Vocabulary
A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z
B
Binding is the class of processes that consist of two molecular species combining, usually non-covalently, to form a single complex. Examples are hormones and neurotransmitters binding to their receptors on the cell surface and fatty acids binding to albumin. PET can quantitate the rates of physiological or biochemical processes in vivo. There are three types of dynamic biological processes: translocation, transformation, and binding. Binding is actually a special case of transformation, but as a widespread biological phenomenon it deserves a separate category.
C
Catenary model is a one-dimensional chain of compartments, each connected only to the immediate right and immediate left, i.e. compartments are in series. Name comes from the Latin word for chain. Mixed mammillary/catenary models are commonly used in nuclear medicine.
Compartment is a chemical species in a physical place (in the sense used by modellers); so neither glucose or interstitial space is a compartment, but glucose in interstitial space is one. Inside a compartment the tracer is considered to be distributed uniformly.
Compartmental model assumes that injected isotope exists in the body in a fixed number of physical or chemical states (compartments) with specified interconnections among them; the arrows indicate the possible pathways the tracer can follow. Physiologically the flux of material represents transport from one location to another or a chemical transformation or both. Compartmental models can be described in terms of a set of linear, first-order, constant-coefficient, ordinary differential equations (ODEs). By convention, in the nuclear medicine literature, the first compartment is the blood or plasma pool.
D
(Total) distribution volume (DV or Vd) is defined as the ratio of the tracer concentration in tissue to that in plasma at equilibrium. Therefore, a DV equal to 15 means that the tracer is being concentrated in tissue by 15:1.
E
Effect size is a way of quantifying the effectiveness of a particular intervention, relative to some comparison. It is the standardized mean difference between the two groups: Effect size = (Mean of experimental group - Mean of control group) / Standard deviation. In studies where there is a large control group, its SD should be used in calculation of effect size. If there is not a true control group, or the control group is small, it is better to use a pooled estimate of SD: SDpooled = sqrt(((NE-1)*SDE2 + (NC-1)*SDC2 ) / (NE+NC-2)).
F
f1 is the fraction of free tracer in plasma; thus, the concentration of tracer available for transport into tissue is f1Ca(t).
f2 is the fraction of free tracer in tissue, f2=Cfree/(Cfree+Cnon-specific). 1-f2 represents the fraction of non-specific binding in tissue. In a two-tissue compartment model f2 affects both k2 and k3.
Fitting or parameter estimation: Finding a set of parameters that with measured input function will produce simulated output which is as close as possible to a given set of actual PET measurements. The criterion for goodness of fit is the weighted least squares function. An optimization algorithm is used for iteratively moving from one set of parameters to a better set until progress is stalled or until a fixed maximum number of iterations has passed. If the criterion function has multiple local minima, the iterative search may end up at any one of these. If no constraints are imposed on the parameters, the minimum could correspond to a physically unrealizable set of parameters, e.g. negative rate constants or vascular volume fraction greater than 1.
G
Graphical plots are compartment model independent methods, which deliver less detailed information, but are often less prone to errors. A regression line is fitted to the data after certain integral transformations. The most frequently used graphical methods are the Gjedde-Patlak plot for irreversible tracers and the Logan plot for reversible tracers.
I
Input function (delivery function) describes the concentration of the authentic (original) compound in arterial plasma as a function of time.
Intraclass correlation coefficient (ICC) evaluates the within-subject variablity relative to the between-subject variability. ICC ranges between -1 (no reliability) and 1 (maximum reliability).
L
In compartmental models, from the linearity of the tracer follows that kinetic measurements are the convolution of the tracer input function and the response function of the system. If the input function is also known, the response function of the system can in theory be deduced by deconvolving the input function from the measured kinetics of the system.
Logan plot is a multiple-time graphical analysis for reversible tracers. It produces volume of distribution (DV) in case arterial plasma is measured and used as model input, or distribution volume ratio (DVR) in case a reference region curve is used as model input.
M
Mammillary model (from the Latin word for breast) has a central compartment surrounded by others connected only to the central compartment (like a sow nursing piglets), i.e. compartments are in parallel. Mixed mammillary/catenary models are commonly used in nuclear medicine.
