66 results on '"Adam JF"'
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2. A prediction of cell differentiation and proliferation within a collagen–glycosaminoglycan scaffold subjected to mechanical strain and perfusive fluid flow
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Peter E. McHugh, Fergal J. O'Brien, Kevin B. Heraty, M Browne, and Adam Jf Stops
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Scaffold ,Cellular differentiation ,Finite Element Analysis ,mesenchymal stem-cells ,Biomedical Engineering ,Biophysics ,tissue-engineering scaffolds ,in-vitro ,Computational fluid dynamics ,Mechanotransduction, Cellular ,Models, Biological ,bone ,models ,Bioreactors ,Tissue engineering ,matrices ,Fluid dynamics ,Shear stress ,Animals ,Humans ,Computer Simulation ,Orthopedics and Sports Medicine ,Mechanotransduction ,Cells, Cultured ,Cell Proliferation ,Glycosaminoglycans ,validation ,Tissue Scaffolds ,Chemistry ,business.industry ,Rehabilitation ,Mesenchymal stem cell ,gag scaffolds ,finite-element ,contraction ,Cell Differentiation ,Mesenchymal Stem Cells ,collagen-glycosaminoglycan scaffold ,perfusion bioreactor ,Perfusion ,tissue engineering ,Collagen ,business ,Biomedical engineering - Abstract
Mesenchymal stem cell (MSC) differentiation can be influenced by biophysical stimuli imparted by the host scaffold. Yet, causal relationships linking scaffold strain magnitudes and inlet fluid velocities to specific cell responses are thus far underdeveloped. This investigation attempted to simulate cell responses in a collagen–glycosaminoglycan (CG) scaffold within a bioreactor. CG scaffold deformation was simulated using μ-computed tomography (CT) and an in-house finite element solver (FEEBE/ linear ). Similarly, the internal fluid velocities were simulated using the afore-mentioned μCT dataset with a computational fluid dynamics solver (ANSYS/CFX). From the ensuing cell-level mechanics, albeit octahedral shear strain or fluid velocity, the proliferation and differentiation of the representative cells were predicted from deterministic functions. Cell proliferation patterns concurred with previous experiments. MSC differentiation was dependent on the level of CG scaffold strain and the inlet fluid velocity. Furthermore, MSC differentiation patterns indicated that specific combinations of scaffold strains and inlet fluid flows cause phenotype assemblies dominated by single cell types. Further to typical laboratory procedures, this predictive methodology demonstrated loading-specific differentiation lineages and proliferation patterns. It is hoped these results will enhance in-vitro tissue engineering procedures by providing a platform from which the scaffold loading applications can be tailored to suit the desired tissue.
- Published
- 2010
3. Local and regional mechanical characterisation of a collagen-glycosaminoglycan scaffold using high-resolution finite element analysis
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Fergal J. O'Brien, Peter E. McHugh, Matthew G. Haugh, Noel M. Harrison, and Adam Jf Stops
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Scaffold ,Materials science ,Elastic instability ,pore-size ,Finite Element Analysis ,Biomedical Engineering ,Biocompatible Materials ,tissue-engineering scaffolds ,Models, Biological ,3-dimensional scaffolds ,Biomaterials ,Tissue engineering ,marrow stromal cells ,Physical Stimulation ,Materials Testing ,Relative density ,chondrogenic differentiation ,Stress concentration ,Glycosaminoglycans ,Deformation (mechanics) ,Tissue Engineering ,Tissue Scaffolds ,gag scaffolds ,perfusion bioreactor ,matrix ,Elasticity ,Biomechanical Phenomena ,Mechanics of Materials ,Cell culture ,trabecular bone ,Volume fraction ,Microscopy, Electron, Scanning ,Collagen ,Shear Strength ,Porosity ,Biomedical engineering ,cross-linking - Abstract
Artificial tissue growth requires cells to proliferate and differentiate within the host scaffold. As cell function is governed by mechano-sensitive selection, tissue type is influenced by the microscopic forces exposed to the cells, which is a product of macroscopically straining the scaffold. Accordingly, the microscopic strain environment within a CG scaffold is offered here. Using μ CT to characterise CG scaffold architecture, two high-resolution 3D FE models were used to predict the deformation mechanics. While also providing an analysis of region-specific features, such as relative density, pore diameters and microstructural elastic stability, the deformation patterns afforded strains to be inferred for seeded cells. The results indicate a regional dependence, in terms of architectural and mechanical properties. Specifically, the peripheral regions demonstrated the lowest volume fraction, the highest stress concentrations and the greatest potential for elastic instability. Conversely, the mid-region exhibited the most homogeneous environment. Based on the proviso of mechano-sensitive proliferation and differentiation, the findings suggest cell function will vary between CG scaffold regions. Further work should investigate the possibility of improving the fabrication process in order to deliver a construct in line with the mid-region, or alternatively, isolation of the mid-region may prove beneficial for cell culturing.
- Published
- 2009
4. A finite element prediction of strain on cells in a highly porous collagen-glycosaminoglycan scaffold
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L A McMahon, Patrick J. Prendergast, D. O'Mahoney, Adam Jf Stops, and Peter E. McHugh
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Male ,Scaffold ,Materials science ,Finite Element Analysis ,Biomedical Engineering ,Cell Culture Techniques ,Mechanotransduction, Cellular ,Models, Biological ,Stress (mechanics) ,Mechanobiology ,Tissue engineering ,Physiology (medical) ,Elastic Modulus ,Physical Stimulation ,Animals ,Computer Simulation ,Mechanotransduction ,Rats, Wistar ,Cells, Cultured ,Strain (chemistry) ,Tissue Engineering ,business.industry ,Stem Cells ,Mesenchymal Stem Cells ,Structural engineering ,Finite element method ,Extracellular Matrix ,Rats ,Biophysics ,Stress, Mechanical ,Deformation (engineering) ,business ,Shear Strength ,Porosity - Abstract
Tissue engineering often involves seeding cells into porous scaffolds and subjecting the scaffold to mechanical stimulation. Current experimental techniques have provided a plethora of data regarding cell responses within scaffolds, but the quantitative understanding of the load transfer process within a cell-seeded scaffold is still relatively unknown. The objective of this work was to develop a finite element representation of the transient and heterogeneous nature of a cell-seeded collagen-GAG-scaffold. By undertaking experimental investigation, characteristics such as scaffold architecture and shrinkage, cellular attachment patterns, and cellular dimensions were used to create a finite element model of a cell-seeded porous scaffold. The results demonstrate that a very wide range of microscopic strains act at the cellular level when a sample value of macroscopic (apparent) strain is applied to the collagen-GAG-scaffold. An external uniaxial strain of 10% generated a cellular strain as high as 49%, although the majority experienced less than ∼5% strain. The finding that the strain on some cells could be higher than the macroscopic strain was unexpected and proves contrary to previous in vitro investigations. These findings indicate a complex system of biophysical stimuli created within the scaffolds and the difficulty of inducing the desired cellular responses from artificial environments. Future in vitro studies could also corroborate the results from this computational prediction to further explore mechanoregulatory mechanisms in tissue engineering.
