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Biomedical subjects

A Le Pape

Publications and source records attributed to A Le Pape.

At least 37 records · Page 2Linked to original sources

Potential of T2 relaxation time measurements for early detection of radiation injury to the brain: experimental study in pigs.

PURPOSE: To investigate the MR T2 relaxation time and histologic changes after a single-fraction 25-Gy dose of radiation to the brain of pigs. METHODS: The right hemisphere of 10 Meishan pigs was irradiated with a single dose of 25 GY at the 90% isodose, using a 12-MeV electron beam. T2 relaxation time was measured within three regions of interest in the brain: those that had received 90%, 70%, and 40% of the total dose, respectively. T2 kinetics over time was compared with histologic studies. RESULTS: Brain T2 values were noted to increase within the irradiated areas. T2 kinetics were analyzed in three phases: an immediate transient phase and two long-lasting phases. These two long-lasting phases were correlated with the detection of ventricular compression and necrosis, respectively. The T2 increase within the 90% region of interest was 19%, 22%, and 26% for phases I, II, and III, respectively. T2 measurements within other regions of interest were not significant. CONCLUSION: Although our results suggest a dose threshold for T2 variations, brain T2 values increased after irradiation at a level at which disease could not be seen on conventional MR images. This illustrates the value of using conventional MR imaging in a quantitative manner to assess molecular tissue abnormalities at earlier stages of developing diseases.

Animals↗

Quantitative magnetic resonance and isotopic imaging: early evaluation of radiation injury to the brain.

PURPOSE: Using magnetic resonance (MR) and isotopic imaging to investigate the cerebral alterations after highdose single-fraction irradiation on a pig model. We assessed the nuclear magnetic resonance (NMR) relaxation times as early markers of radiation injury to the healthy brain. METHODS AND MATERIALS: A total of 17 animals was studied; 15 irradiated and 2 unirradiated controls. Pigs were irradiated with a 12 MeV electron beam at a rate of 2 Gy/min. Ten animals received 40 Gy at the 90% isodose, five animals received 60 Gy, and two animals were unirradiated. The follow-up intervals ranged from 2 days to 6 months. T1-weighted scans, T2-weighted scans, and scintigrams were performed on all animals to study neurological abnormalities, cerebral blood flow, and blood-brain barrier (BBB) integrity. T1 and T2 relaxation times were measured in selected regions of interest (ROIs) within the irradiated and contralateral hemispheres. A ratio T1 after irradiation/T1 before irradiation, and a ratio T2 after irradiation/T2 before irradiation, were calculated, pooled for each dose group, and followed as a function of time after irradiation. RESULTS: Scintigraphy visualized the brain perfusion defect and BBB disruption in all irradiated brains. The ratio T2 after irradiation/T2 before irradiation was proportional to the effective dose received. The T2 ratio kinetics could be analyzed in three phases:an immediate and transient phase, two long-lasting phases, which preceded compression of the irradiated lateral ventricle, and edema and necrosis at later stages of radiation injury, respectively. The magnetic resonance imaging (MRI) observations correlated well with histological analysis. CONCLUSION: The results show that quantitative imaging is a sensitive in vivo method for early detection of cerebral radiation injury. The reliability and dose dependence of T2 relaxation time may offer new opportunities to detect and understand brain pathophysiology after high-dose single-fraction irradiation.

Animals↗

Imaging of pulmonary disease in rheumatoid arthritis using J001X scintigraphy: preliminary results.

The purpose of this study was to determine the ability of technetium-99m J001X scintigraphy to image active pulmonary involvement in patients suffering from rheumatoid arthritis (RA). J001X is a fully characterized acylated poly(1,3)galactoside, isolated from Klebsiella membranes, which is able to bind recruited macrophages after aerosol administration. J001X scintigraphy was compared with high-resolution computed tomography (HRCT), pulmonary function tests (PFTs) and bronchoalveolar lavage (BAL) in 15 patients suffering from RA. Patients were considered to have pulmonary involvement when they had an interstitial syndrome on HRCT and a decrease of 20% in TCO/VE (transfer coefficient) on PFTs and/or an abnormal BAL (lymphocytosis higher than 20% and/or percentage of neutrophils higher than 10%). Pulmonary involvement was present in eight patients, and absent in seven. Of the eight patients with pulmonary involvement, all had abnormal BAL, two had an interstitial syndrome on HRCT, two had decreased TCO/VE and three had positive J001X scintigraphy. Of the seven patients without pulmonary involvement, six had normal BAL (not available in one), two had an interstitial syndrome on HRCT, one had decreased TCO/VE and two had positive J001X scintigraphy. According to our gold standard of pulmonary involvement, the sensitivity of J001X scintigraphy for the detection of pulmonary involvement in RA was 37.5%, the specificity was 71.4% and the positive predictive value was 60%. The ability of J001X scintigraphy to detect active pulmonary involvement during RA appears unclear in this study but it may detect processes unnoticed by the other modalities. These patients will be followed 12 and 24 months later and the changes in J001X scintigraphy, HRCT and PFTs will be compared to demonstrate whether J001X scintigraphy is able to assess an active process in the pulmonary involvement during RA and to specify its predictive value.

