Myocardial Strain Imaging: PDF

JACC: CARDIOVASCULAR IMAGING VOL. -, NO. -, 2024 ª 2024 THE AUTHORS. PUBLISHED BY ELSEVIER ON BEHALF OF THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION. THIS IS AN OPEN ACCESS ARTICLE UNDER THE CC BY LIC...

JACC: CARDIOVASCULAR IMAGING VOL. -, NO. -, 2024 ª 2024 THE AUTHORS. PUBLISHED BY ELSEVIER ON BEHALF OF THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION. THIS IS AN OPEN ACCESS ARTICLE UNDER THE CC BY LICENSE (http://creativecommons.org/licenses/by/4.0/). STATE-OF-THE-ART REVIEW Myocardial Strain Imaging Theory, Current Practice, and the Future Otto A. Smiseth, MD, PHD,a Oliver Rider, BA, BMBCH, DPHIL,b Marta Cvijic, MD, PHD,c,d Ladislav Valkovi c, PHD,b,e Espen W. Remme, MSC, PHD,a,f Jens-Uwe Voigt, MD, PHDg,h ABSTRACT Myocardial strain imaging by echocardiography or cardiac magnetic resonance (CMR) is a powerful method to diagnose cardiac disease. Strain imaging provides measures of myocardial shortening, thickening, and lengthening and can be applied to any cardiac chamber. Left ventricular (LV) global longitudinal strain by speckle-tracking echocardiography is the most widely used clinical strain parameter. Several CMR-based modalities are available and are ready to be imple- mented clinically. Clinical applications of strain include global longitudinal strain as a more sensitive method than ejection fraction for diagnosing mild systolic dysfunction. This applies to patients suspected of having heart failure with normal LV ejection fraction, to early systolic dysfunction in valvular disease, and when monitoring myocardial function during cancer chemotherapy. Segmental LV strain maps provide diagnostic clues in specific cardiomyopathies, when evaluating LV dyssynchrony and ischemic dysfunction. Strain imaging is a promising modality to quantify right ventricular function. Left atrial strain may be used to evaluate LV diastolic function and filling pressure. (JACC Cardiovasc Imaging. 2024;-:-–-) © 2024 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). S train is a term that originates from the field of continuum mechanics and may be used to describe deformations of including the heart. In cardiac imaging, the term any structure, circumferential shortening strains and radial thick- ening strain. Both longitudinal and circumferential strains contribute to LV wall thickening. In addition to these orthogonal normal strains, a complete char- strain is used to describe myocardial shortening and acterization of LV deformation includes 3 shear thickening, which are the fundamental features of strains that are less commonly measured: myocardial fiber function. Figure 1A illustrates the circumferential-longitudinal shear, or so-called twist, most commonly measured myocardial strains. These results from 2 short-axis planes rotating relative to include left ventricular (LV) longitudinal and each other, as illustrated in Figure 1B; a From the Institute for Surgical Research, Division of Cardiovascular and Pulmonary Diseases, Oslo University Hospital, b Rikshospitalet, and University of Oslo, Oslo, Norway; Oxford Centre for Clinical Magnetic Resonance Research, RDM Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom; cDepartment of Cardiology, University Medical Centre d Ljubljana, Ljubljana, Slovenia; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; eDepartment of Imaging Methods, Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia; fThe Intervention Center, Oslo g University Hospital, Rikshospitalet, Oslo, Norway; Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium; and the hDepartment of Cardiovascular Sciences, KU Leuven–University of Leuven, Leuven, Belgium. The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center. Manuscript received February 27, 2024; revised manuscript received July 1, 2024, accepted July 3, 2024. ISSN 1936-878X https://doi.org/10.1016/j.jcmg.2024.07.011 2 Smiseth et al JACC: CARDIOVASCULAR IMAGING, VOL. -, NO. -, 2024 Myocardial Strain Imaging: Theory, Practice, and Future - 2024:-–- ABBREVIATIONS circumferential-radial shear can be described used today. When strain based on the Eulerian (εE ) AND ACRONYMS as the subendocardium is rotating more or and Lagrangian approach (εL) are expressed as less than the epicardium; and radial- fractions, they are related as εE ¼ ln(1 þ εL), where 2D = 2-dimensional longitudinal shear involves the subendocar- ln is the natural logarithm. 