Circumferential-longitudinal Shear Research Articles

Left Ventricular Twist and Circumferential Strain from MRI Tagging Predict Early Cardiovascular Disease in Duchenne Muscular Dystrophy

Background/Objectives: Duchenne Muscular Dystrophy (DMD) is a prevalent fatal genetic disorder, and heart failure is the leading cause of mortality. Peak left ventricular (LV) circumferential strain (Ecc), twist, and circumferential-longitudinal shear angle (θCL) are promising biomarkers for the improved and early diagnosis of incipient heart failure. Our goals were as follows: 1) to characterize a spectrum of functional and rotational LV biomarkers in boys with DMD compared with healthy age-matched controls; and 2) to identify LV biomarkers of early cardiomyopathy in the absence of abnormal LVEF or LGE. Methods: Boys with DMD (N = 43) and age-matched healthy volunteers (N = 16) were prospectively enrolled and underwent a 3T CMR exam after obtaining informed consent. Breath-held MRI tagging was used to estimate left ventricular Ecc at the mid-ventricular level as well as the twist, torsion, and θCL between basal and apical LV short-axis slices. A two-tailed t-test with unequal variance was used to test group-wise differences. Multiple comparisons were performed with Holm–Sidak post hoc correction. Multiple-regression analysis was used to test for correlations among biomarkers. A binomial logistic regression model assessed each biomarker’s ability to distinguish the following: (1) healthy volunteers vs. DMD patients, (2) healthy volunteers vs. LGE(−) DMD patients, and (3) LGE(−) DMD patients vs. LGE(+) DMD patients. Results: There was a significant impairment in the peak mid-wall Ecc [−17.0 ± 4.2% vs. −19.5 ± 1.9%, p < 7.8 × 10−3], peak LV twist (10.4 ± 4.3° vs. 15.6 ± 3.1°, p < 8.1 × 10−4), and peak LV torsion (2.03 ± 0.82°/mm vs. 2.8 ± 0.5°/mm, p < 2.6 × 10−3) of LGE(−) DMD patients when compared to healthy volunteers. There was a further significant reduction in the Ecc, twist, torsion, and θCL for LGE(+) DMD patients when compared to LGE(−) DMD patients. In the LGE(+) DMD patients, age significantly correlated with LVEF (r2 = 0.42, p = 9 × 10−3), peak mid-wall Ecc (r2 = 0.27, p = 0.046), peak LV Twist (r2 = 0.24, p = 0.06), peak LV torsion (r2 = 0.28, p = 0.04), and peak LV θCL (r2 = 0.23, p = 0.07). In the LGE(−) DMD patients, only the peak mid-wall Ecc was significantly correlated with age (r2 = 0.25, p = 0.006). The peak LV twist outperformed the peak mid-wall LV Ecc and EF in distinguishing DMD patients from healthy volunteer groups (AUC = 0.88, 0.80, and 0.72), as well as in distinguishing LGE(−) DMD patients from healthy volunteers (AUC = 0.83, 0.74, and 0.62). The peak LV twist and peak mid-wall LV Ecc performed similarly in distinguishing the LGE(−) and LGE(+) DMD cohorts (AUC = 0.74, 0.77, and 0.79). Conclusions: The peak mid-wall LV Ecc, peak LV twist, peak LV torsion, and peak LV θCL were significantly impaired in advance of the decreased LVEF and the development of focal myocardial fibrosis in boys with DMD and therefore were apparent prior to significant irreversible injury.

Evaluation of a Novel Finite Element Model of Active Contraction in the Heart.

Finite element (FE) modeling is becoming a widely used approach for the investigation of global heart function. In the present study, a novel model of cellular-level systolic contraction, which includes both length- and velocity-dependence, was implemented into a 3D non-linear FE code. To validate this new FE implementation, an optimization procedure was used to determine the contractile parameters, associated with sarcomeric function, by comparing FE-predicted pressure and strain to experimental measures collected with magnetic resonance imaging and catheterization in the ventricles of five healthy rats. The pressure-volume relationship generated by the FE models matched well with the experimental data. Additionally, the regional distribution of end-systolic strains and circumferential-longitudinal shear angle exhibited good agreement with experimental results overall, with the main deviation occurring in the septal region. Moreover, the FE model predicted a heterogeneous distribution of sarcomere re-lengthening after ventricular ejection, which is consistent with previous in vivo studies. In conclusion, the new FE active contraction model was able to predict the global performance and regional mechanical behaviors of the LV during the entire cardiac cycle. By including more accurate cellular-level mechanisms, this model could provide a better representation of the LV and enhance cardiac research related to both systolic and diastolic dysfunction.

