An overview of the main studies with T1 mapping/ECV in non-ischemic cardiomyopathies is presented in Tables 2, 3, 4 and 5.

Table 2 An overview of the main studies with T1 mapping/ECV in non-ischemic dilated and Takotsubo cardiomyopathiesTable 3 An overview of the main studies with T1 mapping/ECV in genetic cardiomyopathiesTable 4 An overview of the main studies with T1 mapping/ECV in inflammatory cardiomyopathiesTable 5 An overview of the main studies with T1 mapping/ECV in infiltrative cardiomyopathiesNon-Ischemic Dilated Cardiomyopathy (NIDCM)

NIDCM is considered the end-stage of numerous non-ischemic cardiac diseases. Even with the recent improvement of treatment protocols, the mortality rate is still high (nearly 20%) [46]. At CMR, the evidence of mid-wall LGE predicts an augmented risk of MACEs in these patients [47, 48]; however, LGE sequences alone are not able to provide an accurate quantitative measurement of diffuse myocardium fibrosis that generally affects patients with DCM. Instead, T1 mapping could represent a good, reproducible tool to quantitative measure diffuse fibrosis in this setting[49, 50]. In a prospective longitudinal observational multicenter study including 637 patients with NIDCM, Puntman et al. have demonstrated that non-invasive evaluation of diffuse myocardial fibrosis through T1 mapping is significantly predictive of all causes of mortality (1.5 T T1 values: 1069 ms (1036–1103), p < 0.001 – ECV %: 30 (24–36), p = 0.03; 3 T T1 values: 1183 ms (1126–1211) p < 0.001 – ECV %: 31 (26–35), p = 0.02) and of a composite heart failure (HF) endpoint (HF death and HF hospitalization) in NIDCM [33]; the predictive associations are independent of conventional markers of function, structure, and regional myocardial disease by LGE. These results are partially discordant with another study where ECV was superior to T1 mapping to predict outcomes in NIDCM [51•]. After following their patient for four years, they observed MACE in 15% of the study group. In this subgroup, mean ECV demonstrated strong association with MACE (p < 0.001), superior to native T1 and LGE. These discrepancies between the two studies could be likely due to differences in the CMR techniques and in the studies’ cohort and design. Moreover, calculated ECV is a CMR tool used to describe myocardial extracellular space, and even if in some papers it has been adopted as a surrogate for histological collagen volume fraction in cardiovascular diseases, it does not certainly correlate well with histological fibrosis in DCM. This concept has been clearly elucidated in a single-centre study including a small sample size of NICDM patients where CMR results have been compared to right-sided biopsies of the mid-interventricular septum [52•]. Furthermore, in a recent multicenter study in which a group of 225 patients with NIDCM was followed for two years, Cadour et al. stated that NIDCM patients with HF-related or arrhythmia-related events had higher native T1 and ECV values (Native T1 Z-score: 3.8 ± 2.3, p = 0.001; ECV%: 31.1 ± 4.3, p = 0.001) compared with NIDCM patients without MACEs (Native T1 Z-score: 2.7 ± 2.2, p = 0.001; ECV%: 28.7 ± 3.8, p = 0.001) [34]; non-invasive measures of diffuse interstitial fibrosis by native T1 Z-score (p = 0.008) and ECV (p = 0.001) were significantly predictive of MACEs; the unique significant independent indicator predictive for both HF- and arrhythmia-related events (HR 2.15 [1.14–4.07], p = 0.018) was elevated ECV (cutoff > 32.1%); increased native T1 Z-score (cut-off > 4.2) was also an independent predictor of arrhythmia-related events in NIDCM patients (HR 2.86 [1.06–7.68], p = 0.037).