- Published
- 2008
5. A Finite Element Prediction of Cellular Strain in a GAG-Scaffold
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D. O'Mahoney, Patrick J. Prendergast, Adam Jf Stops, Peter E. McHugh, and Louise A. McMahon
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Stress (mechanics) ,Scaffold ,Mesenchymal Differentiation ,Materials science ,Tissue engineering ,Strain (chemistry) ,Biophysics ,Finite element method ,Biomedical engineering ,Finite element simulation - Abstract
Tissue engineering is an emerging area in bioengineering engaging biomaterials, biology and biomechanics. Current in-vitro studies have shown mesenchymal differentiation into specific cellular lineages when using osteoinductive factors [1], though the quantitative understanding of the load transfer process within a cell-seeded scaffold is still relatively unknown. Here, this paper presents a finite element simulation of the cellular-scaffold interaction so that cellular strain and the corresponding strain mechanisms can be evaluated.Copyright © 2007 by ASME
- Published
- 2007
6. Synchrotron Radiation Therapy from a Medical Physics point of view
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Prezado, Y, Adam, J, Berkvens, P, Martinez-Rovira, I, Fois, G, Thengumpallil, S, Edouard, M, Vautrin, M, Deman, P, Bräuer-Krisch, E, Renier, M, Elleaume, H, Estève, F, Bravin, A, Prezado Y, Adam JF, Berkvens P, Martinez-Rovira I, Fois G, Thengumpallil S, Edouard M, Vautrin M, Deman P, Bräuer-Krisch E, Renier M, Elleaume H, Estève F, Bravin A, Prezado, Y, Adam, J, Berkvens, P, Martinez-Rovira, I, Fois, G, Thengumpallil, S, Edouard, M, Vautrin, M, Deman, P, Bräuer-Krisch, E, Renier, M, Elleaume, H, Estève, F, Bravin, A, Prezado Y, Adam JF, Berkvens P, Martinez-Rovira I, Fois G, Thengumpallil S, Edouard M, Vautrin M, Deman P, Bräuer-Krisch E, Renier M, Elleaume H, Estève F, and Bravin A
- 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.
- Published
- 2010
7. Simulation of dose deposition in stereotactic synchrotron radiation therapy: a fast approach combining Monte Carlo and deterministic algorithms
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Smekens, F, Freud, N, Létang, J, Adam, J, Ferrero, C, Elleaume, H, Bravin, A, Estève, F, Babot, D, Smekens F, Freud N, Létang JM, Adam JF, Ferrero C, Elleaume H, Bravin A, Estève F, Babot D, Smekens, F, Freud, N, Létang, J, Adam, J, Ferrero, C, Elleaume, H, Bravin, A, Estève, F, Babot, D, Smekens F, Freud N, Létang JM, Adam JF, Ferrero C, Elleaume H, Bravin A, Estève F, and Babot D
- Abstract
A hybrid approach, combining deterministic and Monte Carlo (MC) calculations, is proposed to compute the distribution of dose deposited during stereotactic synchrotron radiation therapy treatment. The proposed approach divides the computation into two parts: (i) the dose deposited by primary radiation (coming directly from the incident x-ray beam) is calculated in a deterministic way using ray casting techniques and energy-absorption coefficient tables and (ii) the dose deposited by secondary radiation (Rayleigh and Compton scattering, fluorescence) is computed using a hybrid algorithm combining MC and deterministic calculations. In the MC part, a small number of particle histories are simulated. Every time a scattering or fluorescence event takes place, a splitting mechanism is applied, so that multiple secondary photons are generated with a reduced weight. The secondary events are further processed in a deterministic way, using ray casting techniques. The whole simulation, carried out within the framework of the Monte Carlo code Geant4, is shown to converge towards the same results as the full MC simulation. The speed of convergence is found to depend notably on the splitting multiplicity, which can easily be optimized. To assess the performance of the proposed algorithm, we compare it to state-of-the-art MC simulations, accelerated by the track length estimator technique (TLE), considering a clinically realistic test case. It is found that the hybrid approach is significantly faster than the MC/TLE method. The gain in speed in a test case was about 25 for a constant precision. Therefore, this method appears to be suitable for treatment planning applications. © 2009 Institute of Physics and Engineering in Medicine.
- Published
- 2009
8. Concomitant pulmonary artery and aortic embolectomy
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Schraverus, P, primary and Adam, JF, additional
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- 2013
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9. High-resolution blood-brain barrier permeability and blood volume imaging using quantitative synchrotron radiation computed tomography: study on an F98 rat brain glioma
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Adam, J, Nemoz, C, Bravin, A, Fiedler, S, Bayat, S, Monfraix, S, Berruyer, G, Charvet, A, Le Bas, J, Elleaume, H, Esteve, F, Adam JF, Nemoz C, Bravin A, Fiedler S, Bayat S, Monfraix S, Berruyer G, Charvet AM, Le Bas JF, Elleaume H, Esteve F, Adam, J, Nemoz, C, Bravin, A, Fiedler, S, Bayat, S, Monfraix, S, Berruyer, G, Charvet, A, Le Bas, J, Elleaume, H, Esteve, F, Adam JF, Nemoz C, Bravin A, Fiedler S, Bayat S, Monfraix S, Berruyer G, Charvet AM, Le Bas JF, Elleaume H, and Esteve F
- Abstract
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 (47 x 47 muM(2) 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.
- Published
- 2005
10. QUANTITATIVE FUNCTIONAL IMAGING AND KINETIC STUDIES WITH HIGH-Z CONTRAST AGENTS USING SYNCHROTRON RADIATION COMPUTED TOMOGRAPHY
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Adam, JF, primary, Bayat, S, additional, Porra, L, additional, Elleaume, H, additional, Estève, F, additional, and Suortti, P, additional
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- 2009
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11. Limited internal shocks for atrial fibrillation refractory to external cardioversion
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UCL, Blommaert, Dominique, De Roy, Lucas, Adam, JF, Jamart, Jacques, Mucumbitsi, J, UCL, Blommaert, Dominique, De Roy, Lucas, Adam, JF, Jamart, Jacques, and Mucumbitsi, J
- Abstract
We investigated the feasibility and long-term results of low-energy internal defibrillation using a Limited number of shocks in patients with persistent atrial fibrillation resistant to external cardioversion. A relatively high number of shocks of lower energy are usually required in those cases and can be poorly tolerated. Methods and results: Twenty-five patients with persistent atrial fibrillation underwent internal defibrination, using biphasic R wave synchronous shocks between two catheters in the high right atrium and the coronary sinus. Conversion to sinus rhythm was obtained in all patients, with a median of two shocks. Early recurrence of atrial fibrillation (AF) occurred in eight cases (32%). Seven patients (41%) out of 17 discharged in sinus rhythm remained free of AF after a median follow-up of 8.9 months. Severe mitral insufficiency (P=0.05) and low left ventricle ejection fraction (P=0.002) were correlated with earlier recurrence. Amiodarone significantly favored (P=0.019) maintenance of sinus rhythm. Conclusion: Internal defibrillation using a limited number of shocks equal to or less than 30 Joules is effective in terminating refractory atrial fibrillation and could be more acceptable for patients. However, the recurrence rate remains high, particularly in patients with severe mitral insufficiency or poor ventricular function. Amiodarone delays recurrences of atrial fibrillation. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.
