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. Despite important advances in understanding LVFW passive remodeling in the setting of MI, heterogeneous remodeling in the LVFW active properties and its relationship to organ-level LV function remain understudied. To address these gaps, we developed high-fidelity finite-element (FE) rodent computational cardiac models (RCCMs) of MI using extensive datasets from MI rat hearts representing the heart remodeling from one-week (1-wk) to four-week (4-wk) post-MI timepoints. The rat-specific models (n = 2 for each timepoint) integrate detailed imaging data of the heart geometry, myocardial fiber architecture, and infarct zone determined using late gadolinium enhancement prior to terminal measurements. The computational models predicted a significantly higher level of active tension in remote myocardium in early post-MI hearts (1-wk post-MI) followed by a return to near the control level in late-stage MI (3- and 4-wk post-MI). The late-stage MI rats showed smaller myofiber ranges in the remote region and in-silico experiments using RCCMs suggested that the smaller fiber helicity is consistent with lower contractile forces needed to meet the measured ejection fractions in late-stage MI. In contrast, in-silico experiments predicted that collagen fiber transmural orientation in the infarct region has little influence on organ-level function. In addition, our MI RCCMs indicated that reduced and potentially positive circumferential strains in the infarct region at end-systole can be used to infer information about the time-varying properties of the infarct region. The detailed description of regional passive and active remodeling patterns can complement and enhance the traditional measures of LV anatomy and function that often lead to a gross and limited assessment of cardiac performance. The translation and implementation of our model in patient-specific organ-level simulations offer to advance the investigation of individualized prognosis and intervention for MI.

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. A rare abnormality in a hatchling Alligator mississippiensis is described in which duplication of the skull, face, and brain was incomplete. The rostral skull, face, and associated forebrain, including the olfactory apparatus, were duplicated. However, the caudal skull and brainstem were not. These observations were made with advanced imaging using both computed tomography and magnetic resonance coupled with gross brain dissections. These abnormal features emphasize the complex and intertwined relationship between the development of the brain, face, and skull which are influenced by certain signaling molecules, possible gene mutation(s), and potential environmental factors.

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 (2.32 ± 0.04 × 10−3 mm2/s mean diffusivity, mean ± sem, n = 6, paired t test p < 0.01) that could be attributed to microcirculation in addition to a slower compartment that had similar mean diffusivity as the postmortem nerve (1.04 ± 0.01 vs. 0.96 ± 0.05 × 10−3 mm2/s, p > 0.05). Although further investigation and technical improvement are warranted, this preliminary study demonstrates both the feasibility and potential for applying the IVIM-DTI methodology to peripheral nerves for quantifying perfusion in the presence of anisotropic tissue microstructure.

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. This review covers the anatomical structure of nerve-associated vasculature, and describes the biological processes that makes these vessels critical to successful end-organ reinnervation after severe nerve injuries. We then propose a theoretical framework that incorporates measurements of blood vessel perfusion and inflammation to unify perspectives on all mechanisms of nerve injury.

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. Blood velocities were measured in the aortic root, arch branch vessel, and descending aorta in ApoE-/- mice using phase-contrast MRI. Computational geometries were derived from micro-CT imaging and combinations of high-fidelity or reduced/idealized MR-derived BCs were applied to predict the bulk flow field and hemodynamic metrics (e.g., wall shear stress, WSS; cross-flow index, CFI). Results demonstrate that pressure-free outlet BCs significantly overestimate outlet flow rates as compared to measured values. When compared to models that incorporate 3-component inlet velocity data [[Formula: see text]] and time-varying outlet mass flow splits [[Formula: see text]] (i.e., high-fidelity model), neglecting in-plane inlet velocity components (i.e., [Formula: see text])) leads to errors in WSS and CFI values ranging from 10 to 30% across the model domain whereas the application of a steady outlet mass flow splits results in negligible differences in these hemodynamics metrics. This investigation highlights that 3-component inlet velocity data and at least steady mass flow splits are required for accurate predictions of 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 (Danio rerio) models of VWM, we demonstrate that zebrafish eif2b 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. Expression of human EIF2B2 in the zebrafish eif2b2 mutant rescues lethality and CNS apoptosis, demonstrating conservation of function between zebrafish and human. In the mutants, intron 12 retention leads to expression of a truncated eif2b5 transcript. Expression of the truncated eif2b5 in wild-type larva impairs motor behavior and activates the ISR, suggesting that a feed-forward mechanism in VWM is a significant component of disease pathophysiology.

