ICM - Brain Institute

Author Of 1 Presentation

Neuroprotection, Regeneration and/or Remyelination Oral Presentation

PS11.03 - Lesion-specific perfusion levels affect myelin loss and repair in multiple sclerosis: a positron emission tomography study

Speakers
Presentation Number
PS11.03
Presentation Topic
Neuroprotection, Regeneration and/or Remyelination
Lecture Time
09:45 - 09:57

Abstract

Background

Following demyelination, remyelination may take place in multiple sclerosis (MS) lesions, but this process is heterogeneous and often fails. Brain perfusion was shown to impact remyelination in rodents, but this relationship has never been assessed in patients with MS. Positron emission tomography (PET) with 11C-PiB allows to simultaneously map demyelination and remyelination in vivo, and to generate quantitative maps of brain perfusion.

Objectives

To analyse the relationship between baseline perfusion and subsequent myelin content changes in white matter (WM) lesions.

Methods

11C-PIB PET and 3T MRI were acquired in 15 patients with relapsing-remitting MS at baseline and after 2-4 months. Nine hundred and four lesions were identified at baseline on T2-weighted scans with the exclusion of gadolinium-enhancing lesions to avoid artefacts in perfusion quantification. Logan reference graphical analysis and simplified reference tissue model were used to generate voxelwise maps of distribution volume ratio (DVR) and relative delivery (R1) from 11C-PiB images, respectively. Perfusion at baseline, as measured by R1, and the percentage of demyelinating and remyelinating voxels over the follow-up, derived from DVR maps, were calculated for each lesion.

Mixed-effect models were employed to evaluate the association between perfusion at baseline and the percentage of demyelinating and remyelinating voxels over the follow-up in WM lesions. A logistic regression was employed to determine the impact of perfusion on the probability of lesions to successfully repair, I.e. to remyelinate at least 50% of their demyelinated voxels at baseline and to undergo demyelination over the follow-up in less than 25% of voxels classified as normally myelinated at study entry.

Results

WM lesions showed lower perfusion compared to normal-appearing WM (0.43±0.08 vs 0.49±0.03, p<0.001), although single-lesion R1 values were remarkably heterogeneous (range: [0.08-2.5]). At the single lesion level, a higher perfusion at baseline was associated with a more extensive remyelination (β=0.32, p<0.001) and a reduced demyelination (β=-0.28, p<0.001) over the follow-up. Lesion-specific perfusion at baseline was an independent predictor of successful myelin repair over the follow-up (OR=8.4, p<0.001).

Conclusions

The level of perfusion of single MS lesions is critical for myelin repair and may be one key factor underlying the heterogeneous levels of remyelination across patients with MS.

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Author Of 1 Presentation

Imaging Poster Presentation

P0593 - Increased perfusion and microstructural damage precede demyelination in newly forming MS lesions (ID 1802)

Speakers
Presentation Number
P0593
Presentation Topic
Imaging

Abstract

Background

Microstructural alterations in the Normal-Appearing White Matter (NAWM) preceeding the onset of a new lesion have been described using advanced MRI in patients with MS. However, the biological substrate of these alterations remains poorly understood due to the lack of specificity of the MRI signal. We have previously shown that Positron Emission Tomography (PET) with 11C-PIB has the potential to quantify myelin content changes in WM lesions. Interestingly, dynamic 11C-PIB PET acquisitions, including early frames, enable the estimation of regional brain perfusion too.

Objectives

To characterize whether perfusion changes, microstructural damage and demyelination could precede lesion appearance on T2-weighted (T2-w) MRI images.

Methods

Longitudinal dynamic 11C-PIB PET and 3T MRI, including diffusion weighted and magnetization transfer imaging, were acquired in 19 active patients with relapsing-remitting MS. Following baseline scans, patients underwent a second evaluation after 1-2 month (n= 10) or after 3-4 months (n=9). Prelesional areas were defined as the baseline NAWM areas which became hyperintensities on the second T2-w image. Logan reference graphical analysis and simplified reference tissue model were respectiveley used to generate voxelwise maps of Distribution Volume Ratio (DVR), and relative delivery (R1) from 11C-PIB images. Myelin content, reflected by DVR, and perfusion, measured by R1, were extracted for each prelesional area and the corresonding contralateral area in the NAWM. Magnetization transfer ratio (MTR), fractional anisotropy (FA), radial and axial diffusivity (RD and AD) were calculated in the same areas. Paired t-test were used to test differences in DVR, R1, MTR, FA, RD and AD between the prelesional and its contralateral areas.

Results

We identified 77 prelesional areas. In the subgroup of patients with a 1-2 months follow-up, prelesional areas (45 out of 77) showed a higher perfusion (8.5%, p=0.03), increased RD (4.2%, p=0.003), lower MTR (-1.2%, p=0.008) and reduced FA (-6.2%, p=0.008), compared to contralateral NAWM areas, while no difference was detected in DVR (p=0.4). No statistical differences were found in the subgroup of patients with a follow-up of 3-4 months.

Conclusions

One-two months before becoming hyperintense on T2-w MRI, prelesional areas are characterized by an increased perfusion associated with microstructural changes, but not by demyelination.

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Presenter Of 1 Presentation

Imaging Poster Presentation

P0593 - Increased perfusion and microstructural damage precede demyelination in newly forming MS lesions (ID 1802)

Speakers
Presentation Number
P0593
Presentation Topic
Imaging

Abstract

Background

Microstructural alterations in the Normal-Appearing White Matter (NAWM) preceeding the onset of a new lesion have been described using advanced MRI in patients with MS. However, the biological substrate of these alterations remains poorly understood due to the lack of specificity of the MRI signal. We have previously shown that Positron Emission Tomography (PET) with 11C-PIB has the potential to quantify myelin content changes in WM lesions. Interestingly, dynamic 11C-PIB PET acquisitions, including early frames, enable the estimation of regional brain perfusion too.

Objectives

To characterize whether perfusion changes, microstructural damage and demyelination could precede lesion appearance on T2-weighted (T2-w) MRI images.

Methods

Longitudinal dynamic 11C-PIB PET and 3T MRI, including diffusion weighted and magnetization transfer imaging, were acquired in 19 active patients with relapsing-remitting MS. Following baseline scans, patients underwent a second evaluation after 1-2 month (n= 10) or after 3-4 months (n=9). Prelesional areas were defined as the baseline NAWM areas which became hyperintensities on the second T2-w image. Logan reference graphical analysis and simplified reference tissue model were respectiveley used to generate voxelwise maps of Distribution Volume Ratio (DVR), and relative delivery (R1) from 11C-PIB images. Myelin content, reflected by DVR, and perfusion, measured by R1, were extracted for each prelesional area and the corresonding contralateral area in the NAWM. Magnetization transfer ratio (MTR), fractional anisotropy (FA), radial and axial diffusivity (RD and AD) were calculated in the same areas. Paired t-test were used to test differences in DVR, R1, MTR, FA, RD and AD between the prelesional and its contralateral areas.

Results

We identified 77 prelesional areas. In the subgroup of patients with a 1-2 months follow-up, prelesional areas (45 out of 77) showed a higher perfusion (8.5%, p=0.03), increased RD (4.2%, p=0.003), lower MTR (-1.2%, p=0.008) and reduced FA (-6.2%, p=0.008), compared to contralateral NAWM areas, while no difference was detected in DVR (p=0.4). No statistical differences were found in the subgroup of patients with a follow-up of 3-4 months.

Conclusions

One-two months before becoming hyperintense on T2-w MRI, prelesional areas are characterized by an increased perfusion associated with microstructural changes, but not by demyelination.

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