Nicholas J. Yasillo

Preliminary assessment of extrastriatal dopamine d-2 receptor binding in the rodent and nonhuman primate brains using the high affinity radioligand, 18F-fallypride

We have identified the value of 18F-fallypride [(S)-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-[18F]fluoropropyl)-2, 3-dimethoxybenzamide], as a dopamine D-2 receptor radiotracer for the study of striatal and extrastriatal receptors. Fallypride exhibits high affinities for D-2 and D-3 subtypes and low affinity for D-4 (3H-spiperone IC50s: D-2 = 0.05 nM [rat striata], D-3 = 0.30 nM [SF9 cell lines, rat recombinant], and D-4 = 240 nM [CHO cell lines, human recombinant]). Biodistribution in the rat brain showed localization of 18F-fallypride in striata and extrastriatal regions such as the frontal cortex, parietal cortex, amygdala, hippocampus, thalamus, and hypothalamus. In vitro autoradiographic studies in sagittal slices of the rat brain showed localization of 18F-fallypride in striatal and several extrastriatal regions, including the medulla. Positron emission tomography (PET) experiments with 18F-fallypride in male rhesus monkeys were carried out in a PET VI scanner. In several PET experiments, apart from the specific binding seen in the striatum, specific binding of 18F-fallypride was also identified in extracellular regions (in a lower brain slice, possibly the thalamus). Specific binding in the extrastriata was, however, significantly lower compared with that observed in the striata of the monkeys (extrastriata/cerebellum = 2, striata/cerebellum = 10). Postmortem analysis of the monkey brain revealed significant 18F-fallypride binding in the striata, whereas binding was also observed in extrastriatal regions such as the thalamus, cortical areas, and brain stem.

Design considerations for a single tube gamma camera

It is pointed out that many potentially practical applications for nuclear medicine diagnostic procedures are difficult or impossible to perform because of the physical size of existing mobile gamma cameras. With the commercial availability of position sensitive photomultiplier tubes (PSPMTs) the development of an instrument ideally suited to these applications now appears to be practical. The major components necessary to construct such a camera have been tested, and a circuit configuration designed to provide a high level of clinical performance in such a device is proposed. Spatial resolution and linearity data from a developmental prototype are provided. Measurements have shown that by using conventional sum and difference analog circuits only, a 76-mm/sup 2/ PSPMT has good linearity and therefore uniformity of sensitivity over only the central 60% of its absolute field of view. It is believed that this high-quality imaging area can be increased to virtually the full field of view by implementing a digital geometric correction scheme using a position vector lookup table. >

Relatives of unipolar and bipolar patients have normal pursuit.

Impaired smooth pursuit eye movements are significantly less prevalent among the first-degree relatives of patients who have major affective disorders than among the first-degree relatives of schizophrenics. The distribution of normal and abnormal smooth pursuit among the relatives of unipolar and bipolar patients does not differ from that of normal individuals having no family history of major psychosis. Smooth pursuit impairment is thus specific to relatives of schizophrenic patients and is not characteristic of relatives of patients with major affective disorders.

Simulation of imaging with sodium iodide crystals and position-sensitive photomultiplier tubes

The imaging characteristics of miniature gamma cameras that consist of a single sodium iodide (NaI(Tl)) crystal coupled to a position-sensitive photomultiplier tube (PSPMT) have been studied via Monte Carlo simulations. Images obtained with such cameras with the use of conventional position calculations exhibit considerable distortions, particularly compression. This study demonstrates that the distortions result primarily from nonuniform sensitivities of PSPMTs and secondarily from nonlinear responses of PSPMTs, light-reflection properties resulting from the treatments of crystals, and light-refractive properties of glass interfaces between crystals and photocathodes. Simulation results are compared to images obtained with a prototype miniature gamma camera. >

Psychotropic Drug Effects on Smooth Pursuit Eye Movements: A Summary of Recent Findings

Publisher Summary In studies conducted prior to the availability of psychotropic drug treatments, impaired smooth pursuit eye movements (SPEM) were a more common finding in schizophrenics than among manic-depressives or other psychiatric patients. The results of recent studies on never medicated patients support these early data both in terms of the relative specificity of the eye movement abnormality for schizophrenia and the independence of SPEM impairment from treatment with antipsychotic medications. Karson, for example, reported that pursuit irregularities were rare in never-medicated manic depressives. In contrast, never-medicated schizophrenics had worse pursuit than their medicated counterparts. Unmedicated patients are more the exception than the rule, however, and most of the evidence bearing on the issue of drug effects is indirect. This chapter presents a summary of the longitudinal data on the effects of antipsychotic and antidepressant medications, as well as of lithium carbonate, on smooth pursuit eye movements.

