Automated volumetry and quantitative MRI to diagnose peripheral nerve lesions – translational proposal for a new clinical diagnostic imaging tool
Dr. Olivier Scheidegger, Inselspital Bern
Abstract (Lay summary see below)
In the diagnostic work-up of peripheral nerve disorders, neurophysiological studies are a major element complementing clinical examination to appropriately detect, classify and follow nerve lesions. Treatment decisions rely predominantly on this diagnostic approach. However, neurophysiological studies carry several disadvantages: 1) there is no information about structural changes, and 2) some body parts are hampered by unselective investigations (e.g. brachial plexus). In this project, we aim at developing a novel diagnostic tool that addresses these two problems, and upon completion of the project will be ready for deployment to the community of neuromuscular diseases. MR neurography is a relatively new application of clinical MR sequences optimized for peripheral nerves that provides a high anatomical detail and delineates nerve pathologies for qualitative image analysis. However, MR can also yield quantitative information on physical properties of peripheral nerves. The aim of the project is to develop a new volumetric segmentation algorithm for peripheral nerves that is feasible for clinical practice, provides precise location-dependent volumetric parameters of peripheral nerves, and serves as a template (region/volume-of-interest) for the location dependent analysis of more advanced quantitative MR techniques such as T2 relaxometry and diffusion-weighted imaging. Such a diagnostic tool has not been developed so far. Peripheral nerve lesions lead to secondary changes in muscles they innervate, so the precise analysis of changes in physical properties of muscles using quantitative MR provides additional information on the aetiology of the underlying nerve pathology. The software development aims at integrating muscle segmentation and quantitative MR analysis to assess these secondary changes in affected muscles. Validation data will be gathered in healthy volunteers for upper and lower extremities, and the proof-of-concept of the method will be addressed in a longitudinal study of a cohort of clinically and neurophysiologically defined focal neuropathies. The development of this project will serve as a reference for future investigation of patient cohorts with other types of neuropathies.
Lay summary
Erkrankungen des peripheren Nervensystems, d.h. von Nerven, welche aus dem Rückenmark austreten und im gesamten Rumpf sowie in den Armen und Beinen verlaufen, führen zu Störungen des Gefühls, der Hautbeschaffenheit, und auch der Kraftentfaltung der Muskulatur. Um eine allfällig gezielte Therapie dieser Erkrankungen durchzuführen, muss als erstes die genaue Ursache erfasst werden, welche zum Nervenschaden führt. Hierzu kann der Neurologe neben der Symptombeschreibung auch die körperliche Untersuchung beiziehen. Dies erlaubt teilweise eine lokalisatorische Annäherung des Nervenschadens. Wichtig zur Abklärung der Ursache ist zudem, welcher Nervenbestandteil vorwiegend betroffen ist: die Hülle der Nerven (= Myelin), oder das Innere der Nervenfaser (= Axon). Hierfür kann einzig eine apparative Diagnostik helfen, die sog. Elektroneuromyographie, bei welcher Stromimpulse an den Nerven appliziert werden, und die Weiterleitung dieser Impulse am Nerv oder an der Muskulatur gemessen wird. Stammnahe Nervenabschnitte lassen sich mit dieser Technik jedoch nur ungenügend untersuchen, sodass aktuell bei einigen Erkrankungen eine gewisse diagnostische Unsicherheit besteht resp. die Diagnose nicht oder nur verzögert gestellt werden kann. Unser Forschungsprojekt soll versuchen, diese Lücke zu schliessen. Eingesetzt werden neue bildgebende Verfahren mittels MRI, dank welcher verschiedene Nervenabschnitte des gesamten peripheren Nervens zwischen Austritt aus dem Rückenmark bis hin zur Muskulatur untersucht werden können. Die Entwicklung von ausgeklügelten Programmen basierend auf mathematischen Prinzipien der Mustererkennung soll für die Strukturanalyse der Nerven und Muskeln in den hochaufgelösten MRI Bildern beigezogen werden. Damit und mittels neuer MRI Techniken soll die Analyse unterschiedlicher physikalischer Eigenschaften von Myelin und Axone ermöglicht werden. Ebenso wird der Zusammenhang der bildgebenden Veränderungen der Muskulatur bei Nervenerkrankungen damit untersucht werden. An diesem interdisziplinären Projekt arbeiten Forscher aus dem Institute for Surgical Technology and Biomechanics der Universität Bern, aus der Universitätsklinik für Neurologie des Inselspitals Bern, sowie aus dem Universitätsinstitut für Diagnostische und Interventionelle Neuroradiologie des Inselspitals Bern.
Projets
- Nouveaux projets de recherche dès 2024
- L'importance de la recherche
- Projets financés
- Unstructured proteins as therapeutic targets for neuromuscular diseases
- Open and reproducible pipeline for the acquisition and analysis of muscle MRI data in Facioscapulohumeral Muscular Dystrophy
- Dissecting lysosomal signals to fight Pompe disease
- Functional properties and epigenetic signature of quiescent and early activated human muscle reserve cells
- Activation of human skeletal muscle stem cells:role of Orai3 ans its partner AHNAK2 in physiological condition and in Duchenne Muscular Dystrophy
- Understanding the clinical spectrum associated with VMA21 deficiency
- ANTXR2 as a key player in Collagen VI signaling in muscle stem cells: new therapeutic perspectives for COL6-related myopathies.
