Pluriformity of inflammation in multiple sclerosis shown by ultra-small iron oxide particle enhancement

Gadolinium-DTPA (Gd-DTPA) is routinely used as a marker forinflammation in MRI to visualize breakdown of the blood–brainbarrier (BBB) in multiple sclerosis. Recent data suggest thatultra-small superparamagnetic particles of iron oxide (USPIO)can be used to visualize cellular infiltration, another aspectof inflammation.  This project aimed to compare the novel USPIOparticle SHU555C to the longitudinal pattern of Gd-DTPA enhancementin multiple sclerosis.

Nineteen relapsing-remitting patientswere screened monthly using Gd-enhanced MRI.  In case of newenhancing lesions, USPIO were injected and 24 h later, MRI wasperformed and blood was collected to confirm USPIO loading ofcirculating monocytes.  Lesion development was monitored by 3monthly Gd-DTPA-enhanced scans and a final scan 7–11 monthsafter injection.

USPIO-enhancement was observed as hyperintensityon T₁-weighted images, whereas no signal changes were observedon T₂-weighted-gradient-echo images.

In 14 patients with diseaseactivity, 188 USPIO-positive lesions were seen, 144 of whichwere Gd-negative.  By contrast, there were a total of 59 Gd-positivelesions, 15 of which were USPIO negative.

Three patterns ofUSPIO-enhancement were seen:

(i) focal enhancement;

(ii) ring-likeenhancement and

(iii) return to isointensity of a previouslyhypointense lesion. The latter pattern was most frequently observedfor lesions that turned out to be transiently hypointense onfollow-up scans, and ring-enhancing lesions were less likelyto evolve into black holes at follow-up than lesions withoutring-like USPIO-enhancement; we speculate this to be associatedwith repair.

In 4% of the USPIO-positive/Gd negative lesions,USPIO-enhancement preceded Gd-enhancement by 1 month. USPIO-enhancementremained visible for up to 3 months in 1.5% of all USPIO-positivelesions.  In 29% of the lesions enhancing with both contrastagents, USPIO-enhancement persisted whereas Gd-enhancement hadalready resolved. In conclusion, the new nano-particle SHU555Cprovides complementary information to Gd-enhanced MRI, probablyrelated to monocyte infiltration.  The use of USPIO-enhancedMRI is likely to lead to more insight in the pluriformity ofinflammation in multiple sclerosis.

¹Department of Neurology,

²Department of Cell Biology and Immunology, MS Centre Amsterdam, VU University Medical Centre, Amsterdam,

³Image Sciences Institute, University Medical Center, Utrecht, The Netherlands,

⁴Department of Physics and Medical Technology,

⁵Department of Radiology, MS Centre Amsterdam, VU University Medical Centre, Amsterdam,

⁶Department of Diagnostic Imaging, Bayer Schering Pharma, Berlin, Germany,

⁷Department of Pathology, MS Centre Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands