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F Podo

Publications and source records attributed to F Podo.

At least 37 records · Page 2Linked to original sources

Transient global brain ischemia in the rat: spatial distribution, extension, and evolution of lesions evaluated by magnetic resonance imaging.

A newly developed model of transient global ischemia in the rat was evaluated by magnetic resonance imaging (MRI) in terms of localization of brain lesions, their extent and severity, and temporal evolution. Such a model, consisting of bilateral occlusion of common carotid arteries for 10 minutes and mild hypoxia (15% O2) for 20 minutes induces delayed neuronal degeneration, necrosis, and gliosis (detected histologically and immunohistochemically). Ischemia was assessed by full suppression of spontaneous electroencephalographic activity. A "hybrid" T2-/diffusion-weighted MR sequence enhancing more effectively the contrast between injured and intact tissues as compared to T2-weighted MRI was used at 24, 48, 72, and 96 hours and at 7 days postischemia. Twenty hypoxic-ischemic rats showed a considerable variability in brain damage. In 8, there were no MRI-detectable lesions at any interval. In the other 12 rats, the severity and extension of neuronal damage varied markedly, but the lesions were always localized (monolaterally in 8 and bilaterally in 4 rats) in the occipital, temporal, or parietal cerebral cortex. Mainly, they were of intermediate severity or were severe (as assessed by MRI hyperintensity) and were accompanied by usually less severe lesions in the thalamus and/or caudate putamen. The hippocampus was affected moderately or severely in 4 of 12 rats. In most cases, there was at 48 hours a considerable growth in severity and/or extension of lesions, which usually remained stable at later intervals. In conclusion, MRI allowed us to follow brain lesions during the first week in this relatively simple and noninvasive model of transient global ischemia.

Animals↗

Lower levels of 1H MRS-visible mobile lipids in H-ras transformed tumorigenic fibroblasts with respect to their untransformed parental cells.

High resolution 1H MRS studies report increased mobile neutral lipid (MNL) signals in transformed and malignant as well as in some in vitro cultured embryonic cells. Nature, subcellular localization and biological function of MNL are still under debate. This work was aimed at assessing alterations induced in MNL signals of NIH-3T3 mouse embryo fibroblasts by transformation with human HJ-ras oncogene. Lower MRS-visible MNL levels were unexpectedly detected in ras-transformed, in vivo tumorigenic fibroblasts, with respect to their untransformed and non-tumorigenic parental cells. MRS, gas chromatography and chemical analysis on cells and their lipid extracts indicated that these spectral differences could hardly be attributed to different triacylglycerol, free fatty acids and total cholesterol levels or to changes in the fatty acyl degree of unsaturation and average chain length. Additional, possibly more relevant mechanisms of regulation of MNL mobility may implicate the extensive morphogenetic changes and reorganization of cytoskeleton components (notably actin) associated with ras-transformation.

Animals↗

Quality assessment in in vivo NMR spectroscopy: I. Introduction, objectives, and activities.

By enabling noninvasive measurements of tissue biochemistry, nuclear magnetic resonance spectroscopy (MRS) provides a unique means of characterizing tissues. Differences in equipment, techniques, and methodology between different laboratories cause major difficulties when comparing results, whether from measurements of tissue metabolism, or from the effects of different therapies. This is of concern in critically evaluating work from different laboratories and centres, causing potential difficulties in reproducing results, limiting the establishment of MRS as a standard method of diagnosis and of characterising disease and response to therapy in the laboratory and clinic. It also poses particular problems in establishing the multicentre clinical trials of MRS that are now required to provide adequate statistical power in confirming the encouraging preliminary clinical observations. These difficulties arise principally from imperfect localization of signal from selected regions of interest in the body, and from the subsequent analyses of the MRS spectra. Improvement is possible by establishing agreed procedures for test measurements and for data analysis, and by using appropriate test objects and test substances to establish the quality of measurements. A concerted research project on characterisation of biological tissues by NMR, principally concerned with MR imaging (MRI), was activated in 1984 by the European Economic Community as part of its third Medical and Health Research Programme, under the auspices of the Biomedical Engineering Concerted Actions' Committee (COMAC-BME). In 1988, this project was prolonged for 5 years, when the programme was expanded to encompass MRS.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Quality assessment in in vivo NMR spectroscopy: II. A protocol for quality assessment. EEC Concerted Research Project.