- Published
- 1999
12. Innovative minimally invasive options to treat drug-resistant epilepsies.
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Samalens L, Courivaud C, Adam JF, Barbier EL, Serduc R, and Depaulis A
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- Humans, Radiosurgery methods, Anticonvulsants therapeutic use, Animals, Therapies, Investigational methods, Therapies, Investigational trends, Drug Resistant Epilepsy surgery, Drug Resistant Epilepsy therapy, Minimally Invasive Surgical Procedures methods
- Abstract
Despite the regular discovery of new molecules, one-third of epileptic patients are resistant to antiepileptic drugs. Only a few can benefit from resective surgery, the current gold standard. Although effective in 50-70% of cases, this therapy remains risky, costly, and can be associated with long-term cognitive or neurological side effects. In addition, patients are increasingly reluctant to have a craniotomy, emphasizing the need for new less invasive therapies for focal drug-resistant epilepsies. Here, we review different minimally invasive approaches already in use in the clinic or under preclinical development to treat drug-resistant epilepsies. Localized thermolesion of the epileptogenic zone has been developed in the clinic using high-frequency thermo-coagulations or magnetic resonance imaging-guided laser or ultrasounds. Although less invasive, they have not yet significantly improved the outcomes when compared with resective surgery. Radiosurgery techniques have been used in the clinic for the last 20years and have proven efficiency. However, their efficacy is not better than resective surgery, and various side effects have been reported as well as the potential risk of sudden unexpected death associated with epilepsy. Recently, a new strategy of radiosurgery has emerged using synchrotron-generated X-ray microbeams: microbeam radiation therapy (MRT). The low divergence and high-flux of the synchrotron beams and the unique tolerance to MRT by healthy brain tissues, allows a precise targeting of specific brain regions with minimal invasiveness and limited behavioral or functional consequences in animals. Antiepileptic effects over several months have been recorded in animal models, and histological and synaptic tracing analysis suggest a reduction of neuronal connectivity as a mechanism of action. The possibility of transferring this approach to epileptic patients is discussed in this review., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)
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- 2024
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13. Neurologic Changes Induced by Whole-Brain Synchrotron Microbeam Irradiation: 10-Month Behavioral and Veterinary Follow-Up.
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Eling L, Verry C, Balosso J, Flandin I, Kefs S, Bouchet A, Adam JF, Laissue JA, and Serduc R
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- Animals, Rats, Male, Cranial Irradiation adverse effects, Cranial Irradiation methods, Time Factors, Radiation Injuries, Experimental, Dose-Response Relationship, Radiation, Follow-Up Studies, Radiotherapy Dosage, Synchrotrons, Rats, Inbred F344, Brain radiation effects, Behavior, Animal radiation effects
- Abstract
Purpose: Novel radiation therapy approaches have increased the therapeutic efficacy for malignant brain tumors over the past decades, but the balance between therapeutic gain and radiotoxicity remains a medical hardship. Synchrotron microbeam radiation therapy, an innovative technique, deposes extremely high (peak) doses in micron-wide, parallel microbeam paths, whereas the diffusing interbeam (valley) doses lie in the range of conventional radiation therapy doses. In this study, we evaluated normal tissue toxicity of whole-brain microbeam irradiation (MBI) versus that of a conventional hospital broad beam (hBB)., Methods and Materials: Normal Fischer rats (n = 6-7/group) were irradiated with one of the two modalities, exposing the entire brain to MBI valley/peak doses of 0/0, 5/200, 10/400, 13/520, 17/680, or 25/1000 Gy or to hBB doses of 7, 10, 13, 17, or 25 Gy. Two additional groups of rats received an MBI valley dose of 10 Gy coupled with an hBB dose of 7 or 15 Gy (groups MBI17* and MBI25*). Behavioral parameters were evaluated for 10 months after irradiation combined with veterinary observations., Results: MBI peak doses of ≥680 Gy caused acute toxicity and death. Animals exposed to hBB or MBI dose-dependently gained less weight than controls; rats in the hBB25 and MBI25* groups died within 6 months after irradiation. Increasing doses of MBI caused hyperactivity but no other detectable behavioral alterations in our tests. Importantly, no health concerns were seen up to an MBI valley dose of 17 Gy., Conclusions: While acute toxicity of microbeam exposures depends on very high peak doses, late toxicity mainly relates to delivery of high MBI valley doses. MBI seems to have a low impact on normal rat behavior, but further tests are warranted to fully explore this hypothesis. However, high peak and valley doses are well tolerated from a veterinary point of view. This normal tissue tolerance to whole-brain, high-dose MBI reveals a promising avenue for microbeam radiation therapy, that is, therapeutic applications of microbeams that are poised for translation to a clinical environment., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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14. Neuro-Oncologic Veterinary Trial for the Clinical Transfer of Microbeam Radiation Therapy: Acute to Subacute Radiotolerance after Brain Tumor Irradiation in Pet Dogs.
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Eling L, Kefs S, Keshmiri S, Balosso J, Calvet S, Chamel G, Drevon-Gaud R, Flandin I, Gaudin M, Giraud L, Laissue JA, Pellicioli P, Verry C, Adam JF, and Serduc R
- Abstract
Synchrotron Microbeam Radiation Therapy (MRT) has repeatedly proven its superiority compared with conventional radiotherapy for glioma control in preclinical research. The clinical transfer phase of MRT has recently gained momentum; seven dogs with suspected glioma were treated under clinical conditions to determine the feasibility and safety of MRT. We administered a single fraction of 3D-conformal, image-guided MRT. Ultra-high-dose rate synchrotron X-ray microbeams (50 µm-wide, 400 µm-spaced) were delivered through five conformal irradiation ports. The PTV received ~25 Gy peak dose (within microbeams) per port, corresponding to a minimal cumulated valley dose (diffusing between microbeams) of 2.8 Gy. The dogs underwent clinical and MRI follow-up, and owner evaluations. One dog was lost to follow-up. Clinical exams of the remaining six dogs during the first 3 months did not indicate radiotoxicity induced by MRT. Quality of life improved from 7.3/10 [±0.7] to 8.9/10 [±0.3]. Tumor-induced seizure activity decreased significantly. A significant tumor volume reduction of 69% [±6%] was reached 3 months after MRT. Our study is the first neuro-oncologic veterinary trial of 3D-conformal Synchrotron MRT and reveals that MRT does not induce acute to subacute radiotoxicity in normal brain tissues. MRT improves quality of life and leads to remarkable tumor volume reduction despite low valley dose delivery. This trial is an essential step towards the forthcoming clinical application of MRT against deep-seated human brain tumors.
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- 2024
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15. Monocrystalline diamond detector for online monitoring during synchrotron microbeam radiotherapy.
