Carl Selin

Bio: Carl Selin is an academic researcher from University of California, Los Angeles. The author has contributed to research in topics: Blood flow & Ischemia. The author has an hindex of 26, co-authored 36 publications receiving 10614 citations. Previous affiliations of Carl Selin include National Institutes of Health.

Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: validation of method.

Abstract: Tracer techniques and quantitative autoradiographic and tissue counting models for measurement of metabolic rates were combined with positron computed tomography (PCT) and (F-18)2-fluoro-2-deoxy-D-glucose (FDG) for the measurement of local cerebral metabolic rate for glucose (LCMRGlc) in humans. A three-compartment model, which incorporates hydrolysis of FDG-6-PO4 to FDG, was developed for the measure of kinetic constants and calculation of LCMRGlc. Our model is an extension of that developed by Sokoloff et al. Although small, hydrolysis of FDG-6-PO4 was found to be significant. A PCT system, the ECAT, was used to determine the rate constants, lumped constant, and stability of the model in human beings. The data indicate that cerebral FDG-6-PO4 in humans increases for about 90 minutes, plateaus, and then slowly decreases. After 10 minutes, cerebral blood FDG activity levels were found to be a minor fraction of tissue activity. Precursor pool turnover rate, distribution volumes, and red blood cell-plasma concentration ratios were determined. Reproducibility (precision) of LCMRGlc measurements (approximate 2 cm2 regions) was +/- 5.5% over a 5-hour period. The replacement of arterial blood sampling with venous sampling was validated.

Reduction of prefrontal cortex glucose metabolism common to three types of depression.

Abstract: • Using positron emission tomography, we studied cerebral glucose metabolism in drug-free, age- and sex-matched, righthanded patients with unipolar depression (n =10), bipolar depression (n =10), obsessive-compulsive disorder (OCD) with secondary depression (n =10), OCD without major depression (n =14), and normal controls (n =12). Depressed patients were matched for depression on the Hamilton Depression Rating Scale, and subjects with OCD without depression and OCD with depression had similar levels of OCD pathology. We also studied six non—sex-matched patients with mania. Mean ( ± SD) glucose metabolic rates for the left dorsal anterolateral prefrontal cortex, divided by the rate for the ipsilateral hemisphere as a whole (ALPFC/hem), were similar in the primary depressions (unipolar depression = 1.05 ±0.05; bipolar depression =1.04 ± 0.05), and were significantly lower than those in normal controls (1.12 ± 0.06) or OCD without depression (1.15 ± 0.05). Results for the right hemisphere were similar. Values in subjects with OCD with depression (1.10 0.05) were also significantly lower than in subjects with OCD without depression, and values in subjects with bipolar depression were lower than those in manic subjects (1.12 ± on this measure in the left hemisphere, although results were not significant in the right hemisphere. There was a significant correlation between the HAM-D score and the left ALPFC/hem. With medication for depression (n =12), the left ALPFC/hem increased significantly and the percentage change in the Hamilton scale score correlated with the percentage change in the left ALPFC/hem. These data support other findings that major depression is associated with a left ALPFC abnormality.

Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder.

Abstract: • We used positron emission tomography to investigate local cerebral metabolic rates for glucose (LCMRG1c) in patients with obsessive-compulsive disorder before and after treatment with either fluoxetine hydrochloride or behavior therapy. After treatment, LCMRG1c in the head of the right caudate nucleus, divided by that in the ipsilateral hemisphere (Cd/hem), was decreased significantly compared with pretreatment values in responders to both drug and behavior therapy. These decreases in responders were also significantly greater than right Cd/hem changes in nonresponders and normal controls, in both of whom values did not change from baseline. Percentage change in obsessivecompulsive disorder symptom ratings correlated significantly with the percent of right Cd/hem change with drug therapy and there was a trend to significance for this same correlation with behavior therapy. By lumping all responders to either treatment, right orbital cortex/hem was significantly correlated with ipsilateral Cd/hem and thalamus/ hem before treatment but not after, and the differences before and after treatment were significant. A similar pattern was noted in the left hemisphere. A brain circuit involving these brain regions may mediate obsessivecompulsive disorder symptoms.

Tomographic measurement of local cerebral glucose metabolic rate in humans with (f-18)2-fluoro-2-deoxy-d-glucose: validation of method

Abstract: Tracer techniques and quantitative autoradiographic and tissue counting models for measurement of metabolic rates were combined with positron computed tomography (PCT) and (F-18)2-fluoro-2-deoxy-D-glucose (FDG) for the measurement of local cerebral metabolic rate for glucose (LCMRGlc) in humans. A three-compartment model, which incorporates hydrolysis of FDG-6-PO4 to FDG, was developed for the measure of kinetic constants and calculation of LCMRGlc. Our model is an extension of that developed by Sokoloff et al. Although small, hydrolysis of FDG-6-PO4 was found to be significant. A PCT system, the ECAT, was used to determine the rate constants, lumped constant, and stability of the model in human beings. The data indicate that cerebral FDG-6-PO4 in humans increases for about 90 minutes, plateaus, and then slowly decreases. After 10 minutes, cerebral blood FDG activity levels were found to be a minor fraction of tissue activity. Precursor pool turnover rate, distribution volumes, and red blood cell-plasma concentration ratios were determined. Reproducibility (precision) of LCMRGlc measurements (approximate 2 cm2 regions) was +/- 5.5% over a 5-hour period. The replacement of arterial blood sampling with venous sampling was validated.

