scholarly journals Effects of Blood Flow on [11C]Raclopride Binding in the Brain: Model Simulations and Kinetic Analysis of PET Data

1994 ◽  
Vol 14 (6) ◽  
pp. 995-1010 ◽  
Author(s):  
Jean Logan ◽  
Nora D. Volkow ◽  
Joanna S. Fowler ◽  
Gene-Jack Wang ◽  
Stephen L. Dewey ◽  
...  
Keyword(s):  
Blood Flow ◽  
Region Of Interest ◽  
Receptor Occupancy ◽  
Compartment Model ◽  
Model Parameters ◽  
Individual Model ◽  
Positron Emission ◽  
D2 Antagonist ◽  
The Stability ◽  
The Individual

To assess the stability of different measures of receptor occupancy from [11C]raclopride (a D2 antagonist) studies with positron emission tomography, we analyze data from five test/retest studies in normal volunteers in terms of individual model parameters from a three-compartment model, the distribution volume (DV) and the ratio of DVs from a receptor-containing region of interest to a non-receptor-containing region. Large variations were found in the individual model parameters, limiting their usefulness as an indicator of change in receptor systems. The DV ratio showed the smallest variation. Individual differences were reflected in the greater intersubject variation in DV than intrasubject variation. The potential effects of blood flow on these measurements were addressed both experimentally and by simulation studies using three models that explicitly incorporate blood flow into a compartmental model that also includes receptor–ligand binding. None of the models showed any variation in the DV with changes in blood flow as long as flow was held constant during the simulation. Experimentally, blood flow was significantly reduced by hyperventilation in a human subject. The DV was found to be reduced relative to baseline in the hyperventilation study, but the DV ratio remained unchanged. The effect of elevated and reduced flow was also tested in two baboon experiments in which Pco2 was varied. Some variability in the DV ratio was observed but was not correlated with changes in blood flow. This raises the possibility that other factors indirectly related to changes in blood flow (or Pco2) may cause changes in DV, and these effects need to be considered when evaluating experimental results.

scholarly journals Blood Flow Assessment of Arteriovenous Malformations Using Intraoperative Indocyanine Green Videoangiography

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Naoki Kato ◽  
Vincent Prinz ◽  
Julius Dengler ◽  
Peter Vajkoczy
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Indocyanine Green ◽  
Region Of Interest ◽  
Flow Dynamics ◽  
Flow Index ◽  
Indocyanine Green Videoangiography ◽  
Blood Flow Index ◽  
High Resolution Images ◽  
The Individual

Intraoperative indocyanine green (ICG) videoangiography is widely used in patients undergoing neurosurgery. FLOW800 is a recently developed analytical tool for ICG videoangiography to assess semi-quantitative flow dynamics; however, its efficacy is unknown. In this study, we evaluated its functionality in the assessment of flow dynamics of arteriovenous malformation (AVM) through ICG videoangiography under clinical settings. ICG videoangiography was performed in the exposed AVM in eight patients undergoing surgery. FLOW800 analysis was applied directly, and gray-scale and color-coded maps of the surgical field were obtained. After surgery, a region of interest was placed on the individual vessels to obtain time-intensity curves. Parameters of flow dynamics, including the maximum intensity, transit time, and cerebral blood flow index, were calculated using the curves. The color-coded maps provided high-resolution images; however, reconstruction of colored images was restricted by the depth, approach angle, and brain swelling. Semi-quantitative parameters were similar among the feeders, niduses, and drainers. However, a higher cerebral blood flow index was observed in the feeders of large AVM (>3 cm) than in those of small AVM (P < 0.05). Similarly, the cerebral blood flow index values were positively correlated with the nidus volume (P < 0.01). FLOW800 enabled visualization of the AVM structure and safer resection, except in case of deep-seated AVM. Moreover, semi-quantitative values in the individual vessels through using ICG intensity diagram showed different patterns according to size of the AVM. ICG videoangiography showed good performance in evaluating flow dynamics of the AVM in patients undergoing surgery.

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).

