Cardiac magnetic resonance T2 mapping and T2* mapping for myocardial iron detection in iron-water phantom models and pediatric patients with transfusion-dependent thalassemia: a comparison study

Introduction

Thalassemia is an inherited anemia caused by defects in the gene encoding the globin, and is an autosomal recessive disease (1-3). Based on anemia symptoms, thalassemia is classified as mild, intermediate, or severe. Based on the impairment of the synthesis of the globin peptide chain, thalassemia is classified into five types (i.e., α, β, γ, δ, and δβ), among which, α and β are the most common types in the clinic (4).

Due to the decreased secretion of hepcidin, transfusion-dependent thalassemia (TDT) patients experience increased intestinal iron absorption, and release stored iron from mononuclear macrophages (5,6). In addition, TDT patients receive increased exogenous iron uptake due to prolonged transfusions for recurrent hemolysis and ineffective erythropoiesis (7,8). All of the above-mentioned factors increase the iron content in the body.

The iron excretion capacity of the healthy human body is limited. When the body’s iron content exceeds the storage capacity for ferritin and hemosiderin, free iron levels increase within the cells and create highly reactive hydroxyl radicals, interfering with energy metabolism (9) and resulting in tissue cell damage and organ failure. The most important cause of death in TDT patients is heart failure (10).

Cardiac magnetic resonance (CMR) is a multiparameter and multisequence imaging modality, and is a non-invasive, radiation-free, and reproducible inspection method. It is widely used to evaluate cardiac structure and function. T2 mapping can be used in the assessment of myocardial diseases, such as myocardial ischemia, myocardial infarction, myocarditis, hypertrophic cardiomyopathy, and dilated cardiomyopathy (11-15). T2* mapping is a routine tool for the assessment of iron overload in transfusion-dependent anemias, such as thalassemia and aplastic anemia, as well as in the guidance of iron expectorant therapy (16,17).

Myocardial iron deposition had been shown to shorten the transverse relaxation time and lead to lower T2 values (18). Wang et al. (19) found a positive linear correlation between 1/T2 values and cardiac iron concentration in gerbil iron overload models, iron concentration increased as T2 values decreased. Wood et al. (20) found a positive linear correlation between iron concentration and 1/T2* values in gerbil cardiac iron overload models. Anderson et al. (21) showed that compared with T2 mapping, T2* mapping was more sensitive to the non-uniform magnetic field.

Ferritin and hemosiderin are paramagnetic substances that can disrupt magnetic field uniformity. However, other factors affect magnetic field uniformity in iron overload disease, which may confound the effect of magnetic field inhomogeneities from iron overload on T2* mapping and result in inaccurate T2* values (22). Conversely, T2 mapping is not affected by magnetic field inhomogeneities (23).

To date, few studies have applied T2 mapping to iron deposition. The consistency between T2 mapping and T2* mapping has not yet been fully validated. Thus, this study sought to explore the utility and feasibility of T2 mapping for assessing iron overload in TDT patients, to compare the consistency of T2* mapping and T2 mapping, and to provide an alternative method for the assessment of non-invasive iron overload in clinical practice. We present this article in accordance with the STARD reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-24-1769/rc).

Methods

In vitro iron-water phantom models preparation and scanning

Ultrapure water was injected into 7 Eppendorf (EP) tubes and the volume of ultrapure water was 46, 43, 40, 37, 34, 31, and 28 mL respectively. Next, 4, 7, 10, 13, 16, 19, 22 mL of 10% iron dextran (50 mL: 5 g) were injected into the above 7 EP tubes in order. The total volume of the solution in each EP tube was 50 mL. Seven iron-water models at different concentrations (8, 14, 20, 26, 32, 38, and 44 mg/mL) were prepared, which were numbered 1, 2, 3, 4, 5, 6, and 7. The seven EP tubes were then placed in plastic bottles filled with ultrapure water. These tubes were then scanned with T2 mapping and T2* mapping sequences on a Philips 1.5T magnetic resonance (MR) scanner (Achieva, Philips Healthcare, Best, the Netherlands). The sequence parameters used for the T2 mapping and T2* mapping were the same as those used for the scanned patients (Table 1).

