Biomedical subjects

Jean-François Le Bas

Publications and source records attributed to Jean-François Le Bas.

13 recordsLinked to original sources

PubMed2005

Prolonged survival of Fischer rats bearing F98 glioma after iodine-enhanced synchrotron stereotactic radiotherapy.

PURPOSE: Heavy-atom-enhanced synchrotron stereotactic radiotherapy (SSR) is a treatment that involves selective accumulation of high-Z elements in tumors followed by stereotactic irradiation with X-rays from a synchrotron source. The purpose of this study was to determine whether the efficacy of iodine-enhanced SSR could be further improved in the F98 rodent glioma model, by using a concomitant injection of an iodinated contrast agent and a transient blood-brain barrier opener (mannitol) during irradiation. METHODS AND MATERIALS: Fourteen days after intracerebral inoculations of F98 cells, the rats were irradiated with 50-keV X-rays while receiving an infusion of hyperosmotic mannitol with iodine, either intravenously or via the carotid (9 to 15 rats per group, 117 rats total). RESULTS: For doses<or=15 Gy, the intracarotid infusion of mannitol and iodine improved the rats' survival compared with intravenous injection or irradiation alone. The percentage-increased life spans (ILS) were 91%, 116%, and 169% without iodine, after infusion of iodine and mannitol intravenously, and intracarotid, respectively (15 Gy). At 25 Gy, the rats irradiated without iodine had the longest survival (ILS=607%), but no additional benefit was obtained with iodine and mannitol. CONCLUSIONS: Iodine-enhanced SSR is significantly improved with concomitant intracarotid infusion of iodine and mannitol for radiation doses<or=15 Gy.

Animals↗

PubMed2005

Sensitivity variation of doped Fricke gel irradiated with monochromatic synchrotron X rays between 33.5 and 80 keV.

An experimental binary radiotherapy proposes the concomitant use of a high-Z compound and synchrotron X rays for enhancing radiation dose selectively in tumours by a photoelectric effect. This study aimed at measuring the resulting dose enhancement in irradiated material. A doped Fricke gel dosemeter model was manufactured with 10 mg ml(-1) of iodine (Telebrix) or barium (Micropaque). Samples were irradiated with a monochromatic synchrotron beam at 33.5, 50, 65 and 80 keV. The ensuing enhancement of the sensitivity of the dosemeter was derived from the nuclear magnetic resonance relaxation rates measured at different X-ray doses. Our results demonstrate (1) the preservation of a linear relationship between relaxation rates and X-ray doses for dosemeters doped with high-Z atoms and (2) a clear energy-dependent sensitivity enhancement for barium-doped Fricke gels. This enhancement was neither reproducible with iodinated compounds nor clearly related to the expected dose enhancement factor. However 1% barium sulphate in the gel could significantly improve the gel's response when it was irradiated by low-energy X rays.

Barium Sulfate↗

PubMed2005

Enhanced delivery of iodine for synchrotron stereotactic radiotherapy by means of intracarotid injection and blood-brain barrier disruption: quantitative iodine biodistribution studies and associated dosimetry.

PURPOSE: Synchrotron stereotactic radiotherapy (SSR) is a binary cancer treatment modality that involves the selective accumulation of a high Z element, such as iodine, in tumors, followed by stereotactic irradiation with kilovoltage X-rays from a synchrotron source. The success of SSR is directly related to the absolute amount of iodine achievable in the tumor. The purposes of this preclinical study were to determine whether the delivery of iodine to brain tumor models in rats could be enhanced by the means of its intracarotid injection with or without a hyperosmotic solution and to evaluate corresponding absorbed X-ray doses. METHODS AND MATERIALS: Experiments were performed on four groups of F98 glioma-bearing rats, which received either intracarotid (IC) or intravenous (IV) infusions of a mixture (6 mL in 12 min) of an iodinated contrast agent associated or not with a transient blood-brain barrier opener (mannitol). The mixture volumetric proportions were 8/13 of Iomeron (C = 350 mg/mL) for 5/13 of mannitol or saline, respectively. Absolute iodine concentration kinetic was measured in vivo in the tumor, blood, contralateral and ipsilateral brain, and muscle by monochromatic computed tomography. Associated dosimetry was performed by computing the iodine dose enhancement factor (DEF) in each region and building dose distribution maps by analytical simulations. RESULTS: Infusion of mannitol significantly enhanced iodine tumor uptake compared with the control values (p < 0.0001 and p = 0.0138, for IC and IV protocols, respectively). The mean iodine concentrations (C) reached 20.5 +/- 0.98 mg/mL (DEF = 4.1) after administration of iodine and mannitol vs. 4.1 +/- 1.2 mg/mL i.c. with serum (DEF = 1.6). The tumor iodine uptakes after jugular injection with mannitol (C = 4.4 +/- 2.1 mg/mL, DEF = 1.7) were not significantly different from IC injection of iodine without mannitol (p = 0.8142). The IV injection of iodine with saline led to an iodine concentration in the tumor of 1.2 +/- 0.98 mg/mL and a DEF of 1.2. CONCLUSIONS: This study established that optimizing the delivery of iodine by means of IC injection combined with a blood-brain barrier opener (mannitol) significantly increases the iodine uptake of F98 rat gliomas. This infusion protocol could potentially enhance the efficacy of SSR treatment, because the radiation dose is proportional to the iodine amount present in the irradiation bed.

