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Biomedical subjects

A Lilja

Publications and source records attributed to A Lilja.

72 records · Page 4Linked to original sources

The normal pituitary examined with positron emission tomography and (methyl-11C)-L-methionine and (methyl-11C)-D-methionine.

Four patients with radiologically normal pituitary gland were examined with positron emission tomography after the administration of (methyl-11C)-L-methionine. On a following day the examination was repeated with (methyl-11C)-D-methionine. The accumulation rate of L-methionine in the pituitary was measured, giving a value that was about twice that of normal brain tissue. The accumulation rate of D-methionine in the pituitary was almost a factor of 10 lower than that of L-methionine. In the normal brain tissue that ratio was 2.3. The study clearly indicates that the methionine uptake in the pituitary is stereospecific. 11C-D-methionine is freely distributed in the tissue without entrapment, whereas 11C-L-methionine is irreversibly bound. It is concluded that PET with 11C-L-methionine can be used to study amino acid utilization in the pituitary.

Adult↗

Tumour delineation with magnetic resonance imaging in gliomas. A comparison with positron emission tomography and computed tomography.

In ten patients with histopathologically confirmed low-grade (n = 4) and high-grade (n = 6) cerebral gliomas, the ability of magnetic resonance imaging (MRI) to delineate these tumours was examined. Spin echo (SE) technique with dual and multiple echoes and subtraction of images recorded with multiple echo sequences was applied. Computed tomography (CT) and positron emission tomography (PET) with 11C-L-methionine were used as reference methods. In high-grade gliomas multiple echo sequences and subtractions delineated the tumours better than ordinary SE sequences and equally well as CT, but slightly less well than PET. In low-grade tumours, the tumour delineation was better than with CT and comparable to that obtained with the present PET method. Multiple echo sequences and subtraction increase the reliability of MRI in delineating cerebral gliomas as compared with standard SE sequences.

Adolescent↗

Positron emission tomography in experimental perinatology.

Positron emission tomography (PET) is a new tracer technique by which short-lived radionuclides, such as 11C are used for labeling drugs, amino acids and other compounds. The concentration in the various organs is determined non-invasively after I.V. injection. Positrons, emitted by 11C attract an electron, and the two masses are annihilated by emitting photons. These can be registered by external detectors. Measurement of the radioactivity per volume of tissue as a function of time is accomplished by computerized processing of the data. The PET technique may be used for studies of the kinetics of the injected compound in different organs of the body. However, PET registers only the total radioactivity meaning that the measured 11C-radioactivity represents the sum of the parent compound and the radiolabelled metabolites. Chemical and radiochemical analyses in various body fluids may then help to interpret the PET images.

Animals↗

11C-methionine kinetics in pregnant rhesus monkeys studied by positron emission tomography: a new approach to feto-maternal metabolism.

By use of Positron Emission Tomography (PET), dynamic studies of the metabolism within the feto-maternal unit can be performed using various tracers. Many compounds like amino acids, carbohydrates, fatty acids and drugs can be performed using various tracers. Many compounds like amino acids, carbohydrates, fatty acids and drugs can be labelled with 11C and used as tracers. 11C-labelled L- or D-methionine was injected intravenously into pregnant Rhesus monkeys. The distribution of the radioactivity in maternal muscles, aorta, placenta and the liver of the fetus was quantitatively estimated as a function of time. Simultaneously blood, urine and amniotic fluid samples were analyzed for 11C-activity. The distribution of 11C between the high and the low molecular fraction of plasma (MW greater than 5000) was studied after gel filtration. Both when 11C-L- and D-methionine were given, the radioactivity rapidly crossed the placenta and was accumulated in the fetal liver. In the 11C-L-methionine experiments, about 70 per cent of the radioactivity in plasma was found in the high molecular fraction one hour after injection. A greater part of 11C-D-compared to 11C-L-activity was excreted in the urine.

Amniotic Fluid↗

Adverse effects on the brain in cardiac operations as assessed by biochemical, psychometric, and radiologic methods.

