Comparison of USPIO-enhanced MRI and Gd-DTPA enhancement during the subacute stage of focal cerebral ischemia in rats.
BACKGROUND
Being one class of magnetic resonance imaging (MRI) contrast agents, ultrasmall superparamagnetic particles of iron oxides (USPIO) bear the potential to study neuroinflammation following stroke, but there is still debate over whether the iron oxides particles may enter the brain tissue passively over a damaged blood-brain barrier (BBB).


OBJECTIVE
To compare the enhancement patterns of USPIO and gadopentate dimeglumine (Gd-DTPA) during the subacute stage of focal cerebral ischemia, to examine the relationship between USPIO enhancement and BBB disturbance, as well as with neuroinflammatory cell response.


METHODS
Multiple MR sequences were obtained on days 3 and 6 after transient middle cerebral artery occlusion induced in rats with and without the application of USPIO and Gd-DTPA. The enhancement patterns of the two contrast agents were compared and correlated to histology, including IgG for BBB permeability, Prussian Blue staining for iron particle detection, and CD68 immunohistochemistry staining to identify macrophage/microglia.


RESULTS
Gd-DTPA enhancement depicted BBB breakdown being in line with IgG leakage. The USPIO enhanced images demonstrated both diffuse and focal signal alteration in ischemic lesions. The diffuse enhanced pattern had a similar spatial and temporal profile as with Gd-DTPA enhancement. In addition, focal enhanced signal loss was visible on T1-, T2-, and T2*-weighted images, with a peak tendency of MR signal loss, macrophage/microglia concentration and iron particle accumulation at a later phase of the study.


CONCLUSIONS
After focal cerebral ischemia, Gd-DTPA-enhanced MRI showed a higher sensitivity in detecting BBB alterations than did USPIO enhancement. USPIO provided complementary information regarding inflammatory cell activity in neuroinflammatory to cerebral ischemia that had not been visualized using conventional Gd-DTPA. The assessment using multiple MR parameters may identify intracellular and extracellular USPIO in vivo.
Department of Radiology, Huashan Hospital, Fudan University, Shanghai, PR China yym9876@sohu.com.
Yan Mei
YM
Yang
Department of Radiology, Huashan Hospital, Fudan University, Shanghai, PR China.
XiaoYuan
X
Feng
Department of Radiology, Huashan Hospital, Fudan University, Shanghai, PR China.
Le Kang
le K
Yin
Department of Radiology, Huashan Hospital, Fudan University, Shanghai, PR China.
Chan Chan
CC
Li
Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai, PR China.
Jie
J
Jia
Department of Pathology, Huashan Hospital, Fudan University, Shanghai, PR China.
Zun Guo
ZG
Du
D000208:Acute Disease; D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology*; D003287:Contrast Media; D003911:Dextrans; D004660:Encephalitis / Q000209:etiology / Q000473:pathology*; D019786:Gadolinium DTPA; D007089:Image Enhancement / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; C097921:ferumoxtran-10; D019786:Gadolinium DTPA
Focal cerebral ischemia; Gd-DTPA; USPIO; blood brain barrier; magnetic resonance imaging; neuroinflammation