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Biomedical subjects

A Syrota

Publications and source records attributed to A Syrota.

At least 109 records · Page 6Linked to original sources

[The role of isotope methods in evaluating the left ventricular function].

Cardiac angioscintigraphy is a non-invasive, reproducible and reliable technique used to obtain a number of cardiac function parameters, the most important of which is left ventricular ejection fraction. Methodologically, the examination is simple. Fourier's analysis (a mathematical decomposition of ventricular mechanics) provides additional information on some abnormalities and is particularly useful in segmental kinetics studies and in the topographical diagnosis of cardiac rhythm disorders. The technique is indicated mainly for prognostic evaluation and follow-up of patients with left ventricular dysfunction. Metaiodobenzylguanidine (MIBG) cardiac scintigraphy makes it possible to evaluate the reuptake of noradrenaline by neurons, which represents the inactivation pathway of adrenergic neurotransmission and is the principal factor of noradrenaline extraction. MIBG scintigraphy is an indirect way of evaluating left ventricular function in congestive heart failure, as suggested by the results of studies showing correlations between MIBG uptake, left ventricular function indices and disease severity as judged on the basis of evolutive parameters.

3-Iodobenzylguanidine↗

[Spectroscopy of the liver in vivo using nuclear magnetic resonance. A new approach in hepatic physiopathology].

Nuclear magnetic resonance (NMR) spectroscopy is a non-invasive means of detecting numerous compounds, thus enabling real-time studies to be carried out on such topics as energy metabolism, intracellular pH and main intermediate metabolism pathways. This method has been used for several years to study perfused livers and rat livers in vivo, but its application to man has just begun. We describe some of its principal uses, with emphasis on the possibilities it offers to investigate the metabolic pathways. With the rapid advances made in this field, and particularly spectroscopic imaging, NMR spectroscopy should prove valuable in four main branches of research: understanding of physiological and pathological metabolic mechanisms, diagnosis with the possibility of functional tests, follow-up and assessment of new medical treatments, and pharmacology.

Carbon Isotopes↗

Discriminant factor analysis of 31P NMR spectroscopic data in myopathies.

Discriminant factor analysis (DFA) enables one to distinguish among diagnostic groups using diagnostic variables. It provides discriminant functions that are linear combinations of the diagnostic variables and that optimally separate diagnostic groups. It was used to enhance the accuracy of 31P NMR data in the diagnosis of myopathies. DFA allowed a good separation of normal subjects, congenital neuromuscular disorders with type I fiber predominance, and McArdle's diseases. It elicited an unexpected homogeneity of idiopathic rhabdomyolyses, the metabolic origin of which is unknown, and suggested that the abnormality could involve the mitochondrial oxidative metabolism in some of them. In mitochondrial myopathies, an expected heterogeneity is shown by DFA. It may allow an automatic diagnosis of some myopathies from 31P NMR data or guide biochemists by comparing biochemical features of a new patient to those of previously established groups.

Adult↗

Spectroscopic MRI: a tool for the evaluation of systemic lipid storage disease.

Spectroscopic MR imaging allows to measure the lipid content of a region inside the human body. This technique has been applied to the case of a woman with a severe multisystemic triglyceride storage disease. Lipid contents of liver, pancreas, kidneys, left ventricle, skeletal muscles (calves, thighs, arms) were measured by using the Dixon spectroscopic imaging sequence. In some heterogeneous muscles, localized proton spectra were recorded. Results agreed with clinical findings (muscle weakness, normal renal and cardiac function, diabetes). These techniques could help to quantify the severity of the disease and to follow up its evolution under therapy.

Adult↗

Filters and Fourier analysis of gated blood pool studies: a search for the optimal combination.

