François Estève

Joseph Fourier University | UJF · UFR Médecine

Background. Since vascular responses to hypoxia in both healthy high-altitude natives and chronic mountain sickness (a maladaptive high-altitude pathology characterised by excessive erythrocytosis and the presence of symptoms – CMS) remain unclear, the role of inflammation and oxidative/nitrosative stress on the endothelium-dependent and -independe...

To develop a simplified magnetic resonance imaging method (MRI) to assess total adipose tissue (AT) and adipose tissue free mass (ATFM) from three single MRI slices in people with overweight/obesity in order to implement body composition follow-up in a clinical research setting. Body composition of 310 participants (70 women and 240 men, age: 50.8...

Left/right prefrontal cortex (PFC) activation is linked to positive/negative affects, respectively. Besides, larger left PFC oxygenation during exercise relates to higher cardiorespiratory fitness (CRF). High-intensity interval training (HIIT) is superior to moderate-intensity continuous training (MICT) in improving CRF. The influence of training o...

Introduction Chronic mountain sickness (CMS) is a condition characterized by excessive erythrocytosis in response to chronic hypobaric hypoxia. CMS frequently triggers cardiorespiratory diseases such as pulmonary hypertension and right or left heart failure. Ambient hypoxia might be further amplified night-time by intermittent hypoxia related to sl...

Introduction The high potential of Microbeam Radiation Therapy (MRT) in improving tumor control whilst reducing side effects has been shown by numerous preclinical studies. MRT offers a widened therapeutic window by using the periodical spatial fractionation of synchrotron generated x-rays into an array of intense parallel microbeams. MRT now enter...

Background Considering the potential greater cardiocirculatory effects of high intensity interval training (HIIT), we hypothesized that a 2-month supervised a high volume short interval HIIT would induce greater improvements in CRF and cardiometabolic risk and increase long-term maintenance compared to isocaloric moderate intensity continuous train...

Background. Physical activity is a cornerstone for the management of obesity. Owing to, in part, lower pleasure, this population however perform very little exercise.[1] From a physiopsychological standpoint, left and right prefrontal cortex (PFC) activation are thought to be related to positive and negative affects, respectively.[2] Moreover, larg...

Purpose: Positive expiratory pressure (PEP) breathing has been shown to increase arterial oxygenation during acute hypoxic exposure but the underlying mechanisms and consequences on symptoms during prolonged high-altitude exposure remain to be elucidated. Methods: Twenty-four males (41 ± 16 years) were investigated, at sea level and at 5,085 m afte...

New findings: What is the central question of this study? This study is the first investigating the effects of high-altitude trekking on biventricular mechanics including measurements of left ventricular (LV) subendocardial and subepicardial function. What is the main finding and its importance? We provide new evidence that an increased contractil...

Since the invention of Computed Tomography (CT), many technological advances emerged to improve the image sensitivity and resolution. However, no new source types were developed for clinical use. In this study, for the first time, coherent monochromatic X-rays from a synchrotron radiation source were used to acquire 3D CTs on patients. The aim of t...

Microbeam irradiation is spatially fractionated radiation on a micrometer scale. Microbeam irradiation with therapeutic intent has become known as microbeam radiation therapy (MRT). The basic concept of MRT was developed in the 1980s, but it has not yet been tested in any human clinical trial, even although there is now a large number of animal stu...

A computational model was developed to describe experimentally observed vascular changes induced by the introduction of a tumour on a mouse equipped with a dorsal skinfold chamber. The vascular structure of the host tissue was segmented from in vivo images and transposed into the computational framework. Simulations of tumour-induced vascular chang...

Objective: Hypoxic exposure in healthy subjects can induce acute mountain sickness including headache, lethargy, cerebral dysfunction, and substantial cerebral structural alterations which, in worst case, can lead to potentially fatal high altitude cerebral edema. Within this context, the relationships between high altitude-induced cerebral edema,...

Synchrotron-generated X-ray (SRX) microbeams deposit high radiation doses to submillimetric targets whilst minimizing irradiation of neighboring healthy tissue. We developed a new radiosurgical method which demonstrably transects cortical brain tissue without affecting adjacent regions. We made such image-guided SRX microtransections in the left so...