Study population

The clinical trial registration number was ChiCTR2200064307. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013), and was reviewed and approved by the Medical Ethics Committee of West China Second University Hospital of Sichuan University (No. 2022YFS0243). Written informed consent was obtained from all the participants and their legal guardians.

According to the relevant literature on the use of T2 mapping and T2*mapping in thalassemia (24), we used the result of Pearson’s correlation test to calculate the sample size of our study using PASS 2023 software {version 23.0.2, Power Analysis and Sample Size Software [2023], NCSS, LLC, Kaysville, Utah, USA} with the following metrics: 1−β=0.9, α=0.05, ρ0=0, and ρ1=0.445. The calculated sample size of the study was N=48.

From May 2022 to May 2024, 113 thalassemia patients were prospectively recruited for the study and underwent CMR to quantify their myocardial iron content at the West China Second University Hospital of Sichuan University. The inclusion criterion was a diagnosis of TDT by genetic testing and clinical presentation (n=99). The exclusion criteria were as follows: general contraindications to CMR (n=0), and/or an inability to tolerate a complete examination (n=7). Ultimately, 92 TDT patients (53 males and 39 females) undergoing long-term transfusion and iron chelation therapy were included in the study. The median age of the patients was 9.6 [7.7, 11.9] years. Additionally, age- and sex-matched healthy controls (8 females and 5 males) without any cardiovascular and iron deposition disease and with a median age of 9.7 [8.2, 10.9] years were included in the study.

According to the existing international consensus of iron overload in TDT, myocardial iron overload was diagnosed as cardiac T2* <20 ms (21,25).

Imaging protocol

All participants were scanned using a Philips 1.5T MR scanner (Achieva, Philips Healthcare, Best, the Netherlands) and a 16-channel body coil with the participant in the supine position and head ahead. The signal acquisition was triggered by cardiac gating. The participants were instructed not to move around at will and to listen to the machine commands of inhaling-exhaling-breathing hold. T2 and T2* mapping in three short-axis slices of the left ventricle (i.e., the basal, middle, and apical segments) were acquired during the breath-holding period, and the scanning parameters are listed in Table 1. The short-axis images and relaxation recovery curves for the CMR T2 and T2* mapping of a representative patient are shown in Figures 1,2.

Figure 1 T2 mapping and relaxation recovery curve at the short-axis level of left ventricle. (A) Original T2 mapping, images of 9 echo times are obtained. The echo time of each image gradually increases from left to right, in the order of 8.3, 16.7, 25, 33.4, 41.7, 50.1, 58.4, 66.8, and 75.1 ms. (B) Signal intensity/echo time fitting relaxation recovery curves. SI, signal intensity; TE, echo time.

Figure 2 T2* mapping and relaxation recovery curve at the short-axis level of left ventricle. (A) Original T2* mapping, images of 15 echo times are obtained. The echo time of each image gradually increases from left to right, in the order of 1.3, 2.5, 3.7, 4.9, 6.1, 7.3, 8.5, 9.7, 10.9, 12.1, 13.3, 14.6, 15.8, 17.0, and 18.2 ms. (B) Signal intensity/echo time fitting relaxation recovery curves. SI, signal intensity; TE, echo time.

Image analysis

Two experienced radiologists assessed the quality of all the acquired images and excluded myocardial segments with poor image quality caused by artifacts from the T2 and T2* mapping techniques. Ultimately, 85 apical, 85 middle, and 63 basal segments were included in the image analysis (Figure 3).

Figure 3 Flowchart of the inclusion of study subjects according to the study eligibility criteria. AHA, American Heart Association; CMR, cardiac magnetic resonance; s, segments.

All of the above included images were analyzed using the professional post-processing software CVI42 (Circle Cardiovascular Imaging, version 5.17, Calgary, Canada). To obtain the myocardial T2* and T2 values, the endocardium and epicardium borders were sketched manually in the short-axis position of the left ventricle at three different levels of the apical, middle, and basal segments.

