F Estève

University of Grenoble, Grenoble, Rhône-Alpes, France

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Publications (65)171.59 Total impact

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    ABSTRACT: Epilepsy is one of the most important neurological diseases. It concerns about 1% of the population worldwide. Despite the discovery of new molecules, one third of epileptic patients are resistant to anti-epileptic drugs and among them only a few can benefit from resective surgery. In this context, radiotherapy is an interesting alternative to the other treatments and several clinical devices exist (e.g., Gamma Knife(®)). The European Synchrotron Radiation Facility offers the possibility to develop new methods of radiosurgery and to study their antiepileptic effects. Here, we discuss several studies that we performed recently to test and try to understand the antiepileptic effects of X-ray synchrotron microbeams in different animal models of epilepsy. We showed a decrease of seizures after Interlaced Microbeam Radiotherapy (IntMRT) of the somatosensory cortex, known as the seizure generator, in a genetic model of absence epilepsy. These antiepileptic effects were stable over 4 months and with low tissular and functional side-effects. The irradiated pyramidal neurons still displayed their physiological activity but did not synchronize anymore. We also obtained a lasting suppression of seizures after IntMRT of the dorsal hippocampus in a mouse model of mesiotemporal lobe epilepsy. However, an important variability of antiepileptic efficiency was observed probably due to the small size of the targeted structure. Despite these encouraging proofs-of-concepts, there is now a need to adapt IntMRT to other models of epilepsy in rodents which are close to refractory forms of epilepsy in human patients and to implement this approach to non-human primates, before moving to clinical trials. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
    Full-text · Article · Apr 2015 · Physica Medica
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    ABSTRACT: Background Exercise training has been shown to improve cardiometabolic health in obese adolescents. Objectives Evaluate the impact of a 12-week exercise-training programme (without caloric restriction) on obese adolescents' cardiometabolic and vascular risk profiles. Methods We measured systemic markers of oxidation, inflammation, metabolic variables and endothelial function in 20 obese adolescents (OB) (age: 14.51.5years; body mass index: 34.04.7kgm(-2)) and 20 age- and gender-matched normal-weight adolescents (NW). Body composition was assessed by magnetic resonance imagery. Peak aerobic capacity and maximal fat oxidation were evaluated during specific incremental exercise tests. OB participated in a 12-week exercise-training programme. ResultsOB presented lower peak aerobic capacity (24.2 +/- 5.9 vs. 39.8 +/- 8.3mLkg(-1)min(-1), P<0.05) and maximal fat oxidation compared with NW (P<0.05). OB displayed greater F2t-Isoprostanes (20.5 +/- 6.7 vs. 13.4 +/- 4.2ngmmol(-1) creatinine), Interleukin-1 receptor antagonist (IL-1Ra) (1794.8 +/- 532.2 vs. 835.1 +/- 1027.4pgmL(-1)), Tumor Necrosis Factor- (TNF-) (2.1 +/- 1.2 vs. 1.5 +/- 1.0pgmL(-1)), Soluble Tumor Necrosis Factor- Type II Receptor (sTNFRII), leptin, insulin, homeostasis model assessment of insulin resistance, version 2 (HOMA2-IR), high-sensitive C-reactive protein, triglycerides and lower adiponectin and high-density lipoprotein cholesterol (all P<0.05). After exercise training, despite lack of weight loss, VO2peak (mL.kg(-1).min(-1)) and maximal fat oxidation increased (P<0.05). IL-1Ra and IFN-gamma-inducible protein 10 (IP-10) decreased (P<0.05). Insulin and HOMA2-IR decreased (14.8 +/- 1.5 vs. 10.2 +/- 4.2 UImL(-1) and 1.9 +/- 0.8 vs. 1.3 +/- 0.6, respectively, P<0.05). Change in visceral fat mass was inversely associated with change in maximal fat oxidation (r=-0.54; P=0.024). The subgroup of participants that lost visceral fat mass showed greater improvements in triglycerides, insulin resistance and maximal fat oxidation. Conclusion Our data confirms the role of exercise training on improving the inflammatory profile and insulin resistance of OB in the absence of weight loss. However, those who lost a greater amount of visceral fat mass showed greater benefits in terms of insulin profile, triglycerides and maximal fat oxidation.
    Full-text · Article · Aug 2014 · Pediatric Obesity
  • L Obeid · M Schmitt · F Esteve · J Adam
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    ABSTRACT: Purpose: Iodine-enhanced radiotherapy is an innovative treatment combining the selective accumulation of an iodinated contrast agent in brain tumors with irradiations using monochromatic medium energy x-rays. The radiation dose enhancement depends on the time course of iodine in the tumors. A prolonged CT scanning (∼30 min) is required to follow-up iodine kinetics for recruited patients. This protocol could lead to substantial radiation dose to the patient. A novel method is proposed to reduce the acquisition time.
    No preview · Article · Jun 2014 · Medical Physics
  • L Obeid · A Tessier · J Balosso · F Esteve · J.F. Adam
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    ABSTRACT: Purpose: Synchrotron stereotactic radiotherapy (SSRT) is an innovative treatment combining the selective accumulation of heavy elements in tumors with stereotactic irradiations using monochromatic medium energy x-rays from a synchrotron source. Phase I/II clinical trials on brain metastasis are underway using venous infusion of iodinated contrast agents. The radiation dose enhancement depends on the amount of iodine in the tumor and its time course. In the present study, the reproducibility of iodine concentrations between the CT planning scan day (Day 0) and the treatment day (Day 10) was assessed in order to predict dose errors.
    No preview · Article · Jun 2014 · Medical Physics