Local Cerebral Glucose Metabolic Rates in Obsessive-Compulsive Disorder: A Comparison With Rates in Unipolar Depression and in Normal Controls

Abstract: We studied 14 patients with obsessive-compulsive disorder (OCD) by positron emission tomography and the fluorodeoxyglucose method, looking for abnormalities in local cerebral metabolic rates for glucose in brain structures that have been hypothesized to function abnormally in OCD. These patients were compared with 14 normal controls and 14 patients with unipolar depression. The patients with unipolar depression and OCD did not differ in levels of anxiety, tension, or depression. In OCD, metabolic rates were significantly increased in the left orbital gyrus and bilaterally in the caudate nuclei. This was apparent on all statistical comparisons with both controls and unipolar depression. The right orbital gyrus showed at least a trend to an increased metabolic rate in all comparisons. The metabolic rate in the left orbital gyrus, relative to that in the ipsilateral hemisphere (orbital gyrus/hemisphere ratio), was significantly elevated compared to controls and subjects with unipolar depression, and stayed high even with successful drug treatment. Though it was in the normal range in the morbid state, with improvement in OCD symptoms after drug treatment, the caudate/hemisphere metabolic ratio increased uniformly and significantly bilaterally. This ratio did not increase in patients who did not respond to treatment. Thus, OCD showed cerebral glucose metabolic patterns that differed from controls in both the symptomatic and recovered states.

Blood Flow, Oxygen and Nutrient Supply, and Metabolic Microenvironment of Human Tumors: A Review

Abstract: The objective of this review article is to summarize current knowledge of blood flow and perfusion-related parameters, which usually go hand in hand and in turn define the cellular metabolic microenvironment of human malignancies. A compilation of available data from the literature on blood flow, oxygen and nutrient supply, and tissue oxygen and pH distribution in human tumors is presented. Whenever possible, data obtained for human tumors are compared with the respective parameters in normal tissues, isotransplanted or spontaneous rodent tumors, and xenografted human tumors. Although data on human tumors in situ are scarce and there may be significant errors associated with the techniques used for measurements, experimental evidence is provided for the existence of a compromised and anisotropic blood supply to many tumors. As a result, O2-depleted areas develop in human malignancies which coincide with nutrient and energy deprivation and with a hostile metabolic microenvironment (e.g., existence of severe tissue acidosis). Significant variations in these relevant parameters must be expected between different locations within the same tumor, at the same location at different times, and between individual tumors of the same grading and staging. Furthermore, this synopsis will attempt to identify relevant pathophysiological parameters and other related areas future research of which might be most beneficial for designing individually tailored treatment protocols with the goal of predicting the acute and/or long-term response of tumors to therapy.

Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, "prefrontal" and "limbic" functions.

Abstract: The central theme of the "segregated circuits" hypothesis is that structural convergence and functional integration occurs within, rather than between, each of the identified circuits Admittedly, the anatomical evidence upon which this scheme is based remains incomplete The hypothesis continues to be predicated largely on comparisons of anterograde and retrograde labeling studies carried out in different sets of animals Only in the case of the "motor" circuit has evidence for the continuity of the loop been demonstrated directly in individual subjects; for the other circuits, such continuity is inferred from comparisons of data on different components of each circuit obtained in separate experiments Because of the marked compression of pathways leading from cortex through basal ganglia to thalamus, comparisons of projection topography across experimental subjects may be hazardous Definitive tests of the hypothesis of maintained segregation await additional double- and multiple-label tract-tracing experiments wherein the continuity of one circuit, or the segregation of adjacent circuits, can be examined directly in individual subjects It is worthy of note, however, that the few studies to date that have employed this methodology have generated results consistent with the segregated circuits hypothesis Moreover, single cell recordings in behaving animals have shown striking preservation of functional specificity at the level of individual neurons throughout the "motor" and "oculomotor" circuits It is difficult to imagine how such functional specificity could be maintained in the absence of strict topographic specificity within the sequential projections that comprise these two circuits This is not to say, however, that we expect the internal structure of functional channels (eg, the "arm" channel within the "motor" circuit) to have cable-like, point-to-point topography When the grain of analysis is sufficiently fine, anatomical studies have shown repeatedly that the terminal fields of internuclear projections (eg, to striatum, pallidum, nigra, thalamus, etc) often appear patchy and highly divergent, suggesting that neighboring groups of projection cells tend to influence interdigitating clusters of postsynaptic neurons While more intricate and complex than simple point-to-point topography, however, this type arrangement should also be capable of maintaining functional specificity As discussed briefly above, it is not yet clear to what extent the inputs to the "motor" circuit from the different precentral motor fields (eg, MC, SMA, APA) are integrated in their passage through the circuit It now appears that at the level of the putamen such inputs remain segregated(ABSTRACT TRUNCATED AT 400 WORDS)