Magnetic Resonance

European Radiology

, Volume 23, Issue 1, pp 37-47

First online:

Monitoring therapeutic effects in experimental stroke by serial USPIO-enhanced MRI

  • Marilena MarinescuAffiliated withUMR CNRS 5520 CREATIS, Hopital Louis Pradel, Université de Lyon, Lyon 1
  • , Fabien ChauveauAffiliated withUMR CNRS 5520 CREATIS, Hopital Louis Pradel, Université de Lyon, Lyon 1CNRS, UMR 5220; INSERM, U1044; INSA de Lyon; Hospices Civils de Lyon; CREATIS; Lyon
  • , Anne DurandAffiliated withUMR CNRS 5520 CREATIS, Hopital Louis Pradel, Université de Lyon, Lyon 1CNRS, UMR 5220; INSERM, U1044; INSA de Lyon; Hospices Civils de Lyon; CREATIS; Lyon
  • , Adrien RiouAffiliated withUMR CNRS 5520 CREATIS, Hopital Louis Pradel, Université de Lyon, Lyon 1CNRS, UMR 5220; INSERM, U1044; INSA de Lyon; Hospices Civils de Lyon; CREATIS; Lyon
  • , Tae-Hee ChoAffiliated withUMR CNRS 5520 CREATIS, Hopital Louis Pradel, Université de Lyon, Lyon 1CNRS, UMR 5220; INSERM, U1044; INSA de Lyon; Hospices Civils de Lyon; CREATIS; Lyon
  • , Anne DencausseAffiliated withGuerbet Research Group
  • , Sébastien BalletAffiliated withGuerbet Research Group
  • , Norbert NighoghossianAffiliated withUMR CNRS 5520 CREATIS, Hopital Louis Pradel, Université de Lyon, Lyon 1CNRS, UMR 5220; INSERM, U1044; INSA de Lyon; Hospices Civils de Lyon; CREATIS; Lyon
  • , Yves BerthezèneAffiliated withUMR CNRS 5520 CREATIS, Hopital Louis Pradel, Université de Lyon, Lyon 1CNRS, UMR 5220; INSERM, U1044; INSA de Lyon; Hospices Civils de Lyon; CREATIS; Lyon
    • , Marlène WiartAffiliated withUMR CNRS 5520 CREATIS, Hopital Louis Pradel, Université de Lyon, Lyon 1 Email author 

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Abstract

Objectives

This study sought to evaluate whether the therapeutic effects of an anti-inflammatory drug such as minocycline could be monitored by serial ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced MRI in experimental stroke.

Methods

Mice received a three-dose minocycline treatment (n = 12) or vehicle (n = 12) after permanent middle cerebral artery occlusion. USPIOs were administered 5 h post-surgery. MRI was performed before, 24 h and 48 h post-USPIO administration. MRI endpoints were the extent of signal abnormalities on R2 maps (=1/T2) and quantitative R2 changes over time (∆R2). Post-mortem brains were prepared either for immunohistology (n = 16) or for iron dosage (n = 8).

Results

As expected, treatment with minocycline significantly reduced infarct size, blood-brain barrier permeability and F4/80 immunostaining for microglia/macrophages. Areas of R2 maps > 35 ms-1 also appeared significantly decreased in minocycline-treated mice (ANOVA for repeated measures, P = 0.017). There was a fair correlation between these areas and the amount of iron in the brain (R2 = 0.69, P = 0.010), but no significant difference in ∆R2 was found between the two groups.

Conclusions

This study showed that the extent of signal abnormalities on R2 maps can be used as a surrogate marker to detect minocycline effects in a murine experimental model of stroke.

Key Points

Ultrasmall superparamagnetic particles of iron oxide offer new avenues for MRI research

Treatment of the inflammatory response following ischaemic stroke is currently undergoing evaluation.

Minocycline treatment significantly reduced areas of signal abnormalities on USPIO-enhanced MRI.

These areas correlated with the amount of iron in the brain.

Thus USPIO-enhanced MRI might provide a surrogate marker to monitor treatment

Keywords

MRI USPIO Inflammation Cerebral ischaemia Treatment monitoring