Animals↗

PubMed2005

Comparison of synchrotron radiation angiography with conventional angiography for the diagnosis of in-stent restenosis after percutaneous transluminal coronary angioplasty.

AIMS: Synchrotron radiation angiography (SRA) is a novel tool for minimally invasive coronary artery imaging. The method uses subtraction of two images produced at energies bracketing the iodine K-edge after intravenous infusion of iodinated contrast agent. We investigated the accuracy of SRA for detecting in-stent restenosis (ISR). METHODS AND RESULTS: We recruited 57 men, 4-6 months after successful PTCA. We visualized the right coronary artery (RCA) in 27 patients with 36 stented segments [12 segments with ISR>50% by quantitative coronary angiography (QCA)], and the left anterior descending artery (LAD) in 30 patients with 37 stented segments (10 ISR). SRA and QCA were performed within 2 days of each other. Two experienced observers unaware of QCA data evaluated the SRA results. Image quality was good or excellent in most patients. Global sensitivity was 64%, specificity was 95%, and positive and negative predictive values were approximately 85%. Inter-observer kappa concordance coefficient was 0.86. False negatives involved short eccentric lesions and superimposed segments, most frequently of the LAD. False positives occurred in intermediate stenoses slightly overestimated by SRA. CONCLUSION: In men, this minimally invasive approach, using small radiation doses, detects significant ISR in the RCA, but the LAD poses difficulties because of superimposition with others structures.

Adult↗

PubMed2005

High-resolution blood-brain barrier permeability and blood volume imaging using quantitative synchrotron radiation computed tomography: study on an F98 rat brain glioma.

The authors previously provided evidence of synchrotron radiation computed tomography (SRCT) efficacy for quantitative in vivo brain perfusion measurements using monochromatic X-ray beams. However, this technique was limited for small-animal studies by partial volume effects. In this paper, high-resolution absolute cerebral blood volume and blood-brain barrier permeability coefficient measurements were obtained on a rat glioma model using SRCT and a CCD camera (47x47 microm2 pixel size). This is the first report of in vivo high-resolution brain vasculature parameter assessment. The work gives interesting perspectives to quantify brain hemodynamic changes accurately in healthy and pathological small animals.

Animals↗

PubMed2004

In vivo measurement of gadolinium concentration in a rat glioma model by monochromatic quantitative computed tomography: comparison between gadopentetate dimeglumine and gadobutrol.

RATIONALE AND OBJECTIVES: Monochromatic quantitative computed tomography allows a nondestructive and quantitative measurement of gadolinium (Gd) concentration. This technique was used in the C6 rat glioma model to compare gadopentetate dimeglumine and gadobutrol. METHODS: Rats bearing late-stage gliomas received 2.5 mmol/kg (392.5 mg Gd/kg) of gadopentetate dimeglumine (n = 5) and gadobutrol (n = 6) intravenously before the imaging session performed at the European Synchrotron Radiation Facility. RESULTS: Monochromatic quantitative computed tomography enabled in vivo follow-up of Gd concentration as a function of time in specified regions of interest. Surprisingly, after gadobutrol injection, Gd concentrations in the center and periphery of the tumor were higher than those after gadopentetate injection, although identical in normal and contralateral area of the brain. CONCLUSION: The in vivo assessment of absolute Gd concentrations revealed differences in gadobutrol and gadopentetate dimeglumine behaviors in tumoral tissues despite injections in the same conditions. These differences might be attributed to different characteristics of the contrast agents.

Animals↗

PubMed2004

Macrophage imaging in central nervous system and in carotid atherosclerotic plaque using ultrasmall superparamagnetic iron oxide in magnetic resonance imaging.