The design of a patient-specific virtual tumour is an important step towards Personalized Medicine. However this requires to capture the description of many key events of tumour development, including angiogenesis, matrix remodelling, hypoxia, and cell state heterogeneity that will all influence the tumour growth kinetics and degree of tumour invas...

Simulation of tumour growth over 28 days corresponding to the experimental cas M4-L displayed in figure 4.

The present study assessed the isolated and synergetic effects of hypoxic exposure and prolonged exercise on cerebral volume and subedema and symptoms of acute mountain sickness (AMS). Twelve healthy males performed three semirandomized blinded 11-hour sessions with (1) an inspiratory oxygen fraction (FiO2) of 12% and 4-hour cycling, (2) FiO2=21% a...

Contrast-enhanced radiotherapy is an innovative treatment that combines the selective accumulation of heavy elements in tumors with stereotactic irradiations using medium energy X-rays. The radiation dose enhancement depends on the absolute amount of iodine reached in the tumor and its time course. Quantitative, postinfusion iodine biodistribution...

Unlabelled: Radiosensitization efficacy of gold nanoparticles (AuNPs) with low energy radiations (88 keV) was evaluated in vitro and in vivo on rats bearing glioma. In vitro, a significant dose-enhancement factor was measured by clonogenic assays after irradiation with synchrotron radiation of F98 glioma cells in presence of AuNPs (1.9 and 15 nm i...

Cerebral blood flow (CBF) is the most common parameter for the quantification of brain's function. Literature data indicate a widespread dispersion of values that might be related to some differences in the measurement conditions that are not properly taken into account in CBF evaluation. Using recent high-resolution imaging of the complete cortica...

Performing exercise during the first hours of hypoxic exposure is thought to exacerbate acute mountain sickness (AMS), but whether this is due to increased hypoxemia or other mechanisms associated with exercise remains unclear. In 12 healthy males, AMS symptoms were assessed during three 11-h experimental sessions: i) in Hypoxia-exercise, inspirato...

Background The purpose of the present study was to compare side-by-side the therapeutic efficacy of a 6-day infusion of carboplatin, followed by X-irradiation with either 6 MV photons or synchrotron X-rays, tuned above the K-edge of Pt, for treatment of F98 glioma bearing rats. Methods Carboplatin was administered intracerebrally (i.c.) to F98 gli...

A computational model is potentially a powerful tool to apprehend complex phenomena like solid tumour growth and to predict the outcome of therapies. To that end, the confrontation of the model with experiments is essential to validate this tool. In this study, we develop a computational model specifically dedicated to the interpretation of tumour...

The purpose of this study was to evaluate high-dose single fraction delivered with monochromatic X-rays minibeams for the radiotherapy of primary brain tumors in rats. Two groups of healthy rats were irradiated with one anteroposterior minibeam incidence (four minibeams, 123 Gy prescribed dose at 1 cm depth in the brain) or two interleaved incidenc...

Reduction of aerobic exercise performance observed under hypoxic conditions is mainly attributed to altered muscle metabolism due to impaired O(2) delivery. It has been recently proposed that hypoxia-induced cerebral perturbations may also contribute to exercise performance limitation. A significant reduction in cerebral oxygenation during whole bo...

Although the quality of imaging techniques available for neurovascular angiography in the hospital environment has significantly improved over the last decades, the equipment used for clinical work is not always suited for neurovascular research in animal models. We have previously investigated the suitability of synchrotron-based K-edge digital su...

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 tria...

After decades of intensive research, high-grade gliomas are still resistant to therapies, including surgery, chemotherapy, and radiotherapy or a combination thereof. The most important advance in the treatment of these tumors has been the introduction of a new chemotherapy drug called temozolomide, in combination with external beam photon irradiati...

Gliomas are the most common primary brain tumor affecting human adults and remain a therapeutic challenge because cells of origin are still unknown. Here, we investigated the cellular origin of low-grade gliomas in a rat model based on transplacental exposure to N-ethyl-N-nitrosourea (ENU). Longitudinal magnetic resonance imaging coupled to immunoh...

