European Radiology

, Volume 23, Issue 7, pp 1871–1881 | Cite as

MR relaxometry and perfusion of the myocardium in spontaneously hypertensive rat: correlation with histopathology and effect of anti-hypertensive therapy

  • Jérôme CaudronEmail author
  • Paul Mulder
  • Lionel Nicol
  • Vincent Richard
  • Christian Thuillez
  • Jean-Nicolas Dacher



To investigate myocardial relaxation times and perfusion values in spontaneously hypertensive rats (SHRs) at various stages of the disease, with or without anti-fibrotic therapy, and to correlate magnetic resonance imaging (MRI) findings with histopathological myocardial fibrosis and capillary density.


Five groups of rats underwent MRI at 4.7 T. They were either untreated or treated with an aldosterone-synthase inhibitor. T1, T2 and T2* relaxation times were determined and myocardial perfusion was quantified from an arterial spin labelling sequence. MR relaxation times and perfusion values were compared with the fibrotic content and capillary density of the myocardium obtained at histology after euthanasia.


T1 values significantly increased during the course of hypertensive disease, and correlated with myocardial fibrosis (R = 0.71, P < 0.001); T2 values also increased but were weakly correlated with myocardial fibrosis (R = 0.27,P = 0.047). Myocardial perfusion and capillary density significantly decreased with hypertensive disease but they did not correlate. Following prolonged treatment, we observed a trend associating T1 decrease and improved perfusion compared with untreated SHRs.


Myocardial T1 and T2 values increase with hypertensive disease, whereas myocardial perfusion decreases. The correlation between T1 values and collagen density suggests that the former could be considered as a non-invasive marker of myocardial fibrosis.

Key Points

MR is increasingly used to assess alteration in myocardial tissue content.

MR relaxometry and perfusion can be assessed in rats without exogenous contrast agents.

Myocardial T1 and T2 values significantly increase during the course of hypertensive heart disease.

T1 values correlate significantly with myocardial collagen content.

Myocardial perfusion values decrease with hypertensive disease.


Cardiac MRI Myocardial fibrosis MR relaxometry Arterial spin labelling Spontaneously hypertensive rat 



Arterial spin labelling


Cardiac magnetic resonance


Heart failure


Late gadolinium enhancement


Left ventricle


Spontaneously hypertensive rat



This work received a research award from the Société Française de Radiologie, 2011 Annual Meeting

This work was presented as a scientific presentation during the 2011 RSNA Annual Meeting (SSK03-03).

The authors are grateful to Novartis Institutes for BioMedical Research (East Hanover, New Jersey, USA) that provided the aldosterone synthase inhibitor FAD286 used in the present study.

Supported by a research grant, “Médaille d’Or des Hôpitaux de Rouen”.


