Magnetic susceptibility and R2* of myocardial reperfusion injury at 3T and 7T.

PURPOSE: Magnetic susceptibility (Δχ) alterations have shown association with myocardial infarction (MI) iron deposition, yet there remains limited understanding of the relationship between relaxation rates and susceptibility or the effect of magnetic field strength. Hence, Δχ and R2∗ in MI were compared at 3T and 7T. METHODS: Subacute MI was induced by coronary artery ligation in male Yorkshire swine. 3D multiecho gradient echo imaging was performed at 1-week postinfarction at 3T and 7T. Quantitative susceptibility mapping images were reconstructed using a morphology-enabled dipole inversion. R2∗ maps and quantitative susceptibility mapping were generated to assess the relationship between R2∗ , Δχ, and field strength. Infarct histopathology was investigated. RESULTS: Magnetic susceptibility was not significantly different across field strengths (7T: 126.8 ± 41.7 ppb; 3T: 110.2 ± 21.0 ppb, P = NS), unlike R2∗ (7T: 247.0 ± 14.8 Hz; 3T: 106.1 ± 6.5 Hz, P < .001). Additionally, infarct Δχ and R2∗ were significantly higher than remote myocardium. Magnetic susceptibility at 7T versus 3T had a significant association (ß = 1.02, R2 = 0.82, P < .001), as did R2∗ (ß = 2.35, R2 = 0.98, P < .001). Infarct pathophysiology and iron deposition were detected through histology and compared with imaging findings. CONCLUSION: R2∗ showed dependence and Δχ showed independence of field strength. Histology validated the presence of iron and supported imaging findings.

Self-gated MRI of multiple beat morphologies in the presence of arrhythmias.

PURPOSE: Develop self-gated MRI for distinct heartbeat morphologies in subjects with arrhythmias. METHODS: Golden angle radial data was obtained in seven sinus and eight arrhythmias subjects. An image-based cardiac navigator was derived from single-shot images, distinct beat types were identified, and images were reconstructed for repeated morphologies. Image sharpness, contrast, and volume variation were quantified and compared with self-gated MRI. Images were scored for image quality and artifacts. Hemodynamic parameters were computed for each distinct beat morphology in bigeminy and trigeminy subjects and for sinus beats in patients with infrequent premature ventricular contractions. RESULTS: Images of distinct beat types were reconstructed except for two patients with infrequent premature ventricular contractions. Image contrast and sharpness were similar to sinus self-gated images (contrast = 0.45 ± 0.13 and 0.43 ± 0.15; sharpness = 0.21 ± 0.11 and 0.20 ± 0.05). Visual scoring was highest in self-gated images (4.1 ± 0.3) compared with real-time (3.9 ± 0.4) and ECG-gated cine (3.4 ± 1.5). ECG-gated cine had less artifacts than self-gating (2.3 ± 0.7 and 2.1 ± 0.2), but was affected by misgating in two subjects. Among arrhythmia subjects, post-extrasystole/sinus (58.1 ± 8.6 mL) and interrupted sinus (61.4 ± 5.9 mL) stroke volume was higher than extrasystole (32.0 ± 16.5 mL; P < 0.02). CONCLUSION: Self-gated imaging can reconstruct images during ectopy and allowed for quantification of hemodynamic function of different beat morphologies. Magn Reson Med 78:678-688, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Assessment of myocardial injury after reperfused infarction by T1ρ cardiovascular magnetic resonance.

