Author + information
- Matthias G. Friedrich, MD∗ ()
- Departments of Medicine and Radiology, Université de Montréal, Montreal, Quebec, Canada; Philippa and Marvin Carsley CMR Centre at the Montreal Heart Institute, Montreal, Quebec, Canada; and the Departments of Cardiac Sciences and Radiology, University of Calgary, Calgary, Alberta, Canada
- ↵∗Reprint requests and correspondence:
Dr. Matthias G. Friedrich, Montreal Heart Institute, 5000 Rue Belanger, Montreal, Quebec H1T 1C8, Canada.
Obstacles are those frightful things you see when you take your eyes off your goal.
—Henry Ford (1)
Biomarker, a naturally occurring molecule, gene, or characteristic by which a particular pathological or physiological process, disease, etc. can be identified.
—Oxford Dictionary (2)
In addition to being very powerful for analyzing volumes, function, morphology, mass, flow, perfusion, and more, cardiac magnetic resonance (CMR) has become an indispensable tool for myocardial tissue characterization. During a magnetic resonance imaging scan, short high-frequency pulses interfere with the magnetic equilibrium of protons, which quickly recovers as protons “relax.” The relaxation process has 2 major time components: 1) T1, the spin-lattice (longitudinal) relaxation time; and 2) T2, the spin-spin (transversal) relaxation time. Importantly, these times are modified by the immediate molecular environment and thus can be understood as basic quantitative markers for the behavior of myocardial tissue in a strong magnetic field and ultimately for myocardial tissue composition. Native (i.e., without contrast agents) T1 is increased in the presence of myocardial edema and reduced in the presence of myocardial iron or fat, whereas after administration of a gadolinium-based (paramagnetic) contrast agent, T1 is shortened in myocardium with increased interstitial space, such as scar, diffuse fibrosis, and infiltration. T1 can be presented as a color-coded myocardial map and appears very useful for all clinical applications where an abnormality of the myocardial tissue is expected, especially in nonischemic cardiomyopathies. Because the degree of T1 deviation correlates with the extent of the tissue abnormality (e.g., a more severe edema will cause a more extensive T1 prolongation), specific thresholds may be applicable to differentiate disease severity or stage.
Approximately 30 years after Raymond Damadian’s first report on T1 and T2 relaxation for detecting tumors, the first human myocardial T1 maps (i.e., a color-coded map presentation of myocardial relaxation times) was reported in patients with acute myocardial infarction (3).
In this issue of iJACC, Hinojar et al. (4) report the use of T1 mapping for differentiating acute from convalescent myocarditis. In 165 patients, they performed native (i.e., noncontrast-enhanced) T1 mapping at 1.5-T and 3.0-T early and 6 months after clinical onset of disease. Compared with 40 control subjects, values >5 SD above normal values in controls were associated with acute myocarditis, whereas values between 2 SD and 5 SD were found 6 months later. In the convalescent stage, an abnormal signal in late gadolinium enhancement (LGE) images, if present, further added diagnostic value. There are some important observations: Native T1 clearly outperformed LGE in detecting acute myocarditis (sensitivity 98% vs. 72%), whereas the convalescent-stage LGE was more sensitive (86% vs. 76%); even better than LGE alone, however, was a combination of native T1 and LGE (95% vs. 86%). On a multivariate analysis, native T1 remained the only variable of statistical significance. Differences and accuracies were consistent between field strengths, albeit the diagnostic performance tended to be better at 3.0-T.
The data confirm a previous report by Ferreira et al. (5), who found a sensitivity of 90% (vs. 72% for LGE) in patients with acute myocarditis and thus indicate that native T1 mapping with predefined thresholds may be an alternative to the current diagnostic CMR criteria (Lake Louise Criteria).
The discrimination of acute from convalescent myocarditis by 2 different thresholds (signal intensity of >5 SD and signal intensity of <5 SD and >2 SD above mean) is a very interesting concept, although the data are mainly associative. There are also some limitations to a generalized applicability of the data. The high incidence of elevated troponin indicates that most of the myocarditis cases were necrotizing and thus may be more severe than in other populations. As the definition of myocarditis was based on apparent clinical grounds, the added value of CMR in less severe cases remains to be defined.
Finally, the predictive value of native T1 for functional outcome, which was found for T2, should be investigated.
Native T1 mapping, although still evolving, has already demonstrated the ability to provide incremental diagnostic information in several clinical entities (Table 1) (5–9), where abnormalities were related to acute injury, fibrous degeneration, and infiltration.
Native T1 does not require the injection of contrast agents and thus has advantages with respect to patient safety and cost. Although the risk of adverse events associated with gadolinium injection is much less than commonly perceived (0.17%) and serious concerns about systemic fibrosis are no longer warranted, side effects such as nausea, headaches, and, very rarely, allergic reactions may occur. Image acquisition must be performed during specific time windows after injection and cannot be immediately repeated. Thus, although the addition of contrast agents may be necessary for assessing extracellular volume fraction or hyperemia associated with inflammation, a native technique may be sufficient in suspected acute myocarditis.
T1 mapping is rapidly evolving, and there are published recommendations for terms and its standardized use (10). Reference values have been published for different scanners and commonly used field strengths (11,12). It, therefore, can be used by experienced centers in the absence of better disease markers (e.g., suspected diffuse fibrosis). However, there are still limitations that should be kept in mind (Table 1), as it is sensitive to variability caused by specific acquisition hardware and software. CMR centers, therefore, should still establish local datasets for normal T1 values.
Future clinical research must investigate the utility, efficacy, efficiency, and cost-efficiency of native (and post-contrast) T1 mapping in various clinical contexts. Furthermore, studies are needed to demonstrate the specific impact of myocardial tissue pathology on T1 and T2. This may also require validation against histopathology, although this is a methodologically challenging gold standard. Eventually we will also have to verify a positive impact of myocardial relaxation time mapping on patient outcome.
The paper by Hinojar et al. (4) indicates the clinical utility of native T1 mapping for monitoring tissue changes after acute disease. It underscores the potential of myocardial relaxation time mapping to attain a noninvasive assessment of tissue pathology. As the ejection fraction (with all its limitations) is used as a single number to describe a global systolic functional status of the heart, native T1 mapping used within a clinical context is about to emerge as a novel biomarker for the status of the myocardium.
↵∗ Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Dr. Friedrich is a board member, advisor, and shareholder of Circle Cardiovascular Imaging Inc.
- American College of Cardiology Foundation
- ↵Henry Ford. Available at: http://www.quotes.net/quote/6034. Accessed November 7, 2014.
- ↵Oxford Dictionary. Available at: http://www.oxforddictionaries.com/definition/english/biomarker. Accessed November 7, 2014.
- Hinojar R.,
- Foote L.,
- Arroyo Ucar E.,
- et al.
- Dass S.,
- Suttie J.J.,
- Piechnik S.K.,
- et al.
- Puntmann V.O.,
- D'Cruz D.,
- Smith Z.,
- et al.
- Fontana M.,
- Banypersad S.M.,
- Treibel T.A.,
- et al.
- h-Ici D.O.,
- Jeuthe S.,
- Al-Wakeel N.,
- et al.
- Moon J.C.,
- Messroghli D.R.,
- Kellman P.,
- et al.