3D = 3-dimensional dium is moving more or less longitudinally Strain imaging provides complementary informa- CMR = cardiac magnetic than the epicardium. tion to LV ejection fraction (LVEF), as it allows the resonance When calculating myocardial strain, it is quantification of segmental as well as global func- EF = ejection fraction most common to use a Lagrangian descrip- tion and can be used to assess both systolic and FT = feature tracking tion that uses the end-diastolic length as a diastolic function. Whereas myocardial strain imag- GLS = global longitudinal reference (L0 and T 0 in Figure 1) and ex- ing has traditionally been applied to study the LV, it strain presses the change in length as a percent- is currently implemented also as a tool for the LA = left atrial/atrium age of this reference length. A Eulerian quantification of right ventricular (RV) and left atrial LV = left ventricle/ventricular description uses the deformed configuration (LA) function. In this paper we review the theory LVEF = left ventricular ejection as a reference. Historically, this was the behind strain as a measure of myocardial function, fraction first type of strain that was introduced in current clinical applications of strain imaging, and ROI = region of interest echocardiographic software, as it was prospects for the technology. The Central Illustration RV = right ventricle/ventricular calculated by integrating strain rate from summarizes the current strain technologies and STE = speckle-tracking tissue velocity measurements, but it is less applications. echocardiography F I G U R E 1 Definition of Myocardial Strain A Myocardium B - Strain is a measure of deformation Relaxed Contracted - In addition to shortening along its main calculated as relative(%) change in axis (normal strains), the left ventricle length (Lagrangian strain). undergoes torsional deformation, measured Shortening and as shear strain in degrees (°) or radians. - Strain imaging is used clinically to measure myocardial shortening thickening and thickening. Shear Strain Circumferential-longitudinal shear strain Myocardial Shortening Myocardial Thickening Longitudinal Circumferential Radial Measured clinically as LV twist, calculated as difference strain strain strain between rotations at apex and base LV base LV Shear strain LV LV LV apex Percentage Thickening = (T-T0)/T0 Percentage End-systole Shortening = (L-L0)/L0 Rotation (°) Rotation (°) Apical End-systole (T) + End-diastole (L0) + 0 0 0 Strain (%) Strain (%) Basal – – End-systole ECG End-systole (L) 0 End-diastole (T0) Time ECG ECG Time Time Myocardial strain imaging quantifies cardiac deformation. (A) The most widely used left ventricular (LV) strain measures are myocardial shortening in the longitudinal and circumferential directions and thickening in the radial direction (normal strains). (B) Illustration of LV circumferential-longitudinal shear or so-called twist, calculated as the difference between rotations at the apex and base. ECG ¼ electrocardiogram. JACC: CARDIOVASCULAR IMAGING, VOL. -, NO. -, 2024 Smiseth et al 3 - 2024:-–- Myocardial Strain Imaging: Theory, Practice, and Future C ENTR AL I LL U STRA T I O N Strain Imaging: Technologies and Clinical Applications Technologies y Ma ph gn ra et og ic di Speckle tracking Feature tracking r es r ca on ho an Ec ce Strain G L S is a s e n LV global Shortening Thickening er of Left atrial strain HFpEF, longitudinal strain mark Strain (%) Strain (%) 30 0 sit i v valv itive e pa GLS ular ens Reservoir strain ram e an g p is a s dis 0 e −20 ECG sur ECG LV segmental strains eas et e d d res in ro tra f s ring ir s lin ys vo to ch u fil r lic dy se LV re em sfu ri al ot ncti at he o ft ra n in Le py Asymetric septal HCM Amyloidosis Segm ental strain ntify maps can ide specific cardiomyopathies Clinica l applications Smiseth OA, et al. JACC Cardiovasc Imaging. 