Cardiac magnetic resonance imaging assessment of myocardial disease in children and adolescents

Introduction

Cardiac magnetic resonance (CMR) imaging offers superior anatomical and functional information compared to traditional imaging modalities, enabling a comprehensive assessment of morphology, ventricular function, flow, and perfusion. Beyond these unique assets, CMR has emerged as a pivotal tool for myocardial tissue characterization. Complementing scar imaging by late gadolinium enhancement (LGE), parametric mapping of T1, T2, and T2* allows for the visualization and quantification of changes induced by myocardial edema, diffuse interstitial fibrosis, iron deposition and storage diseases. In concert, these findings provide crucial insights into the pathophysiology of various conditions, guiding diagnosis and management. This review explores the current state of CMR myocardial assessment in pediatrics, highlighting its strengths, limitations, and future directions.

Techniques

LGE

LGE imaging is the gold standard for the assessment of focal myocardial fibrosis. Following contrast administration, extracellular gadolinium-based contrast agents enter the myocardium and subsequently wash out into the blood pool as the concentration gradient reverses with renal excretion (1). While this occurs rapidly in healthy myocardium, contrast lingers longer focally by entering the disrupted cardiomyocytes (in acute injury) or accumulating within the extracellular matrix (in chronic scarring). These focal areas can be visualized by a heavily T1 weighted sequence, preceded by an inversion pulse to null the signal of normal myocardium (Figure 1) (2).

Figure 1 Tissue characterization in myocarditis: short axis CMR images showing myocardial late gadolinium enhancement in the basal inferolateral segment (top left), hyperintensity on T2 weighted imaging (top right), focally increased T1 values (bottom left) and increased T2 values (bottom right) on T1 and T2 color maps, respectively. CMR, cardiac magnetic resonance; LGE, late gadolinium enhancement.

T1 mapping and extra-cellular volume (ECV)

T1 relaxation time is the time that it takes for longitudinal magnetization of a tissue to return to its equilibrium following an inversion or saturation radiofrequency pulse. This time constant is determined by the tissue composition. Typically, T1 times are derived from a T1 recovery curve that is obtained by fitting signal intensities against time on a series of co-registered images acquired at different stages of T1 recovery (3-5). A T1 map is a single parametric image where the T1 times of tissue voxels are reflected by the corresponding pixel signal intensities on an absolute scale or in color, to enable visual interpretation (Figure 1). The modified Look-Locker inversion recovery (6) pulse sequence is the most widely used T1 mapping technique and has been extensively validated (7). Other sequences based on saturation-recovery are also emerging which aim to minimize acquisition times and sources of error. T1 parametric acquisitions without the administration of a paramagnetic contrast agent are referred to as “native” myocardial T1 mapping. Native myocardial T1 time reflects the combined signal from the myocytes and the interstitium. Native myocardial T1 is increased by increased collagen content such as in diffuse myocardial fibrosis, but also by myocardial edema and inflammation.

ECV: gadolinium-based contrast agents shorten T1 time and remain extracellular unless there is myocyte necrosis. Therefore, accumulation of contrast in the myocardial interstitium shortens T1 time in a degree proportional to expansion of the extracellular space. However isolated post-contrast myocardial T1 times are also influenced by a number of other factors including type and dose of contrast, timing of image acquisition and patient specific factors (8). To reduce the impact of these factors ECV is commonly employed as a contrast-enhanced metric of expansion of the myocardial extracellular space. It is calculated from the pre and post contrast T1 times and corrected for the patient’s hematocrit (8). In contrast to focal scarring that is detected by LGE imaging, ECV is a surrogate diffuse fibrosis by measuring the myocardial interstitial volume (relative to the total volume) and has shown good correlation with histologic collagen volume fraction (9,10).

T2 and T2* mapping

T2 time is the time decay constant for relaxation of the transverse magnetization after an excitation pulse. Free water has slower decay in the transverse magnetization plane and relatively long T2 relaxation times. Hence, myocardial T2 increases in the presence of edema (5,11-15). Analogous to T1 maps, T2 maps generate a single parametric image that encodes T2 relaxation times (Figure 1). T2 mapping has been shown to be more sensitive than T2-weighted imaging for detecting myocardial edema in various settings, including acute myocardial infarction, acute myocarditis, systemic inflammatory states and cardiac transplant rejection (8,11,14). The exponential decay in signal resulting from the combination of T2 relaxation and field inhomogeneities is measured by T2*—the effective transverse relaxation time. The presence of iron in tissues shortens T2* relaxation time by increasing tissue inhomogeneity.

