TY - JOUR
T1 - nonparametric residue analysis of dynamic PET data with application to cerebral FDG studies in normals
AU - O'sullivan, Finbarr
AU - Muzi, Mark
AU - Spence, Alexander M.
AU - Mankoff, David M.
AU - O'sullivan, Janet N.
AU - Fitzgerald, Niall
AU - Newman, George C.
AU - Krohn, Kenneth A.
N1 - Funding Information:
Finbarr O’Sullivan is Professor of Statistics, University College Cork, Ireland and Affiliate Professor of Radiology, University of Washington, Seattle, WA 98195 (E-mail: f.osullivan@ucc.ie). Mark Muzi is Director of Image Analysis, Department of Radiology, University of Washington, Seattle, WA 98195. Alexander M. Spence is Professor of Neurology, University of Washington, Seattle, WA 98195. David M. Mankoff is Professor of Radiology, University of Washington, Seattle, WA 98195. Janet N. O’Sullivan is Research Scientist, University College Cork, Ireland. Niall Fitzgerald is Ph.D. student, University College Cork, Ireland. George C. Newman is Chair of Neurosensory Sciences, Albert Einstein Medical Center, Philadelphia, PA. Kenneth A. Krohn is Professor of Radiology, University of Washington, Seattle, WA 98195. This research was supported in part by the National Institutes of Health (USA) under CA-42045 and by the Health Research Board (Ireland) under RP-289 and Science Foundation Ireland under MI-2007.
PY - 2009/6
Y1 - 2009/6
N2 - Kinetic analysis is used to extract metabolic information from dynamic positron emission tomography (PET) uptake data. The theory of indicator dilutions, developed in the seminal work of Meier and Zierler (1954), provides a probabilistic framework for representation of PET tracer uptake data in terms of a convolution between an arterial input function and a tissue residue. The residue is a scaled survival function associated with tracer residence in the tissue. Nonparametric inference for the residue, a deconvolution problem, provides a novel approach to kinetic analysis-critically one that is not reliant on specific compartmental modeling assumptions. A practical computational technique based on regularized cubic B-spline approximation of the residence time distribution is proposed. Nonparametric residue analysis allows formal statistical evaluation of specific parametric models to be considered. This analysis needs to properly account for the increased flexibility of the nonparametric estimator. The methodology is illustrated using data from a series of cerebral studies with PET and fluorodeoxyglucose (FDG) in normal subjects. Comparisons are made between key functionals of the residue, tracer flux, flow, etc., resulting from a parametric (the standard two-compartment of Phelps et al. 1979) and a nonparametric analysis. Strong statistical evidence against the compartment model is found. Primarily these differences relate to the representation of the early temporal structure of the tracer residencelargely a function of the vascular supply network. There are convincing physiological arguments against the representations implied by the compartmental approach but this is the first time that a rigorous statistical confirmation using PET data has been reported. The compartmental analysis produces suspect values for flow but, notably, the impact on the metabolic flux, though statistically significant, is limited to deviations on the order of 3%-4%. The general advantage of the nonparametric residue analysis is the ability to provide a valid kinetic quantitation in the context of studies where there may be heterogeneity or other uncertainty about the accuracy of a compartmental model approximation of the tissue residue.
AB - Kinetic analysis is used to extract metabolic information from dynamic positron emission tomography (PET) uptake data. The theory of indicator dilutions, developed in the seminal work of Meier and Zierler (1954), provides a probabilistic framework for representation of PET tracer uptake data in terms of a convolution between an arterial input function and a tissue residue. The residue is a scaled survival function associated with tracer residence in the tissue. Nonparametric inference for the residue, a deconvolution problem, provides a novel approach to kinetic analysis-critically one that is not reliant on specific compartmental modeling assumptions. A practical computational technique based on regularized cubic B-spline approximation of the residence time distribution is proposed. Nonparametric residue analysis allows formal statistical evaluation of specific parametric models to be considered. This analysis needs to properly account for the increased flexibility of the nonparametric estimator. The methodology is illustrated using data from a series of cerebral studies with PET and fluorodeoxyglucose (FDG) in normal subjects. Comparisons are made between key functionals of the residue, tracer flux, flow, etc., resulting from a parametric (the standard two-compartment of Phelps et al. 1979) and a nonparametric analysis. Strong statistical evidence against the compartment model is found. Primarily these differences relate to the representation of the early temporal structure of the tracer residencelargely a function of the vascular supply network. There are convincing physiological arguments against the representations implied by the compartmental approach but this is the first time that a rigorous statistical confirmation using PET data has been reported. The compartmental analysis produces suspect values for flow but, notably, the impact on the metabolic flux, though statistically significant, is limited to deviations on the order of 3%-4%. The general advantage of the nonparametric residue analysis is the ability to provide a valid kinetic quantitation in the context of studies where there may be heterogeneity or other uncertainty about the accuracy of a compartmental model approximation of the tissue residue.
KW - Deconvolution
KW - Functional inference
KW - Kinetic analysis
KW - Regularization
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U2 - 10.1198/jasa.2009.0021
DO - 10.1198/jasa.2009.0021
M3 - Article
AN - SCOPUS:66549096654
SN - 0162-1459
VL - 104
SP - 556
EP - 571
JO - Journal of the American Statistical Association
JF - Journal of the American Statistical Association
IS - 486
ER -