Construction of a whole body blood flow model for use in positron emission tomography imaging with [15O]water

A whole body blood flow model (WBBFM) was developed and tested using STELLA II, an icon-driven mathematical simulation software package. The WBBFM uses parallel chambers to represent gray and white areas of the brain, body organs such as lungs, heart (right and left halves), injection site, and blood sampling sites. Input values to the WBBFM include organ blood flows, organ volumes, tissue:blood partition coefficients, injected activity, and data acquisition times for a positron emission tomography (PET) camera. Input variables included an injection function (e.g., bolus), and a blood flow function (e.g., transient variations in flow). The kinetic behavior of [15O]water, a freely diffusible radiotracer employed in PET to characterize blood flow was examined by the WBBFM. The physiologic behavior of water in the human body was emulated using the WBBFM and the model's predictive value was verified by comparing calculated results with the following properties of water: diffusibility, tissue:blood partition coefficient of [15O]water, and the mixing of [15O]water with total body water. The WBBFM simulated Kety's autoradiographic method used in the estimation of regional cerebral blood flow by PET using [15O]water. The application of the model to a cognitive activation study paradigm based on Kety's method is presented and its results compared to published literature data. With appropriate modification in the half-life, tissue:blood partition coefficient, and the amount of administered radioactivity, the WBBFM should prove useful as a tool to examine kinetics of other freely diffusible radiotracers used in PET.     

Cerebral blood flow and personality: a positron emission tomography study

OBJECTIVE: To determine current practice patterns of obtaining informed consent for infertility treatment by reproductive endocrinologists and to assess changes in response to reports of an association between ovulation induction and ovarian cancer. METHODS: Board-certified reproductive endocrinologists (n = 575) were surveyed by mail regarding how they informed patients and obtained consent for infertility treatments and how their practices had been influenced by studies suggesting a link between ovulation induction and ovarian cancer. Data were analyzed using chi2 and logistic regression analyses. RESULTS: The return rate was 62.1% (357 of 575 surveys). Most respondents (92%) used discussions with physicians to inform their patients of risks and benefits of all infertility treatments. Additional means, such as audiovisual aids, were used significantly more often for assisted reproductive technologies (including intracytoplasmic sperm injection and use of donated eggs) than for less invasive therapies (31-43% versus 4-11%, P < .001). Most physicians (46-66%) used verbal consent alone for hysterosalpingogram, intrauterine insemination, and ovulation induction. Formal written consent was used significantly more often for the various assisted reproductive technologies than for hysterosalpingogram, intrauterine insemination, or ovulation induction (94-95% versus 26-44%). Although most physicians (70%) did not believe that ovulation induction increases the risk of ovarian cancer, 83% addressed this risk when obtaining consent and 47% reported changing their practices since an association was reported. Common changes included limiting length of treatment and addressing ovarian cancer risk. CONCLUSION: Current practice patterns of obtaining informed consent for various infertility treatments by board-certified reproductive endocrinologists show, as expected, that informed consent is more rigorous for assisted reproductive technologies. Although most surveyed did not believe that ovulation induction increases risk of ovarian cancer, the majority of physicians addressed that risk when obtaining consent and nearly half changed their practices on the basis of a possible association.     

Reduced regional brain glucose metabolism assessed by positron emission tomography in electrodermal nonresponder schizophrenics: A pilot study.

Examined whether electrodermal nonresponder and responder subgroups of schizophrenic patients differ in regional brain metabolism assessed by positron emission tomography during a continuous performance test. In comparison to both 6 normal controls and 3 responder schizophrenics, the 3 nonresponder schizophrenics showed about a 20% reduction in metabolic rate across the entire brain. Nonresponder schizophrenics tended to have lower absolute metabolic rates than responders in lateral and medial frontal, thalamic, and hippocampal areas. Nonresponders also had significantly lower relative metabolic rates in medial frontal and hippocampal areas as well as the right amygdala. These data suggest that electrodermal subgroups of schizophrenics differ in both regionally specific brain metabolic processes thought to be involved in electrodermal activity and in generalized brain metabolism. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Frontotemporal cerebral blood flow change during executive and declarative memory tasks in schizophrenia: A positron emission tomography study.