Takotsubo Cardiomyopathy

Takotsubo cardiomyopathy (TTC) is considered as an acute cardiovascular syndrome which generally presents as a temporary left ventricular dysfunction with a typical cardiac kinesis pattern without the presence of CAD [53]. In subacute clinical setting, CMR plays an important role in detecting TTC since LGE sequences typically show no enhancement and this can be helpful in differentiate the disease from MI or acute myocarditis [24]. One of the most important features of TTC is represented by diffuse myocardial oedema, which generally involve the whole LV even if it can be more intense in the hypokinetic segments. CMR can easily detect oedema via T2W imaging using the short-tau inversion recovery (STIR), however the introduction of T1 mapping sequences could guarantee a faster (single breath-hold) and quantitative evaluation of oedema without the need of a reference ROI as for T2 STIR sequences. Ferreira et al. stated that high native T1 values in TTC affected the myocardium as well as even in normal wall motion and a negative correlation between baseline LV ejection fraction (EF) and native T1 [54]. They found elevated T1 values in patient segments with preserved and not preserved wall motion when compared to the control group (1029 ± 59 ms, 1113 ± 94 ms and 944 ± 17 ms, respectively; p < 0.001) and established that a T1 value cut-off > 990 ms was optimal to differentiate segments affected by oedema from normal segments at 1.5 T, with a 92% sensitivity and specificity. More recently, Aikawa et al. explored the clinical relevance of T1 mapping for the mid-term evaluation of myocardial impairment in TTC [35]. During the acute phase, when compared to the control group, TTC patients demonstrated elevated native T1 (1438 ± 162 vs. 1251 ± 90 ms, P < 0.001), ECV (35 ± 5% vs. 29 ± 4%, P < 0.001), and T2 (90 ± 34 vs. 68 ± 12 ms, P < 0.001) for the entire heart. Importantly, they observed that native T1 mapping outperformed conventional T2 mapping for detecting myocardial oedema (AUC: 0.96 vs 0.86; P = 0.005) and that a T1 cut-off value > 1339 ms at three months follow-up scan was significantly correlated to prolonged LV wall motion recovery.

Genetic CardiomyopathiesHypertrophic Cardiomyopathy

Hypertrophic Cardiomyopathy (HCM) is a condition in which heart walls are thicker than normal and this anomaly cannot be explained by abnormal preload or afterload [55, 56]; in 30–60% of cases, the disease is the consequence of a sarcomere gene mutation inherited with autosomal dominance and it is generally identified in younger patients with family history of HCM [57]. Sudden cardiac death (SCD) is the most feared complication of the disease and to establish the risk of SCD is one of the most important objectives of the clinical management in these patients [58•]. As known, CMR-LGE can non-invasively detect and quantify myocardial fibrosis which possibly represent the basis for dangerous ventricular arrhythmias (VA) [59, 60]. The American HCM guidelines recommend LGE ≥ 15% of LV mass as a marker of SCD risk [55] and recently European guidelines for the prevention of SCD confirm this indication [61]. However, since a variable quote of LGE is present in 60–90% of HCM patients, its value as a risk stratifier is quite weak [62]. An accurate quantification of the LGE burden could reduce the impact of this limitation, but the differences in LGE scanning sequences and LGE quantification methods make the clinical implementation of LGE quantification challenging. Native T1 mapping and ECV could represent an interesting alternative to LGE as they have shown a good correlation with SCD risk for this disease; ECV also demonstrated a good association with SCD independent of LVEF [63, 64].

Qin et al. explored the capability of native T1 mapping and ECV to predict MACE in this category of patients [63]. In their HCM-MACE subgroup, global T1 mapping (1341.2 ± 39.6 ms) values were significantly higher than the HCM group that did not experience MACE (1277.9 ± 45.2 ms) and it was independently associated with MACE (HR: 1.446; 95%; CI: 1.195–1.749; P < 0.001). Moreover, in a subgroup of patients with low SCD risk established by conventional guidelines (T1 map not included), statistical analysis showed that global native T1 mapping was independently associated with MACE (HR: 1.532; 95% CI: 1.221–1.922; P < 0.001), highlighting that it could improve and support the current guidelines in the prediction of MACE.

More recently, it has been suggested that both native T1 values and ECV can outperform LGE to discriminate between HCM and hypertensive heart disease [36]. In particular, Liang et al. observed that in their cohort of patients, native T1 values were significantly higher in patients with HCM (1293.6 ± 53.8 ms) than in patients with HHD (1264.3 ± 67.7 ms) and in healthy controls (1236.1 ± 42.6 ms) (P < 0.001) [36]. Similarly, significantly higher ECV percentages were observed in HCM patients (34.9 ± 9.8%) when compared with HHD patients (27.1 ± 6.7%) and healthy controls (26.8 ± 5.8%) (P = 0.001). The Authors also identified a cut-off value of 28.8% for ECV, which was able to distinguish between HCM and HHD with 85% sensitivity, 62.07% specificity, and an AUC of 0.772. They demonstrated that these two methods can play an important role in clinical discrimination between HCM and HHD. However, the important overlap of native T1 values between normal and pathological myocardium represents a critical problem; for this reason, temporal or regional variations of T1 values in a single specific patient can represent an essential clinical information while comparisons among different patients could not be of value. Radiomics is a rapidly evolving field that uses data-characterization algorithms to extract data from medical images [65, 66]. It has recently been shown that radiomics phenotyping of native T1 mapping using machine learning could distinguish healthy versus hypertrophic myocardium and can also differentiate LVH aetiology, including HCM or cardiac amyloid [67,68,69].