Adult↗

Lymphoscintigraphy via the targeting of macrophages with 99mTc-J001X poly-galactoside in a model of pyogranulomas developed in sheep lymph nodes.

Lymphoscintigraphy usually involves labeled microparticles or colloids that distribute in the lymph flow. A new strategy for imaging pathological lymph nodes would be the targeting of macrophages recruited in these lesions. The potential for lymphoscintigraphy of the highly diffusible J001X acylated polygalactoside labeled with 99mTc was studied and compared to usual colloidal agents in a model of infectious granulomas developed in sheep. Scintigraphic and histological assessment of the specificity of targeting was performed using a MAb (OM1) raised against ovine macrophages taken as reference. This study has evidenced the ability of J001X specifically to image pathologic lymph nodes and more especially the second lymph node in the same chain with a significant scintigraphic contrast.

Animals↗

Magnetic resonance imaging in vivo monitoring of T2 relaxation time: quantitative assessment of primate brain maturation.

This work describes quantitative MRI assessment of primate brain maturation. Nine young baboons were followed from the age of one to 30 months. Assessment of myelination was based on the gray/white matter contrast on MR images and the evolution of T2 relaxation time respectively. The brain maturation began in the posterior fossa and progressed to the olfactory bulbs corresponding to decreasing white matter T2 values. Relaxation parameters provide new opportunities to trace the myelination process in vivo.

Aging↗

T1 mapping from spin echo and stimulated echoes.

We present an imaging method to obtain a map of the spin-lattice relaxation time. Images were acquired with the same spatial resolution and in the same time as for a regular spin-echo acquisition. The sequence was based on the simultaneous acquisition of a spin echo and several stimulated echoes with the same intensity except for T1 weighting which increases with the interval between the excitation pulse and the readout pulse. T1 values obtained on phantoms were compared to those from the inversion-recovery method and show the accuracy (2%) and the precision (5%) of the method. T1 images of the brain of a healthy volunteer are presented and demonstrate the ability of the method to obtain T1 mapping in vivo in 12 min and without susceptibility artifacts. In vivo and in vitro results were compared to those obtained by a TOMROP sequence in the same acquisition time.

Biophysical Phenomena↗

Deposition of amphotericin B aerosols in pulmonary aspergilloma.

The aim of the present study was to characterize amphotericin B aerosols nebulized by ultrasonic and jet nebulizers and to study their deposition and pharmacokinetics in patients with pulmonary mycetoma. The aerodynamic behaviour and pulmonary deposition of amphotericin B particles were measured using a direct isotopic method based on stable labelling of the drug with 99mTc. Each nebulizer was bench tested for inhaled mass and particle size distribution. Three patients suffering from pulmonary aspergilloma were enrolled for a 4 week clinical study. They received 5 mg of amphotericin B daily delivered by either Fisoneb or DP100 (ultrasonic) or Respirgard II (jet) nebulizers. Deposition of radiolabelled amphotericin B was measured once with each nebulizer using a gamma-camera. In two patients, amphotericin B serum concentration was monitored over a 330 min period after the nebulization had been completed. Inhaled masses of the three nebulizers, assessed as % of labelled drug caught in inspiratory filter in duplicate experiments, were: 5.8 and 3.6% for Respirgard II; 26.5 and 28.3% with Fisoneb; 5.9 and 6.3% for DP100. Mass median aerodynamic diameter (mean +/- SD) results were: 0.28 +/- 0.04 micron with Respirgard II; 4.82 +/- 0.78 microns with Fisoneb; and 2.27 +/- 1.14 microns with DP100. Because of larger particles and significantly greater inhaled mass, Fisoneb delivered more amphotericin B to the central airways, the lung periphery and in the mycetoma lung regions. Amphotericin B serum concentrations correlated with pulmonary deposition and remained below 25 ng.mL-1. No untoward effects were reported by the patients during the 4 week trial.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

201T1 and 99Tcm-J001X macrophage scintigraphy: two radionuclide imaging techniques for the surveillance of acute localized radiation over-exposures.

