Quantitative analysis of hypertrophic myocardium using diffusion tensor magnetic resonance imaging

Systemic hypertension is a causative factor in left ventricular hypertrophy (LVH). This study is motivated by the potential to reverse or manage the dysfunction associated with structural remodeling of the myocardium in this pathology. Using diffusion tensor magnetic resonance imaging, we present an analysis of myocardial fiber and laminar sheet orientation in ex vivo hypertrophic (6 SHR) and normal (5 WKY) rat hearts using the covariance of the diffusion tensor. First, an atlas of normal cardiac microstructure was formed using the WKY b0 images. Then, the SHR and WKY b0 hearts were registered to the atlas. The acquired deformation fields were applied to the SHR and WKY heart tensor fields followed by the preservation of principal direction (PPD) reorientation strategy. A mean tensor field was then formed from the registered WKY tensor images. Calculating the covariance of the registered tensor images about this mean for each heart, the hypertrophic myocardium exhibited significantly increased myocardial fiber derangement (p ¼ 0.017) with a mean dispersion of 38.7 deg, and an increased dispersion of the laminar sheet normal (p = 0.030) of 54.8 deg compared with 34.8 deg and 51.8 deg, respectively, in the normal hearts. Results demonstrate significantly altered myocardial fiber and laminar sheet structure in rats with hypertensive LVH

A level set approach to segmenting a deforming myocardium from dynamically acquired SPECT projection data

Dynamic cardiac single photon emission computed tomography (SPECT) offers an effective way for observing fundamental physiological functions of organs and could aid in the early diagnosis of cardiovascular disease, in particular, for those patients with minimal disease. This would improve the chances of recovery by initiating appropriate therapy and an altered life style. To make dynamic cardiac SPECT viable with present clinical scanners methods need to be developed that reconstruct time activity curves from dynamically moving organs representing the change of tracer concentration as a function of time from projection data acquired from slowly rotating gamma cameras. This type of data analysis faces the challenge of modeling both rigid and non-rigid body deformation as well as modeling of a time varying tracer concentration. In the work presented here, we develop methods for segmenting the beating heart using an approach based upon level sets, which can deal naturally with topological changes. A variational formulation of the level set method was implemented. This allowed the inclusion of a priori information and was computationally efficient. The algorithm was first evaluated with simulated dynamic cardiac image data. The MCAT phantom was used to generate data containing 32 time frames over one cardiac cycle. Each frame had a matrix size of 64×64×32 voxels with a resolution of 6.25 mm. Starting with an initial estimate of the boundary, the algorithm then converged to an accurate segmentation of the deforming heart. The initial estimate was not important and we could segment simultaneously both interior and exterior boundaries. This algorithm forms the foundation for the segmentation of the boundary of the deforming myocardium directly from projection data

Diffusion tensor magnetic resonance imaging-derived myocardial fiber disarray in hypertensive left ventricular hypertrophy: visualization, quantification and the effect on mechanical function

Left ventricular hypertrophy induced by systemic hypertension is generally regarded a morphological precursor of unfortunate cardiovascular events. Myocardial fiber disarray has been long recognized as a prevalent hallmark of this pathology. In this chapter, ex vivo diffusion tensor magnetic resonance imaging is employed to delineate the regional loss of myocardial organization that is present in the excised heart of a spontaneously hypertensive rat, as opposed to a control. Fiber tracking results are provided that illustrate in great detail the alterations in the integrity of cardiac muscle microstructure due to the disease. A quantitative analysis is also performed. Another contribution of this chapter is the model-based assessment of the role of the myofiber disarray in modulating the mechanical properties of the myocardium. The results of this study improve our understanding of the structural remodeling mechanisms that are associated with hypetensive left ventricular hypertrophy and their role

Multi-Scale Modeling of Hypertension

The focus of this work is the coupling of a 1-D lumped parameter model representing the circulatory system to a 3-D finite element based left ventricle (LV) model in order to study the effects of mild hypertension on the cardiovascular system. A Finite Element LV model under normotensive loading (116/80 mmHg) was developed as well as a mild hypertension (165/90 mmHg) model. In both cases, coupled analysis was utilized so that at one diastolic time point and four systolic time points the values for the LV volumes and pressures were determined from the steady-state JSim solution. The normotensive model had an average first principal stress of 39.1KPa while the hypertensive case showed an increased value of 51.8KPa representing a 32.3 % increase. A relatively mild increase in the afterload resulted in a pronounced increase in workload to maintain the same systemic flow. 1