Cephalad Movement of Morphine and Fentanyl in Humans after Intrathecal Injection

2003 ◽  
Vol 99 (1) ◽  
pp. 166-173 ◽  
Author(s):  
James C. Eisenach ◽  
David D. Hood ◽  
Regina Curry ◽  
Steven L. Shafer
Keyword(s):  
Time Course ◽  
Pharmacokinetic Model ◽  
Intrathecal Injection ◽  
Initial Distribution ◽  
Model Parameters ◽  
Resonance Imaging ◽  
Individual Model ◽  
Primary Determinant ◽  
The Individual ◽  
Lower Lumbar

Background Despite decades of use, controversy remains regarding the extent and time course of cephalad spread of opioids in cerebrospinal fluid (CSF) after intrathecal injection. The purpose of this study was to examine differences between two often used opioids, morphine and fentanyl, in distribution in the CSF after intrathecal injection. Methods Eight healthy volunteers received intrathecal injection of morphine (50 microg) plus fentanyl (50 microg) at a lower lumbar interspace. CSF was sampled through a needle in an upper lumbar interspace for 60-120 min. At the end of this time, a sample was taken from the lower lumbar needle, and both needles were withdrawn. CSF volume was determined by magnetic resonance imaging. Pharmacokinetic modeling was performed with NONMEM. Results Morphine and fentanyl peaked in CSF at the cephalad needle at similar times (41 +/- 13 min for fentanyl, 57 +/- 12 min for morphine). The ratio of morphine to fentanyl in CSF at the cephalad needle increased with time, surpassing 2:1 by 36 min and 4:1 by 103 min. CSF concentrations did not correlate with weight, height, or lumbosacral CSF volume. The concentrations of morphine and fentanyl at both sampling sites were well described by a simple pharmacokinetic model. The individual model parameters did not correlate with the distance between the needles, CSF volume, patient height, or patient weight. Conclusions Fentanyl is cleared more rapidly from CSF than morphine, although their initial distribution in the first hour after injection does not differ greatly. The pharmacokinetic model demonstrates that mixing is the primary determinant of early concentrations and is highly variable among individuals.

Early Amygdala Activation and Later Ventromedial Prefrontal Cortex Activation During Anger Induction and Imagery

2020 ◽  
Vol 1 (1) ◽  
pp. 1-8
Author(s):  
Darin D. Dougherty ◽  
Tina Chou ◽  
Ulrike Buhlmann ◽  
Scott L. Rauch ◽  
Thilo Deckersbach
Keyword(s):  
Prefrontal Cortex ◽  
Time Course ◽  
A Priori ◽  
Region Of Interest ◽  
Ventromedial Prefrontal Cortex ◽  
Amygdala Activation ◽  
Positron Emission ◽  
Initial Onset ◽  
The Individual ◽  
Neutral Conditions

Background: Neurobiological studies implicate the amygdala and related limbic/paralimbic structures, such as the ventromedial prefrontal cortex (VMPFC), in anger and aggression. Previous studies of self-generated anger using Positron Emission Tomography (PET) have consistently documented a lack of amygdala activation during anger. Objective: We investigated the hypothesis that a lack of amygdala activation during anger is due to differences in the time course of amygdala and VMPFC activation. Specifically, we explored whether the amygdala is involved in the early phases of anger experience which is later followed by increased VMPFC activation. Methods: Eighteen healthy control participants underwent fMRI. We adapted an anger induction paradigm previously used in our PET study, in which neutral and angry states were induced using autobiographical scripts. The hypothesized time course of amygdala and VMPFC activation during acute anger induction and imagery were modeled. Region of interest (ROI) analyses were used to identify significant a priori region activation, and correlations were run between signal values and VAS anger ratings. Results: Amygdala activation increased during the acute phase of anger induction and decreased during the later phase of anger imagery, whereas VMPFC activation decreased during anger induction and increased during anger imagery, compared to the neutral conditions. In addition, negative correlations were found between self-ratings of anger and bilateral VMPFC activation. Conclusions: Overall, our results suggest that the amygdala may be active at the initial onset of anger while the VMPFC is activated over time as the individual sustains and perhaps regulates that emotional state.

Modulation of muscle and pulmonary O2 uptakes by circulatory dynamics during exercise

1990 ◽  
Vol 68 (3) ◽  
pp. 979-989 ◽  
Author(s):  
T. J. Barstow ◽  
N. Lamarra ◽  
B. J. Whipp
Keyword(s):  
Blood Flow ◽  
Phase 1 ◽  
Compartment Model ◽  
Model Parameters ◽  
Base Line ◽  
O2 Uptake ◽  
Flow Adjustment ◽  
Body Compartments ◽  
Exercise Induced ◽  
O2 Delivery