Increased left ventricular extracellular volume and enhanced twist function in type 1 diabetic individuals.

Individuals with type 1 diabetes (T1D) characteristically have high glycemic levels that over time can result in reactive fibrosis and abnormalities in myocardial function. T1 mapping with magnetic resonance imaging (MRI) can estimate the extent of reactive fibrosis by measurement of the extracellular volume fraction (ECV). The extent of alterations in the ECV and associated changes in left ventricular (LV) function and morphology in individuals with T1D is unknown. Fourteen individuals with long-term T1D and 14 sex-, age-, and body mass index-matched controls without diabetes underwent MRI measurement of myocardial T1 and ECV values as well as LV function and morphology. Ventricular mass, volumes, and global function (LVEF and circumferential/longitudinal/radial strain) were similar in those with T1D and controls. However, those with T1D had larger myocardial ECV (22.1 ± 1.8 vs. 20.1 ± 2.1, P = 0.008) and increased native (noncontrast) myocardial T1 values (1,211 ± 44 vs. 1,172 ± 43 ms, P < 0.001) as compared with controls. Both the ECV and native T1 values significantly correlated with several components of torsion and circumferential-longitudinal shear strain (Ecl, the shear strain component associated with twist). Individuals with T1D had increased systolic torsion (P = 0.035), systolic torsion rate (P = 0.032), peak Ecl (P = 0.001), and rates of change of systolic (P = 0.007) and diastolic (P = 0.007) Ecl Individuals with T1D, with normal structure, LVEF, and strain, have increased extracellular volume and increased native T1 values with associated augmented torsion and Ecl These measures may be useful in detecting the early stages of diabetic cardiomyopathy and warrant larger prospective studies.NEW & NOTEWORTHY Individuals with type 1 diabetes, with normal left ventricular structure and function (ejection fraction and strain), have signs of interstitial fibrosis, measured with MRI as increased extracellular volume fraction and increased native myocardial T1, which significantly correlated with a number of measures of augmented left ventricular twist function. These measures may be useful in detecting the early stages of diabetic cardiomyopathy.

Regional quantification of myocardial mechanics in rat using 3D cine DENSE cardiovascular magnetic resonance.

Rat models have assumed an increasingly important role in cardiac research. However, a detailed profile of regional cardiac mechanics, such as strains and torsion, is lacking for rats. We hypothesized that healthy rat left ventricles (LVs) exhibit regional differences in cardiac mechanics, which are part of normal function. In this study, images of the LV were obtained with 3D cine displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance in 10 healthy rats. To evaluate regional cardiac mechanics, the LV was divided into basal, mid-ventricular, and apical regions. The myocardium at the mid-LV was further partitioned into four wall segments (i.e. septal, inferior, lateral, and anterior) and three transmural layers (i.e. sub-endocardium, mid-myocardium, and sub-epicardium). The six Lagrangian strain components (i.e. Err , Ecc , Ell , Ecl , Erl , and Ecr ) were computed from the 3D displacement field and averaged within each region of interest. Torsion was quantified using the circumferential-longitudinal shear angle. While peak systolic Ecl differed between the mid-ventricle and apex, the other five components of peak systolic strain were similar across the base, mid-ventricle, and apex. In the mid-LV myocardium, Ecc decreased gradually from the sub-endocardial to the sub-epicardial layer. Ell demonstrated significant differences between the four wall segments, with the largest magnitude in the inferior segment. Err was uniform among the four wall segments. Ecl varied along the transmural direction and among wall segments, whereas Erl differed only among the wall segments. Erc was not associated with significant variations. Torsion also varied along the transmural direction and among wall segments. These results provide fundamental insights into the regional contractile function of healthy rat hearts, and form the foundation for future studies on regional changes induced by disease or treatments.

Effect of free-breathing on left ventricular rotational mechanics in healthy subjects and patients with duchenne muscular dystrophy.