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di Franco F, Rosuel N, Gallin-Martel L, Gallin-Martel ML, Ghafooryan-Sangchooli M, Keshmiri S, Motte JF, Muraz JF, Pellicioli P, Ruat M, Serduc R, Verry C, Dauvergne D, and Adam JF
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- Dose Fractionation, Radiation, X-Rays, Phantoms, Imaging, Radiotherapy, Monte Carlo Method, Diamond, Synchrotrons, Radiometry methods
- Abstract
Microbeam radiation therapy (MRT) is a radiotherapy technique combining spatial fractionation of the dose distribution on a micrometric scale, X-rays in the 50-500 keV range and dose rates up to 16 × 10
3 Gy s-1 . Nowadays, in vivo dosimetry remains a challenge due to the ultra-high radiation fluxes involved and the need for high-spatial-resolution detectors. The aim here was to develop a striped diamond portal detector enabling online microbeam monitoring during synchrotron MRT treatments. The detector, a 550 µm bulk monocrystalline diamond, is an eight-strip device, of height 3 mm, width 178 µm and with 60 µm spaced strips, surrounded by a guard ring. An eight-channel ASIC circuit for charge integration and digitization has been designed and tested. Characterization tests were performed at the ID17 biomedical beamline of the European Synchrotron Radiation Facility (ESRF). The detector measured direct and attenuated microbeams as well as interbeam fluxes with a precision level of 1%. Tests on phantoms (RW3 and anthropomorphic head phantoms) were performed and compared with simulations. Synchrotron radiation measurements were performed on an RW3 phantom for strips facing a microbeam and for strips facing an interbeam area. A 2% difference between experiments and simulations was found. In more complex geometries, a preliminary study showed that the absolute differences between simulated and recorded transmitted beams were within 2%. Obtained results showed the feasibility of performing MRT portal monitoring using a microstriped diamond detector. Online dosimetric measurements are currently ongoing during clinical veterinary trials at ESRF, and the next 153-strip detector prototype, covering the entire irradiation field, is being finalized at our institution., (open access.)- Published
- 2023
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16. Toward Neuro-Oncologic Clinical Trials of High-Dose-Rate Synchrotron Microbeam Radiation Therapy: First Treatment of a Spontaneous Canine Brain Tumor.
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Adam JF, Balosso J, Bayat S, Berkvens P, Berruyer G, Bräuer-Krisch E, Brochard T, Chamel G, Desagneaux A, Drevon-Gaud R, Eling L, Estève F, Flandin I, Gaudin M, Giraud JY, Giraud L, Gonzalez H, Kefs S, Keshmiri S, Krainik A, Krisch M, Laissue JA, Lemaire G, Mauro A, Nemoz C, Pellicioli P, Renier M, Verry C, and Serduc R
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- Animals, Dogs, Quality of Life, Synchrotrons, Brain Neoplasms diagnostic imaging, Brain Neoplasms radiotherapy, Brain Neoplasms veterinary, Glioma diagnostic imaging, Glioma pathology, Glioma radiotherapy, Radiosurgery methods
- Abstract
Purpose: The high potential of microbeam radiation therapy (MRT) in improving tumor control while 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 enters a clinical transfer phase. As proof of principle and cornerstone for the safe clinical transfer of MRT, we conducted a "first in dog" trial under clinical conditions. In this report, we evaluated whether a 3-dimensional conformal MRT can be safely delivered as exclusive radiosurgical treatment in animal patients METHODS AND MATERIALS: We irradiated a 17.5-kg French bulldog for a spontaneous brain tumor (glioma suspected on magnetic resonance imaging) with conformal high-dose-rate microbeam arrays (50-µm-wide microbeams, replicated with a pitch of 400 μm) of synchrotron-generated x-rays. The dose prescription adjusted a minimal cumulated valley dose of 2.8 Gy to the plnning target volume (PTV) (cinical target volume (CTV)+ 1 mm). Thus, each beam delivered 20 to 25 Gy to the target as peak doses, and ∼1 Gy as valley doses RESULTS: The treatment was successfully delivered. Clinical follow-up over 3 months showed a significant improvement of the dog's quality of life: the symptoms disappeared. Magnetic resonance imaging, performed 3 months after irradiation, revealed reduction in tumor size (-87.4%) and mass effect with normalization of the left lateral ventricle., Conclusions: To our knowledge, this neuro-oncologic veterinary trial is the first 3-dimensional conformal synchrotron x-ray MRT treatment of a spontaneous intracranial tumor in a large animal. It is an essential last step toward the clinical transfer of MRT in the near future to demonstrate the feasibility and safety of treating deep-seated tumors using synchrotron-generated microbeams., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2022
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17. A high-resolution dose calculation engine for X-ray microbeams radiation therapy.
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Keshmiri S, Brocard S, Serduc R, and Adam JF
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- Humans, Monte Carlo Method, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted methods, Reproducibility of Results, Synchrotrons, X-Rays, X-Ray Therapy
- Abstract
Background: Microbeam radiation therapy (MRT) is a treatment modality based on spatial fractionation of synchrotron generated X-rays into parallel, high dose, microbeams of a few microns width. MRT is still an underdevelopment radiosurgery technique for which, promising preclinical results on brain tumors and epilepsy encourages its clinical transfer., Purpose: A safe clinical transfer of MRT needs a specific treatment planning system (TPS) that provides accurate dose calculations in human patients, taking into account the MRT beam's properties (high-dose gradients, spatial fractionation, polarization effects). So far, the most advanced MRT TPS, based on a hybrid dose calculation algorithm, is limited to a macroscopic rendering of the dose and does not account for the complex dose distribution inherent to MRT if delivered as conformal irradiations with multiple incidences. For overcoming these limitations, a multi-scale full Monte-Carlo calculation engine called penMRT has been developed and benchmarked against two general-purpose Monte Carlo (MC) codes: penmain based on PENELOPE and Gate based on Geant4., Methods: PenMRT, is based on the PENELOPE (2018) MC code, modified to take into account the voxelized geometry of the patients (computed tomography [CT]-scans) and is offering an adaptive micrometric dose calculation grid independent of the CT size, location, and orientation. The implementation of the dynamic memory allocation in penMRT, makes the simulations feasible within a huge number of dose scoring bins. The possibility of using a source replication approach to simulate arrays of microbeams, and the parallelization using OpenMPI have been added to penMRT in order to increase the calculation speed for clinical usages. This engine can be implemented in a TPS as a dose calculation core., Results: The performance tests highlight the reliability of penMRT to be used for complex irradiation conditions in MRT. The benchmarking against a standard PENELOPE code did not show any significant difference for calculations in centimetric beams, for a single microbeam and for a microbeam array. The comparisons between penMRT and Gate as an independent MC code did not show any difference in the beam paths, whereas, in valley regions, relative differences between the two codes rank from 1% to 7.5% which are probably due to the differences in physics lists that are used in these two codes. The reliability of the source replication approach has also been tested and validated with an underestimation of no more than 0.6% in low-dose areas., Conclusions: Good agreements (a relative difference between 0% and 8%) were found when comparing calculated peak to valley dose ratio values using penMRT, for irradiations with a full microbeam array, with calculated values in the literature. The high-resolution calculated dose maps obtained with penMRT are used to extract differential and cumulative dose-volume histograms (DVHs) and analyze treatment plans with much finer metrics regarding the irradiation complexity. To our knowledge, these are the first high-resolution dose maps and associated DVHs ever obtained for cross-fired microbeams irradiation, which is bringing a significant added value to the field of treatment planning in spatially fractionated radiation therapy., (© 2022 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)
- Published
- 2022
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18. Stereotaxic Implantation of F98 Cells in Fischer Rats: A Syngeneic Model to Investigate Photodynamic Therapy Response in Glioma.