BACKGROUND: The evolution of T1ρ and of other endogenous contrast methods (T2, T1) in the first month after reperfused myocardial infarction (MI) is uncertain. We conducted a study of reperfused MI in pigs to serially monitor T1ρ, T2 and T1 relaxation, scar size and transmurality at 1 and 4 weeks post-MI. METHODS: Ten Yorkshire swine underwent 90 min of occlusion of the circumflex artery and reperfusion. T1ρ, T2 and native T1 maps and late gadolinium enhanced (LGE) cardiovascular magnetic resonance (CMR) data were collected at 1 week (n = 10) and 4 weeks (n = 5). Semi-automatic FWHM (full width half maximum) thresholding was used to assess scar size and transmurality and compared to histology. Relaxation times and contrast-to-noise ratio were compared in healthy and remote myocardium at 1 and 4 weeks. Linear regression and Bland-Altman was performed to compare infarct size and transmurality. RESULTS: Relaxation time differences between infarcted and remote myocardial tissue were ∆T1 (infarct-remote) = 421.3 ± 108.8 (1 week) and 480.0 ± 33.2 ms (4 week), ∆T1ρ = 68.1 ± 11.6 and 74.3 ± 14.2, and ∆T2 = 51.0 ± 10.1 and 59.2 ± 11.4 ms. Contrast-to-noise ratio was CNRT1 = 7.0 ± 3.5 (1 week) and 6.9 ± 2.4 (4 week), CNRT1ρ = 12.0 ± 6.2 and 12.3 ± 3.2, and CNRT2 = 8.0 ± 3.6 and 10.3 ± 5.8. Infarct size was not significantly different for T1ρ, T1 and T2 compared to LGE (p = 0.14) and significantly decreased from 1 to 4 weeks (p < 0.01). Individual infarct size changes were ∆T1ρ = -3.8%, ∆T1 = -3.5% and ∆LGE = -2.8% from 1 - 4 weeks, but there was no observed change in infarct size for T2 or histologically. CONCLUSIONS: T1ρ was highly correlated with alterations left ventricle (LV) pathology at 1 and 4 weeks post-MI and therefore it may be a useful method endogenous contrast imaging of infarction.

Preclinical evaluation of the engineered stem cell chemokine stromal cell-derived factor 1α analog in a translational ovine myocardial infarction model.

RATIONALE: After myocardial infarction, there is an inadequate blood supply to the myocardium, and the surrounding borderzone becomes hypocontractile. OBJECTIVE: To develop a clinically translatable therapy, we hypothesized that in a preclinical ovine model of myocardial infarction, the modified endothelial progenitor stem cell chemokine, engineered stromal cell-derived factor 1α analog (ESA), would induce endothelial progenitor stem cell chemotaxis, limit adverse ventricular remodeling, and preserve borderzone contractility. METHODS AND RESULTS: Thirty-six adult male Dorset sheep underwent permanent ligation of the left anterior descending coronary artery, inducing an anteroapical infarction, and were randomized to borderzone injection of saline (n=18) or ESA (n=18). Ventricular function, geometry, and regional strain were assessed using cardiac MRI and pressure-volume catheter transduction. Bone marrow was harvested for in vitro analysis, and myocardial biopsies were taken for mRNA, protein, and immunohistochemical analysis. ESA induced greater chemotaxis of endothelial progenitor stem cells compared with saline (P<0.01) and was equivalent to recombinant stromal cell-derived factor 1α (P=0.27). Analysis of mRNA expression and protein levels in ESA-treated animals revealed reduced matrix metalloproteinase 2 in the borderzone (P<0.05), with elevated levels of tissue inhibitor of matrix metalloproteinase 1 and elastin in the infarct (P<0.05), whereas immunohistochemical analysis of borderzone myocardium showed increased capillary and arteriolar density in the ESA group (P<0.01). Animals in the ESA treatment group also had significant reductions in infarct size (P<0.01), increased maximal principle strain in the borderzone (P<0.01), and a steeper slope of the end-systolic pressure-volume relationship (P=0.01). CONCLUSIONS: The novel, biomolecularly designed peptide ESA induces chemotaxis of endothelial progenitor stem cells, stimulates neovasculogenesis, limits infarct expansion, and preserves contractility in an ovine model of myocardial infarction.

Computational Investigation of Transmural Differences in Left Ventricular Contractility.

Myocardial contractility of the left ventricle (LV) plays an essential role in maintaining normal pump function. A recent ex vivo experimental study showed that cardiomyocyte force generation varies across the three myocardial layers of the LV wall. However, the in vivo distribution of myocardial contractile force is still unclear. The current study was designed to investigate the in vivo transmural distribution of myocardial contractility using a noninvasive computational approach. For this purpose, four cases with different transmural distributions of maximum isometric tension (Tmax) and/or reference sarcomere length (lR) were tested with animal-specific finite element (FE) models, in combination with magnetic resonance imaging (MRI), pressure catheterization, and numerical optimization. Results of the current study showed that the best fit with in vivo MRI-derived deformation was obtained when Tmax assumed different values in the subendocardium, midmyocardium, and subepicardium with transmurally varying lR. These results are consistent with recent ex vivo experimental studies, which showed that the midmyocardium produces more contractile force than the other transmural layers. The systolic strain calculated from the best-fit FE model was in good agreement with MRI data. Therefore, the proposed noninvasive approach has the capability to predict the transmural distribution of myocardial contractility. Moreover, FE models with a nonuniform distribution of myocardial contractility could provide a better representation of LV function and be used to investigate the effects of transmural changes due to heart disease.

