Synopsis

Keywords: Myocardium, Ischemia, dobutamine

Myocardial T1 reactivity, defined as the relative T1 change from rest to stress, has been proposed as a marker for detection of ischemic heart disease. Commonly used MOLLI T1 mapping is sensitive to B0 field inhomogeneities and can have susceptibility/banding artifacts because of bSSFP readouts, especially at 3T. In this study, we investigated the feasibility of free-breathing SR-FLASH T1 mapping for ferumoxytol-enhanced (FE) dobutamine-stress T1 reactivity studies at 3T in preclinical settings. We showed the feasibility of using a widely available perfusion sequence for T1 reactivity studies under Ferumoxytol-enhancement.

Background

Myocardial T1 reactivity, defined as the myocardial T1 change in response to exercise or pharmacological stress relative to the baseline/resting T1 value, has been proposed as a novel marker for detection of ischemic heart disease.^1,2 In such studies, MOLLI-based T1 mapping is commonly used due to its high precision and wide availability across different scanner platforms.^3-5 MOLLI uses balanced steady-state (bSSFP) readouts and hence is sensitive to B0 field inhomogeneities which can result in susceptibility/banding artifacts, especially at 3T. Furthermore, in T1 reactivity patient studies which require either exercise or pharmacological stress, it may not be feasible to perform breath-hold scans. In such settings, free-breathing MOLLI scans will need to be performed which, due to the varying tissue/blood contrasts (across different inversion times), may lead to inaccurate T1 values as a result of imperfect registration. In this work, we propose a “single-point T1 mapping” approach using a saturation-recovery (SR) prepared FLASH (SR-FLASH) with a fixed SR time, which is the same pulse sequence as the one commonly used for first-pass myocardial perfusion MRI studies.⁶ Although SR-FLASH-based imaging has lower signal-to-noise ratio (SNR) than bSSFP-based T1 mapping techniques, this can be compensate for by (1) continuous acquisition of multiple frames to “average out” the noise in the image series, (2) SNR enhancement by administering a T1-reducing intravascular contrast agent such as ferumoxytol. In addition, the consistent contrast in SR-FLASH image series enables inline nonrigid motion correction to perform consistently in free-breathing settings. In this study, we investigated the feasibility of free-breathing SR-FLASH T1 mapping for ferumoxytol-enhanced (FE) dobutamine-stress T1 reactivity studies at 3T in a preclinical setting.

Methods

We conducted stress/rest FE studies on a clinical whole-body scanner (Siemens) at 3T in 6 healthy pigs under a wide range of dobutamine-induced stress heart rates (to mimic exercise stress). Data was acquired using both the established MOLLI-based T1 mapping approach and our proposed SR-FLASH-based T1 reactivity mapping. For SR-FLASH scans, we used a widely available perfusion sequence with following parameters: TE/TR = 1.08/1.97 ms, flip angle = 14o, SR time = 150 ms, matrix = 130x160 with GRAPPA factor = 2. We acquired 1 proton-density (PD) weighted and 28 T1-weighted images and used the “single-point T1 mapping” approach often used in quantitative perfusion techniques. ⁶ To validate our T1 quantification scheme, we conducted phantom studies with ferumoxytol-doped agar to compare vs MOLLI. In the pig studies, we manually segmented the myocardium (2 readers in consensus) avoiding partial volume effects, and performed the analysis on a “bull’s eye map” by dividing the myocardium into 12 angular and 3 radial subsectors. We evaluated the agreement between SR-FLASH and MOLLI in the anteroseptal sector as in-vivo validation for SR-FLASH. We then analyzed the agreement between neighboring subsectors in anterior wall (the region that is less prone to bSSFP-related artifacts) and the inferior wall (the region more sensitive to bSSFP-related artifacts) for both MOLLI and SR-FLASH maps.

Results

Our phantom studies showed excellent correlation between SR-FLASH and MOLLI T1 maps with R = 0.99 and p < 10-4 (Figure 1). MOLLI T1 values were 10% lower than SR-FLASH T1 values on average as expected because of MOLLI’s known T1 underestimation. Although free-breathing MOLLI at rest performed well, it occasionally failed at stress. SR-FLASH, on the other hand, was much more robust to very high heart rates (Figure 2). Moreover, even breathhold MOLLI scans were sensitive to susceptibility/banding artifacts in lateral wall (Figure 3). Fig 4 shows example MOLLI T1 maps for native rest and FE rest/stress scans in a representative animal. As highlighted with arrows, FE stress T1 values are lower than FE rest indicating increased myocardial blood volume during dobutamine stress. SR-FLASH and MOLLI T1 reactivities showed good correlation in the anteroseptal sector (R = 0.76, p<0.001). For comparison, the agreement between T1 reactivities obtained by 2 different sets of MOLLI scans were R = 0.85, which shows the natural variability in T1 reactivity studies. SR-FLASH and MOLLI T1 reactivities both performed well in terms of the agreement between neighboring subsectors in anterior wall (R = 0.75 and R = 0.83, respectively). However, SR-FLASH outperformed better MOLLI in terms of agreement between neighboring subsectors in the inferior wall (R = 0.76 vs R = 0.40). A representative case is shown in Fig 5, where MOLLI has a severe susceptibility/banding artifact in inferior/lateral wall whereas SR-FLASH is artifact-free in the same region.

Discussion/Conclusion

In this study, we showed the feasibility of using a widely available SR-prepared FLASH pulse sequence (typically used for myocardial perfusion imaging) to enable free-breathing FE T1 reactivity studies at high stress/rest heart rates. Our results demonstrated that the proposed SR-FLASH T1 reactivity mapping technique is robust to susceptibility/banding artifacts which can affect MOLLI especially in the as lateral and inferior sectors. Finally, since the image series acquired with SR-FLASH has a consistent tissue/bloodpool contrast, it is well suited for inline motion-correction which in turn enables rapid free-breathing T1 reactivity mapping in ferumoxytol-enhanced with exercise or pharmacological stress.

Acknowledgements

No acknowledgement found.