| 1. |
- Caravaggio, Fernando, et al.
(författare)
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Trait impulsivity is not related to post-commissural putamen volumes : A replication study in healthy men
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- High levels of trait impulsivity are considered a risk factor for substance abuse and drug addiction. We recently found that non-planning trait impulsivity was negatively correlated with post-commissural putamen volumes in men, but not women, using the Karolinska Scales of Personality (KSP). Here, we attempted to replicate this finding in an independent sample using an updated version of the KSP: the Swedish Universities Scales of Personality (SSP). Data from 88 healthy male participants (Mean Age: 28.16 +/- 3.34), who provided structural T1-weighted magnetic resonance images (MRIs) and self-reported SSP impulsivity scores, were analyzed. Striatal sub-region volumes were acquired using the Multiple Automatically Generated Templates (MAGeT-Brain) algorithm. Contrary to our previous findings trait impulsivity measured using SSP was not a significant predictor of post-commissural putamen volumes (beta = .14, df = 84, p = .94). A replication Bayes Factors analysis strongly supported this null result. Consistent with our previous findings, secondary exploratory analyses found no relationship between ventral striatum volumes and SSP trait impulsivity (beta = -.05, df = 84, p = .28). An exploratory analysis of the other striatal compartments showed that there were no significant associations with trait impulsivity. While we could not replicate our previous findings in the current sample, we believe this work will aide future studies aimed at establishing meaningful brain biomarkers for addiction vulnerability in healthy humans.
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| 2. |
- Jangard, Simon, et al.
(författare)
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Striatal dopamine D2 receptor availability as a predictor of subsequent alcohol use in social drinkers.
- 2023
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Ingår i: Addiction. - : Wiley. - 0965-2140 .- 1360-0443. ; 118:6, s. 1053-1061
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Whereas striatal dopamine D2 receptor (D2R) availability has shown to be altered in individuals with alcohol use disorder (AUD) and in healthy individuals with a family history of AUD, the role of D2R in the development of AUD is unknown. In this positron emission tomography (PET) study, we measured whether D2R availability is associated with subsequent alcohol use and alcohol-related factors, at a follow-up 8-to-16-years post PET scan, in social drinkers.DESIGN: Longitudinal study following healthy individuals.SETTING: Academic research imaging centre in Stockholm, Sweden.PARTICIPANTS: 71 individuals (68 of whom had evaluable PET data, 5 females, 42.0 years mean age) from a series of previous PET studies.MEASUREMENTS: One PET examination with the D2R antagonist radioligand [11 C]raclopride at baseline, and self-report measures assessing alcohol use, drug use, impulsivity, reward sensitivity, and family history of alcohol- or substance use disorder at follow-up.FINDINGS: We found no evidence for an association between D2R availability and later alcohol use (B = -.019, B 95% confidence interval [CI] = -.043-(-).006, p = .147), nor for the majority of the alcohol-related factors (B 95 % CI = -.034-.004, p = .273-.288). A negative association with a small effect size was found between D2R availability and later impulsivity (B = -.017, B 95% CI = -.034-(-).001, p = .046).CONCLUSIONS: Low striatal dopamine D2 receptor availability may not be a strong predictor in the development of alcohol use disorder.
