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Federico E Turkheimer

Publications and source records attributed to Federico E Turkheimer.

5 recordsLinked to original sources

On the logic of hypothesis testing in functional imaging.

Statistics is nowadays the customary language of functional imaging. It is common to express an experimental setting as a set of null hypotheses over complex models and to present results as maps of p-values derived from sophisticated probability distributions. However, the growing interest in the development of advanced statistical algorithms is not always paralleled by similar attention to how these techniques may regiment the ways in which users draw inferences from their data. This article investigates the logical bases of current statistical approaches in functional imaging and probes their suitability to inductive inference in neuroscience. The frequentist approach to statistical inference is reviewed with attention to its two main constituents: Fisherian "significance testing" and Neyman-Pearson "hypothesis testing". It is shown that these conceptual systems, which are similar in the univariate testing case, dissociate into two quite different methods of inference when applied to the multiple testing problem, the typical framework of functional imaging. This difference is explained with reference to specific issues, like small volume correction, which are most likely to generate confusion in the practitioner. Further insight into this problem is achieved by recasting the multiple comparison problem into a multivariate Bayesian formulation. This formulation introduces a new perspective where the inferential process is more clearly defined in two distinct steps. The first one, inductive in form, uses exploratory techniques to acquire preliminary notions on the spatial patterns and the signal and noise characteristics. The (smaller) set of likely spatial patterns generated is then tested with newer data and a more rigorous multiple hypothesis testing technique (deductive step).

Algorithms↗

Rank-shaping regularization of exponential spectral analysis for application to functional parametric mapping.

Compartmental models are widely used for the mathematical modelling of dynamic studies acquired with positron emission tomography (PET). The numerical problem involves the estimation of a sum of decaying real exponentials convolved with an input function. In exponential spectral analysis (SA), the nonlinear estimation of the exponential functions is replaced by the linear estimation of the coefficients of a predefined set of exponential basis functions. This set-up guarantees fast estimation and attainment of the global optimum. SA, however, is hampered by high sensitivity to noise and, because of the positivity constraints implemented in the algorithm, cannot be extended to reference region modelling. In this paper, SA limitations are addressed by a new rank-shaping (RS) estimator that defines an appropriate regularization over an unconstrained least-squares solution obtained through singular value decomposition of the exponential base. Shrinkage parameters are conditioned on the expected signal-to-noise ratio. Through application to simulated and real datasets, it is shown that RS ameliorates and extends SA properties in the case of the production of functional parametric maps from PET studies.

Algorithms↗

On the undecidability among kinetic models: from model selection to model averaging.

This article deals with the problem of model selection for the mathematical description of tracer kinetics in nuclear medicine. It stems from the consideration of some specific data sets where different models have similar performances. In these situations, it is shown that considerate averaging of a parameter's estimates over the entire model set is better than obtaining the estimates from one model only. Furthermore, it is also shown that the procedure of averaging over a small number of "good" models reduces the "generalization error," the error introduced when the model selected over a particular data set is applied to different conditions, such as subject populations with altered physiologic parameters, modified acquisition protocols, and different signal-to-noise ratios. The method of averaging over the entire model set uses Akaike coefficients as measures of an individual model's likelihood. To facilitate the understanding of these statistical tools, the authors provide an introduction to model selection criteria and a short technical treatment of Akaike's information-theoretic approach. The new method is illustrated and epitomized by a case example on the modeling of [11C]flumazenil kinetics in the brain, containing both real and simulated data.

Carbon Radioisotopes↗

A linear wavelet filter for parametric imaging with dynamic PET.

This paper describes a new filter for parametric images obtained from dynamic positron emission tomography (PET) studies. The filter is based on the wavelet transform following the heuristics of a previously published method that are here developed into a rigorous theoretical framework. It is shown that the space-time problem of modeling a dynamic PET sequence reduces to the classical one of estimation of a normal multivariate vector of independent wavelet coefficients that, under least-squares risk, can be solved by straightforward application of well established theory. From the study of the distribution of wavelet coefficients of PET images, it is inferred that a James-Stein linear estimator is more suitable for the problem than traditional nonlinear procedures that are incorporated in standard wavelet filters. This is confirmed by the superior performance of the James-Stein filter in simulation studies compared to a state-of-the-art nonlinear wavelet filter and a nonstationary filter selected from literature. Finally, the formal framework is interpreted for the practitioner's point of view and advantages and limitations of the method are discussed.

Aged↗

Positron emission tomography compartmental models: a basis pursuit strategy for kinetic modeling.

A kinetic modeling approach for the quantification of in vivo tracer studies with dynamic positron emission tomography (PET) is presented. The approach is based on a general compartmental description of the tracer's fate in vivo and determines a parsimonious model consistent with the measured data. The technique involves the determination of a sparse selection of kinetic basis functions from an overcomplete dictionary using the method of basis pursuit denoising. This enables the characterization of the systems impulse response function from which values of the systems macro parameters can be estimated. These parameter estimates can be obtained from a region of interest analysis or as parametric images from a voxel-based analysis. In addition, model order estimates are returned that correspond to the number of compartments in the estimated compartmental model. Validation studies evaluate the methods performance against two preexisting data led techniques, namely, graphical analysis and spectral analysis. Application of this technique to measured PET data is demonstrated using [11C]diprenorphine (opiate receptor) and [11C]WAY-100635 (5-HT1A receptor). Although the method is presented in the context of PET neuroreceptor binding studies, it has general applicability to the quantification of PET/SPECT radiotracer studies in neurology, oncology, and cardiology.

Artifacts↗