Cardiac Phase-Resolved T2* Magnetic Resonance Imaging Reveals Differences Between Normal Hearts and a Humanized Mouse Model of Hypertrophic Cardiomyopathy

Figures

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  Figure 1. Data acquisition and retrospective gated image reconstruction scheme used for cardiac phase-resolved, whole cardiac cycle T2* mapping of the mouse heart. Data acquisition framework: MRI data acquisition is performed continuously. Synchronization is achieved by recording the pulse-oximetry trace and the scanner’s TTL trigger signal. Following data collection, retrospective gating based on recorded signals is performed. Reconstruction framework: Each k-space line is assigned to the corresponding cardiac phase and then averaged to yield 10 cardiac phases, each with 7 echoes obtained for different echo times. T2* maps are generated via pixel-wise mono-exponential fitting of the T2* signal decay.

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  Figure 2. Summary of results obtained from the validation of temporal phase-resolved, retrospectively gated T2* mapping in a phantom study. To emulate the in vivo situation, a simulated heart rate was used. The T2* mapping performance was evaluated as a function of the heart period, the number of cardiac phases, and the number of repetitions (average). (A) Robustness of the proposed binning method against R-R interval length, mimicking the in vivo situation. (B) Effect of the number of cardiac phases with a total cardiac phase of one representing a static acquisition without binning, used as the reference. (C) The impact of averaging, showing that, as the number of repetitions increases, the T2* values converge toward the reference, particularly at 300 repetitions. Averaging is performed in the k-space domain. (D) The relationship between SNR and the number of averages for a representative vial with 0.75 µg ferumoxytol per ml of distilled water, illustrating that both the reference and retrospective gating methods exhibit similar SNR trends, though the binning approach results in slightly lower SNR values compared to the reference protocol. Abbreviations: Card Dur: cardiac duration, # of…

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  Figure 3. Validation of temporal phase-resolved T2* mapping for phantoms using ferumoxytol solutions to mimic myocardial T2* properties. (A) Qualitative comparison of T2* maps. An exemplary first echo image (TE = 1.5) of six iron concentrations reconstructed by the retrospective gating approach together with T2* maps of the phantom obtained from reference MGE and from a retrospective gating MGE sorted by a real pulse-oximetry signal recorded from a mouse. (B) The retrospective gating approach shows strong correlation with the reference method, as indicated by R2 ~ 1. The dotted line shows the identity line, while the solid line illustrates the linear regression fitting. The correlation was assessed using Pearson’s regression. (C) The Bland–Altman plot demonstrates a good agreement between the reference and the retrospective gating approach. Each colored circle represents a different ferumoxytol concentration. The dashed lines indicate a confidence level of 95%, while the continuous lines depict the average percentage variances.

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  Figure 4. Characterization of the mice cohort using in vivo cardiac MRI shows severe cardiac dysfunction in the HCM (Mybpc3-KI) mice. Top: Mice cohort included the Mybpc3-KI mice (male: n = 3, female: n = 3) that were compared to the WT mice (male: n = 3, female: n = 3). (A) LV mass normalized to body weight showing significant increase in the Mybpc3-KI mice compared to the WT mice. (B,C) LV mass comparison at both end systole (ES) and end diastole (ED) demonstrates severe hypertrophy in the Mybpc3-KI mice compared to the WT mice. (D) Cardiac chamber quantification and functional assessments, including left ventricular ejection fraction (LVEF), were conducted on a slice-by-slice basis using manually segmented endo- and epi-cardiac borders in end-systole and end-diastole obtained from short-axis 2D CINE images. LVEF assessment reveals a significant decrease in the Mybpc3-KI mice compared to the WT groups. (E,F) Higher ES and ED volumes in the Mybpc3-KI mice indicates reduced cardiac contractility and possible ventricular dilation. All data are presented as a mean ± standard error of the mean. Due to the relatively small sample size in this study, a non-parametric Mann–Whitney U test was…

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  Figure 5. In vivo myocardial T2* measurement covering the whole cardiac cycle in WT and in HCM mice. (A) Representative T2* maps superimposed to anatomic images obtained for 10 cardiac phases for a male WT control mouse (top) and a male Mybpc3-KI mouse (bottom) with yellow arrows showing regions of increased T2*. (B) Comparison of T2* between the WT controls and the Mybpc3-KI HCM mice reveals elevated T2* values in the HCM mice across all cardiac phases (P1-P10, n = 6 mice for each group). (C) Mean myocardial T2*, averaged over the cardiac cycle for each mouse is significantly higher in the HCM mice compared to controls (n = 6, 3 females). Mann–Whitney U test was used to compare differences in variable between the HCM and the control groups. ** p < 0.01. Abbreviations: KI: Mybpc3-KI; WT: wild type.

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  Figure 6. Correlation analysis reveals significant relationships between LV mass and T2* in the Mybpc3-KI HCM mice. (A) A very strong, significant correlation was observed between T2* and LV mass in the Mybpc3-KI HCM mice (red ), while no significant correlation was found in the Mybpc3-WT mice (blue ). (B) No significant correlation was detected between the T2* and the LV ejection fraction in either group. Associations were assessed using Spearman’s rank correlation coefficient (ρ), and were considered significant at p < 0.05. Abbreviations: LV: left ventricle; KI: Mybpc3-KI; WT: wild type.