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| 3. |
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| 4. |
- Matheson, Granville James
(författare)
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Reliability, replicability and reproducibility in PET imaging
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Positron Emission Tomography (PET) is a non-invasive biomedical imaging method which can quantify biochemical markers as well as functional and metabolic activity in vivo. Following image analysis, quantification can be performed using various pharmacokinetic models, or using simplified semi-quantitative methods. There are numerous methods by which PET data can be analysed, and outcomes which can be reported, which differ in their accuracy, stability and specificity. The quantification of PET data, as well as the statistical procedures used to test clinical hypotheses, leads to conclusions which may differ in their degree of correctness. This thesis explores themes of reliability, replicability and reproducibility for PET research. Reliability concerns the consistency and accuracy of an outcome for distinguishing between individuals. Replicability concerns the accuracy of research conclusions, and whether they can be obtained again using the same procedures in new studies. Reproducibility concerns steps towards increasing the transparency of data analysis, by recording and sharing the exact procedures used to arrive at the conclusions. Across the studies in this thesis, these themes are detailed, expanded upon, and used in a series of methodological and applied clinical PET studies. In Study I, the performance of surface-based methods for normalisation and smoothing of PET data were compared with volumetric methods for exploratory parametric analysis using PET test-retest data measuring [11C]SCH23390 BPND in cortical regions. We replicated previous results of decreased spread, and showed that these methods also show improved test-retest repeatability. In Study II, using the same data we evaluated the performance of post-reconstruction movement correction as well as automatic and manual methods for delineation of regions of interest. We showed that motion correction improves the reliability and repeatability of binding estimates, and that automatic methods for delineation do not perform less well than manual methods, and appear to be more consistent. Study III evaluated the test-retest performance of simplified ratio-based outcome measures for quantification of translocator protein (TSPO) binding using [11C]PBR28. We showed that these methods exhibit poor reliability, and little to no association with the gold-standard outcome measure VT, suggesting that caution is warranted for interpretation of studies making use of these measures. In Study IV, diurnal and seasonal changes in the availability of the serotonin 1A receptor and the serotonin transporter were measured across the day and year in a large sample of healthy controls. We replicated previous findings of seasonal changes in the availability of the serotonin 1A receptor, failed to replicate findings of seasonal changes in the availability of the serotonin transporter, and additionally showed diurnal changes in both targets. In Study V, the importance of reliability is discussed with reference to study design, and a new method is presented for making approximations of the reliability for new samples. This approach allows researchers to more effectively gauge the feasibility of new between-individual studies before collection of any data, and to focus their efforts on research questions which can be expected to yield more interpretable outcomes. In Study VI, we perform a direction replication of a previous finding of a strong association between the Self-Transcendence scale of the Temperament and Character Inventory using a much larger sample to assess the veracity of the original findings. We showed moderate to strong evidence for no effect relative to the the previous results, suggesting that the original results were more likely to be either a false positive or greatly overestimated. In Study VII, we carried out an individual-participant data meta-analysis of TSPO binding measured using second-generation tracers in healthy controls compared with schizophrenia and psychotic disorder patients. Contrary to the original hypothesis of increases in TSPO binding, we showed strong evidence for decreases in TSPO in patients compared to controls in both cortical and subcortical regions. In Studies VIII and IX, we hypothesised that D1 receptor binding would be higher with increasing proneness to develop psychosis and in the early stages of the disease prior to medication exposure, respectively. In Study VIII, we showed convergent evidence of no association between D1 receptor availability and delusional ideation in healthy controls. In Study IX, contrary to our hypotheses, we found moderate evidence in favour of lower levels of D1 receptor availability in the dorsolateral prefrontal cortex of first-episode drug-naive psychosis patients compared to healthy controls. While reliability and replicablity of previous findings were directly assessed, the theme of reproducibility concerned our sharing the analysis code, and the data where possible, such that all analysis steps including those which could not be adequately described in the papers were recorded to ensure transparency, and demonstrate the correctness of our conclusions. All of the three themes of the thesis concern efforts to improve the quality, robustness, and utility of scientific research. For a field such as PET imaging, which is not only resource-intensive, but also requires exposing participants to harmful radiation, it is especially important both from a scientific as well as an ethical perspective that data are processed and analysed in a manner which is transparent, generalisable and optimal such that they are made use of to their full potential.
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| 5. |
- Plaven-Sigray, Pontus, et al.
