New MRI, 18F-DOPA and 11C-(+)-α-dihydrotetrabenazine templates for Macaca fascicularis neuroimaging: Advantages to improve PET quantification

Small Animal Imaging Research Unit, Center for Applied Medical Research (CIMA) and Clínica Universidad de Navarra, Pamplona, Spain.
NeuroImage (Impact Factor: 6.36). 06/2009; 47(2):533-9. DOI: 10.1016/j.neuroimage.2009.04.078
Source: PubMed


Normalization of neuroimaging studies to a stereotaxic space allows the utilization of standard volumes of interest (VOIs) and voxel-based analysis (SPM). Such spatial normalization of PET and MRI studies requires a high quality template image. The aim of this study was to create new MRI and PET templates of (18)F-DOPA and (11)C-(+)-alpha-dihydrotetrabenazine ((11)C-DTBZ) of the Macaca fascicularis brain, an important animal model of Parkinson's disease. MRI template was constructed as a smoothed average of the scans of 15 healthy animals, previously transformed into the space of one representative MRI. In order to create the PET templates, (18)F-DOPA and (11)C-DTBZ PET of the same subjects were acquired in a dedicated small animal PET scanner and transformed to the created MRI template space. To validate these templates for PET quantification, parametric values obtained with a standard VOI-map applied after spatial normalization to each template were statistically compared to results computed using individual VOIs drawn for each animal. The high correlation between both procedures validated the utilization of all the templates, improving the reproducibility of PET analysis. To prove the utility of the templates for voxel-based quantification, dopamine striatal depletion in a representative monkey treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was assessed by SPM analysis of (11)C-DTBZ PET. A symmetric reduction in striatal (11)C-DTBZ uptake was detected in accordance with the induced lesion. In conclusion, templates of M. fascicularis brain have been constructed and validated for reproducible and automated PET quantification. All templates are electronically available via the internet.

