Tracer Deposits Research Articles

Effects of substrate availability on myocardial C-11 palmitate kinetics by positron emission tomography in normal subjects and patients with ventricular dysfunction

The possibility of demonstrating noninvasively with C-11 palmitate and positron emission tomography (PET) changes in myocardial substrate metabolism in normal and diseased human myocardium in response to altered substrate availability in blood and disease-related abnormalities was examined in five normal volunteers and 16 patients with ventricular dysfunction. C-11 palmitate injection and serial PET imaging were performed after an overnight fast (control period) and again 2 hours later after oral glucose (50 gm). Myocardial C-11 time-activity curves from serial PET images revealed a biexponential clearance pattern. An early rapid phase, defined by relative size and clearance half-time, reflects C-11 palmitate oxidation and the late slow phase tracer deposition in the endogenous lipid pool. During the control period, the tracer fraction entering the early rapid phase averaged 47 ± 13% (SD) in normal subjects and 45 ± 12% in patients. Corresponding clearance half-times were 19 ± 7 and 20 ± 5 minutes, respectively. Heart rate and blood pressure remained unchanged after glucose, but plasma glucose levels rose by 72.5% in normal subjects and by 98.9% in patients, while free fatty acid levels fell by 72% and 42% ( p < 0.001), respectively. In normal subjects, the tracer fraction in the early rapid phase fell by 43% ( p < 0.005) and the clearance half-time increased by 46% ( p < 0.01). In patients, the response of C-11 palmitate tissue kinetics to glucose was variable. In nine patients, it was similar to that in normal subjects while in the other seven patients a “paradoxic” response occurred. The tracer fraction entering the rapid clearance phase increased after glucose by 30% ( p < 0.05) associated with a 36% ( p < 0.05) decline in clearance half-times. The paradoxic response was unrelated to disease etiology or plasma substrate levels but occurred mostly in left ventricles with more severely depressed function. Thus, PET and C-11 palmitate allow the noninvasive demonstration of the known response of substrate metabolism of the human heart to altered substrate availability. Glucose administration in fasted humans serves as a provocative test of substrate regulation which can be abnormal in myocardial disease and can be demonstrated noninvasively.

A clinically applicable method for assessing lung permeability in the non-steady-state

A clinically applicable method for assessing the permeability of the alveolar-capillary barrier under non-steady-state conditions has been developed. Following deposition of a suitable tracer in the lungs, its rate of entry into the blood can be measured using blood samples alone, without the necessity for external monitoring. A second reference tracer must be infused in order to compensate for renal excretion and for redistribution of tracer in the extravascular space. Tracers of any convenient molecular weight and physical properties can be used, either unlabelled, or labelled with stable or radioactive isotopes. The method was examined by computer simulation in order to assess its sensitivity to measurement “noise”. In contrast to other non-steady-state tracer techniques, it is markedly less sensitive to experimental uncertainty, and measurements to an accuracy of 1–2% (coefficient of variation) should suffice for most purposes. The method was also validated by in vivo experiment in the pig, using a constant intravenous infusion of 51 Cr-EDTA as the reference tracer and a variable intravenous infusion of 99m Tc-DTPA to simulate entry from the alveoli. Good agreement was obtained between the calculated entry rate of the 99m Tc-DTPA and the true entry rate known from the infusion pump rate.

The neostriatal mosaic. I. compartmental organization of projections from the striatum to the substantia nigra in the rat