A protocol has been developed for quality assessment in in vivo NMR spectroscopy (MRS) on whole body and animal systems. The protocol, which has been evaluated in a series of international trials, defines procedures, objects and substances to evaluate the localisation of common slice and volume selection sequences, and to assess other relevant aspects of system performance, including: signal-to-noise; signal loss; relation between signal strength, concentration and volume; selective suppression of spectral lines; spectrometer stability.

Animals↗

Quality assessment in in vivo NMR spectroscopy: III. Clinical test objects: design, construction, and solutions.

Based on the requirements of test protocols developed to evaluate clinical MRS single slice and volume localisation sequences, two clinical test objects, STO1 and STO2 have been developed. The properties of a range of potential construction materials have been assessed, demonstrating that the water/Perspex interface produced minimum susceptibility effects. The design of the objects has been evaluated in trials on different magnetic resonance instruments, with size and loading being adjusted to allow use on currently available equipment. Appropriate test solutions for 31P and 1H measurements have been developed and their properties evaluated.

Magnetic Resonance Spectroscopy↗

Quality assessment in in vivo NMR spectroscopy: V. Multicentre evaluation of prototype test objects and protocols for performance assessment in small bore MRS equipment.

This paper reports the results of multicentre studies aimed at designing, constructing, and evaluating prototype test objects for performance assessment in small-bore MRS systems, by utilizing the test protocols already proposed by the EEC COMAC-BME Concerted Action for clinical MRS equipment. Three classes of test objects were considered: (1) a multicompartment test object for 31P MRS measurements performed with slice-selective sequences; (2) a two-compartment test object for volume-selection 1H MRS; and (3) two-compartment test objects for assessing the performance of experimental systems using ISIS as volume localization sequence in 31P MRS. The results suggested the interest of adopting some of these prototypes for improving the comparison of spectroscopy data obtained from different sites, for providing useful means of quality assurance in experimental MRS, and facilitating the validation of new localization sequences.

Magnetic Resonance Spectroscopy↗

[Quality control in magnetic resonance for clinical use].

This chapter summarizes requirements, rationale and main steps in the recent evolution of protocols adopted at international level for quality controls in clinical magnetic resonance imaging (MRI) and spectroscopy (MRS). An accurate assessment of instrumental performance in MRI and MRS is essential for enhancing the clinical value of these methodologies, both in terms of anatomical and physio-pathological information. In the field of MRI, a series of Concerted Actions, carried out in the frame of the medical and health research programmes of the European Economic Communities (EEC), led to the definition of standardized methodologies and to the construction of five test objects for assessing the quality of fourteen instrumental parameters, inherent to: signal uniformity and linearity; geometry; slice position and thickness; spatial resolution; signal-to-noise and contrast-to-noise ratios; T1 and T2 precision and accuracy. The first part of this paper devotes particular attention to the protocols adopted by the EEC Concerted Actions and by the National Electrical Manufacturers Association (NEMA, US), for assessing signal uniformity, geometric distortion and signal-to-noise ratio in MRI. A brief description is also given of the rationale and protocols for measuring other MRI parameters. The second part is devoted to describe eleven parameters of instrumental performance, two test objects and the measuring protocols recently proposed by the EEC Concerted Actions for quality control in single-volume localized MRS, following their validation in a series of experimental multi-centre trials.

Artifacts↗

[Introduction to magnetic resonance for clinical use. Physical principles and instrumentation].

The recent technological developments in nuclear magnetic resonance (NMR) have made it possible to extend the use of this methodology to the formation of body images (MRI), as well as to the in vivo detection of metabolites in tissues and organs, by means of localized magnetic resonance spectroscopy (MRS). After presenting a brief semi-classical introduction to the NMR phenomenon, this article illustrates the principles of MRI, starting from phase encoding to the most commonly used pulse sequences. The main techniques of localized MRS are then introduced, with particular attention to their major advantages and limitations. The last session is devoted to the schematic description of a system for magnetic resonance imaging and spectroscopy.

Magnetic Resonance Imaging↗

[Limits of exposure to magnetic fields and national standards for the safety of the patient during magnetic resonance examination].