  • No preview · Article · Apr 2014 · Radiotherapy and Oncology
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    ABSTRACT: This study investigated the changes in cerebral near-infrared spectroscopy (NIRS) signals, cerebrovascular and ventilatory responses to hypoxia and CO2 during altitude exposure. At sea level (SL), after 24 hours and 5 days at 4,350 m, 11 healthy subjects were exposed to normoxia, isocapnic hypoxia, hypercapnia, and hypocapnia. The following parameters were measured: prefrontal tissue oxygenation index (TOI), oxy- (HbO2), deoxy- and total hemoglobin (HbTot) concentrations with NIRS, blood velocity in the middle cerebral artery (MCAv) with transcranial Doppler and ventilation. Smaller prefrontal deoxygenation and larger ΔHbTot in response to hypoxia were observed at altitude compared with SL (day 5: ΔHbO2-0.6±1.1 versus -1.8±1.3 μmol/cmper mm Hg and ΔHbTot 1.4±1.3 versus 0.7±1.1 μmol/cm per mm Hg). The hypoxic MCAv and ventilatory responses were enhanced at altitude. Prefrontal oxygenation increased less in response to hypercapnia at altitude compared with SL (day 5: ΔTOI 0.3±0.2 versus 0.5±0.3% mm Hg). The hypercapnic MCAv and ventilatory responses were decreased and increased, respectively, at altitude. Hemodynamic responses to hypocapnia did not change at altitude. Short-term altitude exposure improves cerebral oxygenation in response to hypoxia but decreases it during hypercapnia. Although these changes may be relevant for conditions such as exercise or sleep at altitude, they were not associated with symptoms of acute mountain sickness.Journal of Cerebral Blood Flow & Metabolism advance online publication, 25 September 2013; doi:10.1038/jcbfm.2013.167.
    Full-text · Article · Sep 2013 · Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism
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    ABSTRACT: Synchrotron radiation (SR), which combines extremely high intensity, high collimation, tunability, and continuous energy spectrum, allows the development of advanced X-ray based techniques that are becoming a uniquely useful tool in life science research, along providing exciting opportunities in biomedical imaging and radiotherapy. This review summarize emerging techniques and their potential to greatly enhance the exploration of dynamical biological process occurring across various spatial and temporal regimes, from whole body physiology, down to the location of individual chemical species within single cells. In recent years pediatric research and clinic practice have started to profit from these new opportunities, particularly by extending the diagnostic and therapeutic capabilities of these X-ray based techniques. In diagnosis, technical advances in DEI and KES imaging modalities have been demonstrated as particularly valuable for children and women since SR allows dose minimization, with significant reductions compared to conventional approaches. However, the greatest expectations are in the field of SR based radiotherapy, increasingly studies are demonstrating SR radiotherapy provides improved chances of recovery; this is especially the case for pediatric patients. In addition, we report on the applicability of advanced X-ray microscopy techniques that offer exceptional spatial and quantitative resolution in elemental detection. These techniques, which are useful for in vitro studies, will be particularly advantageous where investigators seek deeper understanding of diseases where mismetabolism of metals, either physiological important (i.e. Ca, Zn) or outright toxic (i.e. Hg, Pb), underlies pathogenesis.
    No preview · Article · Feb 2013 · Current Medicinal Chemistry
