PET imaging of mitochondrial function in acute doxorubicin-induced cardiotoxicity: a proof-of-principle study.

Mitochondrial dysfunction plays a key role in doxorubicin-induced cardiotoxicity (DIC). In this proof-of-principle study, we investigated whether PET mapping of cardiac membrane potential, an indicator of mitochondrial function, could detect an acute cardiotoxic effect of doxorubicin (DOX) in a large animal model. Eight Yucatan pigs were imaged dynamically with [F](4-Fluorophenyl)triphenylphosphonium ([F]FTPP) PET/CT.

Quantification of Myocardial Mitochondrial Membrane Potential Using PET.

Purpose Of Review: To present a method enabling in vivo quantification of tissue membrane potential (ΔΨ), a proxy of mitochondrial membrane potential (ΔΨ), to review the origin and role of ΔΨ, and to highlight potential applications of myocardial ΔΨ imaging.

Recent Findings: Radiolabelled lipophilic cations have been used for decades to measure ΔΨ in vitro. Using similar compounds labeled with positron emitters and appropriate compartment modeling, this technique now allows in vivo quantification of ΔΨ with positron emission tomography.

In vivo quantitative mapping of human mitochondrial cardiac membrane potential: a feasibility study.

Purpose: Alteration in mitochondrial membrane potential (ΔΨ) is an important feature of many pathologic processes, including heart failure, cardiotoxicity, ventricular arrhythmia, and myocardial hypertrophy. We present the first in vivo, non-invasive, assessment of regional ΔΨ in the myocardium of normal human subjects.

Methods: Thirteen healthy subjects were imaged using [F]-triphenylphosphonium ([F]TPP+) on a PET/MR scanner.

PET imaging of neurotransmission using direct parametric reconstruction.

Receptor ligand-based dynamic Positron Emission Tomography (PET) permits the measurement of neurotransmitter release in the human brain. For single-scan paradigms, the conventional method of estimating changes in neurotransmitter levels relies on fitting a pharmacokinetic model to activity concentration histories extracted after PET image reconstruction. However, due to the statistical fluctuations of activity concentration data at the voxel scale, parametric images computed using this approach often exhibit low signal-to-noise ratio, impeding characterization of neurotransmitter release.

Imaging of Mitochondrial Depolarization of Myocardium With Positron Emission Tomography and a Proton Gradient Uncoupler.

Background: We recently reported a method using positron emission tomography (PET) and the tracer F-labeled tetraphenylphosphonium (F-TPP) for mapping the tissue (i.e., cellular plus mitochondrial) membrane potential (ΔΨ) in the myocardium.

Body motion detection and correction in cardiac PET: Phantom and human studies.

Purpose: Patient body motion during a cardiac positron emission tomography (PET) scan can severely degrade image quality. We propose and evaluate a novel method to detect, estimate, and correct body motion in cardiac PET.

Methods: Our method consists of three key components: motion detection, motion estimation, and motion-compensated image reconstruction.

Quantitative in vivo mapping of myocardial mitochondrial membrane potential.

Background: Mitochondrial membrane potential (ΔΨm) arises from normal function of the electron transport chain. Maintenance of ΔΨm within a narrow range is essential for mitochondrial function. Methods for in vivo measurement of ΔΨm do not exist.

Frontostriatal and Dopamine Markers of Individual Differences in Reinforcement Learning: A Multi-modal Investigation.

Prior studies have shown that dopamine (DA) functioning in frontostriatal circuits supports reinforcement learning (RL), as phasic DA activity in ventral striatum signals unexpected reward and may drive coordinated activity of striatal and orbitofrontal regions that support updating of action plans. However, the nature of DA functioning in RL is complex, in particular regarding the role of DA clearance in RL behavior. Here, in a multi-modal neuroimaging study with healthy adults, we took an individual differences approach to the examination of RL behavior and DA clearance mechanisms in frontostriatal learning networks.

Rapid computation of single PET scan rest-stress myocardial blood flow parametric images by table look up.

Purpose: We have recently reported a method for measuring rest-stress myocardial blood flow (MBF) using a single, relatively short, PET scan session. The method requires two IV tracer injections, one to initiate rest imaging and one at peak stress. We previously validated absolute flow quantitation in ml/min/cc for standard bull's eye, segmental analysis.

Validation of Bayesian analysis of compartmental kinetic models in medical imaging.

Introduction: Kinetic compartmental analysis is frequently used to compute physiologically relevant quantitative values from time series of images. In this paper, a new approach based on Bayesian analysis to obtain information about these parameters is presented and validated.

Materials And Methods: The closed-form of the posterior distribution of kinetic parameters is derived with a hierarchical prior to model the standard deviation of normally distributed noise.

