Biomedical subjects

F Lazeyras

Publications and source records attributed to F Lazeyras.

49 records · Page 3Linked to original sources

PubMed1992

Prevention of cardiac allograft rejection by FK506 and rapamycin: assessment by histology and nuclear magnetic resonance.

We assessed the effect of FK506 and rapamycin (RPM) in a heterotopic abdominal rat heart transplant model using a major histocompatibility mismatch (DA to LEW). The end-point of our study was the histologic grading of rejection (Stanford) and 31P magnetic resonance spectroscopy (MRS) at 1 week after transplantation. Two dosages of FK506 (2.0 and 8.0 mg/kg per os daily) and RPM (1.5 and 6.0 mg/kg intraperitoneally daily) were compared in allografts without and with cyclosporine (12.5 mg/kg per os daily) treatment. The results show: Weak heartbeat and full rejection at day 5 in all untreated allografts; severe rejection in groups on a low dose of FK506 and RPM; mild rejection in both high dose groups comparable to the results of the hearts treated with cyclosporine; MRS does not allow differentiation between no or mild forms of rejection. Energy-rich phosphates are near normal in the high dosage immunosuppression groups but show a significant reduction in the low dosage groups. We conclude that all three tested drugs can reduce the degree of rejection from severe (untreated allografts) to mild if given in an adequate dosage. MRS correlates well with the degree of histologic rejection but permits only the diagnosis of moderate or severe rejection.

Animals↗

PubMed1992

Lactate mapping in ischemic rat kidneys using 1H spectroscopic imaging.

RATIONALE AND OBJECTIVES: Biochemical studies have shown that during renal ischemia, lactate is built up predominantly in the medulla and less in the cortex. The authors intend to confirm such a difference in lactate concentration between these two zones of the kidney by means 1H magnetic resonance (MR) spectroscopy. METHODS: In 10 rats, the authors used four-dimensional (n = 4) and three-dimensional (n = 6) spectroscopic imaging to investigate the left kidney after occlusion of the renal artery. RESULTS: By this technique, a map of the intrarenal lactate distribution was obtained during ischemia. It was determined that lactate concentration is indeed higher in the medulla than in the cortex, as verified by chemical analysis (17 +/- 4 versus 9 +/- 4 mumol/g). CONCLUSIONS: By correlating biochemical and morphologic information, localized MR spectroscopy combined with imaging is a powerful tool for investigating pathophysiologic mechanisms.

Animals↗

PubMed1991

Differentiation of cardiac ischemia and rejection by nuclear magnetic spectroscopy.

Nuclear magnetic resonance (NMR) criteria of early cardiac rejection are similar to those seen in myocardial ischemia, that is, a reduction of high energy phosphatases (Pc; ATP) and an increase of inorganic phosphates (Pi). Our aim was to assess in vivo changes of phosphorous spectroscopy (31P) induced by cardiac rejection and myocardial ischemia in the same animal. Heterotopic heart isografts (n = 5) and untreated allografts (n = 5) were examined at seven days on a two tesla wide-bore magnet with a surface coil. Subtotal global ischemia was produced for sequential NMR measurements, followed by heart excision for histological rejection grading (Billingham). Results 1. Isograft served as controls and showed normal energy-rich phosphate compounds and pH. 2. Rejecting (moderate to severe) allografts showed a decrease of Pc/Pi and beta-ATP/Pi ratio compared with isografts. However no significant pH drop could be detected. 3. Induced ischemia was confirmed by marked ECG-ST elevation and showed a significant early global myocardial acidosis (pH less than 6.9) particularly in severe prolonged ischemia (p less than 0.05). 4. Using 31P NMR techniques, ischemically induced changes were similar in isografts and allografts with a trend towards a more pronounced extent in the latter groups. In conclusion, magnetic resonance spectroscopy (31P and pH) allows in vivo differentiation between cardiac rejection and acute myocardial ischemia.

Acute Disease↗

PubMed1991

Magnetic resonance in preterm and term newborns: 1H-spectroscopy in developing human brain.

Localized proton magnetic resonance spectra were recorded from human cerebellum in vivo with a 1.5-T magnet. The spectra from healthy adults and preterm and term babies showed resonances from N-acetylaspartate, creatine and phosphocreatine, choline-containing compounds such as phosphocholine and glycerophosphocholine, taurine, and inositol. The age-dependent changes of in vivo molar concentrations of N-acetylaspartate, choline, taurine, and inositol were estimated in preterm babies, babies at term, and adults. The range of postconceptional age in the studied babies was 31 to 45 wk. Taking the biochemically measured creatine concentrations in age-corresponding autopsy material as an internal standard, the in vivo concentrations of the other metabolites were calculated from the proton spectra. N-acetylaspartate showed an increase from 1.9 mM in preterm babies to 3.1 mM in term babies and to 6.5 mM in adult brain. Taurine was noted to increase from 1.1 mM in preterm infants to 2.3 mM in term infants and did not decrease significantly in adult brain. Choline and inositol concentrations did not change significantly throughout the studied age groups. These new data on in vivo, localized 1H-spectroscopy show that it is a sensitive method for studying early metabolic brain development in humans.

