Highly Sensitive 3-Tesla Real Inversion Recovery MRI Detects Leptomeningeal Contrast Enhancement in Chronic Active Multiple Sclerosis

Abstract

Background: Leptomeningeal contrast enhancement (LME) on T2-weighted Fluid-Attenuated Inversion Recovery (T2-FLAIR) MRI is a reported marker of leptomeningeal inflammation, which is known to be associated with progression of multiple sclerosis (MS). However, this MRI approach, as typically implemented on clinical 3-tesla (T) systems, detects only a few enhancing foci in ~25% of patients and has thus been criticized as poorly sensitive.

Purpose: To compare an optimized 3D real-reconstruction inversion recovery (Real-IR) MRI sequence on a clinical 3 T scanner to T2-FLAIR for prevalence, characteristics, and clinical/radiological correlations of LME.

Materials and methods: We obtained 3D T2-FLAIR and Real-IR scans before and after administration of standard-dose gadobutrol in 177 scans of 154 participants (98 women, 64%; mean ± SD age: 49 ± 12 years), including 124 with an MS-spectrum diagnosis, 21 with other neurological and/or inflammatory disorders, and 9 without neurological history. We calculated contrast-to-noise ratios (CNR) in 20 representative LME foci and determined association of LME with cortical lesions identified at 7 T (n = 19), paramagnetic rim lesions (PRL) at 3 T (n = 105), and clinical/demographic data.

Results: We observed focal LME in 73% of participants on Real-IR (70% in established MS, 33% in healthy volunteers, P < 0.0001), compared to 33% on T2-FLAIR (34% vs. 11%, P = 0.0002). Real-IR showed 3.7-fold more LME foci than T2-FLAIR ( P = 0.001), including all T2-FLAIR foci. LME CNR was 2.5-fold higher by Real-IR ( P < 0.0001). The major determinant of LME status was age. Although LME was not associated with cortical lesions, the number of PRL was associated with the number of LME foci on both T2-FLAIR ( P = 0.003) and Real-IR ( P = 0.0003) after adjusting for age, sex, and white matter lesion volume.

Conclusions: Real-IR a promising tool to detect, characterize, and understand the significance of LME in MS. The association between PRL and LME highlights a possible role of the leptomeninges in sustaining chronic inflammation.

Figure 1:

Construction of the study cohort. Abbreviations: CEL, contrast-enhancing lesion; CL, cortical lesions; CIS, clinically isolated syndrome; GBCA, gadolinium-based contrast agent; HAM/TSP, human T-lymphotropic virus-1 associated myelopathy/tropical spastic paraparesis; LME, leptomeningeal enhancement; MS, multiple sclerosis: NIND, noninflammatory neurological disorders; OIND, other inflammatory neurological disorders; PRL, paramagnetic rim lesions; Real-IR, real-reconstruction inversion recovery; RIS, radiologically isolated syndrome; T1-MP2RAGE, T1-weighted magnetization prepared 2 inversions rapid gradient echo; T2-FLAIR, T2-weighted fluid-attenuated inversion recovery; T2*-EPI, T2*-weighted echo-planar imaging. (Created with BioRender.com)

Figure 2:

Representative images from 2 individuals showing improved visualization of leptomeningeal enhancement (LME) and higher contrast-to-noise ratio (CNR) on Real-IR compared to T2-FLAIR. (A) Axial pre-GBCA (column I), post-GBCA (column II), subtraction (column III), and sagittal post-GBCA (column IV) T2-FLAIR (rows a & c) and Real-IR (rows b & d) images of two LME foci in a 34-year-old woman with relapsing-remitting multiple sclerosis. A spread/fill LME in a left posterior medial sulcus detected on both T2-FLAIR and Real-IR (rows a & b, yellow arrows), whereas a nodular LME in a right cerebellar sulcus was solely visible on Real-IR (row d, red arrows). (B) Representative region of interest (magnified in white circles) depicting LME visualized on T2-FLAIR (a), and with better CNR and larger volume on Real-IR (b), in a 44-year-old woman with relapsing-remitting MS. (C) Scatter plots of measurements from 20 LME foci visible on both T2-FLAIR and Real-IR showing higher CNR values on post-GBCA Real-IR (Wilcoxon signed-rank test, p<0.0001). Abbreviations: T2-FLAIR, T2-weighted fluid-attenuated inversion recovery; GBCA, gadolinium-based contrast agent; Real-IR, real-reconstruction inversion recovery; ROI, region of interest.

Figure 3:. Representative case with leptomeningeal enhancement.

Axial 3T pre-GBCA (I), post-GBCA (II), and subtraction (III), and sagittal post-GBCA (IV) T2-FLAIR (A, B) and Real-IR (C, D) scans of a 40-year-old woman with relapsing-remitting multiple sclerosis. A focus of leptomeningeal enhancement in a left intraparietal sulcus (white boxes, yellow arrows) is more easily visualized on post-GBCA and subtraction Real-IR compared to T2-FLAIR. Its location in the subarachnoid space is confirmed through visualization on at least two imaging planes (IV).

Figure 4:. Representative case for assessment of paramagnetic rim lesions and leptomeningeal enhancement.

Co-registered 3T pre-GBCA T1-MP2RAGE (A), post-GBCA T2-FLAIR (B), pre-GBCA unwrapped phase from T2*-EPI (C), and post-GBCA Real-IR (D) images from a 66-year-old man with secondary progressive multiple sclerosis, depicting a juxtacortical lesion (yellow arrows) with a paramagnetic rim (C) and an LME focus visualized only on post-GBCA Real-IR (red arrow, D). Note that the lesion itself is hyperintense on pre-GBCA real-IR images (not shown). Abbreviations: T2-FLAIR, T2-weighted fluid-attenuated inversion recovery; T2*-EPI, T2*-weighted echo-planar imaging; GBCA, gadolinium-based contrast agent; T1-MP2RAGE, T1-weighted magnetization prepared 2 inversions rapid gradient echo; Real-IR, real-reconstruction inversion recovery.

Figure 5:. Representative case for assessment of cortical lesions and leptomeningeal enhancement.

Pre-GBCA 7T T1-MP2RAGE (I) and pre-GBCA T2*-weighted gradient-echo (II) images are shown along with co-registered 3T post-GBCA T2-FLAIR (III) and Real-IR (IV) in a 71-year-old man with relapsing-remitting multiple sclerosis depicts a leptomeningeal enhancement focus with no nearby cortical lesion (yellow boxes in A, magnified in B with yellow arrows) and a cortical lesion with no nearby leptomeningeal enhancement (white boxes in A, magnified in C with white arrows). Abbreviations: T2-FLAIR, fluid-attenuated inversion recovery; GBCA, gadolinium-based contrast agent; T1-MP2RAGE, T1-weighted magnetization prepared 2 inversions rapid gradient echo; Real-IR, real-reconstruction inversion recovery.