Mapping the distribution of serotonin transporter in the human brainstem with high-resolution PET: Validation using postmortem autoradiography data

Fazio, Patrik; Schain, Martin; Varnäs, Katarina; Halldin, Christer; Farde, Lars; Varrone, Andrea

doi:10.1016/j.neuroimage.2016.03.019

Cited by 11 publications

(12 citation statements)

References 28 publications

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“…We are not the first to examine individual raphe nuclei in vivo via PET imaging; others have delineated individual nuclei using the serotonin transporter (5-HTT) (Fazio et al, 2016; Son et al, 2014). An advantage to our approach of using 5-HT 1A as opposed to 5-HTT is that 5-HT 1A has a more specific differential distribution across the raphe nuclei (Stockmeier, Shapiro, Haycock, Thompson, & Lowy, 1996), which allows us to target somato-dendritic autoreceptors with greater precision.…”

Section: Discussionmentioning

confidence: 99%

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Will imaging individual raphe nuclei in males with major depressive disorder enhance diagnostic sensitivity and specificity?

et al. 2018

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Will imaging individual raphe nuclei in males with major depressive disorder enhance diagnostic sensitivity and specificity?

et al. 2018

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“…The parametric images were spatially normalized based on parameters obtained from segmentation and coregistration of MR images. Regions of interest (ROIs) for analysis of [ 11 C]PBR28 binding in the cerebellum, limbic cortices and thalamus were defined using the automated anatomical labelling template [31], and ROIs for analysis of radioligand binding in nigrostriatal regions and tracts were defined using a [ 18 F]FE-PE2I PET template according to previously described procedures [32]. In addition, the software package FreeSurfer v. 5.0 [33, 34] was applied for parcellation of brain structures for volumetric analysis based on individual MR images.…”

Section: Methodsmentioning

confidence: 99%

PET imaging of [11C]PBR28 in Parkinson’s disease patients does not indicate increased binding to TSPO despite reduced dopamine transporter binding

Varnäs

Cselényi

Jučaitė

et al. 2018

Eur J Nucl Med Mol Imaging

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PurposeTo examine the hypothesis that cerebral binding to the 18 kDa translocator protein (TSPO), a marker of microglia activation, is elevated in Parkinson’s disease (PD), and to assess the relationship between brain TSPO binding and dopaminergic pathology in PD.MethodsThe radioligand [11C]PBR28 was used for quantitative assessment of brain TSPO in 16 control subjects and 16 PD patients. To analyse the relationship between dopaminergic pathology and brain TSPO binding, PET studies of the dopamine transporter (DAT) were undertaken in PD patients using the DAT radioligand [18F]FE-PE2I. The total distribution volume of [11C]PBR28 was quantified in nigrostriatal regions, limbic cortices and thalamus, and the binding potential of [18F]FE-PE2I was quantified in nigrostriatal regions.ResultsBased on genotype analysis of the TSPO rs6971 polymorphism, 16 subjects (8 control subjects and 8 PD patients) were identified as high-affinity binders, and the remaining subjects were identified as mixed-affinity binders. A two-way ANOVA showed a strong main effect of TSPO genotype on the cerebral binding of [11C]PBR28, whereas no statistically significant main effect of diagnostic group, or a group by genotype interaction was found for any of the regions analysed. [18F]FE-PE2I PET studies in patients indicated a marked reduction in nigrostriatal binding to DAT. However, no correlations between the binding parameters were found for [11C]PBR28 and [18F]FE-PE2I.ConclusionThe findings do not support the hypothesis of elevated cerebral TSPO binding or a relationship between TSPO binding and dopaminergic pathology in PD.Electronic supplementary materialThe online version of this article (10.1007/s00259-018-4161-6) contains supplementary material, which is available to authorized users.

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“…We were specifically interested to examine the impairment of SERT availability in the brainstem nuclei and in relevant projection areas using a high-resolution PET system. In order to accomplish our objective, a methodological approach that we have recently developed and validated for the quantification of SERT availability in the brainstem [19] was used. In addition to the traditional region-based appoach, we also aimed to characterize network characteristic with explorative graph analysis.…”

Section: Introductionmentioning

confidence: 99%

High-resolution PET imaging reveals subtle impairment of the serotonin transporter in an early non-depressed Parkinson’s disease cohort

Fazio

Ferreira

Svenningsson

et al. 2020

Eur J Nucl Med Mol Imaging

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Purpose The serotonin transporter (SERT) is a biochemical marker for monoaminergic signaling in brain and has been suggested to be involved inthe pathophysiology of Parkinson's disease (PD). The aim of this PET study was to examine SERT availability in relevant brain regions in early stages ofnon-depressed PD patients. Methods In a cross-sectional study, 18 PD patients (13 M/5F, 64 ± 7 years, range 46-74 years, disease duration 2.9 ± 2.6 years; UPDRS motor 21.9 ± 5.2) and 20 age-and gender-matched healthy control (HC) subjects (15 M/5F, 61 ± 7 years, range 50-72 years) were included. In a subsequent longitudinal phase, ten of the PD patients (7 M/3F, UPDRS motor 20.6 ± 6.9) underwent a second PET measurement after 18-24 months. After a 3-T MRI acquisition, baseline PET measurements were performed with [ 11 C]MADAM using a high-resolution research tomograph. The non-displaceablebinding potential (BP ND) was chosen as the outcome measure and was estimated at voxel level on wavelet-aided parametric images, by using the Logan graphical analysis and the cerebellum as reference region. A molecular template was generated to visualize and define different subdivisions of the raphe nuclei in the brainstem. Subortical and cortical regions of interest were segmented using FreeSurfer. Univariate analyses and multivariate network analyses were performed on the PET data. Results The univariate region-based analysis showed no differences in SERT levels when the PD patients were compared with the HC neither at baseline or after 2 years of follow-up. The multivariate network analysis also showed no differences at baseline. However, prominent changes in integration and segregation measures were observed at follow-up, indicating a disconnection of the cortical and subcortical regions from the three nuclei of the raphe. Conclusion We conclude that the serotoninergic system in PD patients seems to become involved with a network dysregulation as the disease progresses, suggesting a disturbed serotonergic signaling from raphe nuclei to target subcortical and cortical regions.

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Mapping the distribution of serotonin transporter in the human brainstem with high-resolution PET: Validation using postmortem autoradiography data

Cited by 11 publications

References 28 publications

Will imaging individual raphe nuclei in males with major depressive disorder enhance diagnostic sensitivity and specificity?

Will imaging individual raphe nuclei in males with major depressive disorder enhance diagnostic sensitivity and specificity?

PET imaging of [11C]PBR28 in Parkinson’s disease patients does not indicate increased binding to TSPO despite reduced dopamine transporter binding

High-resolution PET imaging reveals subtle impairment of the serotonin transporter in an early non-depressed Parkinson’s disease cohort

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