Repeatability validation

For the intra-observer analysis, the values of T2* mapping and T2 mapping were measured twice by one of the two radiologists at a time interval of at least one month. Another radiologist, who was blind to the results of the first observer, re-analyzed the same patients to assess inter-observer variability.

Statistical analysis

The statistical analysis was conducted and diagrams were drawn with SPSS software (version 27.0, International Business Machines, Armonk, New York, USA), GraphPad Prism (version 10.1.2, GraphPad Software, LLC, Boston, USA) and MedCalc software (version 20.2, MedCalc Software, Mariakerke, Belgium). The Shapiro-Wilk test was performed to evaluate the normality of the continuous variables. The normally distributed continuous data were expressed as the mean ± standard deviation, while the non-normally distributed continuous data were expressed as the median (25%, 75% interquartile range). The categorical variables were presented as the frequency (%), and the Chi-squared test was used to compare the constituent ratio between the two groups. The Student’s t-test or Mann-Whitney U test was used to compare the controls and TDT patients. Pearson correlation analyses were conducted to compare the correlations among the vitro iron concentration, the T2* values, and the T2 values. The consistency of the T2 and T2* mapping in detecting myocardial iron content was evaluated by Bland-Altman analyses. Receiver operating characteristic (ROC) curve analyses was conducted to determine the T2 mapping cut-off value for diagnosing myocardial iron overload, and the area under the curve (AUC) was calculated. The intraclass correlation coefficient (ICC) was used to assess the reproducibility of intra-observer and inter-observer agreement in the myocardial T2 and T2* values. Reproducibility was considered poor if the ICC was <0.50, moderate if the ICC was 0.50–0.75, good if the ICC was 0.75–0.90, and excellent if the ICC was >0.90 (26). A P value <0.05 was considered statistically significant.

Results

Baseline characteristics of the study population

No statistically significant difference was found between the controls and TDT patients in terms of age, sex, body mass index (BMI), and body surface area (BSA) (Table 2). The type of affected globin chain in the TDT patients was the beta peptide chain, and all the included patients received iron chelation therapy. The values of ferritin, hemoglobin, and red blood cells in the TDT patients were 1,187.0 [920.1, 1,782.6] ng/mL, 98 [88, 106] g/L and (3.5±0.5)×10¹²/L, respectively.

The vitro validation of the correlation between T2 and T2* mapping by iron-water phantom models

The T2 and T2* values of the seven different iron concentration models are shown in Table 3. The corresponding color-coded maps for T2 and T2* mapping are shown in Figure 4. The correlations among iron concentration, the T2 value, and the T2* value are shown in Figure 5. As the true iron concentration increased, the T2 and T2* values of the vitro iron-water phantom models gradually decreased. The true iron concentration was strongly negatively correlated with the T2 value (r=−0.888, P=0.008) and the T2* value (r=−0.919, P=0.003). Further, the T2 value and T2* value were closely positively correlated (r=0.997, P<0.001).

Figure 4 T2 and T2* mapping color-coded images of the vitro iron-water models.

Figure 5 The correlation among the iron concentration, T2 values, and T2* values.

The agreement between T2 and T2* mapping in TDT patients

Bland-Altman plots for the vivo validation of the consistency of T2 and T2* mapping are shown in Figure 6. For the basal, middle, and apical segments, the corresponding mean values of (T2–T2*) were 21.2, 18.8, and 23.0 ms, and the 95% CIs were 3.5 to 39.0, 1.0 to 36.6, and 7.5 to 38.6 ms, respectively.

Figure 6 Bland-Altman plots showing the agreement of T2 and T2* mapping in the basal, middle, and apical segments of the myocardium (the horizontal coordinates represents the mean value of T2 + T2*, and the vertical coordinates represents the difference values between T2 and T2*). (A) Basal segment. (B) Middle segment. (C) Apical segment. SD, standard deviation.

