TEMPO-conjugated tobacco mosaic virus as a magnetic resonance imaging contrast agent for detection of superoxide production in the inflamed liver.

Superoxide, an anionic dioxygen molecule, plays a crucial role in redox regulation within the body but is implicated in various pathological conditions when produced excessively. Efforts to develop superoxide detection strategies have led to the exploration of organic-based contrast agents for magnetic resonance imaging (MRI). This study compares the effectiveness of two such agents, nTMV-TEMPO and kTMV-TEMPO, for detecting superoxide in a mouse liver model with lipopolysaccharide (LPS)-induced inflammation.

Differential requirements for mitochondrial electron transport chain components in the adult murine liver.

Mitochondrial electron transport chain (ETC) dysfunction due to mutations in the nuclear or mitochondrial genome is a common cause of metabolic disease in humans and displays striking tissue specificity depending on the affected gene. The mechanisms underlying tissue-specific phenotypes are not understood. Complex I (cI) is classically considered the entry point for electrons into the ETC, and in vitro experiments indicate that cI is required for basal respiration and maintenance of the NAD/NADH ratio, an indicator of cellular redox status.

Ultrasound Based Radiomics Features of Chronic Kidney Disease.

Rationale And Objectives: Interstitial fibrosis, common to most chronic kidney diseases, can potentially affect the speckle patterns of kidney ultrasound (US). Here we use Radiomics features derived from US images to identify kidneys with chronic kidney disease.

Materials And Methods: B-mode US without speckle reduction was performed on a cohort of CKD patients (n = 75) and healthy subjects (n = 27).

A novel ultrasound technique to detect early chronic kidney disease.

Chronic kidney disease (CKD) of unknown etiology is recognized as a major public health challenge and a leading cause of morbidity and mortality in the dry zone in Sri Lanka. CKD is asymptomatic and are diagnosed only in late stages. Evidence points to strong correlation between progression of CKD and kidney fibrosis.

Sickle cell anemia mice develop a unique cardiomyopathy with restrictive physiology.

Cardiopulmonary complications are the leading cause of mortality in sickle cell anemia (SCA). Elevated tricuspid regurgitant jet velocity, pulmonary hypertension, diastolic, and autonomic dysfunction have all been described, but a unifying pathophysiology and mechanism explaining the poor prognosis and propensity to sudden death has been elusive. Herein, SCA mice underwent a longitudinal comprehensive cardiac analysis, combining state-of-the-art cardiac imaging with electrocardiography, histopathology, and molecular analysis to determine the basis of cardiac dysfunction.

Genetic diminution of circulating prothrombin ameliorates multiorgan pathologies in sickle cell disease mice.

Sickle cell disease (SCD) results in vascular occlusions, chronic hemolytic anemia, and cumulative organ damage. A conspicuous feature of SCD is chronic inflammation and coagulation system activation. Thrombin (factor IIa [FIIa]) is both a central protease in hemostasis and a key modifier of inflammatory processes.

Disturbance in Z-disk mechanosensitive proteins induced by a persistent mutant myopalladin causes familial restrictive cardiomyopathy.

Background: Familial restrictive cardiomyopathy (FRCM) has a poor prognosis due to diastolic dysfunction and restrictive physiology (RP). Myocardial stiffness, with or without fibrosis, underlie RP, but the mechanism(s) of restrictive remodeling is unclear. Myopalladin (MYPN) is a messenger molecule that links structural and gene regulatory molecules via translocation from the Z-disk and I-bands to the nucleus in cardiomyocytes.

Methodology for implementing patient-specific spatial boundary condition during a cardiac cycle from phase-contrast MRI for hemodynamic assessment.

Pulmonary insufficiency (PI) can render the right ventricle dysfunctional due to volume overloading and hypertrophy. The treatment requires a pulmonary valve replacement surgery. However, determining the right time for the valve replacement surgery has been difficult with currently employed clinical techniques such as, echocardiography and cardiac MRI.

Asymmetric cell-matrix and biomechanical abnormalities in elastin insufficiency induced aortopathy.

Aortopathy is characterized by vascular smooth muscle cell (VSMC) abnormalities and elastic fiber fragmentation. Elastin insufficient (Eln (+/-)) mice demonstrate latent aortopathy similar to human disease. We hypothesized that aortopathy manifests primarily in the aorto-pulmonary septal (APS) side of the thoracic aorta due to asymmetric cardiac neural crest (CNC) distribution.

