Cardiac Diffusion: Technique and Practical Applications
Corresponding Author
Sonia Nielles-Vallespin PhD
Cardiovascular MR Unit, Royal Brompton And Harefield NHS Foundation Trust, London, UK
NHLI, Imperial College of Science, Technology and Medicine, London, UK
Address reprint requests to: S.N.-V., CMR Unit, Royal Brompton Hospital, London SW3 6NP, UK. E-mail: [email protected] or [email protected]Search for more papers by this authorAndrew Scott PhD
Cardiovascular MR Unit, Royal Brompton And Harefield NHS Foundation Trust, London, UK
NHLI, Imperial College of Science, Technology and Medicine, London, UK
Search for more papers by this authorPedro Ferreira PhD
Cardiovascular MR Unit, Royal Brompton And Harefield NHS Foundation Trust, London, UK
NHLI, Imperial College of Science, Technology and Medicine, London, UK
Search for more papers by this authorZohya Khalique MD
Cardiovascular MR Unit, Royal Brompton And Harefield NHS Foundation Trust, London, UK
NHLI, Imperial College of Science, Technology and Medicine, London, UK
Search for more papers by this authorDudley Pennell MD
Cardiovascular MR Unit, Royal Brompton And Harefield NHS Foundation Trust, London, UK
NHLI, Imperial College of Science, Technology and Medicine, London, UK
Search for more papers by this authorDavid Firmin PhD
Cardiovascular MR Unit, Royal Brompton And Harefield NHS Foundation Trust, London, UK
NHLI, Imperial College of Science, Technology and Medicine, London, UK
Search for more papers by this authorCorresponding Author
Sonia Nielles-Vallespin PhD
Cardiovascular MR Unit, Royal Brompton And Harefield NHS Foundation Trust, London, UK
NHLI, Imperial College of Science, Technology and Medicine, London, UK
Address reprint requests to: S.N.-V., CMR Unit, Royal Brompton Hospital, London SW3 6NP, UK. E-mail: [email protected] or [email protected]Search for more papers by this authorAndrew Scott PhD
Cardiovascular MR Unit, Royal Brompton And Harefield NHS Foundation Trust, London, UK
NHLI, Imperial College of Science, Technology and Medicine, London, UK
Search for more papers by this authorPedro Ferreira PhD
Cardiovascular MR Unit, Royal Brompton And Harefield NHS Foundation Trust, London, UK
NHLI, Imperial College of Science, Technology and Medicine, London, UK
Search for more papers by this authorZohya Khalique MD
Cardiovascular MR Unit, Royal Brompton And Harefield NHS Foundation Trust, London, UK
NHLI, Imperial College of Science, Technology and Medicine, London, UK
Search for more papers by this authorDudley Pennell MD
Cardiovascular MR Unit, Royal Brompton And Harefield NHS Foundation Trust, London, UK
NHLI, Imperial College of Science, Technology and Medicine, London, UK
Search for more papers by this authorDavid Firmin PhD
Cardiovascular MR Unit, Royal Brompton And Harefield NHS Foundation Trust, London, UK
NHLI, Imperial College of Science, Technology and Medicine, London, UK
Search for more papers by this authorAbstract
The 3D microarchitecture of the cardiac muscle underlies the mechanical and electrical properties of the heart. Cardiomyocytes are arranged helically through the depth of the wall, and their shortening leads to macroscopic torsion, twist, and shortening during cardiac contraction. Furthermore, cardiomyocytes are organized in sheetlets separated by shear layers, which reorientate, slip, and shear during macroscopic left ventricle (LV) wall thickening. Cardiac diffusion provides a means for noninvasive interrogation of the 3D microarchitecture of the myocardium. The fundamental principle of MR diffusion is that an MRI signal is attenuated by the self-diffusion of water in the presence of large diffusion-encoding gradients. Since water molecules are constrained by the boundaries in biological tissue (cell membranes, collagen layers, etc.), depicting their diffusion behavior elucidates the shape of the myocardial microarchitecture they are embedded in. Cardiac diffusion therefore provides a noninvasive means to understand not only the dynamic changes in cardiac microstructure of healthy myocardium during cardiac contraction but also the pathophysiological changes in the presence of disease. This unique and innovative technology offers tremendous potential to enable improved clinical diagnosis through novel microstructural and functional assessment. in vivo cardiac diffusion methods are immediately translatable to patients, opening new avenues for diagnostic investigation and treatment evaluation in a range of clinically important cardiac pathologies. This review article describes the 3D microstructure of the LV, explains in vivo and ex vivo cardiac MR diffusion acquisition and postprocessing techniques, as well as clinical applications to date.