The long blood circulating time and the progressive macrophage uptake in inflammatory tissues of ultrasmall superparamagnetic iron oxide (USPIO) particles are 2 properties of major importance for magnetic resonance imaging (MRI) pathologic tissue characterization. This article reviews the proof of principle of applications such as imaging of carotid atherosclerotic plaque, stroke, brain tumor characterization, or multiple sclerosis. In the human carotid artery, USPIO accumulation in activated macrophages induced a focal drop in signal intensity compared with preinfusion MRI. The USPIO signal alterations observed in ischemic areas of stroke patients is probably related to the visualization of inflammatory macrophage recruitment into human brain infarction since animal experiments in such models demonstrated the internalization of USPIO into the macrophages localized in these areas. In brain tumors, USPIO particles which do not pass the ruptured blood-brain barrier at early times postinjection can be used to assess tumoral microvascular heterogeneity. Twenty-four hours after injection, when the cellular phase of USPIO takes place, the USPIO tumoral contrast enhancement was higher in high-grade than in low-grade tumors. Several experimental studies and a pilot multiple sclerosis clinical trial in 10 patients have shown that USPIO contrast agents can reveal the presence of inflammatory multiple sclerosis lesions. The enhancement with USPIO does not completely overlap with the gadolinium chelate enhancement. While the proof of concept that USPIO can visualize macrophage infiltrations has been confirmed in animals and patients in several applications (carotid atherosclerotic lesions, stroke, brain tumors and multiple sclerosis), larger prospective clinical studies are needed to demonstrate the clinical benefit of using USPIO as an MRI in vivo surrogate marker for brain inflammatory diseases.

Arteriosclerosis↗

PubMed2003

Synchrotron photoactivation of cisplatin elicits an extra number of DNA breaks that stimulate RAD51-mediated repair pathways.

Combination of cis-platinum with ionizing radiation is one of the most promising anticancer treatments that appears to be more efficient than radiotherapy alone. Unlike conventional X-ray emitters, accelerators of high energy particles like synchrotrons display powerful and monochromatizable radiation that makes the induction of an Auger electron cascade in cis-platinum molecules [also called photoactivation of cis-platinum (PAT-Plat)] theoretically possible. Here, we examined the molecular consequences of one of the first attempts of synchrotron PAT-Plat, performed at the European Synchrotron Research Facility (Grenoble-France). PAT-Plat was found to result in an extra number of slowly repairable DNA double-strand breaks, inhibition of DNA-protein kinase activity, dramatic nuclear relocalization of RAD51, hyperphosphorylation of the BRCA1 protein, and activation of proto-oncogenic c-Abl tyrosine kinase.

Active Transport, Cell Nucleus↗

PubMed2003

Absolute cerebral blood volume and blood flow measurements based on synchrotron radiation quantitative computed tomography.

Synchrotron radiation computed tomography opens new fields by using monochromatic x-ray beams. This technique allows one to measure in vivo absolute contrast-agent concentrations with high accuracy and precision, and absolute cerebral blood volume or flow can be derived from these measurements using tracer kinetic methods. The authors injected an intravenous bolus of an iodinated contrast agent in healthy rats, and acquired computed tomography images to follow the temporal evolution of the contrast material in the blood circulation. The first image acquired before iodine infusion was subtracted from the others to obtain computed tomography slices expressed in absolute iodine concentrations. Cerebral blood volume and cerebral blood flow maps were obtained after correction for partial volume effects. Mean cerebral blood volume and flow values (n = 7) were 2.1 +/- 0.38 mL/100 g and 129 +/- 18 mL. 100 g-1. min-1 in the parietal cortex; and 1.92 +/- 0.32 mL/100 g and 125 +/- 17 mL. 100 g-1. min-1 in the caudate putamen, respectively. Synchrotron radiation computed tomography has the potential to assess these two brain-perfusion parameters.

Animals↗

PubMed2003

Epilepsy and hypothalamic hamartoma: look at the hand Pallister-Hall syndrome.

We report the case of a 29-year-old patient, who suffered from drug resistant laughing seizures since childhood. The clinical examination was normal, except for sequelae of hand and feet surgery during infancy for post-axial polydactyly. Cerebral MRI showed a hypothalamic hamartoma. The association of complex limb abnormalities with hypothalamic hamartoma lead to the diagnosis of Pallister-Hall syndrome. This syndrome is related to a mutation of gene GLI3, located on chromosome 7p13, and its inheritance is autosomal dominant. In the case of laughing seizures, a cerebral MRI should be performed to look for a hypothalamic hamartoma. The observation of such lesions indicates the necessity of standard radiographies of the hands and feet, to search for associated abnormalities. These findings might help to recognize a Pallister-Hall syndrome, thus allowing genetic counseling.

Adult↗

PubMed2003

MRI morphological and volumetric study of the cingulate gyrus and its relevance in partial epileptic patients.