Arrhythmogenic Right Ventricular Cardiomyopathy

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is a genetic cardiac condition in which the continuous fibro-fatty replacement of the normal cardiomyocytes becomes the substrate of VAs and SCD [70, 71]. ARVC diagnosis has always been based on the presence of genetic mutations, ECG abnormalities or VAs, but recently at least one morpho-functional right ventricle (RV) or LV is necessary for the diagnosis[72]. On this ground, CMR with cine sequences and tissue characterization with LGE imaging has become the leading imaging technique to detect the disease phenotype [72]. ARVC is increasingly recognized as a biventricular disease, and LV involvement is increasingly observed in up to 80% of relatives of sudden death victims diagnosed with ARVC on post-mortem examination [73, 74]. T1 mapping diagnostic potentials has been recently explored also for this cardiomyopathy. Bourfiss et al. evaluated native T1 mapping values and its dispersion in genotype positive ARVC patients and their families, also in comparison with control groups [37]. Their results demonstrated significantly (p = 0.04) higher native T1 values (1067 ± 41 ms) for genetically confirmed ARVC patients where controls showed significantly lower values (1038 ± 27 ms); these results also suggest a critical role of LV replacement fibrosis in the pathogenesis of the disease, maybe superior than fat infiltration. On the contrary, when compared with controls, a larger T1 values dispersion has been found in genotype-positive ARVC patients and their family members, that is probably a consequence of regional microstructure changes. Some Authors believe that native T1 variations can precede LV focal abnormalities in ARVC, favoring an early detection of these subjects and consequently improving prognosis. In a recent study, Georgiopoulos et al. discovered that native myocardial T1 values were higher than normal in 37% of their ARVC patients (1.5 T: 977 ± 39 ms, n.v. 950 ± 21 ms; 3 T:1189 ± 102 ms, n.v. 1052 ± 23 ms), including a proportion of patients who would have been otherwise classified as normal using conventional methods [75]. Higher T1 values were also observed in 33% of first-degree relatives who did not exhibit a cardiomyopathy phenotype after extensive investigations. Their observation could suggest a critical role for T1 mapping to early detect patients with ARCV.

Left Ventricular Noncompaction

Left ventricular non-compaction (LVNC) is a cardiomyopathy whose pathogenesis probably resides in a failure of myocardial compaction process during fetal development; this mainly results in an excessive trabeculation of myocardial walls, typically divided in a thick trabeculated non-compacted layer and a thin compacted myocardial one [76, 77]. LVNC is probably due to specific genes mutations, with a great genetic variability and since now no genetic test demonstrated acceptable performance [78]. In some cases, other systemic or cardiovascular conditions may develop in association with abnormal trabeculations [79]. Overall, LVNC clinical manifestations can vary from no symptoms to SCD [80]. Thanks to its spatial and contrast resolution, CMR is generally requested to confirm echocardiographic findings, providing better visualization of cardiac morphology, precise ventricular volumes and above all it can detect fibrosis through LGE sequences [81]. Recently, Araujo-Filho et al. have used T1 mapping in tissue characterization of LVNC providing new insights into the pathophysiology of this disease and suggesting a myocardial extracellular expansion by diffuse fibrosis [38]. LVNC patients presented a very low increment of native T1 (1024 ± 43 ms vs. 995 ± 22 ms, P = 0.01) with an elevated ECV (28.0 ± 4.5% vs. 23.5 ± 2.2%, P < 0.001) compared to controls. ECV was also independently associated with LVEF and Vas, over and above LGE, but not with the amount of non-compacted myocardium. Even if these findings suggest that native T1 mapping can be used earlier than LGE for detecting myocardial fibrosis in LVNC patients, the literature is still poor, and more research is needed for its application in a clinical setting.