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    ABSTRACT: Changes in cerebral perfusion and CO(2) cerebrovascular reactivity during and immediately after a sojourn at high altitude remain unclear but may be critical for acclimatization. The aim of the present study was to assess the effects of 6days at 4,350m on cerebral perfusion and cerebrovascular reactivity (CVR) to CO(2) by arterial spin labeling (ASL) magnetic resonance imaging at sea level and to compare it with transcranial Doppler (TCD) results at altitude. Eleven healthy male subjects, non-acclimatized to altitude, stayed for 6days at 4,350m (Observatoire Vallot, massif du Mont-Blanc). Prior to the stay and within 6h after returning to sea level, subjects were investigated using pseudo-continuous ASL at 3T during a block-design inhalation paradigm to measure basal cerebral blood flow (CBF) and CO(2) CVR. End-tidal CO(2) (PetCO(2)), respiratory rate, heart rate and oxygen saturation were recorded during the exam. Subjects were also examined using TCD prior to and on day 5 of the stay at altitude to measure blood velocity in the middle cerebral artery (MCAv) and CO(2) CVR. CO(2) CVR was expressed as percent change in ASL CBF or TCD MCAv per mmHg change in PetCO(2). PetCO(2) was significantly decreased during and after altitude. Significant increases in TCD MCAv compared to before altitude measurements were observed on day 5 at altitude (+20.5±15.5 %). Interestingly, ASL CBF remained increased in the MCA and anterior vascular territories (+22.0±24.1 % and 20.5±20.3 %, respectively) after altitude under normoxic conditions. TCD CVR tended to decrease on day 5 at 4,350m (-12.3±54.5 % in the MCA) while the ASL CVR was significantly decreased after altitude (-29.5±19.8 % in the MCA). No correlation was observed between cerebral hemodynamic changes and symptoms of acute mountain sickness at high altitude. In conclusion, prolonged exposure to high altitude significantly increases blood flow during the altitude stay and within 6h after returning to sea level. Decreased CO(2) CVR after prolonged altitude exposure was also observed using ASL. Changes in cerebral hemodynamics with altitude exposure probably involve other mechanisms than the vasodilatory effect of hypoxia only, since it persists under normoxia several hours following the descent.
    Full-text · Article · Feb 2013 · NeuroImage
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    ABSTRACT: The aim of this study was to examine ventilatory responses to training in obese adolescents. We assessed body composition, pulmonary function and ventilatory responses (among which expiratory flow limitation and operational lung volumes) during progressive cycling exercise in 16 obese adolescents (OB) before and after 12 weeks of exercise training and in 16 normal-weight volunteers. As expected, obese adolescents' resting expiratory reserve volume was lower and inversely correlated with thoraco-abdominal fat mass (r=-0.74, p<0.0001). OB presented lower end expiratory (EELV) and end inspiratory lung volumes (EILV) at rest and during submaximal exercise, and modest expiratory flow limitation. After training, OB increased maximal aerobic performance (+19%) and maximal inspiratory pressure (93.7±31.4 vs 81.9±28.2cmH(2)O, +14%) despite lack of decrease in trunk fat and body weight. Furthermore, EELV and EILV were greater during submaximal exercise (+11% and +9% in EELV and EILV, respectively), expiratory flow limitation delayed but was not accompanied by increased V(T). However, submaximal exertional symptoms (dyspnea and leg discomfort) were significantly decreased (-71.3% and -70.7%, respectively). Our results suggest that exercise training can improve pulmonary function at rest (static inspiratory muscle strength) and exercise (greater operating lung volumes and delayed expiratory flow limitation) but these modifications did not entirely account for improved dyspnea and exercise performance in obese adolescents.
    Full-text · Article · Aug 2012 · Respiratory Physiology & Neurobiology