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. Addressing these questions is complicated by the substantial variations in infarct type and extent, as well as limited understanding of the underlying mechanisms. Herein, we present an investigation on how hydrogel inclusions affect the effective tissue-level stiffness and strain fields in myocardium using full three-dimensional (3D) finite element simulations at early and late post-MI time points. We calibrated our simulations to triaxial mechanical and structural measurements of cuboidal LV myocardial specimens of post-infarcted myocardium, 0 and 4 weeks post-MI, injected with a dual-crosslinking hyaluronic acid-based hydrogel. Simulations included multiple deformation modes that spanned the anticipated physiological range in order to assess the effects of variations in inclusion size, location, and modulus on tissue-level myocardial mechanics. We observed significant local stiffening in the hydrogel-injected specimens that was highly dependent on the volume and mechanical properties of the injected hydrogel. Simulations revealed that the primary effect of the injections under physiological loading was a reduction in myocardial strain. This result suggests that hydrogel injections reduce infarct expansion by limiting the peak strains over the cardiac cycle. Overall, our study indicated that modulation of local effective tissue stiffness and corresponding strain reduction are governed by the volume and stiffness of the hydrogel, but relatively insensitive to its transmural placement. These findings provide important insights into mechanisms for ameliorating post-MI remodeling, as well as guidance for the future design of post-MI therapies.

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. However, existing studies have primarily examined large, heavily myelinated fiber tracts. Whether tractography can visualize fiber bundles that contain thin and poorly myelinated axons is uncertain. To address this question, the midbrain auditory pathway to the thalamus was investigated in Alligator. This species was chosen because of its evolutionary importance as it is the reptilian group most closely related to birds and because its brain contains many thin and poorly myelinated tracts. Furthermore, this auditory pathway is well documented in other reptiles, including a related crocodilian. Histological observations and experimental determination of anterograde connections confirmed this path in Alligator. Tractography identified these tracts in Alligator and provided a 3-dimensional picture that accurately identified the neural elements of this circuit. In addition, tractography identified one possible unrecognized pathway. These results demonstrate that tractography can visualize circuits containing thin, poorly myelinated fibers. These findings open the door for future studies to examine these types of pathways in other vertebrates.

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. 339 (1), 1983). While there have been extensive studies since, none have been based on full 3D kinematic data, nor have they utilized optimal experimental design to estimate constitutive parameters, which may limit their predictive capability. Herein we have applied our novel 3D numerical-experimental methodology (Avazmohammadi et al., Biomechanics Model. Mechanobiol. 2018) to explore the applicability of an orthotropic constitutive model for passive ventricular myocardium (Holzapfel and Ogden, Philos. Trans. R. Soc. Lond.: Math. Phys. Eng. Sci. 367, 2009) by integrating 3D optimal loading paths, spatially varying material structure, and inverse modeling techniques. Our findings indicated that the initial model form was not successful in reproducing all optimal loading paths, due to previously unreported coupling behaviors via shearing of myofibers and extracellular collagen fibers in the myocardium. This observation necessitated extension of the constitutive model by adding two additional terms based on the I8(C) pseudo-invariant in the fiber-normal and sheet-normal directions. The modified model accurately reproduced all optimal loading paths and exhibited improved predictive capabilities. These unique results suggest that more complete constitutive models are required to fully capture the full 3D biomechanical response of left ventricular myocardium. The present approach is thus crucial for improved understanding and performance in cardiac modeling in healthy, diseased, and treatment scenarios.

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). We used variable-flip angle (VFA), random view ordering (RVO), and sliding spokes, and compared the performances to constant flip angle (CFA), smooth view ordering (SVO), and identical spoke averaging, respectively. For each technique, we performed numerical simulation and MRI experiments on a fluid phantom as well as in-vivo human brain studies with a 3 T MRI system. RESULTS: Using VFA, optimal SNR was acquired for 2D ss-rDWI. Using SVO, the high signal is clustered at specific quadrant in 2D k-space: the first quadrant using high initial flip angle or the last quadrant using the low flip angle. This clustered signal in k-space led to geometric distortion in image space. 2D ss-rDWI using RVO spreads the high signaled spokes over all angular directions and removes the view-order-related distortion. The in-vivo images using 2D ss-rDWI with VFA and RVO show no geometric distortion at the skull base brain, but greatly reduced SNR compared with those using 2D ss-DWEPI. CONCLUSION: 2D ss-rDWI is optimized by using VFA with RVO. The resultant DWI using 2D ss-rDWI is insensitive to motion-induced artifacts and geometric distortion. Even with low SNR, it may be useful for DWI of organs limited by severe susceptibility-induced geometric distortion.

