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B R Zeeberg

Publications and source records attributed to B R Zeeberg.

33 records · Page 2Linked to original sources
PubMed1992

Pharmacokinetic simulations of SPECT quantitation of the M2 muscarinic neuroreceptor subtype in disease states using radioiodinated (R,R)-4IQNB.

Alzheimer's disease (AD) involves selective loss of muscarinic M2, but not M1, subtype neuroreceptors in the posterior parietal cortex of the human brain. Emission tomographic study of the loss of M2 receptors in AD is limited by the fact that there is currently no available M2-selective radioligand which can penetrate the blood-brain barrier. However, by taking advantage of the different pharmacokinetic properties of (R,R)-[123I]IQNB for the M1 and M2 subtypes, it may be possible to estimate losses in M2. It has previously been hypothesized that the difference between an early study and a late study should provide information on the M2 receptor population. In order to test this hypothesis, we present here the results of pharmacokinetic simulations of the in vivo localization of (R,R)-[123I]IQNB in brain regions containing various proportions of M1 and M2 subtypes. These results permit us to conclude that SPECT imaging of (R,R)-[123I]IQNB localization can potentially be used to quantitate changes in the M2 subtype in a disease state within a brain region for which the ratio M2/M1 is sufficiently high in normal individuals.

Alzheimer Disease↗
PubMed1992

Compensation for three-dimensional detector response, attenuation and scatter in SPECT grey matter imaging using an iterative reconstruction algorithm which incorporates a high-resolution anatomical image.

The use of SPECT to diagnose physiological alterations in disease states depends on the potential of SPECT to provide a quantitatively accurate reconstructed image. However, the reconstructed values depend upon the shape and size of the brain region as strongly as they depend upon true radioactivity concentration. We report here the results of applying an iterative reconstruction algorithm (IRA) to compensate for shape- and size-dependence, as well as for attenuation and scatter. The IRA is designed only for the reconstruction of images for which the true radioactivity in the white matter within the actual brain is negligible compared with the true radioactivity in the grey matter within the actual brain. The IRA incorporates an accurate three-dimensional model of detector response and utilizes an MRI image which defines the anatomical features of the brain being imaged by segmenting the grey, white and ventricular regions. It is the assumption of radioactivity localization exclusively in the grey matter which permits the efficient incorporation of the MRI image. The IRA was validated by simulation studies that utilized a slice through the basal ganglia in the realistic Hoffman three-dimensional mathematical brain model. FBP images deviate significantly from true radioactivity distribution, whereas IRA images are nearly identical to true radioactivity distribution, except for random fluctuations due to the presence of statistical noise. These results indicate that the application of the IRA will permit SPECT to distinguish deficits due to true physiological changes from apparent deficits due to imaging/reconstruction artifacts.

Algorithms↗
PubMed1991

Binding of radioiodinated SPECT ligands to transfected cell membranes expressing single muscarinic receptor subtypes.

The equilibrium dissociation constant and the kinetic rate constants were determined for the binding of (R)-[3H]3-quinuclidinyl benzilate ([3H]QNB) and [125I]3-quinuclidinyl-4-iodobenzilate ((R,R)- and (R,S)-[125I]IQNB) to transfected cell membranes expressing one single muscarinic acetylcholine receptor (mAChR) subtype. The association and dissociation kinetics for the m2 subtype were more rapid than for the m1 and m3 subtypes. The differential kinetic properties may be useful for the single photon emission computed tomographic (SPECT) evaluation of regional mAChR subtype alterations in disease states.

Animals↗
PubMed1991

In vivo dissociation kinetics of [3H]quinuclidinyl benzilate: relationship to muscarinic receptor concentration and in vitro kinetics.

