Synopsis

Cardiac MRF (cMRF) has recently emerged as a method of rapidly characterizing myocardial tissue. It has been shown to be robust to different and varying heart rates with high reproducibility in T₁ and T₂ regardless of the length and regularity of the cardiac cycle. While these techniques have been validated in healthy volunteers, patient studies have yet to be performed. Therefore, in this abstract, we present the first use of cMRF in a patient population - heart transplant recipients - and show initial results.

Introduction

Cardiac MRF (cMRF) has recently emerged as a method of rapidly characterizing myocardial tissue. It has been shown to be robust to different and varying heart rates (1) with high reproducibility in T₁ and T₂ regardless of the length and regularity of the cardiac cycle. While these techniques have been validated in healthy volunteers, patient studies have yet to be performed. Therefore we present the first use of cMRF in a patient population - heart transplant recipients - and show initial results.

In heart transplant patients, cardiac health is routinely diagnosed by histological assessment of endomyocardial biopsies, which can detect inflammation, fibrosis, and the associated myocyte damage (2). However, biopsy is invasive and localized to the apico-septal region of the heart, which results in low sensitivity and makes ongoing monitoring of rejection challenging. A more desirable approach would be to diagnose and characterize graft health non-invasively, such as with cardiac MRI. Myocardial T₁ has been shown to correlate with fibrosis (3), whereas T₂ correlates with edema, a hallmark sign of graft rejection. Some initial work has demonstrated the utility of cardiac MRI for transplant patients (4,5), though existing protocols are lengthy and still under development. Additionally, traditional cardiac parameter mapping techniques are sensitive to heart-rate variability and can suffer from low inter-scan reproducibility. Therefore, cMRF may provide a robust, easily repeatable, and non-invasive alternative for providing quantitative information about transplanted heart health.

Methods

Heart transplant recipients (n=13, age=53.1±13.7) and healthy controls (n=5, age=32.6±6.3) were recruited for this IRB-approved study. Endomyocardial biopsy was performed in all patients and acted as the gold standard measure of graft rejection. Both patients and controls were scanned with an ECG-triggered cMRF sequence (1) using a 48-fold undersampled spiral readout (NUFFT gridded), a 192x192 matrix, and a 300x300mm² FoV on a 3T clinical scanner (MAGNETOM Prisma, Siemens). Short-axis basal and medial slices were each acquired during a single-breathhold scan of 15 heartbeats, with 50 TRs/heartbeat. Flip angles varied between 4-25° with a 5.1ms TR. Five magnetization preparation modules were alternated prior to each heartbeat (Inversion Recovery=21ms, No Preparation, TE-T₂-Prep=30,50,80ms). For each subject, an MRF dictionary was simulated incorporating the scan-specific heart rate timings of each acquisition, and dot-product matching (6) was used to reconstruct T₁, T₂, and M₀ maps. The mean myocardial T₁ and T₂ were then recorded for each slice. In patients, this was repeated both pre- and post-contrast, though controls did not receive contrast injections. Commercial T₁ and T₂ mapping sequences (Myomaps, Siemens), based on MOLLI and T₂-Prepared bSSFP, were also used pre-contrast (and post-contrast for T₁ mapping). Pearson correlations between cMRF and Myomap were established, and Bland-Altman plots were generated to determine agreement between the sequences. An unpaired Student's t-test was also used to compare mean parameter measurements in both patients and controls.

Results

Cardiac MRF images were successfully acquired in all subjects. From a single breathhold, it was possible to reconstruct T₁, T₂, and M₀ maps from a short-axis slice acquisition (Figure 1). Whole slice T₁ measurements correlated well between cMRF and Myomap (pre-contrast: basal r=0.59, medial r=0.47; post contrast: basal r=0.87, medial r=0.86, and Bland-Altman analysis also demonstrated good agreement [pre-contrast: basal mean=-7.3ms (CI=±64.1ms), medial mean=-10.9ms (CI=±123ms); post contrast: basal mean=-1.3ms (CI=±95.6ms), medial mean=2.0ms (CI=±88.1ms )]. Likewise, T₂ measurements showed both good correlation (pre-contrast: basal r=0.40, medial r=0.73) and good Bland-Altman agreement [pre-contrast: basal mean=0.5ms (CI=±6.5ms), medial mean =1.9ms (CI=±6.9ms)]. T₁ and T₂ values were lower in controls than patients (Table 1), though this was not statistically significant in all cases.

In this study, histology indicated no graft rejection in any of the 13 patients. The range of myocardial T₂ values measured by cMRF (basal: 33.3-46.1ms; medial: 34.4-50.8ms) were nonetheless consistent with those previously reported in non-rejecting heart transplant recipients (3), demonstrating agreement with previous studies, and providing a range of myocardial T₁ and T₂ values for cMRF in non-rejecting heart transplants.

Discussion & Conclusion

This study shows the first use of cMRF in patients and demonstrates its feasibility in scanning heart transplant recipients. In a single breathhold, it was possible to obtain T₁, T₂, and M₀ maps, as compared to a routine clinical mapping technique (Myomap), which only yielded a single parameter per breathhold (e.g. T₁). Additionally, a range of cMRF-measured T₁ and T₂ values were measured for non-rejecting heart transplant recipients, which differed from those of healthy controls, providing a potential baseline for future comparisons to actual rejection. Interestingly, and perhaps due to motion correction or other filters, standard deviation in T₂ across patients was notably higher with cMRF than Myomap. Nonetheless, this work demonstrates the potential of cMRF to increase the available diagnostic information provided by MRI when ongoing monitoring of cardiac health is paramount.

Acknowledgements

This work was in part supported by the Swiss National Science Foundation grants #320030_143923, #326030_150828, #PZ00P3_154719, and #P2LAP3_164909; NIH grants R01HL094557 and R01DK098503; and Siemens Medical Solutions.Additional support was provided in part by the Centre d’Imagerie BioMedical (CIBM) of the UNIL, EPFL, UNIGE, CHUV, and HUG, as well as the Jeantet and Leenaards Foundations. We would also like to thank Dr. Jessica Bastiaansen for her aid with data collection.

References

1. Hamilton et al, Mag Res Med 77.

2. From et al, Mayo Clinic Proc. 86.

3. Ambale-Venkatesh et al, Nature Rev. Cardio. 12.

4. Van Heeswijk et al, JCMR 2014;16(S1):M11.

5. Butler et al, J. Heart & Lung Trans 34.

6. Ma et al, Nature 495.