The ability of T2 mapping to distinguish between TDT patients with myocardial iron overload and healthy controls

In total, 13 TDT patients were diagnosed with myocardial iron overload and had cardiac T2* values in any of the basal, middle, or apical segments that met the diagnostic criteria (T2* value <20 ms). The significant differences in the T2* and T2 values between controls and the patients with myocardial iron overload are shown in Table 4. Both T2 and T2* mapping could significantly distinguish between the healthy controls and myocardial iron overload patients.

Diagnostic efficiency of T2 mapping

ROC curves were plotted to distinguish between the healthy controls and patients with myocardial iron overload (Table 5 and Figure 7). The sensitivity of T2 mapping in diagnosing myocardial iron overload ranged from 80% to 100%, and the specificity ranged from 76.9% to 92.3%. Thus, T2 mapping could be used to diagnose myocardial iron overload using the basal, middle, and apical segments in the TDT patients (AUCs: 0.78, 0.95, and 0.89, respectively).

Figure 7 ROC curves showing the ability of T2 mapping to discriminate between the myocardial iron overload of transfusion-dependent thalassemia patients and the healthy controls in the basal (A), middle (B), and apical (C) segments. AUCs with 95% confidence intervals in parentheses are shown in the figure. AUC, area under the curve; ROC, receiver operating characteristic.

Reproducibility analysis of T2 and T2* mapping

The reproducibility results for the T2 and T2* mapping are presented in Tables 6,7. Notably, the ICCs of the T2* and T2 mapping were all >0.9, indicating excellent reproducibility.

Discussion

In this study, we found strong correlations among the iron concentration, T2 values, and T2* values in the vitro iron-water phantom models, which indicated that T2 mapping agreed well with T2* mapping in vitro phantom models, and can be used to precisely measure the true iron content. Additionally, the consistency analysis of the basal, middle, and apical segments of the TDT patients showed good agreement between the T2 and T2* mapping. Further, the ROC analysis results showed that T2 mapping could distinguish between myocardial iron overload and normal myocardium, and had good accuracy, high sensitivity, and high specificity in diagnosing myocardial iron overload in the TDT patients.

Iron overload cardiomyopathy is reversible in the early stage (27). Once heart failure develops in TDT patients, the outlook is usually poor even if intensified expectorant iron therapy was applied. Therefore, the early detection of myocardial iron overload and the early intensification of iron chelation therapy are greatly benefitial to TDT patients. Myocardial iron deposition is unevenly distributed, mainly in the epicardium (28). Myocardial biopsy can be used to examine the endocardium but is invasive, which limits its clinical application. CMR has become the main method for organ iron assessment (29).

In the present study, we used vitro validation phantom models with known iron concentrations to exclude the influence of other factors on the T2 and T2* values in humans, and the results showed strong agreement between the actual iron content and the T2 and T2* values. In the color-coded maps of the iron-water phantom models, the T2 color images were much more even than the T2* color images, which suggests that iron is a paramagnetic substance that can disrupt magnetic field uniformity. T2* mapping is sensitive to the non-uniform magnetic field (30), while T2 mapping is insensitive to the non-uniform magnetic field (31). Further, the results of the vitro validation iron-water models revealed good consistency between the myocardial T2 and T2* mapping of the TDT patients. The T2 and T2* values were similar to those reported in previous studies that used a 1.5T MR scanner (32,33). Krittayaphong et al. (33) and Feng et al. (22) reported a positive correlation between T2 and T2* values in thalassaemia patients, which were consistent with our findings. The present study and previous research had provided consolidated evidence that T2 mapping could serve as an alternative method for evaluating iron overload.

Given the good agreement between T2 and T2* mapping in vivo and in vitro, it has been conjectured that T2 mapping could be valuable in evaluating the myocardial iron metabolism abnormalities in vivo, and could serve as an alternative and complementary method to T2* mapping in the non-invasive iron overload assessment. For the diagnostic accuracy analysis, the AUC of the T2 values in the middle slice was better than the AUCs of both the basal and apical slices. In Meloni et al.’s study, the correlation in segments 7–12 was also better than that in the basal and apical slices (34). It may be that the basal segment is more affected by artery pulse and the apical segment is more affected by diaphragm movement. Therefore, based on our findings and those of Meloni et al., it is recommended that the T2 value of the middle segment be used for post-processing in clinical settings.