In order to describe subclinical brain injury in conjunction with cardiac operations 94 patients were prospectively studied with three brain injury assessment methods: CSF analyses 24 hours after bypass, psychometry, and computed tomography of the brain. Adenylate kinase (AK), a marker of ischemic brain cell injury, was measured in cerebrospinal fluid (CSF) and in serum. In 13% of the patients, a considerable increase in CSF-AK was seen, in 46% there was a moderate increase, and in 41% no or trivial increase. Psychometry measured as change between preoperative scores in a test battery (SS3) revealed a moderate decrease in intellectual function after operation. There was a significant inverse correlation between CSF-AK and SS3 (r = -0.46, p less than 0.001, r2 = 0.21, n = 71). Computed tomography (CT) of the brain was performed preoperatively and postoperatively in 54 patients. Two of these had cerebral infarctions visible on the CT, despite an essentially normal postoperative state. There was no correlation between indices of brain injury and patient diagnosis and length of perfusion. It is concluded that subclinical brain injury is often seen after cardiac operations. Most often the injury appears trivial and/or reversible, but in a minority of cases there is evidence that the brain injury is irreversible. Factor analysis favors the view that the microembolism theory might no longer be a valid concept in modern cardiopulmonary bypass (CPB). Instead, circumstances in the operative field seem more likely to be important causative factors. This interpretation calls for new principles in the search for an improved cerebral protection during cardiac operations.

Adenylate Kinase↗

Discrepancies in brain tumor extent as shown by computed tomography and positron emission tomography using [68Ga]EDTA, [11C]glucose, and [11C]methionine.

A patient with an anaplastic (malignant) astrocytoma was examined with computed tomography (CT) and with positron emission tomography (PET), in the latter case using [68Ga]EDTA, [11C]glucose, and [11C]methionine. The CT examination as well as the [68Ga]EDTA study showed a small tumor located in the region of the head of the left caudate nucleus. The [11C]glucose examination showed increased uptake on the same region, as did the [11C]methionine examination, but the latter also showed a considerable uptake in the entire left thalamic region. The patient died 15 days after the [11C]methionine study and a histologic evaluation of thin sections obtained at autopsy showed excellent agreement between tumor extent and activity distribution after [11C]methionine administration. The tumor tissue seen only with [11C]methionine was histologically different from that part of the tumor observed with the other tracers. Although cytologically similar, the latter showed large necrotic areas and an ability to induce marked endothelial proliferation, whereas in the former neither necroses nor notable endothelial proliferation was seen. In this case more than 50% of the tumor would have remained radiologically imperceptible without the [11C]methionine PET examination.

Astrocytoma↗

Reliability of computed tomography in assessing histopathological features of malignant supratentorial gliomas.

A new method was developed whereby close comparisons can be made between components of a computed tomography (CT) image and neuropathological findings. This was achieved by a combination of intravital (terminal) CT, postmortem CT, and whole brain sectioning of formalin-fixed tissue. The method was applied in seven cases of malignant supratentorial astrocytic gliomas (Kernohan Grades III and IV) and in one case of thalamic ependymoma. The glioblastoma-like parts of the astrocytic gliomas were usually correctly delineated by postcontrast CT, although there were exceptions to this rule. Tumor components consisting of diffusely growing malignant astrocytoma were difficult or impossible to delineate by CT. Necrotic areas within the tumors were accurately outlined by postcontrast CT. Peritumoral edema was correctly delineated by CT, but growth of diffuse astrocytoma or the presence of astrocytic gliosis within this edematous area seems difficult or impossible to evaluate by current CT techniques.

Adult↗

Psychological profile related to malignant tumours of different histopathology.

In a previous preoperative study of patients with gliomas, we made the original observation that patients with high grade as opposed to those with low-grade gliomas have a psychological profile marked by extreme emotional reactivity. In this postoperative study of the psychological profiles of patients with breast cancer, the main funding was unexpectedly analogous with the findings in the brain tumour study. The patients with poorly differentiated ductal carcinomas showed a specific and, compared to the patients with well differentiated carcinomas, outstanding psychological profile marked by extreme emotional reactivity as well as by genuine creativity. Some of the present patients with well differentiated carcinomas showed personality profiles marked by compulsive inhibition, also described earlier in the literature of patients with breast cancer. The psychobiological relations between emotional reactivity and aggressiveness of tumour growth are discussed.

