Contractile Adaptation of the Left Ventricle Post-myocardial Infarction: Predictions by Rodent-Specific Computational Modeling.

Myocardial infarction (MI) results in cardiac myocyte death and the formation of a fibrotic scar in the left ventricular free wall (LVFW). Following an acute MI, LVFW remodeling takes place consisting of several alterations in the structure and properties of cellular and extracellular components with a heterogeneous pattern across the LVFW. The normal function of the heart is strongly influenced by the passive and active biomechanical behavior of the LVFW, and progressive myocardial structural remodeling can have a detrimental effect on both diastolic and systolic functions of the LV leading to heart failure.

A rare case of partial skull and brain duplication in a hatchling Alligator mississippiensis.

Errors in development occur in all vertebrates. When severe, these anomalies are lethal and frequently escape attention. In rare cases, animals with profound malformations are born and can provide a glimpse into structures and their respective function that would otherwise go unnoticed.

Simultaneous Quantification of Anisotropic Microcirculation and Microstructure in Peripheral Nerve.

Peripheral nerve injury is a significant public health challenge, and perfusion in the nerve is a potential biomarker for assessing the injury severity and prognostic outlook. Here, we applied a novel formalism that combined intravoxel incoherent motion (IVIM) and diffusion tensor imaging (DTI) to simultaneously characterize anisotropic microcirculation and microstructure in the rat sciatic nerve. Comparison to postmortem measurements revealed that the in vivo IVIM-DTI signal contained a fast compartment (2.

Incorporating Blood Flow in Nerve Injury and Regeneration Assessment.

Peripheral nerve injury is a significant public health challenge, with limited treatment options and potential lifelong impact on function. More than just an intrinsic part of nerve anatomy, the vascular network of nerves impact regeneration, including perfusion for metabolic demands, appropriate signaling and growth factors, and structural scaffolding for Schwann cell and axonal migration. However, the established nerve injury classification paradigm proposed by Sydney Sunderland in 1951 is based solely on hierarchical disruption to gross anatomical nerve structures and lacks further information regarding the state of cellular, metabolic, or inflammatory processes that are critical in determining regenerative outcomes.

Effect of Subject-Specific, Spatially Reduced, and Idealized Boundary Conditions on the Predicted Hemodynamic Environment in the Murine Aorta.

Mouse models of atherosclerosis have become effective resources to study atherogenesis, including the relationship between hemodynamics and lesion development. Computational methods aid the prediction of the in vivo hemodynamic environment in the mouse vasculature, but careful selection of inflow and outflow boundary conditions (BCs) is warranted to promote model accuracy. Herein, we investigated the impact of animal-specific versus reduced/idealized flow boundary conditions on predicted blood flow patterns in the mouse thoracic aorta.

Vanishing white matter disease expression of truncated EIF2B5 activates induced stress response.

Vanishing white matter disease (VWM) is a severe leukodystrophy of the central nervous system caused by mutations in subunits of the eukaryotic initiation factor 2B complex (eIF2B). Current models only partially recapitulate key disease features, and pathophysiology is poorly understood. Through development and validation of zebrafish () models of VWM, we demonstrate that zebrafish mutants phenocopy VWM, including impaired somatic growth, early lethality, effects on myelination, loss of oligodendrocyte precursor cells, increased apoptosis in the CNS, and impaired motor swimming behavior.

How hydrogel inclusions modulate the local mechanical response in early and fully formed post-infarcted myocardium.

Expansion of myocardium after myocardial infarction (MI) has long been identified as the primary mechanism that drives adverse left ventricular (LV) remodeling towards heart failure and death. Direct injection of hydrogels into the myocardium to mechanically constrain the infarct has demonstrated promise in limiting its remodeling and expansion. Despite early successes, there remain open questions in the determination of optimal hydrogel therapies, key application characteristics for which include injected polymer volume, stiffness, and spatial placement.

Magnetic resonance diffusion tensor tractography of a midbrain auditory circuit in Alligator.

Knowledge of brain circuitry is critical for understanding the organization, function, and evolution of central nervous systems. Most commonly, brain connections have been elucidated using histological and experimental methods that require animal sacrifice. On the other hand, magnetic resonance diffusion tensor imaging and associated tractography have emerged as a preferred method to noninvasively visualize brain white matter tracts.

Insights into the passive mechanical behavior of left ventricular myocardium using a robust constitutive model based on full 3D kinematics.

