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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

MRI evaluation of injectable hyaluronic acid-based hydrogel therapy to limit ventricular remodeling after myocardial infarction.

Injectable biomaterials are an attractive therapy to attenuate left ventricular (LV) remodeling after myocardial infarction (MI). Although studies have shown that injectable hydrogels improve cardiac structure and function in vivo, temporal changes in infarct material properties after treatment have not been assessed. Emerging imaging and modeling techniques now allow for serial, non-invasive estimation of infarct material properties. Specifically, cine magnetic resonance imaging (MRI) assesses global LV structure and function, late-gadolinium enhancement (LGE) MRI enables visualization of infarcted tissue to quantify infarct expansion, and spatial modulation of magnetization (SPAMM) tagging provides passive wall motion assessment as a measure of tissue strain, which can all be used to evaluate infarct properties when combined with finite element (FE) models. In this work, we investigated the temporal effects of degradable hyaluronic acid (HA) hydrogels on global LV remodeling, infarct thinning and expansion, and infarct stiffness in a porcine infarct model for 12 weeks post-MI using MRI and FE modeling. Hydrogel treatment led to decreased LV volumes, improved ejection fraction, and increased wall thickness when compared to controls. FE model simulations demonstrated that hydrogel therapy increased infarct stiffness for 12 weeks post-MI. Thus, evaluation of myocardial tissue properties through MRI and FE modeling provides insight into the influence of injectable hydrogel therapies on myocardial structure and function post-MI.

Temporal Changes in Infarct Material Properties: An In Vivo Assessment Using Magnetic Resonance Imaging and Finite Element Simulations.

BACKGROUND: Infarct expansion initiates and sustains adverse left ventricular (LV) remodeling after myocardial infarction (MI) and is influenced by temporal changes in infarct material properties. Data from ex vivo biaxial extension testing support this hypothesis; however, infarct material properties have never been measured in vivo. The goal of the current study was to serially quantify the in vivo material properties and fiber orientation of infarcted myocardium over a 12-week period in a porcine model of MI. METHODS: A combination of magnetic resonance imaging (MRI), catheterization, finite element modeling, and numeric optimization was used to analyze posterolateral MI. Specifically, properties were determined by minimizing the difference between in vivo strains and volume calculated from MRI and strains and volume predicted by finite element modeling. RESULTS: In 1 week after MI, the infarct region was found to be approximately 20 times stiffer than normal diastolic myocardium. Over the course of 12 weeks, the infarct region became progressively less stiff as the LV dilated and ejection fraction decreased. The infarct thinned by nearly half during the remodeling period, and infarct fiber angles became more circumferentially oriented. CONCLUSIONS: The results reported here are consistent with previously described ex vivo biaxial extension studies of infarct material properties and the circumferential change of collagen orientation in posterolateral infarcts. The current study represents a significant advance in that the method used allows for the serial assessment of an individual infarct in vivo over time and avoids the inherent limitations related to the testing of excised tissues.

The Influence of Mitral Annuloplasty on Left Ventricular Flow Dynamics.

BACKGROUND: Mitral valve (MV) repair using annuloplasty rings is the preferred method of treatment for MV regurgitation, but the impact of annuloplasty ring placement on left ventricular intraventricular flow has not been studied. METHODS: Annuloplasty rings of varying sizes were placed in 5 healthy sheep (intercommissural ring sizes were 24, 26, 28, 30, and 32 mm), and three-dimensional phase contrast magnetic resonance imaging (4D flow MRI) was performed before and 1 week after ring placement. RESULTS: Normal diastolic flow consisted of diastolic intraventricular vortices that naturally unwound during systole. Postsurgical intraventricular flow was highly disturbed in all sheep, and the disturbance was greatest for undersized rings. Ring size was highly correlated with the diastolic inflow angle (Pearson's r = -0.62, p < 0.1, 95% confidence interval: -0.92 to 0.14). There was a mean angle increase of mean diastolic inflow angle increase of 12.3 degrees (< 30 mm, p < 0.01, 95% confidence interval: 4.8 to 19.6) for rings less than 30 mm. There was an inverse relationship between peak velocity and annuloplasty ring area (Pearson's r = -0.80, p < 0.05, 95% confidence interval: -0.96 to -0.2). Transmitral pressure gradients increased significantly from baseline 0.73 ± 0.18 mm Hg to after annuloplasty 2.31 ± 1.04 mm Hg (p < 0.05). CONCLUSIONS: Mitral valve annuloplasty ring placement disturbs normal left ventricular intraventricular flow patterns, and the degree of disturbance is closely associated with annuloplasty ring size.

Regional myocardial three-dimensional principal strains during postinfarction remodeling.

