Visual phenomena noted by human subjects on exposure to neutrons of energies less than 25 million electron volts.

Six subjects reported multiple starlike flashes and short streaks on exposure to neutrons of energies up to 25 million electron volts. The probable mechanism is interaction with the retinal rods by proton recoils and by alpha particles released from neutron reactions with carbon and oxygen. These observations are similar to light flashes and streaks seen by astronauts who are exposed to high-energy cosmic rays on translunar flight.

Nuclear magnetic resonance technology for medical studies.

Nuclear magnetic resonance proton imaging provides anatomical definition of normal and abnormal tissues with a contrast and detection sensitivity superior to those of x-ray computed tomography in the human head and pelvis and parts of the cardiovascular and musculoskeletal systems. Recent improvements in technology should lead to advances in diagnostic imaging of the breast and regions of the abdomen. Selected-region nuclear magnetic resonance spectroscopy of protons, carbon-13, and phosphorus-31 has developed into a basic science tool for in vivo studies on man and a unique tool for clinical diagnoses of metabolic disorders. At present, nuclear magnetic resonance is considered safe if access to the magnet environment is controlled. Technological advances employing field strengths over 2 teslas will require biophysical studies of heating and static field effects.

Positron tomography and nuclear magnetic resonance imaging.

Noninvasive imaging methods for medical diagnosis and biological investigations, have evolved from qualitative radiological techniques to quantitative methods of measuring biochemical and physiological processes in human body. In particular, new developments in emission tomography, nuclear magnetic resonance imaging, and in vivo spectroscopy offer new horizons for medical research and clinical activities. These methods and their potentials are reviewed and contrasted.

Multipole shimming of permanent magnets using harmonic corrector rings.

Shimming systems are required to provide sufficient field homogeneity for high resolution nuclear magnetic resonance (NMR). In certain specialized applications, such as rotating-field NMR and mobile ex situ NMR, permanent magnet-based shimming systems can provide considerable advantages. We present a simple two-dimensional shimming method based on harmonic corrector rings which can provide arbitrary multipole order shimming corrections. Results demonstrate, for example, that quadrupolar order shimming improves the linewidth by up to an order of magnitude. An additional order of magnitude reduction is in principle achievable by utilizing this shimming method for z-gradient correction and higher order xy gradients.

Tracer kinetic evidence for abnormal methyl metabolism in schizophrenia.

The original transmethylation hypothesis of schizophrenia has evolved with time and experiment to the present concept that a defect in the methyl-carbon metabolic pathway may be causative in this illness. Various researchers have proposed that specific steps in the methyl-carbon pathway may be defective, and have presented evidence to support these possibilities. We have tested the general concept of the hypothesis by administering methionine labeled with 11C or 14C in the S-methyl carbon to patients with schizophrenia and to controls and measured the expiration of 11CO2 and 14CO2. We found that the rate and total expiration of labeled CO2 were three times less in the patients than in the controls, with no overlap of data points in the two groups. Specific steps in the methylcarbon pathway that might be defective and produce the results seen here are discussed in light of this and other researchers' findings.

Diminished glucose transport in Alzheimer's disease: dynamic PET studies.

Dynamic positron emission tomography with [18F]fluorodeoxyglucose was used in six patients with Alzheimer's disease (AD) and seven healthy age-matched control subjects to estimate the kinetic parameters K1*, k2*, and k3* that describe glucose transport and phosphorylation. A high-resolution tomograph was used to acquire brain uptake data in one tomographic plane, and a radial artery catheter connected to a plastic scintillator was used to acquire arterial input data. A nonlinear iterative least-squares fitting procedure that included terms for the vascular fraction and time delay to the peripheral sampling site was used to fit a three-compartment model to the brain data. Regions studied included frontal, temporal, occipital, and the entire cortex and subcortical white matter. The values obtained for the individual rate constants and regional CMRglc (rCMRglc; calculated using regional values of the rate constants) were higher than those reported previously. A significant (p less than 0.05) decrease was found in K1* in frontal and temporal cortex in the AD patients compared with the controls, with values of 0.157 and 0.161 ml/g/min in frontal and temporal cortex, respectively, of controls and 0.127 and 0.126 ml/g/min in frontal and temporal cortex of the AD patients. rCMRglc was also significantly (p less than 0.02) lower in the AD patients than controls in all cortical brain regions. Lower values of k3* were found in all brain regions in the AD patients, although these were not statistically significant. These findings provide evidence of an in vivo abnormality of forward glucose transport in AD.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulsed magnetic field effects on calcium signaling in lymphocytes: dependence on cell status and field intensity.

