Purpose

Myocardial stiffness plays an important role in cardiac function. Increased stiffness in the myocardium can cause poor function and restrictive diastolic filling, which can lead to heart failure symptoms, even with a normal left ventricular (LV) ejection fraction (1). Myocardial infarcts can cause abnormal tissue stiffness that can affect LV wall stress and the pattern of LV remodeling (2). Shear wave elastography is an emerging imaging approach for measuring myocardial stiffness in vivo (3-10). Recently, a 3D high frequency cardiac MR elastography (MRE) technique, which has shown a high level of agreement with dynamic material testing (intra-class correlation coefficient up to 0.99) (11), has been shown to be feasible in normal volunteers (12). However, the feasibility of 3D high frequency cardiac MRE has not been evaluated in a patient cohort. Cardiac amyloidosis is an established disease of myocardial stiffening and this patient group is an excellent candidate for evaluating if elevated myocardial stiffness can be detected with MRE. The objective of this study is to evaluate if 3D high frequency cardiac MRE can measure increased myocardial stiffness in cardiac amyloidosis patients compared to healthy volunteers.

Methods

Twenty-two patients with cardiac amyloidosis and 16 healthy volunteers were enrolled after receiving institutional review board and written informed consent approval. All subjects underwent cardiac MRI/MRE and echocardiography with speckle tracking strain imaging Doppler evaluation of diastolic function. Patients with tissue diagnosis of amyloidosis and left ventricular maximal wall thickness of greater than 12 mm by echocardiography were classified as having cardiac amyloidosis. Cardiac MRE was used to quantitatively measure myocardial stiffness across the left ventricle of each subject. The experimental set up is shown in Figure 1. MRE Imaging was conducted at a vibration frequency of 140Hz using the same procedure as previously described (12). To establish a noise baseline, the MRE exam was repeated with the vibrational motion turned off (“no motion” scan) and the octahedral shear strain signal to noise ratio (OSS-SNR) (13) was calculated. An MRE exam was considered successful only if the mean OSS-SNR in the myocardium was at least two standard deviations above the median OSS-SNR of all no-motion scans (i.e. noise) across all subjects. Statistical analysis was done using a commercial software package (OriginPro 2015, OriginLab Corporation, Northampton, MA) that implemented a Mann-Whitney U test of significance (14). A p-value of less than 0.05 was considered statistically significant.

Results

The group-wise median OSS-SNR for the “no motion” scans was 0.96 and an OSS-SNR value of 1.17 (two standard deviations above the median) was used as a quantitative quality factor threshold to exclude MRE exams with poor image quality (Figure 2). The mean OSS-SNR of 6 patients and 5 volunteers fell below this threshold and thus these exams were excluded from the study. The LV myocardial stiffness of the 16 cardiac amyloid patients (median: 11.4 kPa, min: 9.2, max: 15.7), measured with cardiac MRE, was significantly higher (p < 0.01) than the LV myocardium of 11 normal healthy volunteers (median: 8.2 kPa, min: 7.2, max: 11.8) (Figure 3). Typical short-axis elastograms from the mid-section of the left ventricle in a healthy volunteer and an age- and sex-matched amyloidosis patient are shown in Figure 4A) and 4B), respectively. The MRE stiffness values for each cohort have been listed at the top of Table 2. MRI imaging demonstrated that patients with amyloidosis had significantly thicker diastolic and systolic left ventricular wall thickness, a greater LVEDVi and LV mass, and lower LVEF than normal healthy volunteers. Echocardiography showed that the amyloidosis group had significantly lower e’, increased E/e’ ratio, lower longitudinal and basal strain, and greater left atrial volume index than the healthy volunteer group. All bSSFP and echocardiography parameters have been listed in Table 1.

Discussion and Conclusions

This study demonstrates the feasibility of 3D high-frequency cardiac MRE as a contrast-agent-free diagnostic imaging technique for quantitatively measuring myocardial stiffness; validated in a cardiac amyloidosis patient cohort. The myocardial stiffness of cardiac amyloid patients (median: 11.4 kPa, min: 9.2, max: 15.7) was found to be significantly stiffer (p < 0.01) than healthy controls (median: 8.2 kPa, min: 7.2, max: 11.8). These results motivate future investigation of 3D high frequency cardiac MRE in different patient cohorts, in therapy monitoring studies, and future prognostic evaluation studies where myocardial stiffness measurements could play a potential role in early disease diagnosis and therapy monitoring.

Acknowledgements

This work was supported by National Institutes of Health (NIH) grants 5R01HL115144 and EB001981 and the Mayo Clinic Center for Individualized Medicine, Imaging Biomarker Discovery Program.

References

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