The heart rate of children is higher than that of adults, and children often cannot cooperate with breath-holding. Thus, these factors might affect the image quality of T2* mapping and its use in pediatrics. TDT often occurs in infants and children, who require long-time organ iron overload monitoring, especially of the liver and heart. Therefore, it is crucial that an alternative method be found for pediatric TDT patients. The present study focused on children, and showed that T2 mapping technology can serve as a reliable tool for the quantitative assessment of myocardial iron in pediatric TDT patients. With the application of free breathing technology, T2 and T2* mapping can effectively decrease artifacts and accurately evaluate myocardial iron deposition (35). The application of T2 and T2* mapping could be further expanded to a wider age range of patients, allowing younger patients to benefit from myocardial iron management.

Conversely, as field strength increases, the T2* value decreases (36,37), and there is an increased likelihood of artifacts (27), which limits the application of 3.0T MR scanners in the assessment of iron overload in severe iron overload cardiomyopathy. Therefore, T2* mapping is often performed on a 1.5T MR scanner (36). Kritsaneepaiboon et al. (31) found that the T2* values in 3.0T MR decreased in comparison with those in 1.5T MR, while the T2 values in 3.0T MR were almost equal to those in 1.5T MR. This indicates that the application of T2* mapping is limited under high magnetic field strength, and T2 mapping can be used as an alternative to T2* mapping. The development of MR scanners from 1.5T to 3.0T shortened the scanning time, improved the signal-to-noise ratio (38), and increased the temporal and spatial resolution (39). Thus, T2 mapping using 3.0T MR scanners may be more clinically applicable than T2* mapping using 3.0T MR scanners in pediatric patients with iron overload cardiomyopathy.

This study had some limitations. First, the sample size of patients with myocardial iron overload in this study was small; however, TDT is a rare disease. Second, the patients included in our study were actively receiving iron chelation therapy, so there were few TDT patients with myocardial iron overload. Third, we only conducted a preliminary study using a 1.5T MR scanner and did not conduct a validation analysis using a 3.0T MR scanner. The median age of TDT patients in our study was 9.6 years old, and they showed poor cooperation during scanning. Therefore, the CMR scanning was only performed using a 1.5T MR scanner, and we could not acquire images and data for the same patients using a 3.0T CMR scanner. Thus, we were unable to examine whether T2 mapping using a 3.0T CMR scanner may be more clinically applicable. In the future, we intend to examine this conjecture by conducting a study with an older age cohort. A further in-depth analysis needs to be conducted to examine the image artifacts and measurement accuracy of 3.0T MR scanners, which represents another future research direction. Using the iron-water phantom models, we showed that T2 mapping was very closely correlated with T2* mapping; however, some other contents such as inflammation may affect the T2 value and T2* value, which may reduce the degree of agreement. Thus, in clinical practice, T2 mapping may serve as an alternative tool to T2* mapping, when T2* mapping fails to be acquired. Further research also needs to be conducted on the tissue characteristics of T2 mapping in TDT disease.

Conclusions

Through in vitro iron-water phantom models and in vivo TDT patients, we found that T2 mapping and T2* mapping were consistent in evaluating myocardial iron content in pediatric patients. The T2 mapping technique may serve as an alternative to the T2* mapping technique in assessing iron overload in TDT patients.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STARD reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-24-1769/rc

Funding: This work was supported by the National Natural Science Foundation of China (Nos. 82120108015, 81971586, 82071874, 81901712, 82102020, and 82271981); the Sichuan Science and Technology Program (Nos. 2020YFS0050, 2020YJ0029, 2021YFS0175, 2022NSFSC1494, 2023YFG0284, and 24NSFSC1085); the Clinical Research Finding of Chinese Society of Cardiovascular Disease (CSC) of 2019 (No. HFCSC2019B01); and the Sichuan Provincial Health Commission (No. 21PJ048).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-1769/coif). The authors have no 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. This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and approved by the Medical Ethics Committee of West China Second Hospital of Sichuan University (No. 2022YFS0243). Written informed consent was obtained from all the participants and their legal guardians.

