Assessment of [11C]-L-methionine transport into the human brain.

Neutral amino acid transport into human brain was measured using a dual-probe positron detection system or positron emission tomography (PET). Rate constants (ml/min/cc) for brain accumulation of [11C]L-methionine measured with the dual detector ranged from 0.012 to 0.078 (average 0.031) under baseline conditions and from 0.010 to 0.017 (average 0.014) after administration of nonradioactive L-phenylalanine (100 mg/kg). The net rate of brain accumulation of L-methionine ranged from 0.42 to 2.89 (average 1.28) nmol/min/cc, and decreased by 27.5-91.2% (average 53.9%) after L-phenylalanine. PET-estimated accumulation rates (ml/min/cc) of [11C]L-methionine ranged from 0.004 to 0.028 (average 0.016) baseline and from 0.010 to 0.021 (average 0.017) after L-phenylalanine. Initial volumes of distribution (ml/cc) of [11C]L-methionine (dual detector) were 0.044-0.070 (average 0.058) baseline and 0.032-0.074 (average 0.051) after phenylalanine and (PET) 0.026-0.098 (average 0.051) baseline and 0.021-0.061 (average 0.042) after phenylalanine. PET permits more accurate measurement of tracer accumulation by brain, excluding noncerebral regions included in dual-detector measurements. The dual-detector system permits better temporal resolution, facilitating kinetic analysis, and requires only one-fortieth the dose of tracer needed for PET. Multiple studies in the same patient are thus possible at low cost.

A method for imaging therapeutic doses of iodine-131 with a clinical gamma camera.

Imaging therapeutic doses of 131I-labeled monoclonal antibody would provide valuable biodistribution data for dosimetry, but gamma cameras are unable to accurately handle the corresponding high counting rate. To image patients undergoing radioimmunotherapy, we attached 1.6- to 6.4-mm-thick Pb sheets to the front face of a high-energy parallel-hole collimator. With this method, we were able to acquire planar images of up to 700 mCi of radiolabeled antibody 1 hr after infusion. Monte Carlo simulations indicated that less than 7% of the events counted in the photopeak window were due to 364-keV photons that scattered in the Pb attenuator. Measurements indicated that the Pb sheets degraded system resolution by no more than 13%. A quantitative comparison of trace and therapy biodistribution data from planar images of the same patient was made using corrections for Pb sheet attenuation and camera deadtime.

Evaluation of a clinical scintillation camera with pulse tail extrapolation electronics.

The performance of a new scintillation camera, designed for high event rate capability, was evaluated. The system consisted of a 400 mm field-of-view Nal(T1) camera with 61 photomultiplier tubes and modified General Electric Starport electronics. A significant feature of the system was circuitry for performing pulse tail extrapolation and separation of individual pulses involved in pulse pile-up events. System deadtime, flood field uniformity, energy resolution, linearity, spatial resolution, and bar phantom image quality were evaluated for count rates up to 200 kcps in a 20% photopeak window. Our results indicate that this camera design does not compromise image quality at normal clinical count rates and at higher event rates can provide better image quality and increased sensitivity over many Anger cameras currently employed in nuclear medicine.

Duration of occupancy of opiate receptors by naltrexone.

To determine the duration of blockade of mu-opiate receptors by naltrexone, we measured the binding of [11C]carfentanil in the brain of five normal volunteers with a positron radiation detection system before and 1, 48, 72, 120, and 168 hr after naltrexone administration. The half-time of blockade by naltrexone in the brain ranged from 72 to 108 hr which is greater than the fast plasma clearance components (4-12 hr) of naltrexone or its metabolite, beta-naltrexol, but corresponds well to the half-time of the terminal phase of plasma naltrexone clearance (96 hr). These results are consistent with the duration of the pharmacologic effects of naltrexone in response to heroin administration and indicate that 50 mg/day of oral naltrexone results in plasma levels in excess of that needed to saturate opiate receptors. This is the first example of the use of a simple dual-detector system with positron-emitting radioactive drugs to provide information regarding the duration of action of the drug on its specific receptor site. The plasma clearance half-time of a drug may not give an accurate reflection of the duration of action of the drug on a specific neuroreceptor site. Direct measurement of drug effects on recognition sites greatly extend current studies of pharmacokinetics.