BACKGROUND: The purpose of this study was to quantify myocardial three-dimensional (3D) principal strains as the left ventricle (LV) remodels after myocardial infarction (MI). Serial quantification of myocardial strains is important for understanding the mechanical response of the LV to MI. Principal strains convert the 3D LV wall-based strain matrix with three normal and three shear elements, to a matrix with three nonzero normal elements, thereby eliminating the shear elements, which are difficult to physically interpret. METHODS: The study was designed to measure principal strains of the remote, border zone, and infarct regions in a porcine model of post-MI LV remodeling. Magnetic resonance imaging was used to measure function and strain at baseline, 1 week, and 4 weeks after infarct. Principal strain was measured using 3D acquisition and the optical flow method for displacement tracking. RESULTS: Principal strains were altered as the LV remodeled. Maximum principal strain magnitude decreased in all regions, including the noninfarcted remote, while maximum principal strain angles rotated away from the radial direction in the border zone and infarct. Minimum principal strain magnitude followed a similar pattern; however, strain angles were altered in all regions. Evolution of principal strains correlated with adverse LV remodeling. CONCLUSIONS: Using a state-of-the-art imaging and optical flow method technique, 3D principal strains can be measured serially after MI in pigs. Results are consistent with progressive infarct stretching as well as with decreased contractile function in the border zone and remote myocardial regions.

Estimating passive mechanical properties in a myocardial infarction using MRI and finite element simulations.

Myocardial infarction (MI) triggers a series of maladaptive events that lead to structural and functional changes in the left ventricle. It is crucial to better understand the progression of adverse remodeling, in order to develop effective treatment. In addition, being able to assess changes in vivo would be a powerful tool in the clinic. The goal of the current study is to quantify the in vivo material properties of infarcted and remote myocardium 1 week after MI, as well as the orientation of collagen fibers in the infarct. This will be accomplished by using a combination of magnetic resonance imaging (MRI), catheterization, finite element modeling, and numerical optimization to analyze a porcine model ([Formula: see text]) of posterolateral myocardial infarction. Specifically, properties will be determined by minimizing the difference between in vivo strains and volume calculated from MRI and finite element model predicted strains and volume. The results indicate that the infarct region is stiffer than the remote region and that the infarct collagen fibers become more circumferentially oriented 1 week post-MI. These findings are consistent with previous studies, which employed ex vivo techniques. The proposed methodology will ultimately provide a means of predicting remote and infarct mechanical properties in vivo at any time point post-MI.

Injectable microsphere gel progressively improves global ventricular function, regional contractile strain, and mitral regurgitation after myocardial infarction.

BACKGROUND: There is continued need for therapies which reverse or abate the remodeling process after myocardial infarction (MI). In this study, we evaluate the longitudinal effects of calcium hydroxyapatite microsphere gel on regional strain, global ventricular function, and mitral regurgitation (MR) in a porcine MI model. METHODS: Twenty-five Yorkshire swine were enrolled. Five were dedicated weight-matched controls. Twenty underwent posterolateral infarction by direct ligation of the circumflex artery and its branches. Infarcted animals were randomly divided into the following 4 groups: 1-week treatment; 1-week control; 4-week treatment; and 4-week control. After infarction, animals received either twenty 150 µL calcium hydroxyapatite gel or saline injections within the infarct. At their respective time points, echocardiograms, cardiac magnetic resonance imaging, and tissue were collected for evaluation of MR, regional and global left ventricular function, wall thickness, and collagen content. RESULTS: Global and regional left ventricular functions were depressed in all infarcted subjects at 1 week compared with healthy controls. By 4-weeks post-infarction, global function had significantly improved in the calcium hydroxyapatite group compared with infarcted controls (ejection fraction 0.485 ± 0.019 vs 0.38 ± 0.017, p < 0.01). Similarly, regional borderzone radial contractile strain (16.3% ± 1.5% vs 11.2% ± 1.5%, p = 0.04), MR grade (0.4 ± 0.2 vs 1.2 ± 0.2, p = 0.04), and infarct thickness (7.8 ± 0.5 mm vs 4.5 ± 0.2 mm, p < 0.01) were improved at this time point in the treatment group compared with infarct controls. CONCLUSIONS: Calcium hydroxyapatite injection after MI progressively improves global left ventricular function, borderzone function, and mitral regurgitation. Using novel biomaterials to augment infarct material properties is a viable alternative in the current management of heart failure.

Real-time magnetic resonance imaging technique for determining left ventricle pressure-volume loops.

BACKGROUND: Rapid determination of the left ventricular (LV) pressure-volume (PV) relationship as loading conditions are varied is the gold standard for assessment of LV function. Cine magnetic resonance imaging (MRI) does not have sufficient spatiotemporal resolution to assess beat-to-beat changes of the LV PV relationship required to measure the LV end-systolic elastance (EES) or preload-recruitable stroke work (PRSW). Our aim was to investigate real-time MRI and semiautomated LV measurement of LV volume to measure PV relations in large animals under normal and inotropically stressed physiologic conditions. METHODS: We determined that PV relationships could be accurately measured using an image exposure time Tex less than 100 ms and frame rate Tfr less than 50 ms at elevated heart rates (∼140 beats per minute) using a golden angle radial MRI k-space trajectory and active contour segmentation. RESULTS: With an optimized exposure time (Tex=95 ms and frame rate Tfr=2.8 ms), we found that there was no significant difference between cine and real-time MRI at rest in end-diastolic volume, end-systolic volume, ejection fraction, stroke volume, or cardiac output (n=5, p<0.05) at either normal or elevated heart rates. We found EES increased from 1.9±0.7 to 3.1±0.3 mm Hg/mL and PRSW increased from 6.2±1.2 to 9.1±0.9 mm Hg during continuous intravenous dobutamine infusion (n=5, p<0.05). CONCLUSIONS: Real-time MRI can assess LV volumes, EES, and PRSW at baseline and elevated inotropic states.