Skip to main content
SpringerLink
Log in

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

  • Experimental
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

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.

Methods

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.

Results

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.

Conclusions

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

ASL:

Arterial spin labelling

CMR:

Cardiac magnetic resonance

HF:

Heart failure

LGE:

Late gadolinium enhancement

LV:

Left ventricle

SHR:

Spontaneously hypertensive rat

References

  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–e220

    Article  PubMed  Google Scholar 

  2. Mann DL (1999) Mechanisms and models in heart failure: a combinatorial approach. Circulation 100:999–1008

    Article  PubMed  CAS  Google Scholar 

  3. Martos R, Baugh J, Ledwidge M et al (2007) Diastolic heart failure: evidence of increased myocardial collagen turnover linked to diastolic dysfunction. Circulation 115:888–895

    Article  PubMed  Google Scholar 

  4. Mewton N, Liu CY, Croisille P, Bluemke D, Lima JA (2011) Assessment of myocardial fibrosis with cardiovascular magnetic resonance. J Am Coll Cardiol 57:891–903

    Article  PubMed  Google Scholar 

  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 115:2108–2118

    Article  PubMed  CAS  Google Scholar 

  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 105:2512–2517

    Article  PubMed  CAS  Google Scholar 

  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 102:2700–2706

    Article  PubMed  CAS  Google Scholar 

  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 124:1059–1069

    Article  PubMed  Google Scholar 

  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 28:3076–3093

    Article  PubMed  Google Scholar 

  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 23:1445–1451

    Article  PubMed  CAS  Google Scholar 

  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 52:2017–2028

    Article  PubMed  Google Scholar 

  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 71:740–744

    Article  PubMed  CAS  Google Scholar 

  13. Verjans JW, Lovhaug D, Narula N et al (2008) Noninvasive imaging of angiotensin receptors after myocardial infarction. J Am Coll Cardiol Img 1:354–362

    Google Scholar 

  14. Finn JP, Nael K, Deshpande V, Ratib O, Laub G (2006) Cardiac MR imaging: state of the technology. Radiology 241:338–354

    Article  PubMed  Google Scholar 

  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 54:1407–1424

    Article  PubMed  Google Scholar 

  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 52:1574–1580

    Article  PubMed  Google Scholar 

  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 122:138–144

    Article  PubMed  Google Scholar 

  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 4:636–640

    Article  PubMed  Google Scholar 

  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 7:643–648

    Article  PubMed  CAS  Google Scholar 

  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 26:227–232

    Article  PubMed  CAS  Google Scholar 

  21. Scholz TD, Ceckler TL, Balaban RS (1993) Magnetization transfer characterization of hypertensive cardiomyopathy: significance of tissue water content. Magn Reson Med 29:352–357

    Article  PubMed  CAS  Google Scholar 

  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–W635

    Article  PubMed  Google Scholar 

  23. Abdel-Aty H, Simonetti O, Friedrich MG (2007) T2-weighted cardiovascular magnetic resonance imaging. J Magn Reson Imaging 26:452–459

    Article  PubMed  Google Scholar 

  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 102:633–639

    Article  PubMed  Google Scholar 

  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 5:102–110

    Article  PubMed  Google Scholar 

  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 30:62–68

    Article  PubMed  Google Scholar 

  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 47:319–323

    Article  PubMed  Google Scholar 

  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 51:62–67

    Article  PubMed  Google Scholar 

  29. Doggrell SA, Brown L (1998) Rat models of hypertension, cardiac hypertrophy and failure. Cardiovasc Res 39:89–105

    Article  PubMed  CAS  Google Scholar 

  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 29:2171–2179

    Article  PubMed  CAS  Google Scholar 

  31. Heijman E, de Graaf W, Niessen P et al (2007) Comparison between prospective and retrospective triggering for mouse cardiac MRI. NMR Biomed 20:439–447

    Article  PubMed  CAS  Google Scholar 

  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 109:1674–1679

    Article  PubMed  CAS  Google Scholar 

  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–S34

    PubMed  CAS  Google Scholar 

  34. Schlosser T, Hunold P, Herborn CU et al (2005) Myocardial infarct: depiction with contrast-enhanced MR imaging—comparison of gadopentetate and gadobenate. Radiology 236:1041–1046

    Article  PubMed  Google Scholar 

  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 5:726–733

    Article  PubMed  Google Scholar 

  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 247:788–796

    Article  PubMed  Google Scholar 

  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 119:1768–1775

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

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”.

Author information

Authors and Affiliations

  1. Inserm U1096, Rouen, France

    Jérôme Caudron, Paul Mulder, Lionel Nicol, Vincent Richard, Christian Thuillez & Jean-Nicolas Dacher

  2. Institute for Research and Innovation in Biomedicine, University of Rouen, 22 Blvd Gambetta, 76183, Rouen, France

    Jérôme Caudron, Paul Mulder, Lionel Nicol, Vincent Richard, Christian Thuillez & Jean-Nicolas Dacher

  3. Department of Radiology, Rouen University Hospital, Rouen, France

    Jérôme Caudron & Jean-Nicolas Dacher

Authors
  1. Jérôme Caudron
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul Mulder
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lionel Nicol
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vincent Richard
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christian Thuillez
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jean-Nicolas Dacher
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jérôme Caudron.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Caudron, J., Mulder, P., Nicol, L. et al. MR relaxometry and perfusion of the myocardium in spontaneously hypertensive rat: correlation with histopathology and effect of anti-hypertensive therapy. Eur Radiol 23, 1871–1881 (2013). https://doi.org/10.1007/s00330-013-2801-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00330-013-2801-6

Keywords

Search

Navigation