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Bulin AL, Adam JF, and Elleaume H
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- Animals, Cell Line, Tumor, Humans, Rats, Rats, Inbred F344, Brain Neoplasms drug therapy, Brain Neoplasms pathology, Glioblastoma drug therapy, Glioblastoma pathology, Glioma drug therapy, Glioma pathology, Photochemotherapy
- Abstract
When investigating the promise of novel therapeutic modalities, the choice of an appropriate and reproducible in vivo model is critical to determine the relevance of the findings. In the case of glioblastoma, a high-grade glioma tumor that is clinically characterized by a high infiltrative pattern, no existing model exactly mimics the clinical features of these tumors. However, a syngeneic rat model of glioblastoma in which F98 cells are orthotopically implanted can recapitulate most of the characteristics of glioma as observed in patients, including a highly aggressive nature, a high degree of infiltration of cancer cells into healthy tissue, and a strong resistance to commonly used treatments including radiotherapy and chemotherapy. Here, we provide a detailed protocol to stereotaxically implant F98 cells in the rat brain and obtain a reproducible and clinically representative glioma model in rodents., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2022
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19. Unexpected Benefits of Multiport Synchrotron Microbeam Radiation Therapy for Brain Tumors.
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Eling L, Bouchet A, Ocadiz A, Adam JF, Kershmiri S, Elleaume H, Krisch M, Verry C, Laissue JA, Balosso J, and Serduc R
- Abstract
Delivery of high-radiation doses to brain tumors via multiple arrays of synchrotron X-ray microbeams permits huge therapeutic advantages. Brain tumor (9LGS)-bearing and normal rats were irradiated using a conventional, homogeneous Broad Beam (BB), or Microbeam Radiation Therapy (MRT), then studied by behavioral tests, MRI, and histopathology. A valley dose of 10 Gy deposited between microbeams, delivered by a single port, improved tumor control and median survival time of tumor-bearing rats better than a BB isodose. An increased number of ports and an accumulated valley dose maintained at 10 Gy delayed tumor growth and improved survival. Histopathologically, cell death, vascular damage, and inflammatory response increased in tumors. At identical valley isodose, each additional MRT port extended survival, resulting in an exponential correlation between port numbers and animal lifespan (r
2 = 0.9928). A 10 Gy valley dose, in MRT mode, delivered through 5 ports, achieved the same survival as a 25 Gy BB irradiation because of tumor dose hot spots created by intersecting microbeams. Conversely, normal tissue damage remained minimal in all the single converging extratumoral arrays. Multiport MRT reached exceptional ~2.5-fold biological equivalent tumor doses. The unique normal tissue sparing and therapeutic index are eminent prerequisites for clinical translation.- Published
- 2021
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20. [On the use of corticosteroids for critically ill patients with SARS-CoV-2 interstitial pneumonia].
- Author
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Mingoia A, Lejeune F, Sottiaux T, Van Brussel C, and Adam JF
- Subjects
- Adrenal Cortex Hormones therapeutic use, Betacoronavirus, COVID-19, Humans, SARS-CoV-2, Coronavirus Infections, Critical Illness, Lung Diseases, Interstitial, Pandemics, Pneumonia, Viral
- Abstract
The health crisis caused by SARS-Cov2 continues to question the scientific community on an effective treatment to combat the disease. To do this, understanding the pathophysiology is a key element of the research. Although the use of corticosteroids is debated, recent publications on pathogenesis and histologic pattern allow us to consider their use on a different way. Through these two case reports, it seemed interesting to take stock of the most recent data in the literature and on the potential interest of the corticotherapy in specific critically ill patient's cases.
- Published
- 2020
21. Locomotion and eating behavior changes in Yucatan minipigs after unilateral radio-induced ablation of the caudate nucleus.
- Author
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Coquery N, Adam JF, Nemoz C, Janvier R, Livingstone J, Chauvin A, Kefs S, Guerineau C, De Saint Jean L, Ocadiz A, Bouchet A, Bartzsch S, Schültke E, Siegbahn A, Bräuer-Krisch E, Lemasson B, Barbier EL, Laissue J, Balosso J, Val-Laillet D, and Serduc R
- Subjects
- Animals, Brain radiation effects, Caudate Nucleus radiation effects, Male, Radiation Injuries etiology, Swine, Swine, Miniature, Synchrotrons, Behavior, Animal radiation effects, Brain pathology, Caudate Nucleus pathology, Cranial Irradiation adverse effects, Feeding Behavior radiation effects, Locomotion radiation effects, Radiation Injuries pathology
- Abstract
The functional roles of the Caudate nucleus (Cd) are well known. Selective Cd lesions can be found in neurological disorders. However, little is known about the dynamics of the behavioral changes during progressive Cd ablation. Current stereotactic radiosurgery technologies allow the progressive ablation of a brain region with limited adverse effects in surrounding normal tissues. This could be of high interest for the study of the modified behavioral functions in relation with the degree of impairment of the brain structures. Using hypofractionated stereotactic radiotherapy combined with synchrotron microbeam radiation, we investigated, during one year after irradiation, the effects of unilateral radio-ablation of the right Cd on the behavior of Yucatan minipigs. The right Cd was irradiated to a minimal dose of 35.5 Gy delivered in three fractions. MRI-based morphological brain integrity and behavioral functions, i.e. locomotion, motivation/hedonism were assessed. We detected a progressive radio-necrosis leading to a quasi-total ablation one year after irradiation, with an additional alteration of surrounding areas. Transitory changes in the motivation/hedonism were firstly detected, then on locomotion, suggesting the influence of different compensatory mechanisms depending on the functions related to Cd and possibly some surrounding areas. We concluded that early behavioral changes related to eating functions are relevant markers for the early detection of ongoing lesions occurring in Cd-related neurological disorders.
- Published
- 2019
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22. Ultra high dose rate Synchrotron Microbeam Radiation Therapy. Preclinical evidence in view of a clinical transfer.
- Author
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Eling L, Bouchet A, Nemoz C, Djonov V, Balosso J, Laissue J, Bräuer-Krisch E, Adam JF, and Serduc R
- Subjects
- Animals, Brain Neoplasms blood supply, Clinical Protocols, Disease Models, Animal, Humans, X-Rays, Brain Neoplasms radiotherapy, Radiosurgery methods, Synchrotrons
- Abstract
This paper reviews the current state of the art of an emerging form of radiosurgery dedicated to brain tumour treatment and which operates at very high dose rate (kGy·s
-1 ). Microbeam Radiation Therapy uses synchrotron-generated X-rays which triggered normal tissue sparing partially mediated by FLASH effect., (Copyright © 2019 Elsevier B.V. All rights reserved.)- Published
- 2019
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23. Film dosimetry studies for patient specific quality assurance in microbeam radiation therapy.
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Ocadiz A, Livingstone J, Donzelli M, Bartzsch S, Nemoz C, Kefs S, Pellicioli P, Giraud JY, Balosso J, Krisch M, Bräuer-Krisch E, Serduc R, and Adam JF
- Subjects
- Brain Neoplasms radiotherapy, Dose Fractionation, Radiation, Humans, Phantoms, Imaging, Radiometry methods, Radiotherapy Dosage, Synchrotrons, X-Rays, Film Dosimetry methods, Radiotherapy methods
- Abstract
Microbeam radiation therapy (MRT) uses synchrotron arrays of X-ray microbeams to take advantage of the spatial fractionation effect for normal tissue sparing. In this study, radiochromic film dosimetry was performed for a treatment where MRT is introduced as a dose boost in a hypofractionated stereotactic radiotherapy (SRT) scheme. The isocenter dose was measured using an ionization chamber and two dimensional dose distributions were determined using radiochromic films. To compare the measured dose distribution to the MRT treatment plan, peak and valley were displayed in separate dosemaps. The measured and computed isocenter doses were compared and a two-dimensional 2%/2 mm normalized γ-index analysis with a 90% passing rate criterion was computed. For SRT, a difference of 2.6% was observed in the dose at the isocenter from the treatment plan and film measurement, with a passing rate of 96% for the γ-index analysis. For MRT, peak and valley doses differences of 25.6% and 8.2% were observed, respectively but passing rates of 96% and 90% respectively were obtained from the normalized γ-index maps. The differences in isocenter doses measured in MRT should be further investigated. We present the methodology of patient specific quality assurance (QA) for studying MRT dose distributions and discuss ideas to improve absolute dosimetry. This patient specific QA will be used for large animal trials quality assurance where MRT will be administered as a dose boost in conventional SRT. The observed remaining discrepancies should be studied against approximations in the TPS phantom materials, beams characteristics or film read-out procedures., (Copyright © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2019
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24. Significant dose reduction using synchrotron radiation computed tomography: first clinical case and application to high resolution CT exams.