2024;-(-):-–-. GLS ¼ global longitudinal strain; HCM ¼ hypertrophic cardiomyopathy; HFpEF ¼ heart failure with preserved ejection fraction; LA ¼ left atrium; LV ¼ left ventricle/ventricular; RV ¼ right ventricle. MYOCARDIAL STRAIN: HISTORY OF derive the deformations.2 Myocardial strain imaging THE TECHNOLOGY as a clinical modality is rooted in cardiac magnetic resonance (CMR). The earliest CMR methods used The quantification of myocardial deformation has radiofrequency pulses and multiple saturation been available for a long time in cardiac physiology planes, which resulted in distinct lines in the using implanted ultrasonic dimension crystals 1 myocardium that could be used as a means of tissue (Figure 2) or radiopaque markers implanted in a grid tagging, as they follow myocardial deformation pattern so their 3-dimensional (3D) movement could throughout the cardiac cycle.3 By the late 1980s, this be tracked by high-speed biplane cineradiography to had been refined to produce a 3D grid of tags known 4 Smiseth et al JACC: CARDIOVASCULAR IMAGING, VOL. -, NO. -, 2024 Myocardial Strain Imaging: Theory, Practice, and Future - 2024:-–- F I G U R E 2 History of Myocardial Strain Technologies A Sonomicrometry D LV Pressure Speckle Tracking Echocardiography mm Hg 100 4CH Strain by Implanted 0 AVC Ultrasonic Crystals 0 Myocardial Thickness Strain (%) 12.2 —11.1 mm 11.4 —22.2 Myocardial Length SL 9.3 mm 0 Time (s) 1 % 10.3 Clinical method for measuring myocardial shortening, thickening and torsion. Experimental reference method for myocardial shortening and thickening. B CMR Tissue Tagging E CMR Feature Tracking 0 B Strain (%) A —20 Clinical reference method for myocardial shortening, Clinical method for measuring myocardial shortening. thickening and torsion. C Tissue Doppler Echocardiography F DENSE Imaging CMR Longitudinal strain 0.05 0.00 —0.05 EII —0.10 —0.15 —0.20 0 20 40 Cardiac Frame Clinical method for measuring myocardial shortening. Novel clinical method using measurement ot tissue displacement to calculate strain. Graphical illustration of the history of strain imaging. (A) Data from an experimental study in which sonomicrometry was used to measure myocardial percentage shortening and thickening. Adapted with permission from Bugge-Asperheim et al.1 (B) Illustration of left ventricular (LV) strain measured by cardiac magnetic resonance (CMR) with tissue tagging. Adapted under CC BY-NC-ND 4.0 license from Shehata et al.234 (C) Illustration of LV strain measured using tissue Doppler echocardiography. (D) Illustration of LV strain measured using speckle-tracking echocardiography. (E) Illustration of strain by CMR feature tracking. Adapted under CC BY 4.0 license from Backhaus et al.235 (F) Displacement encoding with stimulated echoes (DENSE) imaging CMR is an emerging clinical method for strain measurement. Adapted under CC BY-NC-ND 4.0 license from Auger et al.236 4CH ¼ 4-chamber view; AVC ¼ aortic valve closure. as spatial modulation of magnetization, 4 and it was hypertrophied myocardium.4,6,7 This method, which 5 applied to interrogate myocardial velocities in 1991. is primarily a research tool, is considered the clinical This method enabled characterizations of segmental gold standard for the validation of new strain strains in both healthy and diseased myocardium, methods such as those based on echocardiography. with early studies focusing mainly on the infarcted or Contemporaneously with the development of spatial JACC: CARDIOVASCULAR IMAGING, VOL. -, NO. -, 2024 Smiseth et al 5 - 2024:-–- Myocardial Strain Imaging: Theory, Practice, and Future STE has also been applied to 3D data sets, theo- F I G U R E 3 Strain by Myocardial Tissue Tagging retically overcoming the problem of through-plane motion of 2D speckle tracking and allows a compre- hensive description of the deformation of the entire ventricle. Nevertheless, challenging data acquisition as well as the lower temporal and spatial resolution of 3D STE limit its clinical use. Interestingly, a recent study showed that the analysis of myocardial deformation is also feasible on time-resolved 3D cardiac computed tomographic im- ages.17 The method