Cardiovascular magnetic resonance imaging exams can be performed during free-breathing. This may be especially important for boys with Duchenne muscular dystrophy (DMD) given their frequently limited breath-hold abilities. The impact of the respiratory compensation method on quantitative measurements of left ventricular (LV) rotational mechanics is incompletely understood. The purpose of this study was to evaluate differences in LV rotational mechanics acquired during breath-holding (BH), free-breathing with averaging (AVG), and free-breathing with respiratory bellows gating (BEL). LV short-axis tagged images from healthy subjects (N = 16) and DMD patients (N = 5) were acquired with BH, AVG, and BEL. LV twist and circumferential-longitudinal shear (CL-shear) angle were measured using the Fourier Analysis of STimulated echoes (FAST) method. Peak LV twist estimates using BEL were significantly lower compared with BH in both healthy subjects (10.2 ± 3.6 ° versus 12.9 ± 2.3 °, P = 0.003) and patients with DMD (8.6 ± 3.6 ° versus 10.5 ± 3.6 °, P = 0.004). AVG results were in between BEL and BH. No significant differences in CL-shear were detected between BEL and BH. Breath-holding directly affects estimates of peak LV twist, but not CL-shear. Using a free-breathing strategy for the evaluation of cardiac function is important for intrasubject longitudinal studies, intersubject comparisons, and multicenter trials for patients with DMD. Magn Reson Med 77:864-869, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Evaluation of left ventricular torsion using cardiac MRI. Validation of feature tracking

LV torsion Left ventricular torsion may be more sensitive in detecting pathology before changes in more traditional functional parameters, and the onset of symptoms. The current gold standard for evaluating torsion is CMR, but a wide variety of techniques exist and as yet the advantages and disadvantages remain to be determined. The use of feature tracking software offers a method using standard untagged SSFP images with a potential benefit of shorter scan time. Torsional shear angle is probably the best current measure of true torsion, but requires several parameters to be defined and no commercially available software exists to calculate this. The purpose of the study was to validate the CMR derived torsion,using an in-house developed software program using data from featuretracking. Methods 15 healthy volunteers underwent a low-dose dobutamine stress CMR (baseline, 7.5mcg/kg/min, 15mcg/kg/min). In-house developed software CMRTorsion is an Excelbased macro programme using Visual Basic that facilitates the calculation and graphical representation of principal strains, twist, torsion and circumferential longitudinal shear from processed bSSFP cine images obtained by a Siemens 1.5T Avanto CMR scanner. This was further refined to allow data derived from feature tracking software to be processed.

118 Multiparametric Cardiovascular Magnetic Resonance Surveillance of Acute Cardiac Allograft Rejection and Characterisation of Transplantation-associated Myocardial Injury

BackgroundAcute cardiac allograft rejection (ACAR) affects approximately 20% of patients in the first year post-transplantation, represents a leading cause of death during this period and confers higher mortality in patients...

Left ventricular twist, but not circumferential-longitudinal shear angle, increases with increasing age in normal subjects

Background Left Ventricular (LV) twist, defined as the difference in rotation between the apex and the base, has recently been suggested as a diagnostic imaging biomarker for LV dysfunction [1]. Increasing age is associated with an increase in apical rotation, which leads to an increase LV twist [2-4]. Recently, it has been suggested that LV circumferential-longitudinal shear angle (CL-shear angle) [5] may be a more robust imaging biomarker than LV twist, due to normalization within the formula for ventricular size and slice separation [6]. However, changes in CL-shear angle with respect to age have not been reported. CL-shear angle is defined as the difference between apical rotation times the epicardial radius of the apex and basal rotation times the epicardial radius of the base, divided by the distance between the apex and base. The purpose of this study was to evaluate age related changes in CL-shear angle.

