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

Tsartsalis, Stergios; Tournier, Benjamin B.; C, Graf; Ginovart, Nathalie; Ibáñez, Vicente; Millet, Philippe

doi:10.1371/journal.pone.0203589

Cited by 5 publications

(3 citation statements)

References 48 publications

(70 reference statements)

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“…Since β must be reliably estimated, ROI-level data are the likely current limit for this approach because the level of statistical noise for voxel data may not yield reliable estimation of β . Denoising algorithms 16,17 may prove useful to improve β estimation, particularly for regions with small volumes. In these data, 30 min of dynamic data were acquired in 5 min bins, allowing for 6 data points to estimate β.…”

Section: Discussionmentioning

confidence: 99%

Quantification of PET infusion studies without true equilibrium: A tissue clearance correction

Hillmer

Carson

2019

J Cereb Blood Flow Metab

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In some positron emission tomography (PET) studies, a reversibly binding radioligand is administered as a constant infusion to establish true equilibrium for quantification. This approach reduces scanning time and simplifies data analysis, but assumes similar behavior of the radioligand in plasma across the study population to establish true equilibrium in all subjects. Bias in outcome measurements can result if this assumption is not met. This work developed and validated a correction that reduces bias in total distribution volume ( VT) estimates when true equilibrium is not present. This correction, termed tissue clearance correction (TCC), took the form [Formula: see text], where β is the radioligand clearance rate in tissue, γ is a radiotracer-specific constant, and VT(A) is the apparent VT. Simulations characterized the robustness of TCC across imperfect values of γ and β and demonstrated reduction to false positive rates. This approach was validated with human infusion data for three radiotracers: [18F]FPEB, (−)-[18F]flubatine, and [11C]UCB-J. TCC reduced bias in VT estimates for all radiotracers and significantly reduced intersubject variance in VT for [18F]FPEB data in some brain regions. Thus, TCC improves quantification of data acquired from PET infusion studies.

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Section: Discussionmentioning

confidence: 99%

Quantification of PET infusion studies without true equilibrium: A tissue clearance correction

Hillmer

Carson

2019

J Cereb Blood Flow Metab

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“…For 5-HT 2A R binding, parametric images of SUR were compared between groups using the SPM12 software (Wellcome Trust Centre for Neuroimaging, UCL, London, UK) and the Small Animal Molecular Imaging Toolbox 28 (SAMIT, Groningen, Netherlands) in Matlab (R2019, Mathworks Inc, USA). An uncorrected p at 0.001 with a cluster size threshold of 100 voxels was employed 29 , 30 . All the statistical tests were two-sided.…”

Section: Methodsmentioning

confidence: 99%

Effect of 5-HT2A receptor antagonism on levels of D2/3 receptor occupancy and adverse behavioral side-effects induced by haloperidol: a SPECT imaging study in the rat

et al. 2021

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Several studies suggested that 5-HT2A receptor (5-HT2AR) blockade may provide a more favorable efficacy and side-effect profile to antipsychotic treatment. We hypothesized that a combined haloperidol (a D2/3 receptor (D2/3R) antagonist) and MDL-100,907 (a 5-HT2AR antagonist) treatment would reverse the side effects and the neurochemical alterations induced by haloperidol alone and would potentialize its efficacy. We thus chronically treated male Mdr1a knock-out rats with several doses of haloperidol alone or in combination with a saturating dose of a MDL-100,907. Receptor occupancy at clinically relevant levels was validated with a dual-radiotracer in-vivo SPECT imaging of D2/3R and 5-HT2AR occupancy. Experimental tests of efficacy (dizocilpine-disrupted prepulse inhibition (PPI) of the startle reflex) and side effects (catalepsy, vacuous chewing movements) were performed. Finally, a second dual-radiotracer in-vivo SPECT scan assessed the neurochemical changes induced by the chronic treatments. Chronic haloperidol failed to reverse PPI disruption induced by dizocilpine, whilst administration of MDL-100,907 along with haloperidol was associated with a reversal of the effect of dizocilpine. Haloperidol at 0.5 mg/kg/day and at 1 mg/kg/day induced catalepsy that was significantly alleviated (by ~50%) by co-treatment with MDL-100,907 but only at 0.5 mg/kg/day dose of haloperidol. Chronic haloperidol treatment, event at doses as low as 0.1 mg/kg/day induced a significant upregulation of the D2/3R in the striatum (by over 40% in the nucleus accumbens and over 20% in the caudate-putamen nuclei), that was not reversed by MDL-100,907. Finally, an upregulation of 5-HT2AR after chronic haloperidol treatment at a moderate dose only (0.25 mg/kg/day) was demonstrated in frontal cortical regions and the ventral tegmental area. Overall, a partial contribution of a 5-HT2AR antagonism to the efficacy and side-effect profile of antipsychotic agents is suggested.

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“…Radioactive decay correction was performed, while correction for attenuation or scatter was not. Following reconstruction, dynamic images from the partial saturation experiment were denoised with factor analysis (FA) using Pixies software (Apteryx, Issyles-Moulineaux, France) as previously described [23,27,35]. FA allows the decomposition of a dynamic signal into a few elementary components, termed factors [27,28,36].…”

Section: Methodsmentioning

confidence: 99%

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

Cited by 5 publications

References 48 publications

Quantification of PET infusion studies without true equilibrium: A tissue clearance correction

Quantification of PET infusion studies without true equilibrium: A tissue clearance correction

Effect of 5-HT2A receptor antagonism on levels of D2/3 receptor occupancy and adverse behavioral side-effects induced by haloperidol: a SPECT imaging study in the rat

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

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