Schizophrenia affects prefrontal and temporal-limbic networks. These regions were examined by contrasting regional cerebral blood flow (rCBF) during executive (Wisconsin Card Sorting Test [WCST]), and declarative memory tasks (Paired Associate Recognition Test [PART]). The tasks, and a resting baseline, were administered to 15 patients with schizophrenia and 15 healthy controls during 10 min positron emission tomography 1?O-water measures of rCBE Patients were worse on both tasks. Controls activated inferior frontal, occipitotemporal, and temporal pole regions for both tasks. Similar results were obtained for controls matched to level of patient performance. Patients showed no activation of hypothesized regions during the WCST and activated the dorsolateral prefrontal cortex during the PART. On the PART, occipitotemporal activation correlated with better performance for controls only. Better WCST performance correlated with CBF increase in prefrontal regions for controls and in the parahippocampal gyrus for patients. Results suggest that schizophrenia may involve a breakdown in the integration of a frontotemporal network that is responsive to executive and declarative memory demands in healthy individuals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Technetium-99m hexamethylpropylene amine oxime single-photon emission tomography of regional cerebral blood flow in insulin-dependent diabetes

The experience of major paediatric trauma presenting both directly and indirectly over ten years to a Paediatric Teaching Hospital is presented. Of the 185 patients assessed and treated in the Resuscitation Room, 131 were considered to have sustained significant trauma: 99 being admitted to the Intensive Therapy Unit and 32 transferred to the regional Neurosurgical centre. Road traffic accidents were responsible for the majority of serious injuries and eight of the 11 deaths, emphasising the need for further preventative measures. There were 95 interhospital transfers amongst the 131 patients judged to have sustained significant trauma. The potential benefits of centralisation of services to manage major paediatric trauma, in terms of both a reduction in interhospital transfers and early involvement of experienced staff, are proposed.     

Noninvasive quantification of regional myocardial metabolic rate for oxygen by use of 15O2 inhalation and positron emission tomography. Theory, error analysis, and application in humans

BACKGROUND: A method has been developed to measure the regional myocardial metabolic rate of oxygen consumption (rMMRO2) and oxygen extraction fraction (rOEF) quantitatively and noninvasively in humans by use of 15O2 inhalation and positron emission tomography. This article describes the theory, an error analysis of the technique, and procedures of the method used in a human feasibility study. METHODS AND RESULTS: Inhaled 15O2 is transported to peripheral tissues, where it is converted to 15O-labeled water of metabolism, which exchanges with the relatively large extravascular tissue space. Quantification of this buildup of radioactivity allows the calculation of rMMRO2 and rOEF. However, a correction for the spillover of the pulmonary gas radioactivity signal into myocardial regions is required and has been made by use of a gas volume distribution estimated from the transmission scan. This was validated by comparative measurements using the inert gas [11C]CH4 in four greyhounds. Spillover of the cardiac chamber radioactivity has been corrected for with an inhaled [13O]CO (blood volume) scan. The underestimation of myocardial radioactivity due to wall motion and thickness has been corrected for by use of values of tissue fraction obtained from the flow measurement [15OKCO2 scan). Values of rOEF were similar (within 4%) whether obtained from gas volume measurements determined from the transmission or [11C]CH4 scan data. 15O2 scan information from six healthy volunteers showed a clear distribution of myocardial radioactivity after the vascular and pulmonary gas 15O background was subtracted. Subsequent compartmental analysis resulted in values for rOEF and rMMRO2 of 0.60 +/- 0.11 and 0.10 +/- 0.03 mL.min-1.g-1 in the human myocardium at rest. CONCLUSIONS: The results of this study are in good agreement with established values. This is the first known approach to allow the direct quantitative determination of rOEF and oxygen metabolism to be made noninvasively on a regional basis.     

Comparison of functional MR and H2 15O positron emission tomography in stimulation of the primary visual cortex

PURPOSE: To locate spoiled gradient-echo functional MR signal changes in relation to brain parenchyma. METHODS: The region of the primary visual cortex was evaluated using functional MR and H2 15O positron emission tomography in each of six male subjects who were being visually stimulated by means of red light-emitting diode flash goggles. RESULTS: The positron emission tomography technique demonstrated substantially greater relative signal change with visual stimulation than did the functional MR technique. Furthermore, the functional MR signal changes were concentrated in loci around the periphery of brain parenchyma exhibiting increased radiotracer activity, as opposed to being collocated. CONCLUSIONS: Signal changes found using functional MR based on gradient-echo techniques reflect primarily phenomena occurring within small veins and underrepresent activity intrinsic to brain parenchyma, thus introducing potential inaccuracies in locating regions of activated brain tissue. Positron emission tomography, however, directly measures changes in metabolically related activity within the parenchyma.     

