Direct estimation of kinetic parametric images for dynamic PET.

Dynamic positron emission tomography (PET) can monitor spatiotemporal distribution of radiotracer in vivo. The spatiotemporal information can be used to estimate parametric images of radiotracer kinetics that are of physiological and biochemical interests. Direct estimation of parametric images from raw projection data allows accurate noise modeling and has been shown to offer better image quality than conventional indirect methods, which reconstruct a sequence of PET images first and then perform tracer kinetic modeling pixel-by-pixel. Direct reconstruction of parametric images has gained increasing interests with the advances in computing hardware. Many direct reconstruction algorithms have been developed for different kinetic models. In this paper we review the recent progress in the development of direct reconstruction algorithms for parametric image estimation. Algorithms for linear and nonlinear kinetic models are described and their properties are discussed

Comparison of Lesion Detection and Quantification in MAP Reconstruction with Gaussian and Non-Gaussian Priors

Statistical image reconstruction methods based on maximum a posteriori (MAP) principle have been developed for emission tomography. The prior distribution of the unknown image plays an important role in MAP reconstruction. The most commonly used prior are Gaussian priors, whose logarithm has a quadratic form. Gaussian priors are relatively easy to analyze. It has been shown that the effect of a Gaussian prior can be approximated by linear filtering a maximum likelihood (ML) reconstruction. As a result, sharp edges in reconstructed images are not preserved. To preserve sharp transitions, non-Gaussian priors have been proposed. However, their effect on clinical tasks is less obvious. In this paper, we compare MAP reconstruction with Gaussian and non-Gaussian priors for lesion detection and region of interest quantification using computer simulation. We evaluate three representative priors: Gaussian prior, Huber prior, and Geman-McClure prior. We simulate imaging a prostate tumor using positron emission tomography (PET). The detectability of a known tumor in either a fixed background or a random background is measured using a channelized Hotelling observer. The bias-variance tradeoff curves are calculated for quantification of the total tumor activity. The results show that for the detection and quantification tasks, the Gaussian prior is as effective as non-Gaussian priors

Optimization of Bayesian emission tomographic reconstruction for region-of-interest quantitation

Region of interest (ROI) quantitation is an important task in emission tomography (e.g., positron emission tomography and single photon emission computed tomography). It is essential for exploring clinical factors such as tumor activity, growth rate, and the efficacy of therapeutic interventions. Bayesian methods based on the maximum a posteriori principle (or called penalized maximum likelihood methods) have been developed for emission image reconstructions to deal with the low signal to noise ratio of the emission data. Similar to the filter cut-off frequency in the filtered backprojection method, the smoothing parameter of the image prior in Bayesian reconstruction controls the resolution and noise trade-off and hence affects ROI quantitation. In this paper we present an approach for choosing the optimum smoothing parameter in Bayesian reconstruction for ROI quantitation. Bayesian reconstructions are difficult to analyze because the resolution and noise properties are nonlinear and object-dependent. Building on the recent progress on deriving the approximate expressions for the local impulse response function and the covariance matrix, we derived simplied theoretical expressions for the bias, the variance, and the ensemble mean squared error (EMSE) of the ROI quantitation. One problem in evaluating ROI quantitation is that the truth is often required for calculating the bias. This is overcome by using ensemble distribution of the activity inside the ROI and computing the average EMSE. The resulting expressions allow fast evaluation of the image quality for different smoothing parameters. The optimum smoothing parameter of the image prior can then be selected to minimize the EMSE

Subsecond total-body imaging using ultrasensitive positron emission tomography.

A 194-cm-long total-body positron emission tomography/computed tomography (PET/CT) scanner (uEXPLORER), has been constructed to offer a transformative platform for human radiotracer imaging in clinical research and healthcare. Its total-body coverage and exceptional sensitivity provide opportunities for innovative studies of physiology, biochemistry, and pharmacology. The objective of this study is to develop a method to perform ultrahigh (100 ms) temporal resolution dynamic PET imaging by combining advanced dynamic image reconstruction paradigms with the uEXPLORER scanner. We aim to capture the fast dynamics of initial radiotracer distribution, as well as cardiac motion, in the human body. The results show that we can visualize radiotracer transport in the body on timescales of 100 ms and obtain motion-frozen images with superior image quality compared to conventional methods. The proposed method has applications in studying fast tracer dynamics, such as blood flow and the dynamic response to neural modulation, as well as performing real-time motion tracking (e.g., cardiac and respiratory motion, and gross body motion) without any external monitoring device (e.g., electrocardiogram, breathing belt, or optical trackers)

Simultaneous in vivo positron emission tomography and magnetic resonance imaging

Positron emission tomography (PET) and magnetic resonance imaging (MRI) are widely used in vivo imaging technologies with both clinical and biomedical research applications. The strengths of MRI include high-resolution, high-contrast morphologic imaging of soft tissues; the ability to image physiologic parameters such as diffusion and changes in oxygenation level resulting from neuronal stimulation; and the measurement of metabolites using chemical shift imaging. PET images the distribution of biologically targeted radiotracers with high sensitivity, but images generally lack anatomic context and are of lower spatial resolution. Integration of these technologies permits the acquisition of temporally correlated data showing the distribution of PET radiotracers and MRI contrast agents or MR-detectable metabolites, with registration to the underlying anatomy. An MRI-compatible PET scanner has been built for biomedical research applications that allows data from both modalities to be acquired simultaneously. Experiments demonstrate no effect of the MRI system on the spatial resolution of the PET system and <10% reduction in the fraction of radioactive decay events detected by the PET scanner inside the MRI. The signal-to-noise ratio and uniformity of the MR images, with the exception of one particular pulse sequence, were little affected by the presence of the PET scanner. In vivo simultaneous PET and MRI studies were performed in mice. Proof-of-principle in vivo MR spectroscopy and functional MRI experiments were also demonstrated with the combined scanner

Functionally distinct and selectively phosphorylated GPCR subpopulations co-exist in a single cell.

G protein-coupled receptors (GPCRs) transduce pleiotropic intracellular signals in a broad range of physiological responses and disease states. Activated GPCRs can undergo agonist-induced phosphorylation by G protein receptor kinases (GRKs) and second messenger-dependent protein kinases such as protein kinase A (PKA). Here, we characterize spatially segregated subpopulations of β2-adrenergic receptor (β2AR) undergoing selective phosphorylation by GRKs or PKA in a single cell. GRKs primarily label monomeric β2ARs that undergo endocytosis, whereas PKA modifies dimeric β2ARs that remain at the cell surface. In hippocampal neurons, PKA-phosphorylated β2ARs are enriched in dendrites, whereas GRK-phosphorylated β2ARs accumulate in soma, being excluded from dendrites in a neuron maturation-dependent manner. Moreover, we show that PKA-phosphorylated β2ARs are necessary to augment the activity of L-type calcium channel. Collectively, these findings provide evidence that functionally distinct subpopulations of this prototypical GPCR exist in a single cell