Adaptation, Psychological↗

Placental transfer of methionine during protein restriction in the rhesus monkey studied by position emission tomography.

Four pregnant Rhesus monkeys were given a 1 week protein restricted diet with the objective to monitor possible effects on transplacental transfer of [11CH3]-L-methionine with positron emission tomography (PET). The weight was reduced in all monkeys, two of which later had an intrauterine fetal death. The mean venous serum concentrations of free methionine in the mothers were not significantly changed during the study period, although a tendency towards lower values during protein restriction was noted like in the majority of the amino acids. The uptake of trace amount of [11CH3]-L-methionine in the fetus was studied with PET before the reduced diet, after 1 week on the reduced diet and after the return to a habitual diet. Our results indicate an increase in the uptake of radioactivity in the amniotic cavity after protein restriction. The PET-technique in its present form seems to be a useful method in the investigation of transplacental transfer of several natural amino acids as well as of other compounds labelled with 11C.

Animals↗

Tacrine restores cholinergic nicotinic receptors and glucose metabolism in Alzheimer patients as visualized by positron emission tomography.

Three patients with Alzheimer's disease, a 68-year-old woman with mild dementia and 2 men (aged 64 and 72 years) with moderate dementia were treated orally with the cholinesterase inhibitor tacrine (tetrahydroaminoacridine), 80 mg daily, for several months. The patients were investigated using positron emission tomography (PET) prior to, and after 3 weeks and 3 months of treatment. The PET studies involved a multi-tracer system consisting of [18F]-fluoro-deoxy-glucose (18F-FDG) (tracer for glucose metabolism); 11C-butanol (cerebral blood flow) and (S)(-)- and (R)(+)-[N-11C-methyl]-nicotine (nicotinic receptors; cholinergic neural activity). Tacrine treatment increased the uptake of 11C-nicotine to the brain. Significant reduced difference in uptake between the two enantiomers (S)(-)- and (R)(+)11C-nicotine was observed in the frontal and temporal cortices after tacrine treatment in all three patients. The kinetic analysis indicated increased binding of (S)(-)11C-nicotine in brain compatible with a restoration of nicotinic cholinergic receptors. The most pronounced effect was observed after 3 weeks and 3 months treatment in the patient with mild dementia. An increase in cerebral glucose utilization was found in the 68-year-old patient with mild dementia but also slightly in the 64-year-old man with moderate dementia when treated with tacrine for 3 months. Tacrine administration did not affect cerebral blood flow. The PET data obtained after 3 weeks of tacrine treatment was paralleled by improvement in neuropsychological performance. This study shows in vivo by PET neurochemical effects induced in brain by treatment with tacrine to Alzheimer patients. Intervention with tacrine in the early course of the disease might be necessary for clinical improvement.

Aged↗

Positron emission tomography with ([11C]methyl)-L-methionine, [11C]D-glucose, and [68Ga]EDTA in supratentorial tumors.

Sixteen patients with supratentorial tumors were examined with positron emission tomography (PET) using [( 11C]methyl)-L-methionine, [11C]D-glucose, and [68Ga]EDTA as well as CT. There were nine astrocytomas (grade II), three oligoastrocytomas (grade II), two anaplastic astrocytomas (grade III), and two meningiomas. Six patients with low-grade astrocytomas and all three patients with oligoastrocytomas had an accumulation of [11C]methionine varying from slightly to intensely increased as compared with normal brain tissue. There was a markedly increased uptake of methionine in the anaplastic astrocytomas. Three of the low-grade astrocytomas had a decreased uptake of [11C]methionine in at least part of the tumor as compared with normal brain tissue. Contrast enhancement on CT or uptake of [68Ga]EDTA was not a prerequisite for increased accumulation of methionine. Uptake of [11C]glucose was lower than or equal to that of normal brain tissue in the low-grade tumors and also in one of the two anaplastic astrocytomas and in the bulk of the other. In each individual case the methionine uptake tended to be higher--or less decreased--than the glucose uptake. In the low-grade tumors the uptake of methionine and that of glucose were often different, occasionally markedly different, as far as the tumoral-peritumoral areas involved. These differences were even more remarkable in the two anaplastic astrocytomas. An increased uptake of methionine was often seen in areas appearing normal on CT. It appears that PET with [11C]glucose has limitations with regard to delineation of the low-grade astrocytomas, whereas PET with [11C]methionine usually better reflects the extent of these tumors and, to a lesser degree, the extent of the high-grade neoplasms. The results of PET with [68Ga]EDTA were similar to those with postcontrast CT in most patients. The two meningiomas exhibited a high uptake of all tracers used for PET as well as a marked contrast enhancement on CT. The extent of the meningiomas judged by PET with the various tracers correlated well with the extent assessed by postcontrast CT.