Fourier analysis of gated blood pool studies is performed after filtering the raw data by a spatial median 3 x 3, 9 x 9 or temporo-spatial 9 x 9 x 9 filter. 20 patients and a dynamic cardiac phantom were studied to determine the quantitative effects of these filters and of multiharmonic Fourier filtering (MHFF). The filtered MHFF data, with or without preprocessing, were compared with a 3 D or 2 D filter to the raw data using a chi 2 distribution. The MHFF (two or three harmonics) procedure applied to the raw data of patients without any preprocessing produced the smallest chi 2 value, thus demonstrating the very close relationship between filtered images and raw data. Preprocessing the raw data by the median filter also preserved the signal when two or three harmonics were applied, whereas the 3 D and 2 D (9 x 9) filters did not. The phantom study also demonstrated that MHFF preserved the signal better than any other preprocessing. The median filter introduced a smaller distortion than the 2 D (9 x 9) and 3 D filters. It is concluded that MHFF applied with two or three harmonics on the raw data or after preprocessing by a median (3 x 3) filter is the most successful way of preserving the real signal. It is believed that the other filters should be avoided. The clinical advantage of MHFF processing is to provide both very accurate filtering and parametric images.

Fourier Analysis↗

Identifiability analysis and parameter identification of an in vivo ligand-receptor model from PET data.

Identifiability problem is a very important topic in the framework of model justification and not accounting for it during the modeling procedure can lead to meaningless results. While studying the receptor-ligand model parameter estimation from dynamic positron emission tomography data, each of the three possible conclusions to the identifiability problem (i.e., unidentifiable model, multiple solutions, or unique solution) are reached depending on the experimental protocol used. The identification of the model parameters from data obtained with a single tracer injection leads to disappointing numerical results since most of the parameters have to be considered as unidentifiable. A protocol including two injections, a first injection of the labeled ligand and a second injection of the cold ligand (displacement experiment) leads to two very different numerical solutions, which is surprising since such multiplicity of solutions was not indicated by a preliminary theoretical identifiability study. We show that a three-injections protocol, including both a displacement and coinjection experiment, allows to determine which of these two solutions is biologically valid.

Animals↗

Noninvasive quantification of muscarinic receptors in vivo with positron emission tomography in the dog heart.

The in vivo quantification of myocardial muscarinic receptors has been obtained in six closed-chest dogs by using positron emission tomography. The dogs were injected with a trace amount of 11C-labeled methylquinuclidinyl benzilate (MQNB), a nonmetabolized antagonist of the muscarinic receptor. This was followed 30 minutes later by an injection of an excess of unlabeled MQNB (displacement experiment). Two additional injections of unlabeled MQNB with [11C]MQNB (coinjection experiment) and without [11C]MQNB (second displacement experiment) were administered after 70 and 120 minutes, respectively. This protocol allowed a separate evaluation of the quantity of available receptors (B'max) as well as the association and dissociation rate constants (k+1 and k-1) in each dog. The parameters were calculated by using a nonlinear mathematical model in regions of interest over the left ventricle and the interventricular septum. The average value of B'max was 42 +/- 11 pmol/ml tissue, the rate constants k+1, k-1, and Kd were 0.6 +/- 0.1 ml.pmol-1.min-1, 0.27 +/- 0.03 ml.pmol-1.min-1, and 0.49 +/- 0.14 pmol.ml-1, respectively, taking into account the MQNB reaction volume estimated to 0.15 ml/ml tissue. Although [11C]MQNB binding would appear irreversible, our findings indicate that the association of the antagonist is very rapid and that the dissociation is far from negligible. The dissociated ligand, however, has a high probability of rebinding to a free receptor site instead of escaping into the microcirculation. We deduce that the positron emission tomographic images obtained after injecting a trace amount of [11C]MQNB are more representative of blood flow than of receptor density or affinity. We also suggest a simplified protocol consisting of a tracer injection of [11C]MQNB and a second injection of an excess of cold MQNB, which is sufficient to measure B'max and Kd in humans.

Animals↗

Left prefrontal glucose hypometabolism in the depressed state: a confirmation.

The resting-state cerebral metabolic rates for glucose of 10 severely depressed patients (seven bipolar and three unipolar) were compared, before and after treatment with tricyclic antidepressants, to those of 10 control subjects of similar age by means of positron emission tomography and the fluorodeoxyglucose method. Significant left-right prefrontal asymmetry was present in the patients before but not after successful treatment, suggesting that medication can reduce this asymmetry. Also, significant hypofrontality and whole-cortex hypometabolism were found in the patients in the depressed state and persisted in the treated state, despite clinical improvement, suggesting that these abnormalities are not state dependent.

