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Biomedical subjects

M Diksic

Publications and source records attributed to M Diksic.

At least 127 records · Page 7Linked to original sources
PubMed1987

Estimation of cerebral oxygen utilization rate by single-bolus 15O2 inhalation and dynamic positron emission tomography.

This study shows that regional CMRO2 can be estimated by means of nonlinear regression using dynamic positron emission tomographic data acquired during 1 min following single-bolus inhalation of 15O2. The feasibility of simultaneous estimation of CBF, cerebral blood volume (CBV), oxygen extraction ratio (OER), and CMRO2 was assessed by simulations using the model of Mintun et al. Four oxygen metabolic measurements, each consisting of a CBF, CBV, and 15O2 bolus study, were carried out on three volunteers. Regional values for CBF, CBV, OER, and CMRO2 were derived in two ways: from the fits of the time-activity curves of the dynamic 15O2 bolus study alone [CMRO2(fit)] and from the three separate studies [CMRO2 (control)]. For the 56 regions of interest analyzed, using a fit interval of 60 s, CMRO2(fit) was 93.4 +/- 7.8% of CMRO2(control) (mean +/- SD) with a correlation coefficient of r = 0.95. CMRO2(control) ranged from 87 to 290 mumol/min/100 g. Individual simultaneous estimates of CBF, CBV, and OER were not reliable. Finally, we found that the validity of the model was limited in practice to the first minute after tracer inhalation.

Administration, Inhalation↗
PubMed1987

Hemodynamic and metabolic effects of cerebral revascularization.

Pre- and postoperative positron emission tomography (PET) was performed in six patients undergoing extracranial to intracranial bypass procedures for the treatment of symptomatic extracranial carotid occlusion. The six patients were all men, aged 52 to 68 years. Their symptoms included transient ischemic attacks (five cases), amaurosis fugax (two cases), and completed stroke with good recovery (one case). Positron emission tomography was performed within 4 weeks prior to surgery and between 3 to 6 months postoperatively, using oxygen-15-labeled CO, O2, and CO2 and fluorine-18-labeled fluorodeoxyglucose. Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rates for oxygen and glucose (CMRO2 and CMRGlu), and the oxygen extraction fraction (OEF) were measured in both hemispheres. Preoperatively, compared to five elderly control subjects, patients had increased CBV, a decreased CBF/CBV ratio, and decreased CMRO2, indicating reduced cerebral perfusion pressure and depressed oxygen metabolism. The CBF was decreased in only one patient who had bilateral carotid occlusions; the OEF, CMRGlu, and CMRO2/CMRGlu and CMRGlu/CBF ratios were not significantly different from control measurements. All bypasses were patent and all patients were asymptomatic following surgery. Postoperative PET revealed decreased CBV and an increased CBF/CBV ratio, indicating improved hemodynamic function and oxygen hypometabolism. This was associated with increased CMRO2 in two patients in whom the postoperative OEF was also increased. The CMRGlu and CMRGlu/CBF ratio were increased in five patients. Changes in CBF and the CMRO2/CMRGlu ratio were variable. One patient with preoperative progressive mental deterioration, documented by serial neuropsychological testing and decreasing CBF and CMRO2, had improved postoperative CBF and CMRO2 concomitant with improved neuropsychological functioning. It is concluded that symptomatic carotid occlusion is associated with altered hemodynamic function and oxygen hypometabolism. Cerebral revascularization results in decreased CBV, indicating improved hemodynamic reserve, but does not consistently improve oxygen metabolism.

Aged↗
PubMed1987

Radiation dose to upper airways from inhaled oxygen-15 carbon dioxide.

According to Powell et al., significant retention of 15O in the tracheal mucosa results in a radiation absorbed dose of 75 to 200 rad upon breathing of 15O-CO2 for one hour at 1 mCi/liter. Such a high dose would seriously compromise the 15O-CO2 inhalation method for positron emission tomographic (PET) measurement of cerebral blood flow (CBF). In order to verify these results, we have assayed 15O activity in the tracheal region of three volunteers by PET during inhalation of 15O-CO2 and 15O-O2. Using methods similar to those of the above authors for estimating absorbed dose in the tracheal mucosa, we have obtained a value of 14-38 rad, which is more in keeping with 3-5 rad found by Bigler et al. from direct assay of mucus and saliva. We conclude that the 15O-CO2 inhalation method is a safe and practical means of measuring CBF by PET.