Quantitative myocardial perfusion in mice based on the signal intensity of flow sensitized CMR.

Background: In the conventional approach to arterial spin labeling in the rodent heart, the relative difference in the apparent T(1) relaxation times corresponding to selective and non-selective inversion is related to perfusion via a two compartment model of tissue. But accurate determination of T(1) in small animal hearts is difficult and prone to errors due to long scan times and high heart rates. In this study we introduce the theoretical frame work for an alternative method (SI-method) based purely on the signal intensity of slice-select and non-select inversion recovery images at a single inversion time at short repetition time.

Early cardiac dysfunction in pediatric patients on maintenance dialysis and post kidney transplant.

Background: Children with advanced chronic kidney disease (CKD) frequently develop left ventricular (LV) hypertrophy. The extent of hypertrophy that results in cardiac dysfunction is unknown. Systolic function, routinely determined by ejection fraction (EF), is usually preserved in these patients.

Presence of mechanical dyssynchrony in Duchenne muscular dystrophy.

Background: Cardiac dysfunction in boys with Duchenne muscular dystrophy (DMD) is a leading cause of death. Cardiac resynchronization therapy (CRT) has been shown to dramatically decrease mortality in eligible adult population with congestive heart failure. We hypothesized that mechanical dyssynchrony is present in DMD patients and that cardiovascular magnetic resonance (CMR) may predict CRT efficacy.

Patterns of left ventricular remodeling in patients with Duchenne Muscular Dystrophy: a cardiac MRI study of ventricular geometry, global function, and strain.

The cardiac disease ubiquitously associated in Duchenne Muscular Dystrophy (DMD) has traditionally been considered a progressive dilated cardiomyopathy (DCM). However, left ventricular (LV) dilatation as measured with cardiac MRI has not been a consistent finding in this population, even as circumferential strain (ε(cc)) declines with advancing disease. We hypothesized that a distinct pattern of changes in LV geometry, during the course of ε(cc) decline, distinguishes DMD associated heart disease from DCM.

Cardiac and skeletal muscle defects in a mouse model of human Barth syndrome.

Barth syndrome is an X-linked genetic disorder caused by mutations in the tafazzin (taz) gene and characterized by dilated cardiomyopathy, exercise intolerance, chronic fatigue, delayed growth, and neutropenia. Tafazzin is a mitochondrial transacylase required for cardiolipin remodeling. Although tafazzin function has been studied in non-mammalian model organisms, mammalian genetic loss of function approaches have not been used.

Magnetic resonance imaging assessment of cardiac dysfunction in δ-sarcoglycan null mice.

Delta-sarcoglycan (δ-sarcoglycan) null, Scgd(-/-), mice develop cardiac and skeletal muscle histopathological alterations similar to those in humans with limb-girdle muscular dystrophy. The objective of this study was to assess the feasibility of using MRI to investigate cardiac dysfunction in Scgd(-/-) mice. Cardiac MRI of 8 month old Scgd(-/-) and wild type (WT) mice was performed.

HIFU lesion volume as a function of sonication time, as determined by MRI, histology, and computations.

Characterization of high-intensity focused ultrasound (HIFU) systems using ex vivo tissues is an important part of the preclinical testing for new HIFU devices. In ex vivo characterization, the lesion volume produced by the absorption of HIFU energy is quantified as operational parameters are varied. This paper examines the three methods used for lesion-volume quantification: histology, magnetic resonance (MR) imaging, and numerical calculations.

Detection of progressive cardiac dysfunction by serial evaluation of circumferential strain in patients with Duchenne muscular dystrophy.

The present study evaluated progressive cardiac dysfunction using serial circumferential strain (epsilon(cc)) measurements in patients with Duchenne muscular dystrophy (DMD). DMD is characterized by progressive cardiac dysfunction and myocardial fibrosis late in the disease process. We hypothesized that serial epsilon(cc) changes could be detected in individual patients with DMD during a time when the left ventricular ejection fraction (EF) changes are insignificant.

High levels of placenta growth factor in sickle cell disease promote pulmonary hypertension.