Combined neuroanatomical techniques were used to examine the organization of the striatal projection to the substantia nigra in the rat. Both double anterograde axonal tracing methods (Phaseolus vulgaris leuco-agglutinin (PHA-L) and 3H-amino acid tract tracing) and double fluorescent retrograde axonal transport tracing methods were used to examine the relationship among striatal neurons projecting to separate areas of the substantia nigra. Additionally, the distributions of retrogradely labeled striatonigral projection neurons were charted relative to the neurochemically distinct striatal "patch" compartment, identified by substance P- or leu-enkephalin-like immunoreactivity, and the complementary "matrix" compartment, identified by somatostatin-like immunoreactive fibers. These studies show two distinct types of organization in the striatonigral projections. One type is topographic in that the mediolateral relationships among these striatal efferent neurons are roughly maintained by their termination patterns in the substantia nigra, while the dorsoventral relationships are inverted. Projections from any part of the striatum, however, are distributed throughout the rostrocaudal axis of the substantia nigra. Despite their general topographic organization, the variable and dispersed nature of such projections from individual striatal loci results in partial overlap of afferent fields from separate striatal areas. The second type of organization is nontopographic and provides a different system for convergence of inputs from separated striatal areas that is superimposed on the rough topographic system. In this other projection system the mediolateral and dorsoventral relationships typical of the topographically ordered system are not maintained and are sometimes reversed. For example, PHA-L injected into the dorsal striatum labels a topographic (inverted relationship) projection to the ventral substantia nigra pars reticulata but also a smaller and separate projection to the dorsal pars reticulata and adjacent pars compacta. Retrograde tracer deposits in the pars compacta label neurons in the ventral striatum (the inverted relationship) but also clusters of neurons in the dorsal striatum. These clusters are in the neurochemically defined patch compartment whereas neurons in the matrix are labeled by injections into the pars reticulata. The dendrites of both retrogradely filled patch and matrix neurons are confined to the compartment containing their cell bodies, suggesting a restriction that would functionally segregate extrinsic striatal afferents shown in other studies to be confined to either patches or matrix.(ABSTRACT TRUNCATED AT 400 WORDS)

Estimation of parameters affecting the uptake of 99mTc-methylenediphosphonate in rat femur with model simulation.

The uptake of 99mTc-methylenediphosphonate (MDP) in different parts of rat femur was simulated using a local three-space model for tracer transfer. The model consisted of bone blood, bone ECF-space and space for tracer deposition. The measured 99mTc-MDP concentration in the systemic blood and the local bone blood flow measured by 131I-macroaggregated albumin microspheres were used as input parameters. The measured blood flow values were 6.3, 3.1 and 15.3 ml/100 g/min for proximal, middle and distal femur, respectively. The model parameters that gave the best fit to measured 99mTc-MDP uptake curves in computer simulation showed that bone blood flow, volume of ECF-space, permeability surface area product and accretion constant from ECF-space to space for tracer deposition were highest in distal and lowest in middle femur. The values corresponded to peak extraction fractions of 0.38, 0.62, and 0.31 for proximal, middle and distal femur, respectively. We conclude that the simulation gives acceptable model parameters, and indicates applicability of a similar model into clinical quantitative bone scintigraphy.

The interconnections of the inferior colliculi through their commissure.

Much is known of the sources and manner of termination of ascending and descending input to the inferior colliculus (IC) but its commissural connections are less well understood. Most studies of the commissure have utilized small lesions or tracer deposits; while all agree that commissural axons terminating in the IC do so in its superficial and dorsomedial sectors, it is not clear where projecting cell bodies are located in the IC. The present study attempted total infiltration of the commissure of the cat IC with horseradish peroxidase (HRP) in an effort to label all neuronal somas whose axons cross in the commissure. The distribution of labeled cells after the brachium of the IC (BIC) was cut unilaterally and infiltrated with HRP was also examined to enable comparison of the locations and approximate proportions of cells projecting to the contralateral IC and medial geniculate body (MGB). The cells giving rise to commissural axons form an array tilted dorsally from caudal to rostral that spreads mediolaterally through the central nucleus into the external nucleus of the IC, but largely excludes the dorsomedial sector at posterior levels. A similar distribution of labeled cells, but with reduced numbers, is found when large HRP deposits are made in the contralateral BIC. These results, in conjunction with those from studies of the terminations of commissural axons made by others, suggest that the interconnections of the inferior colliculi through their commissure are complementary, rather than reciprocal.

The lateral suprasylvian corticotectal projection in cats.

