Cyclosporine A Delays the Terminal Disease Stage in the Tfam KO Mitochondrial Myopathy Mouse Model Without Improving Mitochondrial Energy Production.

Introduction And Aims: Mitochondrial myopathies are rare genetic disorders for which no effective treatment exists. We previously showed that the pharmacological cyclophilin inhibitor cyclosporine A (CsA) extends the lifespan of fast-twitch skeletal muscle-specific mitochondrial transcription factor A knockout (Tfam KO) mice, lacking the ability to transcribe mitochondrial DNA and displaying lethal mitochondrial myopathy. Our present aim was to assess whether the positive effect of CsA was associated with improved in vivo mitochondrial energy production.

Beyond weakness: Exploring intramuscular fat and quadriceps atrophy in ACLR recovery.

Muscle weakness following anterior cruciate ligament reconstruction (ACLR) increases the risk of posttraumatic osteoarthritis (OA). However, focusing solely on muscle weakness overlooks other aspects like muscle composition, which could hinder strength recovery. Intramuscular fat is a non-contractile element linked to joint degeneration in idiopathic OA, but its role post-ACLR has not been thoroughly investigated.

Effect of knee joint angle on vastus medialis and vastus lateralis rigidity during isometric submaximal voluntary knee extensions.

The use of shear wave elastography during voluntary contraction has enabled the non-invasive assessment of load sharing strategies between agonist muscles. However, the change in joint angle and voluntary contraction intensity can modify contribution between muscles. The aim of this study was to investigate the effect of knee joint angle on the local mechanical properties of the vastus medialis (VM) and the vastus lateralis (VL) during isometric submaximal voluntary contractions from shear wave elastography mapping.

Quantification of muscle involvement in familial amyloid polyneuropathy using MRI.

Background And Purpose: Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a rare genetic disease with autosomal-dominant inheritance. In this study, we aimed to quantify fatty infiltration (fat fraction [FF]) and magnetization transfer ratio (MTR) in individual muscles of patients with symptomatic and asymptomatic TTR-FAP using magnetic resonance imaging. Secondarily, we aimed to assess correlations with clinical and electrophysiological variables.

Ultra-high field magnetic resonance imaging of the quadriceps tendon enthesis in healthy subjects.

Purpose: Although enthesitis is a hallmark of several rheumatologic conditions, current imaging methods are still unable to characterize entheses changes because of the corresponding short transverse relaxation times (T2). A growing number of MR studies have used Ultra-High Field (UHF) MRI in order to assess low-T2 tissues e.g.

Four-dimensional reconstruction and characterization of bladder deformations.

Background And Objective: Pelvic floor disorders are prevalent diseases and patient care remains difficult as the dynamics of the pelvic floor remains poorly understood. So far, only 2D dynamic observations of straining exercises at excretion are available in the clinics and 3D mechanical defects of pelvic organs are not well studied. In this context, we propose a complete methodology for the 3D representation of non-reversible bladder deformations during exercises, combined with a 3D representation of the location of the highest strain areas on the organ surface.

The Impact of Fatty Infiltration on MRI Segmentation of Lower Limb Muscles in Neuromuscular Diseases: A Comparative Study of Deep Learning Approaches.

Background: Deep learning methods have been shown to be useful for segmentation of lower limb muscle MRIs of healthy subjects but, have not been sufficiently evaluated on neuromuscular disease (NDM) patients.

Purpose: Evaluate the influence of fat infiltration on convolutional neural network (CNN) segmentation of MRIs from NMD patients.

Study Type: Retrospective study.

Mineralocorticoid receptor antagonism in diabetes reduces albuminuria by preserving the glomerular endothelial glycocalyx.

The glomerular endothelial glycocalyx (GEnGlx) forms the first part of the glomerular filtration barrier. Previously, we showed that mineralocorticoid receptor (MR) activation caused GEnGlx damage and albuminuria. In this study, we investigated whether MR antagonism could limit albuminuria in diabetes and studied the site of action.

