title: Construction and evaluation of quantitative small-animal PET probabilistic atlases for [¹⁸F]FDG and [¹⁸F]FECT functional mapping of the mouse brain.
abstract: Automated voxel-based or pre-defined volume-of-interest (VOI) analysis of small-animal PET data in mice is necessary for optimal information usage as the number of available resolution elements is limited. We have mapped metabolic ([(18)F]FDG) and dopamine transporter ([(18)F]FECT) small-animal PET data onto a 3D Magnetic Resonance Microscopy (MRM) mouse brain template and aligned them in space to the Paxinos co-ordinate system. In this way, ligand-specific templates for sensitive analysis and accurate anatomical localization were created. Next, using a pre-defined VOI approach, test-retest and intersubject variability of various quantification methods were evaluated. Also, the feasibility of mouse brain statistical parametric mapping (SPM) was explored for [(18)F]FDG and [(18)F]FECT imaging of 6-hydroxydopamine-lesioned (6-OHDA) mice.
  
  
  METHODS
  Twenty-three adult C57BL6 mice were scanned with [(18)F]FDG and [(18)F]FECT. Registrations and affine spatial normalizations were performed using SPM8. [(18)F]FDG data were quantified using (1) an image-derived-input function obtained from the liver (cMRglc), using (2) standardized uptake values (SUVglc) corrected for blood glucose levels and by (3) normalizing counts to the whole-brain uptake. Parametric [(18)F]FECT binding images were constructed by reference to the cerebellum. Registration accuracy was determined using random simulated misalignments and vectorial mismatch determination.
  
  
  RESULTS
  Registration accuracy was between 0.21-1.11 mm. Regional intersubject variabilities of cMRglc ranged from 15.4% to 19.2%, while test-retest values were between 5.0% and 13.0%. For [(18)F]FECT uptake in the caudate-putamen, these values were 13.0% and 10.3%, respectively. Regional values of cMRglc positively correlated to SUVglc measured within the 45-60 min time frame (spearman r = 0.71). Next, SPM analysis of 6-OHDA-lesioned mice showed hypometabolism in the bilateral caudate-putamen and cerebellum, and an unilateral striatal decrease in DAT availability.
  
  
  CONCLUSIONS
  MRM-based small-animal PET templates facilitate accurate assessment and spatial localization of mouse brain function using VOI or voxel-based analysis. Regional intersubject- and test-retest variations indicate that for these targets accuracy comparable to humans can be achieved.
authors.affiliation: Division of Nuclear Medicine, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium. cindy.casteels@med.kuleuven.be
authors.forename: Cindy
authors.initials: C
authors.lastname: Casteels
authors.forename: Kathleen
authors.initials: K
authors.lastname: Vunckx
authors.forename: Sarah-Ann
authors.initials: SA
authors.lastname: Aelvoet
authors.forename: Veerle
authors.initials: V
authors.lastname: Baekelandt
authors.forename: Guy
authors.initials: G
authors.lastname: Bormans
authors.forename: Koen
authors.initials: K
authors.lastname: Van Laere
authors.forename: Michel
authors.initials: M
authors.lastname: Koole
mesh_terms: D000716:Anatomy, Artistic; D000818:Animals; D001271:Atlases as Topic; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D001931:Brain Mapping; D003042:Cocaine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D007091:Image Processing, Computer-Assisted; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015233:Models, Statistical; D016627:Oxidopamine; D049268:Positron-Emission Tomography
chemical_list: C095071:2'-fluoroethyl 8-methyl-3-(4-chlorophenyl)-8-azabicyclo(3.2.1)octane-2-carboxylate; D019788:Fluorodeoxyglucose F18; D016627:Oxidopamine; D003042:Cocaine