The projection from the lateral suprasylvian visual areas to the superior colliculus was investigated in cats using both anterograde and retrograde tracing techniques. The retrograde transport of horseradish peroxidase (HRP) or wheat germ agglutinin-HRP (WGA-HRP) from their site of deposit in the superior colliculus indicates that all divisions of the lateral suprasylvian visual areas project to both the superficial and deep layers of the superior colliculus. However, following tracer deposits in the superior colliculus that are confined to the layers below the stratum opticum (deep layers), more neurons are labeled along the lateral bank than along the medial bank of the middle suprasylvian sulcus. Conversely, tracer deposits in the superior colliculus dorsal to and including the stratum opticum label more cells in the medial than the lateral bank. These retrograde experiments also confirm that the visual cortex along the lateral gyrus (areas 17 and 18) projects to the superficial, but apparently not to the deep layers. The visual area in the cortex surrounding the caudal two-thirds of the anterior ectosylvian sulcus projects to the deep, but not to the superficial layers. The laminar and areal patterns of anterograde axon labeling in the superior colliculus were examined after single deposits of 3H-amino acids (autoradiography), HRP, or WGA-HRP in the lateral suprasylvian cortical regions, or combined isotope and WGA-HRP deposits. Axon labeling in the superior colliculus is generally densest in the stratum opticum and extends either dorsally into the superficial layers or ventrally into the intermediate gray layer. Specifically, the anterior divisions of the lateral suprasylvian cortex project primarily to the lateral portion of the superior colliculus, with the projection from the medial bank biased toward the superficial layers and axons from the lateral bank aimed mainly at the intermediate gray layer with some axons even reaching the deepest gray layer of the superior colliculus. Both the posteromedial and posterolateral divisions of the lateral suprasylvian cortex project to more extensive portions of the mediolateral and rostrocaudal dimensions of the superior colliculus than the anterior divisions. However, the posterolateral division projects more heavily to the intermediate gray layer than the posteromedial division; from the latter, axons distribute more superficially in the superior colliculus. Finally, the cortex surrounding the posterior suprasylvian sulcus projects primarily to the medial part of the superficial layers of the superior colliculus.(ABSTRACT TRUNCATED AT 400 WORDS)

Projections from the pretectal complex to the thalamic lateral dorsal nucleus of the cat.

The subcortical projections to the lateral dorsal nucleus (LD) of the cat thalamus were studied with retrograde transport techniques. Deposits of horseradish peroxidase (HRP) or fluorescent tracers were placed unilaterally in LD of adult cats, using electrophoretic or pressure injection techniques. Following post-injection survival periods of 1, 2 or 3 days, HRP retrogradely labeled cells were identified in sections reacted with benzidine dihydrochloride; fluorescent labeled cells were identified by fluorescent microscopy. Injections in LD result in retrogradely labeled neurons in all nuclei of the pretectal complex, including the nucleus of the optic tract (NTO), the posterior pretectal nucleus (NPP), the anterior pretectal nucleus (NPA), the pretectal olivary nucleus (NOL), and the medial pretectal nucleus (NPM). Small electrophoretic injections of HRP were used to investigate a possible topographic organization of the pretectal projections. Results from a variety of injection sites indicate only a subtle rostral-caudal gradient. That is, small injection sites in rostral LD result in retrograde labeling of neuron somata in the rostral parts of NTO, NPA and NPP, and throughout NPM. Injections in caudal LD result in labeled cells more caudally situated in NTO, NPA, NPP, and throughout NPM. Injections in the pulvinar (Pul) also result in retrogradely labeled cells in the pretectal complex, particularly NTO, NPP, and NOL. Experiments with injections of distinguishable fluorescent tracers in LD and Pul reveal that many more cells project to Pul than to LD. These experiments also reveal that while neurons that project to LD are intermingled with neurons that project to Pul, the two projections originate from separate subpopulations of cells. These results are discussed in regard to phylogenetic comparison of pretectal projections and subcortical pathways of sensory input to the limbic system.

Further studies on hypothermia and the blood-brain barrier system

Rats subjected to five episodes of recurrent, progressively deeper hypothermia showed no difference in cerebral deposition of rubidium tracer at 16 °C and/or apnea from animals lowered to this temperature and/or condition only once. Rats allowed to rewarm from 16 °C showed persisting increased cerebral deposition of tracer at 20 °C with gradual diminution at higher temperatures; at 37 °C, deposition of rubidium tracer in brains of rewarmed rats was not different from that of euthermic rats which were not subjected to hypothermia.