Myocardium possesses a hierarchical structure that results in complex three-dimensional (3D) mechanical behavior, forming a critical component of ventricular function in health and disease. A wide range of constitutive model forms have been proposed for myocardium since the first planar biaxial studies were performed by Demer and Yin (J. Physiol.

Diffusion MRI using two-dimensional single-shot radial imaging (2D ss-rDWI) with variable flip angle and random view ordering.

Purpose: The main objective of this study is to develop a 2D single-shot radial-DWI (2D ss-rDWI) technique to reduce motion artifacts and geometric distortion in DW images.

Method: A diffusion-preparation module is developed and applied prior to the data acquisition. Because the diffusion-prepared longitudinal magnetization is measured over multiple RF excitations in each shot, 2D ss-rDWI is subject to low signal-to-noise ratio (SNR).

A Computational Cardiac Model for the Adaptation to Pulmonary Arterial Hypertension in the Rat.

Pulmonary arterial hypertension (PAH) imposes pressure overload on the right ventricle (RV), leading to RV enlargement via the growth of cardiac myocytes and remodeling of the collagen fiber architecture. The effects of these alterations on the functional behavior of the right ventricular free wall (RVFW) and organ-level cardiac function remain largely unexplored. Computational heart models in the rat (RHMs) of the normal and hypertensive states can be quite valuable in simulating the effects of PAH on cardiac function to gain insights into the pathophysiology of underlying myocardium remodeling.

Right Ventricular Fiber Structure as a Compensatory Mechanism in Pressure Overload: A Computational Study.

Right ventricular failure (RVF) is a lethal condition in diverse pathologies. Pressure overload is the most common etiology of RVF, but our understanding of the tissue structure remodeling and other biomechanical factors involved in RVF is limited. Some remodeling patterns are interpreted as compensatory mechanisms including myocyte hypertrophy, extracellular fibrosis, and changes in fiber orientation.

Diffusion tensor imaging and histology of developing hearts.

Diffusion tensor imaging (DTI) has emerged as a promising method for noninvasive quantification of myocardial microstructure. However, the origin and behavior of DTI measurements during myocardial normal development and remodeling remain poorly understood. In this work, conventional and bicompartmental DTI in addition to three-dimensional histological correlation were performed in a sheep model of myocardial development from third trimester to postnatal 5 months of age.

Micro-Computed Tomography for the Quantitative 3-Dimensional Assessment of the Compact Myocardium in the Mouse Embryo.

Background: Ventricular non-compaction is characterized by a thin layer of compact ventricular myocardium and it is an important abnormality in the mouse heart. It is reminiscent of left ventricular non-compaction, a fairly common human congenital cardiomyopathy. Non-compaction in transgenic mice has been classically evaluated by measuring the thickness of the compact myocardium through histological techniques involving image analysis of 2-dimensional (D) sections.

Evaluation of Multiple Biological Therapies for Ischemic Cardiac Disease.

The development of cell- and gene-based strategies for regenerative medicine offers a therapeutic option for the repair and potential regeneration of damaged cardiac tissue post-myocardial infarction (MI). Human umbilical cord subepithelial cell-derived stem cells (hUC-SECs), human bone marrow-derived mesenchymal stem cells (hBM-MSCs), and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), all derived from human tissue, have been shown to have in vitro and in vivo therapeutic potential. Additionally, S100a1, VEGF165, and stromal-derived factor-1α (SDF-1α) genes all have the potential to improve cardiac function and/or effect adverse remodeling.

Parametric Modeling of the Mouse Left Ventricular Myocardial Fiber Structure.

Magnetic resonance diffusion tensor imaging (DTI) has greatly facilitated detailed quantifications of myocardial structures. However, structural patterns, such as the distinctive transmural rotation of the fibers, remain incompletely described. To investigate the validity and practicality of pattern-based analysis, 3D DTI was performed on 13 fixed mouse hearts and fiber angles in the left ventricle were transformed and fitted to parametric expressions constructed from elementary functions of the prolate spheroidal spatial variables.

Assessment of the Characteristics of Orientation Distribution Functions in HARDI Using Morphological Metrics.

Orientation distribution functions (ODFs) are widely used to resolve fiber crossing problems in high angular resolution diffusion imaging (HARDI). The characteristics of the ODFs are often assessed using a visual criterion, although the use of objective criteria is also reported, which are directly borrowed from classic signal and image processing theory because they are intuitive and simple to compute. However, they are not always pertinent for the characterization of ODFs.

Orientation dependence of microcirculation-induced diffusion signal in anisotropic tissues.

