A single-scan protocol for absolute D2/3 receptor quantification with [123I]IBZM SPECT

Tsartsalis, Stergios; Tournier, Benjamin B.; Aoun, Karl; Habiby, Selim; Pandolfo, Diego; Dimiziani, Andrea; Ginovart, Nathalie; Millet, Philippe

doi:10.1016/j.neuroimage.2016.12.050

Cited by 11 publications

(20 citation statements)

References 83 publications

(110 reference statements)

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“…SPECT data were corrected for radioactive decay but not for attenuation, and scatter was applied. A factor analysis denosing was applied on dynamic images, as previously described Tsartsalis et al, 2017). Summed SPECT images (10-60 min) were manually coregistered to a magnetic resonance imaging (MRI) atlas of the mouse brain using the PMOD software.…”

Section: Immunochemistrymentioning

confidence: 99%

TSPO and amyloid deposits in sub-regions of the hippocampus in the 3xTgAD mouse model of Alzheimer’s disease

Tournier

Tsartsalis

Rigaud

et al. 2019

Neurobiology of Disease

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Section: Immunochemistrymentioning

confidence: 99%

TSPO and amyloid deposits in sub-regions of the hippocampus in the 3xTgAD mouse model of Alzheimer’s disease

Tournier

Tsartsalis

Rigaud

et al. 2019

Neurobiology of Disease

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“…Of these, 3 rats were employed in an in vivo multiinjection SPECT imaging protocol for absolute D 2/3 receptor quantification (SPECT-MI in Table 1). Four rats were employed in an arterial plasma analysis for the study of plasma kinetics of the radiotracer and the estimation of the free parent radiotracer fraction (TLC in Table 1) [23]. Four rats were employed in a SPECT experiment with a partial D 2/3 receptor saturation design for the determination of B avail and appK d parameters from an in vivo Scatchard plot (SPECT-PSA in Table 1) [23].…”

Section: Methodsmentioning

confidence: 99%

“…Indeed, appK d is directly related to the affinity of the radiotracer for the receptor (1/appK d ) and may vary as a result of variations in the endogenous ligand of the receptor (i.e., dopamine). This protocol has been recently employed by our group [23] and others [24,25] for D 2/3 imaging using [ 123 I]IBZM and [ 11 C]raclopride in small animals. Overall, this approach has been used to quantify radiotracers with rapid kinetics and this work presents that first application for a radiotracer with slow kinetics, such as [ 123 I]epidepride.…”

Section: Introductionmentioning

confidence: 99%

“…In this paper, we firstly perform a full quantification of [ 123 I]epidepride kinetics using a multi-injection imaging protocol [23,[26][27][28], which separately identifies B avail and appK d . The results of the multi-injection protocol serve as a "gold-standard" for the validation of the partial saturation approach, which is applied at the region-and at the voxel-level.…”

Section: Introductionmentioning

confidence: 99%

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In vivo absolute quantification of striatal and extrastriatal D2/3 receptors with [123I]epidepride SPECT

2020

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Background: [ 123 I]epidepride is a high-affinity radiotracer used in single-photon emission computed tomography (SPECT) imaging of the D 2/3 receptors. It binds with high affinity to striatal and extrastriatal receptors. Nevertheless, its slow kinetics in the striatum impedes quantification in this region. Thus, an approach that would allow a simultaneous quantification of both striatal and extrastriatal D 2/3 receptors would be of interest for preclinical and clinical SPECT neuroimaging. We describe a partial saturation protocol that allows us to produce an in vivo Scatchard plot and thus estimate B avail and appK d separately in both striatal and extrastriatal regions, through a single dynamic SPECT session. To validate this approach, a multi-injection protocol is used for the full kinetic modeling of [ 123 I]epidepride using a two-tissue compartment, 5-parameter model (2T-5k). Methods: Eighteen male rats were used. Binding parameters were estimated using the multi-injection protocol. Various simulations were performed to estimate the optimal conditions for the partial saturation protocol, which was applied at the region and voxel level. The results of the partial saturation study were compared to those obtained with the 2T-5k model. To illustrate the interest of the partial saturation approach, we performed a preliminary study of the effect of a chronic, subcutaneous administration of haloperidol (1 mg/kg/day), a D 2 receptor antagonist, on the B avail of [ 123 I]epidepride in the rat striatum. Results: A series of simulations demonstrated that a mass of 3 ug/kg of unlabeled epidepride allows the formation of an in vivo Scatchard plot. The partial saturation study led to robust estimations of B avail in all brain regions that highly correlated (r = 0.99) with the corresponding values from the multi-injection study. A chronic haloperidol treatment resulted in a 17.9% increase in the B avail values in the left Caudate Putamen nucleus (CP) (p = 0.07) and a 13.8% increase in the right CP (p = 0.12). Conclusion: A partial saturation method allowed the robust quantification of D 2/3 receptors in striatal and extrastriatal D 2/3 receptors with a single-scan approach. This approach may be applied in the mapping of the D 2/3 receptor in translational biological studies and potentially, in clinical SPECT imaging.

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“…Among these methods, factor analysis (FA) has shown its potential in denoising cardiological [11] and, more recently, small-animal brain imaging data [12, 13]. FA separates the signal of dynamic images into a finite number of factor-images [11, 14–16].…”

Section: Introductionmentioning

confidence: 99%

Dynamic image denoising for voxel-wise quantification with Statistical Parametric Mapping in molecular neuroimaging

Tsartsalis

Tournier

et al. 2018

PLoS ONE

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PurposePET and SPECT voxel kinetics are highly noised. To our knowledge, no study has determined the effect of denoising on the ability to detect differences in binding at the voxel level using Statistical Parametric Mapping (SPM).MethodsIn the present study, groups of subject-images with a 10%- and 20%- difference in binding of [123I]iomazenil (IMZ) were simulated. They were denoised with Factor Analysis (FA). Parametric images of binding potential (BPND) were produced with the simplified reference tissue model (SRTM) and the Logan non-invasive graphical analysis (LNIGA) and analyzed using SPM to detect group differences. FA was also applied to [123I]IMZ and [11C]flumazenil (FMZ) clinical images (n = 4) and the variance of BPND was evaluated.ResultsEstimations from FA-denoised simulated images provided a more favorable bias-precision profile in SRTM and LNIGA quantification. Simulated differences were detected in a higher number of voxels when denoised simulated images were used for voxel-wise estimations, compared to quantification on raw simulated images. Variability of voxel-wise binding estimations on denoised clinical SPECT and PET images was also significantly diminished.ConclusionIn conclusion, noise removal from dynamic brain SPECT and PET images may optimize voxel-wise BPND estimations and detection of biological differences using SPM.

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A single-scan protocol for absolute D2/3 receptor quantification with [123I]IBZM SPECT

Cited by 11 publications

References 83 publications

TSPO and amyloid deposits in sub-regions of the hippocampus in the 3xTgAD mouse model of Alzheimer’s disease

TSPO and amyloid deposits in sub-regions of the hippocampus in the 3xTgAD mouse model of Alzheimer’s disease

In vivo absolute quantification of striatal and extrastriatal D2/3 receptors with [123I]epidepride SPECT

Dynamic image denoising for voxel-wise quantification with Statistical Parametric Mapping in molecular neuroimaging

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