Meningeal contrast enhancement in multiple sclerosis: Assessment of field strength, acquisition delay, and clinical relevance

Abstract

Background/purpose: Leptomeningeal enhancement (LME) on post-contrast FLAIR is described as a potential biomarker of meningeal inflammation in multiple sclerosis (MS). Here we report an assessment of the impact of MRI field strength and acquisition timing on meningeal contrast enhancement (MCE).

Methods: This was a cross-sectional, observational study of 95 participants with MS and 17 healthy controls (HC) subjects. Each participant underwent an MRI of the brain on both a 7 Tesla (7T) and 3 Tesla (3T) MRI scanner. 7T protocols included a FLAIR image before, soon after (Gd+ Early 7T FLAIR), and 23 minutes after gadolinium (Gd+ Delayed 7T FLAIR). 3T protocol included FLAIR before and 21 minutes after gadolinium (Gd+ Delayed 3T FLAIR).

Results: LME was seen in 23.3% of participants with MS on Gd+ Delayed 3T FLAIR, 47.4% on Gd+ Early 7T FLAIR (p = 0.002) and 57.9% on Gd+ Delayed 7T FLAIR (p < 0.001 and p = 0.008, respectively). The count and volume of LME, leptomeningeal and paravascular enhancement (LMPE), and paravascular and dural enhancement (PDE) were all highest for Gd+ Delayed 7T FLAIR and lowest for Gd+ Delayed 3T FLAIR. Non-significant trends were seen for higher proportion, counts, and volumes for LME and PDE in MS compared to HCs. The rate of LMPE was different between MS and HCs on Gd+ Delayed 7T FLAIR (98.9% vs 82.4%, p = 0.003). MS participants with LME on Gd+ Delayed 7T FLAIR were older (47.6 (10.6) years) than those without (42.0 (9.7), p = 0.008).

Conclusion: 7T MRI and a delay after contrast injection increased sensitivity for all forms of MCE. However, the lack of difference between groups for LME and its association with age calls into question its relevance as a biomarker of meningeal inflammation in MS.

Fig 1. Identification of meningeal enhancement.

Shown are Gd+ MP2RAGE T1W (A, F, K, P), Gd- 7T FLAIR (B, G, L, Q), Gd+ Delayed 7T FLAIR (C, H, M, R), FLAIR subtraction maps (D, I, N, S), and FLAIR subtraction maps with overlaid enhancement masks (E, J, O, T). Regions of enhancement were first identified on FLAIR subtraction maps, and then confirmed by evaluation on FLAIR and T1W images. Subtypes were then classified, and masks drawn as the focus appeared on the subtraction map. A nodular focus (red mask) is shown on the top row and a spread/fill focus (green mask) is shown on in the 2nd row. Together, these subtypes were classified as leptomeningeal enhancement (LME). Note the proximity of both types of LME foci to meningeal blood vessels on Gd+ T1W. Multiple paravascular foci (blue masks) are shown in the 3rd row. Note the location of enhancements to be immediately external to enhancing meningeal blood vessel lumens on Gd+ T1W. A dural nodule focus (yellow mask) is shown in the 4th row. Note the co-localization of this focus to enhancing structures in the falx cerebri on Gd+ T1W. Paravascular and dural nodules together were termed paravascular and dural enhancement (PDE).

Fig 2. Example of LME as visualized on various Gd+ imaging protocols.

Shown is Gd+ Delayed 3T FLAIR (A), Gd+ Early 7T FLAIR (B), and Gd+ Delayed 7T FLAIR (C). Also shown are subtraction maps created by subtraction of A from pre-Gd 3T FLAIR (D) and B and C subtracted from pre-Gd 7T FLAIR (E and F, respectively). Yellow arrows indicate a focus of LME readily visible, but which is barely visible on Gd+ Delayed 3T FLAIR (red arrow). Note that although the focus is seen on Gd+ Early 7T FLAIR (B, E), it is thicker/more prominent on Gd+ Delayed 7T FLAIR (C, F).

Fig 3. Examples of PDE as visualized on various Gd+ imaging protocols.

Shown is Gd+ Delayed 3T FLAIR (A), Gd+ Early 7T FLAIR (B), and Gd+ Delayed 7T FLAIR (C). Also shown are subtraction maps created by subtraction of A from pre-Gd 3T FLAIR (D) and B and C subtracted from pre-Gd 7T FLAIR (E and F, respectively). Yellow arrows indicate foci of PDE seen on all 3 protocols. Red arrows indicate regions where PDE was seen on both 7T protocols but could not be seen on Gd+ Delayed 3T FLAIR. The green arrow indicates a region where PDE was seen on Gd+ Delayed 7T FLAIR, but could not be seen on Gd+ FLAIR or Gd+ Early 7T FLAIR.

Fig 4. LME in healthy controls.

Shown are axial Gd+ Delayed 7T FLAIR images with LME highlighted by red ovals. Examples of LME in healthy controls as seen in a 40-year-old woman (B) and a 47-year-old woman (D) with no known neurological conditions. No leptomeningeal hyperintensity is seen in the same location on pre-contrast images (A,C).