The effect of 3-Hz, monopolar, quasi-rectangular magnetic field pulses on 45Ca2+ uptake in resting and mitogen-treated rat thymic lymphocytes was evaluated. A 30-min, non-thermal exposure to the pulsed magnetic field (Bpeak = 6.5 mT, Emax = 0.69 mV/cm, Jmax = 2.6 microA/cm2) reduced Concanavalin A-induced 45Ca2+ uptake by 45%. It was observed that (i) the induction of the 3-Hz field response depended on Ca2+ signal transduction activation; (ii) the response direction (stimulation or inhibition) depended on the level of lymphocyte mitogen responsiveness, and (iii) the field response magnitude increased with increasing magnetic field flux densities (Bpeak = 0, 1.6, 6.5 and 28 mT). Our results demonstrate field effects at Bmax nearly 10(4) greater than that of the average human environment for low-frequency magnetic fields and they are consistent with the independent results from other 3-Hz pulsed magnetic field studies with lymphocytes.

The diagnosis of dementia with single photon emission computed tomography.

Single photon emission computed tomography is a practical modality for the study of physiologic cerebral activity in vivo. We utilized single photon emission computed tomography and N-isopropyl-p-iodoamphetamine iodine 123 to evaluate regional cerebral blood flow in nine patients with Alzheimer's disease (AD), five healthy elderly control subjects, and two patients with multi-infarct dementia. We found that all subjects with AD demonstrated flow deficits in temporoparietal cortex bilaterally, and that the ratio of activity in bilateral temporoparietal cortex to activity in the whole slice allowed the differentiation of all patients with AD from both the controls and from the patients with multi-infarct dementia. Furthermore, this ratio showed a strong correlation with disease severity in the AD group. Single photon emission computed tomography appears to be useful in the differential diagnosis of dementia and reflects clinical features of the disease.

Alzheimer's disease. Age at onset and single-photon emission computed tomographic patterns of regional cerebral blood flow.

We performed this study to determine whether early- and late-onset Alzheimer's disease differ physiologically. Ten patients with a presenile (before 65 years old) onset of the disease and 16 with senile onset of the disease were evaluated clinically and neuropsychologically and studied with single photon emission computed tomography using the blood flow tracer [123I]N-isopropyl-p-iodoamphetamine. Although the presenile subjects had more severe neuropsychological abnormalities in all realms of cognitive function, including language, and showed greater reductions in regional blood flow than the older patients, they were also more severely demented, thus complicating interpretation of the results. Two indexes of cerebral perfusion, a ratio of regional flow compared with occipital flow and a left-right asymmetry index, demonstrated relative left frontal hypoperfusion in presenile- but not senile-onset patients and did not appear to be an artifact of the severity differences. Although no asymmetry of cognitive function was noted, the perfusion asymmetry provides biological evidence for an alteration in left-hemisphere function in patients with the early onset of Alzheimer's disease.

Longitudinal studies of regional cerebral metabolism in Alzheimer's disease.

Measurement of cerebral glucose metabolism in six patients with Alzheimer's disease using positron emission tomography demonstrated that hypometabolism remained relatively more severe in parietal cortex than in frontal cortex over time. Lateral metabolic asymmetries were preserved in less severely involved brain regions, but were less stable in parietal cortex.

Regional cerebral glucose transport and utilization in Alzheimer's disease.

We performed dynamic positron emission tomographic (PET) studies of glucose utilization, using (18F) 2-fluoro-2-deoxy-D-glucose (FDG), in patients with probable Alzheimer's disease (AD) and healthy age-matched controls, to evaluate blood-brain-barrier glucose transport and glucose utilization rates in the disease. We found no significant differences in rate constants for glucose transport (k1 and k2) and phosphorylation (k3), nor for the vascular fraction (fv), between the 2 groups, although k3 and fv were relatively depressed in temporal cortex in AD. Absolute rates of glucose use were depressed in temporal and parietal cortex, and relative rCMRglc rates were lower in frontal, temporal, parietal, and occipital cortices. These data suggest that in AD bidirectional glucose transport is intact, and that temporal-parietal hypometabolism is present upon a background of widespread cortical metabolic impairment.

Temporal lobe metabolic differences in medication-free outpatients with schizophrenia via the PET-600.