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. Taher AT, Otrock ZK, Uthman I, Cappellini MD. Thalassemia and hypercoagulability. Blood Rev 2008;22:283-92. [Crossref] [PubMed]
2. Galanello R. Recent advances in the molecular understanding of non-transfusion-dependent thalassemia. Blood Rev 2012;26:S7-S11. [Crossref] [PubMed]
3. Kattamis A, Kwiatkowski JL, Aydinok Y. Thalassaemia. Lancet 2022;399:2310-24. [Crossref] [PubMed]
4. Xu X, Wu X. Epidemiology and treatment of beta thalassemia major in China. Pediatr Investig 2020;4:43-7. [Crossref] [PubMed]
5. Nemeth E. Hepcidin in beta-thalassemia. Ann N Y Acad Sci 2010;1202:31-5. [Crossref] [PubMed]
6. Nemeth E. Hepcidin and β-thalassemia major. Blood 2013;122:3-4. [Crossref] [PubMed]
7. Pasricha SR, Frazer DM, Bowden DK, Anderson GJ. Transfusion suppresses erythropoiesis and increases hepcidin in adult patients with β-thalassemia major: a longitudinal study. Blood 2013;122:124-33. [Crossref] [PubMed]
8. Marsella M, Borgna-Pignatti C. Transfusional iron overload and iron chelation therapy in thalassemia major and sickle cell disease. Hematol Oncol Clin North Am 2014;28:703-27. vi. [Crossref] [PubMed]
9. Hershko C. Pathogenesis and management of iron toxicity in thalassemia. Ann N Y Acad Sci 2010;1202:1-9. [Crossref] [PubMed]
10. Muncie HL Jr, Campbell J. Alpha and beta thalassemia. Am Fam Physician 2009;80:339-44.
11. Park CH, Choi EY, Kwon HM, Hong BK, Lee BK, Yoon YW, Min PK, Greiser A, Paek MY, Yu W, Sung YM, Hwang SH, Hong YJ, Kim TH. Quantitative T2 mapping for detecting myocardial edema after reperfusion of myocardial infarction: validation and comparison with T2-weighted images. Int J Cardiovasc Imaging 2013;29:65-72. [Crossref] [PubMed]
12. Spieker M, Katsianos E, Gastl M, Behm P, Horn P, Jacoby C, Schnackenburg B, Reinecke P, Kelm M, Westenfeld R, Bönner F. T2 mapping cardiovascular magnetic resonance identifies the presence of myocardial inflammation in patients with dilated cardiomyopathy as compared to endomyocardial biopsy. Eur Heart J Cardiovasc Imaging 2018;19:574-82. [Crossref] [PubMed]
13. Huang L, Ran L, Zhao P, Tang D, Han R, Ai T, Xia L, Tao Q. MRI native T1 and T2 mapping of myocardial segments in hypertrophic cardiomyopathy: tissue remodeling manifested prior to structure changes. Br J Radiol 2019;92:20190634. [Crossref] [PubMed]
14. Gastl M, Lachmann V, Christidi A, Janzarik N, Veulemans V, Haberkorn S, Holzbach L, Jacoby C, Schnackenburg B, Berrisch-Rahmel S, Zeus T, Kelm M, Bönner F. Cardiac magnetic resonance T2 mapping and feature tracking in athlete's heart and HCM. Eur Radiol 2021;31:2768-77. [Crossref] [PubMed]
15. O'Brien AT, Gil KE, Varghese J, Simonetti OP, Zareba KM. T2 mapping in myocardial disease: a comprehensive review. J Cardiovasc Magn Reson 2022;24:33. [Crossref] [PubMed]
16. Ouederni M, Ben Khaled M, Mellouli F, Ben Fraj E, Dhouib N, Yakoub IB, Abbes S, Mnif N, Bejaoui M. Myocardial and liver iron overload, assessed using T2* magnetic resonance imaging with an excel spreadsheet for post processing in Tunisian thalassemia major patients. Ann Hematol 2017;96:133-9. [Crossref] [PubMed]
