Tracer kinetic model of regional pulmonary function using positron emission tomography

2002 ◽  
Vol 93 (3) ◽  
pp. 1104-1114 ◽  
Author(s):  
Gaetano G. Galletti ◽  
José G. Venegas
Keyword(s):  
Positron Emission Tomography ◽  
Pulmonary Function ◽  
Goodness Of Fit ◽  
Molecular Nitrogen ◽  
Region Of Interest ◽  
Emission Tomography ◽  
Gas Content ◽  
Pulmonary Vasculature ◽  
Model Parameters ◽  
Positron Emission

To determine the spatial distributions of pulmonary perfusion, shunt, and ventilation, we developed a compartmental model of regional 13N-labeled molecular nitrogen (13NN) kinetics measured from positron emission tomography (PET) images. The model features a compartment for right heart and pulmonary vasculature and two compartments for each region of interest: 1) aerated alveolar units and 2) alveolar units with no gas content (shunting). The model was tested on PET data from normal animals (dogs and sheep) and from animals with experimentally injured lungs simulating acute respiratory distress syndrome. The analysis yielded estimates of regional perfusion, shunt fraction, and specific ventilation with excellent goodness-of-fit to the data ( R 2 > 0.99). Model parameters were estimated to within 10% accuracy in the presence of exaggerated levels of experimental noise by using a Monte Carlo sensitivity analysis. Main advantages of the present model are that 1) it separates intraregional blood flow to aerated alveolar units from that shunting across nonaerated units and 2) it accounts and corrects for intraregional tracer removal by shunting blood when estimating ventilation from subsequent washout of tracer. The model was thus found to provide estimates of regional parameters of pulmonary function in sizes of lung regions that could potentially approach the intrinsic resolution for PET images of 13NN in lung (∼7.0 mm for a multiring PET camera).

scholarly journals Network Diffusion Modeling Explains Longitudinal Tau PET Data

2020 ◽  
Vol 14 ◽  
Author(s):  
Amelie Schäfer ◽  
Elizabeth C. Mormino ◽  
Ellen Kuhl
Keyword(s):  
Positron Emission Tomography ◽  
Clinical Symptoms ◽  
Dynamic Network ◽  
Network Models ◽  
Brain Regions ◽  
Brain Network ◽  
Emission Tomography ◽  
Model Parameters ◽  
Positron Emission ◽  
Network Diffusion

Alzheimer's disease is associated with the cerebral accumulation of neurofibrillary tangles of hyperphosphorylated tau protein. The progressive occurrence of tau aggregates in different brain regions is closely related to neurodegeneration and cognitive impairment. However, our current understanding of tau propagation relies almost exclusively on postmortem histopathology, and the precise propagation dynamics of misfolded tau in the living brain remain poorly understood. Here we combine longitudinal positron emission tomography and dynamic network modeling to test the hypothesis that misfolded tau propagates preferably along neuronal connections. We follow 46 subjects for three or four annual positron emission tomography scans and compare their pathological tau profiles against brain network models of intracellular and extracellular spreading. For each subject, we identify a personalized set of model parameters that characterizes the individual progression of pathological tau. Across all subjects, the mean protein production rate was 0.21 ± 0.15 and the intracellular diffusion coefficient was 0.34 ± 0.43. Our network diffusion model can serve as a tool to detect non-clinical symptoms at an earlier stage and make informed predictions about the timeline of neurodegeneration on an individual personalized basis.

scholarly journals The Quantitative Analysis of D2-Dopamine Receptors in Baboon Striatum in vivo with 3-N-[2'-18F]Fluoroethylspiperone Using Positron Emission Tomography

1990 ◽  
Vol 10 (5) ◽  
pp. 720-726 ◽  
Author(s):  
S. Jovkar ◽  
K. Wienhard ◽  
G. Pawlik ◽  
H. H. Coenen
Keyword(s):  
Positron Emission Tomography ◽  
Kinetic Model ◽  
Dopamine Receptors ◽  
Specific Activity ◽  
Emission Tomography ◽  
Parameter Estimates ◽  
Model Parameters ◽  
Positron Emission ◽  
Model Configuration