Purpose: Synchrotron stereotactic radiotherapy (SSRT) is a treatment that involves the targeting of high-Z elements into tumors followed by stereotactic irradiation with monochromatic x-rays from a synchrotron source, tuned at an optimal energy. The irradiation geometry, as well as the secondary particles generated at a higher yield by the medium...

Microbeam Radiation Therapy (MRT) is a preclinical form of radiosurgery dedicated to brain tumor treatment. It uses micrometer-wide synchrotron-generated X-ray beams on the basis of spatial beam fractionation. Due to the radioresistance of normal brain vasculature to MRT, a continuous blood supply can be maintained which would in part explain the s...

We have evaluated the efficacy of intracerebral (i.c.) convection-enhanced delivery (CED) of cisplatin in combination with photon irradiation for the treatment of F98 glioma-bearing rats. One thousand glioma cells were stereotactically implanted into the brains of Fischer rats and 13 days later cisplatin (6 microg/20 microl) was administered i.c. b...

To analyze the effects of the microbeam width (25, 50 and 75 microm) on the survival of 9L gliosarcoma tumor-bearing rats and on toxicity in normal tissues in normal rats after microbeam radiation therapy (MRT), 9L gliosarcomas implanted in rat brains, as well as in normal rat brains, were irradiated in the MRT mode. Three configurations (MRT25, MR...

The high temporal, spatial and contrast resolution of synchrotron radiation imaging (SYRI) allows the measurement of the residual density of an injected contrast medium with high precision and delivers absolute values. This was exploited with measurements on pigs where it could be shown that the identification and characterization of the relevant c...

Iodine-enhanced synchrotron stereotactic radiotherapy takes advantage of the radiation dose-enhancement produced by high-Z elements when irradiated with mono-energetic beams of synchrotron X-rays. In this study it has been investigated whether therapeutic efficacy could be improved using a thymidine analogue, 5-iodo-2'-deoxyuridine (IUdR), as a rad...

K-edge digital subtraction angiography (KEDSA) combined with the tunability of synchrotron beam yields an imaging technique that is highly sensitive to low concentrations of contrast agents. Thus, contrast agent can be administered intravenously, obviating the need for insertion of a guided catheter to deliver a bolus of contrast agent close to the...

The first practical application of X-rays, more than 100 years ago, was for biomedical imaging. Although not central to the initial development of 3rd generation synchrotron light sources, imaging techniques have today established themselves as a core element of the research program at all major light sources, including the ESRF, where X-ray imagin...

The goal of the present study was to evaluate the efficacy of intracerebral (i.c.) administration of carboplatin by means of convection-enhanced delivery (CED) in combination with fractionated, external beam photon irradiation for the treatment of F98 glioma-bearing rats. Carboplatin (20 microg/20 microL) was administrated i.c. by CED to F98 glioma...

To evaluate direct intracerebral and intratumoral iodine delivery as means to improve iodine distribution for synchrotron stereotactic radiotherapy (SSR) and to evaluate the corresponding X-ray dose distribution. Healthy rats and F98 glioma-bearing rats received an iodinated contrast agent (iopamidol) intracerebrally either by bolus injection (5 mi...

At the medical beamline of the European Synchrotron Radiation Facility (ESRF), a new radiotherapy technique called synchrotron stereotactic radiotherapy (SSR) is under development. During an SSR treatment, it has been demonstrated that iodine should perfuse the tumour for achieving acceptable dose distributions within a human head (Boudou C, Baloss...

The specificity of synchrotron stereotactic radiotherapy requires new developments in dose calculation and appropriate experimental procedures. The medical beamline of the European Synchrotron Radiation Facility allows quantitative synchrotron radiation CT (SRCT) images to be obtained from a monochromatic x-ray beam. This paper investigates initial...

K-edge digital subtraction angiography (KEDSA), a recently developed synchrotron-based technique, utilizes monochromatic radiation and allows acquisition of high-quality angiography images after intravenous administration of contrast agent. We tested KEDSA for its suitability for intravenous cerebral angiography in an animal model. Adult male New Z...

A hybrid approach is proposed to compute the dose deposited in cancerous and healthy tissues during stereotactic synchrotron radiotherapy treatment. In this approach the computation is divided into two parts: (1) the primary dose is calculated using a deterministic algorithm based on ray casting; (2) the secondary dose (due to scattering and fluore...