The effect of cardiovascular adjustments on the coupling of cellular to pulmonary gas exchange during unsteady states of exercise remains controversial. Computer simulations were performed to assess these influences on O2 delivery and pulmonary O2 uptake (pVO2). Algorithms were developed representing muscle and “rest-of-body” compartments, connected in parallel by arterial and venous circulations to a pump-and-lungs compartment. Exercise-induced increases in VO2 and cardiac output went to the muscle compartment. Model parameters [e.g., time constants for blood flow and muscle O2 uptake (mVO2)] could be varied independently. Simulation results demonstrated that 1) the rise in pVO2 during exercise contains three phases; 2) the contribution of changes in venous O2 stores to pVO2 kinetics and the O2 deficit occur almost entirely in phase 1; 3) under a wide variety of manipulations, the kinetics of pVO2 in phase 2 were within a couple of seconds of that assigned to mVO2 (i.e., there is not an obligatory slowing of VO2 kinetics at the lungs relative to those at the muscles; 4) by use of available estimates of blood flow adjustment, O2 delivery would not limit mVO2 after exercise onset; and 5) blood flow could limit O2 delivery in recovery, if blood flow returned to base-line levels at rates similar to those during the on-transient phase.

scholarly journals In vivo evaluation of [11C]preladenant positron emission tomography for quantification of adenosine A2A receptors in the rat brain

2016 ◽  
Vol 37 (2) ◽  
pp. 577-589 ◽  
Author(s):  
Xiaoyun Zhou ◽  
Shivashankar Khanapur ◽  
Johan R de Jong ◽  
Antoon TM Willemsen ◽  
Rudi AJO Dierckx ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Receptor Occupancy ◽  
Compartment Model ◽  
Emission Tomography ◽  
Rat Striatum ◽  
Receptor Density ◽  
Reference Tissue ◽  
Tissue Compartment ◽  
Positron Emission ◽  
The Brain

[11C]Preladenant was developed as a novel adenosine A2A receptor positron emission tomography radioligand. The present study aims to evaluate the suitability of [11C]preladenant positron emission tomography for the quantification of striatal A2A receptor density and the assessment of striatal A2A receptor occupancy by KW-6002. Sixty- or ninety-minute dynamic positron emission tomography imaging was performed on rats. Tracer kinetics was quantified by the two-tissue compartment model, Logan graphical analysis and several reference tissue-based models. Test–retest reproducibility was assessed by repeated imaging on two consecutive days. Two-tissue compartment model and Logan plot estimated comparable distribution volume ( VT) values of ∼10 in the A2A receptor-rich striatum and substantially lower values in all extra-striatal regions (∼1.5–2.5). The simplified reference tissue model with midbrain or occipital cortex as the reference region proved to be the best non-invasive model for quantification of A2A receptor, showing a striatal binding potential ( BPND) value of ∼5.5, and a test–retest variability of ∼5.5%. The brain metabolite analysis showed that at 60-min post injection, 17% of the radioactivity in the brain was due to radioactive metabolites. The ED50 of KW-6002 in rat striatum for i.p. injection was 0.044–0.062 mg/kg. The study demonstrates that [11C]preladenant is a suitable tracer to quantify striatal A2A receptor density and assess A2A receptor occupancy by A2A receptor-targeting molecules.

scholarly journals Estimation of Local Cerebral Protein Synthesis Rates with L-[1-11C]Leucine and PET: Methods, Model, and Results in Animals and Humans

1989 ◽  
Vol 9 (4) ◽  
pp. 446-460 ◽  
Author(s):  
Randall A. Hawkins ◽  
Sung-Cheng Huang ◽  
Jorge R. Barrio ◽  
Randy E. Keen ◽  
Dagan Feng ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Compartment Model ◽  
Input Function ◽  
Model Parameters ◽  
Positron Emission ◽  
Human Volunteers ◽  
Normal Human ◽  
Three Compartment Model ◽  
Computer Simulation Studies ◽  
Cerebral Protein Synthesis

We have estimated the cerebral protein synthesis rates (CPSR) in a series of normal human volunteers and monkeys using l-[1-11C]leucine and positron emission tomography (PET) using a three-compartment model. The model structure, consisting of a tissue precursor, metabolite, and protein compartment, was validated with biochemical assay data obtained in rat studies. The CPSR values estimated in human hemispheres of about 0.5 nmol/min/g agree well with hemispheric estimates in monkeys. The sampling requirements (input function and scanning sequence) for accurate estimates of model parameters were investigated in a series of computer simulation studies.