In vivo chronic myocardial infarction characterization by spin locked cardiovascular magnetic resonance.

BACKGROUND: Late gadolinium enhanced (LGE) cardiovascular magnetic resonance (CMR) is frequently used to evaluate myocardial viability, estimate total infarct size and transmurality, but is not always straightforward is and contraindicated in patients with renal failure because of the risk of nephrogenic systemic fibrosis. T2- and T1-weighted CMR alone is however relatively insensitive to chronic myocardial infarction (MI) in the absence of a contrast agent. The objective of this manuscript is to explore T1ρ-weighted rotating frame CMR techniques for infarct characterization without contrast agents. We hypothesize that T1ρ CMR accurately measures infarct size in chronic MI on account of a large change in T1ρ relaxation time between scar and myocardium. METHODS: 7Yorkshire swine underwent CMR at 8 weeks post-surgical induction of apical or posterolateral myocardial infarction. Late gadolinium enhanced and T1ρ CMR were performed at high resolution to visualize MI. T1ρ-weighted imaging was performed with a B1 = 500 Hz spin lock pulse on a 3 T clinical MR scanner. Following sacrifice, the heart was excised and infarct size was calculated by optical planimetry. Infarct size was calculated for all three methods (LGE, T1ρ and planimetry) and statistical analysis was performed. T1ρ relaxation time maps were computed from multiple T1ρ-weighted images at varying spin lock duration. RESULTS: Mean infarct contrast-to-noise ratio (CNR) in LGE and T1ρ CMR was 2.8 ± 0.1 and 2.7 ± 0.1. The variation in signal intensity of tissues was found to be, in order of decreasing signal intensity, LV blood, fat and edema, infarct and healthy myocardium. Infarct size measured by T1ρ CMR (21.1% ± 1.4%) was not significantly different from LGE CMR (22.2% ± 1.5%) or planimetry (21.1% ± 2.7%; p < 0.05).T1ρ relaxation times were T1ρinfarct = 91.7 ms in the infarct and T1ρremote = 47.2 ms in the remote myocardium. CONCLUSIONS: T1ρ-weighted imaging using long spin locking pulses enables high discrimination between infarct and myocardium. T1ρ CMR may be useful to visualizing MI without the need for exogenous contrast agents for a wide range of clinical cardiac applications such as to distinguish edema and scar tissue and tissue characterization of myocarditis and ventricular fibrosis.

Multimodal image analysis and subvalvular dynamics in ischemic mitral regurgitation.

Background: The exact geometric pathogenesis of leaflet tethering in ischemic mitral regurgitation (IMR) and the relative contribution of each component of the mitral valve complex (MVC) remain largely unknown. In this study, we sought to further elucidate mitral valve (MV) leaflet remodeling and papillary muscle dynamics in an ovine model of IMR with magnetic resonance imaging (MRI) and 3-dimensional echocardiography (3DE). Methods: Multimodal imaging combining 3DE and MRI was used to analyze the MVC at baseline, 30 minutes post-myocardial infarction (MI), and 12 weeks post-MI in ovine IMR models. Advanced 3D imaging software was used to trace the MVC from each modality, and the tracings were verified against resected specimens. Results: 3DE MV remodeling was regionally heterogenous and observed primarily in the anterior leaflet, with significant increases in surface area, especially in A2 and A3. The posterior leaflet was significantly shortened in P2 and P3. Mean posteromedial papillary muscle (PMPM) volume was decreased from 1.9 ± 0.2 cm3 at baseline to 0.9 ± 0.3 cm3 at 12 weeks post-MI (P < .05). At 12 weeks post-MI, the PMPM was predominately displaced horizontally and outward along the intercommissural axis with minor apical displacement. The subvalvular contribution to tethering is a combination of unilateral movement, outward displacement, and degeneration of the PMPM. These findings have led to a proposed new framework for characterizing PMPM dynamics in IMR. Conclusions: This study provides new insights into the complex interrelated and regionally heterogenous valvular and subvalvular mechanisms involved in the geometric pathogenesis of IMR tethering.

