Analysis of the distribution of MRI contrast agents in the livers of small animals by means of complementary microscopies.
BACKGROUND
Magnetic resonance imaging (MRI) contrast agents contain magnetic molecules such as iron (Fe) or gadolinium (Gd) that are injected in vivo into rats or mice to study their distribution inside the liver. Fluorescent europium (Eu) can be used as a model of Gd to obtain comparable information of this distribution of corresponding contrast agents. In a similar approach, Fe can be attached to Texas Red and used as a model of ferumoxides and be detected by fluorescence.


METHODS
To combine and compare the advantages of different microscopic imaging modes, characterization studies were carried out by means of a confocal laser scanning microscope (CLSM), a secondary ion mass spectrometric (SIMS) microscope, and an electron energy loss spectrometric (EELS) microscope. In the case of CLSM, the locations of fluorescent signals inside preparations were determined by factor analysis of biomedical image sequences (FAMIS) and selection of image sequences at emission.


RESULTS
By CLSM and FAMIS, we distinguished chelated Eu and Texas Red attached to Fe. By SIMS microscopy, we distinguished Eu and Gd of chlorides and chelates and Fe of a ferumoxide. By EELS microscopy, we distinguished Eu and Gd of chlorides.


CONCLUSIONS
Analysis of compounds inside correlative specimens by means of CLSM, SIMS, and EELS microscopes provided complementary results.
Kahn
E
E
INSERM U494, CHU Pitié-Salpétrière, 75634 Paris Cedex 13, France. kahn@imed.jussieu.fr
Tessier
C
C
Lizard
G
G
Petiet
A
A
Bernengo
J-C
JC
Coulaud
D
D
Fourré
C
C
Frouin
F
F
Clément
O
O
Jourdain
J-R
JR
Delain
E
E
Guiraud-Vitaux
F
F
Colas-Linhart
N
N
Siauve
N
N
Cuenod
C-A
CA
Frija
G
G
Todd-Pokropek
A
A
D000818:Animals; D002712:Chlorides / Q000032:analysis; D003287:Contrast Media / Q000032:analysis*; D005063:Europium / Q000032:analysis / Q000493:pharmacokinetics; D005260:Female; D005456:Fluorescent Dyes; D005682:Gadolinium / Q000032:analysis / Q000493:pharmacokinetics; D007091:Image Processing, Computer-Assisted / Q000295:instrumentation / Q000379:methods; D007501:Iron / Q000032:analysis / Q000493:pharmacokinetics; D008099:Liver / Q000166:cytology / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D018629:Spectrometry, Mass, Secondary Ion / Q000379:methods*
D002712:Chlorides; D003287:Contrast Media; D005456:Fluorescent Dyes; D005063:Europium; D005682:Gadolinium; D007501:Iron