Clinical applications

Myocarditis

Myocarditis, an inflammatory condition of the myocardium, presents with a broad clinical spectrum from asymptomatic patients to those presenting with fulminant disease and decompensated heart failure, making diagnosis challenging in some patients. The Lake Louise criteria for the CMR guided diagnosis were initially proposed in 2009 and revised in 2018 (16). The current version includes T1 and T2 mapping, as well as LGE and T2 weighted imaging. Specifically, in pediatric patients, mean global native T1, ECV values are strong differentiators of acute myocarditis compared to healthy controls and served to improve the detection of myocarditis in this age group (17).

Myocardial tissue characterization has also been useful to assess disease severity and may aid in risk prediction: LGE was found to be a harbinger of poor outcomes in pediatric patients with acute myocarditis (18). Higher T1 and T2 values at presentation were also associated with reduced left ventricular ejection fraction (LVEF) (18-21), as they likely reflect worse inflammation and edema. Thus, parametric mapping is not only critical for the diagnosis but also a valuable tool to track disease activity, therapeutic response and prognosis.

Cardiac allograft rejection

Cardiac allograft rejection, which occurs when the recipient’s immune system attacks the transplanted heart tissue, is an important cause of mortality and morbidity after heart transplantation. Early detection of rejection improves outcomes, but can be challenging because of often insidious clinical presentation. The current gold standard, direct pathologic evaluation of the myocardium via endomyocardial biopsy is invasive, carries inherent risks, is expensive, and can be limited by sampling error (22). Myocardial parametric mapping parameters have shown promise for the detection and surveillance of acute allograft rejection. Imran et al. (23), in their histologically confirmed study of adult transplanted hearts reported that T1 mapping was highly sensitive (93%) for diagnosis of clinically significant cardiac allograft rejection with an excellent negative predictive value of 99%. T2 relaxation time has been shown to increase in allograft rejection (24). Others have also combined T1, T2 and ECV parameters showing that multiparametric mapping can aid in the diagnosis of acute allograft rejection (24). While the data on using parametric mapping, specifically in the pediatric cardiac transplant recipients is limited, several studies suggest that myocardial tissue characterization may be of value. Native T1 values (25) as well as T2 and ECV (26,27) all track with the presence of clinical rejection and graft dysfunction in pediatric heart transplant patients. CMR shows promise to serve as a screening tool for surveillance of rejection, reserving endomyocardial biopsy for targeted testing of patients as part of a multifaceted approach to early detection and treatment of acute allograft rejection.

Kawasaki disease (KD)

KD, an acute systemic vasculitis, is well known for causing coronary artery aneurysms, but histological studies have also shown that myocarditis is common in KD (28,29). This has been corroborated by CMR studies (30) that found prolonged T2 times in patients with KD, especially during the acute phase of the illness. Muthusami et al. (31) have demonstrated that pediatric patients with KD have increased ECV compared to controls in both areas of affected by coronary lesions as well as remote regions, correlating with reduced contractility. Long term outcome studies have linked the presence of LGE with chronic ventricular dysfunction. These findings have implications in acute and long-term surveillance of patients with KD, potentially aiding with risk stratification and targeted surveillance of patients who are at risk of adverse ventricular modeling.

Genetic cardiomyopathies

Dilated cardiomyopathy (DCM)

DCM, a condition characterized by impaired ventricular contractility and myocardial dilation, is associated with diffuse myocardial fibrosis, which plays a key role in adverse myocardial remodeling. Analogous to several large adult studies Raj et al. (32) reported that native T1 values were elevated in children with DCM. Al-Wakeel-Marquard et al. (33) showed in their prospective study of pediatric patients with DCM that T1 and ECV values correlate with endpoints of impaired left ventricle (LV) function and N-terminal pro-B-type natriuretic peptide (NT-pro BNP). Native T1 and ECV are increasingly recognized as valuable prognostic imaging biomarkers that can complement comprehensive goal-directed medical therapy in pediatric heart failure.

Hypertrophic cardiomyopathy (HCM)

HCM, a condition characterized by abnormal thickening of the heart muscle, is associated with myocardial fibrosis, which can be assessed using CMR for surveillance and risk stratification. LGE is suspected to be the nidus of ventricular arrhythmias and has been identified as a risk factor for sudden cardiac death in adults with HCM. Recent studies linked LGE to a higher sudden cardiac death risk in children and adolescents as well, confirming earlier pilot data (34-36). LGE occurs in a similar pattern to adults in children and adolescents with HCM (37). It is progressive over time and confers an increased risk of adverse events when present. The extent of LGE was also found to be an important risk factor for ventricular arrhythmias (34-36,38). Parekh et al. and others have reported higher native T1 in the LV in children with HCM. Notably, even the segments without hypertrophy showed higher native T1 than controls (39,40). These findings are similar to adult studies that found increased T1 times in both hypertrophied and remote non-hypertrophied myocardium in patients with HCM (41). These observations may have implications for early identification of individuals with an abnormal myocardium who are genotype +, but phenotype negative and also aid in the screening of family members of genotype negative patients with HCM.

