title: Quantification of GABAA receptors in the rat brain with [(123)I]Iomazenil SPECT from factor analysis-denoised images.
abstract: OBJECTIVE
  In vivo imaging of GABAA receptors is essential for the comprehension of psychiatric disorders in which the GABAergic system is implicated. Small animal SPECT provides a modality for in vivo imaging of the GABAergic system in rodents using [(123)I]Iomazenil, an antagonist of the GABAA receptor. The goal of this work is to describe and evaluate different quantitative reference tissue methods that enable reliable binding potential (BP) estimations in the rat brain to be obtained.
  
  
  METHODS
  Five male Sprague-Dawley rats were used for [(123)I]Iomazenil brain SPECT scans. Binding parameters were obtained with a one-tissue compartment model (1TC), a constrained two-tissue compartment model (2TCc), the two-step Simplified Reference Tissue Model (SRTM2), Logan graphical analysis and analysis of delayed-activity images. In addition, we employed factor analysis (FA) to deal with noise in data.
  
  
  RESULTS
  BPND obtained with SRTM2, Logan graphical analysis and delayed-activity analysis was highly correlated with BPF values obtained with 2TCc (r=0.954 and 0.945 respectively, p<0.0001). Equally significant correlations were found between values obtained with 2TCc and SRTM2 in raw and FA-denoised images (r=0.961 and 0.909 respectively, p<0.0001). Scans of at least 100min are required to obtain stable BPND values from raw images while scans of only 70min are sufficient from FA-denoised images. These images are also associated with significantly lower standard errors of 2TCc and SRTM2 BP values.
  
  
  CONCLUSIONS
  Reference tissue methods such as SRTM2 and Logan graphical analysis can provide equally reliable BPND values from rat brain [(123)I]Iomazenil SPECT. Acquisitions, however, can be much less time-consuming either with analysis of delayed activity obtained from a 20-minute scan 50min after tracer injection or with FA-denoising of images.
authors.affiliation: Clinical Neurophysiology and Neuroimaging Unit, Division of Neuropsychiatry, Department of Psychiatry, University Hospitals of Geneva, Switzerland.
authors.forename: Stergios
authors.initials: S
authors.lastname: Tsartsalis
authors.affiliation: Clinical Neurophysiology and Neuroimaging Unit, Division of Neuropsychiatry, Department of Psychiatry, University Hospitals of Geneva, Switzerland; INSERM Unit 1039, J. Fourier University, La Tronche, France.
authors.forename: Marcelle
authors.initials: M
authors.lastname: Moulin-Sallanon
authors.affiliation: Clinical Neurophysiology and Neuroimaging Unit, Division of Neuropsychiatry, Department of Psychiatry, University Hospitals of Geneva, Switzerland.
authors.forename: Noé
authors.initials: N
authors.lastname: Dumas
authors.affiliation: Department of Psychiatry, University of Geneva, Switzerland.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Tournier
authors.affiliation: INSERM Unit 1039, J. Fourier University, La Tronche, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Ghezzi
authors.affiliation: Morphology Unit, Division of Neuropsychiatry, Department of Psychiatry, University Hospitals of Geneva, Switzerland.
authors.forename: Yves
authors.initials: Y
authors.lastname: Charnay
authors.affiliation: Department of Psychiatry, University of Geneva, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ginovart
authors.affiliation: Clinical Neurophysiology and Neuroimaging Unit, Division of Neuropsychiatry, Department of Psychiatry, University Hospitals of Geneva, Switzerland. Electronic address: Philippe.Millet@hcuge.ch.
authors.forename: Philippe
authors.initials: P
authors.lastname: Millet
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005163:Factor Analysis, Statistical; D005442:Flumazenil / Q000031:analogs & derivatives*; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D007700:Kinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D059629:Signal-To-Noise Ratio; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D011963:Receptors, GABA-A; D005442:Flumazenil; C063038:iomazenil
keywords: Benzodiazepine receptor; Factor analysis; GABA(A) receptor; Iomazenil; SPECT