Molecular MRI of intracranial thrombus in a rat ischemic stroke model.
OBJECTIVE
Intracranial thrombus is a principal feature in most ischemic stroke, and thrombus location and size may correlate with outcome and response to thrombolytic therapy. EP-2104R is a fibrin-specific molecular MR agent that has previously been shown to enhance extracranial and venous sinus thrombi in animal models and, recently, in clinical trials. In this study, we examined whether this fibrin-specific MR probe could noninvasively characterize intracranial arterial thrombi.


METHODS
Embolic stroke was induced in adult rats by occlusion of the right internal carotid artery with an aged thrombus. We used diffusion-weighted imaging, time of flight angiography, and high-resolution 3-dimensional T1-weighted MRI at 4.7 T before and after use of contrast agents EP-2104R (n=6) and gadopentetate dimeglumine (n=5).


RESULTS
In all animals, MR angiography revealed a flow deficit and diffusion-weighted imaging showed hyperintensity consistent with ischemia. Using EP-2104R-enhanced MRI, we saw occlusive thrombi and vessel wall enhancement in all 6 animals with high contrast to noise relative to blood, whereas gadopentetate dimeglumine-injected animals showed no occlusive thrombus or vessel wall enhancement. The concentration of gadolinium in the thrombus after EP-2104R was 18 times that in the blood pool.


CONCLUSIONS
EP-2104R-enhanced MRI successfully identifies intracranial thrombus in a rat embolic stroke model.
Uppal
Ritika
R
Department of Radiology, Massachusetts General Hospital-East, 149 13th Street, Suite 2301, Charlestown, MA 02129, USA.
Ay
Ilknur
I
Dai
Guangping
G
Kim
Young Ro
YR
Sorensen
A Gregory
AG
Caravan
Peter
P
D000818:Animals; D002545:Brain Ischemia / Q000000981:diagnostic imaging*; D003287:Contrast Media / Q000494:pharmacology*; D004195:Disease Models, Animal; D005682:Gadolinium / Q000494:pharmacology*; D020767:Intracranial Thrombosis / Q000000981:diagnostic imaging*; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D011859:Radiography; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000000981:diagnostic imaging*; D015912:Thrombolytic Therapy
D003287:Contrast Media; C503783:EP-2104R; D010455:Peptides; D005682:Gadolinium
Radiology. 1987 Feb;162(2):575-7
3797675
Invest Radiol. 2009 Mar;44(3):146-50
19151606
Neuroradiology. 1989;31(4):312-5
2797422
Stroke. 1992 Mar;23(3):317-24
1542889
Contrast Media Mol Imaging. 2009 Mar-Apr;4(2):89-100
19177472
Circulation. 2005 Jul 19;112(3):396-9
16009790
Stroke. 2009 Jan;40(1):134-9
19038918
Neurology. 2006 Apr 25;66(8):1171-4
16636232
Invest Radiol. 2007 Aug;42(8):586-95
17620942
Rofo. 2007 Nov;179(11):1166-73
17948194
Am J Respir Crit Care Med. 2005 Aug 15;172(4):494-500
15937292
Circulation. 2008 Jul 15;118(3):258-67
18574047
Stroke. 2006 Aug;37(8):2086-93
16794209
Circulation. 2005 Sep 13;112(11):1594-600
16145001
Stroke. 1999 Apr;30(4):769-72
10187877
Stroke. 2006 Feb;37(2):399-403
16397187
Circulation. 2005 Mar 22;111(11):1377-82
15738354
Invest Radiol. 2005 Nov;40(11):715-24
16230904
Blood. 1987 Apr;69(4):1038-45
2950941
Lancet. 2008 May 10;371(9624):1612-23
18468545
Stroke. 2004 Oct;35(10):2320-5
15322298
Invest Radiol. 2009 Nov;44(11):697-704
19809344
Stroke. 2003 Nov;34(11):2636-40
14593125
Stroke. 2007 May;38(5):1476-81
17379818
Circulation. 2004 Sep 14;110(11):1463-6
15238457
Blood. 1984 May;63(5):1216-24
6231967
Eur Radiol. 2008 Sep;18(9):1995-2005
18425519
Brain Res. 1997 Aug 22;766(1-2):83-92
9359590
Circulation. 2001 Sep 11;104(11):1280-5
11551880
Circulation. 2003 Jun 24;107(24):3047-52
12796133
J Am Chem Soc. 2008 May 7;130(18):6025-39
18393503
Stroke. 2008 Feb;39(2):379-83
18096842
Thromb Haemost. 2006 Jul;96(1):60-7
16807652