Left ventricular non-compaction (LVNC)

LVNC is a distinct myocardial abnormality caused by the arrest of the normal compaction of the endocardial layer of the myocardium during fetal development that results in a thickened, spongy, and hypertrabeculated myocardium with deep intra-trabecular recesses. Cheng et al. (42) studied a large cohort of children with isolated LVNC and reported an overall prevalence of LGE of 25%. Patients with LGE exhibited worse adverse LV remodeling and a higher incidence of cardiovascular death and heart transplantation.

Congenital heart disease

Tetralogy of Fallot (TOF)

TOF is a congenital heart defect involving four key structural abnormalities: a ventricular septal defect, pulmonary stenosis, right ventricular hypertrophy, and an overriding aorta. CMR is an important tool in the long-term surveillance of patients with repaired TOF as thresholds for reintervention hinge on CMR derived ventricular volumes and function. CMR assessment of the myocardium by tissue mapping can add further data in the surveillance of long-term ventricular remodeling in this patient group. The presence of LGE has been shown to be associated with reduced ventricular function, limited exercise capacity, and sudden death in adults with TOF (43). In addition to focal scarring by LGE imaging, diffuse fibrosis has been found in both the right ventricle (RV) and LV in adults with repaired TOF (44). Diffuse fibrosis is also associated with adverse clinical outcomes. Yim et al. (45) reported higher native T1 values in the RV myocardium of children and adolescents with repaired TOF. This suggests that diffuse myocardial fibrosis in repaired TOF starts early in life and likely progresses. There also appears to be a genetic predisposition for fibrotic remodeling in repaired TOF: Hoang et al. (46) discovered that indexed fibrotic volume and fibrotic score, derived from LGE by CMR were associated with certain genetic variants. Similarly, in another TOF study (47), polymorphisms in the same genes which are tied to fibrotic remodeling were linked to increased T1 values as a marker of diffuse fibrotic remodeling in the right ventricular myocardium.

Aortic disease

Fibrosis, confirmed by histology, has been shown to be present in patients with aortic valve stenosis, correlates with hemodynamic markers of myocardial performance, such as end-diastolic pressure and left ventricular ejection fraction (48), and has been associated clinical severity and need for earlier aortic valve intervention (49). While so-called replacement fibrosis, typically identified by LGE, occurs late in the disease process and is irreversible (50), diffuse interstitial fibrosis happens early and can regress following aortic valve replacement in adult studies of aortic stenosis. Young patients with congenital aortic stenosis also exhibit LGE compared with healthy controls, which correlates with myocardial function parameters such as LV strain and atrial dilation (49,51).

Single ventricle heart disease

Single ventricle heart disease refers to a condition in which patients have a functionally single ventricle, often due to congenital heart defects, and these patients remain at risk for ventricular dysfunction, arrhythmias, and sudden cardiac death (52). Rathod et al. studied myocardial scarring by LGE imaging in a cohort of late Fontan survivors and reported that myocardial scarring was not only common, but also associated with a more dilated, hypertrophied, and poorly functioning systemic ventricle as well as with a higher frequency of non-sustained ventricular tachycardia (53)—features which in turn are predictors of mortality and morbidity (54). Diffuse fibrosis by T1 mapping have also been shown to be present and associated with decreased myocardial contractility and Fontan failure in children with Fontan circulation (55,56).

Ebstein’s anomaly

Ebstein’s anomaly is characterized by failure of delamination of the tricuspid valve leaflet with resultant tricuspid regurgitation and an atrialized RV with progressive RV dilation and dysfunction. LV function is also known to be impacted in Ebstein’s anomaly and can be a marker for worse outcomes (57,58). In a mixed cohort of adult and adolescent patients with Ebstein’s anomaly, the LV myocardial ECV was significantly increased in patients and was significantly correlated with New York Heart Association (NYHA) class, tricuspid regurgitation severity and LVEF (59). In the same cohort LGE was also noted to present, however only 10% of patients showed focal fibrosis while diffuse fibrosis was more common and independently associated with LV function. Similarly, in a pediatric study of unrepaired Ebstein’s anomaly patients (60), higher ECV compared with controls was observed, while none had LGE. Higher extracellular volume and T1 values were associated with age, higher severity index values, lower exercise capacity, lower resting oxygen saturation and lower circumferential strain. CMR assessment of fibrosis could detect subtle changes in LV myocardial health to guide medical management.

