Three-dimensional visualization and quantification of the benzodiazepine receptor population within a living human brain using PET and MRI

Positron emission tomography (PET) in combination with receptor-selective high-affinity radioligands allows the characterization of neuroreceptor distributions in the living human brain. Thus far, the visualization and quantification of receptors with PET have been limited to series of two-dimensional (2D) image planes of the anatomic receptor distribution. The development of high-resolution PET has increased the number of planes to approximately 50, supplying an excessive amount of image information from a single experiment. The inherent limitations of 2D techniques make them insufficient to apprehend and efficiently analyze this cumbersome amount of data. In the present communication we describe procedures to visualize and quantify in three dimensions (3D) the total image information from the compound set of 47 2D planes of a PET experiment using commercially available software. Three-dimensional computer graphic and volume rendering techniques were used to analyze and display the results. For the experimental application the benzodiazepine (BZ) antagonist [t1C]flumazenil was used as radioligand to visualize the BZ receptor (BZR) population in the brain of a healthy human subject. Three-dimensional images of the radioligand binding receptor population were displayed with regard to volume and form in relation to the corresponding anatomic structures in the brain reconstructed from MR images. The volume-rendering technique allowed the inspection of PET signals representing BZR populations in the interior of the hemisphere as viewed from the medial projection. Thresholding and seeding techniques were used to define volumes and quantities. Using the PET data and volume rendering, the total amount of cerebral BZRs (NCerebrum) and the apparent volume they take into account (VappBZR, Cerebrum) could be calculated for the first time using an automated procedure. The cerebrum of the healthy subject contained 17.6 nmol of BZRs in a voulume of approximately 1.25 L. The principles and application of the technical development described offer new dimensions to clinical neuroscience and should be practically useful for automated quantitative determination of neuroreceptor number in brain regions of patients with neuropsychiatric disorders and in relation to drug treatment.