- Author
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Labriet H, Nemoz C, Renier M, Berkvens P, Brochard T, Cassagne R, Elleaume H, Estève F, Verry C, Balosso J, Adam JF, and Brun E
- Subjects
- Algorithms, Equipment Design, Humans, Phantoms, Imaging, Radiation Dosage, Radiographic Image Interpretation, Computer-Assisted instrumentation, Synchrotrons, Radiographic Image Interpretation, Computer-Assisted standards, Tomography, X-Ray Computed instrumentation
- Abstract
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 this work was to evaluate the clinical potential of the images acquired using Synchrotron Radiation CT (SRCT). SRCTs were acquired using monochromatic X-rays tuned at 80 keV (0.350 × 0.350 × 2 mm
3 voxel size). A quantitative image quality comparison study was carried out on phantoms between a state of the art clinical CT and SRCT images. Dedicated iterative algorithms were developed to optimize the image quality and further reduce the delivered dose by a factor of 12 while keeping a better image quality than the one obtained with a clinical CT scanner. We finally show in this paper the very first SRCT results of one patient who received Synchrotron Radiotherapy in an ongoing clinical trial. This demonstrates the potential of the technique in terms of image quality improvement at a reduced radiation dose for inner ear visualization.- Published
- 2018
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25. Evaluation of the Roche® Elecsys and the Diasorin® Liaison S100 kits in the management of mild head injury in the emergency room.
- Author
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Delefortrie Q, Lejeune F, Kerzmann B, Levy R, Adam JF, Sottiaux T, Grimmelprez A, Vankerkhoven P, and Hachimi-Idrissi S
- Subjects
- Adolescent, Adult, Brain Concussion therapy, Brain Injuries blood, Child, Child, Preschool, Craniocerebral Trauma blood, Craniocerebral Trauma therapy, Emergency Medical Services methods, Emergency Service, Hospital, Female, Humans, Immunoassay, Infant, Male, Prospective Studies, S100 Calcium Binding Protein beta Subunit analysis, Sensitivity and Specificity, Tomography, X-Ray Computed, Brain Concussion diagnosis, S100 Calcium Binding Protein beta Subunit blood
- Abstract
Introduction: The aim of this single-center prospective study is to compare two commercially available S100ß kits (the Roche® Elecsys and the Diasorin® Liaison S100 kits) in terms of analytical and clinical performances in a population admitted in the emergency room for mild traumatic brain injury (mTBI)., Material and Method: 110 patients were enrolled from September 2014 to May 2015. Blood sample draws were performed within 3h after head trauma and the study population was split into pediatric and adult subpopulations (>18years of age)., Results: Although both kits correlated well, we observed a significant difference in terms of S100ß levels (P value<0.05) in both subpopulations. In the pediatric subpopulation, both kits showed elevated S100ß levels for the only patient (3.5%) who displayed abnormal findings on a CT-scan. However, we observed a poor agreement between both kits (Cohen's kappa=0.345, P value=0.077). In the adult subpopulation, a total of 10 patients (12.2%) had abnormal head computed tomography scans. Using the Roche® (cut off=0.1μg/L) and the Diasorin® (cut off=0.15μg/L) S100ß kits, brain injuries were detected with a sensitivity of 100% (95% CI: 65-100%) and 100% (95% CI: 63-100%) and a specificity of 15.28% (95% CI: 7.9-25.7%) and 24.64% (95% CI: 15-36.5) respectively. Finally, a moderate agreement was concluded between both kits (Cohen's kappa=0.569, P value=0.001)., Conclusion: Although a good correlation could be found between both kits, emergency physicians should be aware of discrepancies observed between both methods, making those immunoassays not interchangeable. Furthermore, more studies are still needed to validate cut off used according to technique and to age, especially in the population below the age of 2years., (Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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26. Experimental optimisation of the X-ray energy in microbeam radiation therapy.
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Livingstone J, Stevenson AW, Häusermann D, and Adam JF
- Subjects
- Computer Simulation, Head radiation effects, Humans, Models, Biological, Radiometry, Synchrotrons, Water, X-Rays, Radiotherapy methods, X-Ray Therapy
- Abstract
Microbeam radiation therapy has demonstrated superior normal tissue sparing properties compared to broadbeam radiation fields. The ratio of the microbeam peak dose to the valley dose (PVDR), which is dependent on the X-ray energy/spectrum and geometry, should be maximised for an optimal therapeutic ratio. Simulation studies in the literature report the optimal energy for MRT based on the PVDR. However, most of these studies have considered different microbeam geometries to that at the Imaging and Medical Beamline (50 μm beam width with a spacing of 400 μm). We present the first fully experimental investigation of the energy dependence of PVDR and microbeam penumbra. Using monochromatic X-ray energies in the range 40-120 keV the PVDR was shown to increase with increasing energy up to 100 keV before plateauing. PVDRs measured for pink beams were consistently higher than those for monochromatic energies similar or equivalent to the average energy of the spectrum. The highest PVDR was found for a pink beam average energy of 124 keV. Conversely, the microbeam penumbra decreased with increasing energy before plateauing for energies above 90 keV. The effect of bone on the PVDR was investigated at energies 60, 95 and 120 keV. At depths greater than 20 mm beyond the bone/water interface there was almost no effect on the PVDR. In conclusion, the optimal energy range for MRT at IMBL is 90-120 keV, however when considering the IMBL flux at different energies, a spectrum with 95 keV weighted average energy was found to be the best compromise., (Copyright © 2017 Associazione Italiana di Fisica Medica. All rights reserved.)
- Published
- 2018
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27. [Oxynorm® instant versus Tradonal® odis as level 2 analgesic in an emergency service : a monocentric double blind randomized non-inferiority study].
- Author
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Van Brussel C, Delefortrie Q, Kerzmann B, Grégoire C, and Adam JF
- Subjects
- Adult, Belgium, Double-Blind Method, Female, Humans, Male, Pain Measurement, Prospective Studies, Analgesics, Opioid therapeutic use, Emergency Service, Hospital, Oxycodone therapeutic use, Tramadol therapeutic use
- Abstract
Pain is one of the most common reasons for consultation in the ER. As far as class II analgesics are concerned, tramadol is most usually used. According to some data from the literature, it would seem that oxycodone and tramadol are equivalent in terms of analgesia. We have tried to prove that oxycodone (Oxynorm® instant) is not less effective than tramadol (Tradonal® odis) in an emergency unit. This is a prospective, monocentric, randomized study carried out amongst ambulatory patients. Those included in the study were given 1 g of paracetamol and a weight-ajusted dose of either tramadol or oxycodone. Every 30 minutes, a simple numerical scale (NS) was established and the clinical parameters were checked. We studied a total of 121 patients divided into 2 groups. There is an average difference of -1.47 between the average ?NS of the oxycodone group and the average ?NS of the tramadol group, with a confidence interval of 95 % (-9.42 - 6.48). The confidence interval does not cross the -10 line considered as the acceptable loss of efficiency, which allows us to conclude that oxycodone is not inferior to tramadol. As far as the adverse effects studied are concerned, there is no significant link between the treatment and the appearance of any side effect.