A model is a simultaneous system of differential equations and associated algebraic equations that defines the state variables and rate laws for a particular physical, chemical or biological system. A model is an analogue that behaves like the real system.
Modelling gives us tools for investigating, understanding, and predicting various phenomena in science. In PET the mathematical models describe the dynamic behavior of the tracer in terms of mathematical representations. Known information about the tracer and process (biochemical reaction sequence, membranes that must be crossed, etc.) is incorporated by restricting the representation to a limited set of functions.
Molecular imaging is the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems. To elaborate; Molecular imaging typically includes 2- or 3-dimensional imaging as well as quantification over time. The techniques used include radiotracer imaging/nuclear medicine, MR imaging, MR spectroscopy, optical imaging, ultrasound, and others. (definition by MICoE and SNM).
Multiple-time graphical analysis, MTGA, is a method where PET time-radioactivity curves of region-of-interest and "model input" (reference region or arterial plasma) are normalized and plotted in a graph. The slope of the linear part of the plot represents the net uptake rate of the tracer (so called Gjedde-Patlak plot for irreversible tracers) or volume of distribution (so called Logan plot for reversible tracers).
P
Parameters of the model are the transfer rates between compartments, and other constants in compartmental model, e.g. vascular fraction.
Partial volume effect (PVE): when the volume of the structure of interest is small in comparison to the resolution of the scanner, the radioactivity in the structure is artifactually reduced from its true value, while it is artifactually increased in its surrounding region.
Gjedde-Patlak plot is a multiple-time graphical analysis for irreversible tracers, e.g. [18F]FDG. It produces net influx rate (Ki). Either arterial plasma or reference region curve can be used as model input.
R
Rate constant denotes the fraction of the total tracer that will leave the compartment per unit time (fractional clearance). It has the unit of inverse time. Rate constants can still have values over 1.0; if the concentration declines to zero, the flow of material will also be zero, since the amount of substance transferred per unit time is equal to the product of rate constant and the amount of tracer in the originating compartment. Rate constants are related to classical enzyme kinetics.
Relative residence time, RRT, is used to measure the clearance of PET tracer from region-of-interest relative to reference region. In practise, it is the negative of the intercept in the Logan plot (multiple-time graphical analysis for reversible binding) with reference tissue input. See Shoghi-Jadid et al. Am J Geriatr Psychiatry 2002; 10(1): 24-35.
Repeatability coefficient (RC) is calculated as RC = 2 * SD(scan1 - scan2) in PET test-retest study.
S
Simulation means the calculation of the perfect (noise-free) data from solving the equations for a particular model with a given blood input function and a given set of parameters.
T
Test-retest variability (TRV) is calculated as the absolute value of the difference between test and retest values, divided by the mean of both measurements. The percentage mean TRV ± SD is usually reported.
Tracer is a positron emitting isotope labeled molecule, that is either structurally related to the natural substrate or involved in the dynamic process. Tracer is introduced to system in a trace amount i.e. with a high specific activity; process being measured is not perturbed by it. In general, the amount of tracer is at least a couple of orders of magnitude smaller than the natural substance, tracee. Dynamic process is evaluated in a steady state: rate of process is not changing with time, and amount of natural substance is constant during the evaluation period. Steady state of the tracer is not required. When these requirements are satisfied, the processes can be described with first-order rate constants.
Transformation is the class of processes that results in conversion of one molecular species to another (biochemical reactions). These may be catalyzed by enzymes, or may be spontaneous reactions. The other classes of dynamic biological processes are translocation and binding.
Translocation is the class of processes that results in movement of a chemical species from one location to another. Examples are diffusion and traversing a membrane. The other classes of dynamic biological processes are transformation and binding.
U
Uncertainty is a parameter, associated with the result of a measurement, that characterises the dispersion of the values that could reasonably be attributed to the measurand (International Vocabulary of Basic and General Terms in Metrology, VIM, ISO, Geneva, 1993). Results without uncertainty should not be taken seriously.