(författare)
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Is dopamine D1 receptor availability related to social behavior? : A positron emission tomography replication study
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- Background Associations between dopamine receptor levels and pro- and antisocial behavior have previously been demonstrated in human subjects using positron emission tomography (PET) and self-rated measures of personality traits. So far, only one study has focused on the dopamine D1-receptor (D-1-R), finding a positive correlation with the trait social desirability, which is characterized by low dominant and high affiliative behavior, while physical aggression showed a negative correlation. The aim of the present study was to replicate these previous findings using a new independent sample of subjects.Materials and methods Twenty-six healthy males were examined with the radioligand [C-11]SCH-23390, and completed the Swedish universities Scales of Personality (SSP) which includes measures of social desirability and physical trait aggression. The simplified reference tissue model with cerebellum as reference region was used to calculate BPND values in the whole striatum and limbic striatum. The two regions were selected since they showed strong association between D-I-R availability and personality scores in the previous study. Pearson's correlation coefficients and replication Bayes factors were then employed to assess the replicability and robustness of previous results.Results There were no significant correlations (all p values >0.3) between regional BPND values and personality scale scores. Replication Bayes factors showed strong to moderate evidence in favor no relationship between Dl-receptor availability and social desirability (striatum BF01 = 12.4; limbic striatum BF01 = 7.2) or physical aggression scale scores (limbic striatum BF01 = 3.3), compared to the original correlations.Discussion We could not replicate the previous findings of associations between D1-R availability and either pro- or antisocial behavior as measured using the SSP. Rather, there was evidence in favor of failed replications of associations between BPND and scale scores. Potential reasons for these results are restrictive variance in both PET and personality outcomes due to high sample homogeneity, or that the previous findings were false positives.
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| 6. |
- Plaven-Sigray, Pontus, et al.
(författare)
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Test-retest reliability and convergent validity of (R)-[11C]PK11195 outcome measures without arterial input function
- 2018
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Ingår i: EJNMMI Research. - : Springer Nature. - 2191-219X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The PET radioligand (R)-[C-11]PK11195 is used to quantify the 18-kDa translocator protein (TSPO), a marker for glial activation. Since there is no brain region devoid of TSPO, an arterial input function (AIF) is ideally required for quantification of binding. However, obtaining an AIF is experimentally demanding, is sometimes uncomfortable for participants, and can introduce additional measurement error during quantification. The objective of this study was to perform an evaluation of the test-retest reliability and convergent validity of techniques used for quantifying (R)-[C-11]PK11195 binding without an AIF in clinical studies.Methods: Data from six healthy individuals who participated in two PET examinations, 6weeks apart, were analyzed. Regional non-displaceable binding potential (BPND) values were calculated using the simplified reference tissue model, with either cerebellum as reference region or a reference input derived using supervised cluster analysis (SVCA). Standardized uptake values (SUVs) were estimated for the time interval of 40-60min.Results: Test-retest reliability for BPND estimates were poor (80% of ICCs <0.5). BPND estimates derived without an AIF were not correlated with BPND, total or specific distribution volume from the 2TCM using an AIF (all R-2<12%). SUVs showed moderate reliability but no correlation to any other outcome measure.Conclusions: Caution is warranted when interpreting patient-control comparisons employing (R)-[C-11]PK11195 outcome measures obtained without an AIF.
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| 7. |
- Tjerkaski, Jonathan, et al.
(författare)
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Kinfitr - an open-source tool for reproducible PET modelling : validation and evaluation of test-retest reliability
- 2020
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Ingår i: EJNMMI Research. - : Springer Nature. - 2191-219X. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In positron emission tomography (PET) imaging, binding is typically estimated by fitting pharmacokinetic models to the series of measurements of radioactivity in the target tissue following intravenous injection of a radioligand. However, there are multiple different models to choose from and numerous analytical decisions that must be made when modelling PET data. Therefore, it is important that analysis tools be adapted to the specific circumstances, and that analyses be documented in a transparent manner. Kinfitr, written in the open-source programming language R, is a tool developed for flexible and reproducible kinetic modelling of PET data, i.e. performing all steps using code which can be publicly shared in analysis notebooks. In this study, we compared outcomes obtained using kinfitr with those obtained using PMOD: a widely used commercial tool.RESULTS: Using previously collected test-retest data obtained with four different radioligands, a total of six different kinetic models were fitted to time-activity curves derived from different brain regions. We observed good correspondence between the two kinetic modelling tools both for binding estimates and for microparameters. Likewise, no substantial differences were observed in the test-retest reliability estimates between the two tools.CONCLUSIONS: In summary, we showed excellent agreement between the open-source R package kinfitr, and the widely used commercial application PMOD. We, therefore, conclude that kinfitr is a valid and reliable tool for kinetic modelling of PET data.
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