Deep phenotyping the right ventricle to establish translational MRI biomarkers for characterization of adaptive and maladaptive states in pulmonary hypertension.

Deep phenotyping the right ventricle (RV) is essential for understanding the mechanisms of adaptive and maladaptive RV responses to pulmonary hypertension (PH). In this study, feature selection coupled with machine learning classification/ranking of specific cardiac magnetic resonance imaging (MRI) features from cine-MRI, flow-sensitized, and extracellular-volume techniques were used to assess RV remodelling in monocrotaline (MCT) and Sugen hypoxia (SuHx) PH rats. Early physiological changes associated with RV adaptation were detected along with prediction of RV maladaptive outcomes.

The influence of geometry on intervertebral disc stiffness.

Geometry plays an important role in intervertebral disc (IVD) mechanics. Previous computational studies have found a link between IVD geometry and stiffness. However, few experimental studies have investigated this link, possibly due to difficulties in non-destructively quantifying internal geometric features.

Quantifying internal intervertebral disc strains to assess nucleus replacement device designs: a digital volume correlation and ultra-high-resolution MRI study.

Nucleus replacement has been proposed as a treatment to restore biomechanics and relieve pain in degenerate intervertebral discs (IVDs). Multiple nucleus replacement devices (NRDs) have been developed, however, none are currently used routinely in clinic. A better understanding of the interactions between NRDs and surrounding tissues may provide insight into the causes of implant failure and provide target properties for future NRD designs.

Restoration of Foxp3 Regulatory T Cells by HDAC-Dependent Epigenetic Modulation Plays a Pivotal Role in Resolving Pulmonary Arterial Hypertension Pathology.

Immune dysregulation is a common feature of pulmonary arterial hypertension (PAH). Histone deacetylase (HDAC)-dependent transcriptional reprogramming epigenetically modulates immune homeostasis and is a novel disease-oriented approach in modern times. To identify a novel functional link between HDAC and regulatory T cells (Tregs) in PAH, aiming to establish disease-modified biomarkers and therapeutic targets.

An comparison of three nucleus pulposus removal techniques for partial intervertebral disc replacement: An ultra-high resolution MRI study.

Background: Nuclectomy, also known as nucleotomy, is a percutaneous surgical procedure performed to remove nucleus material from the center of the disc. Multiple techniques have been considered to perform a nuclectomy, however, the advantages and disadvantages of each are not well understood.

Aims: This biomechanical investigation on human cadaveric specimens aimed to quantitatively compare three nuclectomy techniques performed using an automated shaver, rongeurs, and laser.

TLR7/8 activation induces autoimmune vasculopathy and causes severe pulmonary arterial hypertension.

https://bit.ly/3P3H5V0

Sensitivity of Intervertebral Disc Finite Element Models to Internal Geometric and Non-geometric Parameters.

Finite element models are useful for investigating internal intervertebral disc (IVD) behaviours without using disruptive experimental techniques. Simplified geometries are commonly used to reduce computational time or because internal geometries cannot be acquired from CT scans. This study aimed to (1) investigate the effect of altered geometries both at endplates and the nucleus-anulus boundary on model response, and (2) to investigate model sensitivity to material and geometric inputs, and different modelling approaches (graduated or consistent fibre bundle angles and glued or cohesive inter-lamellar contact).

Multiscale modelling of cerebrovascular injury reveals the role of vascular anatomy and parenchymal shear stresses.

Neurovascular injury is often observed in traumatic brain injury (TBI). However, the relationship between mechanical forces and vascular injury is still unclear. A key question is whether the complex anatomy of vasculature plays a role in increasing forces in cerebral vessels and producing damage.

Annexin A1 restores cerebrovascular integrity concomitant with reduced amyloid-β and tau pathology.

Alzheimer's disease, characterized by brain deposits of amyloid-β plaques and neurofibrillary tangles, is also linked to neurovascular dysfunction and blood-brain barrier breakdown, affecting the passage of substances into and out of the brain. We hypothesized that treatment of neurovascular alterations could be beneficial in Alzheimer's disease. Annexin A1 (ANXA1) is a mediator of glucocorticoid anti-inflammatory action that can suppress microglial activation and reduce blood-brain barrier leakage.

The Effect of Degeneration on Internal Strains and the Mechanism of Failure in Human Intervertebral Discs Analyzed Using Digital Volume Correlation (DVC) and Ultra-High Field MRI.

The intervertebral disc (IVD) plays a main role in absorbing and transmitting loads within the spinal column. Degeneration alters the structural integrity of the IVDs and causes pain, especially in the lumbar region. The objective of this study was to investigate non-invasively the effect of degeneration on human 3D lumbar IVD strains ( = 8) and the mechanism of spinal failure ( = 10) under pure axial compression using digital volume correlation (DVC) and 9.

From biomechanics to pathology: predicting axonal injury from patterns of strain after traumatic brain injury.

The relationship between biomechanical forces and neuropathology is key to understanding traumatic brain injury. White matter tracts are damaged by high shear forces during impact, resulting in axonal injury, a key determinant of long-term clinical outcomes. However, the relationship between biomechanical forces and patterns of white matter injuries, associated with persistent diffusion MRI abnormalities, is poorly understood.

Type 2 MI induced by a single high dose of isoproterenol in C57BL/6J mice triggers a persistent adaptive immune response against the heart.

Heart failure is the common final pathway of several cardiovascular conditions and a major cause of morbidity and mortality worldwide. Aberrant activation of the adaptive immune system in response to myocardial necrosis has recently been implicated in the development of heart failure. The ß-adrenergic agonist isoproterenol hydrochloride is used for its cardiac effects in a variety of different dosing regimens with high doses causing acute cardiomyocyte necrosis.