Carbon Dioxide↗
PubMed1987

Metabolic and hemodynamic evaluation of gliomas using positron emission tomography.

Positron emission tomography (PET) was used on 16 patients with untreated cerebral gliomas to measure cerebral glucose and oxygen metabolism, oxygen extraction, blood flow, and blood volume. In addition, pH values were obtained for seven cases. Gliomas were later proven by biopsy; two patients had tumors with degrees of malignancy of grade II, two patients had grade III, and 12 patients had grade IV tumors. Compared with homologous gray matter regions in the opposite hemisphere, tumor tissue showed increased blood volume, but decreased oxygen extraction and oxygen metabolism. Compared with grade II tumors, grade IV tumors demonstrated higher blood volumes, but lower relative oxygen extraction and utilization. Tumor blood flow was variable, but was lower in the higher grade tumors. Rates of glucose utilization in tumor, calculated by using individually determined rate constants, were variable, and did not correlate with tumor size or tumor grade. Parietal tumors (n = 6) tended to have higher relative glucose utilization and blood flow, and lower relative oxygen extraction, when compared with frontal tumors (n = 4). Tumor pH differed significantly from the pH in contralateral brain (p less than 0.005); alkalotic pH values were consistently seen. These findings in and around cerebral gliomas studied before intervention differ from the results found in gliomas after exposure to radiation or chemotherapy.

Blood Volume↗
PubMed1987

Alternative approach to estimate lumped constant in the deoxyglucose model: simulation and validation.

An alternative method of estimating the lumped constant (LC) in the deoxyglucose model was developed. The LC was estimated using data obtained during the first 10 min after injection of the tracer by a nonlinear least-squares (NLSQ) method. The method does not require a constant plasma concentration. This approach was evaluated in a computer simulation by adding different levels of noise and considering various input functions. Errors in the estimated LC in this and Sokoloff et al.'s conventional method were compared. We found that the approach proposed here results in more reliable estimates of LC. The study in completed in a shorter experimental period, and any shape of the input function can be used. The new technique was then applied to measure whole brain LC and rate constants in cat brain for 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG). Measured mean value (+/-s.e.m.) for the whole brain LC = 0.443 +/- 0.012 (N = 7), for the whole brain k2* = 0.124 +/- 0.009 and k3* = 0.024 +/- 0.001 (N = 7).

Animals↗
PubMed1986

Effect of vascular activity in the determination of rate constants for the uptake of 18F-labeled 2-fluoro-2-deoxy-D-glucose: error analysis and normal values in older subjects.

Regional cerebral blood volume (CBV) can be calculated using data obtained during the kinetic analysis of 18F-labeled 2-fluoro-2-deoxy-D-glucose (FDG) uptake measured by positron emission tomography (PET). As a result the influence of vascular activity upon the determination of FDG rate constants can be minimized. The method is investigated by simulation experiments and by analysis of PET studies on seven older, healthy human volunteers aged 52-70 years. The accuracy of measured FDG rate constants k1, k2, and k3, obtained either by omitting the early portion of the uptake curve or by explicit inclusion of CBV as a fit parameter, is compared. The root mean square error in measured rate constant for the latter method is equivalent to that obtained by omitting the first 2.5-3 min of tissue data and neglecting the CBV term. Hence, added information about the physiological state of the tissue is obtained without compromising the accuracy of the (FDG) rate constant measurement. In hyperemic tissue the explicit determination of the vascular fraction results in more accurate estimates of the FDG rate constants. The ratio of CBV determined by this method to CBV obtained using C15O in six subjects with CBV in the normal range was 0.92 +/- 0.32. A comparison of the CBV image obtained by this method with that obtained using C15O in an arteriovenous malformation case demonstrates the accuracy of the approach over a wide range of CBV values. The mean value for CBV fraction in gray matter obtained by this method in the older control group was 0.040 +/- 0.014. Average gray matter rate constants obtained were k1 = 0.084 +/- 0.012, k2 = 0.150 +/- 0.071, and k3 = 0.099 +/- 0.045 min-1.