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. We thus developed high-fidelity biventricular finite element RHMs for the normal and post-PAH hypertensive states using extensive experimental data collected from rat hearts. We then applied the RHM to investigate the transmural nature of RVFW remodeling and its connection to wall stress elevation under PAH. We found a strong correlation between the longitudinally-dominated fiber-level adaptation of the RVFW and the transmural alterations of relevant wall stress components. We further conducted several numerical experiments to gain new insights on how the RV responds both normally and in the post-PAH state. We found that the effect of pressure overload alone on the increased contractility of the RV is comparable to the effects of changes in the RV geometry and stiffness. Furthermore, our RHMs provided fresh perspectives on long-standing questions of the functional role of the interventricular septum in RV function. Specifically, we demonstrated that an inaccurate identification of the mechanical adaptation of the septum can lead to a significant underestimation of RVFW contractility in the post-PAH state. These findings show how integrated experimental-computational models can facilitate a more comprehensive understanding of the cardiac remodeling events during PAH.

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. However, the specific implications of these changes, especially in relation to clinically observable measurements, are difficult to investigate experimentally. In this computational study, we hypothesized that, with other variables constant, fiber orientation alteration provides a quantifiable and distinct compensatory mechanism during RV pressure overload (RVPO). Numerical models were constructed using a rabbit model of chronic pressure overload RVF based on intraventricular pressure measurements, CINE magnetic resonance imaging (MRI), and diffusion tensor MRI (DT-MRI). Biventricular simulations were conducted under normotensive and hypertensive boundary conditions using variations in RV wall thickness, tissue stiffness, and fiber orientation to investigate their effect on RV pump function. Our results show that a longitudinally aligned myocardial fiber orientation contributed to an increase in RV ejection fraction (RVEF). This effect was more pronounced in response to pressure overload. Likewise, models with longitudinally aligned fiber orientation required a lesser contractility for maintaining a target RVEF against elevated pressures. In addition to increased wall thickness and material stiffness (diastolic compensation), systolic mechanisms in the forms of myocardial fiber realignment and changes in contractility are likely involved in the overall compensatory responses to pressure overload.

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. Comparing the earliest time points in the third trimester with the postnatal 5 month group, the scalar transverse diffusivities preferentially increased in both left ventricle (LV) and right ventricle (RV): secondary eigenvalues D2 increased by 54% (LV) and 36% (RV), whereas tertiary eigenvalues D3 increased by 85% (LV) and 67% (RV). The longitudinal diffusivity D1 changes were small, which led to a decrease in fractional anisotropy by 41% (LV) and 33% (RV) in 5 month versus fetal hearts. Histological analysis suggested that myocardial development is associated with hyperplasia in the early stages of the third trimester followed by myocyte growth in the later stages up to 5 months of age (increased average myocyte width by 198%, myocyte length by 128%, and decreased nucleus density by 70% between preterm and postnatal 5 month hearts.) In a few histological samples (N = 6), correlations were observed between DTI longitudinal diffusivity and myocyte length (r = 0.86, P < 0.05), and transverse diffusivity and myocyte width (r = 0.96, P < 0.01). Linear regression analysis showed that transverse diffusivities are more affected by changes in myocyte size and nucleus density changes than longitudinal diffusivities, which is consistent with predictions of classical models of diffusion in porous media. Furthermore, primary and secondary DTI eigenvectors during development changed significantly. Collectively, the findings demonstrate a role for DTI to monitor and quantify myocardial development, and potentially cardiac disease. Copyright © 2016 John Wiley & Sons, Ltd.

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. Given the 3D nature of the heart, the aim of this study was to determine whether a technique for the non-destructive, 3D assessment of the mouse embryonic compact myocardium could be developed. METHODS AND RESULTS: Micro-computed tomography (micro-CT), in combination with iodine staining, enabled the differentiation of the trabecular from the compact myocardium in wild-type mice. The 3D and digital nature of the micro-CT data allowed computation anatomical techniques to be readily applied, which were demonstrated via construction of group atlases and atlas-based descriptive statistics. Finally, micro-CT was used to identify the presence of non-compaction in mice with a deletion of the cell cycle inhibitor protein, p27(Kip1). CONCLUSIONS: Iodine staining-enhanced micro-CT with computational anatomical analysis represents a valid addition to classical histology for the delineation of compact myocardial wall thickness in the mouse embryo. Given the quantitative 3D resolution of micro-CT, these approaches might provide helpful information for the analysis of non-compaction. (Circ J 2016; 80: 1795-1803).