Heritable thoracic aortic disease

The most common heritable thoracic aortic diseases are Marfan syndrome and Loeys-Dietz syndrome. The genetic mutations in these conditions are involved in coding for the components of the extracellular matrix or vascular smooth muscle apparatus. The role of the extracellular matrix in the structural integrity of the myocardium and its link to myocardial health is being increasingly recognized in this patient population (61,62). Savolainen and colleagues (63) and others have reported intrinsic myocardial dysfunction in Marfan syndrome. Karur et al. (64) showed increased left and right ventricular volumes along with diffuse myocardial fibrosis on CMR in children with Marfan syndrome and Loeys-Dietz syndrome. Interestingly, in their study, patients on losartan therapy had lower fibrosis markers. These findings support the concept of a primary cardiomyopathy associated with connective tissue disorders and indicate that angiotensin receptor blockers may be of benefit not only on a vascular, but also on a myocardial tissue level.

Iron overload states

Iron deposition in tissues can be assessed by T2* quantification. Cardiac siderosis is the most common cause of mortality in patients with thalassaemia major and other conditions that lead to iron overload through chronic transfusion needs. Ventricular dysfunction is a late phenomenon and iron chelation and elimination from the body must occur earlier in the process. Myocardial T2* mapping is crucial to guide early initiation of chelation therapy and monitor the treatment response in hemosiderosis (65).

Challenges and limitations

While CMR imaging is highly useful for a tissue-based assessment of the myocardium and has been referred to as a virtual biopsy, it also faces several challenges and limitations: Although T1 mapping sequences are available from all major vendors, they are not yet routinely performed in all pediatric cardiac imaging programs. A wider clinical application of parametric mapping needs establishment of robust normal ranges in large cohorts with standardized protocols, sequences and post processing methodology. This is hampered by several confounding factors, such as the interdependence between parameters and patient-specific factors. As a result, most published normal values in children remain limited to smaller single-center studies. Partial volume effects, where the voxel of interest contains a mixture of tissues like myocardium, blood pool, and epicardial fat, can also affect the quantitative measurements. Evaluating LGE and parametric mapping in small children, the non-hypertrophied RV, and thin-walled atria is technically limited due to a finite spatial resolution. Further, analysis and post-processing are time-consuming, presenting barriers to widespread clinical use.

Future directions

Future advancements in cardiac mapping are expected to focus on standardizing data acquisition and post-processing, as well as optimizing workflows. Accelerated image acquisition methods like compressed-sensing may enable significant reductions in scan times or improvements in image quality and spatial resolution. Three-dimensional mapping may provide more complete heart coverage and better characterization of complex regional disease patterns. Newer parametric mapping approaches hold the promise of yielding additional tissue information: T1 rho mapping, also called spin lattice relaxation, for example, can be detect the presence of interstitial fibrosis and other myocardial disease processes without the need for contrast agents (66,67). Magnetic resonance imaging (MRI) fingerprinting, is a technique that can simultaneously acquire T1, T2, ECV, and T2* maps, capture tissue perfusion and diffusion, T2* in a single sequence without the need for exogenous contrast agents. This technique, enhanced by machine learning algorithms that can segment and analyze imaging data accurately, has great potential to offer dual benefits of time-saving and removal of confounding factors that occur while acquiring parametric mapping parameters in a sequential fashion over a longer period of time (68-70). Concurrent to technical advances, the clinical utility of mapping techniques must be thoroughly explored for various cardiovascular diseases to further define where mapping parameters can accurately establish diagnoses, guide treatment decisions, and predict prognosis. While the precision, bias, and reproducibility of these novel techniques require careful quantification, they could lead to vast improvements in both clinical efficiency and diagnostic accuracy. In the future, the combination of parametric mapping techniques with radiomics-and artificial-intelligence based approaches to image analysis will likely push the boundaries of what cardiovascular magnetic resonance can achieve in the assessment and management of cardiovascular diseases.

