F Estève

University of Grenoble, Grenoble, Rhône-Alpes, France

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Publications (64)168.2 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.
    Physica Medica 04/2015; DOI:10.1016/j.ejmp.2015.04.005 · 1.85 Impact Factor
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    ABSTRACT: Exercise training has been shown to improve cardiometabolic health in obese adolescents.
    Pediatric Obesity 08/2014; DOI:10.1111/ijpo.255 · 2.42 Impact Factor
  • 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.
    Medical Physics 06/2014; 41(6):379-379. DOI:10.1118/1.4888993 · 3.01 Impact Factor
  • 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.
    Medical Physics 06/2014; 41(6):381-381. DOI:10.1118/1.4889001 · 3.01 Impact Factor
  • Radiotherapy and Oncology 04/2014; 111:S81-S82. DOI:10.1016/S0167-8140(15)30310-8 · 4.86 Impact Factor
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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.
    Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 09/2013; DOI:10.1038/jcbfm.2013.167 · 5.34 Impact Factor
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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.
    NeuroImage 02/2013; 72. DOI:10.1016/j.neuroimage.2013.01.066 · 6.36 Impact Factor
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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.
    Respiratory Physiology & Neurobiology 08/2012; 184(1):73-9. DOI:10.1016/j.resp.2012.08.001 · 1.97 Impact Factor
  • Journal of Neuroradiology 03/2012; 39(1):36. DOI:10.1016/j.neurad.2012.01.109 · 1.13 Impact Factor
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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).
    Physics in Medicine and Biology 06/2011; 56(14):4465-80. DOI:10.1088/0031-9155/56/14/015 · 2.92 Impact Factor
  • Medical Physics 05/2011; 99. DOI:10.1016/S0167-8140(11)71698-X · 3.01 Impact Factor
  • H. Elleaume · J. Rousseau · J.-F. Adam · F. Estève
    Cancer/Radiothérapie 04/2011; 15(2):161-164. DOI:10.1016/j.canrad.2010.07.637 · 1.11 Impact Factor
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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.
    Medical Physics 03/2011; 38(3):1709-17. DOI:10.1118/1.3556561 · 3.01 Impact Factor
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    M Fernandez · JF Adam · F Estève · H Elleaume
  • Medical Physics 01/2011; 38(6):3534-. DOI:10.1118/1.3612157 · 3.01 Impact Factor
  • Medical Physics 01/2011; 38(6):3564-. DOI:10.1118/1.3612289 · 3.01 Impact Factor
  • H Elleaume · J Rousseau · J-F Adam · F Estève
    Cancer/Radiothérapie 12/2010; 15(2):161-4; author reply 164-7. · 1.11 Impact Factor
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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.
    La Revue de Médecine Interne 08/2010; 31(8):586-9. · 1.32 Impact Factor
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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.
    La Revue de Médecine Interne 08/2010; 31(8):586-589. DOI:10.1016/j.revmed.2009.12.012 · 1.32 Impact Factor
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    ABSTRACT: Synchrotron radiation (SR) therapy is a promising alternative to treat brain tumors, whose management is limited due to the high morbidity of the surrounding healthy tissues. Several approaches are being explored by using SR at the European Synchrotron Radiation Facility (ESRF), where three techniques are under development: Synchrotron Stereotactic Radiation Therapy (SSRT), Microbeam Radiation Therapy (MRT) and Minibeam Radiation Therapy (MBRT). The sucess of the preclinical studies on SSRT and MRT has paved the way to clinical trials currently in preparation at the ESRF. With this aim, different dosimetric aspects from both theoretical and experimental points of view have been assessed. In particular, the definition of safe irradiation protocols, the beam energy providing the best balance between tumor treatment and healthy tissue sparing in MRT and MBRT, the special dosimetric considerations for small field dosimetry, etc will be described. In addition, for the clinical trials, the definition of appropiate dosimetry protocols for patients according to the well established European Medical Physics recommendations will be discussed. Finally, the state of the art of the MBRT technical developments at the ESRF will be presented. In 2006 A. Dilmanian and collaborators proposed the use of thicker microbeams (0.36-0.68 mm). This new type of radiotherapy is the most recently implemented technique at the ESRF and it has been called MBRT. The main advantage of MBRT with respect to MRT is that it does not require high dose rates. Therefore it can be more easily applied and extended outside synchrotron sources in the future.
    07/2010; 1266(1):101-106. DOI:10.1063/1.3478185

Publication Stats

866 Citations
168.20 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
  • 1997–2010
    • Unité Inserm U1077
      Caen, Lower Normandy, France