Aging↗
PubMed1986

Effects of rapid mannitol infusion on cerebral blood volume. A positron emission tomographic study in dogs and man.

Positron emission tomography was used to study the effect of a rapid infusion of mannitol on cerebral blood volume (CBV) in five dogs and in three human subjects. The ability of mannitol to reduce intracranial pressure (ICP) has always been attributed to its osmotic dehydrating effect. The effects of mannitol infusion include increased osmolality, total blood volume, central venous pressure (CVP), and cerebral blood flow, and decreased hematocrit, hemoglobin concentration, serum sodium level, and viscosity. Mannitol's ability to dilate the cerebral vasculature, either directly or indirectly, and thus to transiently increase ICP, is a subject of controversy. By in vivo labeling of red cells with carbon-11, the authors were able to demonstrate an early increase in CBV in dogs of 20%, 27%, and 23% (mean increase, p less than 0.05) at 1, 2, and 3 minutes, respectively, after an infusion of 20% mannitol (2 gm/kg over a 3-minute period). The animals' muscle blood volume increased by 27% (mean increase, p less than 0.05) 2 minutes after infusion. In the human subjects, lower doses and a longer duration of infusion (1 gm/kg over 4 minutes) resulted in an increase in CBV of 8%, 14% (p less than 0.05), and 10% at 1, 2, and 3 minutes, respectively, after infusion. In dogs, ICP increased by 4 mm Hg (mean increase, p less than 0.05) 1 minute after the infusion, before decreasing sharply. The ICP was not measured in the human subjects. Hematocrit, hemoglobin, sodium, potassium, osmolality, heart rate, mean arterial pressure (MAP), and CVP were measured serially. Results of these measurements, as well as the significant decrease in MAP that occurred after mannitol infusion, are discussed. This study demonstrated that rapid mannitol infusion increases CBV and ICP. The increase in muscle blood volume, in the presence of a decreased MAP and an adequate CVP, suggests that mannitol may have caused vasodilation in these experiments.

Adult↗
PubMed1986

High yield synthesis of 6-[18F]fluoro-L-dopa by regioselective fluorination of protected L-dopa with [18F]acetylhypofluorite.

Regioselective fluorination of a completely protected phosgene derivative of 3,4-dihydroxy-phenyl-L-alanine (5-(benzyl-3',4'-carbonate)-oxazolidine-2,5-dione) with gaseous 18F-labeled acetylhypofluorite and [18F]F2 in acetonitrile is described. Fluorination with [18F]acetylhypofluorite yields 6-[18F]fluoro-L-dopa with 95% radiochemical purity; fluorination of the same substrate with [18F]F2 yields a mixture of all three structural isomers in a ratio of 70:16:14 for 6-, 5-, and 2-fluoro compounds. Radiochemical yield, relative to [18F] acetylhypofluorite, measured at the end of the synthesis, is (21 +/- 4)% (N = 8). The synthesis requires approximately 40 min (50 min if HPLC was done) and yields the final radiopharmaceutical in a two-step procedure. The specific activity of the final product was approximately 763 mCi/mmol at the end of a 40-min synthesis when 30-min irradiation was used.

Acetates↗
PubMed1986

Pharmacokinetics of superselective intra-arterial and intravenous [11C]BCNU evaluated by PET.

The pharmacokinetics of i.v. and superselective intra-arterial carbon-11 1,3-bis-(2-chloroethyl)-1-nitrosourea ([11C]BCNU) were directly compared for the first time in ten patients with recurrent gliomas using positron emission tomography (PET). Intra-arterial administration of [11C]BCNU achieved concentrations of the drug in the tumor that averaged 50 times higher than with a comparable i.v. dose. These preliminary results suggest that the degree of early metabolic trapping of BCNU in tumor correlates with the clinical response to this chemotherapy.

Adult↗
PubMed1985

Pharmacokinetics of 11C-BCNU in experimental brain tumor.