Adult↗

Cardiac receptors studied by positron emission tomography.

Changes in number and/or affinity of cardiac neurotransmitter receptors have been associated with myocardial ischemia and infarction, congestive heart failure, cardiomyopathy, as well as diabetes or thyroid-induced heart muscle disease. These alterations of cardiac receptors have been demonstrated in vitro on membrane homogenates from samples collected mainly during surgery or post mortem. The disadvantage of these in vitro binding techniques is that receptors lose their natural environment and their relationships with the other components of the tissue. In vitro autoradiographic techniques in human tissue offer several advantages over homogenate-binding techniques: an increase in sensitivity and the possibility of anatomic resolution allowing light microscopic mapping of relationships between the distribution of specific cell populations and neurotransmitter receptors. However, the evolution of receptor changes as the disease progresses or as the effect of a drug cannot be analyzed. With the advent of positron emission tomography it is now possible to achieve, non-invasively, quantitative determination of regional biochemical processes in the heart.

Heart↗

MIBG scintigraphic assessment of cardiac adrenergic activity in response to altitude hypoxia.

High altitude hypoxia induces a decrease in the cardiac chronotropic function at maximal exercise or in response to isoproterenol infusion, suggesting an alteration in the cardiac sympathetic activation. Iodine-123 metaiodobenzylguanidine [( 123I]MIBG) was used to map scintigraphically the cardiac sympathetic neuronal function in six male subjects (aged 32 +/- 7 yr) after an exposure to high altitude that created hypoxic conditions. Results obtained just after return to sea level (RSL) were compared with the normal values obtained after 2 or 3 mo of normoxia (N). A static image was created as the sum of the 16-EKG gated images recorded for 10 min in the anterior view of the chest at 20, 60, 120, and 240 min after injection. Regions of interest were located over the heart (H), lungs (L), and mediastinum (M) regions. There was a significant decrease in the H/M and the L/M ratios in RSL compared to N condition. Plasma norepinephrine concentration was elevated during the stay at altitude but not significantly different in RSL compared to N. In conclusion, cardiac [123I]MIBG uptake is reduced after an exposure to altitude hypoxia, supporting the hypothesis of an hypoxia-induced reduction of adrenergic neurotransmitter reserve in the myocardium. Furthermore, the observed significant decrease in pulmonary MIBG uptake suggests an alteration of endothelial cell function after exposure to chronic hypoxia.

3-Iodobenzylguanidine↗

Improved detection of anterior left ventricular aneurysm with multiharmonic fourier analysis.

Single and multiharmonic Fourier analysis of LAO 30-45 degrees gated blood-pool studies were performed in a selected group of 30 patients with a left ventricular anterior aneurysm proven by contrast angiography. The sensitivity of the first harmonic phase image for the diagnosis of ventricular aneurysm was 80%. The clear phase shift (greater than 110 degrees) between the normal and the aneurysmal areas was missing in six patients. Peak acceleration images (negative maximum of the second derivative of the Fourier series) were calculated for each pixel with the analytical Fourier formula using two or three harmonics. A clear phase shift (greater than 126 degrees) than appeared in all the patients. This improvement was related to the increased weight of the second and third harmonics in the aneurysmal area when compared to control patients or to patients with dilative cardiomyopathy. Multiharmonic Fourier analysis clearly improved the sensitivity of the diagnosis of anterior left ventricular aneurysm on LAO 30 degrees-45 degrees gated blood-pool images.

Cardiomyopathy, Dilated↗

Correction of distortions due to the pulsed magnetic field gradient-induced shift in B0 field by postprocessing.

Gradient pulses used in most localization techniques induce time-dependent shifts in B0 that strongly distort NMR signals. A postprocessing correction method requiring no additional hardware is proposed. The phase shift produced by the B0 shift is calculated from a reference free induction decay (FID) and used to correct any FID acquired with the same sequence.

Magnetic Resonance Spectroscopy↗

Experimental design optimisation: theory and application to estimation of receptor model parameters using dynamic positron emission tomography.

