Leptomeningeal Enhancement at 7T in Multiple Sclerosis: Frequency, Morphology, and Relationship to Cortical Volume

Abstract

Background and Purpose Perform an investigation of the frequency and distribution of leptomeningeal enhancement on post-gadolinium magnetization-prepared FLAIR (MPFLAIR) in multiple sclerosis (MS) on 7 Tesla (7T) MRI and to relate this finding to measures of brain structure and lesion volumes. Methods Twenty-nine participants with MS underwent 7T MRI of the brain. Three healthy volunteers (HV) were scanned for comparison. Areas of post-contrast leptomeningeal enhancement were identified. Images were segmented for brain structure and lesion volumes. The relationship between leptomeningeal enhancement and clinical and volumetric data was explored. Results Two patterns of enhancement were found: “nodular” (discrete, spherical nodules at the pial surface or subarachnoid space) and “spread/fill” (appearance of contrast spread through the subarachnoid space). Twenty-six of 29 (90%) MS participants had at least one focus of leptomeningeal enhancement. Nodular foci were present in 15/29 (51%) MS participants. Spread/fill foci were present in 22/29 (76%) MS participants. Two HVs had examples of nodular foci, but none had spread/fill enhancement. MS participants with spread/fill foci were older (48.9 years (SD 8.3)) than those without (33.3 years (SD 11.5), p = 0.005). MS participants with spread/fill foci had reduced cortical gray matter volume compared to those without (p = 0.020). Conclusions Leptomeningeal enhancement on post-contrast 7T MPFLAIR is more prevalent than prior reports at 3T – occurring at frequencies closer to histopathologic data. Spread/fill foci are associated with reduced cortical GM volumes and may represent blood-meningeal barrier breakdown near sites of meningeal inflammation, whereas nodular foci may be a normal variant.

Longitudinal Persistence of Meningeal Enhancement on Postcontrast 7T 3D-FLAIR MRI in Multiple Sclerosis

“…Although no direct 3T versus 7T comparisons have been made in the same study population, up to 90% of MS patients undergoing contrast-enhanced brain MRI at 7T demonstrated at least one enhancing focus. 9 This result closely approximates the 89% of MS patients reported to show some element of leptomeningeal inflammation at autopsy. 10,11 Given this radiologic-pathologic concordance, it is conceivable that 7T 3D FLAIR may soon provide a non-invasive in-vivo method of detecting and accurately quantifying the extent of meningeal inflammation in patients with MS. Meningeal enhancement was noted to be a persistent phenomenon in prior 3T studies; 7 however, at 7T where sensitivity for meningeal enhancement in MS appears to be significantly higher, it remains unknown whether smaller, more subtle foci of enhancement wax and wane in a predictable pattern over time or whether they remain longitudinally stable.…”

“…In this study, we catalogued two enhancement patterns described in prior analysis (subarachnoid nodular and subarachnoid spread/fill) 7,9 in addition to describing two new patterns of meningeal enhancement for the first time: vessel wall enhancement and dural foci. Previous studies without pre-contrast comparison sequences excluded from consideration regions of postcontrast hyperintensity in/near dural sinuses, large subarachnoid veins, and the basal meninges in order to reduce false positives, because these structures often manifest pre-contrast T1 or FLAIR hyperintensity.…”

“…Previous studies without pre-contrast comparison sequences excluded from consideration regions of postcontrast hyperintensity in/near dural sinuses, large subarachnoid veins, and the basal meninges in order to reduce false positives, because these structures often manifest pre-contrast T1 or FLAIR hyperintensity. 7,9 Using similar technique to the recent investigation by Zivadinov et al 8 , we coregistered and subtracted pre- and post-contrast MP-FLAIR sequences in all cases. Given this protocol, we did not have to exclude any structures a priori, and we were confident in our ability to differentiate true vessel wall and dural foci enhancement from intrinsically increased signal.…”

“…Also unknown is the degree to which enhancement persistence over time is associated with previously described enhancement shape and morphology, including subarachnoid spread/fill and subarachnoid nodular patterns. 7,9 As prior studies have shown that the prevalence of meningeal enhancement varies with enhancement morphology, 7,9 in this study we hypothesized that persistence of meningeal enhancement in MS would vary based on morphology of enhancement as well as demographic and clinical factors such as treatment status, disease phenotype, and disability scores. Greater understanding of the imaging and clinical characteristics of meningeal enhancement is necessary if these features are to aid in the diagnosis of and prognosis for MS patients.…”

Imaging Mechanisms of Disease Progression in Multiple Sclerosis: Beyond Brain Atrophy

“…Delayed‐acquisition and postcontrast 3‐dimensional FLAIR acquired at 7T may reveal that LME occurs at an even higher rate, with one series describing LME in up to 90% of cases with MS 86 . 7T data also suggests that longitudinally persistent, rather than transient, foci of LME are associated with disability progression, 87 but there is controversy regarding whether there is a spatial colocalization with MRI‐visible cortical lesions 85,88 .…”