Wistar rats implanted intracerebrally with AA ascites tumor were injected seven or eight days later with 11C-labelled BCNU. Radioactive compounds in samples of plasma, tumor, and contralateral brain were identified after injection at intervals by doing chloroform extraction and thin layer radiochromatography. At 60 min after injection radioactivity levels were 56% higher in the tumor than in contralateral brain. This increase was due mainly to 2-chlorethyl isocyanate, which binds to amino groups and/or nucleic acid. The results demonstrated both a higher concentration and a faster decomposition of BCNU in the tumor.

Animals↗
PubMed1985

Regional glucose utilization and blood flow in experimental brain tumors studied by double tracer autoradiography.

Coupling of regional glucose utilization (GLU) and blood flow (CBF) was examined in rats with implanted brain tumors (AA ascites tumor) by quantitative double tracer autoradiography using 18F-2-fluorodeoxyglucose and 14C-iodoantipyrine. Four to 13 days after implantation, the animals were injected with the two tracers to obtain autoradiograms from the same brain section before and after the decay of 18F. The autoradiograms were then analyzed by an image processor to obtain a metabolic coupling index (MCI = GLU/CBF). In the tumor, high GLU and low CBF were uncoupled to give a high MCI which implied anerobic glycolysis. In large tumors, the CBF was even lower. In the peri-tumoral region, GLU was reduced (especially in gray matter) and reduction was lowest around the larger tumors. CBF in the peri-tumoral region was also reduced, but this reduction became less as the distance from the tumor margin increased. These changes in the peri-tumoral region may be secondary to edema. The GLU and CBF of white matter was little influenced by the presence of tumors except for some reduction in these values in relation to the larger tumors. On a narrow margin of tumor and brain, corresponding to a zone of increased vascularity, CBF was moderately high. The MCI in the tumor was higher than in the cortex of the same as well as the opposite hemisphere. These findings indicate that the metabolism and blood flow of the tumor and surrounding brain are variable and directly related to tumor size.

Animals↗
PubMed1985

Mild and regiospecific synthesis of 18F-labelled vinyl fluoride using [18F]fluorine reacted with silane.

A labelled vinyl fluoride of biological interest was prepared in good radiochemical yield by direct fluorination of the corresponding silane. The synthesis of 18F-labelled 4-fluoroantipyrine, a cerebral blood flow tracer, involved the reaction of 4-(trimethylsilyl) antipyrine with [18F]F2 (0.5% fluorine in neon) or 5% F2 in nitrogen in freon-11 as solvent. A radiochemical (chemical) yield of about 18% (42%) was obtained in a 25-min synthesis. The radiochemical and chemical purity of the final products was 99% after purification by HPLC.

Acrylic Resins↗
PubMed1985

Quantification of glucose utilization in an experimental brain tumor model by the deoxyglucose method.

Reevaluation of lumped and rate constants is necessary when Sokoloff's 2-deoxyglucose (DG) method is used to measure glucose utilization in pathological tissue. We describe here a modification of Sokoloff's lumped constant measurement that permits simultaneous estimation of both lumped and rate constants from a single animal experiment. A subcutaneous tumor model (AA ascites tumor) was used for measurement of these constants with a procedure similar to Sokoloff's that kept the plasma tracer concentration constant. Measured constants were as follows: lumped constant, 0.654 +/- 0.081; k1, 0.196 +/- 0.038 min-1; k2, 0.262 +/- 0.067 min-1; k3, 0.117 +/- 0.044 min-1. These constants were used to quantify glucose utilization in the implanted brain tumor. To test the validity of this method, we compared a fraction of the free DG pool calculated using the tumor constants with a fraction measured directly by chromatographic analysis of tissue samples from both subcutaneous tumor and implanted brain tumor. The values derived by chemical analysis agreed well with those predicted by the calculations. The value of k4 varied from 0.0031 +/- 0.0018 min-1 for the tumor tissue to 0.0214 +/- 0.0024 min-1 for tumors with a large necrotic center. This method would be especially useful when applied to xenograft human gliomas in nude mice for quantification of glucose utilization in human gliomas by means of positron emission tomography.