is based on the calculations of global strain based entirely on the 3D displacement of the segmental myocardial volumes over the cardiac cycle using a deformable image registration–based tracking approach. The proposed method was re- ported to allow automatic and robust tracking of the LV myocardium using clinical computed tomographic image sequences, but data on clinical applications are still lacking. Tagged Image METHODOLOGY: CMR Image showing myocardial tagging: a grid of dark tag lines applied across a short-axis image. A wide range of CMR methods are available to assess myocardial strain. These methods offer various ap- proaches to quantify strain, enabling clinicians and researchers to comprehensively analyze cardiac me- modulation of magnetization tagging methods, CMR chanics. Brief descriptions of the main approaches tissue phase velocity mapping methods for strain 8 (myocardial tagging and FT) are provided in the imaging also surfaced. This technique in general has following sections, with the main focus on imaging of not been adopted widely, because of lower temporal the LV. More detailed information can be found resolution. This was overcome by the development of elsewhere. 18,19 navigated high–temporal resolution sequences by 2006, 9 but long acquisition times have limited its use. MYOCARDIAL TAGGING. With this method, perturb- Strain rate and strain by echocardiography were ing the magnetization with radiofrequency saturation first introduced as a 1-dimensional tissue Doppler pulses creates a grid of visible markers (“tags”) in the imaging–based method. 10,11 For routine clinical use, tissue (Figure 3). Myocardial strain is measured by this method was later superseded by 2-dimensional tracking these markers during the cardiac cycle (2D) speckle-tracking echocardiography (STE), which (Video 1). Tags are typically applied at end-diastole, provides multidirectional strains. 12-15 Currently, with imaging being performed across the whole car- strain by STE is the most commonly used method. diac cycle. At lower heart rates, the tags can fade The next phase of CMR strain imaging built on this during early diastole, which limits diastolic func- echocardiography approach, which was applied to tional assessment. Higher field strength 3-T magnets standard CMR cine images as feature tracking (FT). can result in longer tag duration throughout the car- Despite greater variability and some discrepancy from diac cycle. the earlier “gold standard” tagging methods, as a CMR TAGGING SEQUENCES. All CMR tagging se- result of the simplicity of postprocessing of standard quences consist of 2 main parts, the tagging part and cine images FT CMR is now the dominant strain the image acquisition part. It is the differences in how method used by the CMR community. More recently, tagging and data acquisition are performed that make other methods have emerged, including 3D FT and each of the techniques unique. techniques such as displacement encoding with The simplest and most commonly used method for stimulated echoes and strain-encoded magnetic tagging is called spatial modulation of magnetization. resonance imaging. The latter has superior spatial Its tagging part consists of 2 nonselective radio- and temporal resolution compared with tagging16 and frequency pulses (usually 90 ), separated by a tagging affords the opportunity of real-time imaging. gradient (Figure 4). After the first pulse, the tagging 6 Smiseth et al JACC: CARDIOVASCULAR IMAGING, VOL. -, NO. -, 2024 Myocardial Strain Imaging: Theory, Practice, and Future - 2024:-–- technique, which uses a stimulated echo acquisition F I G U R E 4 A Representative Tagging Sequence mode sequence for tagging (Figure 5). Stimulated 90° 90° echo acquisition mode consists of 3 90  pulses to generate a stimulated echo. Equal-magnitude displacement encoding (modulation) and decoding RF (demodulation) gradients are added after the first and third pulses of the stimulated echo acquisition mode Tag sequence, respectively. To eliminate any remaining Data Acquisition transverse magnetization, crusher gradients are Gradient applied during the mixing period in between