Multivariate analysis of PET pharmacokinetic parameters improves inferential efficiency

Abstract Purpose In positron emission tomography quantification, multiple pharmacokinetic parameters are typically estimated from each time activity curve. Conventionally all but the parameter of interest are discarded before performing subsequent statistical analysis. However, we assert that these...

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Main Authors: Granville J. Matheson, R. Todd Ogden
Format: Article
Language:English
Published: SpringerOpen 2023-03-01
Series:EJNMMI Physics
Subjects:
Online Access:https://doi.org/10.1186/s40658-023-00537-8
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author Granville J. Matheson
R. Todd Ogden
author_facet Granville J. Matheson
R. Todd Ogden
author_sort Granville J. Matheson
collection DOAJ
description Abstract Purpose In positron emission tomography quantification, multiple pharmacokinetic parameters are typically estimated from each time activity curve. Conventionally all but the parameter of interest are discarded before performing subsequent statistical analysis. However, we assert that these discarded parameters also contain relevant information which can be exploited to improve the precision and power of statistical analyses on the parameter of interest. Properly taking this into account can thereby draw more informative conclusions without collecting more data. Methods By applying a hierarchical multifactor multivariate Bayesian approach, all estimated parameters from all regions can be analysed at once. We refer to this method as Parameters undergoing Multivariate Bayesian Analysis (PuMBA). We simulated patient–control studies with different radioligands, varying sample sizes and measurement error to explore its performance, comparing the precision, statistical power, false positive rate and bias of estimated group differences relative to univariate analysis methods. Results We show that PuMBA improves the statistical power for all examined applications relative to univariate methods without increasing the false positive rate. PuMBA improves the precision of effect size estimation, and reduces the variation of these estimates between simulated samples. Furthermore, we show that PuMBA yields performance improvements even in the presence of substantial measurement error. Remarkably, owing to its ability to leverage information shared between pharmacokinetic parameters, PuMBA even shows greater power than conventional univariate analysis of the true binding values from which the parameters were simulated. Across all applications, PuMBA exhibited a small degree of bias in the estimated outcomes; however, this was small relative to the variation in estimated outcomes between simulated datasets. Conclusion PuMBA improves the precision and power of statistical analysis of PET data without requiring the collection of additional measurements. This makes it possible to study new research questions in both new and previously collected data. PuMBA therefore holds great promise for the field of PET imaging.
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spelling doaj.art-5b36d480a15a46ddb6ba1e06d287ffb42023-03-22T12:25:24ZengSpringerOpenEJNMMI Physics2197-73642023-03-0110112110.1186/s40658-023-00537-8Multivariate analysis of PET pharmacokinetic parameters improves inferential efficiencyGranville J. Matheson0R. Todd Ogden1Department of Psychiatry, Columbia UniversityDepartment of Psychiatry, Columbia UniversityAbstract Purpose In positron emission tomography quantification, multiple pharmacokinetic parameters are typically estimated from each time activity curve. Conventionally all but the parameter of interest are discarded before performing subsequent statistical analysis. However, we assert that these discarded parameters also contain relevant information which can be exploited to improve the precision and power of statistical analyses on the parameter of interest. Properly taking this into account can thereby draw more informative conclusions without collecting more data. Methods By applying a hierarchical multifactor multivariate Bayesian approach, all estimated parameters from all regions can be analysed at once. We refer to this method as Parameters undergoing Multivariate Bayesian Analysis (PuMBA). We simulated patient–control studies with different radioligands, varying sample sizes and measurement error to explore its performance, comparing the precision, statistical power, false positive rate and bias of estimated group differences relative to univariate analysis methods. Results We show that PuMBA improves the statistical power for all examined applications relative to univariate methods without increasing the false positive rate. PuMBA improves the precision of effect size estimation, and reduces the variation of these estimates between simulated samples. Furthermore, we show that PuMBA yields performance improvements even in the presence of substantial measurement error. Remarkably, owing to its ability to leverage information shared between pharmacokinetic parameters, PuMBA even shows greater power than conventional univariate analysis of the true binding values from which the parameters were simulated. Across all applications, PuMBA exhibited a small degree of bias in the estimated outcomes; however, this was small relative to the variation in estimated outcomes between simulated datasets. Conclusion PuMBA improves the precision and power of statistical analysis of PET data without requiring the collection of additional measurements. This makes it possible to study new research questions in both new and previously collected data. PuMBA therefore holds great promise for the field of PET imaging.https://doi.org/10.1186/s40658-023-00537-8Positron emission tomographyBayesian statisticsPrecisionPowerPharmacokinetic modelling
spellingShingle Granville J. Matheson
R. Todd Ogden
Multivariate analysis of PET pharmacokinetic parameters improves inferential efficiency
EJNMMI Physics
Positron emission tomography
Bayesian statistics
Precision
Power
Pharmacokinetic modelling
title Multivariate analysis of PET pharmacokinetic parameters improves inferential efficiency
title_full Multivariate analysis of PET pharmacokinetic parameters improves inferential efficiency
title_fullStr Multivariate analysis of PET pharmacokinetic parameters improves inferential efficiency
title_full_unstemmed Multivariate analysis of PET pharmacokinetic parameters improves inferential efficiency
title_short Multivariate analysis of PET pharmacokinetic parameters improves inferential efficiency
title_sort multivariate analysis of pet pharmacokinetic parameters improves inferential efficiency
topic Positron emission tomography
Bayesian statistics
Precision
Power
Pharmacokinetic modelling
url https://doi.org/10.1186/s40658-023-00537-8
work_keys_str_mv AT granvillejmatheson multivariateanalysisofpetpharmacokineticparametersimprovesinferentialefficiency
AT rtoddogden multivariateanalysisofpetpharmacokineticparametersimprovesinferentialefficiency