Pulmonary hypertension is associated with reduced nitric oxide bioavailability and early mortality in sickle cell disease (SCD). We previously demonstrated that placenta growth factor (PlGF), an angiogenic factor produced by erythroid cells, induces hypoxia-independent expression of the pulmonary vasoconstrictor endothelin-1 in pulmonary endothelial cells. Using a lentivirus vector, we simulated erythroid expression of PlGF in normal mice up to the levels seen in sickle mice.

Left ventricular T2 distribution in Duchenne muscular dystrophy.

Background: Although previous studies have helped define the natural history of Duchenne muscular dystrophy (DMD)-associated cardiomyopathy, the myocardial pathobiology associated with functional impairment in DMD is not yet known.The objective of this study was to assess the distribution of transverse relaxation time (T2) in the left ventricle (LV) of DMD patients, and to determine the association of myocardial T2 heterogeneity to the severity of cardiac dysfunction. DMD patients (n = 26) and normal control subjects (n = 13) were studied by cardiovascular magnetic resonance (CMR).

Comparison of magnetic resonance feature tracking for strain calculation with harmonic phase imaging analysis.

Objectives: To compare a steady-state free precession cine sequence-based technique (feature tracking [FT]) to tagged harmonic phase (HARP) analysis for peak average circumferential myocardial strain (epsilon(cc)) analysis in a large and heterogeneous population of boys with Duchenne muscular dystrophy (DMD).

Background: Current epsilon(cc) assessment techniques require cardiac magnetic resonance-tagged imaging sequences, and their analysis is complex. The FT method can readily be performed on standard cine (steady-state free precession) sequences.

Quantification of aortic compliance in mice using radial phase contrast MRI.

Purpose: To investigate the feasibility of radial phase contrast MR imaging to measure in vivo pulse wave velocity (PWV) and wall shear stress (WSS) in small animals on a 7 Tesla scanner.

Materials And Methods: The aortic compliance of 9-month-old ApoE deficient (ApoE-KO) mice (n = 10) on a normal diet was studied in comparison to that of wild-type (WT) mice (n = 10). An undersampled, asymmetric echo radial phase contrast MR technique was developed to measure through plane blood flow velocity at axial slices along the descending aorta.

Circumferential strain analysis identifies strata of cardiomyopathy in Duchenne muscular dystrophy: a cardiac magnetic resonance tagging study.

Objectives: This study sought to evaluate the natural history of occult cardiac dysfunction in Duchenne muscular dystrophy (DMD).

Background: Duchenne muscular dystrophy is characterized by progressive cardiac dysfunction and myocardial fibrosis late in the disease process. We hypothesized that left ventricular myocardial peak circumferential strain (epsilon(cc)) would decrease in DMD before global systolic functional abnormalities regardless of age or ventricular ejection fraction (EF).

Nix-mediated apoptosis links myocardial fibrosis, cardiac remodeling, and hypertrophy decompensation.

Background: Pathological cardiac hypertrophy inevitably remodels, leading to functional decompensation. Although modulation of apoptosis-regulating genes occurs in cardiac hypertrophy, a causal role for programmed cardiomyocyte death in left ventricular (LV) remodeling has not been established.

Methods And Results: We targeted the gene for proapoptotic Nix, which is transcriptionally upregulated in pressure overload and Gq-dependent hypertrophies, in the mouse germ line or specifically in cardiomyocytes (knockout [KO]) and conditionally overexpressed it in the heart (transgenic [TG]).

Inhibition of ischemic cardiomyocyte apoptosis through targeted ablation of Bnip3 restrains postinfarction remodeling in mice.

Following myocardial infarction, nonischemic myocyte death results in infarct expansion, myocardial loss, and ventricular dysfunction. Here, we demonstrate that a specific proapoptotic gene, Bnip3, minimizes ventricular remodeling in the mouse, despite having no effect on early or late infarct size. We evaluated the effects of ablating Bnip3 on cardiomyocyte death, infarct size, and ventricular remodeling after surgical ischemia/reperfusion (IR) injury in mice.

Abdominal fat-water separation with SSFP at 3 Tesla.

The ability of the phase-sensitive steady-state free precession (SSFP) technique to distinguish subcutaneous and visceral adipose tissue in the abdomen at 3 T was evaluated. A phased array receiver radiofrequency coil and a commercially available SSFP sequence were used for imaging. The raw image data were postprocessed to generate fat-only and water-only images.