Functional activation of cerebral blood flow abolished by scopolamine is reversed by cognitive enhancers associated with cholinesterase inhibition: a positron emission tomography study in unanesthetized monkeys

The effects of somatosensory stimulation on the regional cerebral blood flow (rCBF) response were studied in unanesthetized monkeys before and after treatment with scopolamine and three cognitive enhancers (physostigmine, E2020 and tacrine) that inhibit cholinesterase, using 15O-labeled water and high-resolution positron emission tomography. Under control conditions, somatosensory stimulation induced a significant increase in the rCBF response in the contralateral somatosensory cortex of monkey brain. Intravenous administration of scopolamine (50 microg/kg) resulted in abolishment of the rCBF response to stimulation. The rCBF response abolished by pretreatment with scopolamine was recovered by administration of physostigmine (1 or 10 microg/kg), E2020 (10 or 100 microg/kg) or tacrine (100 or 1000 microg/kg), in a dose-dependent manner. The effect of E2020 (100 microg/kg) on the rCBF response lasted for >4 hr, whereas the effects of physostigmine and tacrine were of shorter duration. These findings suggest that these compounds reversed the scopolamine-abolished rCBF response to somatosensory stimulation via enhancement of cholinergic neurotransmission, which was mainly induced by cholinesterase inhibition.     

Stimulation of human thalamus for pain relief: possible modulatory circuits revealed by positron emission tomography

Stimulation of human thalamus for pain relief: possible modulatory circuits revealed by positron emission tomography. J. Neurophysiol. 80: 3326-3330, 1998. Stimulation of the somatosensory thalamus was used for more than 2 decades to treat chronic pain in the human. However, despite clinical reports of successful results, little is known about the actual mechanisms mediating this form of stimulation-produced analgesia. To reveal possible neuronal pathways evoked by thalamic stimulation, we measured regional changes in cerebral blood flow (rCBF) in five patients who received successful long-term relief of chronic pain with somatosensory thalamic stimulation. Positron emission tomography during thalamic stimulation revealed significant activation of the thalamus in the region of the stimulating electrodes as well as activation of the insular cortex ipsilateral to the thalamic electrodes (contralateral to the patients' clinical pain). For these patients, thalamic stimulation also evoked paresthesiae that included thermal sensations in addition to tingling sensations. Results of this study indicate that in some cases somatosensory thalamic stimulation may activate a thalamocortical pain modulation circuit that involves thermal pathways. These results are consistent with other recent reports suggesting that activation of thermal pathways may contribute to modulation of nociceptive information.     

Adult age differences in regional cerebral blood flow during visual world identification: evidence from H215O PET

We used H215O PET to investigate adult age differences in regional cerebral blood flow (rCBF) during the performance of a visual word identification task. The study participants were 20 healthy, right-handed men: 10 young adults between 18 and 27 years of age, and 10 older adults between 63 and 75 years of age. The word identification task comprised six blocks of test trials representing four task conditions; subjects responded manually. The task conditions varied with regard to whether semantic retrieval was required (e.g., word/nonword discrimination vs simple response to each stimulus) and with regard to the difficulty of visual encoding (e.g., words presented normally vs words with asterisks inserted between adjacent letters). Each subject performed all six trial blocks, concurrently with each of six H215O PET scans. Analyses of quantitative CBF data obtained from the arterial time-activity curve demonstrated a significant age-related decline in global CBF rate. Analyses of the changes in rCBF between task conditions indicated that retrieval of semantic information sufficient to distinguish words from nonwords is mediated by a ventral occipitotemporal cortical pathway. Specific areas within this pathway were also associated with visual encoding processes. Several rCBF activations were significantly greater for young adults than for older adults, indicating an age-related decline in processing efficiency within this ventral occipitotemporal pathway. Although the performance data demonstrated a greater age-related slowing for visual encoding than for semantic retrieval, these age-related performance changes were not associated with corresponding changes in rCBF activation.     

