Quantitative T1 mapping detects blood-brain barrier breakdown in apparently non-enhancing multiple sclerosis lesions

Abstract

Objectives: The disruption of the blood-brain barrier (BBB) is a key and early feature in the pathogenesis of demyelinating multiple sclerosis (MS) lesions and has been neuropathologically demonstrated in both active and chronic plaques. The local overt BBB disruption in acute demyelinating lesions is captured as signal hyperintensity in post-contrast T1-weighted images because of the contrast-related shortening of the T1 relaxation time. On the contrary, the subtle BBB disruption in chronic lesions is not visible at conventional radiological evaluation but it might be of clinical relevance. Indeed, persistent, subtle BBB leakage might be linked to low-grade inflammation and plaque evolution. Here we hypothesised that 3D Quantitative Transient-state Imaging (QTI) was able to reveal and measure T1 shortening (ΔT1) reflecting small amounts of contrast media leakage in apparently non-enhancing lesions (ANELs).

Materials and methods: Thirty-four patients with relapsing remitting MS were included in the study. All patients underwent a 3 T MRI exam of the brain including conventional sequences and QTI acquisitions (1.1 mm isotropic voxel) performed both before and after contrast media administration. For each patient, a ΔT1 map was obtained via voxel-wise subtraction of pre- and post- contrast QTI-derived T1 maps. ΔT1 values measured in ANELs were compared with those recorded in enhancing lesions and in the normal appearing white matter. A reference distribution of ΔT1 in the white matter was obtained from datasets acquired in 10 non-MS patients with unrevealing MR imaging.

Results: Mean ΔT1 in ANELs (57.45 ± 48.27 ms) was significantly lower than in enhancing lesions (297.71 ± 177.52 ms; p < 0. 0001) and higher than in the normal appearing white matter (36.57 ± 10.53 ms; p < 0.005). Fifty-two percent of ANELs exhibited ΔT1 higher than those observed in the white matter of non-MS patients.

Conclusions: QTI-derived quantitative ΔT1 mapping enabled to measure contrast-related T1 shortening in ANELs. ANELs exhibiting ΔT1 values that deviate from the reference distribution in non-MS patients may indicate persistent, subtle, BBB disruption. Access to this information may be proved useful to better characterise pathology and objectively monitor disease activity and response to therapy.

Keywords: Blood-brain barrier; Magnetic resonance fingerprinting; Magnetic resonance imaging; Multiple sclerosis; Quantitative imaging; Quantitative transient-state imaging; T1 mapping.

Fig. 1

Representative images obtained in one patient with multiple sclerosis, co-registered to the pre-contrast T1-mapping acquisition. Top row shows pre-contrast FLAIR (A), T1-weighted FSPGR (B) and T1-maps obtained with QTI before (C) and after (D) contrast media administration. Grayscale bars in (C) and (D) cover a range of T1-values between 0 and 3000 ms. In the bottom row: (E) shows lesion ROIs (in red) drawn on the FLAIR image; (F) shows the partial volume map of white matter, ranging between 0 (red) and 100% (yellow), superimposed to the T1-weighted image; (G) shows the ROI representing the normal appearing white matter (NAWM, green), which is defined as the eroded binary mask obtained from the subtraction of dilated lesions (blue) from the binarized white matter map (yellow). ROIs representing multiple sclerosis lesions and NAWM are shown also in (H), superimposed to the quantitative map of contrast-related T1-shortening (ΔT1) after contrast media administration; the bar in (H) ranges between −3000 ms and 3000 ms. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Boxplot showing differences in ΔT1 between ANELs and NAWM, and between ANELs and ELs. Solid and dashed lines superimposed to the graph represent the reference distribution of white matter ΔT1 values across non-MS patients (mean ± 1.96*standard deviation). NAWM, normal appearing white matter; ANELs, apparently non-enhancing demyelinating multiple sclerosis lesions; ELs, enhancing demyelinating multiple sclerosis lesions. * p < 0.005; ** p < 0.0001.