modu- Crusher lation and demodulation. Similar to spatial modula- tion of magnetization, the acquisition part uses conventional imaging readout. Displacement encod- RF ¼ radiofrequency pulse. ing with stimulated echoes provides higher spatial resolution and uses pixel-by-pixel displacement, making it possible to draw representative displace- ment vectors, with vector magnitude and direction gradient disperses the excited spins, creating a mod- representing the displacement value and orientation. ulation on the basis of incremental phase shifts. The Figure 6 shows an example of displacement encoding second pulse then stores the modulated spins in the with stimulated echoes imaging CMR. longitudinal plane, and a spoiler gradient is then Another example of advanced tagging sequence is applied to remove any remaining transverse magne- strain-encoded imaging, which uses similar tagging tization. Spatial modulation of magnetization uses part as spatial modulation of magnetization, but in conventional data acquisition for imaging. this case, the tagging gradients are applied parallel to More advanced CMR tagging techniques use a and inside the imaging plane to capture through- combination of modulation and demodulation gradi- plane strain (Figure 7). During the imaging part of ents to better store strain information. One example strain-encoded magnetic resonance imaging, further is the displacement encoding with stimulated echoes demodulation (tuning) gradients are applied between the section selection and data readout gradients to reduce scan time. Two sets of demodulated images are ultimately acquired. The low-tuning images rep- F I G U R E 5 A Representative Displacement Encoding With Stimulated Echoes Sequence resents static tissue, and the high-tuning images 3 represent contracting tissue, exhibiting a high mod- 1 2 ulation frequency caused by tissue contraction. By TE/2 TM TE/2 comparing the image pixel by pixel and comparing RF the low-tuning and high-tuning images, myocardial strain can be quantified into a strain map. modulation demodulation Another CMR tagging technique is called tissue X gradient phase mapping. It uses velocity-encoded bipolar Crusher gradients to encode the tissue velocity in the phase of Data Acquisition the signal. This allows the calculation of the velocities of different points within the myocardium. Myocar- Y gradient dial velocities are then integrated in 3 directions (and over time) to show myocardial displacement and allow the evaluation of regional strains in the longi- tudinal, circumferential, and radial directions. As this Z gradient method involves long imaging times, which can result in motion artifacts, strain derivation is thus poten- tially less accurate, and 3D velocity data are typically reported rather than the strain (Figure 8). The time between the first and second radiofrequency pulses (RFs; a1 and a2) is equal to the time between the third RF pulse (a3) and data acquisition (echo time [TE]/2). FT. CMR FT is a postprocessing method for quanti- TM ¼ mixing time. fying tissue deformation that uses routinely acquired contrast-free CMR cine images (Figure 9). It is based JACC: CARDIOVASCULAR IMAGING, VOL. -, NO. -, 2024 Smiseth et al 7 - 2024:-–- Myocardial Strain Imaging: Theory, Practice, and Future F I G U R E 6 CMR Displacement Encoding With Stimulated Echoes Imaging Magnitude & Phase Displacement Strain Map D Strain Time Curves 0.05 0.00 —0.05 Ecc —0.10 —0.15 0.2 —0.20 —0.25 0 20 40 Cardiac Frame A B C Ant. Septum Inferior Ant. Lateral Inf. Septum Inf. Lateral Anterior H 0.05 0.00 —0.05 Ecc —0.10 —0.15 —0.20 E F G —0.25 0 20 40 0 Cardiac Frame L 0.05 0.00 —0.05 EII —0.10 —0.15 I J K —0.20 0 20 40 Cardiac Frame P 0.05 0.00 —0.05 EII —0.10 —0.2 —0.15 M N O —0.20 0 20 40 Cardiac Frame Reproduced with permission under CC BY-NC-ND 4.0 license from Auger et al.236 Ant. ¼ anterior; Inf. ¼ inferior; other abbreviation as in Figure 2. on tracking small image features (eg, details of the images (Figure 9). In the following step, the software endocardial contour) from frame to frame. Combining detects and tracks features and produces a 2D strain information on the