title: The neuronal component of gray matter damage in multiple sclerosis: A [(11) C]flumazenil positron emission tomography study.
abstract: OBJECTIVE
  Using positron emission tomography (PET) with [(11) C]flumazenil ([(11) C]FMZ), an antagonist of the central benzodiazepine site located within the GABAA receptor, we quantified and mapped neuronal damage in the gray matter (GM) of patients with multiple sclerosis (MS) at distinct disease stages. We investigated the relationship between neuronal damage and white matter (WM) lesions and evaluated the clinical relevance of this neuronal PET metric.
  
  
  METHODS
  A cohort of 18 MS patients (9 progressive and 9 relapsing-remitting) was compared to healthy controls and underwent neurological and cognitive evaluations, high-resolution dynamic [(11) C]FMZ PET imaging and brain magnetic resonance imaging. [(11) C]FMZ binding was estimated using the partial saturation protocol providing voxel-wise absolute quantification of GABAA receptor concentration. PET data were evaluated using a region of interest (ROI) approach as well as on a vertex-by-vertex basis.
  
  
  RESULTS
  [(11) C]FMZ binding was significantly decreased in the cortical GM of MS patients, compared to controls (-10%). Cortical mapping of benzodiazepine receptor concentration ([(11) C]FMZ Bmax) revealed significant intergroup differences in the bilateral parietal cortices and right frontal areas. ROI analyses taking into account GM volume changes showed extensive decrease in [(11) C]FMZ binding in bilateral parietal, cingulate, and insular cortices as well as in the thalami, amygdalae, and hippocampi. These changes were significant in both progressive and relapsing-remitting forms of the disease and correlated with WM T2-weighted lesion load. [(11) C]FMZ cortical binding correlated with cognitive performance.
  
  
  CONCLUSIONS
  This pilot study showed that PET with [(11) C]FMZ could be a promising and sensitive quantitative marker to assess and map the neuronal substrate of GM pathology in MS.
authors: Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, and CNRS UMR 7225, and ICM, Paris, France.|AP-HP, Hopital Saint-Antoine and Hopital Pitié Salpêtrière, Paris, France.|Service Hospitalier Frederic Joliot, DSV, CEA, Orsay, France.|Department of Neurology, University of Texas Health Science Center at Houston, Houston, TX.
authors: Léorah
authors: L
authors: Freeman
authors: Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, and CNRS UMR 7225, and ICM, Paris, France.|Institut des Neurosciences translationnelles de Paris (IHU-A-ICM), Paris, France.
authors: Daniel
authors: D
authors: Garcia-Lorenzo
authors: Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, and CNRS UMR 7225, and ICM, Paris, France.|AP-HP, Hopital Saint-Antoine and Hopital Pitié Salpêtrière, Paris, France.|Service Hospitalier Frederic Joliot, DSV, CEA, Orsay, France.
authors: Laure
authors: L
authors: Bottin
authors: Service Hospitalier Frederic Joliot, DSV, CEA, Orsay, France.
authors: Claire
authors: C
authors: Leroy
authors: Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, and CNRS UMR 7225, and ICM, Paris, France.|AP-HP, Hopital Saint-Antoine and Hopital Pitié Salpêtrière, Paris, France.
authors: Céline
authors: C
authors: Louapre
authors: Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, and CNRS UMR 7225, and ICM, Paris, France.|AP-HP, Hopital Saint-Antoine and Hopital Pitié Salpêtrière, Paris, France.|Service Hospitalier Frederic Joliot, DSV, CEA, Orsay, France.
authors: Benedetta
authors: B
authors: Bodini
authors: Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, and CNRS UMR 7225, and ICM, Paris, France.|AP-HP, Hopital Saint-Antoine and Hopital Pitié Salpêtrière, Paris, France.
authors: Caroline
authors: C
authors: Papeix
authors: AP-HP, Hopital Saint-Antoine and Hopital Pitié Salpêtrière, Paris, France.
authors: Rana
authors: R
authors: Assouad
authors: AP-HP, Hopital Saint-Antoine and Hopital Pitié Salpêtrière, Paris, France.
authors: Benjamin
authors: B
authors: Granger
authors: Centre Hospitalo-Universitaire de Reims, Université Champagne Ardennes, Reims, France.
authors: Ayman
authors: A
authors: Tourbah
authors: Service Hospitalier Frederic Joliot, DSV, CEA, Orsay, France.
authors: Frédéric
authors: F
authors: Dollé
authors: Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, and CNRS UMR 7225, and ICM, Paris, France.|AP-HP, Hopital Saint-Antoine and Hopital Pitié Salpêtrière, Paris, France.|Service Hospitalier Frederic Joliot, DSV, CEA, Orsay, France.|Institut des Neurosciences translationnelles de Paris (IHU-A-ICM), Paris, France.
authors: Catherine
authors: C
authors: Lubetzki
authors: Service Hospitalier Frederic Joliot, DSV, CEA, Orsay, France.
authors: Michel
authors: M
authors: Bottlaender
authors: Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, and CNRS UMR 7225, and ICM, Paris, France.|AP-HP, Hopital Saint-Antoine and Hopital Pitié Salpêtrière, Paris, France.|Service Hospitalier Frederic Joliot, DSV, CEA, Orsay, France.
authors: Bruno
authors: B
authors: Stankoff
mesh_terms: D000328:Adult; D002250:Carbon Radioisotopes / Q000378:metabolism; D005260:Female; D005442:Flumazenil / Q000378:metabolism; D066128:Gray Matter / Q000000981:diagnostic imaging* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging* / Q000378:metabolism; D009474:Neurons / Q000000981:diagnostic imaging* / Q000378:metabolism; D009929:Organ Size; D010865:Pilot Projects; D049268:Positron-Emission Tomography / Q000379:methods
chemical_list: D002250:Carbon Radioisotopes; D005442:Flumazenil