title: Is the cerebellum the optimal reference region for intensity normalization of perfusion MR studies in early Alzheimer's disease?
abstract: The cerebellum is the region most commonly used as a reference when normalizing the intensity of perfusion images acquired using magnetic resonance imaging (MRI) in Alzheimer's disease (AD) studies. In addition, the cerebellum provides unbiased estimations with nuclear medicine techniques. However, no reports confirm the cerebellum as an optimal reference region in MRI studies or evaluate the consequences of using different normalization regions. In this study, we address the effect of using the cerebellum, whole-brain white matter, and whole-brain cortical gray matter in the normalization of cerebral blood flow (CBF) parametric maps by comparing patients with stable mild cognitive impairment (MCI), patients with AD and healthy controls. According to our results, normalization by whole-brain cortical gray matter enables more sensitive detection of perfusion abnormalities in AD patients and reveals a larger number of affected regions than data normalized by the cerebellum or whole-brain white matter. Therefore, the cerebellum is not the most valid reference region in MRI studies for early stages of AD. After normalization by whole-brain cortical gray matter, we found a significant decrease in CBF in both parietal lobes and an increase in CBF in the right medial temporal lobe. We found no differences in perfusion between patients with stable MCI and healthy controls either before or after normalization.
authors.affiliation: Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Leganés, Madrid, Spain ; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain ; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Lacalle-Aurioles
authors.affiliation: Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain ; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
authors.forename: Yasser
authors.initials: Y
authors.lastname: Alemán-Gómez
authors.affiliation: Servicio de Radiodiagnóstico. Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Juan Adán
authors.initials: JA
authors.lastname: Guzmán-De-Villoria
authors.affiliation: Servicio de Neurología, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Cruz-Orduña
authors.affiliation: Servicio de Neurología, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Olazarán
authors.affiliation: Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain ; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: José María
authors.initials: JM
authors.lastname: Mateos-Pérez
authors.affiliation: Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: María Elena
authors.initials: ME
authors.lastname: Martino
authors.affiliation: Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Leganés, Madrid, Spain ; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain ; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Desco
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D002531:Cerebellum / Q000473:pathology*; D054022:Cerebrum / Q000098:blood supply; D060825:Cognitive Dysfunction; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D012016:Reference Values; D012039:Regional Blood Flow