Rotating frame spin lattice relaxation in a swine model of chronic, left ventricular myocardial infarction.

T1ρ relaxation times were quantified in a swine model of chronic, left ventricular myocardial infarction. It was found that there were low frequency relaxation mechanisms that suppress endogenous contrast at low spin-lock amplitudes and in T2-weighted images. A moderate amplitude spin-locking pulse could overcome these relaxation mechanisms. Relaxation dispersion data were measured over a range of RF field amplitudes, and a model was formulated to include dipole-dipole relaxation modulated by molecular rotation and an apparent exchange mechanism. These techniques may find some use in the clinic for the observation of chronic, left ventricular cardiac remodeling.

Deformation analysis of 3D tagged cardiac images using an optical flow method.

BACKGROUND: This study proposes and validates a method of measuring 3D strain in myocardium using a 3D Cardiovascular Magnetic Resonance (CMR) tissue-tagging sequence and a 3D optical flow method (OFM). METHODS: Initially, a 3D tag MR sequence was developed and the parameters of the sequence and 3D OFM were optimized using phantom images with simulated deformation. This method then was validated in-vivo and utilized to quantify normal sheep left ventricular functions. RESULTS: Optimizing imaging and OFM parameters in the phantom study produced sub-pixel root-mean square error (RMS) between the estimated and known displacements in the x (RMSx = 0.62 pixels (0.43 mm)), y (RMSy = 0.64 pixels (0.45 mm)) and z (RMSz = 0.68 pixels (1 mm)) direction, respectively. In-vivo validation demonstrated excellent correlation between the displacement measured by manually tracking tag intersections and that generated by 3D OFM (R >or= 0.98). Technique performance was maintained even with 20% Gaussian noise added to the phantom images. Furthermore, 3D tracking of 3D cardiac motions resulted in a 51% decrease in in-plane tracking error as compared to 2D tracking. The in-vivo function studies showed that maximum wall thickening was greatest in the lateral wall, and increased from both apex and base towards the mid-ventricular region. Regional deformation patterns are in agreement with previous studies on LV function. CONCLUSION: A novel method was developed to measure 3D LV wall deformation rapidly with high in-plane and through-plane resolution from one 3D cine acquisition.

Closed-loop control of k-space sampling via physiologic feedback for cine MRI.

BACKGROUND: Segmented cine cardiac MRI combines data from multiple heartbeats to achieve high spatiotemporal resolution cardiac images, yet predefined k-space segmentation trajectories can lead to suboptimal k-space sampling. In this work, we developed and evaluated an autonomous and closed-loop control system for radial k-space sampling (ARKS) to increase sampling uniformity. METHODS: The closed-loop system autonomously selects radial k-space sampling trajectory during live segmented cine MRI and attempts to optimize angular sampling uniformity by selecting views in regions of k-space that were not previously well-sampled. Sampling uniformity and the ability to detect cardiac phase in vivo was assessed using ECG data acquired from 10 normal subjects in an MRI scanner. The approach was then implemented with a fast gradient echo sequence on a whole-body clinical MRI scanner and imaging was performed in 4 healthy volunteers. The closed-loop k-space trajectory was compared to random, uniformly distributed and golden angle view trajectories via measurement of k-space uniformity and the point spread function. Lastly, an arrhythmic dataset was used to evaluate a potential application of the approach. RESULTS: The autonomous trajectory increased k-space sampling uniformity by 15±7%, main lobe point spread function (PSF) signal intensity by 6±4%, and reduced ringing relative to golden angle sampling. When implemented, the autonomous pulse sequence prescribed radial view angles faster than the scan TR (0.98 ± 0.01 ms, maximum = 1.38 ms) and increased k-space sampling mean uniformity by 10±11%, decreased uniformity variability by 44±12%, and increased PSF signal ratio by 6±6% relative to golden angle sampling. CONCLUSION: The closed-loop approach enables near-uniform radial sampling in a segmented acquisition approach which was higher than predetermined golden-angle radial sampling. This can be utilized to increase the sampling or decrease the temporal footprint of an acquisition and the closed-loop framework has the potential to be applied to patients with complex heart rhythms.

Iron imaging in myocardial infarction reperfusion injury.

