ECTRIMS eLearning

Dynamic assessment of macrophages infiltration and microstructural damage within MS lesions
Author(s): ,
A Kerbrat
Affiliations:
Neurologie, CHU de Rennes
,
B Combes
Affiliations:
INRIA Rennes - VisAGeS Team, Rennes
,
O Commowick
Affiliations:
INRIA Rennes - VisAGeS Team, Rennes
,
A Maarouf
Affiliations:
APHM, Hôpital de la Timone, Pôle d'Imagerie Médicale, CEMEREM, Marseille
,
E Bannier
Affiliations:
INRIA Rennes - VisAGeS Team, Rennes
,
J.C Ferrè
Affiliations:
Radiology, CHU de Rennes, Rennes
,
A Tourbah
Affiliations:
CHU de Reims, Reims
,
I Berry
Affiliations:
CHU de Toulouse, Toulouse
,
J.P Ranjeva
Affiliations:
Aix-Marseille Université, CNRS, CRMBM UMR 7, Marseille, France
,
C Barillot
Affiliations:
INRIA Rennes - VisAGeS Team, Rennes
G Edan
Affiliations:
Neurologie, CHU de Rennes
ECTRIMS Learn. Kerbrat A. 09/14/16; 146956; 74
Anne Kerbrat
Anne Kerbrat
Contributions
Abstract

Abstract: 74

Type: Oral

Abstract Category: Pathology and pathogenesis of MS - Imaging

Background: Identifying in vivo the dynamic pathophysiological processes leading to various degrees of demyelination and axonal loss in MS lesions is challenging. In MS patients, macrophages infiltration can be detected using Ultra-Small Super-Paramagnetic Iron Oxide (USPIO) while tissue microstructure changes can be assessed using quantitative MRI.

Objectives: We combined USPIO and quantitative imaging to:

i) Describe the dynamic of macrophages infiltration within MS lesions;

ii) Describe the relationship between macrophages infiltration and tissue changes within MS lesions over two years.

Methods: Sixteen untreated patients were included in a prospective longitudinal study within 3 months after a first inflammatory event. Lesions development was assessed at baseline, 3, 6 and 9 months on gadolinium-MRI to display blood brain barrier integrity and USPIO to study macrophages infiltration. UPSIO enhancement was delineated on T1-w scans and quantified using T2 and T2* relaxometry difference maps (post-pre USPIO). Microstructure changes were assessed over 2 years using magnetization transfer imaging (MTI) and diffusion-weighted imaging (DWI) within lesions.

Results: Out of the 52 MRI scans acquired before and after USPIO, there were 62 gadolinium positive lesions and 23 USPIO positive lesions. 21 lesions were USPIO+/Gd + (U+). 41 lesions were USPIO-/ Gd+ (G+). One lesion experienced a sustained gadolinium enhancement at 3 months, whereas USPIO enhancement was no longer visible. U+ lesions labelled on T1-w images were clearly visible on the post-pre USPIO T2 and T2* maps with various levels of signal decrease.

At baseline and compared to G+ lesions, U+ lesions experienced a stronger average decrease in MTR values (U+: 0.37 and G+: 0.43, p=0.0001) and a stronger average decrease in FA values (normalized using a template) (U+: -0.24 and G+: -0.14, p=0.0002). Moreover, in average, MTR and FA values in G+ and U+ lesions progressively increased over the 2-year follow-up. Nevertheless the MTR and FA values in U+ lesions remained inferior compared to the G+ lesions.

Conclusion: The combination of USPIO and quantitative imaging allows a characterization of the pathophysiological processes of MS lesions. We observed that

i) massive blood born monocytes infiltration is a transient phenomenon characterized by a large range of intensities among lesions;

ii) stronger/longer macrophagic activities are associated to more severe initial tissue damages and lower recoveries.

Disclosure:

Anne Kerbrat, Benoit Combes, Olivier Commowick, Adil Maarouf, Elise Bannier, Jean Christophe Ferré, Ayman Tourbah, Isabelle Berry, Jean-Philippe Ranjeva, Christian Barillot have nothing to disclose

Gilles Edan reports grants and personal fees from Merck Serono, grants and personal fees from Teva Pharma, personal fees from Biogen, grants and personal fees from Novartis, personal fees from Sanofi

Abstract: 74

Type: Oral

Abstract Category: Pathology and pathogenesis of MS - Imaging

Background: Identifying in vivo the dynamic pathophysiological processes leading to various degrees of demyelination and axonal loss in MS lesions is challenging. In MS patients, macrophages infiltration can be detected using Ultra-Small Super-Paramagnetic Iron Oxide (USPIO) while tissue microstructure changes can be assessed using quantitative MRI.

Objectives: We combined USPIO and quantitative imaging to:

i) Describe the dynamic of macrophages infiltration within MS lesions;

ii) Describe the relationship between macrophages infiltration and tissue changes within MS lesions over two years.

Methods: Sixteen untreated patients were included in a prospective longitudinal study within 3 months after a first inflammatory event. Lesions development was assessed at baseline, 3, 6 and 9 months on gadolinium-MRI to display blood brain barrier integrity and USPIO to study macrophages infiltration. UPSIO enhancement was delineated on T1-w scans and quantified using T2 and T2* relaxometry difference maps (post-pre USPIO). Microstructure changes were assessed over 2 years using magnetization transfer imaging (MTI) and diffusion-weighted imaging (DWI) within lesions.

Results: Out of the 52 MRI scans acquired before and after USPIO, there were 62 gadolinium positive lesions and 23 USPIO positive lesions. 21 lesions were USPIO+/Gd + (U+). 41 lesions were USPIO-/ Gd+ (G+). One lesion experienced a sustained gadolinium enhancement at 3 months, whereas USPIO enhancement was no longer visible. U+ lesions labelled on T1-w images were clearly visible on the post-pre USPIO T2 and T2* maps with various levels of signal decrease.

At baseline and compared to G+ lesions, U+ lesions experienced a stronger average decrease in MTR values (U+: 0.37 and G+: 0.43, p=0.0001) and a stronger average decrease in FA values (normalized using a template) (U+: -0.24 and G+: -0.14, p=0.0002). Moreover, in average, MTR and FA values in G+ and U+ lesions progressively increased over the 2-year follow-up. Nevertheless the MTR and FA values in U+ lesions remained inferior compared to the G+ lesions.

Conclusion: The combination of USPIO and quantitative imaging allows a characterization of the pathophysiological processes of MS lesions. We observed that

i) massive blood born monocytes infiltration is a transient phenomenon characterized by a large range of intensities among lesions;

ii) stronger/longer macrophagic activities are associated to more severe initial tissue damages and lower recoveries.

Disclosure:

Anne Kerbrat, Benoit Combes, Olivier Commowick, Adil Maarouf, Elise Bannier, Jean Christophe Ferré, Ayman Tourbah, Isabelle Berry, Jean-Philippe Ranjeva, Christian Barillot have nothing to disclose

Gilles Edan reports grants and personal fees from Merck Serono, grants and personal fees from Teva Pharma, personal fees from Biogen, grants and personal fees from Novartis, personal fees from Sanofi

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