title: In vivo magnetization transfer and diffusion-weighted magnetic resonance imaging detects thrombus composition in a mouse model of deep vein thrombosis.
abstract: BACKGROUND
  Deep vein thrombosis remains a major health problem necessitating accurate diagnosis. Thrombolysis is associated with significant morbidity and is effective only for the treatment of unorganized thrombus. We tested the feasibility of in vivo magnetization transfer (MT) and diffusion-weighted magnetic resonance imaging to detect thrombus organization in a murine model of deep vein thrombosis.
  
  
  RESULTS
  Deep vein thrombosis was induced in the inferior vena cava of male BALB/C mice. Magnetic resonance imaging was performed at days 1, 7, 14, 21, and 28 after thrombus induction using MT, diffusion-weighted, inversion-recovery, and T1-mapping protocols. Delayed enhancement and T1 mapping were repeated 2 hours after injection of a fibrin contrast agent. Finally, excised thrombi were used for histology. We found that MT and diffusion-weighted imaging can detect histological changes associated with thrombus aging. MT rate (MTR) maps and percentage of MT rate (%MTR) allowed visualization and quantification of the thrombus protein content, respectively. The %MTR increased with thrombus organization and was significantly higher at days 14, 21, and 28 after thrombus induction (days 1, 7, 14, 21, 28: %MTR=2483±451, 2079±1210, 7029±2490, 10 295±4356, 32 994±25 449; PANOVA<0.05). There was a significant positive correlation between the %MTR and the histological protein content of the thrombus (r=0.70; P<0.05). The apparent diffusion coefficient was lower in erythrocyte-rich and collagen-rich thrombus (0.72±0.10 and 0.69±0.05 [×10(-3) mm(2)/s]). Thrombus at days 7 and 14 had the highest apparent diffusion coefficient values (0.95±0.09 and 1.10±0.18 [×10(-3) mm(2)/s]).
  
  
  CONCLUSIONS
  MT and diffusion-weighted magnetic resonance imaging sequences are promising for the staging of thrombus composition and could be useful in guiding medical intervention.
authors.affiliation: Division of Imaging Science and Biomedical Engineering (A.P., M.E.A., R.M.B.), Cardiovascular Division, Academic Department of Surgery (P.S., B.M., A.S.), Cardiovascular Division, BHF Centre of Excellence (A.P., P.S., A.S., R.M.B.), Wellcome Trust and EPSRC Medical Engineering Center (R.M.B.), King's College London, London, UK; and Radiology Department, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile (M.E.A.).
authors.forename: Alkystis
authors.initials: A
authors.lastname: Phinikaridou
authors.affiliation: Division of Imaging Science and Biomedical Engineering (A.P., M.E.A., R.M.B.), Cardiovascular Division, Academic Department of Surgery (P.S., B.M., A.S.), Cardiovascular Division, BHF Centre of Excellence (A.P., P.S., A.S., R.M.B.), Wellcome Trust and EPSRC Medical Engineering Center (R.M.B.), King's College London, London, UK; and Radiology Department, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile (M.E.A.).
authors.forename: Marcelo E
authors.initials: ME
authors.lastname: Andia
authors.affiliation: Division of Imaging Science and Biomedical Engineering (A.P., M.E.A., R.M.B.), Cardiovascular Division, Academic Department of Surgery (P.S., B.M., A.S.), Cardiovascular Division, BHF Centre of Excellence (A.P., P.S., A.S., R.M.B.), Wellcome Trust and EPSRC Medical Engineering Center (R.M.B.), King's College London, London, UK; and Radiology Department, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile (M.E.A.).
authors.forename: Prakash
authors.initials: P
authors.lastname: Saha
authors.affiliation: Division of Imaging Science and Biomedical Engineering (A.P., M.E.A., R.M.B.), Cardiovascular Division, Academic Department of Surgery (P.S., B.M., A.S.), Cardiovascular Division, BHF Centre of Excellence (A.P., P.S., A.S., R.M.B.), Wellcome Trust and EPSRC Medical Engineering Center (R.M.B.), King's College London, London, UK; and Radiology Department, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile (M.E.A.).
authors.forename: Bijan
authors.initials: B
authors.lastname: Modarai
authors.affiliation: Division of Imaging Science and Biomedical Engineering (A.P., M.E.A., R.M.B.), Cardiovascular Division, Academic Department of Surgery (P.S., B.M., A.S.), Cardiovascular Division, BHF Centre of Excellence (A.P., P.S., A.S., R.M.B.), Wellcome Trust and EPSRC Medical Engineering Center (R.M.B.), King's College London, London, UK; and Radiology Department, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile (M.E.A.).
authors.forename: Alberto
authors.initials: A
authors.lastname: Smith
authors.affiliation: Division of Imaging Science and Biomedical Engineering (A.P., M.E.A., R.M.B.), Cardiovascular Division, Academic Department of Surgery (P.S., B.M., A.S.), Cardiovascular Division, BHF Centre of Excellence (A.P., P.S., A.S., R.M.B.), Wellcome Trust and EPSRC Medical Engineering Center (R.M.B.), King's College London, London, UK; and Radiology Department, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile (M.E.A.).