The cingulate gyrus (CG) is often involved during partial epileptic seizures. The purpose of the study was to analyse the CG morphology and to measure the CG volume in epileptic patients, in order to detect subtle MRI abnormalities such as atrophy, which could be indicative of its implication in the epileptogenic area. The population consisted of 20 epileptic patients (31.2 +/- 9.4 years) and 20 normal volunteers (31.8 +/- 7.7 years). The epileptic patients underwent intracerebral recordings, and were sub-divided into five patients presenting with seizures involving the CG (CG 1), seven patients in whom the CG was only secondarily involved (CG 2) and eight patients in whom the CG was not invoved at all (CG 3). All subjects were investigated by MRI (1.5 tesla Gyroscan Philips): axial T1w 3D Gradient Echo acquisitions, thickness 1.5 mm, reconstructions in all planes. At first, we described the sulcal limits of the CG, trying to define a "normalised CG". In a second step, we segmented the CG intrasulcal grey matter using the "Surgiscope Scopeplan" (Elekta). We compared (Mann and Whitney U test [alpha=0.05]), the CG volumes of CG 1 to CG 2 + 3, and the volume of CG 1 and of CG 1 + 2 + 3 to that of normal volunteers. There was no significant difference between CG 1 and CG 2 + 3 (P= 0.89), between CG 1 and normal volunteers (P= 0.75) or between CG1 + 2 + 3 and normal volunteers (P = 0.83). The volumetric analysis showed no atrophy of the CG in epileptic patients and did not distinguish the group in whom seizures involved the CG, from the other groups.

Adult↗

PubMed2002

Imaging of subthalamic nucleus and ventralis intermedius of the thalamus.

The techniques of targeting the subthalamic nucleus (STN) and the ventralis intermedius nucleus (Vim) are similar, only the coordinates are different. Targeting ideally consists of gathering all data about a target and positioning the electrode correctly within that target. The electrode should be positioned within a statistical range of coordinates, where the neuronal firing fits a given pattern and responds to external stimuli, particularly to proprioceptive inputs, in a somatotopically organized manner. Moreover, final placement should provide the best clinical improvement of symptoms under the stimulation parameters expected to be used in the long term. This latter criterion is by far the most important, because intraoperative findings indicate the functional benefit for the patient, which is the ultimate purpose of this surgery. A variety of radiological modalities are available to provide data for electrode placement, but each type has its drawbacks. Ventriculography, although safe when performed accordingly to strict technical procedure, is the most precise method but provides more indirect targeting and is more invasive than magnetic resonance imaging (MRI). MRI is the best method for visualizing the STN and, to some extent, for discerning the Vim, but it is plagued with unpredictable and nonreproducible deformations that induce a systematic distortion. These shortcomings no doubt will be corrected in the near future, and the technologies will better assist us in the proper placement of electrodes, which will provide the patient with the highest possible benefit.

Cerebral Ventriculography↗

PubMed2002

Surgical pathology of drug-resistant partial epilepsy. A 10-year-experience with a series of 327 consecutive resections.

Herein we reviewed the histopathological findings in 327 consecutive surgical specimens from patients with pharmaco-resistant epilepsy (PRE). Three major pathological groups (78.3% of all cases) were identified: Ammon's horn sclerosis (85 cases as an isolated lesion plus 18 as one part of a dual pathology), tumors (94 cases), and malformations (77 cases). Tumors, often associated with cortical dysplasias (CDs), were all of low histological grade and included 61 dysembryoplastic neuroepithelial tumors (DNTs), 29 gangliogliomas, and 4 pleomorphic xanthoastrocytomas (PXAs). Among the malformations were observed 52 CDs, 13 cavernomas, 8 cortical tubers, and 4 cysts. The remaining findings consisted of 16 scars (mostly post-traumatic) and 4 Rasmussen's encephalitis. Fifty-one (15.6%) specimens contained non-specific changes, and histological samples from 215 patients with presurgical implantation of electrodes revealed iatrogenic changes. All these figures are in agreement with the most recent and comparable series, and confirm the high incidence of DNTs that appear clearly as the most common tumoral entity in PRE. Our data also support the hypothesis of a close histogenetic relationship between DNT, ganglioglioma, and PXA, with a putative common origin from pluripotential progenitor CD34 positive cells of the subpial granular layer. As for CDs, our study confirms the clinical relevance of two main subtypes: severe CD (or Taylor's type CD) with neuronal cytomegaly and balloon cells, and non-Taylor's type CDs with a better outcome. Eventually, this series demonstrates that most patients have significant histopathological lesions, among which, aspects that are relevant to the diagnostic surgical pathologist are highlighted [published with a complete image database on CD-Rom].

Adolescent↗