Direct MRI detection of impending plaque development in multiple sclerosis

Abstract

Objectives: To detect and localize MRI signal changes prior to the parenchymal contrast enhancement that classically defines the radiologic onset of the developing white matter lesion in multiple sclerosis (MS).

Methods: We reviewed 308 high-resolution (≤1 mm(3) voxels) MRI scans at 3T and 7T in 29 patients with active MS. The presence of pre-parenchymal enhancement abnormalities before the appearance of parenchymal enhancement was evaluated in all available scans.

Results: Pre-enhancement signal changes were noted in 26 of 162 enhancing lesions (16%) as linear enhancement of the central vein and/or perivenular hyperintense signal on T2 fluid-attenuated inversion recovery or T2* images. They occur up to 2 months before focal enhancement within the parenchyma in 10% of cases.

Conclusions: In some lesions, the abrupt opening of the blood-brain barrier, detected by contrast enhancement on MRI, can have directly visible antecedent MRI changes centered on the central vein. We propose that these findings might be the basis for prior reports of subtle pre-parenchymal enhancement changes in quantitative MRI indices. In line with the venulocentric model of lesion development, our findings are consistent with the centrality of early perivenular events in lesion formation in vivo.

Figure 1. Short-term pre-parenchymal enhancement MRI changes

(A) Even in the absence of postcontrast 3T T2 fluid-attenuated inversion recovery (FLAIR) signal abnormality, isolated linear intravascular enhancement (arrow) is depicted on postcontrast T1 magnetization-prepared rapid gradient-echo (MPRAGE) images 8 days before the development of an enhancing lesion in the right parietal white matter (37-year-old man with relapsing-remitting multiple sclerosis [MS], Expanded Disability Status Scale [EDSS] score 0, and disease duration 0.8 years). (B) On 7T T2*-weighted images, subtle hyperintense signal around a prominent central vein (arrow) is discerned 44 days before, but not 3 months before, parenchymal lesion enhancement (38-year-old woman with relapsing-remitting MS, EDSS score 1.5, and disease duration 7.6 years). (C) Linear intravascular enhancement (arrow) on postcontrast 7T T1-MPRAGE and hyperintensity around the central vein (diameter 3 mm, arrow) on 7T T2*-weighted images were detected 14 days before the appearance of parenchymal enhancement in the right frontal white matter. No corresponding signal abnormalities were detected in postcontrast 7T T1-MPRAGE and T2*-weighted images acquired 5.6 months before (49-year-old woman with progressive MS, EDSS score 5.5, and disease duration 21 years).

Figure 2. Long-lasting pre-parenchymal enhancement MRI findings

Patient 1 (A.a–A.c). A new right juxtacortical parietal lesion develops at time 0 (same patient as in figure 1C). In A.a, a small area, hyperintense on T2 fluid-attenuated inversion recovery (FLAIR) and hypointense on postcontrast T1 magnetization-prepared rapid gradient-echo (MPRAGE) images (diameter 1.7 and 1.4 mm, respectively), is clearly visible several months before parenchymal enhancement and remains stable in size. At time 0, the lesion enhances centrifugally from the central vein; at month 1, the enhancement pattern is centripetal. (A.b, A.c) On 7T T2*-weighted axial and coronal magnified views, subtle bright signal around the prominent central vein is seen 4 months before parenchymal lesion enhancement. Patient 2 (B.a–B.c). A new right parietal white matter lesion in a 42-year-old woman with relapsing-remitting multiple sclerosis (Expanded Disability Status Scale score 3, disease duration 3 years). In B.a, a long-lasting hyperintense area on 3T T2-FLAIR (diameter 3.1 mm) is detected in all previous available scans but not in all the postcontrast T1-MPRAGE images. On 3T T2*-weighted images, its elongated structure around the central vein (B.b, axial and sagittal magnified views) is seen a month before parenchymal enhancement (B.c, time 0).