The current article presents theory for compartmental models used in positron emission tomography (PET). Both plasma input models and reference tissue input models are considered. General theory is derived and the systems are characterized in terms of their impulse response functions. The theory shows that the macro parameters of the system may be determined simply from the coefficients of the impulse response functions. These results are discussed in the context of radioligand binding studies. It is shown that binding potential is simply related to the integral of the impulse response functions for all plasma and reference tissue input models currently used in PET. This article also introduces a general compartmental description for the behavior of the tracer in blood, which then allows for the blood volume-induced bias in reference tissue input models to be assessed.
This study was designed to explore the feasibility of PET using [11C](R)-PK11195 as an in vivo marker of activated microglia/brain macrophages for the assessment of neuroinflammation in Rasmussen's encephalitis (RE). [11C](R)-PK11195 PET was carried out in four normal subjects, two patients with histologically confirmed RE, and three patients with clinically stable hippocampal sclerosis and low seizure frequency. Binding potential maps showing specific binding of [11C](R)-PK11195 were generated for each subject. Regional binding potential values were calculated for anatomically defined regions of interest after coregistration to and spatial transformation into the subjects' own MRI. In one patient with RE who underwent hemispherectomy, the resected, paraffin-embedded brain tissue was stained with an antibody (CR3/43) that labels activated human microglia. Whereas specific binding of [11C](R)-PK11195 in clinically stable hippocampal sclerosis was similar to that in normal brain, patients with RE showed a focal and diffuse increase in binding throughout the affected hemisphere. In RE, [11C](R)-PK11195 PET can reveal in vivo the characteristic, unilateral pattern known from postmortem neuropathologic study. PET imaging of activated microglia/brain macrophages offers a tool for investigation of a range of brain diseases where neuroinflammation is a component and in which conventional MRI does not unequivocally indicate an inflammatory tissue reaction. [11C](R)-PK11195 PET may help in the choice of appropriate biopsy sites and, further, may allow assessment of the efficacy of antiinflammatory disease-modifying treatment.
A kinetic modeling approach for the quantification of in vivo tracer studies with dynamic positron emission tomography (PET) is presented. The approach is based on a general compartmental description of the tracer's fate in vivo and determines a parsimonious model consistent with the measured data. The technique involves the determination of a sparse selection of kinetic basis functions from an overcomplete dictionary using the method of basis pursuit denoising. This enables the characterization of the systems impulse response function from which values of the systems macro parameters can be estimated. These parameter estimates can be obtained from a region of interest analysis or as parametric images from a voxel-based analysis. In addition, model order estimates are returned that correspond to the number of compartments in the estimated compartmental model. Validation studies evaluate the methods performance against two preexisting data led techniques, namely, graphical analysis and spectral analysis. Application of this technique to measured PET data is demonstrated using [11C]diprenorphine (opiate receptor) and [11C]WAY-100635 (5-HT1A receptor). Although the method is presented in the context of PET neuroreceptor binding studies, it has general applicability to the quantification of PET/SPECT radiotracer studies in neurology, oncology, and cardiology.
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