Inflammatory CardiomyopathiesAcute myocarditis

Acute myocarditis (AM) is an inflammatory myocardial disease that may be the underlying basis for approximately 10% of dilated cardiomyopathies; furthermore, it is the leading cause of SCD in young people. Although the molecular and cellular pathophysiology may differ between different etiologies, cellular infiltration, oedema, necrosis and (in later stages) fibrotic scars are standard features [82]. The reference standard for diagnosing AM is endomyocardial biopsy. However, CMR, with the aid of the Lake Louise criteria, proposed in 2009 [83] and updated in 2018 [84], is widely used to guide clinical decision-making [85] and has become a non-invasive alternative to confirm the presence of disease. The introduction of T1 mapping increased diagnostic accuracy, discrimination of stages and activity of disease [86]. The Lake-Louise Criteria represented a first step towards a non-invasive diagnosis, while T1 and T2 mapping represent a step forward through a robust, short and quantifiable imaging application [87].

In a first exploratory study Ferreira V et al. compared native T1 values obtained through shMOLLI sequences with the T2wMRI sequences in patients with myocardial oedema [88]. They proved the excellent capability of native T1 sequences in detecting acute myocardial oedema (cutoff > 990 ms) (AUC: 0.94) when related to the use of skeletal muscle referencing (dark blood T2, AUC: 0.89; bright blood T2, AUC 0.84), or remote myocardium referencing (dark blood T2, AUC 0.58; bright blood T2, AUC 0.72). In 2013, the same group demonstrated that in their cohort of patients with clinical myocarditis, native T1 quantification (using the ShMOLLI sequence) had sensitivity, specificity and accuracy of 90%, 91% and 91%, respectively, while LGE sequences showed a specificity of 97% and a sensitivity of 74% [89].

In a recent meta-analysis on studies of patients with myocarditis, the Authors discovered that MRI-T1 values published in the selected papers had a specificity of 87% and an overall sensitivity of 82% in detecting the disease, resulting as the most sensitive MRI parameter [90]. However, regarding CMR predictors of prognosis in myocarditis, the Authors reported that the only independent predictors of MACE were LGE and baseline LVEF.

In another meta-analysis, Kotanidis et al. analysed a different set of studies and reported a diagnostic accuracy for T1 quantification that was superior to all other MRI parameters (AUC:0.95) [91]. Of note, they report an AUC for the original LLC criteria of 0.81.

In a recent prospective single-centre study, Kersten et al. evaluated the importance of CMR in the diagnosis of myocarditis, with particular consideration to absolute T1 values [92]. They discovered a good diagnostic performance of T1 mapping (cutoff > 1019 ms) in recognizing acute myocarditis patients from healthy subjects (AUC: 0.835, sensitivity 73.7%, specificity 72.4%); however, in a sub-cohort of patients where myocarditis was excluded, the established cutoff value had a false-positive rate of 56.6%. The group concluded that T1 mapping could play an important role in the diagnosis of myocarditis; however, the disease should always be diagnosed based on clinical and imaging factors.

Early post-gadolinium chelate–enhanced T1 mapping values have not yet been integrated into the most recent update of Lake Louise criteria because of their limited robustness compared with the other criteria [93], but recently it has been shown that it is a specific marker of acute myocardial inflammation, allowing a pixel-wise quantification of myocardial hyperemia and may potentially improve cardiac MRI accuracy in the diagnosis of acute myocarditis, once integrated with Lake Louise criteria [39]. Among a wide range of cardiovascular manifestations, AM is a possible complication of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection responsible for the current COVID-19 pandemic [94, 95]. Myocardial native T1 and T2 measures provided the best discriminatory value against healthy controls and risk factor–matched controls for exclusion of any myocardial disease or confirmation of COVID–19–related involvement, respectively [40]. However, more recently, it has been shown that T2-mapping values increase is the prevalent imaging biomarker of myocardial involvement in active COVID-19 [41].

Cardiac Sarcoidosis

Sarcoidosis is a systemic, inflammatory condition characterized by non-caseating granulomatous infiltration of many different organs. When cardiac involvement is present, patients can experience many different manifestations which can vary from an asymptomatic condition to heart failure and SCD. First line exams such as ECG, electrophysiology testing, echocardiography, and even myocardial perfusion imaging are often not capable to identify this condition because of its patchy nature that is its tendency to affect only some part of the myocardium without impairing LV function. During the last decades, CMR has played a pivotal role in identifying CS, and recently the Heart Rhythm Society has indicated non-ischemic myocardial LGE pattern as an important diagnostic criterion for CS [96]. Unfortunately, in CS regional scar formation is a late-stage consequence of myocardial injury and recently, it has been shown that quantitative CMR may help to detect diffuse fibrosis and inflammation using T1 and T2 mapping [42].

