Patellar tendon biomechanical and morphologic properties and their relationship to serum clinical variables in persons with prediabetes and type 2 diabetes.

Tendon biomechanical properties and fibril organization are altered in patients with diabetes compared to healthy individuals, yet few biomarkers have been associated with in vivo tendon properties. We investigated the relationships between in vivo imaging-based tendon properties, serum variables, and patient characteristics across healthy controls (n = 14, age: 45 ± 5 years, body mass index [BMI]: 24 ± 1, hemoglobin A1c [HbA1c]: 5.3 ± 0.

Investigation of direction- and age-dependent prestretch in mouse cranial dura mater.

Cranial dura mater is a dense interwoven vascularized connective tissue that helps regulate neurocranial remodeling by responding to strains from the growing brain. Previous ex vivo experimentation has failed to account for the role of prestretch in the mechanical behavior of the dura. Here we aim to estimate the prestretch in mouse cranial dura mater and determine its dependency on direction and age.

PPP1R12C Promotes Atrial Hypocontractility in Atrial Fibrillation.

Background: Atrial fibrillation (AF)-the most common sustained cardiac arrhythmia-increases thromboembolic stroke risk 5-fold. Although atrial hypocontractility contributes to stroke risk in AF, the molecular mechanisms reducing myofilament contractile function remain unknown. We tested the hypothesis that increased expression of PPP1R12C (protein phosphatase 1 regulatory subunit 12C)-the PP1 (protein phosphatase 1) regulatory subunit targeting MLC2a (atrial myosin light chain 2)-causes hypophosphorylation of MLC2a and results in atrial hypocontractility.

Application of 4-D ultrasound-derived regional strain and proteomics analysis in -deficient male mice.

The comprehensive characterization of cardiac structure and function is critical to better understanding various murine models of cardiac disease. We demonstrate here a multimodal analysis approach using high-frequency four-dimensional ultrasound (4DUS) imaging and proteomics to explore the relationship between regional function and tissue composition in a murine model of metabolic cardiomyopathy (). The presented 4DUS analysis outlines a novel approach to mapping both circumferential and longitudinal strain profiles through a standardized framework.

Myosin Light Chain Dephosphorylation by PPP1R12C Promotes Atrial Hypocontractility in Atrial Fibrillation.

Background: Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, increases thromboembolic stroke risk five-fold. Although atrial hypocontractility contributes to stroke risk in AF, the molecular mechanisms reducing myofilament contractile function remain unknown. We tested the hypothesis that increased expression of PPP1R12C, the PP1 regulatory subunit targeting atrial myosin light chain 2 (MLC2a), causes hypophosphorylation of MLC2a and results in atrial hypocontractility.

Localized strain characterization of cardiomyopathy in Duchenne muscular dystrophy using novel 4D kinematic analysis of cine cardiovascular magnetic resonance.

Background: Cardiomyopathy (CMP) is the most common cause of mortality in Duchenne muscular dystrophy (DMD), though the age of onset and clinical progression vary. We applied a novel 4D (3D + time) strain analysis method using cine cardiovascular magnetic resonance (CMR) imaging data to determine if localized strain metrics derived from 4D image analysis would be sensitive and specific for characterizing DMD CMP.

Methods: We analyzed short-axis cine CMR image stacks from 43 DMD patients (median age: 12.

Neurovascular hypoxia after mild traumatic brain injury in juvenile mice correlates with heart-brain dysfunctions in adulthood.

Aim: Retrospective studies suggest that mild traumatic brain injury (mTBI) in pediatric patients may lead to an increased risk of cardiac events. However, the exact functional and temporal dynamics and the associations between heart and brain pathophysiological trajectories are not understood.

Methods: A single impact to the left somatosensory cortical area of the intact skull was performed on juvenile mice (17 days postnatal).

Strain Estimation of the Murine Right Ventricle Using High-Frequency Speckle-Tracking Ultrasound.

Right ventricular (RV) strain measurements from ultrasound via speckle-tracking techniques are being used more frequently as a non-invasive diagnostic tool for a variety of cardiopulmonary pathologies. However, despite the clinical utility of ultrasound RV strain measurements, quantification of RV strain in rodents remains difficult owing to unique image artifacts and non-standardized methodologies. We demonstrate here a simple approach for measuring RV strain in both mice and rats using high-frequency ultrasound and automated speckle tracking.

Machine Learning Driven Contouring of High-Frequency Four-Dimensional Cardiac Ultrasound Data.

Automatic boundary detection of 4D ultrasound (4DUS) cardiac data is a promising yet challenging application at the intersection of machine learning and medicine. Using recently developed murine 4DUS cardiac imaging data, we demonstrate here a set of three machine learning models that predict left ventricular wall kinematics along both the endo- and epi-cardial boundaries. Each model is fundamentally built on three key features: (1) the projection of raw US data to a lower dimensional subspace, (2) a smoothing spline basis across time, and (3) a strategic parameterization of the left ventricular boundaries.

Improving characterization of hypertrophy-induced murine cardiac dysfunction using four-dimensional ultrasound-derived strain mapping.