authors.forename: René M
authors.initials: RM
authors.lastname: Botnar
mesh_terms: D000818:Animals; D003094:Collagen / Q000097:blood; D003287:Contrast Media; D038524:Diffusion Magnetic Resonance Imaging; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000378:metabolism; D005240:Feasibility Studies; D005337:Fibrin / Q000378:metabolism; D005682:Gadolinium; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D013997:Time Factors; D014682:Vena Cava, Inferior / Q000378:metabolism / Q000473:pathology*; D020246:Venous Thrombosis / Q000097:blood / Q000175:diagnosis* / Q000473:pathology
chemical_list: D003287:Contrast Media; C503783:EP-2104R; D010455:Peptides; D005337:Fibrin; D003094:Collagen; D005682:Gadolinium
keywords: MRI; diffusion weighting; magnetization transfer; thrombosis; vein
references.citation: Arterioscler Thromb Vasc Biol. 2000 Jul;20(7):1824-30
references.pmid: 10894824
references.citation: Circulation. 2011 Jul 26;124(4):416-24
references.pmid: 21747055
references.citation: AJNR Am J Neuroradiol. 1993 Jul-Aug;14(4):871-80
references.pmid: 8352159
references.citation: Arterioscler Thromb Vasc Biol. 2011 Mar;31(3):506-12
references.pmid: 21325673
references.citation: Cochrane Database Syst Rev. 2004 Oct 18;(4):CD002783
references.pmid: 15495034
references.citation: J Vasc Surg. 2010 Apr;51(4):908-12
references.pmid: 20347687
references.citation: Arterioscler Thromb Vasc Biol. 1997 Mar;17(3):542-6
references.pmid: 9102174
references.citation: Am Heart J. 2007 Nov;154(5):808-14
references.pmid: 17967583
references.citation: J Magn Reson Imaging. 2011 Nov;34(5):1167-75
references.pmid: 21928384
references.citation: Perspect Vasc Surg Endovasc Ther. 2009 Dec;21(4):221-4; quiz 224-5
references.pmid: 20047905
references.citation: J Magn Reson Imaging. 2001 Apr;13(4):615-8
references.pmid: 11276107
references.citation: Magn Reson Imaging. 2011 Sep;29(7):975-84
references.pmid: 21641743
references.citation: Magn Reson Med. 1993 Feb;29(2):211-5
references.pmid: 8429785
references.citation: J Cardiovasc Magn Reson. 2012 Jun 25;14:45
references.pmid: 22731842
references.citation: Arterioscler Thromb Vasc Biol. 2005 Jan;25(1):240-5
references.pmid: 15528478
references.citation: Circulation. 2005 Sep 13;112(11):1594-600
references.pmid: 16145001
references.citation: J Am Coll Cardiol. 2002 Apr 17;39(8):1366-73
references.pmid: 11955857
references.citation: N Engl J Med. 2009 May 28;360(22):2319-27
references.pmid: 19474429
references.citation: NMR Biomed. 2010 Jan;23(1):34-40
references.pmid: 19642088
references.citation: J Lab Clin Med. 1990 Jul;116(1):8-17
references.pmid: 2198321
references.citation: Circulation. 2003 Feb 18;107(6):869-75
references.pmid: 12591758
references.citation: Arch Intern Med. 1999 Mar 8;159(5):445-53
references.pmid: 10074952
references.citation: Chest. 2008 Jun;133(6 Suppl):454S-545S
references.pmid: 18574272
references.citation: Radiology. 1987 Feb;162(2):527-30
references.pmid: 3797668
references.citation: AJNR Am J Neuroradiol. 1993 Jul-Aug;14(4):881-91
references.pmid: 8352160
references.citation: MAGMA. 2009 Dec;22(6):375-83
references.pmid: 19946791
references.citation: Radiology. 1993 Oct;189(1):15-26
references.pmid: 8372185
references.citation: Magn Reson Med. 1993 Mar;29(3):352-7
references.pmid: 8383789
references.citation: Circulation. 2001 Sep 11;104(11):1280-5
references.pmid: 11551880
references.citation: Arch Intern Med. 2004 Jan 12;164(1):17-26
references.pmid: 14718318
references.citation: Magn Reson Q. 1992 Jun;8(2):116-37
references.pmid: 1622774
references.citation: Circulation. 2004 Apr 27;109(16):2023-9
references.pmid: 15066940
references.citation: Br J Haematol. 2005 May;129(3):307-21
references.pmid: 15842654
references.citation: Thromb Haemost. 2009 Dec;102(6):1169-75
references.pmid: 19967148
references.citation: Radiology. 1985 Oct;157(1):87-93
references.pmid: 4034983
references.citation: AJR Am J Roentgenol. 1992 Dec;159(6):1279-85
references.pmid: 1442402
references.citation: Arterioscler Thromb Vasc Biol. 1999 Nov;19(11):2756-61
references.pmid: 10559022
references.citation: J Am Coll Cardiol. 2000 Oct;36(4):1336-43
references.pmid: 11028492
references.citation: Thromb Res Suppl. 1988;8:73-80
references.pmid: 3144770
references.citation: Arterioscler Thromb Vasc Biol. 2010 Dec;30(12):2443-51
references.pmid: 20930171
references.citation: Radiology. 1998 Nov;209(2):349-55
references.pmid: 9807558
references.citation: J Cardiovasc Magn Reson. 2011 Nov 22;13:73
references.pmid: 22107813
references.citation: Thromb Haemost. 2005 May;93(5):801-9
references.pmid: 15886791
references.citation: Magn Reson Med. 1993 Jun;29(6):759-66
references.pmid: 8350718
references.citation: Magn Reson Med. 2006 Dec;56(6):1384-8
references.pmid: 17089356
references.citation: Arterioscler Thromb Vasc Biol. 2011 Oct;31(10):2306-13
references.pmid: 21737785
references.citation: N Engl J Med. 2004 Jul 15;351(3):268-77
references.pmid: 15254285