We used the ligand 3- N-[2'-18F]fluoroethylspiperone (FESP), which binds to D2-dopamine receptors in the striatum, and positron emission tomography (PET) to quantify striatal D2-dopamine densities ( Bmax) and binding kinetics in baboon brain in vivo. Sequential PET scans were obtained for 4 h post injection. Various similar models based on a nonlinear kinetic four-compartment model that takes into account the effect of ligand specific activity were used. We investigated the effect of exact model configuration on the reliability of Bmax and other kinetic transfer coefficients. We found that with the ligand FESP and dynamic PET studies, the estimated values of Bmax and other model parameters are sensitive to the choice of model configuration, ligand specific activity, and data analysis technique. The limitations of the reliability of parameter estimates in a complex kinetic model for receptor ligands were studied in simulation calculations. Results showed that the accuracy of estimated values of Bmax is affected by both the ligand binding properties and the injected dose of ligand. The estimated average value of kinetic model parameters was as follows: ligand-receptor dissociation constant k4 = 0.0080 min−1; the product of ligand-receptor association constant and fraction of ligand available to bind to specific receptors f2 ka = 0.0052 (min n M)−1; and D2-dopamine receptor density Bmax = 37.5 pmol g−1.

scholarly journals Anatomical-Functional Correlation Using an Adjustable MRI-Based Region of Interest Atlas with Positron Emission Tomography

1988 ◽  
Vol 8 (4) ◽  
pp. 513-530 ◽  
Author(s):  
A. C. Evans ◽  
C. Beil ◽  
S. Marrett ◽  
C. J. Thompson ◽  
A. Hakim
Keyword(s):  
Positron Emission Tomography ◽  
Region Of Interest ◽  
Brain Structures ◽  
Regions Of Interest ◽  
Emission Tomography ◽  
Utilization Rate ◽  
Positron Emission ◽  
Reproducible Analysis ◽  
Magnetic Resonance Imaging Mri ◽  
Trained Observers

A procedure is described for combining anatomical information from magnetic resonance imaging (MRI) or computerized tomography (CT) and functional information from positron emission tomography (PET) in a rapid fashion. MRI data are combined with a procedure for the definition, storage, and recall of anatomically based regions of interest. An atlas of standard regions of interest, defined for a set of 18 parallel planes spaced at 6-mm intervals, provides an initial region of interest template for each patient slice. Global adjustments to scale, orientation, and position are applied to obtain an initial match. Individual regions of interest may then be moved, deleted, or redrawn as needed. The ability to store region of interest templates ensures reproducibility of analysis over long periods and introduces a standardization of analysis technique. In 25 brain structures, the mean coefficient of variation in cerebral glucose utilization rate (CMRGlc) measurements among five neuroanatomically trained observers was reduced from 8.1% for manual region of interest definition to 4.0% using the template approach with MRI. Template analysis for space-occupying lesions such as tumors or infarcts is illustrated with PET data from a stroke study, emphasizing the facility for rapid, reproducible analysis of multifunctional studies. MRI-PET matching for a structurally intact caudate nucleus having reduced CMRGlc in Huntington's disease emphasizes the accuracy of anatomical localization required to quantify small structures.

scholarly journals Imaging Human Mesolimbic Dopamine Transmission with Positron Emission Tomography. Part II: Amphetamine-Induced Dopamine Release in the Functional Subdivisions of the Striatum

2003 ◽  
Vol 23 (3) ◽  
pp. 285-300 ◽  
Author(s):  
Diana Martinez ◽  
Mark Slifstein ◽  
Allegra Broft ◽  
Osama Mawlawi ◽  
Dah-Ren Hwang ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Regional Differences ◽  
Dopamine Release ◽  
Region Of Interest ◽  
Volume Effect ◽  
Emission Tomography ◽  
Constant Infusion ◽  
Positron Emission ◽  
Amphetamine Administration ◽  
Striatal Function