Conclusions

Significant advancements in the management of pediatric heart disease have placed a new emphasis on preservation of myocardial health as a critical determinant of outcomes in addition to addressing structural/functional abnormalities. In this context, CMR has emerged as a powerful tool for myocardial tissue characterization, enabling detection and quantification of diffuse and focal fibrosis as well as myocardial edema. This capability holds promise for earlier targeted interventions as well as improved treatment monitoring across the spectrum of pediatric heart disease. Long-term longitudinal studies with standardized imaging protocols across various disease states are needed to define the risk factors for the development of fibrosis and to understand the prognostic implications of these imaging biomarkers on patient outcomes.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editor (Harald Kaemmerer) for the series “Current Management Aspects in Adult Congenital Heart Disease (ACHD): Part VI” published in Cardiovascular Diagnosis and Therapy. The article has undergone external peer review.

Peer Review File: Available at https://cdt.amegroups.com/article/view/10.21037/cdt-24-502/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-24-502/coif). The series “Current Management Aspects in Adult Congenital Heart Disease (ACHD): Part VI” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Jimenez Juan L, Crean AM, Wintersperger BJ. Late gadolinium enhancement imaging in assessment of myocardial viability: techniques and clinical applications. Radiol Clin North Am 2015;53:397-411. [Crossref] [PubMed]
2. Kellman P, Arai AE. Cardiac imaging techniques for physicians: late enhancement. J Magn Reson Imaging 2012;36:529-42. [Crossref] [PubMed]
3. Taylor AJ, Salerno M, Dharmakumar R, et al. T1 Mapping: Basic Techniques and Clinical Applications. JACC Cardiovasc Imaging 2016;9:67-81. [Crossref] [PubMed]
4. Hamilton-Craig CR, Strudwick MW, Galloway GJ T. (1) Mapping for Myocardial Fibrosis by Cardiac Magnetic Resonance Relaxometry-A Comprehensive Technical Review. Front Cardiovasc Med 2016;3:49. [Crossref] [PubMed]
5. Ferreira VM, Piechnik SK, Robson MD, et al. Myocardial tissue characterization by magnetic resonance imaging: novel applications of T1 and T2 mapping. J Thorac Imaging 2014;29:147-54. [Crossref] [PubMed]
6. Messroghli DR, Radjenovic A, Kozerke S, et al. Modified Look-Locker inversion recovery (MOLLI) for high-resolution T1 mapping of the heart. Magn Reson Med 2004;52:141-6. [Crossref] [PubMed]
7. Diao KY, Yang ZG, Xu HY, et al. Histologic validation of myocardial fibrosis measured by T1 mapping: a systematic review and meta-analysis. J Cardiovasc Magn Reson 2016;18:92. [Crossref] [PubMed]
8. Moon JC, Messroghli DR, Kellman P, et al. Myocardial T1 mapping and extracellular volume quantification: a Society for Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the European Society of Cardiology consensus statement. J Cardiovasc Magn Reson 2013;15:92. [Crossref] [PubMed]
9. Miller CA, Naish JH, Bishop P, et al. Comprehensive validation of cardiovascular magnetic resonance techniques for the assessment of myocardial extracellular volume. Circ Cardiovasc Imaging 2013;6:373-83. [Crossref] [PubMed]
10. Fontana M, White SK, Banypersad SM, et al. Comparison of T1 mapping techniques for ECV quantification. Histological validation and reproducibility of ShMOLLI versus multibreath-hold T1 quantification equilibrium contrast CMR. J Cardiovasc Magn Reson 2012;14:88. [Crossref] [PubMed]
11. Abdel-Aty H, Zagrosek A, Schulz-Menger J, et al. Delayed enhancement and T2-weighted cardiovascular magnetic resonance imaging differentiate acute from chronic myocardial infarction. Circulation 2004;109:2411-6. [Crossref] [PubMed]
12. Abdel-Aty H, Schulz-Menger J. Cardiovascular magnetic resonance T2-weighted imaging of myocardial edema in acute myocardial infarction. Recent Pat Cardiovasc Drug Discov 2007;2:63-8. [Crossref] [PubMed]
