title: Quantification of [(11)C]PIB PET for imaging myelin in the human brain: a test-retest reproducibility study in high-resolution research tomography.
abstract: An accurate in vivo measure of myelin content is essential to deepen our insight into the mechanisms underlying demyelinating and dysmyelinating neurological disorders, and to evaluate the effects of emerging remyelinating treatments. Recently [(11)C]PIB, a positron emission tomography (PET) tracer originally conceived as a beta-amyloid marker, has been shown to be sensitive to myelin changes in preclinical models and humans. In this work, we propose a reference-region methodology for the voxelwise quantification of brain white-matter (WM) binding for [(11)C]PIB. This methodology consists of a supervised procedure for the automatic extraction of a reference region and the application of the Logan graphical method to generate distribution volume ratio (DVR) maps. This approach was assessed on a test-retest group of 10 healthy volunteers using a high-resolution PET tomograph. The [(11)C]PIB PET tracer binding was shown to be up to 23% higher in WM compared with gray matter, depending on the image reconstruction. The DVR estimates were characterized by high reliability (outliers <1%) and reproducibility (intraclass correlation coefficient (ICC) >0.95). [(11)C]PIB parametric maps were also found to be significantly correlated (R(2)>0.50) to mRNA expressions of the most represented proteins in the myelin sheath. On the contrary, no correlation was found between [(11)C]PIB imaging and nonmyelin-associated proteins.
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Mattia
authors.initials: M
authors.lastname: Veronese
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, King's College London, London, UK.|Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.|Inserm, U 1127, Paris, France.|Service Hospitalier Frédéric Joliot, DSV-I2BM, CEA, Orsay, France.|Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Paris, France.|CNRS, UMR 7225, Paris, France.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Bodini
authors.affiliation: Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.|Inserm, U 1127, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Paris, France.|CNRS, UMR 7225, Paris, France.|Institut des Neurosciences Translationnelles de Paris (IHU-A-ICM), Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: García-Lorenzo
authors.affiliation: Department of Neurological and Behavioural Sciences, University of Siena, Siena, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Battaglini
authors.affiliation: Division of Imaging Sciences and Biomechanical Engineering, The Rayne Institute, King's College London, London, UK.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Bongarzone
authors.affiliation: Service Hospitalier Frédéric Joliot, DSV-I2BM, CEA, Orsay, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Comtat
authors.affiliation: Service Hospitalier Frédéric Joliot, DSV-I2BM, CEA, Orsay, France.|Neurospin, I2BM, DSV, CEA, Gif-sur-Yvette, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Bottlaender
authors.affiliation: Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.|Inserm, U 1127, Paris, France.|Service Hospitalier Frédéric Joliot, DSV-I2BM, CEA, Orsay, France.|Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Paris, France.|CNRS, UMR 7225, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Stankoff
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Federico E
authors.initials: FE
authors.lastname: Turkheimer
mesh_terms: D000328:Adult; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000814:Aniline Compounds; D001271:Atlases as Topic; D052160:Benzothiazoles; D001921:Brain / Q000000981:diagnostic imaging*; D005260:Female; D005786:Gene Expression Regulation; D066128:Gray Matter / Q000000981:diagnostic imaging; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography / Q000379:methods*; D012333:RNA, Messenger / Q000096:biosynthesis; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D013844:Thiazoles; D066127:White Matter / Q000000981:diagnostic imaging
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D009185:Myelin Proteins; D012333:RNA, Messenger; D019275:Radiopharmaceuticals; D013844:Thiazoles