The human striatum is functionally organized into limbic, associative, and sensorimotor subdivisions, which process information related to emotional, cognitive, and motor function. Dopamine projections ascending from the midbrain provide important modulatory input to these striatal subregions. The aim of this study was to compare activation of dopamine D2 receptors after amphetamine administration in the functional subdivisions of the human striatum. D2 receptor availability (V3″) was measured with positron emission tomography and [11C]raclopride in 14 healthy volunteers under control conditions and after the intravenous administration of amphetamine (0.3 mg/kg). For each condition, [11C]raclopride was administered as a priming bolus followed by constant infusion, and measurements of D2 receptor availability were obtained under sustained binding equilibrium conditions. Amphetamine induced a significantly larger reduction in D2 receptor availability (ΔV3″) in limbic (ventral striatum, −15.3 ± 11.8%) and sensorimotor (postcommissural putamen, −16.1 ± 9.6%) regions compared with associative regions (caudate and precommissural putamen, −8.1 ± 7.2%). Results of this region-of-interest analysis were confirmed by a voxel-based analysis. Correction for the partial volume effect showed even greater differences in ΔV3″ between limbic (−17.8 ± 13.8%), sensorimotor (−16.6 ± 9.9%), and associative regions (−7.5 ± 7.5%). The increase in euphoria reported by subjects after amphetamine was associated with larger ΔV3″ in the limbic and sensorimotor regions, but not in the associative regions. These results show significant differences in the dopamine response to amphetamine between the functional subdivisions of the human striatum. The mechanisms potentially accounting for these regional differences in amphetamine-induced dopamine release within the striatum remain to be elucidated, but may be related to the asymmetrical feed-forward influences mediating the integration of limbic, cognitive, and sensorimotor striatal function via dopamine cell territories in the ventral midbrain.

scholarly journals Analysis of PET Neurofunctional Mapping Studies

1995 ◽  
Vol 15 (3) ◽  
pp. 492-504 ◽  
Author(s):  
John R. Votaw ◽  
Hengli H. Li
Keyword(s):  
Positron Emission Tomography ◽  
Region Of Interest ◽  
Functional Mapping ◽  
Emission Tomography ◽  
Data Sets ◽  
Statistical Uncertainty ◽  
Positron Emission

In this work, we present a method for analyzing positron emission tomography (PET) functional mapping experiments. The method is useful for identifying statistically significant differences between two PET data sets. First, uniform-variance Z-images are created and then the statistical uncertainty in region-of-interest values are calculated using a previously published method. The Z-images are calculated from the emission sinograms only

scholarly journals Measurement of Brain pH Using 11CO2 and Positron Emission Tomography

1984 ◽  
Vol 4 (1) ◽  
pp. 8-16 ◽  
Author(s):  
R. B. Buxton ◽  
L. R. Wechsler ◽  
N. M. Alpert ◽  
R. H. Ackerman ◽  
D. R. Elmaleh ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Kinetic Model ◽  
The Body ◽  
Time Dependent ◽  
Emission Tomography ◽  
Model Parameters ◽  
Tissue Ph ◽  
Local Tissue ◽  
Positron Emission ◽  
Brain Ph

We have examined the feasibility of measuring local brain pH in vivo with 11CO2 and positron emission tomography. In particular, we have addressed two objections that have been raised against this method: the assumed need to estimate local tissue Pco2 and the rapid fixation of 11C in tissue. From a reexamination of the basic theory, we argue that after administration of 11CO2 the time-dependent distribution of 11C between tissue and blood is independent of the distribution of CO2 already in the body, making it unnecessary to estimate local tissue Pco2. Assuming that the blood–brain barrier is impermeable to bicarbonate ions, there will be equal partial pressures of 11CO2 in blood and tissue at equilibrium. To overcome the problem of fixation in the tissue we have developed a kinetic model of the time-dependent distribution of 11C that accounts for regional variations in blood flow, CO2 extraction, pH, and rate of fixation. The values of the model parameters can be estimated from sequential measurements of tissue activity concentration during administration of 11CO2. Tissue pH can then be calculated from one of the parameter values, a measurement of arterial pH, and known constants. Numerical calculations based on the kinetic model with assumed values of the parameters were used to optimize the experimental design. The calculations show that problems with fixation are much less severe with continuous infusion of activity than with bolus administration. During infusion the tissue curve depends strongly on tissue pH but only weakly on the rate of fixation. With state of the art tomographic systems it should be possible to measure tissue pH with an error of about 0.04 pH units.

scholarly journals Dual-[11C]Tracer Single-Acquisition Positron Emission Tomography Studies

