Alistair A. Young

Three-dimensional left ventricular deformation in hypertrophic cardiomyopathy.

BackgroundIn hypertrophic cardiomyopathy, ejection fraction is normal or increased, and force-length relations are reduced. However, three-dimensional (3D) motion and deformation in vivo have not been assessed in this condition. We have reconstructed the 3D motion of the left ventricle (LV) during systole in 7 patients with hypertrophic cardiomyopathy (HCM) and 12 normal volunteers by use of magnetic resonance tagging. Methods and ResultsTransmural tagging stripes were automatically tracked to subpixel resolution with an active contour model. A 3D finite-element model was used to interpolate displacement information between short- and long-axis slices and register data on a regional basis. Displacement and strain data were averaged into septal, posterior, lateral, and anterior regions at basal, midventricular, and apical levels. Radial motion (toward the central long axis) decreased slightly in patients with HCM, whereas longitudinal displacement (parallel to the long axis) of the base toward the apex was markedly reduced: 7.5±2.5mm (SD) versus 12.5±2.0 mm, P<.001. Circumferential and longitudinal shortening were both reduced in the septum (P<.01 at all levels). The principal strain associated with 3D maximal contraction was slightly depressed in many regions, significantly in the basal septum (−0.18±0.05 versus −0.22±0.02, P<.05) and anterior (−0.20±0.05 versus −0.23±0.02, P<.05) walls. In contrast, LV torsion (twist of the apex about the long axis relative to the base) was greater in HCM patients (19.9±2.4° versus 14.6±2.7°, P<.01). ConclusionsHCM patients had reduced 3D myocardial shortening on a regional basis; however, LV torsion was increased.

Tracking and finite element analysis of stripe deformation in magnetic resonance tagging

Magnetic resonance tissue tagging allows noninvasive in vivo measurement of soft tissue deformation. Planes of magnetic saturation are created, orthogonal to the imaging plane, which form dark lines (stripes) in the image. The authors describe a method for tracking stripe motion in the image plane, and show how this information can be incorporated into a finite element model of the underlying deformation. Human heart data were acquired from several imaging planes in different orientations and were combined using a deformable model of the left ventricle wall. Each tracked stripe point provided information on displacement orthogonal to the original tagging plane, i.e., a one-dimensional (1-D) constraint on the motion. Three-dimensional (3-D) motion and deformation was then reconstructed by fitting the model to the data constraints by linear least squares. The average root mean squared (rms) error between tracked stripe points and predicted model locations was 0.47 mm (n=3,100 points). In order to validate this method and quantify the errors involved, the authors applied it to images of a silicone gel phantom subjected to a known, well-controlled, 3-D deformation. The finite element strains obtained were compared to an analytic model of the deformation known to be accurate in the central axial plane of the phantom. The average rms errors were 6% in both the reconstructed shear strains and 16% in the reconstructed radial normal strain.

Two-dimensional left ventricular deformation during systole using magnetic resonance imaging with spatial modulation of magnetization.

BackgroundMyocardial tissue tagging with the use of magnetic resonance imaging allows noninvasive regional analysis of heart wall motion and deformation. However, any evaluation of the effect of disease or treatment requires a baseline reference of normal values and variation. We studied the two-dimensional motion of material points imaged within the left ventricular wall using spatial modulation of magnetization (SPAMM) in 12 normal human volunteers. Methods and ResultsFive parallel short-axis and five parallel long-axis slices were acquired at five times during systole. SPAMM tags were generated at end diastole using a 7-mm grid. Intersection point data were analyzed for displacement, rotation, and torsion, and triangles of points were analyzed for local rotation and principal strains. Short-axis displacement was the least in the septum for all longitudinal levels (P < .001). Torsion about the long axis was uniform circumferentially because of the motion of the centroids used to reference the rotation. In the long-axis images, the base displaced longitudinally toward the apex, with the posterior wall moving farther than the anterior wall (13.4±2.2 versus 9.7±1.8 mm, P < .001) in this direction. The largest principal strain (maximum lengthening) was approximately radially oriented in both views. In the short-axis images, the minimum principal strain (maximum shortening) increased in magnitude toward the apex (P < .001) with little circumferential variation, except at midventricle, where the anterior wall showed greater contraction than the posterior wall (−0.21±0.03 versus −0.19±0.02, P < .02). ConclusionsConsistent regional variations in deformation are seen in the normal human heart. Displacement and maximum shortening strains are well characterized with twodimensional magnetic resonance tagging; however, higherresolution images will be required to study transmural variations.