Adult↗

Positron emission tomography and computed tomography in differential diagnosis between recurrent or residual glioma and treatment-induced brain lesions.

In previous studies of supratentorial gliomas with positron emission tomography (PET) and computed tomography (CT), high uptakes of L-methyl-11C-methionine (11C-L-methionine) were found even in astrocytomas without blood-brain barrier defects as judged by CT or 68Ga-EDTA PET. In a number of patients examined after radiation therapy, there were no consistent changes in the high uptake values. In the present investigation PET and CT were compared with regard to their abilities to visualize and delineate recurrent tumors and treatment-induced brain defects and to differentiate between them. The study was undertaken on four patients who were long-term survivors after treatment for high-grade gliomas. For PET, 11C-L-methionine and 68Ga-EDTA were used. In two patients recurrent/residual tumors appeared considerably larger with 11C-L-methionine PET than with CT or 68Ga-EDTA PET. In one patient, no signs of recurrence were seen with any of these three methods, and in a fourth patient, whose condition was clinically stable, the findings at PET with 11C-L-methionine were non-specific. In areas corresponding to the surgical parenchymal defects, the 11C-L-methionine uptake and, except in one case, the local blood volume was markedly reduced. PET with 11C-L-methionine thus has a potential for distinguishing between postoperative brain lesions and tumor recurrence with a higher accuracy than CT.

Adult↗

Comparison of the accumulation kinetics of L-(methyl-11C)-methionine and D-(methyl-11C)-methionine in brain tumors studied with positron emission tomography.

Five patients with glioma were examined with positron emission tomography after the administration of 11C-L-methionine and at a following day with 11C-D-methionine. The rates of accumulation of the tracers were determined in the tumor and in the normal brain tissue according to a graphical technique of Patlak et coll. The accumulation rates for L-methionine were on the average 2.4 times higher than those of D-methionine in the tumors. The corresponding ration for normal brain tissue was 2.3. It is concluded that in this group of tumors without obvious blood-tumor-barrier breakdown, a stereospecific process with similar properties as in the normal brain tissue, is responsible for the accumulation of the labelled methionine.

Astrocytoma↗

Dynamic study of supratentorial gliomas with L-methyl-11C-methionine and positron emission tomography.

The regional kinetics of intravenously injected L-methyl-11C-methionine (11C-L-methionine) in the brain was investigated by positron emission tomography (PET) in 14 patients with gliomas. In both tumor and unaffected brain the tracer uptake reached a nearly constant level in 5 min or less. The ratio between the uptake of 11C-L-methionine by high-grade tumors and the uptake by unaffected brain was 1.9-4.8. In two cases of low-grade astrocytoma the ratio was 0.8-1.0. High uptakes of 11C-L-methionine occurred in gliomas even in the absence of blood-brain barrier defects as observed by other methods. This indicates that besides active transport of amino acid, a larger extracellular space in tumor as compared with unaffected brain tissue may also contribute to the increased uptake of 11C-L-methionine--derived radioactivity. In some patients delineation of the tumors was improved by use of PET with 11C-L-methionine as compared with computed tomography, angiography, and, in some instances, PET with 68Ga-EDTA. PET with 11C-L-methionine permits better evaluation of the tumor extent and may affect preoperative grading.

Adult↗