Brainstem changes in 5-HT1A receptor availability during migraine attack

Cephalalgia ◽  
2010 ◽  
Vol 31 (1) ◽  
pp. 84-94 ◽  
Author(s):  
G Demarquay ◽  
A Lothe ◽  
JP Royet ◽  
N Costes ◽  
G Mick ◽  
...  
Keyword(s):  
Migraine Attack ◽  
Early Stage ◽  
Region Of Interest ◽  
Binding Potential ◽  
Precentral Gyrus ◽  
Individual Level ◽  
Control Subjects ◽  
Pet Tracer ◽  
Positron Emission ◽  
The Individual

Background: Among serotonin receptors, 5-HT1A receptors are implicated in the regulation of central serotoninergic tone and could be involved in the abnormal brain 5-HT turnover suspected in migraineurs. The aim of this study was to investigate 5-HT1A receptors’ availability during migraine attacks. Methods: Ten patients suffering from odor-triggered migraine attacks and 10 control subjects were investigated using positron emission tomography (PET) and [18F]MPPF PET tracer, a selective 5-HT1A antagonist. All subjects underwent calibrated olfactory stimulations prior to the PET study. Results: Four patients developed a migraine attack during the PET study. In these patients, statistical parametrical mapping and region of interest analyses showed an increased [18F]MPPF binding potential (BPND) in the pontine raphe when compared to headache-free migraineurs and control subjects. This ictal change was confirmed at the individual level in each of the four affected patients. In comparison with the headache-free migraineurs, patients with a migraine attack also showed significantly increased [18F]MPPF BPND in the left orbitofrontal cortex, precentral gyrus and temporal pole. No significant change in [18F]MPPF BPND was observed between headache-free migraineurs and controls. Conclusions: Our results emphasize the role of 5HT1A receptors in the pontine raphe nuclei during the early stage of migraine attacks.

scholarly journals A Study of the Single Compartment Tracer Kinetic Model for the Measurement of Local Cerebral Blood Flow Using 15O-Water and Positron Emission Tomography

1987 ◽  
Vol 7 (1) ◽  
pp. 13-20 ◽  
Author(s):  
Sanjiv S. Gambhir ◽  
Sung-Cheng Huang ◽  
Randall A. Hawkins ◽  
Michael E. Phelps
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Data Collection ◽  
Human Subjects ◽  
Compartment Model ◽  
Distribution Volume ◽  
Single Compartment ◽  
Positron Emission ◽  
Single Compartment Model ◽  
Collection Time

The effects of varying the data collection time on the calculation of cerebral blood flow and distribution volume via the integrated projection technique were studied in four human subjects. The significance of these results in terms of the limitations of the single compartment model for 15O-water was explored using computer simulations. The simulations helped to account for causes for the variations seen in blood flow and distribution volume as a function of the data collection time. Two different compartmental models were explored for better quantitation of blood flow and distribution volume.

scholarly journals Effect of Tissue Heterogeneity on the Measurement of Cerebral Blood Flow with the Equilibrium C15O2 Inhalation Technique

1983 ◽  
Vol 3 (4) ◽  
pp. 407-415 ◽  
Author(s):  
Peter Herscovitch ◽  
Marcus E. Raichle
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
White Matter ◽  
Partition Coefficient ◽  
Region Of Interest ◽  
Compartment Model ◽  
Cortical Activation ◽  
Surrounding Tissue ◽  
Inhalation Technique ◽  
Local Flow

The equilibrium C15O2 inhalation method for measuring cerebral blood flow with positron emission tomography (PET) is based on a one-compartment model for which it is assumed that the local flow and partition coefficient are uniform in the tissue region in which flow is to be determined. However, because of the limited spatial resolution of PET, a region of interest will contain a mixture of gray and white matter. We used a computer simulation to examine the effect of this heterogeneity on flow measurement in both normal and pathological states. With gray and white matter flows of 0.80 and 0.20 ml/min/g, respectively, flow is underestimated by a maximum of 20% in a region that is 30% gray. Errors occur not only because of flow heterogeneity, but also because of heterogeneity of partition coefficient and the sensitivity of the method to errors in partition coefficient. Larger errors occur in the case of cerebral hyperemia, although the method becomes more accurate with ischemia. In the case of simulated brain tumor, the accuracy of flow determination varies considerably, depending on the flow and partition coefficient of the tumor and of the surrounding tissue. Finally, incremental changes in gray matter flow, as would occur with functional cortical activation, are not well reflected. Thus, the equilibrium C15O2 inhalation method is limited in its ability to accurately quantitate local cerebral blood flow in heterogeneous tissue regions.

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