  • No preview · Article · Mar 2012 · Journal of Neuroradiology
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    ABSTRACT: Monochromatic x-ray minibeam radiotherapy is a new radiosurgery approach based on arrays of submillimetric interlaced planar x-ray beams. The aim of this study was to characterize the dose distributions obtained with this new modality when being used for preclinical trials. Monte Carlo simulations were performed in water phantoms. Percentage depth-dose curves and dose profiles were computed for single incidences and interleaved incidences of 80 keV planar x-ray minibeam (0.6 × 5 mm) arrays. Peak to valley dose ratios were also computed at various depths for an increasing number of minibeams. 3D experimental polymer gel (nPAG) dosimetry measurements were performed using MRI devices designed for small animal imaging. These very high spatial resolution (50 µm) dose maps were compared to the simulations. Preclinical minibeams dose distributions were fully characterized. Experimental dosimetry correlated well with Monte Carlo calculations (Student t-tests: p > 0.1). F98 tumor-bearing rats were also irradiated with interleaved minibeams (80 keV, prescribed dose: 25 Gy). This associated preclinical trial serves as a proof of principle of the technique. The mean survival time of irradiated glioma-bearing rats increased significantly, when compared to the untreated animals (59.6 ± 2.8 days versus 28.25 ± 0.75 days, p < 0.001).
    Full-text · Article · Jun 2011 · Physics in Medicine and Biology
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    ABSTRACT: Purpose: Contrast‐enhanced stereotactic synchrotron radiation therapy (SSRT) is an innovative technique based on localized dose‐enhancement effects obtained by reinforced photoelectric absorption in the target. Medium energy monochromatic x‐rays (50 –100 keV) are used for irradiating tumors previously loaded with high‐Z elements. SSRT clinical trials are being prepared at the ESRF. The first patients (scheduled in summer‐autumn 2011) should be treated at 80 keV, with 10 conformational beams. The treatment plan will use CTimages acquired prior and after systemic iodine injection. However the exact dose delivered to the patient relies on the exact 3D iodine biodistribution in the tumor during the treatment itself. An in vivo dosimetry methodology based on portal imaging was developed to retrieve the absolute 3D iodine concentrations reached during the treatment. Methods: The proposed algorithm uses the images acquired with a high‐purity germaniumdetector located behind the patient. The proposed methodology has to solve a tomography reconstruction problem with a restricted field of view (local tomography) and a limited number of projections (10 at maximum). None of the currently available algorithms can solve both local and limited projection tomography problems at once while being quantitative. However, in SSRT, a large amount of a priori information is available (three CT‐scans acquired prior the treatment, with and without iodine). Thus the proposed algorithm proposed in this paper is based on filtered backprojection and uses extensively the a priori information related to patient morphology, with a few geometrical hypothesis. Results: The results obtained from numerical simulation on a human head phantom show that the proposed algorithm is able to retrieve the iodine concentrations with a relative error lower than 2%. Conclusions: The in vivo dosimetry methodology for SSRT has been validated with numerical simulations. It has now to be tested on real patient data before the first patient is treated.
    No preview · Article · Jun 2011 · Medical Physics