In a recent study, Puntmann et al. evaluated the capability of native T1 and T2 to distinguish patients with cardiac sarcoidosis from healthy controls [42]. In their results, T1 and T2 mapping showed a better diagnostic accuracy (AUC: 0.96 and 0.89, respectively) in detecting CS patients (T1:1139 ± 65 ms; T2: 54 ± 8 ms) from control subjects (T1:1052 ± 34 ms; T2:45 ± 7 ms) when compared with the standard diagnostic criteria (AUC < 0.67). Native T1 was the independent discriminator between health and disease (specificity, 90%; sensitivity, 96%; accuracy, 94%). Furthermore, they also observed a significant reduction of native T1 and T2 in a follow-up subgroup of patients who underwent treatment (z score: -3.72 and -2.88; P < 0.01). T1 and T2 mapping may enable noninvasive detection of cardiac involvement and activity of inflammation in patients with systemic sarcoidosis.

More recently, Cheung et al. explored the diagnostic performance of Hybrid cardiac 18F-fluorodeoxyglucose (FDG) PET/MRI with T1/T2 mapping in the detection of suspected CS [97]. FDG uptake (69%), FDG uptake co-localizing with LGE (76%) and elevated T2 (79%) reached a specificity of 69%,7 = % and 79% respectively; while sensitivity was highest for LGE, elevated T1 and ECV (100%). Moreover, native T1, FDG uptake, and elevated T2 and resulted being significant predictors of MACE. In Authors opinion, FDG-PET/MRI with T1/T2 mapping could provide important complementary information and predict MACE in patients with suspected CS.

Infiltrative CardiomyopathiesCardiac Amyloidosis

Cardiac amyloidosis (CA) is a rare infiltrative disorder in which abnormally folded proteins are deposited within the myocardium, and it can be regarded as the exemplar of an interstitial disease [98]. LGE is one of the first histologically proven methods for non-invasively detecting CA, and it occurs when gadolinium contrast distributes into the extracellular space without entering intact myocardial cells [99]. Patients with CA present circumferential subendocardial LGE in 80% of cases, particularly evident at the base and mid-ventricle segments, while the rest shows various LGE patterns. The characteristic diffuse LGE enhancement makes nulling of normal myocardium particularly difficult, often leading to confusion in interpretation [100, 101]. T1 mapping, circumventing the limitations of myocardial nulling, provides a quantitative assessment of diffuse extracellular expansion and is a viable option in renal failure, common with amyloid. When conducted sequentially, this approach can serve as a valuable method for tracking treatment responses and shifts in myocardial burden over time [102]. Fontana et al. demonstrated that both types of CA show markedly elevated native T1 values (ATTR T1 values: 1097 ± 43 ms), higher than normal subjects (967 ± 34 ms) and HCM patients (1026 ± 64 ms) (p < 0.0001) [43]. However, in established cardiac ATTR amyloidosis, T1 elevation was not as high as in AL amyloidosis (AL 1130 ± 68 ms; p = 0.01). Through these observations, the group demonstrated how, using native T1, cardiac amyloidosis could be reliably diagnosed and differentiated from other aetiologies of LVH, such as HCM, a clinically relevant differential diagnosis. The widespread infiltration of the interstitial space by the folded proteins in cardiac amyloidosis is the cause of the extremely high ECV values (0.466), more than in other cardiomyopathies [103]. A recent meta-analysis by Pan et al., compared diagnostic and prognostic performance of Native T1, ECV and LGE for CA [104]. Their results suggest that ECV may have better performances than LGE, while T1 mapping was comparable to other modalities in terms of sensitivity and specificity for diagnosing CA without requiring contrast material.