17. Menacho K, Abdel-Gadir A, Moon JC, Fernandes JL. T2* Mapping Techniques: Iron Overload Assessment and Other Potential Clinical Applications. Magn Reson Imaging Clin N Am 2019;27:439-51. [Crossref] [PubMed]
18. Lota AS, Gatehouse PD, Mohiaddin RH. T2 mapping and T2* imaging in heart failure. Heart Fail Rev 2017;22:431-40. [Crossref] [PubMed]
19. Wang ZJ, Lian L, Chen Q, Zhao H, Asakura T, Cohen AR. 1/T2 and magnetic susceptibility measurements in a gerbil cardiac iron overload model. Radiology 2005;234:749-55. [Crossref] [PubMed]
20. Wood JC, Otto-Duessel M, Aguilar M, Nick H, Nelson MD, Coates TD, Pollack H, Moats R. Cardiac iron determines cardiac T2*, T2, and T1 in the gerbil model of iron cardiomyopathy. Circulation 2005;112:535-43. [Crossref] [PubMed]
21. Anderson LJ, Holden S, Davis B, Prescott E, Charrier CC, Bunce NH, Firmin DN, Wonke B, Porter J, Walker JM, Pennell DJ. Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. Eur Heart J 2001;22:2171-9. [Crossref] [PubMed]
22. Feng Y, He T, Carpenter JP, Jabbour A, Alam MH, Gatehouse PD, Greiser A, Messroghli D, Firmin DN, Pennell DJ. In vivo comparison of myocardial T1 with T2 and T2* in thalassaemia major. J Magn Reson Imaging 2013;38:588-93. [Crossref] [PubMed]
23. He T, Gatehouse PD, Anderson LJ, Tanner M, Keegan J, Pennell DJ, Firmin DN. Development of a novel optimized breathhold technique for myocardial T2 measurement in thalassemia. J Magn Reson Imaging 2006;24:580-5. [Crossref] [PubMed]
24. Meloni A, Pistoia L, Garamella D, Parlato A, Positano V, Ricchi P, Casini T, De Marco E, Corigliano E, Borsellino Z, Visceglie D, De Caterina R, Pepe A, Cademartiri F. Early Detection of Myocardial Involvement in Thalassemia Intermedia Patients: Multiparametric Mapping by Magnetic Resonance Imaging. J Magn Reson Imaging 2024; Epub ahead of print. [Crossref]
25. Pennell DJ, Porter JB, Cappellini MD, Chan LL, El-Beshlawy A, Aydinok Y, Ibrahim H, Li CK, Viprakasit V, Elalfy MS, Kattamis A, Smith G, Habr D, Domokos G, Roubert B, Taher A. Continued improvement in myocardial T2* over two years of deferasirox therapy in β-thalassemia major patients with cardiac iron overload. Haematologica 2011;96:48-54. [Crossref] [PubMed]
26. Maceira AM, Tuset-Sanchis L, López-Garrido M, San Andres M, López-Lereu MP, Monmeneu JV, García-González MP, Higueras L. Feasibility and reproducibility of feature-tracking-based strain and strain rate measures of the left ventricle in different diseases and genders. J Magn Reson Imaging 2018;47:1415-25. [Crossref] [PubMed]
27. Nazarova EE, Tereshchenko GV, Kupriyanov DA, Smetanina NS, Novichkova GA. Free-breathing T2* mapping for MR myocardial iron assessment at 3 T. Eur Radiol Exp 2020;4:25. [Crossref] [PubMed]
28. Murphy CJ, Oudit GY. Iron-overload cardiomyopathy: pathophysiology, diagnosis, and treatment. J Card Fail 2010;16:888-900. [Crossref] [PubMed]
29. Wood JC. Use of magnetic resonance imaging to monitor iron overload. Hematol Oncol Clin North Am 2014;28:747-64. vii. [Crossref] [PubMed]
