CMR T1 mapping indices are novel non-invasive imaging biomarkers for myocardial extracellular space measurement [22–24]. There is increasing evidence supporting the clinical utility of T1 mapping quantification as well as of the serial assessment of such values. Multi-center studies using different MR platforms are ultimately required to assess the robustness of T1 measurements as a biomarker. Our major findings are: 1) T1 values by both IR-SE and MOLLI were different across scanners in the same field strength; 2) there was no difference between partition coefficients of 1.5T scanners (47.2% vs. 47.9%, p=0.13) and only slight differences across 3T scanners (49.2% vs. 49.8% vs. 49.9%, p=0.016); 3) partition coefficient had less variability in accuracy across platforms and field strength (8.8% error for 1.5T vs. 8.0% error for 3T, p=0.11) than MOLLI T1 values (6.3% error for 1.5T vs. 10.8% error for 3T, p<0.001); 4) partition coefficient had higher scan/re-scan reproducibility than MOLLI T1 values. In summary, the partition coefficient may be more robust than MOLLI T1 values when comparing between different scanners and field strengths. It is important to note that although only partition coefficient, and not ECV, was evaluated due to lack of hematocrit data, these results can be directly translated to ECV for clinical relevance as the only difference between partition coefficient and ECV is hematocrit correction.
Accuracy was defined as the closeness of a MOLLI measurement to a reference IR-SE value, which was represented by percent error between MOLLI and IR-SE in this study. High T1/ECV accuracy will be particularly important for low to moderate extracellular matrix expansion diseases such as aging , diabetes , and hypertension; compared to diseases with substantial expansion like cardiac amyloidosis . Different accuracy levels due to system differences will increase the inter-site variability and decrease the power of statistical comparison. Our data shows that IR-SE T1 values were different across scanners within the same field strength, validating our method of using scanner-specific IR-SE values to calculate accuracies. 17HB or 11HB protocol did not significantly affect either MOLLI T1 or partition coefficient values (p=0.177 for T1 vs. p=0.574 for partition coefficient). These results are consistent with previous reports on 1.5 and 3T scanners [8, 28]. Unlike MOLLI T1, partition coefficient accuracy was not dependent on field strength (p<0.0001 for T1 vs. p=0.109 for partition coefficient). Within the same field strength, MOLLI T1 values were significantly different across scanners (p<0.0001 for both 1.5T and 3T). However, partition coefficient had no significant difference among 1.5T scanners (p=0.13) and only had a very small difference among 3T scanners (49.2% vs. 49.8% vs. 50.0%, p=0.016).
Newer T1 mapping techniques, such as shortened modified look-locker inversion recovery (shMOLLI)  and saturation recovery sequences [30, 31], which are insensitive to heart rate variation were not available to us at the time of the study. ShMOLLI reduces acquisition time by using sequential inversion recovery measurements in a 5a+1a+1a sampling scheme each separated by only one R-R interval, which does not allow for full recovery of the magnetization for the three inversion pulses. Post-processing of images helps to correct for this problem by excluding data samples that fall outside accurate threshold. Saturation recovery sequences has demonstrated to have less T2 dependence and good agreement with IR-SE, as well as improved acquisition efficiency. As pre- and post-contrast T1 values are inherently different, an adaptive protocol (conditional sampling scheme) that optimizes for specific T1 ranges should improve accuracy. Preliminary data has shown subtle improvements of one such adaptive scheme over the standard MOLLI  with less variation at higher heart rates for 1.5T [9, 33]. In addition, latest MOLLI sequence has offered the flexibility of a fixed time pause in seconds instead of the traditional heartbeats between inversion recovery blocks. This improvement is important for proper magnetization recovery in subjects with fast heart rates, especially at 3T where the pre contrast T1 value is longer.
It is well know that considerable spatial variation in transmit field (B1) exists even at 1.5T and adiabatic pulses are used to reduce the sensitivity to B1 field inhomogeneity. Kellman and et al. demonstrated that a shorter tangent/hyperbolic pulse outperforms the traditional hyperbolic secant pulse with an improved inversion factor of 0.96 . This improved inversion efficiency translates directly into higher MOLLI T1 accuracy and meet the specific absorption rate requirement of both 1.5T and 3T. Future research should explore new T1 acquisition techniques to more accurately assess myocardial and blood pool T1.
Reproducibility or precision is defined as the degree of closeness to which repeated measurements show similar results, which was measured by relative mean percent error between MOLLI scan repetitions. High reproducibility/precision leads to greater reliability of observed changes for a given parameter and significant reduction in sample size needed, as sample size varies with the square of the reproducibility.
Liu et al. reported good ECV and partition coefficient reproducibility for a single center; however, a lack of ECV and partition coefficient reproducibility/precision data exists for multicenter studies . In this study, we demonstrated that although both MOLLI T1 and partition coefficient reproducibility were different across scanners and affected by field strength, they were not affected by heart rate (p=0.432 for T1 vs. p=0.375 for partition coefficient). When comparing partition coefficient to T1 values individually, partition coefficient had better precision than T1 for all vials, with only the “post-contrast blood” vial not showing a significant difference (p=.096 for “post-contrast blood” vial vs. p<0.05 for all others). Tighter limits of agreement for partition coefficient over MOLLI T1 for both 1.5T and 3T via Bland-Altman analysis further demonstrated better reproducibility of partition coefficient over T1 values. Thus, relative measures, such as partition coefficient, displayed its superiority to direct T1 quantification for reproducibility. This will translate directly to better power and smaller sample size requirement for ECV over T1 in multi-center studies .
Several limitations in this study existed. First, no in vivo human data was used for the study. As the purpose of this study was to validate the accuracy and reproducibility of the acquisition technique itself, phantoms provided the most reproducible tools to examine and optimize the various parameters. To test the accuracy and precision across multiple scanners in-vivo, serial contrast-enhanced CMR studies need to be performed on the same subjects within a short time interval on different scanners. Such testing is unlikely due to the risks associated with multiple injections of MR contrast agents within a short time frame. Measurement errors are expected to be higher in patients compared with phantoms because of increased errors associated with physiological variations in-vivo. Additionally, ECV, rather than partition coefficient, is appearing to be more useful in the detection of subtle abnormalities present in diffuse myocardial fibrosis due to the large variability in patient hematocrit data . As the only difference between partition coefficient and ECV is the hematocrit factor of roughly 0.4, the results in this study are easily translatable. Furthermore, only one time point post-contrast was chosen exemplarily. This coincides with most clinical protocols. Lastly, it is well known that T1 values could be affected by many factors, such as, room temperature . Relative, and not absolute, accuracy and reproducibility measurements were reported in this study. Accuracy measures were standardized with IR-SE T1 and precision measures compared two MOLLIs with one another under same technical condition. This approach negates the potential influence of temperature and many other factors that might affect the results of comparison across different scanners.