  1. 1.
    Roger VL, Go AS, Lloyd-Jones DM et al (2012) Heart disease and stroke statistics—2012 update. A report from the American Heart Association. Circulation 125:e2–e220PubMedCrossRefGoogle Scholar
  2. 2.
    Mann DL (1999) Mechanisms and models in heart failure: a combinatorial approach. Circulation 100:999–1008PubMedCrossRefGoogle Scholar
  3. 3.
    Martos R, Baugh J, Ledwidge M et al (2007) Diastolic heart failure: evidence of increased myocardial collagen turnover linked to diastolic dysfunction. Circulation 115:888–895PubMedCrossRefGoogle Scholar
  4. 4.
    Mewton N, Liu CY, Croisille P, Bluemke D, Lima JA (2011) Assessment of myocardial fibrosis with cardiovascular magnetic resonance. J Am Coll Cardiol 57:891–903PubMedCrossRefGoogle Scholar
  5. 5.
    Shiojima I, Sato K, Izumiya Y et al (2005) Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure. J Clin Invest 115:2108–2118PubMedCrossRefGoogle Scholar
  6. 6.
    Diez J, Querejeta R, Lopez B et al (2002) Losartan-dependent regression of myocardial fibrosis is associated with reduction of left ventricular chamber stiffness in hypertensive patients. Circulation 105:2512–2517PubMedCrossRefGoogle Scholar
  7. 7.
    Zannad F, Alla F, Dousset B, Perez A, Pitt B (2000) Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the randomized aldactone evaluation study (RALES). Rales Investigators. Circulation 102:2700–2706PubMedCrossRefGoogle Scholar
  8. 8.
    Banquet S, Gomez E, Nicol L et al (2011) Arteriogenic therapy by Intramyocardial sustained delivery of a novel growth factor combination prevents chronic heart failure. Circulation 124:1059–1069PubMedCrossRefGoogle Scholar
  9. 9.
    Cooper LT, Baughman KL, Feldman AM et al (2007) The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology. Eur Heart J 28:3076–3093PubMedCrossRefGoogle Scholar
  10. 10.
    Lopez B, Gonzalez A, Querejeta R, Diez J (2005) The use of collagen-derived serum peptides for the clinical assessment of hypertensive heart disease. J Hypertens 23:1445–1451PubMedCrossRefGoogle Scholar
  11. 11.
    Van den Borne SW, Isobe S, Verjans JW et al (2008) Molecular imaging of interstitial alterations in remodeling myocardium after myocardial infarction. J Am Coll Cardiol 52:2017–2028PubMedCrossRefGoogle Scholar
  12. 12.
    Hoyt RH, Collins SM, Skorton DJ, Ericksen EE, Conyers D (1985) Assessment of fibrosis in infracted human hearts by analysis of ultrasonic backscatter. Circulation 71:740–744PubMedCrossRefGoogle Scholar
  13. 13.
    Verjans JW, Lovhaug D, Narula N et al (2008) Noninvasive imaging of angiotensin receptors after myocardial infarction. J Am Coll Cardiol Img 1:354–362Google Scholar
  14. 14.
    Finn JP, Nael K, Deshpande V, Ratib O, Laub G (2006) Cardiac MR imaging: state of the technology. Radiology 241:338–354PubMedCrossRefGoogle Scholar
  15. 15.
    Karamitsos TD, Francis JM, Myerson S, Selvanayagam JB, Neubauer S (2009) The role of cardiovascular magnetic resonance imaging in heart failure. J Am Coll Cardiol 54:1407–1424PubMedCrossRefGoogle Scholar
  16. 16.
    Iles L, Pfluger H, Phrommintikul A et al (2008) Evaluation of diffuse myocardial fibrosis in heart failure with cardiac magnetic resonance contrast-enhanced T1 mapping. J Am Coll Cardiol 52:1574–1580PubMedCrossRefGoogle Scholar
  17. 17.
    Flett AS, Hayward MP, Ashworth MT et al (2010) Equilibrum contrast cardiovascular magnetic resonance for the measurement of diffuse myocardial fibrosis: preliminary validation in humans. Circulation 122:138–144PubMedCrossRefGoogle Scholar
  18. 18.
    Messroghli DR, Nordmeyer S, Dietrich T et al (2011) Assessment of diffuse myocardial fibrosis in rats using small-animal Look-Locker inversion recovery T1 mapping. Circ Cardiovasc Imaging 4:636–640PubMedCrossRefGoogle Scholar
  19. 19.
    Scholz TD, Fleagle SR, Burns TL, Skorton DJ (1989) Nuclear magnetic resonance relaxometry of the normal heart: relationship between collagen content and relaxation times of the four chambers. Magn Reson Imaging 7:643–648PubMedCrossRefGoogle Scholar
  20. 20.
    Grover-McKay M, Scholz TD, Burns TL, Skorton DJ (1991) Myocardial collagen concentration and nuclear magnetic resonance relaxation times in the spontaneously hypertensive rat. Invest Radiol 26:227–232PubMedCrossRefGoogle Scholar
  21. 21.