30. Storey P, Thompson AA, Carqueville CL, Wood JC, de Freitas RA, Rigsby CK. R2* imaging of transfusional iron burden at 3T and comparison with 1.5T. J Magn Reson Imaging 2007;25:540-7. [Crossref] [PubMed]
31. Kritsaneepaiboon S, Ina N, Chotsampancharoen T, Roymanee S, Cheewatanakornkul S. The relationship between myocardial and hepatic T2 and T2* at 1.5T and 3T MRI in normal and iron-overloaded patients. Acta Radiol 2018;59:355-62. [Crossref] [PubMed]
32. Casale M, Meloni A, Filosa A, Cuccia L, Caruso V, Palazzi G, Gamberini MR, Pitrolo L, Putti MC, D'Ascola DG, Casini T, Quarta A, Maggio A, Neri MG, Positano V, Salvatori C, Toia P, Valeri G, Midiri M, Pepe A. Multiparametric Cardiac Magnetic Resonance Survey in Children With Thalassemia Major: A Multicenter Study. Circ Cardiovasc Imaging 2015;8:e003230. [Crossref] [PubMed]
33. Krittayaphong R, Zhang S, Saiviroonporn P, Viprakasit V, Tanapibunpon P, Komoltri C, Wangworatrakul W. Detection of cardiac iron overload with native magnetic resonance T1 and T2 mapping in patients with thalassemia. Int J Cardiol 2017;248:421-6. [Crossref] [PubMed]
34. Meloni A, Pistoia L, Positano V, Martini N, Borrello RL, Sbragi S, Spasiano A, Casini T, Bitti PP, Putti MC, Cuccia L, Allò M, Massei F, Sanna PMG, De Caterina R, Quaia E, Cademartiri F, Pepe A. Myocardial tissue characterization by segmental T2 mapping in thalassaemia major: detecting inflammation beyond iron. Eur Heart J Cardiovasc Imaging 2023;24:1222-30. [Crossref] [PubMed]
35. Jin N, da Silveira JS, Jolly MP, Firmin DN, Mathew G, Lamba N, Subramanian S, Pennell DJ, Raman SV, Simonetti OP. Free-breathing myocardial T2* mapping using GRE-EPI and automatic non-rigid motion correction. J Cardiovasc Magn Reson 2015;17:113. [Crossref] [PubMed]
36. Meloni A, Positano V, Keilberg P, De Marchi D, Pepe P, Zuccarelli A, Campisi S, Romeo MA, Casini T, Bitti PP, Gerardi C, Lai ME, Piraino B, Giuffrida G, Secchi G, Midiri M, Lombardi M, Pepe A. Feasibility, reproducibility, and reliability for the T*2 iron evaluation at 3 T in comparison with 1.5 T. Magn Reson Med 2012;68:543-51. [Crossref] [PubMed]
37. Pennell DJ, Udelson JE, Arai AE, Bozkurt B, Cohen AR, Galanello R, Hoffman TM, Kiernan MS, Lerakis S, Piga A, Porter JB, Walker JM, Wood JAmerican Heart Association Committee on Heart Failure and Transplantation of the Council on Clinical Cardiology and Council on Cardiovascular Radiology and Imaging. Cardiovascular function and treatment in β-thalassemia major: a consensus statement from the American Heart Association. Circulation 2013;128:281-308. [Crossref] [PubMed]
38. Chang S, Park J, Yang YJ, Beck KS, Kim PK, Choi BW, Jung JI. Myocardial T2* Imaging at 3T and 1.5T: A Pilot Study with Phantom and Normal Myocardium. J Cardiovasc Dev Dis 2022;9:271. [Crossref] [PubMed]
39. von Knobelsdorff-Brenkenhoff F, Prothmann M, Dieringer MA, Wassmuth R, Greiser A, Schwenke C, Niendorf T, Schulz-Menger J. Myocardial T1 and T2 mapping at 3 T: reference values, influencing factors and implications. J Cardiovasc Magn Reson 2013;15:53. [Crossref] [PubMed]