Adult↗

PubMed1990

Brain damage and recovery in hyperphenylalaninemic rats.

Rats were made hyperphenylalaninemic by injecting a mixture of alpha-methylphenylalanine and phenylalanine. Brain development was measured by biochemical, histological and 31-P nuclear magnetic resonance (NMR) methods. In 17-day-old hyperphenylalaninemic rats, brain myelinogenesis was disturbed. Compared to controls, test animals had lower body weights, brain weights, cerebrosides, sulfatides, myelin basic protein (MBP) and reduced cerebroside sulfotransferase (CST) and 2'3'-cyclic nucleotide-3'-phosphohydrolase (CNP) activities. No changes were found in total proteins, total lipids, total phospholipids, phosphatidylethanolamine and phosphorylethanolamine. In the brain of 17-day-old hyperphenylalaninemic rats no changes in phosphomonoesters, phosphodiester and phosphocreatine were found using in vivo 31-P NMR spectroscopy. Because body weights of hyperphenylalaninemic rats were significantly lower than those of controls, we compared them with undernourished rats. Undernourished rats had lower body weights, brain weights and CNP activity. No other changes were found. Therefore, we conclude that hyperphenylalaninemia per se and not undernutrition affected myelinogenesis in test animals. After treatment was discontinued, test rats recovered completely within 6 weeks with regard to biochemical and histological measurements; at 59 days they had normal body weights, cerebrosides, sulfatides, MBP, total proteins, total lipids, total phospholipids, phosphatidylethanolamine, phosphorylethanolamine and normal CST and CNP activities. Brain weights were significantly reduced.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

PubMed1990

[Energy metabolism of the brain, detected with 31-P magnetic resonance spectroscopy during extracorporeal circulation in the rabbit].

The question of a possible brain damage during open heart surgery using extracorporeal circulation is still a problem, especially in infants with circulatory arrest under deep hypothermia. During the last years Magnetic Resonance Spectroscopy was developed, and with this method we have now a possibility to study brain energy metabolism non-invasively and continuously. Our aim was to develop an animal model (rabbit) for studying brain energy metabolism by 31-P Magnetic Resonance Spectroscopy during extracorporeal circulation. In a first step we have shown that the influence of hypothermia on energy metabolism in the brain can be measured in the intact animal by MR-Spectroscopy. In a second step a non-magnetic heart-lung machine for rabbits was constructed and is described here. We get a completely normal brain spectrum in the beginning and after two hours of extracorporeal circulation. The spectrum is also normal on extracorporeal circulation at 35 degrees C and during cooling down to 18 degrees C. With this animal model it will be possible to study different variables of extracorporeal circulation such as duration of circulatory arrest under deep hypothermia or changes of the priming including pharmacological changes.

Adenosine Triphosphate↗

PubMed1989

In vivo 31P NMR spectroscopy of energy rich phosphates in the brain of the hyperammonemic rat.

Hyperammonemia is a major contributing factor to the neurological abnormalities observed in hepatic encephalopathy and in congenital defects of ammonia detoxication. In rats variable changes in labile energy rich phosphates in the brain have been observed in hyperammonemia using biochemical methods. Using 31P-NMR spectroscopy however no significant changes of the relative concentrations of the energy rich phosphates alpha, beta and gamma-ATP, phosphocreatine, inorganic phosphate and the pH were found in the fronto parietal cortex of the urease treated hyperammonemic rat. Alterations in the metabolites of these compounds do not appear to be a major pathomechanism of ammonia toxicity in this brain area.

Ammonia↗

PubMed1989

Study of acute renal ischemia in the rat using magnetic resonance imaging and spectroscopy.

Magnetic resonance (MR) imaging and spectroscopy, chemical lactate measurements, and microscopic examinations were performed to investigate acute renal ischemia in rats. MR images (1H) and spectra (31P and 1H) were acquired on a 2.0-T superconducting small-bore magnet by using implanted coils. Occlusion of the renal artery induced a significant decrease in signal intensity of the renal parenchyma on T2-weighted images, which was most obvious in the outer medulla (-50 +/- 15%, n = 8, P less than 0.001) and was the result of venous congestion, as verified histologically, 31P spectroscopy demonstrated a drop in pH from 7.3 +/- 0.2 to 6.6 +/- 0.2 (n = 18, P less than 0.001), characterized by a time constant (Tc) in the same range as that of the depletion of ATP (2.3 +/- 1.3 min versus 1.9 +/- 1.2 min, n = 10, P = ns). By means of 1H spectroscopy, a lactate peak was detected within 1.5 to 4 min of ischemia, still increasing in intensity after 1 h of ischemia. The Tc of the lactate buildup (15.9 +/- 7.5 min, n = 8) was significantly longer than that of the drop in pH (P less than 0.005). The chemically measured intrarenal concentration of lactate was 1.3 +/- 0.5 mumol/g in control kidneys and 8.7 +/- 3.2 mumol/g (P less than 0.005) in kidneys made ischemic for 1 h. The present study demonstrated important features of acute renal ischemia: (a) acute ischemia induces venous congestion in the medulla; (b) accumulation of lactate is not the main cause of the intracellular acidification observed during ischemia.