Animals↗
PubMed1985

[Cerebral blood flow, cerebral oxygen metabolism, cerebral glucose metabolism, and tissue pH in human acute cerebral infarction using positron emission tomography].

It is necessary for treatment and deciding prognosis to make clear about changes of cerebral blood flow and metabolism in acute cerebral infarction. This preliminary PET study was designed to investigate physiological and biochemical changes in acute cerebral infarction by positron emission tomography (PET). PET studies were performed in six patients with acute cerebral infarction within 48 hours after onset of stroke using continuous inhalation of C15O2 for cerebral blood flow (CBF), 15O2 for cerebral metabolic rate for oxygen (CMRO2), 11CO for cerebral blood volume, the intravenous injection of 11C-dimethyloxazolidinedione for tissue pH and the intravenous injection of 18F-fluorodeoxyglucose for cerebral metabolic rate for glucose (CMRGlu). Metabolic coupling index (MCI) image was made from CBF image and CMRGlu image to investigate relation between CBF and CMRGlu. Also oxygen glucose index (OGI) image was made from CMRO2 image and CMRGlu image to investigate relation between CMRO2 and CMRGlu. Preliminary results demonstrate that reduction of CBF, CMRO2, and CMRGlu in the affected cortex except for reperfusion case. Increase of OER was recognized four of six cases. Patterns of MCI and OGI in the cortex which CMRO2 value is less than 65 mumol/100 g/min were different from those in the cortex which CMRO2 value is more than 65. MCI of the affected cortex (CMRO2 less than 65) decreased relative to that of the cortex (CMRO2 greater than or equal to 65). OGI of the affected cortex (CMRO2 less than 65) significantly decreased in comparison with that of the cortex (CMRO2 greater than or equal to 65).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1985

New synthesis of fluorine-18-labeled 6-fluoro-L-dopa by cleaving the carbon-silicon bond with fluorine.

A new synthesis of 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine using 6-trimethylsilyl-3,4-dimethoxy-L-dopa-ethylester as a fluorination substrate is described. The silane is prepared from the corresponding bromo compound by reacting the latter with magnesium and trimethylsilyl chloride. Reaction of the silane with [18F]F2 (0.5% F2 in neon) in a mixture of freon-11/CCl4 (1:1) kept in a dry ice bath, subsequent hydrolysis with concentrated HBr in a bath at 140 degrees C, and simple chromatographic purification yielded 18F-labeled 6-fluoro-L-dopa. A radiochemical yield of about 8% was achieved at the end of the 1-hr synthesis. The specific activity at the end of the synthesis was about 680 mCi/mmol after a 30-min irradiation.

Chemical Phenomena↗
PubMed1984

Improved synthesis and low-temperature autoradiographic evaluation of 18F-n-fluoropropane as a myelin tracer for positron emission tomography.

An improved synthesis of the lipophile 18F-fluoropropane, yielding 30-45 mCi 18F-labelled radiopharmaceutical, is described. The radiochemical yield was 55%-66% determined at the end of a 1-h synthesis. Radiochemical and chemical purity of 18F-fluoropropane was 99% as determined by gas chromatography. Low-temperature autoradiography was used to investigate the lipophile 18F-n-fluoropropane as a myelin tracer for use with positron emission tomography. The white to grey matter ratio based on autoradiograms 12 min after administration of the radiotracer was 2:1, the highest reported to date.

Animals↗
PubMed1984

Positron emission tomography.

One of the most exciting new techniques introduced in the last ten years is positron emission tomography (PET). PET provides quantitative, three-dimensional images for the study of specific biochemical and physiological processes in the human body. This approach is analogous to quantitative in vivo autoradiography but has the added advantage of permitting non-invasive in vivo studies. PET scanning requires a small cyclotron to produce short-lived positron emitting isotopes such as oxygen-15, carbon-11, nitrogen-13 and fluorine-18. Proper radiochemical facilities and advanced computer equipment are also needed. Most important, PET requires a multidisciplinary scientific team of physicists, radiochemists, mathematicians, biochemists and physicians. This review analyses the most recent trends in imaging technology, radiochemistry, methodology, and clinical applications of positron emission tomography.

Adolescent↗