Regional cerebral glucose metabolic rates (rCMRglc) were compared in 18 unmedicated outpatients with schizophrenia and 11 normal controls using high resolution positron emission tomography (PET) and the tracer [F-18]-2-fluoro-2D-deoxyglucose (FDG). From previous work we expected to see abnormal hippocampal rCMRglc in the patients, but no striatal abnormalities. Trial-by-trial Stroop cognitive task, which has been shown to activate the anterior cingulate, was performed within a day of the PET study. As our patients performed abnormally on the Stroop we tested for a correlation between the anterior cingulate rCMRglc and Stroop performance. We found no whole slice cortical average glucose metabolic abnormalities. As, predicted we found abnormally decreased left hippocampal rCMRglc in the patients. No striatal or cingulate rCMRglc abnormalities were noted in patients, but they demonstrated a highly positive correlation between anterior and cingulate rCMRglc and Stroop facilitation. Patients with higher Stroop interference had more prominent hippocampal metabolic decreases. These localized temporal lobe abnormalities could account for some of the patient's positive symptoms and are consistent with recent findings in the literature.

Physical attributes of single-photon tomography.

Physical properties important for assessment of the potentials of emission computed tomography implemented by collimated detector systems include sensitivity, statistical and angular sampling requirements, attenuation compensation, resolution uniformity, and multisection design constraints. The limited angular range and sampling interval of coded aperture methods for longitudinal tomography impose severe limitations on quantitative imaging capabilities. These methods are discussed. Disadvantages of limited angular range are avoided by transverse section devices that have lower sensitivity than comparable positron devices. It is shown here, however, that the sensitivity for a single section device for head transverse section 2 cm thick can be congruent to 200 events sec-1 microCi-1 per axial cm for 2 x 2 cm resolution. This is 40% of that for a well-designed positron system of similar resolution. The problem of attenuation compensation for constant attenuation, as in brain imaging, is well understood and a fast algorithm of the convolution type gives excellent results if angular sampling is over 360 degrees. Though there is a need to move the single-photon detector array over wide angular distances for adequate sampling, dynamic ECT is possible for the measurement of biological washout kinetics of clinical importance, such as clearance studies in brain. Based on physical principles, experiences with low sensitivity devices, and the prospects for devices with sensitivity comparable to positron tomographs, single photon tomography has sound potentials for research and clinical studies of the adult brain and whole body in small subjects. Practical whole-body tomography in adults is limited to nonquantitative lesion detection.

Cyclotron-produced Zn-62: its possible use in prostate and pancreas scanning as a Zn-62 amino acid chelate.

Zinc-62 is a positron emitter that localizes in pancreas, prostate, and liver. Cyclotron-produced Zn-62 was separated by column chromatography and evaluated in vivo as the chelate of five amino acids and also as 62ZnCl2. Tissue-distribution studies were done in normal animals from 0.7-23 hr after intravenous administration. Pancreas-to-liver ratios (per gram) of about 1.0 were found at 1.5 hr in studies on rats, dogs, and monkeys. Pancreas was as difficult to separate from liver in Zn-62 (amino acid) images as in [75Se] selenomethionine images. Some studies were done with Zn-65 to determine the effects of carrier zinc and molar ratios of ligand. The highest ratio of pancreas to liver in these studies was 1.44. This uptake ratio decreases with increasing amounts of histidine, but the ratio is increased by adding carrier zinc because there results a decrease in liver uptake and no change in the pancreas uptake. There is sufficient specificity of pancreas and prostate uptake to make feasible emission computed tomography with Zn-62.

Analytical study of a high-resolution positron ring detector system for transaxial reconstruction tomography.

This paper presents an analytical study of a high-resolution positron ring detector system for transaxial reconstruction tomography. Our goal is a combination of good spatial resolution, high sensitivity, rejection of scattered photons, variable section thickness, and the minimization of the number of photomultipliers and coincidence circuits. A circular ring of 288 NaI(Tl) crystals 0.8 cm wide should provide a resolution of 4--7 mm FWHM over a circular region 30 cm in diameter. Coded light pipes permit readout using only 72 photomultipliers and 12 coincidence circuits. With properly designed shielding and an energy resolution of 30% FWHM, a positron activity of 200 muCi per axial centimeter in a 20-cm-diam cylinder of tissue should provide approximately 7,000 events/sex from a 2-cm-thick transaxial section (including a 5% accidental coincident background and a 26% scattered coincident background). This rate is adequate for both static and dynamic imaging. The device can operate at two to three times higher event rates with increased backgrounds.

A comparison of 82Rb+ and 13NH3 for myocardial positron scintigraphy.

Rubidium-82 (75-sec half-life) is eluted from a 82Sr (25-day half-life) generator and infused into phantom and dog to show that it gives images of myocardial accumulation comparable to 13N-ammonia with the positron camera.