13. Abdel-Aty H, Simonetti O, Friedrich MG. T2-weighted cardiovascular magnetic resonance imaging. J Magn Reson Imaging 2007;26:452-9. [Crossref] [PubMed]
14. Giri S, Chung YC, Merchant A, et al. T2 quantification for improved detection of myocardial edema. J Cardiovasc Magn Reson 2009;11:56. [Crossref] [PubMed]
15. Sharma V, Binukrishnan S, Schoepf UJ, et al. Myocardial tissue characterization with magnetic resonance imaging. J Thorac Imaging 2014;29:318-30. [Crossref] [PubMed]
16. Friedrich MG, Sechtem U, Schulz-Menger J, et al. Cardiovascular magnetic resonance in myocarditis: A JACC White Paper. J Am Coll Cardiol 2009;53:1475-87. [Crossref] [PubMed]
17. Cornicelli MD, Rigsby CK, Rychlik K, et al. Diagnostic performance of cardiovascular magnetic resonance native T1 and T2 mapping in pediatric patients with acute myocarditis. J Cardiovasc Magn Reson 2019;21:40. [Crossref] [PubMed]
18. Schumm J, Greulich S, Wagner A, et al. Cardiovascular magnetic resonance risk stratification in patients with clinically suspected myocarditis. J Cardiovasc Magn Reson 2014;16:14. [Crossref] [PubMed]
19. Banka P, Robinson JD, Uppu SC, et al. Cardiovascular magnetic resonance techniques and findings in children with myocarditis: a multicenter retrospective study. J Cardiovasc Magn Reson 2015;17:96. [Crossref] [PubMed]
20. Sachdeva S, Song X, Dham N, et al. Analysis of clinical parameters and cardiac magnetic resonance imaging as predictors of outcome in pediatric myocarditis. Am J Cardiol 2015;115:499-504. [Crossref] [PubMed]
21. Pan JA, Lee YJ, Salerno M. Diagnostic Performance of Extracellular Volume, Native T1, and T2 Mapping Versus Lake Louise Criteria by Cardiac Magnetic Resonance for Detection of Acute Myocarditis: A Meta-Analysis. Circ Cardiovasc Imaging 2018;11:e007598. [Crossref] [PubMed]
22. Seferović PM, Tsutsui H, McNamara DM, et al. Heart Failure Association of the ESC, Heart Failure Society of America and Japanese Heart Failure Society Position statement on endomyocardial biopsy. Eur J Heart Fail 2021;23:854-71. [Crossref] [PubMed]
23. Imran M, Wang L, McCrohon J, et al. Native T(1) Mapping in the Diagnosis of Cardiac Allograft Rejection: A Prospective Histologically Validated Study. JACC Cardiovasc Imaging 2019;12:1618-28. [Crossref] [PubMed]
24. Dolan RS, Rahsepar AA, Blaisdell J, et al. Multiparametric Cardiac Magnetic Resonance Imaging Can Detect Acute Cardiac Allograft Rejection After Heart Transplantation. JACC Cardiovasc Imaging 2019;12:1632-41. [Crossref] [PubMed]
25. Richmann DP, Gurijala N, Mandell JG, et al. Native T1 mapping detects both acute clinical rejection and graft dysfunction in pediatric heart transplant patients. J Cardiovasc Magn Reson 2022;24:51. [Crossref] [PubMed]
26. Sethi N, Doshi A, Doshi T, et al. Quantitative cardiac magnetic resonance T2 imaging offers ability to non-invasively predict acute allograft rejection in children. Cardiol Young 2020;30:852-9. [Crossref] [PubMed]
27. Husain N, Watanabe K, Berhane H, et al. Multi-parametric cardiovascular magnetic resonance with regadenoson stress perfusion is safe following pediatric heart transplantation and identifies history of rejection and cardiac allograft vasculopathy. J Cardiovasc Magn Reson 2021;23:135. [Crossref] [PubMed]
28. Yonesaka S, Takahashi T, Matubara T, et al. Histopathological study on Kawasaki disease with special reference to the relation between the myocardial sequelae and regional wall motion abnormalities of the left ventricle. Jpn Circ J 1992;56:352-8. [Crossref] [PubMed]
29. Yutani C, Okano K, Kamiya T, et al. Histopathological study on right endomyocardial biopsy of Kawasaki disease. Br Heart J 1980;43:589-92. [Crossref] [PubMed]
30. Ishikawa T, Suwa K. Editorial for "Quantitative Assessment of Myocardial Edema by MR T2 Mapping in Children With Kawasaki Disease". J Magn Reson Imaging 2024;59:835-6. [Crossref] [PubMed]
31. Muthusami P, Luining W, McCrindle B, et al. Myocardial Perfusion, Fibrosis, and Contractility in Children With Kawasaki Disease. JACC Cardiovasc Imaging 2018;11:1922-4. [Crossref] [PubMed]
