title: Estimation of in vivo nonspecific binding in positron emission tomography studies without requiring a reference region.
abstract: Estimation of outcome measures in in vivo neuroreceptor mapping with positron emission tomography (PET) commonly depends on an assumption of uniform nondisplaceable binding throughout the brain. In many cases, this can be estimated based on data from a "reference region," an area of the brain devoid of the receptor of interest. However, often such a region does not exist, as there are some receptors everywhere throughout the brain. Erroneously designating a region as a "reference" can lead to biased estimation, and furthermore, if the level of specific binding in the purported reference region differs between comparison groups, the validity of resulting conclusions may be called into question. We present a method for estimation of all common PET outcome measures that can provide good estimates even when no reference region exists. Our aim is to use information from several regions simultaneously to estimate the information common to all regions. By not requiring specification (or validation) of a reference region, such an approach can provide an automated, objective approach for kinetic modeling of PET data. We illustrate the performance of these methods on simulated data, human [(11)C]WAY-100635 data, and [(11)C]CUMI-101 blocking data in baboons. We show close agreement between estimates obtained by using the proposed method (which does not require a reference region) and estimates based on either a reference region or a blocking study.
authors.affiliation: Department of Biostatistics, Columbia University, 10032, New York, NY, USA; Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, 10032, New York, NY, USA. Electronic address: todd.ogden@columbia.edu.
authors.forename: R
authors.initials: R
authors.lastname: Todd Ogden
authors.affiliation: Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, 10032, New York, NY, USA.
authors.forename: Francesca
authors.initials: F
authors.lastname: Zanderigo
authors.affiliation: Departments of Psychiatry and Radiology, Stony Brook University, Stony Brook, 11794, NY, USA.
authors.forename: Ramin V
authors.initials: RV
authors.lastname: Parsey
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D009010:Monte Carlo Method; D059906:Neuroimaging / Q000379:methods*; D010215:Papio; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals
chemical_list: D019275:Radiopharmaceuticals
keywords: Kinetic modeling; Reference region; Simultaneous estimation