Restoration of coronary blood flow after a heart attack can cause reperfusion injury potentially leading to impaired cardiac function, adverse tissue remodeling and heart failure. Iron is an essential biometal that may have a pathologic role in this process. There is a clinical need for a precise noninvasive method to detect iron for risk stratification of patients and therapy evaluation. Here, we report that magnetic susceptibility imaging in a large animal model shows an infarct paramagnetic shift associated with duration of coronary artery occlusion and the presence of iron. Iron validation techniques used include histology, immunohistochemistry, spectrometry and spectroscopy. Further mRNA analysis shows upregulation of ferritin and heme oxygenase. While conventional imaging corroborates the findings of iron deposition, magnetic susceptibility imaging has improved sensitivity to iron and mitigates confounding factors such as edema and fibrosis. Myocardial infarction patients receiving reperfusion therapy show magnetic susceptibility changes associated with hypokinetic myocardial wall motion and microvascular obstruction, demonstrating potential for clinical translation.

Reconstruction of myocardial tissue motion and strain fields from displacement-encoded MR imaging.

A quantitative analysis of myocardial mechanics is fundamental to understanding cardiac function, diagnosis of heart disease, and assessment of therapeutic intervention. Displacement encoding with stimulated-echo (DENSE) magnetic resonance imaging (MRI) technique was developed to track the three-dimensional (3D) displacement vector of discrete material grid points in the myocardial tissue. Despite the wealth of information gained from DENSE images, the current software only provides two-dimensional in-plane deformation. The objective of this study is to introduce a postprocessing method to reconstruct and visualize continuous dynamic 3D displacement and strain fields in the ventricular wall from DENSE data. An anatomically accurate hexagonal finite-element model of the left ventricle (LV) is reconstructed by fitting a prolate spheroidal primitive to contour points of the epi- and endocardial surfaces. The continuous displacement field in the model is described mathematically based on the discrete DENSE vectors using a minimization method with smoothness regularization. Based on the displacement, heart motion and myocardial stretch (or strain) are analyzed. Illustratory computations were conducted with DENSE data of three infarcted and one normal sheep ventricles. The full 3D results show stronger overall axial shortening, wall thickening, and twisting of the normal LV compared with the infarcted hearts. Local myocardial stretches show a dyskinetic LV in the apical region, dilation of apex in systole, and a compensatory increase in strain in the healthy basal region as a compensatory mechanism. We conclude that the proposed postprocessing method significantly extends the utility of DENSE MRI, which may provide a patient-specific 3D model of cardiac mechanics.

Effects of hydrogel injection on borderzone contractility post-myocardial infarction.

Injectable hydrogels are a potential therapy for mitigating adverse left ventricular (LV) remodeling after myocardial infarction (MI). Previous studies using magnetic resonance imaging (MRI) have shown that hydrogel treatment improves systolic strain in the borderzone (BZ) region surrounding the infarct. However, the corresponding contractile properties of the BZ myocardium are still unknown. The goal of the current study was to quantify the in vivo contractile properties of the BZ myocardium post-MI in an ovine model treated with an injectable hydrogel. Contractile properties were determined 8 weeks following posterolateral MI by minimizing the difference between in vivo strains and volume calculated from MRI and finite element model predicted strains and volume. This was accomplished by using a combination of MRI, catheterization, finite element modeling, and numerical optimization. Results show contractility in the BZ of animals treated with hydrogel injection was significantly higher than untreated controls. End-systolic (ES) fiber stress was also greatly reduced in the BZ of treated animals. The passive stiffness of the treated infarct region was found to be greater than the untreated control. Additionally, the wall thickness in the infarct and BZ regions was found to be significantly higher in the treated animals. Treatment with hydrogel injection significantly improved BZ function and reduced LV remodeling, via altered MI properties. These changes are linked to a reduction in the ES fiber stress in the BZ myocardium surrounding the infarct. The current results imply that injectable hydrogels could be a viable therapy for maintaining LV function post-MI.

Cardiac support device modifies left ventricular geometry and myocardial structure after myocardial infarction.