The in vivo washout kinetics of [3H]quinuclidinyl benzilate ([3H]QNB) varies significantly in various structures in the rat brain. The slowest washout rates are from the hippocampus, corpus striatum, and cortex, intermediate rates are exhibited from the thalamus and colliculi, while the fastest washout rate is from the cerebellum. We have also demonstrated a difference in the in vitro dissociation rates (k-1) of [3H]QNB from various structures. The k-1 for the hippocampus, corpus striatum and cortex, is two-fold slower than that observed in the thalamus, colliculi, and cerebellum. The differences in the in vitro dissociation kinetics are not, however, sufficient to explain the differences in the in vivo washout kinetics. We have developed a theoretical formulation which describes conditions under which the washout kinetics are a function of the concentration of receptor in a structure. Furthermore, we present a graphical method in which a plot of the reciprocal of the observed washout rate constant, 1/k(obs), vs receptor concentration is linear. Analysis of the washout kinetics of [3H]QNB from various structures of the CNS of rat were well described by this theory when the differences in in vitro k-1 are included.

Animals↗
PubMed1991

Three-dimensional SPECT simulations of a complex three-dimensional mathematical brain model and measurements of the three-dimensional physical brain phantom.

We have developed a three-dimensional computer simulation of SPECT imaging. We have applied the simulation procedure to the realistic mathematical Hoffman three-dimensional brain model to generate the projection data (in the absence of attenuation, scatter, or noise) of both a parallel-hole and a multidetector SPECT system with point-focusing collimators. The simulated projection data were then reconstructed using standard software. The projection data resulting from the distribution of grey matter alone, or grey and white matter, were simulated. The results of these simulations indicate the existence of significant qualitative and quantitative artifacts in reconstructed human brain images. For example, the reconstructed values for grey matter along a cortical circumferential profile in a transverse slice through the basal ganglia varied by a factor of 2.40 (parallel-hole) and 2.99 (point-focusing), although the original grey matter values were identical in all cortical regions in the model. We have compared the simulated reconstructed images with those obtained by imaging the physical three-dimensional Hoffman brain phantom, which was constructed based upon the same set of data from which the mathematical three-dimensional Hoffman brain model was derived. Although the simulation did not include all of the degrading factors present in the physical imaging, the two images were in good agreement, indicating the applicability of the simulation to a realistic situation and the importance of the detector resolution effect.

Artifacts↗
PubMed1991

Three-dimensional simulations of multidetector point-focusing SPECT imaging.

We have applied an efficient algorithm for mathematically simulating the three-dimensional (3-D) response of a SPECT imaging system with a depth-dependent 3-D point spread function (3-DPSF). The input object whose reconstructed image is to be simulated is restricted to a binary map; more complex objects may be treated as linear combinations of binary maps. The 3-D convolution reduces to a sequence of additions of a 3-D line spread function (3-DLSF), appropriately translated, to the 3-D response. We have simulated the projection data from a multidetector SPECT system with point-focusing collimators. The simulated projection data were then reconstructed using the manufacturer's software. The objects simulated included simple geometrical solids such as spheres and cylinders, as well as the distribution of muscarinic cholinergic receptors in a realistic brain slice. The results of these simulations indicate the existence of significant qualitative and quantitative artifacts in reconstructed human brain images.

Algorithms↗
PubMed1990

Specific in vivo binding of [125I]-iodomelatonin to melatonin receptors in rat brain.

The in vivo distribution of [125I]-2-iodomelatonin in rat brain was determined at different time intervals after intraarterial injection. After one hour, radioactivity in brain areas devoid of melatonin receptors had washed out to very low concentrations, but significant retention occurred in the medial basal hypothalamus (mbh) which contained the median eminence and in the anterior pituitary gland (ap), areas known to contain high concentrations of melatonin receptors. Coinjection of unlabelled melatonin reduced radioactivity concentrations in the ap and mbh by 44% and 75% respectively at one hour, whereas radiotracer concentrations in other regions remained unchanged. These results indicate the potential for the in vivo study of melatonin receptor concentration changes in human brain in disease states by means of single photon emission computed tomography.

Animals↗