Neurokinetics the dynamics of neurobiology in vivo

[...]... example of the use of (1.32), see Fig 5.3 The linearity of the equation can be further evaluated by normalization to eliminate one of the independent variables In this case, the normalization refers to the process of dividing the quantity of tracer in the tissue by the arterial concentrations of tracer obtained in individual experiments, ! R Tm RT m o ca dt o V dt ; (1.33) D Vo C k2 V ca ca where the m=ca... such tracers in brain For these tracers, the brain has two kinetic compartments, the vascular space and an extravascular space, separated by a blood–brain barrier The two states of the tracer cannot be detected separately in vivo because the interface between the compartments is inside the brain tissue For nonbrain tissue, the leaky junctions of the capillary endothelium give access to the first significant... association of the tracer to the recognition site Figure 1.3 illustrates the binding of the dopamine D2 4 receptor ligand N -methylspiperone to its receptor This binding is of such high affinity that it continues irreversibly for the duration of the measurement kcat , the rate-limiting step is the catalysis by the protein In this For koff w case, k3 equals kcat Bmax =.Vd Kd /, according to which the accumulation... which the tracer concentration in the aqueous fraction of the vascular volume, as it exits from the tissue, is identical to the concentration in the aqueous phase of the parenchyma In this case, the tracer in the tissue is distributed in a single compartment with a uniform concentration The quantity of accumulated labeled material, m, in the tissue then can be represented by the product Vcv For the. .. set of compartments that simulate a biological system Compartmental analysis tests the validity of the model of the combined kinetic behavior of the elements of each compartment The model provides the basis for prediction of subsequent behavior Thus, the model is the mathematical expression of the biological system, and the compartmental analysis is the test of predictions generated by the hypothesis... present when the ratio defining the partition coefficient D c2 =c1 D ˛2 =˛1 equals the value of the term e  o zF  / where c1 and c2 are the concentrations and ˛1 and ˛2 are the solubilities, relative to water, in two adjoining media The speed with which secular equilibrium is reached is an important indicator of the composition of the tissue The diffusion velocity is the product of the mobility of the particles... consisting of binding and catalysis (facilitation) can now be evaluated by considering the relative magnitudes of koff and kcat The relaxation constant k3 is defined by this equation as the steady-state (combined forward) rate constant of the binding Precursor Compartment The introduction of a binding, metabolism, or transport compartment that reaches secular equilibrium affects the description of the. .. earlier in (1.38) and is a function of the relationship between the two relaxation constants koff and kcat kcat , the rate-limiting step is the association with the recognition For koff site For this case, k3 equals kon Bmax =Vd as described in (1.38) It is surprising to realize that the highest binding affinities render the accumulation of the tracer in the third compartment a function of the rate of association... decide the validity of the model and obtain the best estimates of the coefficients at the same time Both mathematical simulations of the behavior of the model and actual experiments help justify the choice of the model 1.2 Single Tissue Compartment Analysis A special case of single tissue compartment analysis is quantification of blood flow to a tissue This procedure involves the whole-organ estimate of uptake... solutes from the circulation In brain, the capillary endothelial cells in the tissue have particularly tight (so-called tight tight) junctions that do form such a barrier Thus, in brain, the concentration difference of newly administered polar tracer solutes between the two sides of the endothelium initially is so great that the endothelium may be the only significant barrier to the distribution of such . (2000) and the Blue Brain Project of Markram (2006). In this compendium, we focus on the dynamics of brain physiology in vivo from the perspective of the methods of tracer kinetics (neurokinetics) an increasing understanding of the limits of certainty. Preface vii Competing with this understanding is the rise of information technology, according to which the quantitative properties of the. system. The kinetic analysis of the model (which usually describes a dynamic process) tests the validity of the model of the combined kinetic behavior of the elements of each compartment. The model