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.

Simplified detection system for neuroreceptor studies in the human brain.

A simple, inexpensive dual-detector system has been developed for measurement of positronemitting receptor-binding drugs in the human brain. This high efficiency coincidence counting system requires that only a few hundred microcuries of labeled drug be administered to the subject, thereby allowing for multiple studies without an excessive radiation dose. Measurement of the binding of [11C]carfentanil, a high affinity synthetic opiate, to opiate receptors in the presence and in the absence of a competitive opiate antagonist indicates the potential utility of this system for estimating different degrees of receptor occupation in the human brain.

Circumferential wall thickness measurements of the human left ventricle: reference data for thallium-201 single-photon emission computed tomography.

New heart imaging methods, including echocardiography, single-photon emission computed tomography (SPECT) and nuclear magnetic resonance, involve measurements of left ventricular (LV) wall thickness in cross sections perpendicular to the LV long axis. To provide a reference base, LV myocardial wall thicknesses were measured in human autopsy specimens. Short-axis views were chosen at the base of the heart, at the level of the papillary muscles and at a level close to the apex. At the 3 levels, LV wall thicknesses were measured for each of 36 circumferential sectors. The measurements revealed a nonuniformity of LV myocardial wall thickness, related to the papillary muscles, the anterior and posterior junctions with the right ventricle and the thinness of the ventricular septum. These findings help to explain the structured appearance of SPECT 201-thallium short-axis views.

Differentiating recurrent tumor from radiation necrosis: time for re-evaluation of positron emission tomography?

UNLABELLED: Our purpose was to evaluate the ability of FDG PET to differentiate recurrent tumor from posttherapy radiation necrosis. METHODS: MR images, PET scans, and medical records of 84 consecutive patients with a history of a treated intracranial neoplasm were evaluated retrospectively. In all patients, recurrent tumor or radiation necrosis was suggested by clinical or MR findings. Metabolic activity of the PET abnormality was compared qualitatively with normal contralateral gray and white matter. RESULTS: PET findings were confirmed histologically in 31 patients. With contralateral white matter as the standard of comparison, the PET scan sensitivity and specificity were found to be 86% and 22%, respectively. With contralateral gray matter as the reference standard, the sensitivity and specificity became 73% and 56%, respectively. Overall, nearly one third of the patients would have been treated inappropriately in either scheme had the PET scan been the sole determinant of therapy. CONCLUSION: Our data suggest that the ability of FDG PET to differentiate recurrent tumor from radiation necrosis is limited. Both false-positive and false-negative PET scan results contributed to unacceptably low sensitivity and specificity values.

Post therapy imaging in high dose I-131 radioimmunotherapy patients.

The biodistribution of a trace-labeled I-131 antibody is used to predict the biodistribution of a high dose I-131 antibody for therapy. Internal radiation dose estimates derived from the trace-labeled antibody have been used to determine the I-131 doses in a phase I escalating dose therapy trial for hematologic malignancy. To confirm the hypothesis that the distribution of a trace- and high-dose labeled antibodies are similar, both trace (7-11 mCi, 259-407 MBq) and high-dose (100-800 mCi, 3700-29600 MBq) I-131 radiolabeled antibody infusion were imaged in 12 patients who were treated for leukemia or lymphoma. With specialized imaging techniques using lead attenuation sheets, clearance data from organs were obtained from serial gamma camera images. Biological clearance half times of I-131 from both trace and therapy level doses were in agreement. An exception was a patient who developed human antimouse antibody before therapy, and subsequently had rapid clearance of the therapy dose. The method was feasible, yielded reproducible results, and provided critical data for relating therapy toxicity to radiation absorbed dose estimates.