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 roden...

We present preclinical data showing the in vitro intranuclear uptake of motexafin gadolinium by glioblastoma multiforme cells, which could serve as a prelude to the future development of radiosensitizing techniques, such as gadolinium synchrotron stereotactic radiotherapy (GdSSR), a new putative treatment for glioblastoma multiforme. In this approa...

A radiation dose enhancement can be obtained in brain tumours after infusion of an iodinated contrast agent and irradiation with kilovoltage x-rays in tomography mode. The aim of this study was to assess dosimetric properties of the synchrotron stereotactic radiotherapy technique applied to humans (SSR) for preparing clinical trials. We designed an...

To date, iodinated contrast agents (ICA) are commonly used in medical imaging to improve tumor visualization by attenuating scanners X-rays. However, some adverse reactions to ICAs are still reported, and their molecular origin remains unclear. In 1983, it was proposed to visualize and treat ICA-loaded tumors by using scanners as therapy machines t...

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). We recruited 57 men,...

A medical research protocol on clinical intravenous coronary angiography has been completed at the European Synchrotron Radiation Facility (ESRF) biomedical beamline. The aim was to investigate the accuracy of intravenous coronary angiography based on the K-edge digital subtraction technique for the detection of in-stent restenosis. For each patien...

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 t...

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-b...

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 iodi...

Synchrotron stereotactic radiotherapy (SSR) consists in loading the tumour with a high atomic number element (Z), and exposing it to monochromatic x-rays from a synchrotron source (50-100 keV), in stereotactic conditions. The dose distribution results from both the stereotactic monochromatic x-ray irradiation and the presence of the high Z element....

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. Rats bearing late-stage gliomas received 2.5 mmol/kg (392.5 mg Gd/kg) of gadopentetate dimeglumine (n = 5) and g...

High-grade gliomas are usually of poor prognosis, and conventional radiotherapy, even combined with chemotherapy, still fails to improve the survival of patients. Here, we propose an innovative therapeutic approach combining synchrotron radiation with cis-diamminedichloroplatinum (II) (CDDP). As suggested previously, monochromatic synchrotron irrad...

Nosologic images: a 1H spectroscopic imaging tool for cerebral tumour classification. Proton magnetic resonance spectroscopic imaging (1H MRSI) provides non-invasively biochemical information from tissue. We present 56 patients with brain tumours, who underwent multivoxel 1H MRS examinations. The results were presented in the form of nosologic imag...

Enhancement of the radiation dose delivered to a brain tumor can be achieved by infusing an iodinated contrast agent to the patient and irradiating with kilovoltage X-rays in computed tomography (CT) mode. Synchrotron sources, providing monochromatic tunable intense beams, are ideal for this treatment. The aim of this study is to assess in vivo the...

This work establishes an objective method to measure cell clonogenic survival by computer-assisted image processing using images of cell cultures fixed and stained in Petri dishes. The procedure, developed by Samba Technologies, consists of acquiring Petri dish pictures with a desktop scanner and analysing them by computer, using algorithms based o...

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 c...

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 i...

The European Synchrotron Radiation Facility Medical Research Beamline is now fully operational. One of the primary programs is the development of dual-energy transvenous coronary angiography for in vivo human research protocols. Previous work at this and other synchrotrons has been entirely devoted to the use of the dual-energy digital subtraction...

NMR imaging allow specific study of contrast variations due to intravascular agents. It is possible to measure regional cerebral blood volume (rCBV). In brain tumor, this parameter allow to characterize tumoral vascularisation and blood brain barrier lesions. We use today 1(st) pass bolus technic. Easy to perform in clinical practice, it is useful...

Magnetic resonance spectroscopy (MRS) is a noninvasive means of obtaining metabolic information complementary to magnetic resonance imaging. Its potential is particularly interesting in tissue characterization and follow-up of brain lesions, We present here a review of clinical applications together with a short development of the fundamental princ...

A monochromatic computed tomography (CT) system for clinical studies in brain pathology is part of the medical beamline ID 17 at the ESRF (European Synchrotron Radiation Facility). We have carried out preliminary phantom studies to determine the minimum detectable iodine and gadolinium concentrations by the K-edge subtraction technique as well as t...