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Positron emission tomography (PET) is an imaging technique which can be used to investigate chemical changes in human biological processes such as cancer development or neurochemical reactions. Most dynamic PET scans are currently analyzed based on the assumption that linear first-order kinetics can be used to adequately describe the system under observation. However, there has recently been strong evidence that this is not the case. To provide an analysis of PET data which is free from this compartmental assumption, we propose a nonparametric deconvolution and analysis model for dynamic PET data based on functional principal component analysis. This yields flexibility in the possible deconvolved functions while still performing well when a linear compartmental model setup is the true data generating mechanism. As the deconvolution needs to be performed on only a relative small number of basis functions rather than voxel by voxel in the entire three-dimensional volume, the methodology is both robust to typical brain imaging noise levels while also being computationally efficient. The new methodology is investigated through simulations in both one-dimensional functions and 2D images and also applied to a neuroimaging study whose goal is the quantification of opioid receptor concentration in the brain.

Many longitudinal imaging studies have been/are being widely conducted to use diffusion tensor imaging (DTI) to better understand white matter maturation in normal controls and diseased subjects. There is an urgent demand for the development of statistical methods for analyzing diffusion properties along major fiber tracts obtained from longitudinal DTI studies. Jointly analyzing fiber-tract diffusion properties and covariates from longitudinal studies raises several major challenges including (i) infinite-dimensional functional response data, (ii) complex spatial-temporal correlation structure, and (iii) complex spatial smoothness. To address these challenges, this article is to develop a longitudinal functional analysis framework (LFAF) to delineate the dynamic changes of diffusion properties along major fiber tracts and their association with a set of covariates of interest (e.g., age and group status) and the structure of the variability of these white matter tract properties in various longitudinal studies. Our LFAF consists of a functional mixed effects model for addressing all three challenges, an efficient method for spatially smoothing varying coefficient functions, an estimation method for estimating the spatial-temporal correlation structure, a test procedure with a global test statistic for testing hypotheses of interest associated with functional response, and a simultaneous confidence band for quantifying the uncertainty in the estimated coefficient functions. Simulated data are used to evaluate the finite sample performance of LFAF and to demonstrate that LFAF significantly outperforms a voxel-wise mixed model method. We apply LFAF to study the spatial-temporal dynamics of white-matter fiber tracts in a clinical study of neurodevelopment.

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