This review summarizes experimental bases, limitations and rationale of guide-lines and recommendations adopted by national health authorities for the safety of patients exposed to the magnetic fields utilized during magnetic resonance (MR) examinations: static magnetic field (B0); time-varying magnetic field gradients (dB/dt) and radiofrequency magnetic fields. Although the mechanisms of interaction of these fields with the living matter are today sufficiently understood to identify the main categories of potentially associated health hazards, epidemiological studies and dosimetric concepts are still far from the levels of definition of protection standards adopted in the field of ionizing radiations. The definition of safety thresholds and levels of exposure to magnetic fields during MR examinations has evolved in the last decade and the matter is still under study today. This article summarizes the main steps in this continuous updating process and discusses limitations and criteria, which recently suggested the adoption in some Countries (including Italy) of a two-tier system for the levels of exposure of patients to the magnetic fields generated by clinical MR equipment.

Biophysical Phenomena↗

Tissue characterization by magnetic resonance spectroscopy and imaging: Results of a concerted research project of the European Economic Community. Introduction, objectives, and activities.

The multi-parameter dependence of magnetic resonance (MR) images allows a unique flexibility of soft tissue contrast and gives access to peculiar sources of in vivo tissue characterization, mainly associated with magnetic relaxation properties. However, MR methodologies have not yet expressed their full potential in terms of tissue characterization for several reasons: a) problems of quality control and quantitation have generally not been addressed by centers using MRI equipment, nor in most of the published literature; and b) data scattering of quantitative measurements obtained from tissues in vitro and in vivo appear to be a major factor in inhibiting or limiting the clinical utility of MRI, for a possible in vivo characterization of pathological tissues. An international project, aimed at evaluating the clinical significance of tissue characterization by MR, was activated in 1984 by the Biomedical Engineering Advisory Committee of the European Communities (EC COMAC-BME) within the 3rd EC Medical and Health Research Programme (MHRP). The scientific achievements of this first project (Magn. Reson. Imaging, 6:171-222; 1988) represented the basis for launching and performing a second Concerted Action, in the frame of the 4th MHRP (1988-1992). Main areas of research of this second project were: a) development of standard methodologies for quantitative measurements of MR parameters and correlation with histo- and physiopathology; b) performance assessment and calibration of MR clinical equipment; c) harmonization of test procedures with other centers and industry; and d) pilot multi-center collections of data.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Analysis of the first international data bank on in vitro NMR relaxation times: animal liver.

Based on an international "Interlaboratory Comparison of Protocol Trials for In Vitro Studies by NMR," the EEC COMAC-BME concerted action on "Identification and Characterization of Biological Tissue by NMR" started collection of a data bank for in vitro relaxation time data of normal and pathological tissues. Relaxation time measurements were performed in a frequency range from 10-90 MHz and in a temperature range from 3 to 40 degrees C; data analysis was done using single exponential fitting routines. Specimens were taken from different organs or tissues (n = 19) of various species (n = 5) and both sexes. More than 900 relaxation time data from 12 participating groups were collected. However, for quantitative analysis we concentrated on liver tissue (287 entries). Main results are the high reproducibility of data from different centers, allowing quantification of temperature dependence of T1 and T2, respectively, in fresh mouse (3.9 and 0.41 msec/degrees C), rat (2.1 and 0.24 msec/degrees C), and hamster (2.6 and 0.22 msec/degrees C) liver. Further, a highly significant species difference between mouse and rat liver, not depending on water content, has been established. We discuss results quantitatively as well as consequences for in vitro protocols and future multicenter data collection.

Animals↗

13C and 31P NMR studies of glucose and 2-deoxyglucose metabolism in normal and enzyme-deficient human erythrocytes.

The flux of 13C-labeled glucose through the Embden-Meyerhof and pentose phosphate pathways was studied by 13C NMR in intact erythrocytes isolated from normal subjects or from patients suffering of glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) deficiency. Similar rates of glucose catabolism and similar fluxes of the 13C-label into 2,3-bisphosphoglycerate and lactate were found, under basal conditions, in normal and in G6PD-deficient erythrocytes incubated in the presence of either [1-13C]- or D[6-13C]glucose. Exposure to oxidative stress by preincubation with tert-butylhydroperoxide induced in normal, but not in G6PD-deficient erythrocytes, a significant enhancement of glucose consumption, as well as a substantial reduction in 13C-label transfer from C1-glucose into lactate. It was also possible, by 31P NMR, to evaluate the conversion of 2-deoxyglucose to its phosphate-containing metabolites. The oxidation and subsequent decarboxylation of 2-deoxyglucose-6-phosphate was assessed in reconstituted systems and could subsequently be evidenced also in ethanolic extracts from normal (but not from G6PD-deficient) erythrocytes which had been exposed to oxidative stress. The results indicate that, in terms of glucose flux through the glycolytic pathway, there is little or no difference between normal and G6PD-deficient erythrocytes, regardless of previous exposure to oxidative stress. Faster consumption of either glucose or 2-deoxyglucose is induced, only in normal cells, by treatment with tert-butylhydroperoxide, essentially as a consequence of the activation of the pentose-phosphate pathway.