Scroll-Wave Dynamics in Human Cardiac Tissue: Lessons from a Mathematical Model with Inhomogeneities and Fiber Architecture

Cardiac arrhythmias, such as ventricular tachycardia (VT) and ventricular fibrillation (VF), are among the leading causes of death in the industrialized world. These are associated with the formation of spiral and scroll waves of electrical activation in cardiac tissue; single spiral and scroll waves are believed to be associated with VT whereas their turbulent analogs are associated with VF. Thus, the study of these waves is an important biophysical problem. We present a systematic study of the combined effects of muscle-fiber rotation and inhomogeneities on scroll-wave dynamics in the TNNP (ten Tusscher Noble Noble Panfilov) model for human cardiac tissue. In particular, we use the three-dimensional TNNP model with fiber rotation and consider both conduction and ionic inhomogeneities. We find that, in addition to displaying a sensitive dependence on the positions, sizes, and types of inhomogeneities, scroll-wave dynamics also depends delicately upon the degree of fiber rotation. We find that the tendency of scroll waves to anchor to cylindrical conduction inhomogeneities increases with the radius of the inhomogeneity. Furthermore, the filament of the scroll wave can exhibit drift or meandering, transmural bending, twisting, and break-up. If the scroll-wave filament exhibits weak meandering, then there is a fine balance between the anchoring of this wave at the inhomogeneity and a disruption of wave-pinning by fiber rotation. If this filament displays strong meandering, then again the anchoring is suppressed by fiber rotation; also, the scroll wave can be eliminated from most of the layers only to be regenerated by a seed wave. Ionic inhomogeneities can also lead to an anchoring of the scroll wave; scroll waves can now enter the region inside an ionic inhomogeneity and can display a coexistence of spatiotemporal chaos and quasi-periodic behavior in different parts of the simulation domain. We discuss the experimental implications of our study

Influence of Neonatal Hypothyroidism on Hepatic Gene Expression and Lipid Metabolism in Adulthood

Thyroid hormones are required for normal growth and development in mammals. Congenital-neonatal hypothyroidism (CH) has a profound impact on physiology, but its specific influence in liver is less understood. Here, we studied how CH influences the liver gene expression program in adulthood. Pregnant rats were given the antithyroid drug methimazole (MMI) from GD12 until PND30 to induce CH in male offspring. Growth defects due to CH were evident as reductions in body weight and tail length from the second week of life. Once the MMI treatment was discontinued, the feed efficiency increased in CH, and this was accompanied by significant catch-up growth. On PND80, significant reductions in body mass, tail length, and circulating IGF-I levels remained in CH rats. Conversely, the mRNA levels of known GH target genes were significantly upregulated. The serum levels of thyroid hormones, cholesterol, and triglycerides showed no significant differences. In contrast, CH rats showed significant changes in the expression of hepatic genes involved in lipid metabolism, including an increased transcription of PPARα and a reduced expression of genes involved in fatty acid and cholesterol uptake, cellular sterol efflux, triglyceride assembly, bile acid synthesis, and lipogenesis. These changes were associated with a decrease of intrahepatic lipids. Finally, CH rats responded to the onset of hypothyroidism in adulthood with a reduction of serum fatty acids and hepatic cholesteryl esters and to T3 replacement with an enhanced activation of malic enzyme. In summary, we provide in vivo evidence that neonatal hypothyroidism influences the hepatic transcriptional program and tissue sensitivity to hormone treatment in adulthood. This highlights the critical role that a euthyroid state during development plays on normal liver physiology in adulthood

Fourier domain closed-form formulas for estimation of kinetic parameters in reversible multi-compartment models

Background: Compared with static imaging, dynamic emission computed tomographic imaging with compartment modeling can quantify in vivo physiologic processes, providing useful information about molecular disease processes. Dynamic imaging involves estimati

A comparison of hyperelastic warping of pet images with tagged MRI for the analysis of cardiac deformation

The objectives of the following research were to evaluate the utility of a deformable image registration technique known as hyperelastic warping for the measurement of local strains in the left ventricle through the analysis of clinical, gated PET image d

Longitudinal Evaluation of Myocardial Fatty Acid and Glucose Metabolism in Fasted and Nonfasted Spontaneously Hypertensive Rats Using MicroPET/CT

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