Hybrid MPI-MRI System for Dual-Modal In Situ Cardiovascular Assessments of Real-Time 3D Blood Flow Quantification-A Pre-Clinical In Vivo Feasibility Investigation.

Non-invasive quantification of functional parameters of the cardiovascular system, in particular the heart, remains very challenging with current imaging techniques. This aspect is mainly due to the fact, that the spatio-temporal resolution of current imaging methods, such as Magnetic Resonance Imaging (MRI) or Positron Emission Tomography (PET), does not offer the desired data repetition rates in the context of real-time data acquisition and thus, can cause artifacts and misinterpretations in accelerated data acquisition approaches. We present a fast non-invasive and quantitative dual-modal in situ cardiovascular assessment using a hybrid imaging system which combines the new imaging modality Magnetic Particle Imaging (MPI) and MRI.

Tracing Nutrient Flux Following Monocarboxylate Transporter-1 Inhibition with AZD3965.

The monocarboxylate transporter 1 (MCT1) is a key element in tumor cell metabolism and inhibition of MCT1 with AZD3965 is undergoing clinical trials. We aimed to investigate nutrient fluxes associated with MCT1 inhibition by AZD3965 to identify possible biomarkers of drug action. We synthesized an F-labeled lactate analogue, [F]--fluorolactate ([F]--FL), that was used alongside [F]fluorodeoxyglucose ([F]FDG), and C-labeled glucose and lactate, to investigate the modulation of metabolism with AZD3965 in diffuse large B-cell lymphoma models in NOD/SCID mice.

Ventricular fibrillation mechanism and global fibrillatory organization are determined by gap junction coupling and fibrosis pattern.

Aims: Conflicting data exist supporting differing mechanisms for sustaining ventricular fibrillation (VF), ranging from disorganized multiple-wavelet activation to organized rotational activities (RAs). Abnormal gap junction (GJ) coupling and fibrosis are important in initiation and maintenance of VF. We investigated whether differing ventricular fibrosis patterns and the degree of GJ coupling affected the underlying VF mechanism.

Synthesis and in vivo behaviour of an exendin-4-based MRI probe capable of β-cell-dependent contrast enhancement in the pancreas.

Global rates of diabetes mellitus are increasing, and treatment of the disease consumes a growing proportion of healthcare spending across the world. Pancreatic β-cells, responsible for insulin production, decline in mass in type 1 and, to a more limited degree, in type 2 diabetes. However, the extent and rate of loss in both diseases differs between patients resulting in the need for the development of novel diagnostic tools, which could quantitatively assess changes in mass of β-cells over time and potentially lead to earlier diagnosis and improved treatments.

Neuron labeling with rhodamine-conjugated Gd-based MRI contrast agents delivered to the brain via focused ultrasound.

Gadolinium-based magnetic resonance imaging contrast agents can provide information regarding neuronal function, provided that these agents can cross the neuronal cell membrane. Such contrast agents are normally restricted to extracellular domains, however, by attaching cationic fluorescent dyes, they can be made cell-permeable and allow for both optical and magnetic resonance detection. To reach neurons, these agents also need to cross the blood-brain barrier.

Quantifying deformations and strains in human intervertebral discs using Digital Volume Correlation combined with MRI (DVC-MRI).

Physical disruptions to intervertebral discs (IVDs) can cause mechanical changes that lead to degeneration and to low back pain which affects 75% of us in our lifetimes. Quantifying the effects of these changes on internal IVD strains may lead to better preventative strategies and treatments. Digital Volume Correlation (DVC) is a non-invasive technique that divides volumetric images into subsets, and measures strains by tracking the internal patterns within them under load.

Enhanced Anti-lymphoma Activity of CAR19-iNKT Cells Underpinned by Dual CD19 and CD1d Targeting.

Chimeric antigen receptor anti-CD19 (CAR19)-T cell immunotherapy-induced clinical remissions in CD19 B cell lymphomas are often short lived. We tested whether CAR19-engineering of the CD1d-restricted invariant natural killer T (iNKT) cells would result in enhanced anti-lymphoma activity. CAR19-iNKT cells co-operatively activated by CD1d- and CAR19-CD19-dependent interactions are more effective than CAR19-T cells against CD1d-expressing lymphomas in vitro and in vivo.

Systemic autoimmunity induced by the TLR7/8 agonist Resiquimod causes myocarditis and dilated cardiomyopathy in a new mouse model of autoimmune heart disease.

Systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) show significant heart involvement and cardiovascular morbidity, which can be due to systemically increased levels of inflammation or direct autoreactivity targeting cardiac tissue. Despite high clinical relevance, cardiac damage secondary to systemic autoimmunity lacks inducible rodent models. Here, we characterise immune-mediated cardiac tissue damage in a new model of SLE induced by topical application of the Toll-like receptor 7/8 (TLR7/8) agonist Resiquimod.

Phased-array of microcoils allows MR microscopy of ex vivo human skin samples at 9.4 T.

Purpose: The aim of this study was to demonstrate the feasibility of a custom-made phased-array microcoil within a 400 MHz animal system for the morphological characterization of human skin tissue in correlation with histopathology.

Materials And Methods: A dedicated 7-channel microcoil-based MR detector arranged in a phased-array geometry was developed to combine the advantages of both a large field of view and a high signal-to-noise ratio. Standard gradient echo sequences were adapted for the characterization of skin morphology ex vivo.

Lineage-specific splicing of a brain-enriched alternative exon promotes glioblastoma progression.

Tissue-specific alternative splicing is critical for the emergence of tissue identity during development, yet the role of this process in malignant transformation is undefined. Tissue-specific splicing involves evolutionarily conserved, alternative exons that represent only a minority of the total alternative exons identified. Many of these conserved exons have functional features that influence signaling pathways to profound biological effect.