The effects of low body temperatures on deposition of tracers in the mammalian brain

Different views of the “blood-brain barrier” are described, and the barrier is presented, not as a simple structural or functional barrier similar to a biological membrane, but as a series of structures and mechanisms which determine the rate of deposition of hematogenous substances in the brain. Reported effects of hypothermia and hibernation on this system are reviewed. The deposition of protein, ion and carbohydrate tracers was examined in euthermic and hypothermic rats as well as in euthermic, hypothermic, and hibernating bats, ground squirrels, and hamsters. Artifically hypothermic animals from all mammalian species in the study demonstrated increased uptake of the ion and carbohydrate tracers although not the protein tracer, but hibernating animals with equally low or lower core temperatures showed no increase in cerebral deposition of any of the tracers over that found in euthermic controls. In rats, the increased deposition of rubidium in the hypothermic brain was demonstrated to be independent of the duration of hypothermia, and evidence was gathered which was consistent with the alternate hypothesis that a critical temperature is reached before the change in rate of cerebral deposition of the tracer. Thermistors were implanted in rat brains, and data were gathered to suggest that this critical temperature in the brain is near 18.8 °C. Differential counting and autoradiography demonstrated that the rubidium tracer was fairly equally distributed in the brain. Neonatal rats and poikilothermic frogs did not show increased deposition of tracers in the hypothermic condition, in comparison to euthermic controls. High doses of dexamethasone lessened, but did not eliminate, the increased deposition of rubidium in the brain of hypothermic rats. Large intravenous doses of ouabain moderately increased the deposition of rubidium tracer in the brains of euthermic rats. These findings are discussed in terms of the effect of alterations in the barrier system on hypothermic animals, and the significance of intact barrier systems in hibernating, poikilothermic and neonatal animals.

Effect of Hydrostatic Pressure on Self-Diffusion in Single Crystals of Indium

The pressure effect on the self-diffusion rate in single crystals of indium metal has been measured parallel and perpendicular to the tetragonal axis using a radioactive tracer deposition and sectioning method. The experiments were performed at three different temperatures 118, 132, and 148 °C, and at hydrostatic pressures varying from 1.2 to 9.6 kbar. The diffusion rate was observed to decrease with increasing pressure and the activation volume for the diffusion process was determined to be 8.1 ± 0.4 cm3/mole with no detectable dependence on temperature or crystallographic orientation. Comparison with theoretical relations suggests the vacancy mechanism for diffusion.

Effect of certain non-lattice cations on adsorption of orthophosphate ions on ignited lead chromate

Deposition of carrier-free32P on ignited PbCrO4, as a function of pH and concentration of added lattice and certain non-lattice ions is described. The observed carrying increases with pH and lattice cation concentration whereas it shows a gradual fall in presence of increasing lattice anion concentration. Further, contrary to expectations, the carrying is favoured also in presence of certain non-lattice cations (e. g. Ba2+ and Sr2+) having a similar electric charge and comparable ionic radii. These findings are discussed in the light of observations made in case of deposition of the same tracer on ignited PbSO4 where the carrying is adversely affected in presence of these cations. The assumed anchoring of these non-lattice cations by the lattice anion on the PbSO4 lattice is proposed to be nonexistent in the case of PbCrO4 due to solubility limitations.

Effect of Hydrostatic Pressure on the Diffusion of Silver in Indium

AbstractThe pressure effect on the silver impurity diffusion has been measured parallel and perpendicular to the tetragonal axis in single crystals of indium metal. A thin film radioactive tracer deposition and sectioning method was used. The experiments were performed at 96.1 and 112.3 °C, and at hydrostatic pressures varying from 0.9 to 7.7 kbar. The diffusion rate was observed to decrease with increasing pressure and the activation volume for the diffusion process was determined to (6.4 ± 0.6) cm3/mol, with no detectable dependence on either temperature or crystallographic orientation. Comparison with systematics and theoretical arguments suggests interstitial diffusion.

Scintillomicroscope for radioactive tracer detection.

An image intensifier-microscope system is described that is capable of viewing the spatial distribution of weak radioactive tracer deposits in biological specimens. The radioactive decay products are located by means of the light they emit from thin scintillators placed over the specimen. Comparisons are made with conventional autoradiographic techniques. An analysis is given of the sensitivity of the system. Results obtained from the application of the technique to 14C detection in Schistosoma mansoni are presented and discussed.