    Scholz TD, Ceckler TL, Balaban RS (1993) Magnetization transfer characterization of hypertensive cardiomyopathy: significance of tissue water content. Magn Reson Med 29:352–357PubMedCrossRefGoogle Scholar
  22. 22.
    Sparrow P, Messroghli DR, Reid S, Ridgway JP, Brainbridge G, Sivananthan MU (2006) Myocardial T1 mapping for detection of left ventricular myocardial fibrosis in chronic aortic regurgitation: pilot study. AJR Am J Roentgenol 187:W630–W635PubMedCrossRefGoogle Scholar
  23. 23.
    Abdel-Aty H, Simonetti O, Friedrich MG (2007) T2-weighted cardiovascular magnetic resonance imaging. J Magn Reson Imaging 26:452–459PubMedCrossRefGoogle Scholar
  24. 24.
    Manrique A, Gerbaud E, Derumeaux G et al (2009) Cardiac magnetic resonance demonstrates myocardial oedema in remote tissue early after reperfused myocardial infarction. Arch Cardiovasc Dis 102:633–639PubMedCrossRefGoogle Scholar
  25. 25.
    Thavendiranathan P, Walls M, Giri S et al (2012) Improved detection of myocardial involvement in acute inflammatory cardiomyopathies using T2 mapping. Circ Cardiovasc Imaging 5:102–110PubMedCrossRefGoogle Scholar
  26. 26.
    Ramazzotti A, Pepe A, Positano V et al (2009) Multicenter validation of the magnetic resonance T2* technique for segmental and global quantification of myocardial iron. J Magn Reson Imaging 30:62–68PubMedCrossRefGoogle Scholar
  27. 27.
    Bun SS, Kober F, Jacquier A et al (2012) Value of in vivo T2 measurement for myocardial fibrosis assessment in diabetic mice at 11.75 T. Invest Radiol 47:319–323PubMedCrossRefGoogle Scholar
  28. 28.
    Kober F, Iltis I, Izquierdo M et al (2004) High-resolution myocardial perfusion mapping in small animals in vivo by spin-labeling gradient-echo imaging. Magn Reson Med 51:62–67PubMedCrossRefGoogle Scholar
  29. 29.
    Doggrell SA, Brown L (1998) Rat models of hypertension, cardiac hypertrophy and failure. Cardiovasc Res 39:89–105PubMedCrossRefGoogle Scholar
  30. 30.
    Mulder P, Mellin V, Favre J et al (2008) Aldosterone synthase inhibition improves cardiovascular function and structure in rats with heart failure: a comparison with spironolactone. Eur Heart J 29:2171–2179PubMedCrossRefGoogle Scholar
  31. 31.
    Heijman E, de Graaf W, Niessen P et al (2007) Comparison between prospective and retrospective triggering for mouse cardiac MRI. NMR Biomed 20:439–447PubMedCrossRefGoogle Scholar
  32. 32.
    Mulder P, Barbier S, Chagraoui A et al (2004) Long term heart rate reduction induced by the selective l(f) current inhibitor ivabradine improves left ventricular function and intrinsic myocardial structure in congestive heart failure. Circulation 109:1674–1679PubMedCrossRefGoogle Scholar
  33. 33.
    Contard F, Glukhova M, Sabri A et al (1993) Comparative effects of indapamide and hydrochlorothiazide on cardiac hypertrophy and vascular smooth-muscle phenotype in the stroke-prone, spontaneously hypertensive rat. J Cardiovasc Pharmacol 22(Suppl 6):S29–S34PubMedGoogle Scholar
  34. 34.
    Schlosser T, Hunold P, Herborn CU et al (2005) Myocardial infarct: depiction with contrast-enhanced MR imaging—comparison of gadopentetate and gadobenate. Radiology 236:1041–1046PubMedCrossRefGoogle Scholar
  35. 35.
    Dass S, Suttie JJ, Piechnik SK et al (2012) Myocardial tissue characterization using magnetic resonance noncontrast T1 mapping in hypertrophic and dilated cardiomyopathy. Circ Cardiovasc Imaging 5:726–733PubMedCrossRefGoogle Scholar
  36. 36.
    Helm PA, Caravan P, French BA et al (2008) Postinfarction myocardial scarring in mice: molecular MR imaging with use of a collagen-targeting contrast agent. Radiology 247:788–796PubMedCrossRefGoogle Scholar
  37. 37.
    Spuentrup E, Ruhl KM, Botnar RM et al (2009) Molecular magnetic resonance imaging of myocardial perfusion with EP-3600, a collagen-specific contrast agent: initial feasibility study in a swine model. Circulation 119:1768–1775PubMedCrossRefGoogle Scholar

Copyright information

© European Society of Radiology 2013

Authors and Affiliations

  • Jérôme Caudron
    • 1
    • 2
    • 3
    Email author
  • Paul Mulder
    • 1
    • 2
  • Lionel Nicol
    • 1
    • 2
  • Vincent Richard
    • 1
    • 2
  • Christian Thuillez
    • 1
    • 2
  • Jean-Nicolas Dacher
    • 1
    • 2
    • 3
  1. 1.Inserm U1096RouenFrance
  2. 2.Institute for Research and Innovation in BiomedicineUniversity of RouenRouenFrance
  3. 3.Department of RadiologyRouen University HospitalRouenFrance

Personalised recommendations