2,3-Diphosphoglycerate↗

Spin-lattice relaxation in murine tumors after in vivo treatment with interferon alpha/beta or tumor necrosis factor alpha.

1H NMR spin-lattice relaxation times (T1) were measured in vitro and in vivo in Friend leukemia cell tumors during subcutaneous tumor growth in syngeneic mice and after in vivo administration of either purified murine interferon alpha/beta (IFN) or recombinant tumor necrosis factor alpha (TNF). Untreated tumors exhibited monoexponential T1 relaxation independently of tumor age at least until Day 16 after implantation. Histological examinations showed that under these conditions tumors were highly homogeneous and substantially free of necrotic areas. Peritumoral administrations of either IFN or TNF did not significantly alter the tumor relaxation properties at early stages of inhibition of tumor growth. The longitudinal relaxation decay became instead clearly biexponential at later stages (more than 7 days of IFN treatment or 2 days after TNF administration). While the T1 relaxation behavior could be unequivocally correlated with the presence of necrotic areas in these tumors, it could not be considered as an early marker of the altered growth capability, induced by administration of either IFN or TNF.

Animals↗

[Localized nuclear magnetic resonance spectroscopy in vivo. Physical principles and quantitative problems].

Recent technological developments extended the use of nuclear magnetic resonance to clinical imaging (MRI), as well as to in vivo metabolic studies on tissues and organs by means of localized spectroscopy (MRS). The quantitative determination of absolute metabolic concentrations by in vivo MRS still represents a challenge for technological efforts and biochemical investigations. In fact, the different methodologies today available for spectral acquisition from localized regions within a body organ or pathological lesion should ideally lead to a complete suppression of signals from surrounding tissues, without any appreciable signal loss from the volume of interest. Accurate assessment of deviations of the real from the ideal case represents an essential requirement for either relative or absolute quantification of in vivo localized MR spectra. A review will be presented of the most utilized MRS methodologies, together with a discussion on their potentialities and limitations. Techniques have been classified according to the use of either r.f. (B1) and/or static magnetic field (B0) gradients. The last session will be devoted to the presentation of some results obtained in our laboratory on the use of a particular test-object (constructed at the Deft Institute of Technology) for assessing signal localization efficiency provided by a surface coil in a small scale MRS/MRI equipment (for in vivo biochemical studies on small animals). The surface coil was used in conjunction with a number of sequence (t1-90 degrees-acq; 1-D "chemical shift imaging"; "depth") of either square or adiabatic r.f. pulses. The results allow the selection, on a quantitative basis, of the most appropriate pulse sequence(s) to be used for metabolic studies on superficial experimental tumours (implanted s.c. in small animals), according to the mean area and thickness of the neoplastic lesion. The latter parameters can be non-invasively assessed by previous MRI analysis of the tumour. This study was carried out in the frame of the EC COMAC-BME Concerted Research Project on Tissue Characterization by MRS and MRI.

Animals↗

Alterations of lipid composition in Friend leukemia cell tumors in mice treated with tumor necrosis factor-alpha.

Lipid analyses were carried out on transplantable murine Friend leukemia cell tumors, 6 h after intratumoral administration of tumor necrosis factor-alpha (TNF). The levels of the major phospholipid classes were uniformly decreased to about 70% of control values; free fatty acids were increased to about 170%; diacylglycerol was decreased to about 50% and triacylglycerol, the main lipid component, was not significantly altered. These results analysed in the light of concomitant alterations in the levels of phospholipid precursors and catabolites (determined in previous 31P NMR studies) and histological modifications demonstrated that at early stages of TNF-induced inhibition of tumor growth (a) phospholipid catabolism was significantly enhanced; (b) morphological changes were apparently correlated with alterations in the levels of phosphatidylcholine and its catabolic products.

Animals↗