Download full-text


Available from: Mario Riverol
  • Source
    • "They require a common space, with a normalisation template, and a multi-atlas dataset, and sufficient individuals. Magnetic resonance imaging (MRI) templates are currently available for such species as baboons (Black et al., 2001b; Greer et al., 2002), pig-tailed macaques (Macaca nemestrina) (Black et al., 2001a), rhesus monkeys (Macaca mulatta) (McLaren et al., 2009), chimpanzees (Rilling et al., 2007), Japanese macaques (Macaca fuscata) (Quallo et al., 2010), and more recently, marmoset monkeys (Hikishima et al., 2011), and cynomolgus monkeys (Macaca fascicularis) (Collantes et al., 2009; Frey et al., 2011). It has been recognised that there are differences, although subtle, between the brain structures of different macaque species (Van Der Gucht et al., 2006). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Unlabelled: MRI templates and digital atlases are needed for automated and reproducible quantitative analysis of non-human primate PET studies. Segmenting brain images via multiple atlases outperforms single-atlas labelling in humans. We present a set of atlases manually delineated on brain MRI scans of the monkey Macaca fascicularis. We use this multi-atlas dataset to evaluate two automated methods in terms of accuracy, robustness and reliability in segmenting brain structures on MRI and extracting regional PET measures. Methods: Twelve individual Macaca fascicularis high-resolution 3DT1 MR images were acquired. Four individual atlases were created by manually drawing 42 anatomical structures, including cortical and sub-cortical structures, white matter regions, and ventricles. To create the MRI template, we first chose one MRI to define a reference space, and then performed a two-step iterative procedure: affine registration of individual MRIs to the reference MRI, followed by averaging of the twelve resampled MRIs. Automated segmentation in native space was obtained in two ways: 1) Maximum probability atlases were created by decision fusion of two to four individual atlases in the reference space, and transformation back into the individual native space (MAXPROB)(.) 2) One to four individual atlases were registered directly to the individual native space, and combined by decision fusion (PROPAG). Accuracy was evaluated by computing the Dice similarity index and the volume difference. The robustness and reproducibility of PET regional measurements obtained via automated segmentation was evaluated on four co-registered MRI/PET datasets, which included test-retest data. Results: Dice indices were always over 0.7 and reached maximal values of 0.9 for PROPAG with all four individual atlases. There was no significant mean volume bias. The standard deviation of the bias decreased significantly when increasing the number of individual atlases. MAXPROB performed better when increasing the number of atlases used. When all four atlases were used for the MAXPROB creation, the accuracy of morphometric segmentation approached that of the PROPAG method. PET measures extracted either via automatic methods or via the manually defined regions were strongly correlated, with no significant regional differences between methods. Intra-class correlation coefficients for test-retest data were over 0.87. Conclusions: Compared to single atlas extractions, multi-atlas methods improve the accuracy of region definition. They also perform comparably to manually defined regions for PET quantification. Multiple atlases of Macaca fascicularis brains are now available and allow reproducible and simplified analyses.
    Full-text · Article · Mar 2013 · NeuroImage
  • Source
    • "In addition, regions of interest can be outlined in the template images and propagated from these to the observed data (Gee et al., 1993; Fedorov et al., 2011). A number of MRI-based non-human primate brain atlases are available, including the baboon (Black et al., 2001b) and macaque MRI/PET templates (Black et al., 2001a), the rhesus macaque atlas (McLaren et al., 2009), the common marmoset atlas (Hikishima et al., 2011), the MNI macaque template ( " MNI Monkey Space " ; Collantes et al., 2009), and the NeuroMaps macaque atlas (Kuperman et al., 2006; Bowden and Annese, 2007; Bowden et al., 2007; Dubach and Bowden, 2009). Table 1 provides an overview of image-based atlases for non-human primate brains that are currently available for download, in roughly chronological order. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The INIA19 is a new, high-quality template for imaging-based studies of non-human primate brains, created from high-resolution, T(1)-weighted magnetic resonance (MR) images of 19 rhesus macaque (Macaca mulatta) animals. Combined with the comprehensive cortical and sub-cortical label map of the NeuroMaps atlas, the INIA19 is equally suitable for studies requiring both spatial normalization and atlas label propagation. Population-averaged template images are provided for both the brain and the whole head, to allow alignment of the atlas with both skull-stripped and unstripped data, and thus to facilitate its use for skull stripping of new images. This article describes the construction of the template using freely available software tools, as well as the template itself, which is being made available to the scientific community (
    Full-text · Article · Dec 2012 · Frontiers in Neuroinformatics
  • Source
    • "All PET studies were conducted as previously described (Blesa et al., 2010). Details of the standard acquisition protocol and image analysis have been published previously (Collantes et al., 2009; Quincoces et al., 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Parkinson's disease (PD) is diagnosed when striatal dopamine (DA) loss exceeds a certain threshold and the cardinal motor features become apparent. The presymptomatic compensatory mechanisms underlying the lack of motor manifestations despite progressive striatal depletion are not well understood. Most animal models of PD involve the induction of a severe dopaminergic deficit in an acute manner, which departs from the typical, chronic evolution of PD in humans. We have used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administered to monkeys via a slow intoxication protocol to produce a more gradual development of nigral lesion. Twelve control and 38 MPTP-intoxicated monkeys were divided into four groups. The latter included monkeys who were always asymptomatic, monkeys who recovered after showing mild parkinsonian signs, and monkeys with stable, moderate and severe parkinsonism. We found a close correlation between cell loss in the substantia nigra pars compacta (SNc) and striatal dopaminergic depletion and the four motor states. There was an overall negative correlation between the degree of parkinsonism (Kurlan scale) and in vivo PET ((18)F-DOPA K(i) and (11)C-DTBZ binding potential), as well as with TH-immunoreactive cell counts in SNc, striatal dopaminergic markers (TH, DAT and VMAT2) and striatal DA concentration. This intoxication protocol permits to establish a critical threshold of SNc cell loss and dopaminergic innervation distinguishing between the asymptomatic and symptomatic parkinsonian stages. Compensatory changes in nigrostriatal dopaminergic activity occurred in the recovered and parkinsonian monkeys when DA depletion was at least 88% of control, and accordingly may be considered too late to explain compensatory mechanisms in the early asymptomatic period. Our findings suggest the need for further exploration of the role of non-striatal mechanisms in PD prior to the development of motor features.
    Full-text · Article · Jun 2012 · Neurobiology of Disease
Show more