Deformable models with parameter functions for cardiac motion analysis from tagged MRI data

The authors present a new method for analyzing the motion of the hearts left ventricle (LV) from tagged magnetic resonance imaging (MRI) data. Their technique is based on the development of a new class of physics-based deformable models whose parameters are functions. They allow the definition of new parameterized primitives and parameterized deformations which can capture the local shape variation of a complex object. Furthermore, these parameters are intuitive and require no complex post-processing in order to be used by a physician. Using a physics-based approach, the authors convert the geometric models into dynamic models that deform due to forces exerted from the datapoints and conform to the given dataset. The authors present experiments involving the extraction of the shape and motion of the LVs mid-wall during systole from tagged MRI data based on a few parameter functions. Furthermore, by plotting the variations over time of the extracted LV model parameters from normal and abnormal heart data along the long axis, the authors are able to quantitatively characterize their differences.

Regeneration of the Heart in Diabetes by Selective Copper Chelation

Heart disease is the major cause of death in diabetes, a disorder characterized by chronic hyperglycemia and cardiovascular complications. Although altered systemic regulation of transition metals in diabetes has been the subject of previous investigation, it is not known whether changed transition metal metabolism results in heart disease in common forms of diabetes and whether metal chelation can reverse the condition. We found that administration of the Cu-selective transition metal chelator trientine to rats with streptozotocin-induced diabetes caused increased urinary Cu excretion compared with matched controls. A Cu(II)-trientine complex was demonstrated in the urine of treated rats. In diabetic animals with established heart failure, we show here for the first time that 7 weeks of oral trientine therapy significantly alleviated heart failure without lowering blood glucose, substantially improved cardiomyocyte structure, and reversed elevations in left ventricular collagen and beta(1) integrin. Oral trientine treatment also caused elevated Cu excretion in humans with type 2 diabetes, in whom 6 months of treatment caused elevated left ventricular mass to decline significantly toward normal. These data implicate accumulation of elevated loosely bound Cu in the mechanism of cardiac damage in diabetes and support the use of selective Cu chelation in the treatment of this condition.

Modelling passive diastolic mechanics with quantitative MRI of cardiac structure and function

The majority of patients with clinically diagnosed heart failure have normal systolic pump function and are commonly categorized as suffering from diastolic heart failure. The left ventricle (LV) remodels its structure and function to adapt to pathophysiological changes in geometry and loading conditions, which in turn can alter the passive ventricular mechanics. In order to better understand passive ventricular mechanics, a LV finite element (FE) model was customized to geometric data segmented from in vivo tagged magnetic resonance images (MRI) data and myofibre orientation derived from ex vivo diffusion tensor MRI (DTMRI) of a canine heart using nonlinear finite element fitting techniques. MRI tissue tagging enables quantitative evaluation of cardiac mechanical function with high spatial and temporal resolution, whilst the direction of maximum water diffusion in each voxel of a DTMRI directly corresponds to the local myocardial fibre orientation. Due to differences in myocardial geometry between in vivo and ex vivo imaging, myofibre orientations were mapped into the geometric FE model using host mesh fitting (a free form deformation technique). Pressure recordings, temporally synchronized to the tagging data, were used as the loading constraints to simulate the LV deformation during diastole. Simulation of diastolic LV mechanics allowed us to estimate the stiffness of the passive LV myocardium based on kinematic data obtained from tagged MRI. Integrated physiological modelling of this kind will allow more insight into mechanics of the LV on an individualized basis, thereby improving our understanding of the underlying structural basis of mechanical dysfunction under pathological conditions.

The architecture of the heart: a data–based model

An appropriate mathematical representation of heart structure is central to advancing an integrative approach to cardiac function. The Auckland heart model provides a realistic representation of important aspects of ventricular structure. The finite–element model is based on extensive anatomical data and incorporates detailed information on ventricular geometry and myocyte organization. It includes preliminary descriptions of the Purkinje fibre network, coronary vessels and collagen organization. Comprehensive extension of these data is required to exploit the full potential of computer modelling. In particular, we need to quantify the morphology of the atria, cardiac conduction system and the intramyocardial coronary vessels. This information must span an appropriate range of species and disease states.