direction and magnitude of the map. Myocardial deformation can then be visualized displacement of several features makes it possible to through graphical markers on the image or quantified calculate tissue deformation in all directions within via strain curves. Three-dimensional data sets allow the image plane. When considering frame rate in the simultaneous estimation of radial, circumferen- addition, the method provides information on veloc- tial, and longitudinal strain parameters. ity and strain rate. FT CMR requires high-quality im- age acquisition with adequate temporal and spatial METHODOLOGY: ECHOCARDIOGRAPHY resolution. FT postprocessing begins with defining a region of TISSUE DOPPLER vs SPECKLE TRACKING. interest (ROI), usually comprising the endocardial Echocardiography is currently the method of and epicardial borders on short- or long-axis cine choice for strain assessment in clinical practice. 8 Smiseth et al JACC: CARDIOVASCULAR IMAGING, VOL. -, NO. -, 2024 Myocardial Strain Imaging: Theory, Practice, and Future - 2024:-–- F I G U R E 7 A Representative Strain-Encoding Sequence Modulation Imaging 90° 90° Ramped slice selective RF pulses RF Modulation High Tuning Z gradient Crusher Low Tuning Data acquisition X/Y gradient RF ¼ radiofrequency pulse. Measurements of strain are obtained by STE using analysis in multiple directions and image planes dedicated speckle-tracking software during post- is required. Nevertheless, tissue Doppler imaging processing of regular image loops. Strain based on enables higher temporal resolution than STE, tissue Doppler imaging is also feasible in clinical allows a more reliable assessment of strain rate and a settings but is not widely used, as it requires dedi- better recognition of short-lived events, and can be cated acquisitions, is dependent on the angle of faster for a focal analysis of a certain myocardial insonation, and is more time consuming when region. F I G U R E 8 CMR Tissue Phase Mapping A B C 5.0 5 vr [cm/s] i 0 Vr [cm/s] i −5 −5.0 2 v [cm/s] 0 −2 ii 5 vz [cm/s] ii 0 −5 0 118 236 354 472 590 708 826 (A) Magnitude (i) and phase (ii) images from the tissue phase mapping sequence. (B) Velocity (i) and displacement (ii) maps. (C) Velocity maps in the radial, circumferential, and longitudinal directions obtained. V ¼ velocity; other abbreviation as in Figure 2. JACC: CARDIOVASCULAR IMAGING, VOL. -, NO. -, 2024 Smiseth et al 9 - 2024:-–- Myocardial Strain Imaging: Theory, Practice, and Future F I G U R E 9 CMR Feature Tracking: Circumferential Strain Myocardial Point Feature Tracking Diastole Systole Colour coded strain maps The top panels show the feature points that are tracked, and the bottom panels show resultant displacement by colored strain maps (below) across the cardiac cycle. Abbreviation as in Figure 2. STE is based on tracking bright and dark dots found in direct comparisons of STE and CMR FT (“speckles”) in the myocardium. Speckles do not (Table 1).22 represent tissue structure but represent interference Reliable and meaningful tracking requires an patterns that have been shown to move together with appropriate placement of the ROI and enough track- the tissue for a limited time and distance so that they able features within it. Tracking is performed by some can be used as features for tracking.20,21 In contrast, software solutions by using a relatively thin ROI in CMR FT tracks predominantly the endocardial border, the subendocardial and sometimes in addition in the which explains some of the differences in results midwall and in the subepicardial myocardium. 10 Smiseth et al JACC: CARDIOVASCULAR IMAGING, VOL. -, NO. -, 2024 Myocardial Strain Imaging: Theory, Practice, and Future - 2024:-–- T A B L E 1 Summary of Technical Characteristics of Clinically Used Strain Methods CMR FT 2D STE 3D STE Dominant features used for tracking Endocardial borders Myocardial speckles and contour Myocardial speckles and contour Signal-to-noise ratio High Moderate Low Temporal resolution 30 phases per heart cycle 40-80 frames/s 34-50 frames/s Spatial resolution Reasonable (1-2 mm in plane Good (submillimeter radial; lateral Poor (at least 3-4 times