Histological validation of cardiac magnetic resonance analysis of regional and diffuse interstitial myocardial fibrosis.

AIM Myocardial fibrosis is fundamental in the pathogenesis of heart failure. Late gadolinium enhancement (LGE) with cardiac magnetic resonance (CMR) imaging is commonly assumed to represent myocardial fibrosis; however, comparative human histological data are limited, especially in non-ischaemic cardiac disease. Diffuse interstitial myocardial fibrosis is increasingly recognized as central in the pathogenesis of cardiomyopathy and can be quantified using newer CMR techniques such as T1 mapping. We evaluated the relationship of CMR assessment of regional and diffuse fibrosis with human histology. METHODS AND RESULTS Eleven patients on the waiting list for heart transplantation (43.5 ± 7.6 years, 64% male) and eight patients undergoing surgical myectomy for obstructive hypertrophic cardiomyopathy (57.1 ± 8.6 years, 63% male) were recruited and underwent CMR prior to cardiac transplantation or myectomy. Quantification of fibrosis in explanted hearts using digitally analysed Masson-trichrome-stained slides was validated against picrosirius red-stained slides analysed using Image J, with an excellent correlation (R = 0.95, P < 0.0001). Significant correlations were observed between LGE and histological fibrosis across a range of signal intensity thresholds in the explanted hearts (range: 2-10 standard deviations above reference myocardium), with maximal accuracy at a threshold of 6 SD (R = 0.91, P < 0.001). Assessment of interstitial myocardial fibrosis with post-contrast T1 times demonstrated a significant correlation on both segmental (R = -0.64, P = 0.002) and per-patient (R = -0.78, P = 0.003) analyses. CONCLUSION CMR provides accurate, non-invasive assessment of regional myocardial fibrosis using LGE, while diffuse interstitial myocardial fibrosis is accurately assessed with post-contrast T1 mapping.

[1]  Richard B Thompson,et al.  Saturation recovery single‐shot acquisition (SASHA) for myocardial T1 mapping , 2014, Magnetic resonance in medicine.

[2]  G. Maurer,et al.  Cardiac Magnetic Resonance Postcontrast T1 Time Is Associated With Outcome in Patients With Heart Failure and Preserved Ejection Fraction , 2013, Circulation. Cardiovascular imaging.

[3]  M. Robson,et al.  T1 mapping for myocardial extracellular volume measurement by CMR: bolus only versus primed infusion technique. , 2013, JACC. Cardiovascular imaging.

[4]  Harry Rakowski,et al.  Myocardial fibrosis in hypertrophic cardiomyopathy: accurate reflection of histopathological findings by CMR. , 2013, JACC. Cardiovascular imaging.

[5]  Andrew S Flett,et al.  Comprehensive Validation of Cardiovascular Magnetic Resonance Techniques for the Assessment of Myocardial Extracellular Volume , 2013, Circulation. Cardiovascular imaging.

[6]  Scott D Flamm,et al.  Standardized image interpretation and post processing in cardiovascular magnetic resonance: Society for Cardiovascular Magnetic Resonance (SCMR) Board of Trustees Task Force on Standardized Post Processing , 2013, Journal of Cardiovascular Magnetic Resonance.

[7]  Reza Razavi,et al.  Native T1 mapping in differentiation of normal myocardium from diffuse disease in hypertrophic and dilated cardiomyopathy. , 2013, JACC. Cardiovascular imaging.

[8]  Tevfik F Ismail,et al.  Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy. , 2013, JAMA.

[9]  Glenn S Slavin,et al.  True T1 mapping with SMART1Map (saturation method using adaptive recovery times for cardiac T1 mapping): a comparison with MOLLI , 2013, Journal of Cardiovascular Magnetic Resonance.

[10]  James O. Mudd,et al.  T1 Mapping in cardiomyopathy at cardiac MR: comparison with endomyocardial biopsy. , 2012, Radiology.

[11]  Kevin W Eliceiri,et al.  NIH Image to ImageJ: 25 years of image analysis , 2012, Nature Methods.

[12]  M. Maron,et al.  Clinical Utility of Cardiovascular Magnetic Resonance in Hypertrophic Cardiomyopathy , 2012, Journal of Cardiovascular Magnetic Resonance.

[13]  D. Bluemke,et al.  T1 mapping of the gadolinium‐enhanced myocardium: Adjustment for factors affecting interpatient comparison , 2011, Magnetic resonance in medicine.

[14]  Pierre Croisille,et al.  Assessment of myocardial fibrosis with cardiovascular magnetic resonance. , 2011, Journal of the American College of Cardiology.

[15]  C. Tschöpe,et al.  Diastolic tissue Doppler indexes correlate with the degree of collagen expression and cross-linking in heart failure and normal ejection fraction. , 2011, Journal of the American College of Cardiology.

[16]  P. Kistler,et al.  Myocardial fibrosis predicts appropriate device therapy in patients with implantable cardioverter-defibrillators for primary prevention of sudden cardiac death. , 2011, Journal of the American College of Cardiology.

[17]  Vivek Muthurangu,et al.  Evaluation of techniques for the quantification of myocardial scar of differing etiology using cardiac magnetic resonance. , 2011, JACC. Cardiovascular imaging.

[18]  Peter Kellman,et al.  Late Gadolinium-Enhancement Cardiac Magnetic Resonance Identifies Postinfarction Myocardial Fibrosis and the Border Zone at the Near Cellular Level in Ex Vivo Rat Heart , 2010, Circulation. Cardiovascular imaging.

[19]  M. Hayward,et al.  Equilibrium Contrast Cardiovascular Magnetic Resonance for the Measurement of Diffuse Myocardial Fibrosis: Preliminary Validation in Humans , 2010, Circulation.

[20]  P. Kistler,et al.  Myocardial Fibrosis Predicts Appropriate Device Therapy in Patients with Implantable Cardioverter Defibrillators for Primary Prevention of Sudden Cardiac Death , 2010 .

[21]  Stefan Neubauer,et al.  Society for Cardiovascular Magnetic Resonance guidelines for reporting cardiovascular magnetic resonance examinations , 2009, Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance.

[22]  Sandeep N. Gupta,et al.  Evaluation of diffuse myocardial fibrosis in heart failure with cardiac magnetic resonance contrast-enhanced T1 mapping. , 2008, Journal of the American College of Cardiology.

[23]  J. Núñez,et al.  Usefulness of a comprehensive cardiovascular magnetic resonance imaging assessment for predicting recovery of left ventricular wall motion in the setting of myocardial stunning. , 2005, Journal of the American College of Cardiology.

[24]  C H Lorenz,et al.  Differentiation of Heart Failure Related to Dilated Cardiomyopathy and Coronary Artery Disease Using Gadolinium‐Enhanced Cardiovascular Magnetic Resonance , 2003, Circulation.

[25]  M. Cerqueira,et al.  Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association , 2002, The international journal of cardiovascular imaging.

[26]  O. Simonetti,et al.  The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. , 2000, The New England journal of medicine.

[27]  O. Simonetti,et al.  Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. , 1999, Circulation.

[28]  K. Weber,et al.  Pathological Hypertrophy and Cardiac Interstitium: Fibrosis and Renin‐Angiotensin‐Aldosterone System , 1991, Circulation.