Tracer-Kinetic Models for Measuring Cerebral Blood Flow Using Externally Detected Radiotracers

Abstract

Summary: All tracer-kinetic models currently employed with positron-emission tomography (PET) are based on compartmental assumptions. Our first indication that a compartmental model might suffer from severe limita tions in certain circumstances when used with PET oc curred when we implemented the Kety tissue-autoradiog raphy technique for measuring CBF and observed that the resulting CBF estimates, rather than remaining con stant (to within predictable statistical uncertainty) as ex pected, fe ll with increasing scan duration T when T > 1 min . After ruling out other explanations, we concluded that a one-compartment model does not possess suffi cient realism for adequately describing the movement of labeled water in brain. This article recounts our search for more realistic substitute models. We give our deriva tions and results for the residue-detection impulse re sponses for unit capillary-tissue systems of our two can didate distributed-parameter models. In a sequence of trials beginning with the simplest, we tested fo ur progres-The measurement of CBF is important not only because of the information it provides about the normal and diseased brain, but also because it is essential to other important measurements (e.g. , rate of oxygen consumption). Tr acer-kinetic models are employed with external radiation-detection de vices to interpret dynamic imaging data in terms of the movements of radiolabeled water (H 2 1 50) or other diffusible tracer (e.g. , [ 1 8F] fluoromethane) for the purpose of inferring CBF. The tracer-kinetic model currently employed with positron-emission tomography (PET) for this purpose is based on 443sively more detailed candidate models against data fr om appropriate residue-detection experiments. In these, we generated high-temporal-resolution counting-rate data re flecting the history of radiolabeled-water uptake and washout in the brains of rhesus monkeys. We describe our treatment of the data to yield model-independent em pirical values of CBF and of other parameters. By substi tuting these into our trial-model fu nctions , we were able to make direct comparisons of the model predictions with the experimental dynamic counting-rate histories, con firming that our reservations concerning the one-com partment model were well founded and obliging us to re ject two others . We conclude that a two-barrier distrib uted-parameter model has the potential of serving as a substitute for the Kety model in PET measurements of CBF in patients, especially when scan durations for T> 1 min are desired. Key Words: Cerebral blood flow-Dis tributed-parameter models-Po sitron-emission tomog raphy-Tissue heterogeneity-Tr acer kinetics. compartmental assumptions; that is , tracer is as sumed to move between discrete subvolumes, or "compartments," within each of which tracer is assumed to distribute instantaneously upon arrival. Thus, in a compartmental model, gradients of con centration are assumed to be zero (i.e. , their spatial profiles flat) within each compartment at all times. The compartmental mode...

Uncertainty in the analysis of tracer kinetics using dynamic contrast‐enhanced T1‐weighted MRI

“…However, suitable techniques for comparison are difficult to find. PET has often been quoted as a gold standard technique for measurement of blood flow (8), but the techniques used to interpret PET data are very similar to those now used in MRI and can suffer from similar pitfalls (5). In this study, a realistic, established model has been used to simulate tissue residue curves that closely match existing experimental data.…”

“…Many investigators compare their results with those obtained with positron emission tomography (PET). However, PET shares many of the basic models employed in MRI (5). Similarly, data simulation exercises using Monte-Carlo techniques designed to assess accuracy and precision in parameter estimation often utilize the same model to both generate and analyze the data (6,7).…”

A computational model of oxygen transport from red blood cells to mitochondria

“…The Deussen-Bassingthwaighte model in addition allows axial diffusion parallel to the flow path. Its most important development is not the diffusion, but the transformation of 15 O-oxygen to 15 O-water, making it a dual species model; it is therefore useful for analyzing 15 O-water residue or 15 O-water or 3 H-water outflow curves, 15 Ooxygen, 18 O-water, 17 O-oxygen, or 11 C-carbon monoxide and other solutes that may or may not undergo a single transformation. This model has been applied to studies on the positron emitting tracers mentioned, but has a particularly strong potential for providing estimates of regional oxygen consumption from a sequence of positron emission tomographic (PET) images.…”

“…There is a need to calculate local flow and oxygen consumption in an organ from residue curves of 15 O-oxygen obtained with PET scans. Compartmental models have been used to analyze PET data on tracer oxygen residue curves for the brain [13,14].…”

“…It accounts for a separation between erythrocytes and plasma and for the more rapid velocity of erythrocytes than plasma, a feature whose importance can now be evaluated. The lumped mixing chamber tracer-kinetic models commonly used for PET detection of labeled water residue curves suffer a severe limitation under certain circumstances because of the compartmental assumption [15], and this distributed model being more anatomically realistic avoids this pitfall.…”