- Published
- 2017
28. Preclinical radiotherapy at the Australian Synchrotron's Imaging and Medical Beamline: instrumentation, dosimetry and a small-animal feasibility study.
- Author
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Livingstone J, Adam JF, Crosbie JC, Hall CJ, Lye JE, McKinlay J, Pelliccia D, Pouzoulet F, Prezado Y, Stevenson AW, and Häusermann D
- Subjects
- Animals, Australia, Feasibility Studies, Radiotherapy Dosage, Rats, Brain Neoplasms radiotherapy, Glioma radiotherapy, Radiation Dosage, Synchrotrons
- Abstract
Therapeutic applications of synchrotron X-rays such as microbeam (MRT) and minibeam (MBRT) radiation therapy promise significant advantages over conventional clinical techniques for some diseases if successfully transferred to clinical practice. Preclinical studies show clear evidence that a number of normal tissues in animal models display a tolerance to much higher doses from MRT compared with conventional radiotherapy. However, a wide spread in the parameters studied makes it difficult to make any conclusions about the associated tumour control or normal tissue complication probabilities. To facilitate more systematic and reproducible preclinical synchrotron radiotherapy studies, a dedicated preclinical station including small-animal irradiation stage was designed and installed at the Imaging and Medical Beamline (IMBL) at the Australian Synchrotron. The stage was characterized in terms of the accuracy and reliability of the vertical scanning speed, as this is the key variable in dose delivery. The measured speed was found to be within 1% of the nominal speed for the range of speeds measured by an interferometer. Furthermore, dose measurements confirm the expected relationship between speed and dose and show that the measured dose is independent of the scan direction. Important dosimetric parameters such as peak dose, valley dose, the collimator output factor and peak-to-valley dose ratio are presented for 5 mm × 5 mm, 10 mm × 10 mm and 20 mm × 20 mm field sizes. Finally, a feasibility study on three glioma-bearing rats was performed. MRT and MBRT doses were prescribed to achieve an average dose of 65 Gy in the target, and magnetic resonance imaging follow-up was performed at various time points after irradiation to follow the tumour volume. Although it is impossible to draw conclusions on the different treatments with such a small number of animals, the feasibility of end-to-end preclinical synchrotron radiotherapy studies using the IMBL preclinical stage is demonstrated.
- Published
- 2017
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29. Characterization of a synthetic single crystal diamond detector for dosimetry in spatially fractionated synchrotron x-ray fields.
- Author
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Livingstone J, Stevenson AW, Butler DJ, Häusermann D, and Adam JF
- Subjects
- Calibration, Equipment Design, Linear Models, Photons, Radiometry methods, Radiotherapy instrumentation, Radiotherapy methods, Water, Radiometry instrumentation, Synchrotrons, X-Rays
- Abstract
Purpose: Modern radiotherapy modalities often use small or nonstandard fields to ensure highly localized and precise dose delivery, challenging conventional clinical dosimetry protocols. The emergence of preclinical spatially fractionated synchrotron radiotherapies with high dose-rate, sub-millimetric parallel kilovoltage x-ray beams, has pushed clinical dosimetry to its limit. A commercially available synthetic single crystal diamond detector designed for small field dosimetry has been characterized to assess its potential as a dosimeter for synchrotron microbeam and minibeam radiotherapy., Methods: Experiments were carried out using a synthetic diamond detector on the imaging and medical beamline (IMBL) at the Australian Synchrotron. The energy dependence of the detector was characterized by cross-referencing with a calibrated ionization chamber in monoenergetic beams in the energy range 30-120 keV. The dose-rate dependence was measured in the range 1-700 Gy/s. Dosimetric quantities were measured in filtered white beams, with a weighted mean energy of 95 keV, in broadbeam and spatially fractionated geometries, and compared to reference dosimeters., Results: The detector exhibits an energy dependence; however, beam quality correction factors (kQ) have been measured for energies in the range 30-120 keV. The kQ factor for the weighted mean energy of the IMBL radiotherapy spectrum, 95 keV, is 1.05 ± 0.09. The detector response is independent of dose-rate in the range 1-700 Gy/s. The percentage depth dose curves measured by the diamond detector were compared to ionization chambers and agreed to within 2%. Profile measurements of microbeam and minibeam arrays were performed. The beams are well resolved and the full width at halfmaximum agrees with the nominal width of the beams. The peak to valley dose ratio (PVDR) calculated from the profiles at various depths in water agrees within experimental error with PVDR calculations from Gafchromic film data., Conclusions: The synthetic diamond detector is now well characterized and will be used to develop an experimental dosimetry protocol for spatially fractionated synchrotron radiotherapy.
- Published
- 2016
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30. [Ultrasonographic measurement of the optical nerve sheath for the diagnosis of intracranial hypertension in the emergency room : a case report].
- Author
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Levy R, Kerzmann B, Franssen V, Schwab AS, Adam JF, and Sottiaux T
- Subjects
- Aged, Emergency Service, Hospital, Humans, Intracranial Pressure, Ultrasonography, Intracranial Hypertension diagnostic imaging, Optic Nerve diagnostic imaging
- Abstract
Early diagnosis and treatment of intracranial hypertension (ICHT) are major components of the management of neurological emergencies. The optic nerve sheath diameter is closely dependent on intracranial pressure and can be measured by bedside ultrasound (US). We report the story of a 70-year-old COPD patient initially admitted to the emergency room for a sepsis of pulmonary origin. An unusual confusion prompted us to perform an US of the optic nerve sheath. This exam clearly suggested the presence of an ICHT. Hence, the diagnostic approach was proceeded and a herpetic encephalitis was demonstrated and successfully treated. In this clinical report, the optic nerve sheath US guided the diagnostic approach and, eventually, therapeutic decision. Several papers have shown the close relationship between increased optic nerve sheath diameter and intracranial hypertension, but we still need further studies to validate a threshold value of this diameter. The clinical relevance of the US optic nerve diameter measure appears interesting. However, further studies on larger samples of patients are needed to confirm this and to establish a validated threshold value.
- Published
- 2016
31. Medical physics aspects of the synchrotron radiation therapies: Microbeam radiation therapy (MRT) and synchrotron stereotactic radiotherapy (SSRT).
