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

Serhat Vahip Okar, Henry Dieckhaus, Erin S Beck, María I Gaitán, Gina Norato, Dzung L Pham, Martina Absinta, Irene Cm Cortese, Anita Fletcher, Steven Jacobson, Govind Nair, Daniel S Reich

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. 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. 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. 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. 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.