Adil Maarouf1, Jean-Christophe Ferré2, Wafaa Zaaraoui3, Arnaud Le Troter3, Elise Bannier4, Isabelle Berry5, Maxime Guye6, Laurent Pierot7, Christian Barillot4, Jean Pelletier8, Ayman Tourbah9, Gilles Edan10, Bertrand Audoin8, Jean-Philippe Ranjeva3. 1. Centre Hospitalier Universitaire de Reims, Université de Reims Champagne Ardennes, Service de Neurologie, Reims, France/Aix-Marseille Université, CNRS, CRMBM UMR 7339, Marseille, France/APHM, Hôpital de la Timone, Pôle d'Imagerie Médicale, CEMEREM, Marseille, France adil.maarouf@yahoo.fr. 2. CHU Rennes, Hôpital Pontchaillou, Service de Radiologie, Rennes, France/INRIA Rennes - VisAGeS Team, Rennes, France. 3. Aix-Marseille Université, CNRS, CRMBM UMR 7339, Marseille, France. 4. INRIA Rennes - VisAGeS Team, Rennes, France. 5. CHU Toulouse, Hôpital Rangueil, Toulouse, France. 6. Aix-Marseille Université, CNRS, CRMBM UMR 7339, Marseille, France/APHM, Hôpital de la Timone, Pôle d'Imagerie Médicale, CEMEREM, Marseille, France. 7. Centre Hospitalier Universitaire de Reims, Université de Reims Champagne Ardennes, Service de Radiologie, Reims, France. 8. Aix-Marseille Université, CNRS, CRMBM UMR 7339, Marseille, France/APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, Marseille, France. 9. Centre Hospitalier Universitaire de Reims, Université de Reims Champagne Ardennes, Service de Neurologie, Reims, France/Laboratoire de Psychopathologie et de Neuropsychologie, EA 2027 Université Paris VIII, Saint-Denis Cedex, France. 10. CHU Rennes, Hôpital Pontchaillou, Service de Neurologie, Rennes, France.
Abstract
BACKGROUND: Macrophages are important components of inflammatory processes in multiple sclerosis, closely linked to axonal loss, and can now be observed in vivo using ultra-small superparamagnetic iron oxide (USPIO). In the present 1-year longitudinal study, we aimed to determine the prevalence and the impact on tissue injury of macrophage infiltration in patients after the first clinical event of multiple sclerosis. METHODS: Thirty-five patients, 32 years mean age, were imaged in a mean of 66 days after their first event using conventional magnetic resonance imaging, gadolinium (Gd) to probe blood-brain barrier integrity, USPIO to study macrophage infiltration and magnetization transfer ratio (MTR) to assess tissue structure integrity. Statistics were performed using two-group repeated-measures ANOVA. Any patient received treatment at baseline. RESULTS: At baseline, patients showed 17 USPIO-positive lesions reflecting infiltration of macrophages present from the onset. This infiltration was associated with local higher loss of tissue structure as emphasized by significant lower MTRnorm values (p<0.03) in USPIO(+)/Gd(+) lesions (n=16; MTRnormUSPIO(+)/Gd(+)=0.78 at baseline, MTRnormUSPIO(+)/Gd(+)=0.81 at M12) relative to USPIO(-)/Gd(+) lesions (n=67; MTRnormUSPIO(-)/Gd(+)=0.82 at baseline, MTRnormUSPIO(-)/Gd(+)=0.85 at M12). No interaction in MTR values was observed during the 12 months follow-up (lesion type × time). CONCLUSION: Infiltration of activated macrophages evidenced by USPIO enhancement, is present at the onset of multiple sclerosis and is associated with higher and persistent local loss of tissue structure. Macrophage infiltration affects more tissue structure while tissue recovery during the following year has a similar pattern for USPIO and Gd-enhanced lesions, leading to relative higher persistent local loss of tissue structure in lesions showing USPIO enhancement at baseline.
BACKGROUND: Macrophages are important components of inflammatory processes in multiple sclerosis, closely linked to axonal loss, and can now be observed in vivo using ultra-small superparamagnetic iron oxide (USPIO). In the present 1-year longitudinal study, we aimed to determine the prevalence and the impact on tissue injury of macrophage infiltration in patients after the first clinical event of multiple sclerosis. METHODS: Thirty-five patients, 32 years mean age, were imaged in a mean of 66 days after their first event using conventional magnetic resonance imaging, gadolinium (Gd) to probe blood-brain barrier integrity, USPIO to study macrophage infiltration and magnetization transfer ratio (MTR) to assess tissue structure integrity. Statistics were performed using two-group repeated-measures ANOVA. Any patient received treatment at baseline. RESULTS: At baseline, patients showed 17 USPIO-positive lesions reflecting infiltration of macrophages present from the onset. This infiltration was associated with local higher loss of tissue structure as emphasized by significant lower MTRnorm values (p<0.03) in USPIO(+)/Gd(+) lesions (n=16; MTRnormUSPIO(+)/Gd(+)=0.78 at baseline, MTRnormUSPIO(+)/Gd(+)=0.81 at M12) relative to USPIO(-)/Gd(+) lesions (n=67; MTRnormUSPIO(-)/Gd(+)=0.82 at baseline, MTRnormUSPIO(-)/Gd(+)=0.85 at M12). No interaction in MTR values was observed during the 12 months follow-up (lesion type × time). CONCLUSION: Infiltration of activated macrophages evidenced by USPIO enhancement, is present at the onset of multiple sclerosis and is associated with higher and persistent local loss of tissue structure. Macrophage infiltration affects more tissue structure while tissue recovery during the following year has a similar pattern for USPIO and Gd-enhanced lesions, leading to relative higher persistent local loss of tissue structure in lesions showing USPIO enhancement at baseline.
Authors: Hushan Yuan; Moses Q Wilks; Marc D Normandin; Georges El Fakhri; Charalambos Kaittanis; Lee Josephson Journal: Nat Protoc Date: 2018-01-25 Impact factor: 13.491