The therapeutic or surgical management of acute localized irradiation is very complicated due to the delayed occurrence of ionizing radiation effects. There is a great need for non-invasive imaging techniques to delineate healthy from exposed tissues. Such a technique should be of value considering that spread of damage can occur from apparently silent fibrotic foci. Of the scintigraphic procedures, 99Tcm first-pass scintigraphy has already been recommended by the International Atomic Energy Agency (IAEA) for the evaluation of irradiated tissues. In order to improve the scintigraphic surveillance of accidental over-exposures, the potentials of 201T1 and 99Tcm-J001X were evaluated on an experimental porcine model reproducing the late fibrotic effect encountered after localized irradiation. J001X, an acylated poly-(1,3)-galactoside of bacterial origin, was used for the functional imaging of the inflammatory reaction which took place after irradiation. This scintigraphy, based on targeting of activated macrophages recruited by lesions, was performed together with 201T1 scans for the assessment of blood perfusion and cellular metabolism. Our results demonstrate that these two radiopharmaceuticals provide reliable information for the management of accidental localized over-exposure, J001X allowing the assessment of the inflammatory reaction and 201T1-chloride being mainly useful for imaging the delayed onset of fibrosis.

Animals↗

Experimental MR study of cerebral radiation injury: quantitative T2 changes over time and histopathologic correlation.

PURPOSE: To use the pig brain as a large-animal model to examine the effects of high-dose single-fraction irradiation on MR images, T2 relaxation time, and histologic integrity. METHODS: A total of 24 Meishan pigs were studied: 20 irradiated animals and 4 unirradiated controls. A high dose was delivered to the right hemisphere of the animals, using a 12-MeV electron beam. Ten animals received 40 Gy at the 90% isodose, and 10 animals received 60 Gy. Quantitative measurement of T2 relaxation time was compared with qualitative analysis of T2-weighted images and histologic studies. RESULTS: Quantitative analysis revealed a reproducible increase of the T2 parameter within the irradiated areas. The T2 kinetic could be analyzed in two phases, which appeared before the visualization of ventricle compression, necrosis, and edema. The first is characterized by vascular inflammation and the latter by radiation necrosis and edema. Both are dose dependent. CONCLUSION: These results underline the ability of quantitative MR for early diagnosis of brain radiation lesions in vivo.

Animals↗

31P and 13C nuclear magnetic resonance studies of macrophages.

Biochemical events associated with differentiation and activation of monocyte-macrophage cell lines are of major interest in the understanding of pathophysiological processes as well as in research on immunopharmacological modulation of these cells. Nuclear magnetic resonance is the technique of choice for kinetic studies of metabolic events under such experimental conditions. This approach was used with the P388-D1 model of mature macrophages. Cells primed in vivo were triggered in vitro during NMR analysis and the results were compared to those from chemiluminescence tests performed simultaneously. Three preliminary phases were achieved: (i) 31P and 13C NMR spectroscopy of perchloric acid extracts, (ii) optimization of culture and perfusion conditions with validation of macrophage viability and functionality, and (iii) development of a data processing technique to improve the time resolution of kinetic studies. Based on their phosphocreatine content, cells primed in vivo exhibited maturation than control cells. After the respiratory burst of primed macrophages was triggered by concanavalin A, 31P NMR spectra reflected both a transient increase in ADP phosphorylation and intracellular acidification. 13C NMR studies indicated an acceleration of metabolism following in vitro triggering. The phenomenon was associated with an increased glucose consumption, implicating the hexose monophosphate shunt. These occurred concomitantly with the appearance of new peaks attributed to phosphorylated sugars.

Animals↗

Acquisition of spin echo and stimulated echo by a single sequence: application to MRI of diffusion.

A new method is described to measure the restricted diffusion coefficient with magnetic resonance imaging. The two images necessary to calculate the diffusion image are obtained with a simultaneous acquisition of a spin-echo and a stimulated echo, and so, in half the time needed by usual spin-echo or stimulated echo method. A different diffusion contrast is created on each echo. A map of an estimate of the diffusion coefficient and an estimation of T1 value are obtained with only one experiment. The accuracy of the method has been evaluated on phantom and results are in agreement with values found in previous papers and with measurements performed with a usual spin-echo method. Furthermore, in vivo measurements have shown that this method can be used without electrocardiogram triggering.

Brain↗

Evaluation of possible interference of anti-inflammatory drugs upon scintigraphic imaging with macrophage targeting 99mTc-J001X: effects of methylprednisolone, dexamethasone, indomethacin and methotrexate.

J001X, an acylated poly-(1,3)-galactoside isolated from Klebsiella pneumoniae proteoglycan, has been developed to target cells from the monocyte-macrophage lineage. Recent experimental work and initial clinical trials have proved the potential of this molecule labeled with 99mTc for the scintigraphy of inflammatory foci. In a model of radiation-induced inflammation in pigs, the scintigraphic contrast was observed to be very sensitive to a single injection of methylprednisolone given 12 h before scintigraphy. The present study was undertaken to confirm this effect and to estimate the possible interference of various anti-inflammatory agents on the in vivo targeting of macrophages by J001X. Methylprednisolone, dexamethasone, indomethacin and methotrexate used at an immunosuppressive dose were tested to assess the possible risk of false-negative examinations in patients thus treated. Analysis of the results indicated that among the four drugs tested, only methylprednisolone at 0.5-1 mg/kg could interfere with J001X scintigraphy.