Left ventricular twist and shear-angle in patients with mitral regurgitation

Background Mitral regurgitation(MR) is a common valvular disorder that foments left ventricular(LV) dysfunction. The study of LV twist during the progression of MR is limited to studies performed with ultrasound/echo(1-3) in human subjects or animal studies(4), which suggest that LV twist decreases when MR is present. LV circumferential-longitudinal shear angle (CL-shear angle) has been proposed as a more reproducible measure of LV rotational mechanics, but has not been evaluated in patients with MR. We hypothesized that both LV twist and CL-shear angle would decrease with severity of MR. Methods Normal subjects(n=54), moderate MR patients(n=29), and severe MR patients(n=54) were studied after obtaining informed consent. MRI was performed on a 1.5T scanner (Signa, GE Healthcare, Milwaukee, WI) and grid tagged LV images were collect from the base to the apex(7). LV twist and CL-shear angle measurements were derived from Fourier Analysis of STimulated echoes(FAST)(8). LV twist is defined as the difference in rotation at the apex relative to the base of the heart. Shear-angle is defined as the difference in rotation at the apex times the radius of the apex relative to the base times the radius of the base, divided by the distance between the apex and base(5, 6). Peak LV twist and peak CL-shear angle from the three groups were compared using a one-way ANOVA and Tukey’s least significant difference(LSD) procedure for multiple comparisons. Results Mean peak LV twist for normal subjects, moderate MR patients, and severe MR patients were: 11.5±3.2, 9.0±3.0, 8.8±2.6, respectively. Mean peak CL-shear angle for normal subjects, moderate MR patients, and severe MR patients were: 5.0±1.4, 4.7±1.6, 5.0±1.3 respectively. The one-way ANOVA of peak twist between the groups, showed differences among the groups(p<0.0001). Further investigation with LSD, showed a significant difference between the normal subjects and the moderate MR patients and between the normal subject group and the severe MR patients. However, the one-way ANOVA of peak shear-angle did not reveal any differences between the three groups(p=0.4).

Myocardial Relaxation, Restoring Forces, and Early-Diastolic Load Are Independent Determinants of Left Ventricular Untwisting Rate

Peak left ventricular (LV) untwisting rate (UTR) has been introduced as a clinical marker of diastolic function. This study investigates if early-diastolic load and restoring forces are determinants of UTR in addition to the rate of LV relaxation. In 10 anesthetized dogs we measured UTR by sonomicrometry and speckle tracking echocardiography at varying LV preloads, increased contractility, and myocardial ischemia. UTR was calculated as the time derivative of LV twist. Because preload modified end-diastolic twist, LV systolic twist was calculated in absolute terms with reference to the end-diastolic twist configuration at baseline. Relaxation rate was measured as the time constant (τ) of LV isovolumic pressure decay. Early-diastolic load was measured as LV pressure at the time of mitral valve opening. Circumferential-longitudinal shear strain was used as an index of restoring forces. In a multivariable mixed model analysis a strong association was observed between UTR and LV pressure at the time of mitral valve opening (parameter estimate [β]=6.9; P<0.0001), indicating an independent effect of early-diastolic load. Furthermore, the associations between UTR and circumferential-longitudinal shear strain (β=-11.3; P<0.0001) and τ (β=-1.6, P<0.003) were consistent with independent contributions from restoring forces and rate of relaxation. Maximal UTR before mitral valve opening, however, was determined only by relaxation rate and restoring forces. The present study indicates that early-diastolic load, restoring forces, and relaxation rate are independent determinants of peak UTR. However, only relaxation rate and restoring forces contributed to UTR during isovolumic relaxation.

Alteration in left ventricular normal and shear strains evaluated by 2D‐strain echocardiography in the athlete's heart

The contraction of cardiomyocytes induces a systolic increase in left ventricular (LV) normal (radial, circumferential and longitudinal) and shear strains, whose functional consequences have not been evaluated, so far, in athletes. We used 2D ultrasound speckle tracking imaging (STI) to evaluate LV regional strain in high-level cyclists compared to sedentary controls. Sixteen male elite cyclists and 23 sedentary controls underwent conventional, tissue Doppler, and STI echocardiography at rest. We assessed LV long and short axis normal strains and shear strains. We evaluated circumferential-longitudinal shear strain from LV torsion, and circumferential-radial shear strain from the difference between subendocardial and subepicardial torsion. Apical radial strain (42.7 +/- 10.5% versus 52.2 +/- 14.3%, P < 0.05) and LV torsion (6.0 +/- 1.8 deg versus 9.2 +/- 3.2 deg, P < 0.01) were lower in cyclists than in controls, respectively. Rotations and torsion were higher in the subendocardial than in the subepicardial region in sedentary controls, but not in cyclists. Haemodynamic and tissue Doppler based indexes of global LV diastolic and systolic functions were not different between cyclists and controls. Athlete's heart is associated with specific LV adaptation including lower apical strain and lower myocardial shear strains, with no change in global LV diastolic and systolic function. These mechanical alterations could improve the cardiovascular adjustments to exercise by increasing the radial strain and torsional (and thus untwisting) response to exercise, a key element of diastolic filling and thus of cardiac performance in athletes.