BACKGROUND: Whether mechanical restraint of the left ventricle (LV) can influence remodeling after myocardial infarction (MI) remains poorly understood. This study surgically placed a cardiac support device (CSD) over the entire LV and examined LV and myocyte geometry and function after MI. METHODS AND RESULTS: Post-MI sheep (35 to 45 kg; MI size, 23+/-2%) were randomized to placement of the CorCap CSD (Acorn Cardiovascular, Inc) (MI+CSD; n=6) or remained untreated (MI only; n=5). Uninstrumented sheep (n=10) served as controls. At 3 months after MI, LV end-diastolic volume (by MRI) was increased in the MI only group compared with controls (98+/-8 versus 43+/-4 mL; P<0.05). In the MI+CSD group, LV end-diastolic volume was lower than MI only values (56+/-7 mL; P<0.05) but remained higher than controls (P<0.05). Isolated LV myocyte shortening velocity was reduced by 35% from control values (P<0.05) in both MI groups. LV myocyte beta-adrenergic response was reduced with MI but normalized in the MI+CSD group. LV myocyte length increased in the MI group and was reduced in the MI+CSD group. Relative collagen content was increased and matrix metalloproteinase-9 was decreased within the MI border region of the CSD group. CONCLUSIONS: A CSD beneficially modified LV and myocyte remodeling after MI through both cellular and extracellular mechanisms. These findings provide evidence that nonpharmacological strategies can interrupt adverse LV remodeling after MI.

Slice-by-Slice Pressure-Volume Loop Analysis Demonstrates Native Differences in Regional Cardiac Contractility and Response to Inotropic Agents.

BACKGROUND: Regional changes in diastolic and systolic properties after myocardial infarction contribute to adverse left ventricular (LV) remodeling. Regional function is currently assessed using load-dependent measures such as slice ejection fraction (sEF), wall motion abnormalities, or strain imaging. However, load-independent measures of cardiac function may be useful in the study of the infarction-induced remodeling. METHODS: In this study, we used a recently validated 2-dimensional (2D) real-time magnetic resonance imaging (MRI) technique to evaluate regional variations in load-independent slice-by-slice measures of systolic and diastolic function and compared the values to a load-dependent measure in 11 sheep at rest and during inotropic agent infusion. RESULTS: Slice-derived ejection fraction (sEF) was greater in the apex relative to the midventricular and basal regions, and inotropic infusion increased sEF in the base more than in the apex and midventricle. Slice-derived ESPVR (sESPVR) in the apex was significantly lower than in the midventricle and the base, and inotropic infusion increased sESPVR in the apical slices more than in the midventricle. Similarly, slice-derived volume-axis intercept V0 (sV0) was higher in the base relative to the midventricle and apex. sEDPVR did not demonstrate significant regional variations, but inotropic infusion resulted in a small increase in the apex. CONCLUSIONS: In conclusion, acquisition of slice-derived load-independent measures demonstrated variations that contradict those observed with load-dependent sEF. The approach may provide advanced slice-based measures of function during the LV remodeling process and aid in the development of therapies.

Effects of using the unloaded configuration in predicting the in vivo diastolic properties of the heart.

Computational models are increasingly being used to investigate the mechanical properties of cardiac tissue. While much insight has been gained from these studies, one important limitation associated with computational modeling arises when using in vivo images of the heart to generate the reference state of the model. An unloaded reference configuration is needed to accurately represent the deformation of the heart. However, it is rare for a beating heart to actually reach a zero-pressure state during the cardiac cycle. To overcome this, a computational technique was adapted to determine the unloaded configuration of an in vivo porcine left ventricle (LV). In the current study, in vivo measurements were acquired using magnetic resonance images (MRI) and synchronous pressure catheterization in the LV (N = 5). The overall goal was to quantify the effects of using early-diastolic filling as the reference configuration (common assumption used in modeling) versus using the unloaded reference configuration for predicting the in vivo properties of LV myocardium. This was accomplished by using optimization to minimize the difference between MRI measured and finite element predicted strains and cavity volumes. The results show that when using the unloaded reference configuration, the computational method predicts material properties for LV myocardium that are softer and less anisotropic than when using the early-diastolic filling reference configuration. This indicates that the choice of reference configuration could have a significant impact on capturing the realistic mechanical response of the heart.

Computational Modeling of Healthy Myocardium in Diastole.

