Dataset Information

High long-term test-retest reliability for extrastriatal ¹¹C-raclopride binding in healthy older adults.

ABSTRACT: In vivo dopamine D2-receptor availability is frequently assessed with ¹¹C-raclopride and positron emission tomography. Due to low signal-to-noise ratios for ¹¹C-raclopride in areas with low D2 receptor densities, the ligand has been considered unreliable for measurements outside the dopamine-dense striatum. Intriguingly, recent studies show that extrastriatal ¹¹C-raclopride binding potential (BP_ND) values are (i) reliably higher than in the cerebellum (where D2-receptor levels are negligible), (ii) correlate with behavior in the expected direction, and (iii) showed good test-retest reliability in a sample of younger adults. The present work demonstrates high seven-month test-retest reliability of striatal and extrastriatal ¹¹C-raclopride BP_ND values in healthy, older adults (n = 27, age: 64-78 years). Mean ¹¹C-raclopride BP_ND values were stable between test sessions in subcortical nuclei, and in frontal and temporal cortices (p > 0.05). Across all structures analyzed, intraclass correlation coefficients were high (0.85-0.96), absolute variability was low (mean: 4-8%), and coefficients of variance ranged between 9 and 25%. Furthermore, regional ¹¹C-raclopride BP_ND values correlated with previously determined ¹⁸F-fallypride BP_ND values (ρ = 0.97 and 0.92 in correlations with and without striatal values, respectively, p < 0.01) and postmortem determined D2-receptor densities (including striatum: ρ = 0.92; p < 0.001; excluding striatum: ρ = 0.75; p = 0.067). These observations suggest that extrastriatal ¹¹C-raclopride measurements represent a true D2 signal.

SUBMITTER: Karalija N

PROVIDER: S-EPMC7446562 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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High long-term test-retest reliability for extrastriatal 11C-raclopride binding in healthy older adults.

Karalija Nina N Jonassson Lars L Johansson Jarkko J Papenberg Goran G Salami Alireza A Andersson Micael M Riklund Katrine K Nyberg Lars L Boraxbekk Carl-Johan CJ

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20190910 9

In vivo dopamine D2-receptor availability is frequently assessed with 11C-raclopride and positron emission tomography. Due to low signal-to-noise ratios for 11C-raclopride in areas with low D2 receptor densities, the ligand has been considered unreliable for measurements outside the dopamine-dense striatum. Intriguingly, recent studies show that extrastriatal 11C-raclopride binding potential (BPND) values are (i) reliably higher than in the cerebellum ...[more]

PMID: 31506011

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Project description:Functional connectivity (FC) has become a leading method for resting-state functional magnetic resonance imaging (rs-fMRI) analysis. However, the majority of the previous studies utilized pairwise, temporal synchronization-based FC. Recently, high-order FC (HOFC) methods were proposed with the idea of computing "correlation of correlations" to capture high-level, more complex associations among the brain regions. There are two types of HOFC. The first type is topographical profile similarity-based HOFC (tHOFC) and its variant, associated HOFC (aHOFC), for capturing different levels of HOFC. Instead of measuring the similarity of the original rs-fMRI signals with the traditional FC (low-order FC, or LOFC), tHOFC measures the similarity of LOFC profiles (i.e., a set of LOFC values between a region and all other regions) between each pair of brain regions. The second type is dynamics-based HOFC (dHOFC) which defines the quadruple relationship among every four brain regions by first calculating two pairwise dynamic LOFC "time series" and then measuring their temporal synchronization (i.e., temporal correlation of the LOFC fluctuations, not the BOLD fluctuations). Applications have shown the superiority of HOFC in both disease biomarker detection and individualized diagnosis than LOFC. However, no study has been carried out for the assessment of test-retest reliability of different HOFC metrics. In this paper, we systematically evaluate the reliability of the two types of HOFC methods using test-retest rs-fMRI data from 25 (12 females, age 24.48 ± 2.55 years) young healthy adults with seven repeated scans (with interval = 3-8 days). We found that all HOFC metrics have satisfactory reliability, specifically (1) fair-to-good for tHOFC and aHOFC, and (2) fair-to-moderate for dHOFC with relatively strong connectivity strength. We further give an in-depth analysis of the biological meanings of each HOFC metric and highlight their differences compared to the LOFC from the aspects of cross-level information exchanges, within-/between-network connectivity, and modulatory connectivity. In addition, how the dynamic analysis parameter (i.e., sliding window length) affects dHOFC reliability is also investigated. Our study reveals unique functional associations characterized by the HOFC metrics. Guidance and recommendations for future applications and clinical research using HOFC are provided. This study has made a further step toward unveiling more complex human brain connectome.

Project description:BackgroundThe radioligand [11C]VC-002 was introduced in a small initial study long ago for imaging of muscarinic acetylcholine receptors (mAChRs) in human lungs using positron emission tomography (PET). The objectives of the present study in control subjects were to advance the methodology for quantification of [11C]VC-002 binding in lung and to examine the reliability using a test-retest paradigm. This work constituted a self-standing preparatory step in a larger clinical trial aiming at estimating mAChR occupancy in the human lungs following inhalation of mAChR antagonists.MethodsPET measurements using [11C]VC-002 and the GE Discovery 710 PET/CT system were performed in seven control subjects at two separate occasions, 2-19 days apart. One subject discontinued the study after the first measurement. Radioligand binding to mAChRs in lung was quantified using an image-derived arterial input function. The total distribution volume (VT) values were obtained on a regional and voxel-by-voxel basis. Kinetic one-tissue and two-tissue compartment models (1TCM, 2TCM), analysis based on linearization of the compartment models (multilinear Logan) and image analysis by data-driven estimation of parametric images based on compartmental theory (DEPICT) were applied. The test-retest repeatability of VT estimates was evaluated by absolute variability (VAR) and intraclass correlation coefficients (ICCs).ResultsThe 1TCM was the statistically preferred model for description of [11C]VC-002 binding in the lungs. Low VAR (< 10%) across analysis methods indicated good reliability of the PET measurements. The VT estimates were stable after 60 min.ConclusionsThe kinetic behaviour and good repeatability of [11C]VC-002 as well as the novel lung image analysis methodology support its application in applied studies on drug-induced mAChR receptor occupancy and the pathophysiology of pulmonary disorders.Trial registrationClinicalTrials.gov identifier: NCT03097380, registered: 31 March 2017.

Dataset Information

High long-term test-retest reliability for extrastriatal ¹¹C-raclopride binding in healthy older adults.

Publications

High long-term test-retest reliability for extrastriatal <sup>11</sup>C-raclopride binding in healthy older adults.

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