Whole-muscle fat analysis identifies distal muscle end as disease initiation site in facioscapulohumeral muscular dystrophy.

Background: Facioscapulohumeral dystrophy (FSHD) is a major muscular dystrophy characterized by asymmetric fatty replacement of muscles. We aimed to determine the initiation site and progression profile of the disease in lower extremity muscles of FSHD patients by assessing fat infiltration along their full proximo-distal axis using quantitative MRI.

Methods: Nine patients underwent MRI of lower extremities to assess end-to-end muscle fat fractions (FFs) and inflammatory lesions.

High-content phenotyping of Parkinson's disease patient stem cell-derived midbrain dopaminergic neurons using machine learning classification.

Combining multiple Parkinson's disease (PD) relevant cellular phenotypes might increase the accuracy of midbrain dopaminergic neuron (mDAN) in vitro models. We differentiated patient-derived induced pluripotent stem cells (iPSCs) with a LRRK2 G2019S mutation, isogenic control, and genetically unrelated iPSCs into mDANs. Using automated fluorescence microscopy in 384-well-plate format, we identified elevated levels of α-synuclein (αSyn) and serine 129 phosphorylation, reduced dendritic complexity, and mitochondrial dysfunction.

Patient-Derived Tumor Organoids for Guidance of Personalized Drug Therapies in Recurrent Glioblastoma.

An obstacle to effective uniform treatment of glioblastoma, especially at recurrence, is genetic and cellular intertumoral heterogeneity. Hence, personalized strategies are necessary, as are means to stratify potential targeted therapies in a clinically relevant timeframe. Functional profiling of drug candidates against patient-derived glioblastoma organoids (PD-GBO) holds promise as an empirical method to preclinically discover potentially effective treatments of individual tumors.

The Road Toward Reproducibility of Parametric Mapping of the Heart: A Technical Review.

Parametric mapping of the heart has become an essential part of many cardiovascular magnetic resonance imaging exams, and is used for tissue characterization and diagnosis in a broad range of cardiovascular diseases. These pulse sequences are used to quantify the myocardial T, T, , and T relaxation times, which are unique surrogate indices of fibrosis, edema and iron deposition that can be used to monitor a disease over time or to compare patients to one another. Parametric mapping is now well-accepted in the clinical setting, but its wider dissemination is hindered by limited inter-center reproducibility and relatively long acquisition times.

Characterization of surface motion patterns in highly deformable soft tissue organs from dynamic MRI: An application to assess 4D bladder motion.

Background And Objectives: Dynamic Magnetic Resonance Imaging (MRI) may capture temporal anatomical changes in soft tissue organs with high-contrast but the obtained sequences usually suffer from limited volume coverage which makes the high-resolution reconstruction of organ shape trajectories a major challenge in temporal studies. Because of the variability of abdominal organ shapes across time and subjects, the objective of the present study is to go towards 3D dense velocity measurements to fully cover the entire surface and to extract meaningful features characterizing the observed organ deformations and enabling clinical action or decision.

Methods: We present a pipeline for characterization of bladder surface dynamics during deep respiratory movements.

Personalized functional profiling using patient-derived spheroids points out the potential of an antiangiogenic treatment in a patient with a metastatic lung atypical carcinoid.

Lung carcinoids are neuroendocrine tumors representing 1 to 2% of lung cancers. This study outlines the case of a patient with a metastatic lung atypical carcinoid who presented with a pleural effusion and progression of liver metastases after developing resistance to conventional treatments. Personalized functional profiling (PFP), i.

Impaired aerobic capacity and premature fatigue preceding muscle weakness in the skeletal muscle Tfam-knockout mouse model.