32. Raj S, Kothari R, Arun Kumar N, et al. T1 mapping and conditional survival in paediatric dilated cardiomyopathy with advanced heart failure. Cardiol Young 2021;31:1938-42. [Crossref] [PubMed]
33. Al-Wakeel-Marquard N, Seidel F, Herbst C, et al. Diffuse myocardial fibrosis by T1 mapping is associated with heart failure in pediatric primary dilated cardiomyopathy. Int J Cardiol 2021;333:219-25. [Crossref] [PubMed]
34. Petryka-Mazurkiewicz J, Ziolkowska L, Kowalczyk-Domagala M, et al. LGE for Risk Stratification in Primary Prevention in Children With HCM. JACC Cardiovasc Imaging 2020;13:2684-6. [Crossref] [PubMed]
35. Smith BM, Dorfman AL, Yu S, et al. Clinical significance of late gadolinium enhancement in patients<20 years of age with hypertrophic cardiomyopathy. Am J Cardiol 2014;113:1234-9. [Crossref] [PubMed]
36. Windram JD, Benson LN, Dragelescu A, et al. Distribution of Hypertrophy and Late Gadolinium Enhancement in Children and Adolescents with Hypertrophic Cardiomyopathy. Congenit Heart Dis 2015;10:E258-67. [Crossref] [PubMed]
37. Axelsson Raja A, Farhad H, Valente AM, et al. Prevalence and Progression of Late Gadolinium Enhancement in Children and Adolescents With Hypertrophic Cardiomyopathy. Circulation 2018;138:782-92. [Crossref] [PubMed]
38. Ali LA, Marrone C, Martins DS, et al. Prognostic factors in hypertrophic cardiomyopathy in children: An MRI based study. Int J Cardiol 2022;364:141-7. [Crossref] [PubMed]
39. Parekh K, Markl M, Deng J, et al. T1 mapping in children and young adults with hypertrophic cardiomyopathy. Int J Cardiovasc Imaging 2017;33:109-17. [Crossref] [PubMed]
40. Sunthankar S, Parra DA, George-Durrett K, et al. Tissue characterisation and myocardial mechanics using cardiac MRI in children with hypertrophic cardiomyopathy. Cardiol Young 2019;29:1459-67. [Crossref] [PubMed]
41. Hinojar R, Varma N, Child N, et al. T1 Mapping in Discrimination of Hypertrophic Phenotypes: Hypertensive Heart Disease and Hypertrophic Cardiomyopathy: Findings From the International T1 Multicenter Cardiovascular Magnetic Resonance Study. Circ Cardiovasc Imaging 2015;8:e003285. [Crossref] [PubMed]
42. Cheng H, Lu M, Hou C, et al. Comparison of cardiovascular magnetic resonance characteristics and clinical consequences in children and adolescents with isolated left ventricular non-compaction with and without late gadolinium enhancement. J Cardiovasc Magn Reson 2015;17:44. [Crossref] [PubMed]
43. Babu-Narayan SV, Kilner PJ, Li W, et al. Ventricular fibrosis suggested by cardiovascular magnetic resonance in adults with repaired tetralogy of fallot and its relationship to adverse markers of clinical outcome. Circulation 2006;113:405-13. [Crossref] [PubMed]
44. Broberg CS, Chugh SS, Conklin C, et al. Quantification of diffuse myocardial fibrosis and its association with myocardial dysfunction in congenital heart disease. Circ Cardiovasc Imaging 2010;3:727-34. [Crossref] [PubMed]
45. Yim D, Riesenkampff E, Caro-Dominguez P, et al. Assessment of Diffuse Ventricular Myocardial Fibrosis Using Native T1 in Children With Repaired Tetralogy of Fallot. Circ Cardiovasc Imaging 2017;10:e005695. [Crossref] [PubMed]
46. Hoang TT, Manso PH, Edman S, et al. Genetic variants of HIF1α are associated with right ventricular fibrotic load in repaired tetralogy of Fallot patients: a cardiovascular magnetic resonance study. J Cardiovasc Magn Reson 2019;21:51. [Crossref] [PubMed]
47. Vaikom House AK. Patients with repaired tetralogy of Fallot and the HIF1A1744C/T variant have increased imaging markers of diffuse myocardial fibrosis. Int J Cardiol 2022;350:33-5. [Crossref] [PubMed]
48. Dweck MR, Boon NA, Newby DE. Calcific aortic stenosis: a disease of the valve and the myocardium. J Am Coll Cardiol 2012;60:1854-63. [Crossref] [PubMed]
49. Dusenbery SM, Lunze FI, Jerosch-Herold M, et al. Left Ventricular Strain and Myocardial Fibrosis in Congenital Aortic Stenosis. Am J Cardiol 2015;116:1257-62. [Crossref] [PubMed]