Cerebral perfusion and oxygen metabolism in Parkinson's disease: positron emission tomographic study using oxygen-15-labeled CO2 and O2]

In many previous studies, positron emission tomography (PET) has been used to evaluate cerebral perfusion and oxygen metabolism in Parkinson's disease. In this article, these previous reports are reviewed together with our recent findings. Hypoperfusion and hypometabolism in parkinsonian brains reported previously seemed to be derived chiefly from psychiatric manifestations, including intellectual decline and depression. In our study on 34 patients with asymmetric symptoms, the blood flow and oxygen metabolism were significantly higher in the caudate head and putamen, contralateral to the predominant patient's symptoms, than in the opposite nuclei. The asymmetry in the perfusion and metabolism is clearer in the early stage of the disease or in patients without DOPA therapy. These findings suggest that the striatal dysfunction is caused by uninhibited activities, supersensitivities, or compensatory hyperactivities of the striatum.     

Neural correlates of depth of processing effects on recollection: evidence from brain potentials and positron emission tomography

The probability that words would be recollected during tests of recognition memory was varied by manipulating depth of processing at study. Experiment 1 employed scalp-recorded event-related potentials (ERPs), and identified as a correlate of recollection a late (onset c. 500 ms), strongly left-lateralized positive-going modulation of the ERP waveform. The findings from experiment 2, which employed positron emission tomography (PET), indicated that recollection was associated with activation of the left hippocampal formation together with an extensive region of left temporal and frontal cortex. The findings support current ideas about the role of the hippocampal formation in episodic memory retrieval, and provide complementary information about the time course and localization of the cortical correlates of the recollection of recently experienced words.     

Selective effects of the endogenous cannabinoid arachidonylethanolamide (anandamide) on regional cerebral blood flow in the rat

Chronic focal epilepsy is associated with synaptic plasticity and growth of new connections. Brain-derived neurotrophic factor (BDNF) is associated with each of these processes in normal brain and shows acute up-regulation in models of generalized epilepsy. Here, using an experimental model of focal epilepsy, we show persistent up-regulation of BDNF mRNA, independent of that of other growth factors, in association with the development and persistence of chronic seizures. In situ hybridization histochemistry revealed that rats perfused within 2-3 days after seizure onset had widespread increases in BDNF mRNA levels in the neocortex. Rats perfused at later times, however, showed focal up-regulation of BDNF mRNA at the injection site and down-regulation in a surrounding cortical zone. Nerve growth factor and neurotrophin-3 mRNAs were not significantly altered. These reciprocal changes in BDNF gene expression in the epileptic focus and the cortical surround may contribute to plastic changes in epileptic neuronal circuits that accompany the transition from acute to chronic epilepsy. BDNF down-regulation in the surround is likely to be associated with the inhibitory surround that hampers seizure spread, but facilitates the persistence of a chronic epileptic focus.     

Correlation between myocardial blood flow and fasting glucose metabolism in ischemic heart disease. Quantitative assessment by nitrogen-13 ammonia and fluorine-18 fluorodeoxyglucose positron emission tomography

In Poland cutaneous form of anthrax is occurring sporadically. Most of these cases were recognized in the eastern part of the country adjacent to the eastern border (Lomza region and others). The latest literature on epidemiology, diagnosis, prevention and treatment of anthrax is reviewed in order to spread modern views on anthrax and to implement changes in the diagnostic methods of anthrax in Poland.     

The isolated supported canine heart: a model for the evaluation of drug effects on regional myocardial blood flow