  • No preview · Article · May 2011 · Medical Physics
  • H. Elleaume · J. Rousseau · J.-F. Adam · F. Estève

    No preview · Article · Apr 2011 · Cancer/Radiothérapie
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    ABSTRACT: An adequate dosimetry protocol for synchrotron radiation and the specific features of the ID17 Biomedical Beamline at the European Synchrotron Radiation Facility are essential for the preparation of the forthcoming clinical trials in the synchrotron stereotactic radiation therapy (SSRT). The main aim of this work is the definition of a suitable protocol based on standards of dose absorbed to water. It must allow measuring the absolute dose with an uncertainty within the recommended limits for patient treatment of 2%-5%. Absolute dosimetry is performed with a thimble ionization chamber (PTW semiflex 31002) whose center is positioned at 2 g cm(-2) equivalent depth in water. Since the available synchrotron beam at the ESRF Biomedical Beamline has a maximum height of 3 mm, a scanning method was employed to mimic a uniform exposition of the ionization chamber. The scanning method has been shown to be equivalent to a broad beam irradiation. Different correction factors have been assessed by using Monte Carlo simulations. The absolute dose absorbed to water at 80 keV was measured in reference conditions with a 2% global uncertainty, within the recommended limits. The dose rate was determined to be in the range between 14 and 18 Gy/min, that is to say, a factor two to three times higher than the 6 Gy/min achievable in RapidArc or VMAT machines. The dose absorbed to water was also measured in a RW3 solid water phantom. This phantom is suitable for quality assurance purposes since less than 2% average difference with respect to the water phantom measurements was found. In addition, output factors were assessed for different field sizes. A dosimetry protocol adequate for the specific features of the SSRT technique has been developed. This protocol allows measuring the absolute dose absorbed to water with an accuracy of 2%. It is therefore satisfactory for patient treatment.
    No preview · Article · Mar 2011 · Medical Physics
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    M Fernandez · JF Adam · F Estève · H Elleaume

    Full-text · Article · Jan 2011

  • No preview · Article · Jan 2011 · Medical Physics
  • H Elleaume · J Rousseau · J-F Adam · F Estève

    No preview · Article · Dec 2010 · Cancer/Radiothérapie
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    ABSTRACT: Radiation therapy is commonly used in the treatment of cancer. The normal tissue tolerance can be a limit to deliver enough dose to the tumor to be curative. The synchrotron beam presents some interesting physical properties, which could decrease this limitation. Synchrotron beam is a medium energy X-ray nearly parallel beam with high intensity. Three methods are under preclinical investigations: the microbeam, the minibeam and the stereotactic radiotherapy. The first two use a geometric irradiation effect called spatial fractioning. The last one use highly conformational irradiation geometry combined with a dose enhancement due to the presence of high-Z element in the target. Synchrotron radiotherapy preclinical experiments have shown some curative effect on rodent glioma models. Following these encouraging results a phase I/II clinical trial of iodinated enhanced stereotactic synchrotron radiotherapy is currently being prepared at the European Synchrotron Radiation Facility.
    No preview · Article · Aug 2010 · La Revue de Médecine Interne
  • [Show abstract] [Hide abstract]
    ABSTRACT: Radiation therapy is commonly used in the treatment of cancer. The normal tissue tolerance can be a limit to deliver enough dose to the tumor to be curative. The synchrotron beam presents some interesting physical properties, which could decrease this limitation. Synchrotron beam is a medium energy X-ray nearly parallel beam with high intensity. Three methods are under preclinical investigations: the microbeam, the minibeam and the stereotactic radiotherapy. The first two use a geometric irradiation effect called spatial fractioning. The last one use highly conformational irradiation geometry combined with a dose enhancement due to the presence of high-Z element in the target. Synchrotron radiotherapy preclinical experiments have shown some curative effect on rodent glioma models. Following these encouraging results a phase I/II clinical trial of iodinated enhanced stereotactic synchrotron radiotherapy is currently being prepared at the European Synchrotron Radiation Facility.
    No preview · Article · Aug 2010 · La Revue de Médecine Interne

Publication Stats

1k Citations
171.59 Total Impact Points

Institutions

  • 2012-2015
    • University of Grenoble
      Grenoble, Rhône-Alpes, France
  • 1999-2014
    • Centre Hospitalier Universitaire de Grenoble
      Grenoble, Rhône-Alpes, France
  • 2004-2013
    • University Joseph Fourier - Grenoble 1
      • Grenoble Institut des Neurosciences
      Grenoble, Rhône-Alpes, France
  • 2008-2011
    • European Synchrotron Radiation Facility
      • Division of Experiments
      Grenoble, Rhône-Alpes, France
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 1997
    • Unité Inserm U1077
      Caen, Lower Normandy, France