Mitochondrial diseases are genetic disorders that lead to impaired mitochondrial function, resulting in exercise intolerance and muscle weakness. In patients, muscle fatigue due to defects in mitochondrial oxidative capacities commonly precedes muscle weakness. In mice, deletion of the fast-twitch skeletal muscle-specific Tfam gene (Tfam KO) leads to a deficit in respiratory chain activity, severe muscle weakness and early death.

Overview of MR Image Segmentation Strategies in Neuromuscular Disorders.

Neuromuscular disorders are rare diseases for which few therapeutic strategies currently exist. Assessment of therapeutic strategies efficiency is limited by the lack of biomarkers sensitive to the slow progression of neuromuscular diseases (NMD). Magnetic resonance imaging (MRI) has emerged as a tool of choice for the development of qualitative scores for the study of NMD.

Discovery of 4H-chromeno[2,3-d]pyrimidin-4-one derivatives as senescence inducers and their senescence-associated antiproliferative activities on cancer cells using advanced phenotypic assay.

Current research suggests therapy-induced senescence (TIS) of cancer cells characterized by distinct morphological and biochemical phenotypic changes represent a novel functional target that may enhance the effectiveness of cancer therapy. In order to identify novel small-molecule inducers of cellular senescence and determine the potential to be used for the treatment of melanoma, a new method of high-throughput screening (HTS) and high-contents screening (HCS) based on the detection of morphological changes was designed. This image-based and whole cell-based technology was applied to screen and select a novel class of antiproliferative agents on cancer cells, 4H-chromeno[2,3-d]pyrimidin-4-one derivatives, which induced senescence-like phenotypic changes in human melanoma A375 cells without serious cytotoxicity against normal cells.

Supervised segmentation framework for evaluation of diffusion tensor imaging indices in skeletal muscle.

Diffusion tensor imaging (DTI) is becoming a relevant diagnostic tool to understand muscle disease and map muscle recovery processes following physical activity or after injury. Segmenting all the individual leg muscles, necessary for quantification, is still a time-consuming manual process. The purpose of this study was to evaluate the impact of a supervised semi-automatic segmentation pipeline on the quantification of DTI indices in individual upper leg muscles.

Deep learning-based fully automatic segmentation of wrist cartilage in MR images.

The study objective was to investigate the performance of a dedicated convolutional neural network (CNN) optimized for wrist cartilage segmentation from 2D MR images. CNN utilized a planar architecture and patch-based (PB) training approach that ensured optimal performance in the presence of a limited amount of training data. The CNN was trained and validated in 20 multi-slice MRI datasets acquired with two different coils in 11 subjects (healthy volunteers and patients).

Quantitative assessment of sciatic nerve changes in Charcot-Marie-Tooth type 1A patients using magnetic resonance neurography.

Background And Purpose: Nerve tissue alterations have rarely been quantified in Charcot-Marie-Tooth type 1A (CMT1A) patients. The aim of the present study was to quantitatively assess the magnetic resonance imaging (MRI) anomalies of the sciatic and tibial nerves in CMT1A disease using quantitative neurography MRI. It was also intended to seek for correlations with clinical variables.

Fat fraction distribution in lower limb muscles of patients with CMT1A: A quantitative MRI study.

Objective: To quantitatively describe the MRI fat infiltration pattern of muscle degeneration in Charcot-Marie-Tooth (CMT) type 1A (CMT1A) disease and to look for correlations with clinical variables.

Methods: MRI fat fraction was assessed in lower-limb musculature of patients with CMT1A and healthy controls. More particularly, 14 muscle compartments were selected at leg and thigh levels and for proximal, distal, and medial slices.

Quantitative muscle MRI study of patients with sporadic inclusion body myositis.

Background: Fat infiltration in individual muscles of sporadic inclusion body myositis (sIBM) patients has rarely been assessed.

Methods: Sixteen sIBM patients were assessed using MRI of the thighs and lower legs (LL). The severity of fat infiltration, proximal-to-distal and side asymmetries, and the correlations with clinical and functional parameters were investigated.