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Updated: Apr 1, 2026

Registered Bioimaging of Nanomaterials for Diagnostic and Therapeutic Monitoring
Published on: December 9, 2010
Ultra-small superparamagnetic iron oxide enhancement is associated with higher loss of brain tissue structure in
Adil Maarouf1, Jean-Christophe Ferré2, Wafaa Zaaraoui3
1Centre 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.
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.
Insights
Macrophage infiltration is present at the onset of multiple sclerosis, detected by ultra-small superparamagnetic iron oxide (USPIO). This early macrophage activity is linked to greater and persistent tissue damage in MS lesions.
Area of Science:
- Neuroimmunology
- Neuroinflammation
- Magnetic Resonance Imaging
Background:
- Macrophages play a key role in multiple sclerosis (MS) pathogenesis, correlating with axonal loss.
- In vivo visualization of macrophages is now possible using ultra-small superparamagnetic iron oxide (USPIO).
Purpose of the Study:
- To investigate the prevalence of macrophage infiltration in patients with their first clinical event of MS.
- To assess the impact of macrophage infiltration on tissue injury over a 1-year period.
Main Methods:
- A longitudinal study involving 35 MS patients within 66 days of their first clinical event.
- Utilized conventional MRI, gadolinium (Gd) for blood-brain barrier integrity, USPIO for macrophage infiltration, and MTR for tissue integrity.
- Statistical analysis employed two-group repeated-measures ANOVA.
Main Results:
- USPIO-positive lesions, indicating macrophage infiltration, were detected in 17 patients at baseline.
- Macrophage infiltration (USPIO+/Gd+) was associated with significantly lower MTR values, indicating greater tissue structure loss, compared to lesions without USPIO enhancement (USPIO-/Gd+).
- No significant changes in MTR values were observed over the 12-month follow-up period between lesion types.
Conclusions:
- Activated macrophage infiltration, visualized by USPIO, is present at the onset of MS.
- Early macrophage infiltration is associated with higher and persistent local tissue structure loss.
- While tissue recovery patterns were similar for different lesion types, USPIO-enhanced lesions showed relatively greater persistent tissue loss.

