Mapping 18F-FDG Kinetics Together with Patient-Specific Bootstrap Assessment of Uncertainties: An Illustration with Data from a PET/CT Scanner with a Long Axial Field of View.

The purpose of this study was to examine a nonparametric approach to mapping kinetic parameters and their uncertainties with data from the emerging generation of dynamic whole-body PET/CT scanners. Methods: Dynamic PET 18F-FDG data from a set of 24 cancer patients studied on a long-axial-field-of-view PET/CT scanner were considered. Kinetics were mapped using a nonparametric residue mapping (NPRM) technique. Uncertainties were evaluated using an image-based bootstrapping methodology. Kinetics and bootstrap-derived uncertainties are reported for voxels, maximum-intensity projections, and volumes of interest (VOIs) corresponding to several key organs and lesions. Comparisons between NPRM and standard 2-compartment (2C) modeling of VOI kinetics are carefully examined. Results: NPRM-generated kinetic maps were of good quality and well aligned with vascular and metabolic 18F-FDG patterns, reasonable for the range of VOIs considered. On a single 3.2-GHz processor, the specification of the bootstrapping model took 140 min; individual bootstrap replicates required 80 min each. VOI time-course data were much more accurately represented, particularly in the early time course, by NPRM than by 2C modeling constructs, and improvements in fit were statistically highly significant. Although 18F-FDG flux values evaluated by NPRM and 2C modeling were generally similar, significant deviations between vascular blood and distribution volume estimates were found. The bootstrap enables the assessment of quite complex summaries of mapped kinetics. This is illustrated with maximum-intensity maps of kinetics and their uncertainties. Conclusion: NPRM kinetics combined with image-domain bootstrapping is practical with large whole-body dynamic 18F-FDG datasets. The information provided by bootstrapping could support more sophisticated uses of PET biomarkers used in clinical decision-making for the individual patient.

A Generalized Linear modeling approach to bootstrapping multi-frame PET image data.

PET imaging is an important diagnostic tool for management of patients with cancer and other diseases. Medical decisions based on quantitative PET information could potentially benefit from the availability of tools for evaluation of associated uncertainties. Raw PET data can be viewed as a sample from an inhomogeneous Poisson process so there is the possibility to directly apply bootstrapping to raw projection-domain list-mode data. Unfortunately this is computationally impractical, particularly if data reconstruction is iterative or the acquisition protocol is dynamic. We develop a flexible statistical linear model analysis to be used with multi-frame PET image data to create valid bootstrap samples. The technique is illustrated using data from dynamic PET studies with fluoro-deoxyglucose (FDG) and fluoro-thymidine (FLT) in brain and breast cancer patients. As is often the case with dynamic PET studies, data have been archived without raw list-mode information. Using the bootstrapping technique maps of kinetic parameters and associated uncertainties are obtained. The quantitative performance of the approach is assessed by simulation. The proposed image-domain bootstrap is found to substantially match the projection-domain alternative. Analysis of results points to a close relation between relative uncertainty in voxel-level kinetic parameters and local reconstruction error. This is consistent with statistical theory.

Assessment of Value of Neighborhood Socioeconomic Status in Models That Use Electronic Health Record Data to Predict Health Care Use Rates and Mortality.

Importance: Prediction models are widely used in health care as a way of risk stratifying populations for targeted intervention. Most risk stratification has been done using a small number of predictors from insurance claims. However, the utility of diverse nonclinical predictors, such as neighborhood socioeconomic contexts, remains unknown. Objective: To assess the value of using neighborhood socioeconomic predictors in the context of 1-year risk prediction for mortality and 6 different health care use outcomes in a large integrated care system. Design, Setting, and Participants: Diagnostic study using data from all adults age 18 years or older who had Kaiser Foundation Health Plan membership and/or use in the Kaiser Permantente Northern California: a multisite, integrated health care delivery system between January 1, 2013, and June 30, 2014. Data were recorded before the index date for each patient to predict their use and mortality in a 1-year post period using a test-train split for model training and evaluation. Analyses were conducted in fall of 2019. Main Outcomes and Measures: One-year encounter counts (doctor office, virtual, emergency department, elective hospitalizations, and nonelective), total costs, and mortality. Results: A total of 2 951 588 patients met inclusion criteria (mean [SD] age, 47.2 [17.4] years; 47.8% were female). The mean (SD) Neighborhood Deprivation Index was -0.32 (0.84). The areas under the receiver operator curve ranged from 0.71 for emergency department use (using the LASSO method and electronic health record predictors) to 0.94 for mortality (using the random forest method and electronic health record predictors). Neighborhood socioeconomic status predictors did not meaningfully increase the predictive performance of the models for any outcome. Conclusions and Relevance: In this study, neighborhood socioeconomic predictors did not improve risk estimates compared with what is obtainable using standard claims data regardless of model used.

Kinetic Analysis of Dynamic Positron Emission Tomography Data using Open-Source Image Processing and Statistical Inference Tools.

In dynamic mode, positron emission tomography (PET) can be used to track the evolution of injected radio-labelled molecules in living tissue. This is a powerful diagnostic imaging technique that provides a unique opportunity to probe the status of healthy and pathological tissue by examining how it processes substrates. The spatial aspect of PET is well established in the computational statistics literature. This article focuses on its temporal aspect. The interpretation of PET time-course data is complicated because the measured signal is a combination of vascular delivery and tissue retention effects. If the arterial time-course is known, the tissue time-course can typically be expressed in terms of a linear convolution between the arterial time-course and the tissue residue. In statistical terms, the residue function is essentially a survival function - a familiar life-time data construct. Kinetic analysis of PET data is concerned with estimation of the residue and associated functionals such as flow, flux, volume of distribution and transit time summaries. This review emphasises a nonparametric approach to the estimation of the residue based on a piecewise linear form. Rapid implementation of this by quadratic programming is described. The approach provides a reference for statistical assessment of widely used one- and two-compartmental model forms. We illustrate the method with data from two of the most well-established PET radiotracers, (15)O-H(2)O and (18)F-fluorodeoxyglucose, used for assessment of blood perfusion and glucose metabolism respectively. The presentation illustrates the use of two open-source tools, AMIDE and R, for PET scan manipulation and model inference.