title: A standardized method for the construction of tracer specific PET and SPECT rat brain templates: validation and implementation of a toolbox.
abstract: High-resolution anatomical image data in preclinical brain PET and SPECT studies is often not available, and inter-modality spatial normalization to an MRI brain template is frequently performed. However, this procedure can be challenging for tracers where substantial anatomical structures present limited tracer uptake. Therefore, we constructed and validated strain- and tracer-specific rat brain templates in Paxinos space to allow intra-modal registration. PET [18F]FDG, [11C]flumazenil, [11C]MeDAS, [11C]PK11195 and [11C]raclopride, and SPECT [99mTc]HMPAO brain scans were acquired from healthy male rats. Tracer-specific templates were constructed by averaging the scans, and by spatial normalization to a widely used MRI-based template. The added value of tracer-specific templates was evaluated by quantification of the residual error between original and realigned voxels after random misalignments of the data set. Additionally, the impact of strain differences, disease uptake patterns (focal and diffuse lesion), and the effect of image and template size on the registration errors were explored. Mean registration errors were 0.70 ± 0.32 mm for [18F]FDG (n = 25), 0.23 ± 0.10mm for [11C]flumazenil (n = 13), 0.88 ± 0.20 mm for [11C]MeDAS (n = 15), 0.64 ± 0.28 mm for [11C]PK11195 (n = 19), 0.34 ± 0.15 mm for [11C]raclopride (n = 6), and 0.40 ± 0.13 mm for [99mTc]HMPAO (n = 15). These values were smallest with tracer-specific templates, when compared to the use of [18F]FDG as reference template (p<0.001). Additionally, registration errors were smallest with strain-specific templates (p<0.05), and when images and templates had the same size (p ≤ 0.001). Moreover, highest registration errors were found for the focal lesion group (p<0.005) and the diffuse lesion group (p = n.s.). In the voxel-based analysis, the reported coordinates of the focal lesion model are consistent with the stereotaxic injection procedure. The use of PET/SPECT strain- and tracer-specific templates allows accurate registration of functional rat brain data, independent of disease specific uptake patterns and with registration error below spatial resolution of the cameras. The templates and the SAMIT package will be freely available for the research community [corrected].
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: David
authors.initials: D
authors.lastname: Vállez Garcia
authors.affiliation: Molecular Small Animal Imaging Center (MoSAIC), KU Leuven, Leuven, Belgium.
authors.forename: Cindy
authors.initials: C
authors.lastname: Casteels
authors.affiliation: Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, United States of America.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Schwarz
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Rudi A J O
authors.initials: RA
authors.lastname: Dierckx
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Michel
authors.initials: M
authors.lastname: Koole
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Janine
authors.initials: J
authors.lastname: Doorduin
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D001931:Brain Mapping / Q000379:methods*; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D020891:Raclopride / Q000008:administration & dosage; D011868:Radioisotopes / Q000008:administration & dosage; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D019690:Technetium Tc 99m Exametazime / Q000008:administration & dosage; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D011868:Radioisotopes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D019690:Technetium Tc 99m Exametazime; D020891:Raclopride
references.citation: Neuroimage. 2006 Aug 15;32(2):538-50
references.pmid: 16784876
references.citation: Eur J Nucl Med. 1993 Aug;20(8):661-6
references.pmid: 8404951
references.citation: J Nucl Med. 2006 Nov;47(11):1858-66
references.pmid: 17079820
references.citation: Mol Imaging Biol. 2009 Nov-Dec;11(6):386-98
references.pmid: 19330384
references.citation: Neuroimage. 2012 Oct 15;63(1):47-53
references.pmid: 22776449
references.citation: Neuroinformatics. 2012 Apr;10(2):181-97
references.pmid: 22227717
references.citation: J Neurosci Methods. 2011 Jul 15;199(1):166-72
references.pmid: 21550366
references.citation: Hum Brain Mapp. 2013 Jun;34(6):1306-18
references.pmid: 22287270
references.citation: PLoS One. 2013;8(6):e65286
references.pmid: 23762335
references.citation: Neuroimage. 2014 Feb 15;87:395-402
references.pmid: 24188813
references.citation: Mult Scler. 2014 Oct;20(11):1443-52
references.pmid: 24622349
references.citation: J Neurosci Methods. 2006 Sep 15;155(2):272-84
references.pmid: 16519945
references.citation: J Nucl Med. 2001 Feb;42(2):361-75
references.pmid: 11216537
references.citation: Phys Med Biol. 2003 Jan 21;48(2):211-21
references.pmid: 12587905
references.citation: J Neurosci Methods. 2003 Oct 30;129(2):105-13
references.pmid: 14511814
references.citation: Neuroimage. 2003 Dec;20(4):2100-18
references.pmid: 14683714
references.citation: J Comput Assist Tomogr. 1985 Jan-Feb;9(1):141-53
references.pmid: 3881487
references.citation: J Neurosci Methods. 1985 Apr;13(2):139-43
references.pmid: 3889509