Purpose: To seek a better understanding of the effect of organized capillary flow on the MR diffusion-weighted signal.

Methods: A theoretical framework was proposed to describe the diffusion-weighted MR signal, which was then validated both numerically using a realistic model of capillary network and experimentally in an animal model of isolated perfused heart preparation with myocardial blood flow verified by means of direct arterial spin labeling measurements.

Results: Microcirculation in organized tissues gave rise to an MR signal that could be described as a combination of the bi-exponential behavior of conventional intravoxel incoherent motion (IVIM) theory and diffusion tensor imaging (DTI) -like anisotropy of the vascular signal, with the flow-related pseudo diffusivity represented as the linear algebraic product between the encoding directional unit vector and an appropriate tensor entity.

Quantitative representation and description of intravoxel fiber complexity in HARDI.

Diffusion tensor imaging and high angular resolution diffusion imaging are often used to analyze the fiber complexity of tissues. In these imaging techniques, the most commonly calculated metric is anisotropy, such as fractional anisotropy (FA), generalized anisotropy (GA), and generalized fractional anisotropy (GFA). The basic idea underlying these metrics is to compute the deviation from free or spherical diffusion.

Finite-Element Extrapolation of Myocardial Structure Alterations Across the Cardiac Cycle in Rats.

Myocardial microstructures are responsible for key aspects of cardiac mechanical function. Natural myocardial deformation across the cardiac cycle induces measurable structural alteration, which varies across disease states. Diffusion tensor magnetic resonance imaging (DT-MRI) has become the tool of choice for myocardial structural analysis.

Higher-Order Motion-Compensation for In Vivo Cardiac Diffusion Tensor Imaging in Rats.

Motion of the heart has complicated in vivo applications of cardiac diffusion MRI and diffusion tensor imaging (DTI), especially in small animals such as rats where ultra-high-performance gradient sets are currently not available. Even with velocity compensation via, for example, bipolar encoding pulses, the variable shot-to-shot residual motion-induced spin phase can still give rise to pronounced artifacts. This study presents diffusion-encoding schemes that are designed to compensate for higher-order motion components, including acceleration and jerk, which also have the desirable practical features of minimal TEs and high achievable b-values.

Characterization of regional deformation and material properties of the intact explanted vein by microCT and computational analysis.

Purpose: Detailed mechanical information of the vein is important to better understand remodeling of the vessel in disease states, but has been difficult to obtain due to its thinness, unique geometry, and limitations of mechanical testing. This study presents a novel method for characterizing deformation of the intact explanted vein under physiological loads and determining its material properties by combining high-resolution imaging and computational analysis.

Methods: High-resolution CT (microCT) was used to image an iodine-stained, excised porcine internal jugular vein sample under extension to 100% and 120% of length, and inflation and 2, 10, 20 mmHg of pressure, inside a microCT-compatible hydrostatic loading chamber.

Characterization of diffuse fibrosis in the failing human heart via diffusion tensor imaging and quantitative histological validation.

Non-invasive imaging techniques are highly desirable as an alternative to conventional biopsy for the characterization of the remodeling of tissues associated with disease progression, including end-stage heart failure. Cardiac diffusion tensor imaging (DTI) has become an established method for the characterization of myocardial microstructure. However, the relationships between diffuse myocardial fibrosis, which is a key biomarker for staging and treatment planning of the failing heart, and measured DTI parameters have yet to be investigated systematically.

Accurate high-resolution measurements of 3-D tissue dynamics with registration-enhanced displacement encoded MRI.

Displacement fields are important to analyze deformation, which is associated with functional and material tissue properties often used as indicators of health. Magnetic resonance imaging (MRI) techniques like DENSE and image registration methods like Hyperelastic Warping have been used to produce pixel-level deformation fields that are desirable in high-resolution analysis. However, DENSE can be complicated by challenges associated with image phase unwrapping, in particular offset determination.

Regression of glioma tumor growth in F98 and U87 rat glioma models by the Nitrone OKN-007.

Background: Glioblastoma multiforme, a World Health Organization grade IV glioma, has a poor prognosis in humans despite current treatment options. Here, we present magnetic resonance imaging (MRI) data regarding the regression of aggressive rat F98 gliomas and human U87 glioma xenografts after treatment with the nitrone compound OKN-007, a disulfonyl derivative of α-phenyl-tert-butyl nitrone.

Methods: MRI was used to assess tumor volumes in F98 and U87 gliomas, and bioluminescence imaging was used to measure tumor volumes in F98 gliomas encoded with the luciferase gene (F98(luc)).