Anderson-Fabry Disease

A complete or partial α-galactosidase A enzyme deficiency is the cause of Anderson-Fabry disease, (AFD) a multisystem lysosomal storage condition transmitted via X-linked inheritance; the enzyme deficiency determines progressive intracellular accumulation of glycosphingolipids in multiple organs [105]. Long-term accumulation of glycosphingolipids in the myocardium causes LVH and myocardial fibrosis, which led to different symptoms and complications, such as arrhythmias, valvular dysfunction, and CAD [106]. CMR represents the best imaging modality for a comprehensive evaluation of cardiac involvement in this condition [107, 108]. LGE sequences can identify and quantify myocardial fibrosis which is considered an essential prognostic factor to provide risk stratification in AFD patients [109]. However, LGE cannot be considered a very early biomarker to be used for the identification of myocardial involvement in AFD and to start treatment with the recombinant enzyme.

Sado et al. have shown a low mean septal T1 in AFD [44]. They explored the potential of noncontrast T1 mapping to detect early cardiac involvement and distinguish AFD LVH from other causes. Beyond AFD patients they recruited patients affected by left ventricular hypertrophy of different aetiologies (hypertension, aortic stenosis, HCM) and healthy controls. Compared with controls (968 ± 32 ms), septal T1 was lower in AFD (882 ± 47 ms) and higher in other diseases (1018 ± 74 ms; P < 0.0001). Furthermore, in patients with LVH, T1 absolutely distinguishes AFD from other common causes with no apparent overlap. Noncontrast T1 mapping septal assessment could represent a simple, safe, quick, and useful tool in the diagnostic workup of LVH and the detection of early cardiac involvement in AFD, with potential for therapy monitoring [44]. These results have been confirmed by a recent metanalysis by Ponsiglione et al. aimed to determine the weighted mean native T1 values of AFD patients [110]. Overall, the weighted mean native T1 value was 984 ± 47 ms in AFD patients and 1016 ± 26 ms in healthy subjects (P < 0.0001). These findings confirmed a reduction of native T1 values in AFD patients compared to healthy volunteers, even if there is a need to standardize threshold values according to imaging equipment and protocols.

T1 values in the infero-lateral wall are frequently higher than in ‘remote’ myocardium (i.e. myocardium not including the infero-lateral wall), probably because the inferolateral wall myocardium in AFD undergoes a 4-phase transition from normal value (pre-detectable storage) to a low-value (storage) to pseudonormal value (storage + fibrosis) to a high value (fibrosis) [44]. It has been recently shown that the use of hybrid PET-MR imaging in AFD patients allows to detect different stages of disease progression [111,112,113].

Cardiac Siderosis

Cardiac siderosis or myocardial iron overload is a rare cardiac condition, but it can occur in states such as thalassemia or hemochromatosis; without treatment, it is associated with a significant risk of death and heart failure [114]. To date, T2* has been the most used technique to assess cardiac iron load non-invasively; T2* would be normal above 40 ms- but in practice, a threshold of 20 ms is used to avoid false positives [115]. Some researchers have explored T1 mapping in cardiac siderosis in-vivo, demonstrating superior inter-study reproducibility and T1 reclassification of a significant proportion of patients as having mild iron overload [45, 116]. Alam et al. compared the established 1.5 T BB T2* technique against native T1 values at 1.5 T and 3 T in cardiac siderosis patients and in healthy controls [45]. Iron overload patients (1.5 T T2* values < 20 ms) demonstrated native T1 values < 939 ms at 1.5 T, and < 1056 ms at 3 T, while controls presented a median native T1of 1014 ms (939–1059 ms) at 1.5 T and of 1165 ms (1056–1224 ms) at 3 T. Associations between T2* and T1 were found to be moderate, and T1 reproducibility appeared higher than T2*. The group concluded that T1 mapping has the potential to identify patients with significant iron overload. However, there is a significant scatter between results, probably because of measurement errors, interactions between T1 and T2*, or T1 could have a different sensitivity to iron chemistry. The scanner inter-center variation in absolute T1 values and the lack of calibration against human myocardial iron concentration are some of the limitations that slow its clinical application. Recently, similar results were obtained by another research group that compared T1 mapping using ShMOLLI with a T2* technique [116]. Native T1 was lower in iron overload patients than healthy controls (836 ± 138 ms vs. 968 ± 32 ms, P < 0.0001). Even in this case, interstudy reproducibility of native T1 was significantly superior to T2*, with the results suggesting T1 has potential implications for clinical trial design and therapeutic monitoring. More recently, it has been suggested that in the T2* 20-30 ms range, there might be iron load that is still undetected by this method; in this scenario, T1 measurement at 3 T could be capable of identifying even small amounts of iron accumulating in the heart [45, 117].