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 ◽  
...  

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.

1990 ◽  
Vol 10 (5) ◽  
pp. 720-726 ◽  
Author(s):  
S. Jovkar ◽  
K. Wienhard ◽  
G. Pawlik ◽  
H. H. Coenen

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.


2020 ◽  
Vol 117 (5) ◽  
pp. 2265-2267 ◽  
Author(s):  
Xuezhu Zhang ◽  
Simon R. Cherry ◽  
Zhaoheng Xie ◽  
Hongcheng Shi ◽  
Ramsey D. Badawi ◽  
...  

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).


2002 ◽  
Vol 93 (3) ◽  
pp. 1104-1114 ◽  
Author(s):  
Gaetano G. Galletti ◽  
José G. Venegas

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).


Author(s):  
Barry J. Snow

ABSTRACT:Positron emission tomography (PET) allows the study of physiological and neurochemical processes which would otherwise be inaccessible, using radioactive labels on biological compounds to follow their fate in the body. By analysing changes of concentration with time we can measure blood flow, neuronal metabolism and receptor ligand interactions. In Parkinson’s disease (PD), PET has been used to examine the dopaminergic deficit and its relationship to motor performance. It has also been shown to detect asymptomatic dopaminergic lesions that have implications for the etiology of PD. In untreated PD there is increased density of D2 binding sites, while in chronically treated PD with motor fluctuations, D2 receptor density is reduced. [18F]-fluorodeoxyglucose studies of demented PD patients show a pattern of cortical metabolism similar to Alzheimer’s disease. Activation studies, which measure changes in blood flow during the performance of motor tasks, show reduced activation of medial frontal areas in PD.


2018 ◽  
Vol 185 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Yusuke Inoue ◽  
Kazunori Nagahara ◽  
Hiroko Kudo ◽  
Hiroyasu Itoh

Abstract We performed phantom experiments to investigate radiation dose in the computed tomography component of oncology positron emission tomography/computed tomography in relation to the scan range. Computed tomography images of an anthropomorphic whole-body phantom were obtained from the head top to the feet, from the head top to the proximal thigh or from the skull base to the proximal thigh. Automatic exposure control using the posteroanterior and lateral scout images offered reasonable tube current modulation corresponding to the body thickness. However, when the posteroanterior scout alone was used, unexpectedly high current was applied in the head and upper chest. When effective dose was calculated on a region-by-region basis, it did not differ greatly irrespective of the scan range. In contrary, when effective dose was estimated simply by multiplying the scanner-derived dose-length product by a single conversion factor, estimates increased definitely with the scan range, indicating severe overestimation in whole-body imaging.


2010 ◽  
Vol 37 (8) ◽  
pp. 3995-4010 ◽  
Author(s):  
R. Klein ◽  
R. S. Beanlands ◽  
R. W. Wassenaar ◽  
S. L. Thorn ◽  
M. Lamoureux ◽  
...  

1986 ◽  
Vol 2 (4) ◽  
pp. 577-594 ◽  
Author(s):  
Nora D. Volkow ◽  
Laurence R. Tancredi

Positron emission tomography (PET) is a new nuclear medicine technique that has recently entered the clinical realm of medicine. Although it is a technique that can be utilized for assessment of biochemical and physiological parameters of any organ in the body, it has particular utility in the investigation of the brain. PET poses unique advantages over previous imaging devices. For the first time, it is feasible to investigate directly various biological parameters of the brain in a noninvasive way. PET allows for investigating the functional, biochemical, physiological, and pharmacological characteristics of various areas within the brains of normal and psychiatric or neurological patients. Although it has already started to give promising results, it is too new a technique to obtain an accurate appraisal of its true potentials. This is a problem that seems always to surface when one tries to evaluate the utility of a new technique in a new area of research. The problem is accentuated in the case of PET where there is no other technique available with which to compare results. This paper will discuss the basic principles of PET, its relationship to other existing imaging devices, and the issues to be considered when making a technological assessment of positron emission tomography.


1984 ◽  
Vol 4 (3) ◽  
pp. 458-465 ◽  
Author(s):  
David J. Brooks ◽  
Adriaan A. Lammertsma ◽  
Ronald P. Beaney ◽  
Klaus L. Leenders ◽  
Peter D. Buckingham ◽  
...  

The cerebral pH of four normal human subjects has been measured using continuous inhalation of 11CO2 and positron emission tomography (PET). 11CO2 was administered to each subject at a constant rate for 15 min, during which time serial arterial plasma 11C levels were determined and serial 11C cerebral uptake PET scans were performed at a fixed axial tomographic level. 11C uptake kinetics were analysed using a three-compartment model. Rate constants have been estimated for the free exchange of 11CO2 between plasma and cerebral compartments for each subject, and their cerebral pH calculated. Whole brain pH values ranged from 6.96 to 7.05, and no significant pH difference between regions containing predominantly grey or white matter was noted. Best fits to 11C uptake data were achieved by effectively neglecting the metabolic fixation of 11C by cerebral tissue. The purpose of this study was to test the feasibility of pH measurement using the 11CO2 continuous inhalation technique. It is concluded from the results and the error analysis that continuous 11CO2 inhalation combined with PET is potentially a simple and useful method for determining regional cerebral pH.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Emma Jussing ◽  
Li Lu ◽  
Jonas Grafström ◽  
Tetyana Tegnebratt ◽  
Fabian Arnberg ◽  
...  

Abstract Background Albumin is commonly used as a carrier platform for drugs to extend their circulatory half-lives and influence their uptake into tissues that have altered permeability to the plasma protein. The albumin-binding domain (ABD) protein, which binds in vivo to serum albumin with high affinity, has proven to be a versatile scaffold for engineering biopharmaceuticals with a range of binding capabilities. In this study, the ABD protein equipped with a mal-DOTA chelator (denoted ABY-028) was radiolabeled with gallium-68 (68Ga). This novel radiotracer was then used together with positron emission tomography (PET) imaging to examine variations in the uptake of the ABD-albumin conjugate with variations in endothelial permeability. Results ABY-028, produced by peptide synthesis in excellent purity and stored at − 20 °C, was stable for 24 months (end of study). [68Ga]ABY-028 could be obtained with labeling yields of > 80% and approximately 95% radiochemical purity. [68Ga]ABY-028 distributed in vivo with the plasma pool, with highest radioactivity in the heart ventricles and major vessels of the body, a gradual transport over time from the circulatory system into tissues and elimination via the kidneys. Early [68Ga]ABY-028 uptake differed in xenografts with different vascular properties: mean standard uptake values (SUVmean) were initially 5 times larger in FaDu than in A431 xenografts, but the difference decreased to 3 after 1 h. Cutaneously administered, vasoactive nitroglycerin increased radioactivity in the A431 xenografts. Heterogeneity in the levels and rates of increases of radioactivity uptake was observed in sub-regions of individual MMTV-PyMT mammary tumors and in FaDu xenografts. Higher uptake early after tracer administration could be observed in lower metabolic regions. Fluctuations in the increased permeability for the tracer across the blood-brain-barrier (BBB) direct after experimentally induced stroke were monitored by PET and the increased uptake was confirmed by ex vivo phosphorimaging. Conclusions [68Ga]ABY-028 is a promising new tracer for visualization of changes in albumin uptake due to disease- and pharmacologically altered vascular permeability and their potential effects on the passive uptake of targeting therapeutics based on the ABD protein technology.


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