Quantification of human caudate d2 dopamine receptor density with positron emission tomography: a review of the model.

The radioligand [11C] N-methylspiprone (NMSP) has been used to assess relative and absolute D2 dopamine receptor densities in the living human brain with positron emission tomography (PET). In those studies, a three-compartment model was used to analyze the NMSP accumulation in the caudate nucleus. Absolute receptor densities were determined from studies in both the presence and absence of the inhibitor haloperidol; haloperidol was used to reduce the number of available receptors. We show that the mathematical analysis of the model requires that occupancy of D2 dopamine receptors by NMSP be negligible. The published parameter values (K1, k2, k3 k4(t), and BM'max) for studies in the presence of haloperidol are shown to be inconsistent with this requirement. Potential sources of the inconsistency include a high mass dose of NMSP, as well as the need to assign values for the association and dissociation rate constants for haloperidol, and for the association rate constant for NMSP. For these reasons, the method for absolute receptor density determination may be in error. If sufficiently low masses of NMSP are injected, however, the value of BM'max might provide a measure of relative receptor density.

On estimating the loss of quantification in PET due to finite detector resolution.

In positron emission computed tomography, images are reconstructed from projection data of the slice. Such projection data are inherently subject to bias owing to the detection of coincident annihilation photons with detectors of finite resolution. The influence of these unavoidable effects on reconstructed data is reviewed and a straight forward method is outlined for calculating the loss of quantification of small objects owing to finite detector resolution. A sample calculation using idealized point spread functions is presented.

Absorbed fractions for dose calculations of neuroreceptor PET studies.

A simple Monte Carlo program was constructed for the purpose of calculating absorbed fractions of relevance to neurologic positron-emission-tomography studies. The caudate, putamen, and cerebellum regions of the brain were mathematically modeled to serve as source regions for the absorbed-fraction calculations for positron-annihilation photons. The target organs were the caudate, putamen, cerebellum, brain, spine portion in the head, skull, and head. Absorbed fractions were also calculated for a uniform ring source which encircled the head phantom.

Artifacts in camera based single photon emission tomography due to time activity variation.

Image quality in single photon emission computed tomography (SPECT) using a rotating gamma camera is dependent on the time course of the tracer in the field of view. If acquisition times are slow compared to the tracer turnover, artifacts may occur in the reconstructed images. The properties of such artifacts were studied by computer simulation. Experimental projection data of point sources, cylindrical phantoms, and an anatomically realistic brain phantom were altered by sequentially weighting the projections with a function that varied exponentially or linearly with time. The observed distortion in the reconstructed images could be related to the ratio between the object activity variation and the camera rotation time. If the tracer concentration changed less than a factor of two during one camera rotation then little image distortion was visible although quantitatively the resolution was degraded. If the object's activity variation with time is fast enough to produce noticeable distortion, the artifacts can be reduced by performing multiple, rapid, camera rotations, instead of one rotation, for the same total acquisition time. The proposed procedure is computer storage space intensive and takes longer to produce the transaxial images, but improves image quality.

Comparison of transaxial resolution in 180 degrees and 360 degrees SPECT with a rotating scintillation camera.

Using circular 180 degrees and 360 degrees SPECT acquisition modes the transaxial resolution of line sources in air and water were measured at different positions in the field of view. With the 180 degrees acquisition mode, all line sources in air located off the axis of camera rotation (AoR) showed an oval distortion. This distortion was systematically related to the starting point of the rotating detector. On axis line sources in air were undistorted, regardless of the 180 degrees acquisition starting angle. The 360 degrees acquisition images of the line sources in air showed a similar effect but in a very mild form. In water, transaxial reconstructions of line sources (off axis) showed an enhancement of the oval distortion for both the 180 degrees and 360 degrees acquisitions. Computer simulations of the line source measurements were performed and correlated well with the experimental data. The line source results are explainable by the inherent depth dependent response of the scintillation camera. In clinical SPECT studies, distortions of this nature will be most appreciable with 180 degrees imaging of small organs that are located off the AoR.