A precision flow-controlled Rb-82 generator for bolus or constant-infusion studies of the heart and brain.

A precision flow-controlled rubidium-82 generator has been constructed to deliver 76-sec Rb-82 at either fast or slow flow rates for bolus or constant-infusion studies. A stepping motor drive is interfaced to a microprocessor for pulsed control of flow rate to deliver the saline eluant solution from a large-volume (150 ml) machined pumping syringe through an alumina column that retains the 25-day Sr-82 parent. The generator system delivers 70-90% of the maximum Rb-82 activity in a 20-25 ml bolus elution of 2% NaCl. The Sr-82/Sr-85 breakthrough is 10(-7) - 10(-6). both yield and breakthrough are functions of column length and flow rate. Six separate Sr-82 loadings of the generator were evaluated over a period of nearly 2 yr in studies of myocardial blood perfusion and permeability changes in the blood-brain barrier. Sterility and apyrogenicity of the Rb-82 eluate were maintained during multiple elutions and long-term use of 3-4 mo for each generator loading.

Carbon-11 choline: synthesis, purification, and brain uptake inhibition by 2-dimethylaminoethanol.

We report an improved method for the synthesis and purification of [11C]methylcholine from the precursors [11C]methyliodide and 2-dimethylaminoethanol (deanol). Preparation time, including purification, is 35 min postbombardment. Forty millicuries of purified injectable [11C]choline were produced with a measured specific activity of greater than 300 Ci/mmol and a radiochemical purity greater than 98%. The decay corrected radiochemical yield for the synthesis and purification was approximately 50%. Residual precursor deanol, which inhibits brain uptake of choline, is removed by a rapid preparative high performance liquid chromatography (HPLC) method using a reverse phase cyano column with a biologically compatible 100% water eluent. Evaporation alone did not completely remove the deanol precursor. Brain uptake of the [11C]choline product was six times greater after HPLC removal of deanol because doses of less than 1 microgram/kg significantly inhibit [14C]choline brain uptake.

Evaluation and application of alumina-based Rb-82 generators charged with high levels of Sr-82/85.

Generator-produced Rb-82, a 75-sec positron emitter with potential for myocardial blood-flow imaging, was studied with various ion-exchange columns to evaluate the characteristics of alumina as an adsorber for the 25-day Sr-82 parent. Test columns of alumina, Bio Rex 70, and Chelex 100 were loaded with multimillicurie amounts of no-carrier-added Sr-82/Sr-85 (Sr-85 is a production contaminant). The breakthrough of Sr-82/Sr-85, and the yield of Rb-82, were determined for long-term elutions from each column with up to 4 liter of 2% NaCl solution at pH 8 to 9. The breakthrough of Sr-82/85 was 10(-6)-10(-5) from aluminal 10(-6)-10(-4) from Chelex 100 and Bio Rex 70. The effects of eluent flow rate and concentration, and of alumina volume, on the breakthrough and yield were also studied. An improved and automated Rb-82 generator was used for myocardial and brain blood-flow studies in experimental animals and in man; it was equipped with solenoid flow-control valves and five in. of lead shielding for the alumina columns, which were charged with 25-50 mCi Sr-82 (100-150 mCi Sr-85). The Rb-82 generator with alumina column provided up to 20-40 mCi of Rb-82 as often as every 5-10 min with less than 10(-5) breakthrough of Sr-82/85 over the 2- to 3-mo, useful life of the generator.

Hypoxia in human gliomas: demonstration by PET with fluorine-18-fluoromisonidazole.

Positron emission tomography (PET) with the hypoxic-cell tracer [18F]fluoromisonidazole presents a possible means of noninvasively demonstrating tumor hypoxia. PET studies using this tracer were performed in three patients with malignant glioma, and in all patients the tumor was clearly seen at 5 min postinjection and initial tumor activity exceeded cortical activity. In one patient, there was no tumor retention of [18F] fluoromisonidazole and tumor activity fell while cortical activity increased, with the two tissues reaching equality at 40-50 min. The tumor-to-plasma ratio was 0.71 at 3 hr. The other two patients showed variable tumor retention of [18F]fluoromisonidazole, with tumor-to-plasma ratios of 1.10 and 1.49 at 2 and 3 hr. These results demonstrate the feasibility of using [18F]fluoromisonidazole PET to detect hypoxia in human gliomas in vivo. Clinical trials are needed to determine whether a relationship exists between [18F]fluoromisonidazole uptake and tumor radiation response.