50. Treibel TA, Kozor R, Schofield R, et al. Reverse Myocardial Remodeling Following Valve Replacement in Patients With Aortic Stenosis. J Am Coll Cardiol 2018;71:860-71. [Crossref] [PubMed]
51. Lluri G, Renella P, Finn JP, et al. Prognostic Significance of Left Ventricular Fibrosis in Patients With Congenital Bicuspid Aortic Valve. Am J Cardiol 2017;120:1176-9. [Crossref] [PubMed]
52. Valente AM, Lewis M, Vaziri SM, et al. Outcomes of adolescents and adults undergoing primary Fontan procedure. Am J Cardiol 2013;112:1938-42. [Crossref] [PubMed]
53. Rathod RH, Prakash A, Kim YY, et al. Cardiac magnetic resonance parameters predict transplantation-free survival in patients with fontan circulation. Circ Cardiovasc Imaging 2014;7:502-9. [Crossref] [PubMed]
54. Khairy P, Fernandes SM, Mayer JE Jr, et al. Long-term survival, modes of death, and predictors of mortality in patients with Fontan surgery. Circulation 2008;117:85-92. [Crossref] [PubMed]
55. Pisesky A, Reichert MJE, de Lange C, et al. Adverse fibrosis remodeling and aortopulmonary collateral flow are associated with poor Fontan outcomes. J Cardiovasc Magn Reson 2021;23:134. [Crossref] [PubMed]
56. Kato A, Riesenkampff E, Yim D, et al. Pediatric Fontan patients are at risk for myocardial fibrotic remodeling and dysfunction. Int J Cardiol 2017;240:172-7. [Crossref] [PubMed]
57. Brown ML, Dearani JA, Danielson GK, et al. Effect of operation for Ebstein anomaly on left ventricular function. Am J Cardiol 2008;102:1724-7. [Crossref] [PubMed]
58. Steinmetz M, Schuster A. Left Ventricular Pathology in Ebstein's Anomaly-Myocardium in Motion: CMR Insights Into Left Ventricular Fibrosis, Deformation, and Exercise Capacity. Circ Cardiovasc Imaging 2021;14:e012285. [Crossref] [PubMed]
59. Yang D, Li X, Sun JY, et al. Cardiovascular magnetic resonance evidence of myocardial fibrosis and its clinical significance in adolescent and adult patients with Ebstein's anomaly. J Cardiovasc Magn Reson 2018;20:69. [Crossref] [PubMed]
60. Aly S, Seed M, Yoo SJ, et al. Myocardial Fibrosis in Pediatric Patients With Ebstein's Anomaly. Circ Cardiovasc Imaging 2021;14:e011136. [Crossref] [PubMed]
61. Muiño-Mosquera L, De Backer J. Cardiomyopathy in Genetic Aortic Diseases. Front Pediatr 2021;9:682390. [Crossref] [PubMed]
62. Frangogiannis NG. The Extracellular Matrix in Ischemic and Nonischemic Heart Failure. Circ Res 2019;125:117-46. [Crossref] [PubMed]
63. Savolainen A, Nisula L, Keto P, et al. Left ventricular function in children with the Marfan syndrome. Eur Heart J 1994;15:625-30. [Crossref] [PubMed]
64. Karur GR, Pagano JJ, Bradley T, et al. Diffuse Myocardial Fibrosis in Children and Adolescents With Marfan Syndrome and Loeys-Dietz Syndrome. J Am Coll Cardiol 2018;72:2279-81. [Crossref] [PubMed]
65. Casale M, Meloni A, Filosa A, et al. Multiparametric Cardiac Magnetic Resonance Survey in Children With Thalassemia Major: A Multicenter Study. Circ Cardiovasc Imaging 2015;8:e003230. [Crossref] [PubMed]
66. Bustin A, Toupin S, Sridi S, et al. Endogenous assessment of myocardial injury with single-shot model-based non-rigid motion-corrected T1 rho mapping. J Cardiovasc Magn Reson 2021;23:119. [Crossref] [PubMed]
67. Wang L, Yuan J, Zhang SJ, et al. Myocardial T1 rho mapping of patients with end-stage renal disease and its comparison with T1 mapping and T2 mapping: A feasibility and reproducibility study. J Magn Reson Imaging 2016;44:723-31. [Crossref] [PubMed]
68. Ma D, Gulani V, Seiberlich N, et al. Magnetic resonance fingerprinting. Nature 2013;495:187-92. [Crossref] [PubMed]
69. McGivney DF, Boyacıoğlu R, Jiang Y, et al. Magnetic resonance fingerprinting review part 2: Technique and directions. J Magn Reson Imaging 2020;51:993-1007. [Crossref] [PubMed]
70. Poorman ME, Martin MN, Ma D, et al. Magnetic resonance fingerprinting Part 1: Potential uses, current challenges, and recommendations. J Magn Reson Imaging 2020;51:675-92. [Crossref] [PubMed]