIET may enable improved MS diagnostic specificity and a better understanding of the clinical implications of cortical demyelination.

Figure 1.

Development of the inversion recovery susceptibility weighted imaging with enhanced T2 weighting (IR-SWIET) sequence. A) Mz evolution for IR-SWIET at steady-state. Arrows indicate beginning and end of each epoch. Black arrows indicate beginning and end of data acquisition. GM = gray matter, WM = white matter, CSF = cerebrospinal fluid. B) Schematic diagram for the IR-SWIET sequence. Arrows shown correspond to the magnetization epoch portrayed in (A).

Figure 2.

Inversion recovery susceptibility weighted imaging with enhanced T₂ weighting (IR-SWIET) images. IR-SWIET is a 3D sequence reconstructed with isotropic voxels, allowing for reconstruction in axial (A), coronal (B), and sagittal (C) planes. IR-SWIET images have suppressed CSF signal, making cortical lesions easier to see. (A-C) White matter lesions (yellow arrows) and cortical lesions (red arrows) are conspicuous and central veins (asterisk) can be seen in some lesions. Lesions in the brainstem (D, yellow arrowhead) and cerebellum (E, yellow arrowhead) are also observed. All images are medians of four IR-SWIET acquisitions.

Figure 3.

IR-SWIET improves subpial lesion detection. A) Subpial lesions (red arrow) are well seen on IR-SWIET images compared to other 3T images and are confirmed as lesions on 7T images. B) High magnification view of two subpial lesions identified on IR-SWIET but which are more subtle on other 3T images and are confirmed on 7T images. C) Quantification of sensitivity of individual 3T sequences and 3T multicontrast reads compared to lesions identified on 7T images. *=p<0.05, **=p<0.01, ***=p<0.001, IR-SWIET – inversion recovery susceptibility weighted imaging with enhanced T₂ weighting (x2 - median of two acquisitions, x4 – median of four acquisitions), DIR – double inversion recovery, MP2RAGE – magnetization-prepared 2 rapid gradient echo, T₂*wEPI – T₂* weighted segmented echo-planar imaging, FLAIR – fluid-attenuated inversion recovery, PSIR – phase-sensitive inversion recovery, GRE – gradient recalled echo.

Figure 4.

IR-SWIET improves subpial classification and 3T-7T subpial correlation. A) Subpial lesion classification is more accurate on IR-SWIET than on MP2RAGE, FLAIR, and DIR, and IR-SWIETx2/MP2RAGE/FLAIR is more accurate than DIR/M2RAGE/FLAIR. *=p<0.05, **=p<0.01 B) Correlation between subpial lesions identified on 3T vs 7T is higher for IR-SWIETx4, IR-SWIETx2/MP2RAGE/FLAIR, and DIR/MP2RAGE/FLAIR than for MP2RAGE, DIR, or PSIR. IR-SWIET – inversion recovery susceptibility weighted imaging with enhanced T₂ weighting (x2 - median of two acquisitions, x4 – median of four acquisitions), DIR – double inversion recovery, MP2RAGE – magnetization-prepared 2 rapid gradient echo, T₂*wEPI – T₂* weighted segmented echo-planar imaging, FLAIR – fluid-attenuated inversion recovery, PSIR – phase-sensitive inversion recovery.