Introduction

Myocardial tissue characterization including quantification of fibrosis and oedema plays an important role in the evaluation of many myocardial diseases¹. T₁ mapping has proven to be a valuable tool to assess acute ischemic injury or amyloidosis among other diseases, while T₂ mapping has shown value for assessing inflammation^2,3. T₁ and T₂ maps are typically acquired sequentially in 2D under several breath-holds^2,4. However, misregistration artifacts, low through-plane spatial resolution and incomplete myocardial coverage remain limitations. To address this, a high resolution, motion-compensated joint T₁/T₂ water/fat sequence has been recently proposed and validated in phantom and healthy subjects5. In this study, we demonstrate the feasibility of the proposed approach to obtain whole-heart, motion-compensated, simultaneously acquired, and co-registered T₁, T₂ maps as well as water and fat images in ~9min in patients with cardiovascular disease.

Methods

The joint T₁/T₂ prototype sequence³ (Fig. 1) consists of four interleaved, ECG-triggered spoiled gradient-echo 3D volumes with 2-point bipolar Dixon encoding acquired with a 4x-undersampled Variable Density Cartesian trajectory⁴. The first and fourth volume were preceded by an inversion recovery (TI=120ms) pulse and a T₂-preparation pulse (T₂prep duration=50ms) respectively, whereas no magnetization preparation pulses were applied prior to the second and third volume. Non-rigid motion corrected reconstruction was applied to each in- and out-of-phase volume, employing multi-contrast patch-based higher-order low-rank regularization⁵. A water-fat separation algorithm⁶ was then applied, and water image signal evolution across the four volumes was obtained voxel-wise. A patient-specific dictionary of pre-calculated T₁/T₂ combinations was simulated using Extended-Phase-Graph (EPG⁷) simulations and matched against the measured water image signal evolution. Thirty-four adult participants with suspected cardiovascular disease (n=34; 11 female; mean age=53±12y, body mass index=28.4±5.9kg/m²) were scanned on a 1.5T scanner (MAGNETOM Aera, Siemens Healthcare, Erlangen Germany). Acquisition parameters included FA=8˚, 2 mm³ isotropic resolution, subject specific mid-diastolic trigger-delay and acquisition window of ~100ms, TR=6.67ms, TE1/TE2=2.38/4.76ms, total scan time=~9min. Multi-slice pre- and post-contrast T₁-MOLLI and T₂-bSSFP maps, as well as Late Gadolinium Enhanced (LGE) images were acquired in a short axis (SA) orientation at the apical, mid-cavity and basal levels for comparison and as part of clinical routine. The 3D whole-heart co-registered T₁/T₂ maps were segmented in SA orientation. Subsequently, multi-slice AHA 16-segment⁸ bullseye plots were generated and a quantitative comparison between joint T₁/T₂ maps and their respective reference scans was performed at basal, mid-ventricular and apical levels. The 17th apical segment was excluded from all analyses due to expected high variability. Image quality and diagnostic confidence of joint T₁/T₂ maps against reference maps were evaluated by two expert readers using a 4-point Likert scoring scale ranging from 1 (uninterpretable maps / no diagnostic confidence) to 4 (neglectable blurring or residual artifacts / full diagnostic confidence) for image quality / diagnostic confidence respectively. In addition, an in vivo reproducibility study was carried out on three healthy subjects (n=3; 2 female, mean age = 31±2 years) throughout two different sessions (mean interval = 780 ± 15 days) to assess inter-session reproducibility. Each subject underwent two consecutive scans during the second session to assess intra-session reproducibility. The corresponding quantitative analysis was performed segment-wise.

Results

Short-axis motion-corrected joint T₁/T₂ maps, with their corresponding reference maps, along with LGE images in short-axis orientation, are shown in Fig. 2 for a representative patient presenting with an acute myocardial infraction in the right coronary artery (RCA) territory. Increased myocardial T₁ and T₂ values in the basal to mid-inferoseptum and inferior wall, extending to the apical inferior wall are observed in the proposed joint T₁/T₂ maps and confirmed by the reference parametric maps in the slices available, plus a near transmural sub-endocardial enhancement of the basal to mid-inferoseptum and inferior wall in the LGE scan. The extension of the abnormal T₁ values is better perceived in the proposed whole-heart T₁ map, compared to the single-slice T₁-MOLLI scan available only at mid-ventricular level. Fig. 3 shows T₁ and T₂ quantification from proposed joint T₁/T₂ maps and their reference maps for each subject of the clinical study. Quantification was performed over all available slices for each AHA segment that correspond to mid-ventricular level (i.e., segments 7-12). Image quality and diagnostic confidence (Fig. 4) show similar scores for the proposed and reference methods. Reproducibility study (Fig. 5) show an inter-session variability of 5.1±3.7 % and 5.2±3.4% for T₁ and T₂ respectively and intra-session variability of 6.0±4.3 % and 5.3±3.6 % for T₁ and T₂ respectively.

Discussion and Conclusions

The proposed free-breathing motion corrected 3D joint T₁/T₂ sequence allows the acquisition of isotropic T₁and T₂ maps and complementary co-registered water and fat visualization in a single scan with a total scan time of ~9 min. The technique has been validated in patients presenting with diverse cardiovascular diseases with low inter-session and intra-session variances demonstrating its potential to identify T₁ and T₂ alterations associated with cardiovascular diseases that might be otherwise missed through incomplete coverage by the multi-slice alternatives currently present in the clinical routine.

Acknowledgements

This work was supported by the following grants: EPSRC 1) EP/P032311/1; 2) EP/P007619/1; 3) EP/P001009/1; 4) EP/V044087/1; the Wellcome/EPSRC Centre for Medical Engineering (WT 203148/Z/16/Z), and Fondecyt 1210637. This research was supported by the Department of Health through the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust and by the NIHR MedTech Co-operative for Cardiovascular Disease at Guy’s and St Thomas’ NHS Foundation Trust.