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. In this study, we compared the therapeutic potential of hBM-MSCs, hUC-SECs, and hiPSC-CMs along with plasmid-based genes to evaluate the in vivo potential of intramyocardially injected biologics to enhance cardiac function in a mouse MI model. Human cells derived from various tissue types were expanded under hypoxic conditions and injected intramyocardially into mice that had undergone left anterior descending (LAD) artery ligation. Similarly, plasmids were also injected into three groups of mice after LAD ligation. Seven experimental groups were studied in total: (1) control (saline), (2) hBM-MSCs, (3) hiPSC-CMs, (4) hUC-SECs, (5) S100a1 plasmid, (6) VEGF165 plasmid, and (7) SDF-1α plasmid. We evaluated echocardiography, hemodynamic catheterization measurements, and histology at 4 and 12 weeks post-biologic injection. Significant improvement was observed in cardiac function and contractility in hiPSC-CM and S100a1 groups and a significant reduction in left ventricle scar within the hUC-SEC group and a slight improvement in the SDF-1α and VEGF165 groups compared to the control group. These results demonstrate the potential for new biologic therapies to reduce scar burden and improve contractile function.

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. It was found that, on average, the myocardial fiber helix angle could be represented to 6.5° accuracy by the equivalence of a product of 10th-order polynomials of the radial and longitudinal variables, and 17th-order Fourier series of the circumferential variable. Similarly, the fiber imbrication angle could be described by 10th-order polynomials and 24th-order Fourier series, to 5.6° accuracy. The representations, while relatively concise, did not adversely affect the information commonly derived from DTI datasets including the whole-ventricle mean fiber helix angle transmural span and atlases constructed for the group. The unique ability of parametric models for predicting the 3D myocardial fiber structure from finite number of 2D slices was also demonstrated. These findings strongly support the principle of parametric modeling for characterizing myocardial structures in the mouse and beyond.

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. We propose a more general paradigm for assessing the characteristics of ODFs. The idea consists in regarding an ODF as a three-dimensional (3D) point cloud, projecting the 3D point cloud onto an angle-distance map, constructing an angle-distance matrix, and calculating metrics such as length ratio, separability, and uncertainty. The results from both simulated and real data show that the proposed metrics allow for the assessment of the characteristics of ODFs in a quantitative and relatively complete manner.

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. Very good agreement between theoretical predictions and both numerical and experimental observations were found. CONCLUSION: These findings suggest that the DTI formalism of anisotropic spin motion can be incorporated into the classical IVIM theory to describe the MR signal arising from diffusion and microcirculation in organized tissues. Magn Reson Med 76:1252-1262, 2016. © 2015 Wiley Periodicals, Inc.

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. However, in many cases, the question is not really to know whether it concerns spherical diffusion. Instead, the main concern is to describe and quantify fiber complexity such as fiber crossing in a voxel. In this context, it would be more direct and effective to compute the deviation from a single fiber bundle instead of a sphere. We propose a new metric, called PEAM (PEAnut Metric), which is based on computing the deviation of orientation diffusion functions (ODFs) from a single fiber bundle ODF represented by a peanut. As an example, the proposed PEAM metric is used to classify intravoxel fiber configurations. The results on simulated data, physical phantom data and real brain data consistently showed that the proposed PEAM provides greater accuracy than FA, GA and GFA and enables parallel and complex fibers to be better distinguished.

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. Yet, obtaining the comprehensive structural information of the whole organ, in 3D and time, for subject-specific examination is fundamentally limited by scan time. Therefore, subject-specific finite-element (FE) analysis of a group of rat hearts was implemented for extrapolating a set of initial DT-MRI to the rest of the cardiac cycle. The effect of material symmetry (isotropy, transverse isotropy, and orthotropy), structural input, and warping approach was observed by comparing simulated predictions against in vivo MRI displacement measurements and DT-MRI of an isolated heart preparation at relaxed, inflated, and contracture states. Overall, the results indicate that, while ventricular volume and circumferential strain are largely independent of the simulation strategy, structural alteration predictions are generally improved with the sophistication of the material model, which also enhances torsion and radial strain predictions. Moreover, whereas subject-specific transversely isotropic models produced the most accurate descriptions of fiber structural alterations, the orthotropic models best captured changes in sheet structure. These findings underscore the need for subject-specific input data, including structure, to extrapolate DT-MRI measurements across the cardiac cycle.