A Single-tube Miniature Gamma Camera

A Single-Tube Miniature Gamma Camera NJ Yasillo, RA Mintzer, JN Aarsvold, KL Matthews, SJ Heimsath, CE Ordonez, X Pan, C Wu, TA Block, RN Beck, C-T Chen, and M Cooper Franklin McLean Memorial Research Institute, The University of Chicago 5841 S. Maryland Ave., MC-1037, Chicago, IL 60637 In certain medical gamma imaging applications, conventional cameras are too large for practical use. To address these situations, we have constructed a clinically usable miniature gamma camera for photon energies up to 160 keV. The camera has outer dimensions of 92 mm x 92 mm x 190 mm and weighs 5 kg. Included in that mass is a collimator, an internal high-voltage power supply, and all shielding. The camera also has a position-sensitive photomultiplier tube (PSPMT) coupled to an 8-mm thick NaI(Tl) crystal; this crystal/tube combination provides signals to internal processing circuits. External electronics and analog-to-digital conversion circuits are connected to a Macintosh Quadra computer where additional processing, storage, and display of the signals takes place. Because the PSPMT has non-uniform energy response that results in geometric distortion if conventional position-arithmetic calculations are used, we have implemented a maximumlikelihood position-estimation calculation that produces undistorted images. The present version of the camera has a usable field of view of 48 mm x 48 mm and an intrinsic spatial resolution of 2.4 to 3.8 mm full width at half maximum.

Effects of phencyclidine, secobarbital and diazepam on eye tracking in rhesus monkeys

Rhesus monkeys were trained to track a moving disk using a procedure in which responses on a lever were reinforced with water delivery only when the disk, oscillating in a horizontal plane on a screen at a frequency of 0.4 Hz in a visual angle of 20°, dimmed for a brief period. Pursuit eye movements were recorded by electrooculography (EOG). IM phencyclidine, secobarbital, and diazepam injections decreased the number of reinforced lever presses in a dose-related manner. Both secobarbital and diazepam produced episodic jerky-pursuit eye movements, while phencyclidine had no consistent effects on eye movements. Lever pressing was disrupted at doses which had little effect on the quality of smooth-pursuit eye movements in some monkeys. This separation was particularly pronounced with diazepam. The similarities of the drug effects on smooth-pursuit eye movements between the present study and human studies indicate that the present method using rhesus monkeys may be useful for predicting drug effects on eye tracking and oculomotor function in humans.

Implementations of Maximum-Likelihood Position Estimation in a Four-PMT Scintillation Detector

Maximum-likelihood (ML) position estimation in small scintillation detectors often involves the use of a look-up table (LUT) to map event characterization vectors to the associated position estimates. As the number of possible characterization vectors determines the size of the LUT, the number of these vectors needs to be manageable. This implies that a critical component of an implementation of ML position estimation is the mapping of detector output signals to characterization vectors. The use of different photomultiplier tube (PMT) output mappings in ML estimation in a small camera with four round PMTs and a single 5 x 100 x 100 mm NaI(T1) crystal was investigated. The employed mappings of the four detector signals resulted in 20 (5 bits/PMT), 22 (8 bits each for Anger x and y; 6 bits for the sum signal), 24 (6 bits/PMT), and 28 (7 bits/PMT) bit event characterizations. Using present implementations of ML estimation, significant improvement in image quality results if a 24-bit characterization is used rather than 20 or 22. Improvement in image quality is not as marked when 28-bit characterization is used instead of 24, but measurable improvement is obtained.

Maximum-likelihood calibration of small gamma cameras for 511 keV positron annihilation radiation

The feasibility of employing maximum-likelihood (ML) position estimation in small scintillation cameras for use in FDG coincidence imaging was investigated. A small camera consisting of a Hamamatsu R-2487 position-sensitive photomultiplier tube (PSPMT) coupled to a single 8 mm thick NaI(Tl) crystal was calibrated with a tungsten and lead shielded 511 keV /sup 18/F source. The same calibration method has been previously employed at 140 keV using /sup 99m/Tc. The source was positioned at each location of the image space to determine detector-signal distributions used in look-up table (LUT) generation. Corrected 511 keV point-array and flood images were obtained using the resulting 511 keV calibration LUT. Resolution was 2.0 mm-2.5 mm full-width at half maximum (FWHM). This demonstrates that it may be feasible to use ML estimation to obtain accurate event positioning in similar imaging detectors employing more suitable scintillators.

Count-rate dependent sensitivity in position-sensitive photomultiplier tubes

A significant count-rate dependence of mean scintillation-pulse amplitude has been observed in prototype small gamma cameras employing NaI(Tl) crystals coupled to Hamamatsu R2487 and R3941 position-sensitive photomultiplier tubes (PSPMTs). The magnitude of the effect is position dependent. Within each cameras 56 mm/spl times/56 mm field-of-view, as the scintillation rate is increased from 500 to 10,000 counts per second, the response to 140 keV gamma emissions from a collimated source of Tc-99m increases by approximately 2-8% in the R2487 and 1-6% in the R3941. The count-rate dependent sensitivities of both tubes were investigated by varying the rate and position of LED pulses directed at the face of the tubes with a 1 mm diameter optical fiber. Within the specified effective area of the R2487, the increase in response from a 500 Hz rate to a 100 kHz rate varied from 1.5% in the center to 20% at one edge; corresponding increases in the R3941 were only 1% and 8%. In both cases, most of the response increase occurred between 500 Hz and 10 kHz. Similar LED tests on conventional photomultiplier tubes resulted in no more than 2% increases.<<ETX>>