Age-Related Changes in Myocardial Relaxation Using Three-Dimensional Tagged Magnetic Resonance Imaging

PURPOSE Marked changes in left ventricular diastolic filling occur with advancing age, but alterations in myocardial movement accompanying these findings have not been previously documented. We aimed to identify differences in myocardial motion during relaxation and diastole using magnetic resonance imaging (MRI), with tagging, which uniquely allows accurate, noninvasive assessment of myocardial movement in three dimensions. METHODS Tagged MRI images from two groups of normal individuals were analyzed using dedicated computer software to provide values for group comparison of apical rotation, torsion, and circumferential and longitudinal strain throughout the cardiac cycle. RESULTS The mean age of the younger group was 22 years, (n = 15) and that of the older group was 69 years, (n = 16). In the older group, peak apical rotation and torsion were increased during systole and significantly more apical rotation, torsion, circumferential, and longitudinal strain persisted during myocardial relaxation and diastole. In addition, peak normalized reversal of apical rotation was reduced (-5.1 +/- 1.2 degrees s-1 vs. -6.7 +/- 1.2 degrees s-1, p = 0.001), and there were slower peak rates of circumferential lengthening (76.2 +/- 28% s-1 vs. 142.5 +/- 17% s-1, p < 0.001) and longitudinal lengthening (62.7 +/- 21% s-1 vs. 122.5 +/- 20% s-1, p < 0.001). CONCLUSIONS Tagged MRI is a unique, noninvasive imaging method that can identify significant prolongation and reduction of myocardial relaxation in older compared with young normal individuals.

Regional heterogeneity of function in nonischemic dilated cardiomyopathy

OBJECTIVE To quantify regional three-dimensional (3D) motion and myocardial strain using magnetic resonance (MR) tissue tagging in patients with non-ischemic dilated cardiomyopathy (DCM). METHODS MR grid tagged images were obtained in multiple short- and long-axis planes in thirteen DCM patients. Regional 3D displacements and strains were calculated with the aid of a finite element model. Five of the patients were also imaged after LV volume reduction by partial left ventriculectomy (PLV), combined with mitral and tricuspid valve repair. RESULTS DCM patients showed consistent, marked regional heterogeneity. Systolic lengthening occurred in the septum in both circumferential (%S(C) -5+/-7%) and longitudinal (%S(L) -2+/-5%) shortening components (negative values indicating lengthening). In contrast, the lateral wall showed relatively normal systolic shortening (%S(C) 12+/-6% and %S(L) 6+/-5%, P<0.001 lateral vs. septal walls). A geometric estimate of regional stress was correlated with shortening on a regional basis, but could not account for the differences in shortening between regions. In the five patients imaged post-PLV, septal function recovered (%S(C) 9+/-5%,%S(L) 6+/-5%, P<0.02 pre vs. post) with normalization of wall stress, whereas lateral wall shortening was reduced (%S(C) 7+/-6%,%S(L) 3+/-3%, P<0.02 pre vs. post) around the site of surgical resection. CONCLUSIONS A consistent pattern of regional heterogeneity of myocardial strain was seen in all patients. Reduced function may be related to increased wall stress, since recovery of septal function is possible after PLV. However, simple geometric stress determinants are not sufficient to explain the functional heterogeneity observed.

3‐Dimensional configuration of perimysial collagen fibres in rat cardiac muscle at resting and extended sarcomere lengths

1 We have used fluorescence confocal laser scanning microscopy to attain the three‐dimensional (3‐D) microstructure of perimysial collagen fibres over the range of sarcomere lengths (1.9–2.3 μm) in which passive force of cardiac muscle increases steeply. 2 A uniaxial muscle preparation (right ventricular trabecula of rat) was used so that the 3‐D collagen configuration could be readily related to sarcomere length. Transmission electron microscopy showed that these preparations were structurally homologous to ventricular wall muscle. 3 Trabeculae were mounted on the stage of an inverted microscope and fixed at various sarcomere lengths. After a trabecula was stained with the fluorophore Sirius Red F3BA and embedded in resin, sequential optical sectioning enabled 3‐D reconstruction of its perimysial collagen fibres. The area fraction of these fibres, determined from the cross‐sections of seven trabeculae, was 10.5 ± 3.9 % (means ± s.d.). 4 The reconstructed 3‐D images show that perimysial collagen fibres are wavy (as distinct from coiled) cords which straighten considerably as the sarcomere length is increased from 1.85 ± 0.06 μm (near‐resting length) to 2.3 ± 0.04 μm (means ± s.d., n= 4). These observations are consistent with the notion that the straightening of these fibres is responsible for limiting extension of the cardiac sarcomere to a length of ≈2.3 μm.