- Molecular mechanisms of complement activation and neuromuscular disruption by combinations of autoantibodies from patients with Myasthenia Gravis
- From the investigation of the role of SRSF1 in ALS/FTD to its targeting as a therapeutic strategy
- Molecular crosstalk between muscles and motor neurons and its role in neuromuscular circuit formation
- Molecular Diagnosis and Coping Mechanisms in Mitochondrial Myopathies
- IPRIMYO: Immune-privileged, immortal, myogenic stem cells for gene therapy of Muscular Dystrophy
- Effect of RYR1 mutations on muscle spindle function and their impact on the musculoskeletal system
- Therapeutic potential of human myogenic reserve cells in Duchenne Muscular Dystrophy
- Glutamine metabolism as a potential target for Duchenne Muscular Dystrophy
- Targeting protein s-acylation during Tubular Aggregate Myopathy
- Aggravating the phenotype of dystrophic mice for improving preclinical research and clinical translation for Duchenne muscular dystrophy
- Characterization of autoreactive T cells in Guillain-Barré syndrome
- A vascularized human muscle-on-a-chip to elucidate the contribution of endothelial-mesenchymal transition on the progression of muscular dystrophies
- Characterization of a novel form of ALS associated with changes in the sphingolipid metabolism
- Pre-clinical treatment of mouse models carrying recessive Ryr1 mutations with HDAC/DNA methyltransferase inhibitors.
- New aspects of TGFβ signaling in muscle homeostasis and regeneration
- Inhibition of sphingolipid synthesis as a treatment strategy for Duchenne muscular dystrophy
- Tamoxifen in Duchenne muscular dystrophy (TAMDMD)
- DNA aptamers against the DUX4 protein reveal novel therapeutic implications for FSHD
- Facilitating diagnosis of critical illness myopathy using muscle excitability testing
- Rapid Exploratory Imaging for High-resolution and Whole Extremity Coverage in MR Neurography
- Deciphering novel mechanisms and effectors contributing to muscle dysfunction in Myotonic Dystrophy Type I
- Can HDAC/DNA methyltransferase inhibitors improve muscle function in a congenital myopathy caused by recessive RYR1 mutations?
- Identification of the critical regulators of protein synthesis and degradation in human muscle atrophy
- Exploring peripheral B-cell-helper T cell phenotypes in the blood of patients with Myasthenia gravis using mass cytometry (CyTOF)
- Molecular signature, metabolic profile and therapeutic potential of human myogenic reserve cells
- A multicenter cross-sectional and longitudinal study of the Swiss cohort of Merosin-negative congenital muscular dystrophy
- Targeting NADPH oxidase 4 in models of Duchenne muscular dystrophy
- Characterizing the role of ER stress in C9orf72-linked ALS pathology
- Inducing mitophagy with Urolithin A to restore mitochondrial and muscle function in muscular dystrophy
- Motor unit action potentials analysis in patients with myopathies with a new wireless portable and multichannel Surface EMG device (WPM-SEMG)
- Role and therapeutic potential of PLIN3 in neuromuscular diseases
- Changes in ventilation distribution in children with neuromuscular disease using the insufflator/exsufflator technique: An observational study
- Mechanism and function of genome organization in muscle development and integrity
- Role and therapeutic potential of NADPH oxidases in a mouse model of Duchenne Muscular Dystrophy
- Characterization of pathological pathways activated in muscles of patients with congenital myopathies with disturbed Ca2+ homeostasis
- Creation of a study team to conduct an SMA 1-clinical trial at the Centre for Neuromuscular Diseases of the University Children's Hospital Basel (UKBB)
- Novel treatment to stop progressive neuropathy and muscle weakness in multifocal motor neuropathy
- Understanding the pathomechanisms leading to muscle alterations in Myotonic Dystrophy type I
- Automated volumetry and quantitative MRI to diagnose peripheral nerve lesions – translational proposal for a new clinical diagnostic imaging tool
- Novel approaches against Spinal Muscular Atrophy by targeting splicing regulators
- Protective effects and mechanisms of action of tamoxifen in mice with severe muscular diseases
- Role of the receptor FgfrL1 in the development of slow muscle fibers
- Muscle velocity recovery cycles: A new tool for early diagnosis of critical illness myopathy
- Generation of uncommitted human IPSC derived muscle stem cells for therapeutic applications
- Transposable vectors for dystrophin-expression in a murine model for muscular dystrophy
- Cardiac involvement in patients with Duchenne/Becker Muscular Dystrophy; an observational study
- Deciphering the pathogenic mechanisms of C9ORF72 ALS
- Enhancing estrogenic signalling to fight muscular dystrophies: Mechanisms of action and repurposing clinically approved drugs
- Mechanisms and therapeutic potential of modulating PGC‐1α to alter neuromuscular junction morphology and function
- Triggering human myoblast differentiation: from EGFR to myogenic transcription factors
- Improving cellular therapies of muscle dystrophies by uncovering epigenetic and signaling pathways of muscle formation
- Protein engineering in an attempt to increase the mechanical, integrin dependent cytoskeleton-matrix linkage in muscle fibers
- Muscle velocity recovery cycles: a new tool for characterization of muscle disease in vivo
- Excessive neurotrypsin activation and agrin cleavage-a pathogenic condition leading to sarcopenia-like muscle atrophy?
- Evaluation of novel treatment strategies for dyspherlinopathies in mouse models
- Cell therapy of LGMD2D by donor HLA-characterized human mesoangioblasts (hMABs) produced in GMP conditions
- In search of small molecules targeting protein-RNA complex: a novel approach against Spinal Muscular Atrophy
- Restoration of autophagy as a new strategy for the treatment of congenital muscular dystrophies
- Development of magnetic resonance methods for functional imaging of the skeletal muscle
- Targeting ER stress response: a potential mechanism for neuroprotection in Amyotrophic Lateral Sclerosis
- Generation of uncommitted human IPSC derived muscle stem cells for therapeutic applications
- Brochure décrivant les projets
- SEAL Therapeutics AG
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- Le réseau Myosuisse
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