Characterization of three‐dimensional myocardial deformation in the mouse heart: An MR tagging study

To develop a 3D MR tagging method that combines harmonic phase (HARP) and homogeneous strain analysis methods for quantification of regional myocardial wall motion in mice. 3D tagged images were acquired from seven C57BL/6 mice. Intersecting tag points were reconstructed and 3D strains were quantified at apical, midventricular, and basal levels. Circumferential and radial strains quantified with 2D MR tagging were compared with those calculated from 3D tagged images. Our data showed significant heterogeneity in radial, circumferential, and shear strains. Longitudinal strain was more homogeneous. The circumferential-longitudinal shear strain, a unitless measure of ventricular torsion, was positive throughout the left ventricle. There were strong correlations between 2D and 3D studies at the basal and midventricular levels. This work demonstrates the feasibility of 3D characterization of cardiac function in mouse via the combination of HARP and homogeneous strain analysis.

MR tagging demonstrates quantitative differences in regional ventricular wall motion in mice, rats, and men

Rats and genetically manipulated mouse models have played an important role in the exploration of molecular causes of cardiovascular diseases. However, it has not been fully investigated whether mice or rats and humans manifest similar patterns of ventricular wall motion. Although similarities in anatomy and myofiber architecture suggest that fundamental patterns of ventricular wall motion may be similar, the considerable differences in heart size, heart rate, and sarcomeric protein isoforms may yield quantitative differences in ventricular wall mechanics. To further our understanding of the basic mechanisms of myofiber contractile performance, we quantified regional and global indexes of ventricular wall motion in mice, rats, and men using magnetic resonance (MR) imaging. Both regular cine and tagged MR images at apical, midventricular, and basal levels were acquired from six male volunteers, six Fischer 344 rats, and seven C57BL/6 mice. Morphological parameters and ejection fraction were computed directly from cine images. Myocardial twist (rotation angle), torsion (net twist per unit length), circumferential strain, and normalized radial shortening were calculated by homogeneous strain analysis from tagged images. Our data show that ventricular twist was conserved among the three species, leading to a significantly smaller torsion, measured as net twist per unit length, in men. However, both circumferential strain and normalized radial shortening were the largest in male subjects. Although other parameters, such as circumferential-longitudinal shear strain, need to be evaluated, and the causes of these differences in contractile mechanics remain to be elucidated, the preservation of twist appears fundamental to cardiac function and should be considered in studies that extrapolate data from animals to humans.

Noninvasive quantification of left ventricular rotational deformation in normal humans using magnetic resonance imaging myocardial tagging.

It has been postulated that rotation of the left ventricular apex with respect to the base is a component of normal systolic function in humans, but it has been difficult to measure it noninvasively. Tagging is a new magnetic resonance imaging technique that labels specific areas of myocardium by selective radio-frequency excitation of narrow planes orthogonal to the imaging plane before acquiring an image. Tags appear as black lines and persist in myocardium for 400-500 msec and, if applied at end diastole, will move with the myocardium through systole. Tagging was used to noninvasively quantify left ventricular torsion and circumferential-longitudinal shear (shearCL) in humans. Eight normal volunteers, aged 24-38 years, were imaged in a 0.38-T iron-core resistive magnet. Five short-axis left ventricular images, positioned to encompass the entire left ventricle (LV), were obtained separately at end systole. Four equiangular radial tags had been applied at end diastole, intersecting the myocardium at eight locations. We calculated the difference in angular displacement of each epicardial and endocardial tag point (a tag point being where the tag crossed the epicardium or endocardium) at end systole from the systolic position of the corresponding tag point on the basal plane. This value was called the torsion angle. From this, shearCL, the angle inscribed on the epicardial or endocardial surface between the systolic tag position, the corresponding basal tag position, and its projection onto the slice of interest could be calculated at 32 points in the left ventricular wall.(ABSTRACT TRUNCATED AT 250 WORDS)