National Electrical Manufacturers Association and Clinical Evaluation of a Novel Brain PET/CT Scanner.

Unlabelled: The aim of this study was to determine the performance of a novel mobile human brain/small-animal PET/CT system. The scanner has a 35.7-cm-diameter bore and a 22-cm axial extent.

Mapping (15)O production rate for proton therapy verification.

Purpose: This work was a proof-of-principle study for the evaluation of oxygen-15 ((15)O) production as an imaging target through the use of positron emission tomography (PET), to improve verification of proton treatment plans and to study the effects of perfusion.

Methods And Materials: Dynamic PET measurements of irradiation-produced isotopes were made for a phantom and rabbit thigh muscles. The rabbit muscle was irradiated and imaged under both live and dead conditions.

Bias atlases for segmentation-based PET attenuation correction using PET-CT and MR.

This study was to obtain voxel-wise PET accuracy and precision using tissue-segmentation for attenuation correction. We applied multiple thresholds to the CTs of 23 patients to classify tissues. For six of the 23 patients, MR images were also acquired.

Direct reconstruction of cardiac PET kinetic parametric images using a preconditioned conjugate gradient approach.

Purpose: Our research goal is to develop an algorithm to reconstruct cardiac positron emission tomography (PET) kinetic parametric images directly from sinograms and compare its performance with the conventional indirect approach.

Methods: Time activity curves of a NCAT phantom were computed according to a one-tissue compartmental kinetic model with realistic kinetic parameters. The sinograms at each time frame were simulated using the activity distribution for the time frame.

Neurovascular coupling to D2/D3 dopamine receptor occupancy using simultaneous PET/functional MRI.

This study employed simultaneous neuroimaging with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to demonstrate the relationship between changes in receptor occupancy measured by PET and changes in brain activity inferred by fMRI. By administering the D2/D3 dopamine receptor antagonist [(11)C]raclopride at varying specific activities to anesthetized nonhuman primates, we mapped associations between changes in receptor occupancy and hemodynamics [cerebral blood volume (CBV)] in the domains of space, time, and dose. Mass doses of raclopride above tracer levels caused increases in CBV and reductions in binding potential that were localized to the dopamine-rich striatum.

Dual-tracer PET using generalized factor analysis of dynamic sequences.

Purpose: With single-photon emission computed tomography, simultaneous imaging of two physiological processes relies on discrimination of the energy of the emitted gamma rays, whereas the application of dual-tracer imaging to positron emission tomography (PET) imaging has been limited by the characteristic 511-keV emissions.

Procedures: To address this limitation, we developed a novel approach based on generalized factor analysis of dynamic sequences (GFADS) that exploits spatio-temporal differences between radiotracers and applied it to near-simultaneous imaging of 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) (brain metabolism) and (11)C-raclopride (D2) with simulated human data and experimental rhesus monkey data. We show theoretically and verify by simulation and measurement that GFADS can separate FDG and raclopride measurements that are made nearly simultaneously.

A receptor-based model for dopamine-induced fMRI signal.

This report describes a multi-receptor physiological model of the fMRI temporal response and signal magnitude evoked by drugs that elevate synaptic dopamine in basal ganglia. The model is formulated as a summation of dopamine's effects at D1-like and D2-like receptor families, which produce functional excitation and inhibition, respectively, as measured by molecular indicators like adenylate cyclase or neuroimaging techniques like fMRI. Functional effects within the model are described in terms of relative changes in receptor occupancies scaled by receptor densities and neuro-vascular coupling constants.

MRI-based nonrigid motion correction in simultaneous PET/MRI.

Unlabelled: Respiratory and cardiac motion is the most serious limitation to whole-body PET, resulting in spatial resolution close to 1 cm. Furthermore, motion-induced inconsistencies in the attenuation measurements often lead to significant artifacts in the reconstructed images. Gating can remove motion artifacts at the cost of increased noise.

Parametric imaging with Bayesian priors: a validation study with (11)C-Altropane PET.

It has been suggested that Bayesian estimation methods may be used to improve the signal-to-noise ratio of parametric images. However, there is little experience with the method and some of the underlying assumptions and performance properties of Bayesian estimation remain to be investigated. We used a sample population of 54 subjects, studied previously with (11)C-Altropane, to empirically evaluate the assumptions, performance and some practical issues in forming parametric images.

Dopamine release during human emotional processing.

Involvement of dopamine neurotransmission in human emotional processing is unclear but animal studies have indicated that it is critical for processing of fear response. In this experiment we examined dopaminergic involvement in the processing of human emotions. We used a novel dynamic molecular imaging technique to detect and map dopamine released during presentation of emotional stimuli.