2001 ◽  
Vol 21 (12) ◽  
pp. 1480-1492 ◽  
Author(s):  
Robert A. Koeppe ◽  
David M. Raffel ◽  
Scott E. Snyder ◽  
Edward P. Ficaro ◽  
Michael R. Kilbourn ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Computer Simulations ◽  
Emission Tomography ◽  
Parameter Estimates ◽  
Model Parameters ◽  
Tracer Injection ◽  
Positron Emission ◽  
Dynamic Scan ◽  
Dual Tracer

The ability to study multiple physiologic processes of the brain simultaneously within the same subject would provide a new means to explore the interactions between neurotransmitter systems in vivo. Currently, examination of two distinct neuropharmacologic measures with positron emission tomography (PET) necessitates performing two separate scans spaced in time to allow for radionuclide decay. The authors present results from a dual-tracer PET study protocol using a single dynamic-scan acquisition where the injections of two tracers are offset by several minutes. Kinetic analysis is used to estimate neuropharmacologic parameters for both tracers simultaneously using a combined compartmental model configuration. This approach results in a large reduction in total study time of nearly 2 hours for carbon-11–labeled tracers. As multiple neuropharmacologic measures are obtained at nearly the same time, interventional protocols involving a pair of dual-tracer scans become feasible in a single PET session. Both computer simulations and actual human PET studies were performed using combinations of three different tracers: [11C]flumazenil, N-[11C]methylpiperidinyl propionate, and [11C]dihydrotetrabenazine. Computer simulations of tracer-injection separations of 10 to 30 minutes showed the feasibility of the approach for separations down to 15 to 20 minutes or less. Dual-tracer PET studies were performed in 32 healthy volunteers using injection separations of 10, 15, or 20 minutes. Model parameter estimates for each tracer were similar to those obtained from previously performed single-injection studies. Voxel-by-voxel parametric images were of good quality for injections spaced by 20 minutes and were nearly as good for 15-minute separations, but were degraded noticeably for some model parameters when injections were spaced by only 10 minutes. The authors conclude that dual-tracer single-scan PET is feasible, yields accurate estimates of multiple neuropharmacologic measures, and can be implemented with a number of different radiotracer pairs.

scholarly journals Positron Emission Tomography Quantification of [11C]-DASB Binding to the Human Serotonin Transporter: Modeling Strategies

2001 ◽  
Vol 21 (11) ◽  
pp. 1342-1353 ◽  
Author(s):  
Nathalie Ginovart ◽  
Alan A. Wilson ◽  
Jeffrey H. Meyer ◽  
Doug Hussey ◽  
Sylvain Houle
Keyword(s):  
Positron Emission Tomography ◽  
Serotonin Transporter ◽  
Quantitative Methods ◽  
Goodness Of Fit ◽  
Emission Tomography ◽  
Binding Potential ◽  
Reference Region ◽  
Time Activity ◽  
Healthy Humans ◽  
Positron Emission

[11C]-DASB, namely [11C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile, is a new highly selective radioligand for the in vivo visualization of the serotonin transporter (SERT) using positron emission tomography (PET). The current study evaluates different kinetic modeling strategies for quantification of [11C]-DASB binding in five healthy humans. Kinetic analyses of tissue data were performed with a one-tissue (1CM) and a two-tissue (2CM) compartment model. Time-activity curves were well described by a 1CM for all regions. A 2CM model with four parameters failed to converge reliably. Reliable fits of the data were obtained only if no more than three parameters were allowed to vary. However, even then, the rate constants k3 and k4 were estimated with poor precision. Only the ratio k3/k4 was stable. Goodness of fit was not improved by using a 2CM as compared with a 1CM. The minimal study duration required to obtain stable k3/k4 estimates was 80 minutes. For routine use of [11C]-DASB, several simplified methods using the cerebellum as a reference region to estimate nonspecific binding were also evaluated. The transient equilibrium, the linear graphical analysis, the ratio of target to reference region, and the simplified reference tissue methods all gave binding potential values consistent with those obtained with the 2CM. The suitability of [11C]-DASB for research on the SERT using PET is thus supported by the observations that tissue data can be described using a kinetic analysis and that simplified quantitative methods, using the cerebellum as reference, provide reliable estimates of SERT binding parameters.

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