Evaluation of the Degree of Demyelination and Remyelination in Multiple Sclerosis (MS) Detected by Brain Positron Emission Tomography With Amyloid Markers (PET-CT 18F-Florbetaben) and Comparison With MRI Findings

Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system with consequent onset of various sensory, motor, sphincter and sometimes cognitive symptoms. It is characterised by the presence of lympho-monocytic inflammatory infiltrates, demyelination, axonal damage, activation of innate immunity, astrogliosis and remyelination. In the last few years, Magnetic Resonance Imaging (MRI) has made enormous progress in the diagnosis and follow-up of patients, highlighting encephalic and spinal lesions, their number and relative lesion burden, location and cortical involvement as well as the presence of blood-brain barrier alterations in the earliest stages of the disease, associated with the activation of acquired immunity with subsequent inflammatory damage.

The demyelination plaques have on their outer edge a thin wall of iron-containing microglial cells that can be detected by high-resolution magnetic susceptibility MRI sequences and techniques. Such plaques, known by neuropathologists as 'smoldering' plaques, are characterised by a concentrically widening periphery causing myelin and neuronal damage while in the centre of the lesion the process of myelin loss becomes complete. Smoldering plaques, more frequent in progressive forms of the disease, are peculiar of MS compared to other demyelinating diseases and are associated with a negative prognostic significance.

Positron Emission Tomography (PET) is a technique that allows to analyze the in vivo metabolism of certain components of the central nervous system, such as neurons and glia, and, in particular cases, to highlight synaptic function and abnormal protein accumulations. In recent years, PET has been used in MS especially for research purposes: it allows to assess the degree of demyelination and remyelination by using amyloid tracers that bind to the white substance, as well as the degree of microglial activation or synaptic impairment applying particular tracer radio isotopes (TPSO ligands or the glycoprotein 2A of synaptic vesicles). The combination of MRI and PET could provide detailed information not only on the degree and extent of the nervous system impairment, but also on the most affected cell populations, on the metabolic activity of the affected encephalic areas and on the degree of success of the damage repair attempts.

The aim of this research project is to study, applying MRI and PET techniques, a population of progressive MS patients (PMS) with a relatively significant impairment and a population of patients with a relapsing-remitting form of the disease (RRMS) with a less significant neurological impairment. The purpose is to study chronically active or 'smoldering' plaques, with magnetic susceptibility MRI techniques and PET techniques with amyloid tracers, chronically inactive plaques and more recent T2/Flair positive plaques, with or without contrast enhancement, in order to verify and quantify their presence and to correlate their number, morphology and location with the degree of disability, the clinical course, the evolution of the disease and the laboratory data, evaluating in each case the extent of demyelination and remyelination process and the degree of activation of innate immunity. The data obtained will be processed and evaluated to identify MRI and PET differences in the various disease courses and to obtain information on the different desease development paths in patients.

Study design Enrolled patients will undergo a brain MRI, a brain PET scan with amyloid tracer and functional assessment scales at the time of recruitment.