Animals↗

Imaging of pulmonary disease in scleroderma with J001X scintigraphy.

BACKGROUND: J001X is an acylated poly-galactoside isolated from the membrane of Klebsiella and able to interact with macrophages, mainly in their activated state. The aim of the present study was to determine the ability of 99m-labelled technetium (99mTc)-J001X scintigraphy to image pulmonary disease, defined by high resolution computed tomographic scanning and pulmonary function tests, in patients suffering from scleroderma. METHODS: Patients were considered to have pulmonary disease when they had at least two positive signs on high resolution computed tomography, or a decrease in lung volume and single breath carbon monoxide transfer, or both, with no disease process other than scleroderma in their medical history. Positive J001X scintigraphic imaging was defined by symmetrical bilateral pulmonary fixation three and five hours after inhalation of 99mTc-J001X. J001X scintigraphic results were compared with disease activity as indicated by bronchoalveolar lavage (BAL) fluid lymphocytosis. RESULTS: Seventeen patients were studied, in 12 of whom J001X scintigraphy was positive. There was no correlation between BAL lymphocytosis and J001X scintigraphic findings, nor between BAL and pulmonary scleroderma. This was not surprising because of the high specificity of macrophage targeting by J001X. CONCLUSIONS: Follow up of a larger population over a longer period is needed to establish whether there is a prognostic value for positive J001X scintigraphic findings in scleroderma.

Adult↗

[Characterization by isotope method of the performance of the pneumatic nebulizer NL9 Atomizer in the production of colistin, tobramycin and amiloride aerosols].

The objective of this study was to assess the performance of a new pneumatic nebuliser NL9 Atomisor. The performance was assessed in terms of particle distribution, fraction nebulised, fraction inhaled and percentage of particles of a diameter of between 1 and 4 microns for the nebulisation of physiological serum, colistin, tobramycin and amiloride. The solutions were nebulised in the approved formula for their reconstitution as used in the clinic after the addition of sodium pertechnetate. The validity of this indirect isotopic method has been shown before. The nebuliser was coupled, during the nebulisation, to a pump respirator with six settings. The fraction nebulised was defined as the percentage of the volume of the solution which had left the aerosol generator at the end of the nebulisation. The fraction inhaled was defined as a percentage of the volume of the solution which was gathered at the end of the nebulisation on a filter placed in the inspiratory circuit of the aerosol generator. The study of the distribution of aerosol particle sizes was carried out using a cascade impactor at ten stages. Each of these parameters was determined in triplicate for the four solutions studied. The nebulised fraction consisted of between 33.5 and 58.6% (mean 49.7 +/- 8.1%). The inhaled fraction consisted of between 14 and 30.4% (mean 24.5 +/- 5.5) and the duration of nebulisation was between 10 and 20 minutes. The MMAD was between 1.6 microns with tobramycin 3.5 microns with physiological serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗

Radiofrequency map of an NMR coil by imaging.

We propose a new imaging method to obtain a map of the radiofrequency (RF) field amplitude over a sample. The sequence contains three RF pulses (alpha, 2 alpha, and alpha) and produces two images by a classical spin echo and a stimulated echo. A third image is computed and gives the distribution of the flip angle alpha, and so the RF amplitude, over the sample. The accuracy of the flip angle determination is verified on an homogeneous sample and results show a good correlation between experimental and theoretical flip angles in the range of 50 degrees to 130 degrees. Experiments with a surface coil and a resonator show the method is available in an inhomogeneous RF field. Images obtained on the calf of a volunteer confirms the independence of the computed RF distribution from proton density, T1, or T2 contrast.

Humans↗

Scintigraphic potentials of J001X acylated poly-galactoside for imaging inflammatory lesions in pigs.

Although several approaches already exist for the imaging of inflammatory foci, new specific strategies providing functional data on the lesions are required to determine the extent of the disease and also to assess anti-inflammatory treatment. In our study, we investigated the scintigraphic potential of 99mTc-J001X, an agent developed for the targeting of macrophages. Due to its well documented and progressive evolution of lesions, a model of radiation-induced inflammation in pigs was chosen. Our results demonstrated the ability of J001X to provide images of inflammatory foci with a high contrast. The contribution of some specific and non-specific parameters possibly involved in the scintigraphic behavior of J001X is discussed.

Acetylation↗