Animals↗

PubMed1989

Lactate distribution in ischemic rat kidney by 4D spectroscopic imaging.

A lactate map of the rat kidney is presented, using a four-dimensional spectroscopic imaging technique in connection with a double resonance editing scheme. A voxel size of 12 microL has been obtained, and we show that eddy currents do not affect the line shape of an individual voxel.

Animals↗

PubMed1988

Correlation between 31P NMR phosphomonoester and biochemically determined phosphorylethanolamine and phosphatidylethanolamine during development of the rat brain.

Phosphomonoesters were measured in the developing rat brain by in vivo and in vitro 31P nuclear magnetic resonance (NMR) spectroscopy and by classical biochemical methods. In vitro NMR showed that the main component of the phosphomonoester peak is phosphorylethanolamine. Phosphomonoesters measured by in vivo NMR decreased during development at the same rate as the biochemically estimated phosphorylethanolamine. Phosphorylethanolamine, a precursor of the membrane lipid phosphatidylethanolamine, decreased during development parallel to an increase of the lipid phosphatidylethanolamine, which was measured biochemically. These studies show that 31P NMR can be used to monitor brain development in vivo.

Aging↗

PubMed1988

[Clinical applications of magnetic resonance spectroscopy].

In this overview the physics of magnetic resonance spectroscopy (MRS) are briefly discussed. The biochemical pathways which can be investigated by MRS in physiological and pathological states are presented. The potential clinical applications of this method to the musculoskeletal system, heart, brain, liver and kidney are examined.

Brain↗

PubMedDate not supplied

Specificity of SPIO particles for characterization of liver hemangiomas using MRI.

We investigated the specificity of superparamagnetic iron oxide (SPIO)-enhanced T1-weighted spin-echo (SE) magnetic resonance (MR) images for the characterization of liver hemangiomas. When imaging liver hemangiomas, which are the most frequent benign liver tumors, a method with very high specificity is required, which will obviate other studies, follow-up, or invasive diagnostic procedures such as percutaneous biopsy. Eighty-three lesions were examined by MR imaging at 1.5 T before and after intravenous injection of SPIO particles. Lesions were categorized as follows according to the final diagnosis: 37 hemangiomas, nine focal nodular hyperplasias (FNHs), 19 hepatocellular carcinomas (HCCs), and 18 metastases. Their signal intensity values were normalized to muscle and compared. The only lesions showing a significant increase in signal intensity ratio (lesion to muscle) on postcontrast T1-weighted SE images were hemangiomas (p < 0.001). The signal intensity ratio of hemangiomas increased on average by 70%. Based on receiver operating characteristic analysis and using a cutoff level of 50% signal increase, the specificity and sensitivity of SPIO-enhanced MR imaging for the characterization of hemangiomas would be 100% and 70%, respectively. The T1 effect of SPIO particles can help differentiate hemangiomas from other focal liver lesions such as FNHs, HCCs, and metastases and may obviate biopsy. When using SPIO particles for liver imaging, it is useful to add a T1-weighted sequence to T2-weighted images, thereby providing additional information for lesion characterization.

Adult↗

PubMedDate not supplied

Magnetic resonance spectroscopy for assessing myocardial rejection in the transplanted rat heart.

Traditionally, detection of heart rejection after heart transplantation is based on histologic grading of endomyocardial biopsy specimens. The value of magnetic resonance spectroscopy for determining heart rejection was assessed in rejecting and nonrejecting isografts and allografts using energy-rich phosphate spectroscopy. In 46 rats a heterotopic abdominal heart transplantation was performed, and animals were divided into the following groups: six isografts (no rejection), five untreated allografts (severe rejection), and 35 immunosuppressed allografts (mild to moderate rejection). One week after transplantation magnetic resonance spectroscopy was performed, and data were correlated to histologic findings (rejection grades according to Stanford and the New International Working Formulation classifications and relative volume of viable myocardium). Magnetic resonance spectroscopy allows detection of moderate to severe rejection with significant alterations in the energy-rich phosphates such as a decrease in the ratio of phosphocreatine/inorganic phosphate, phosphomonoester/inorganic phosphate, and beta-adenosine triphosphate/inorganic phosphate. A significant correlation was found between spectroscopic changes (phosphocreatine/inorganic phosphate) and histologic rejection (correlation coefficient r = 0.47, p < 0.005) and/or the amount of relative volume of viable myocardium and phosphocreatine/inorganic phosphate (r = 0.58) or beta-adenosine triphosphate/inorganic phosphate (r = 0.63), respectively. In conclusion magnetic resonance spectroscopy permits detection of moderate to severe degrees of heart rejection with a sensitivity of 85% and a specificity of 61%. Changes in the energy-rich phosphates correlate with the histologic grading of heart rejection and the relative volume of viable myocardium. Magnetic resonance spectroscopy appeared to be a valid technique for detecting myocardial rejection after heart transplantation in the reported experimental model.

Adenosine Triphosphate↗