In order to better understand the mechanics of the heart and its disorders, engineers increasingly make use of the finite element method (FEM) to investigate healthy and diseased cardiac tissue. However, FEM is only as good as the underlying constitutive model, which remains a major challenge to the biomechanics community. In this study, a recently developed structurally based constitutive model was implemented to model healthy left ventricular myocardium during passive diastolic filling. This model takes into account the orthotropic response of the heart under loading. In-vivo strains were measured from magnetic resonance images (MRI) of porcine hearts, along with synchronous catheterization pressure data, and used for parameter identification of the passive constitutive model. Optimization was performed by minimizing the difference between MRI measured and FE predicted strains and cavity volumes. A similar approach was followed for the parameter identification of a widely used phenomenological constitutive law, which is based on a transversely isotropic material response. Results indicate that the parameter identification with the structurally based constitutive law is more sensitive to the assigned fiber architecture and the fit between the measured and predicted strains is improved with more realistic sheet angles. In addition, the structurally based model is capable of generating a more physiological end-diastolic pressure-volume relationship in the ventricle.

Injectable Shear-Thinning Hydrogels for Minimally Invasive Delivery to Infarcted Myocardium to Limit Left Ventricular Remodeling.

BACKGROUND: Injectable, acellular biomaterials hold promise to limit left ventricular remodeling and heart failure precipitated by infarction through bulking or stiffening the infarct region. A material with tunable properties (eg, mechanics, degradation) that can be delivered percutaneously has not yet been demonstrated. Catheter-deliverable soft hydrogels with in vivo stiffening to enhance therapeutic efficacy achieve these requirements. METHODS AND RESULTS: We developed a hyaluronic acid hydrogel that uses a tandem crosslinking approach, where the first crosslinking (guest-host) enabled injection and localized retention of a soft (<1 kPa) hydrogel. A second crosslinking reaction (dual-crosslinking) stiffened the hydrogel (41.4±4.3 kPa) after injection. Posterolateral infarcts were investigated in an ovine model (n≥6 per group), with injection of saline (myocardial infarction control), guest-host hydrogels, or dual-crosslinking hydrogels. Computational (day 1), histological (1 day, 8 weeks), morphological, and functional (0, 2, and 8 weeks) outcomes were evaluated. Finite-element modeling projected myofiber stress reduction (>50%; P<0.001) with dual-crosslinking but not guest-host injection. Remodeling, assessed by infarct thickness and left ventricular volume, was mitigated by hydrogel treatment. Ejection fraction was improved, relative to myocardial infarction at 8 weeks, with dual-crosslinking (37% improvement; P=0.014) and guest-host (15% improvement; P=0.058) treatments. Percutaneous delivery via endocardial injection was investigated with fluoroscopic and echocardiographic guidance, with delivery visualized by magnetic resonance imaging. CONCLUSIONS: A percutaneous delivered hydrogel system was developed, and hydrogels with increased stiffness were found to be most effective in ameliorating left ventricular remodeling and preserving function. Ultimately, engineered systems such as these have the potential to provide effective clinical options to limit remodeling in patients after infarction.

Ventricular constraint using the acorn cardiac support device reduces myocardial akinetic area in an ovine model of acute infarction.

BACKGROUND: Left ventricular remodeling secondary to acute myocardial infarction (AMI) is characterized by ventricular dilatation and regional akinesis. In this study, we investigated the effect of passive constraint on akinetic area development. METHODS AND RESULTS: The effect of passive constraint on akinetic area was investigated in 10 sheep using tissue-tagging magnetic resonance imaging (MRI). A baseline MRI study was followed by the creation of an anterior infarct. After 1 week, the animals received a second MRI study. A cardiac support device (CSD) was then placed over the epicardium in 5 sheep whereas the remaining animals served as controls. A terminal study was performed at the 2-month postinfarct in both groups. The akinetic area at 1-week postinfarct was similar in both groups. At the terminal time-point, the akinetic area in the control group was similar to the 1-week time-point whereas in the CSD group, the area of akinesis decreased (P=0.001). A comparison of the 2 groups at the terminal time-point demonstrates a significantly diminished area of akinesis in the CSD group (P=0.004). The relative area of akinesis followed a similar pattern. End-systolic and end-diastolic wall thickness was significantly greater in the CSD group at terminal (P=0.001). In addition, the minimum wall thickness was greater in the CSD group compared with the controls (P=0.04). CONCLUSIONS: Passive constraint reduced akinetic area development secondary to AMI. The attenuation of regional wall stress may prevent the incorporation of the border zone into the infarct, decreasing infarct size and providing a promising new therapy for patients after an AMI.