The present investigation was designed to determine the effect of propranolol on regional myocardial blood flow and oxygen consumption (MVO2) in the isolated supported dog heart preparation perfused at a constant coronary blood flow. The transmural distribution of blood flow, determined by the radioactive microsphere technique, was expressed as the epicardial/endocardial blood flow ratio (epi/endo). Propranolol (0.5 mg/kg i.v.) produced a significant decrease in heart rate and myocardial contractile force and an increase in coronary artery perfusion pressure due to an increase in coronary vascular resistance. These hemodynamic changes were accompanied by significant decreases in epi/endo (increased endocardial perfusion) and MVO2. Reduction of perfusion pressure to control by a decrease in total coronary blood flow produced no further change in epi/endo or MVO2. However, increasing heart rate to control increased epi/endo to predrug levels. Contractile force and MVO2 remained reduced below control. Norepinephrine infusion (1 mug/min intracoronary) produced a significant increase in heart rate and contractile force and decrease in perfusion pressure. These changes were accompanied by an increase in epi/endo and MVO2. Propranolol (0.5 mg/kg i.v.) abolished the response to norepinephrine. Propranolol may produce beneficial effects in angina pectoris by a decrease in epi/endo (via a reduction in heart rate) and MVO2 and by beta adrenergic blockade of the deleterious effects of catecholamines.     

Relationship between liver function and splenic blood flow (quantitative measurement of splenic blood flow with H2(15)O and a dynamic state method: 2)

A case is reported of persistent primitive trigeminal artery associated with recurrent facial pain and noncomitant strabismus by partial ipsilateral oculomotor palsy. Transcranial Doppler disclosed indirectly persistent carotid-basilar anastomosis. CT and angiography allowed complete diagnosis excluding a posterior communicating artery aneurysm, a Tolosa-Hunt syndrome and an ophthalmoplegic migraine. Steroid therapy is recommended treatment. Surgery should be considered when symptoms are intractable to medical therapy.     

A quantitative study of regional cerebral blood flow in childhood using 123I-IMP-SPECT: with emphasis on age-related changes

Single photon emission computed tomography (SPECT), using N-isopropyl-p-[123I] iodoamphetamine (123I-IMP) was used for quantitative analysis of regional cerebral blood flow (rCBF) on 26 individuals between 0 and 19 years of age. The rCBF showed age-related changes; it was low in early infancy, increased in late infancy through early childhood, and decreased and remained constant after puberty. The rCBF through cerebral cortex varied more greatly than through thalamus and cerebellum, and seemed to depend more closely on age. In the case of 4 months of age rCBF was very low at the frontal region and was very high at the occipital region. In more older cases, rCBF in the cerebral cortex was higher than in the thalamus. In childhood, rCBF was very inconsistent and showed a great inter-individual variance.     

New method for the analysis of multiple positron emission tomography dynamic datasets: an example applied to the estimation of the cerebral metabolic rate of oxygen

Methacrylates are well-known contact sensitizers with increasing frequency of contact leading to occupational skin disease. Here, we developed an animal model to facilitate studies on the sensitizing capacities and cross-reactivity patterns between four clinically most important allergens: methacrylate (MMA), 2-hydroxyethyl methacrylate (2-HEMA), 2-hydroxypropyl methacrylate (2-HPMA) and ethyleneglycol dimethacrylate (EGDMA). Inbred guinea pigs were immunized by ic injections of 300 microliters of 1.0 M methacrylate solutions in Freund's complete adjuvant into both flanks, both ears, and the neck. After 14 days open skin tests were performed with 50% MMA, 2-HEMA, or 2-HPMA or 10% EGDMA solutions in 40% DMSO in ethanol. Cross-reactivities were investigated 14 days later by skin testing with all four methacrylates. Using this newly developed protocol, strongly positive skin tests for methacrylates could be induced in almost all guinea pigs (MMA 26/26, 2-HEMA 16/18, 2-HPMA 15/16 and EGDMA 11/11). Whereas EGDMA induced only weak or infrequent cross-reactivities, 2-HEMA sensitization led to strong cross-reactions to all other methacrylates. Both MMA and 2-HPMA induced strong cross-reactivity to EGDMA but only weak to moderate reactivities to the other methacrylates. The absence of strong cross-reactions with monomethacrylates in EGDMA (dimethacrylate)-sensitized animals may be explained by the predominance of highly EGDMA-specific T-cells in these animals. In contrast, sensitization with MMA, 2-HEMA, and 2-HPMA would lead to recruitment of T-cells cross-reactive to the other monomethacrylates, according to their molecular similarities. The strong skin hypersensitivities observed for EGDMA in these latter groups are ascribed to enzymatic degradation into monomethacrylate compounds, notably 2-HEMA, at a rate sufficient to elicit cognate effector T-cells. The results of this study offer new insights in the development of methacrylate hypersensitivities and common cross-sensitization patterns in clinical practice.