Level of Evidence: 1
Technical Efficacy: Stage 3
J. Magn. Reson. Imaging 2019. J. Magn. Reson. Imaging 2020;52:348–368.
Supporting Information
Filename | Description |
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jmri26912-sup-0001-FigureS1.tiffTIFF image, 563.8 KB | Supplementary Figure 1 Sketch of a helically twisted lazy tong mechanism. As the lazy tong shortens, which represents thinning of the wall in diastole (upper panel), the angle between its struts and the wall plane decreases. As it lengthens with wall thickening (lower panels), the angle increases. Thus the struts swivel from more parallel to the local wall plane in diastole to more perpendicular to it in systole. In this simplified mechanical model, the changes of orientation, from more vertical when the lazy tong shortens, towards more horizontal when the lazy tong extends, may be driven both by their own struts, as well as by those with opposed orientations further down the chain. Together they would result in longitudinal wall shortening, and also torsion of the ventricle (Reproduced with permission from Nielles-Vallespin S. et al. Journal of the American College of Cardiology Feb 2017, 69 (6) 661-676). |
jmri26912-sup-0002-FigureS2.tiffTIFF image, 1.4 MB | Supplementary Figure 2 Deviation of the expected MR signal in DWI from a mono-exponential model. At low b-values IVIM effects due to microscopic perfusion must be considered, while at high b-values kurtosis effects must be considered. |
jmri26912-sup-0003-FigureS3.tiffTIFF image, 4 MB | Supplementary Figure 3In vivo cDTI was acquired throughout the cardiac cycle in healthy swine, followed by in situ and ex vivo cDTI, then validated against corregistered histology. (A) Typical in vivo primary diffusion eigenvector angle (E1A) maps derived from cDTI at 6 time points in the cardiac cycle, and mean E1A against wall depth plots at systole and diastole for all in vivo experiments; inset illustrates E1 and E1A changes with LV wall depth. (B) Typical in situ E1A maps from cDTI after arrest by injection of KCl and BaCl2. See Online Video 2. (C) Typical ex vivo E1A maps at 3 mid-ventricular slices and E1A against wall depth plots in relaxed and contracted hearts. (D) Typical mid-layer wall-parallel histology sections showing circumferentially aligned cardiomyocytes that appear approximately horizontal on the images and expanded views, and their respective radial histograms measuring HA ~0°, with line plots of HA against wall depth derived from multiple wall parallel sections of all relaxed and contracted hearts (Reproduced with permission from Nielles-Vallespin S. et al. Journal of the American College of Cardiology Feb 2017, 69 (6) 661-676). |
jmri26912-sup-0004-FigureS4.tiffTIFF image, 4.9 MB | Supplementary Figure 4In vivo cDTI was acquired throughout the cardiac cycle in healthy swine, followed by in situ and ex vivo cDTI, then validated against corregistered histology. (A) In vivo secondary diffusion tensor eigenvector angle (E2A) maps are depicted at multiple points of the cardiac cycle, together with a plot of E2A throughout the entire cardiac cycle for all in vivo experiments. As the measured planes swivel from diastole to systole, E2A increases and their color changes from blue to red. (B) In situ and (C) ex vivo E2A maps depict relaxed and contracted hearts after injection of potassium chloride (KCl) and barium chloride (BaCl2). (D) Long-axis histological cuts with mesocardial layer details show sheetlets in relaxed and contracted heart tissue samples, with their corresponding angular histograms, demonstrating the sheetlet and cleavage plane reorientation. cDTI cardiac diffusion tensor magnetic resonance imaging (Reproduced with permission from Nielles-Vallespin S. et al. Journal of the American College of Cardiology Feb 2017, 69 (6) 661-676). |
jmri26912-sup-0005-VideoS1.mp4PDF document, 3.1 MB | Supplementary video 1 Example HA histology from epicardium to endocardium with corresponding radial histograms. 81 contiguous transmural slices with a slice gap of 100 micrometres (Reproduced with permission from Nielles-Vallespin S. et al. Journal of the American College of Cardiology Feb 2017, 69 (6) 661-676). |
jmri26912-sup-0006-VideoS2.mp4MPEG-4 video, 13.8 MB | Supplementary video 2 Animation depicting sheetlet tilt leading to LV wall thickening. Schematic diagram of myocardial sheetlet microstructures colour-coded according to the helix angle (HA) contracting and tilting from diastole to systole. The sheetlet angle (SA) is also shown, and it is defined as the angle between the sheetlet and the local epicardial LV wall. In this illustration, SA varies from a low value (SA~15°) in diastole (D) to a high value (SA~60°) in systole (H). This represents the microstructural dynamic basis of the longitudinal and circumferential wall shortening that together deliver proportional wall thickening far greater than that of any single cardiomyocyte (Reproduced with permission from Nielles-Vallespin S. et al. Journal of the American College of Cardiology Feb 2017, 69 (6) 661-676). |
jmri26912-sup-0007-VideoS3.movQuickTime video, 179.3 KB | Supplementary video 3 In STEAM acquisitions, despite the fact that the heart is in the same position when both diffusion encoding gradients are applied, the strain of the heart while the water molecules are diffusing modifies the distance diffused over one cardiac cycle from the values when the heart is static. The upper left panel shows the root mean square displacement of water molecules in 2D from a single initial start point in an isotropic medium without strain. The top right panel shows the effect of cyclical strain on diffusion within the same medium. The black box on the right is distorted according to the strain of the medium and the stretch (current length / initial length) of this box is plotted with normalised cycle time below. |
jmri26912-sup-0008-VideoS4.mp4MPEG-4 video, 10.2 MB | Supplementary video 4 A difference between STEAM and SE methods is in the time over which the diffusion of water molecules is measured. While water molecules diffuse for 1 cardiac cycle (~1s) and would diffuse a root mean square (RMS) distance of ~80μm in each direction in free water at 37°C in a STEAM sequence, the same water molecules would only diffuse ~10μm for MC-SE assuming a diffusion time of 30ms (although the gradient shape means that this time is not well-defined). During the longer STEAM Δ water molecules interact with more microstructural boundaries than with the MC-SE sequence. As a result, the measured mean diffusivity (MD) is reduced using the STEAM sequence and the fractional anisotropy (FA) is increased. The discrepancies between cDTI parameters obtained with STEAM and other sequences, should not, therefore be interpreted as artefactual, but as a reflection of the microstructure at the two different length scales. |
jmri26912-sup-0009-VideoS5.mp4MPEG-4 video, 335.5 KB | Supplementary video 5 Animation depicting sheetlet function is abnormal in DCM with altered systolic conformation (sheetlets appear to not be able to reorientate to achieve healthy systolic angles) and reduced mobility, contrasting with HCM, which demonstrates reduced mobility with altered diastolic conformation (sheetlets appear to not be able to reorientate sufficiently to achieve healthy diastolic angles). |
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