The general framework and various criteria for experimental design optimisation are presented. The methodology is applied to the estimation of receptor-ligand reaction model parameters with dynamic positron emission tomography data. The possibility of improving parameter estimation using a new experimental design combining an injection of the beta+-labelled ligand and an injection of the cold ligand is investigated. Numerical simulations predict a remarkable improvement in the accuracy of the parameter estimates with this new experimental design and particularly the possibility of separate estimations of the association constant (k+1) and of the receptor density (B'max) in a single experiment. Simulation predictions are validated using experimental PET data in which parameter uncertainties are reduced by factors ranging from 17 to 1000.

Computer Simulation↗

[11C]L-methionine uptake in gliomas.

Treatment of gliomas remains disappointing in spite of a great number of experimental biological data and of randomized therapeutic studies. This could be partly explained by the inefficiency of our conventional methods to assess the regional metabolism of these tumors. The use of positron emission tomography (PET) brings encouraging possibilities in this field. We report our preliminary experience of measuring regional cerebral methionine uptake with PET after intravenous injection of [11C]L-methionine. Twenty-two patients with histologically confirmed gliomas were studied. An ECAT II positron emission tomograph was used for scanning. The position of the plane was chosen to include a major section of the tumor in the reconstructed brain slice. The protocol required a two-step examination: 1) after injection of 15 to 25 mCi of [11C]L-methionine, 12 scans were performed over a period of 46 minutes; and 2) 18 hours later, regional cerebral blood volume was measured in the same slice after intravenous injection of 2 to 4 mCi of 68GaCl3. The tumoral region of interest was determined as being the area of maximum activity. For each patient we calculated the ratio, R, between the activity in this tumor region of interest and the activity in the contralateral healthy symmetric region of interest which was used as an "internal standard" for the same patient. We correlated the ratio R with the histological grading. In 22 patients, mean values of R were calculated for each tumor: Grade II (n = 5): R = 1.04 +/- 0.27; Grade III (n = 5): R = 1.68 +/- 0.22; and Grade IV (n = 12): R = 2.33 +/- 0.86.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Regional cerebral blood flow by SPECT imaging in Sturge-Weber disease: an aid for diagnosis.

Regional cerebral blood flow (rCBF) was studied using SPECT (single photon emission computed tomography) with 133-Xenon in 13 patients with confirmed Sturge-Weber disease, aged 9 months to 18 years. CT scan, performed at the same time, showed evident cerebral angioma in 10 but not in three. A marked hypoperfused area was found in all patients, ranging from -32% to -72% and of the same location as the CT signs. The hypoperfusion seems to result from post ictal phenomenon as well as from chronic ischaemia. SPECT imaging is therefore a sensitive method for visualising intracranial angioma in Sturge-Weber disease and it provides an aid for diagnosis when a CT scan is not reliable.

Adolescent↗

In vivo investigation of myocardial perfusion, metabolism and receptors by positron emission tomography.

Positron emission tomography (PET) is a safe noninvasive visualization technique which gives an accurate and quantitative representation of the spatial distribution of a positron-emitting radionuclide in any desired transverse section of the body. Short-lived positron emitters such as Carbon-11 (half-life:20 min.). Nitrogen-13 (10 min), Fluorine-18 (110 min) or Bromine 75 can be incorporated into biological molecules:amino acids, sugars, fatty acids, hormones and receptor agonists or antagonists. The PET approach may be compared to quantitative autoradiography with the added advantage of allowing in vivo kinetic studies in man, under normal and pathological conditions. Regional myocardial perfusion is measured with rubidium-82, 13N-labelled ammonia, H2(15) O or albumin microspheres labelled with Gallium-68. Regional myocardial metabolism is assessed with 11C-palmitate and 18F-fluorodeoxyglucose. A high and spatially homogenous accumulation of 11C-palmitate is seen in normal myocardium. PET delineates an increased regional accumulation of 18F-2-FDG in ischemic areas while 11C-palmitate accumulation is markedly reduced. Positron Emission Tomography offers a unique opportunity to study receptors in vivo in normal and disease conditions. A potent muscarinic antagonist, 11C-MQNB is used to study the myocardial acetylcholine receptor and beta-blockers, 11C-Pindolol and 11C-CGP 12177 are used to study the beta-adrenergic receptor. The peripheral-type benzodiazepine receptor has been characterized with 11C-PK 11195.

Amino Acids↗