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Soutenance de thèse Sara Trombella

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Mme Sara Trombella soutiendra, en vue de l'obtention du grade de docteur ès sciences, mention interdisciplinaire, sa thèse intitulée

Assessment of Muscular Activity by Positron Emission Tomography using [11C]Acetate

  • Sous la direction de: Prof. José Rolim
  • Et la codirection de: Prof. Nadia Magnenat-Thalmann

Résumé:

Musculo-Skeletal Diseases (MSDs) stands for a whole group of diseases that can affect the human musculoskeletal apparatus, being cause for pain and a sensitive reduction in the mobility extent of the involved joints, resulting for the affected patient in a progressive loss of physical autonomy, up to the complete inability to perform specific movements and daily tasks. Among this class of pathologies, Osteoarthritis (OA) is a chronic disease that causes significant social, psychological, and financial burdens to patients, and can most commonly interests the knee joint - Knee Osteoarthritis (KOA).

Declines in leg strength, particularly in the quadriceps of both the knee affected with KOA as well as the quadriceps of the contralateral knee that is asymptomatic for KOA have been observed in the literature. Among biomechanical factors causing OA, the potential contribution of quadriceps muscle weakness to disease pathogenesis has been the target of several investigations. The quadriceps muscle contributes with a primary role to both functional knee joint stability and knee joint loading. Weak quadriceps muscle may be unable to provide adequate control of tibial translation during ambulation, thus compromising dynamic knee joint stability and consequently increasing risk of damage to joint structures. Moreover, weak muscles may fatigue easily leading to poor neuromuscular control, which could allow pathologic joint movement. An impairment in quadriceps sensorimotor function may also lead to an anomalous and injurious loading of articular structures. Thus, there is nowadays an increasing literatural and clinical evidence that muscle weakness might play a contributory role in the onset and progression of OA.

Positron Emission Tomography (PET) allows to study tissue metabolism in vivo  in a non-invasive way. In particular, it enables to quantitatively characterise several physiologic processes in the skeletal muscle, such as muscle perfusion and oxygen consumption. In the literature, an alternative well-established approach to measure muscle metabolic activity, with respect to traditional Electromyography (EMG), is PET with [18F]2-fluoro-2-deoxy-D-glucose (FDG). A relatively poorly investigated PET tracer when dealing with the investigation of skeletal muscle activity, is acetate, or acetic acid, a molecule that is quickly assimilated by cells and converted into acetyl-CoA by acetyl-CoA synthetase, and in this form involved it can be oxidized to CO2  and H2O by the Tricarboxylic Acid Cycle (TCA), thus producing energy. Due to this versatile uptake mechanism, it can result useful in many diagnostic fields, such as cardiology and oncology. Acetate uptake was investigated in the human limbs’ skeletal muscle, however, up to our best knowledge, just a few number of studies in the literaturature investigated the metabolic fate of acetate in the skeletal muscle at rest and after exercise by PET.

The purpose of the present study is to investigate exercise-related changes in the skeletal muscle by PET and [11C]acetate, in the animal and the human. At this purpose, a pre-clinical and a clinical protocol were implemented. The veterinary experiment involved the application of kinetic analysis to investigate the metabolism of the skeletal muscle of the rat and the comparison to more conventional quantitation approaches.

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Date: Mardi 20 septembre 2016 à 13h30

Lieu: Battelle bâtiment A - Salle de cours 301-302 (2ème étage)

7 septembre 2016
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