Mouse models of cardiac disease have become essential tools in the study of pathological mechanisms, but the small size of rodents makes it challenging to quantify heart function with noninvasive imaging. Building off recent developments in high-frequency four-dimensional ultrasound (4DUS) imaging, we have applied this technology to study cardiac dysfunction progression in a murine model of metabolic cardiomyopathy. Cardiac knockout of carnitine palmitoyltransferase 2 () in mice hinders cardiomyocyte bioenergetic metabolism of long-chain fatty acids, and leads to progressive cardiac hypertrophy and heart failure.

Heat therapy improves body composition and muscle function but does not affect capillary or collateral growth in a model of obesity and hindlimb ischemia.

Heat therapy (HT) has emerged as a potential adjunctive therapy to alleviate the symptoms of peripheral artery disease (PAD), but the mechanisms underlying the positive effects of this treatment modality remain undefined. Using a model of diet-induced obesity (DIO) and ischemia-induced muscle damage, we tested the hypothesis that HT would alter body composition, promote vascular growth and mitochondrial biogenesis, and improve skeletal muscle function. Male DIO C57Bl/6J mice underwent bilateral ligation of the femoral artery and were randomly allocated to receive HT or a control intervention for 30 min daily over 3 wk.

Computational Fluid Dynamics of Vascular Disease in Animal Models.

Recent applications of computational fluid dynamics (CFD) applied to the cardiovascular system have demonstrated its power in investigating the impact of hemodynamics on disease initiation, progression, and treatment outcomes. Flow metrics such as pressure distributions, wall shear stresses (WSS), and blood velocity profiles can be quantified to provide insight into observed pathologies, assist with surgical planning, or even predict disease progression. While numerous studies have performed simulations on clinical human patient data, it often lacks prediagnosis information and can be subject to large intersubject variability, limiting the generalizability of findings.

High-Frequency 4-Dimensional Ultrasound (4DUS): A Reliable Method for Assessing Murine Cardiac Function.

In vivo imaging has provided a unique framework for studying pathological progression in various mouse models of cardiac disease. Although conventional short-axis motion-mode (SAX MM) ultrasound and cine magnetic resonance imaging (MRI) are two of the most prevalent strategies used for quantifying cardiac function, there are few notable limitations including imprecision, inaccuracy, and geometric assumptions with ultrasound, or large and costly systems with substantial infrastructure requirements with MRI. Here we present an automated 4-dimensional ultrasound (4DUS) technique that provides comparable information to cine MRI through spatiotemporally synced imaging of cardiac motion.

Multiscale and Spatially-Dependent Biomechanics Reveals Differential Strain Transfer Hierarchy in Skeletal Muscle.

Biological tissues have a complex hierarchical architecture that spans organ to subcellular scales and comprises interconnected biophysical and biochemical machinery. Mechanotransduction, gene regulation, gene protection, and structure-function relationships in tissues depend on how force and strain are modulated from macro to micro scales, and . Traditionally, computational and experimental techniques have been used in common model systems (e.

Cardiac and respiratory-gated volumetric murine ultrasound.

Current cardiovascular ultrasound mainly employs planar imaging techniques to assess function and physiology. These techniques rely on geometric assumptions, which are dependent on the imaging plane, susceptible to inter-observer variability, and may be inaccurate when studying complex diseases. Here, we developed a gated volumetric murine ultrasound technique to visualize cardiovascular motion with high spatiotemporal resolution and directly evaluate cardiovascular health.

Comparison of Traditional and Integrated Digital Anesthetic Vaporizers.

Recent efforts have focused on mitigating anesthetic gas emissions during laboratory animal experiments. A recently developed, digitally controlled, integrated digital vaporizer (IDV) using a syringe pump has been designed to use and administer anesthetic gas to mice and rats more efficiently. The entire IDV system can be placed on a laboratory bench, requires fewer charcoal filters to act as passive scavengers when used at a low gas flow rate, and does not need compressed gas to operate, a requirement for traditional passive systems.

Differentiation of Low- and High-Grade Pediatric Brain Tumors with High b-Value Diffusion-weighted MR Imaging and a Fractional Order Calculus Model.

Purpose: To demonstrate that a new set of parameters (D, β, and μ) from a fractional order calculus (FROC) diffusion model can be used to improve the accuracy of MR imaging for differentiating among low- and high-grade pediatric brain tumors.

Materials And Methods: The institutional review board of the performing hospital approved this study, and written informed consent was obtained from the legal guardians of pediatric patients. Multi-b-value diffusion-weighted magnetic resonance (MR) imaging was performed in 67 pediatric patients with brain tumors.

Mapping putative hubs in human, chimpanzee and rhesus macaque connectomes via diffusion tractography.

Mapping anatomical brain networks with graph-theoretic analysis of diffusion tractography has recently gained popularity, because of its presumed value in understanding brain function. However, this approach has seldom been used to compare brain connectomes across species, which may provide insights into brain evolution. Here, we employed a data-driven approach to compare interregional brain connections across three primate species: 1) the intensively studied rhesus macaque, 2) our closest living primate relative, the chimpanzee, and 3) humans.

Quantitative assessment of a framework for creating anatomical brain networks via global tractography.

Interregional connections of the brain measured with diffusion tractography can be used to infer valuable information regarding both brain structure and function. However, different tractography algorithms can generate networks that exhibit different characteristics, resulting in poor reproducibility across studies. Therefore, it is important to benchmark different tractography algorithms to quantitatively assess their performance.