- Author
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Bräuer-Krisch E, Adam JF, Alagoz E, Bartzsch S, Crosbie J, DeWagter C, Dipuglia A, Donzelli M, Doran S, Fournier P, Kalef-Ezra J, Kock A, Lerch M, McErlean C, Oelfke U, Olko P, Petasecca M, Povoli M, Rosenfeld A, Siegbahn EA, Sporea D, and Stugu B
- Subjects
- Animals, Equipment Design, Evidence-Based Medicine, Humans, Radiometry instrumentation, Radiometry methods, Radiosurgery methods, Radiotherapy Planning, Computer-Assisted instrumentation, Radiotherapy Planning, Computer-Assisted methods, Radiotherapy, High-Energy methods, Swine, Technology Assessment, Biomedical, Treatment Outcome, Brain Neoplasms radiotherapy, Dose Fractionation, Radiation, Neoplasms surgery, Radiosurgery instrumentation, Radiotherapy, High-Energy instrumentation, Synchrotrons instrumentation
- Abstract
Stereotactic Synchrotron Radiotherapy (SSRT) and Microbeam Radiation Therapy (MRT) are both novel approaches to treat brain tumor and potentially other tumors using synchrotron radiation. Although the techniques differ by their principles, SSRT and MRT share certain common aspects with the possibility of combining their advantages in the future. For MRT, the technique uses highly collimated, quasi-parallel arrays of X-ray microbeams between 50 and 600 keV. Important features of highly brilliant Synchrotron sources are a very small beam divergence and an extremely high dose rate. The minimal beam divergence allows the insertion of so called Multi Slit Collimators (MSC) to produce spatially fractionated beams of typically ∼25-75 micron-wide microplanar beams separated by wider (100-400 microns center-to-center(ctc)) spaces with a very sharp penumbra. Peak entrance doses of several hundreds of Gy are extremely well tolerated by normal tissues and at the same time provide a higher therapeutic index for various tumor models in rodents. The hypothesis of a selective radio-vulnerability of the tumor vasculature versus normal blood vessels by MRT was recently more solidified. SSRT (Synchrotron Stereotactic Radiotherapy) is based on a local drug uptake of high-Z elements in tumors followed by stereotactic irradiation with 80 keV photons to enhance the dose deposition only within the tumor. With SSRT already in its clinical trial stage at the ESRF, most medical physics problems are already solved and the implemented solutions are briefly described, while the medical physics aspects in MRT will be discussed in more detail in this paper., (Copyright © 2015. Published by Elsevier Ltd.)
- Published
- 2015
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32. Absolute perfusion measurements and associated iodinated contrast agent time course in brain metastasis: a study for contrast-enhanced radiotherapy.
- Author
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Obeid L, Deman P, Tessier A, Balosso J, Estève F, and Adam JF
- Subjects
- Blood Volume physiology, Brain Neoplasms metabolism, Brain Neoplasms physiopathology, Humans, Infusions, Intravenous, Injections, Intravenous, Iopamidol administration & dosage, Iopamidol pharmacokinetics, Prospective Studies, Radiotherapy Dosage, Synchrotrons, Time Factors, Tissue Distribution, Tomography, X-Ray Computed, Brain Neoplasms radiotherapy, Brain Neoplasms secondary, Cerebrovascular Circulation physiology, Contrast Media administration & dosage, Contrast Media pharmacokinetics, Iopamidol analogs & derivatives, Perfusion Imaging methods
- Abstract
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 and associated brain perfusion parameters were studied in human brain metastasis as key parameters for treatment feasibility and quality. Twelve patients received an intravenous bolus of iodinated contrast agent (CA) (40 mL, 4 mL/s), followed by a steady-state infusion (160 mL, 0.5 mL/s) to ensure stable intratumoral amounts of iodine during the treatment. Absolute iodine concentrations and quantitative perfusion maps were derived from 40 multislice dynamic computed tomography (CT) images of the brain. The postinfusion mean intratumoral iodine concentration (over 30 minutes) reached 1.94 ± 0.12 mg/mL. Reasonable correlations were obtained between these concentrations and the permeability surface area product and the cerebral blood volume. To our knowledge, this is the first quantitative study of CA biodistribution versus time in brain metastasis. The study shows that suitable and stable amounts of iodine can be reached for contrast-enhanced radiotherapy. Moreover, the associated perfusion measurements provide useful information for the patient recruitment and management processes.
- Published
- 2014
- Full Text
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33. Photoactivation of gold nanoparticles for glioma treatment.
- Author
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Bobyk L, Edouard M, Deman P, Vautrin M, Pernet-Gallay K, Delaroche J, Adam JF, Estève F, Ravanat JL, and Elleaume H
- Subjects
- Animals, Brain pathology, Brain radiation effects, Brain ultrastructure, Brain Neoplasms pathology, Brain Neoplasms radiotherapy, Cell Line, Tumor, Cell Survival radiation effects, Drug Administration Routes, Glioma diagnostic imaging, Glioma pathology, Gold toxicity, Kaplan-Meier Estimate, Male, Metal Nanoparticles toxicity, Neostriatum drug effects, Neostriatum pathology, Radiography, Rats, Rats, Inbred F344, Subcellular Fractions metabolism, Subcellular Fractions radiation effects, X-Rays, Brain Neoplasms diagnostic imaging, Glioma radiotherapy, Gold radiation effects, Light, Metal Nanoparticles radiation effects
- Abstract
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 in diameter). In vivo, 1.9 nm nanoparticles were found to be toxic following intracerebral delivery in rats bearing glioma, whether no toxicity was observed using 15 nm nanoparticles at the same concentration (50 mg/mL). The therapeutic efficacy of gold photoactivation was determined by irradiating the animals after intracerebral infusion of AuNPs. Survival of rats that had received the combination of treatments (AuNPs: 50 mg/mL, 15 Gy) was significantly increased in comparison with the survival of rats that had received irradiation alone. In conclusion, this experimental approach is promising and further studies are foreseen for improving its therapeutic efficacy., From the Clinical Editor: These investigators report that gold nanoparticles of the correct size can be used to enhance the effects of irradiation in the context of a glioma model. Since many of the glioma varieties are currently incurable, this or similar approaches may find their way to clinical trials in the near future., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
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34. Intracerebral delivery of carboplatin in combination with either 6 MV photons or monoenergetic synchrotron X-rays are equally efficacious for treatment of the F98 rat glioma.
- Author
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Bobyk L, Edouard M, Deman P, Rousseau J, Adam JF, Ravanat JL, Estève F, Balosso J, Barth RF, and Elleaume H
- Subjects
- Animals, Combined Modality Therapy, Kaplan-Meier Estimate, Male, Photons, Rats, Synchrotrons, X-Ray Therapy, Brain Neoplasms drug therapy, Brain Neoplasms pathology, Brain Neoplasms radiotherapy, Carboplatin administration & dosage, Glioma drug therapy, Glioma pathology, Glioma radiotherapy, Neoplasms, Experimental drug therapy, Neoplasms, Experimental pathology, Neoplasms, Experimental radiotherapy
- Abstract
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 glioma bearing rats over 6 days using AlzetTM osmotic pumps starting 7 days after tumor implantation. Radiotherapy was delivered in a single 15 Gy fraction on day 14 using a conventional 6 MV linear accelerator (LINAC) or 78.8 keV synchrotron X-rays., Results: Untreated control animals had a median survival time (MeST) of 33 days. Animals that received either carboplatin alone or irradiation alone with either 78.8 keV or 6 MV had a MeSTs 38 and 33 days, respectively. Animals that received carboplatin in combination with X-irradiation had a MeST of > 180 days with a 55% cure rate, irrespective of whether they were irradiated with either 78.8 KeV synchrotron X-rays or 6MV photons., Conclusions: These studies have conclusively demonstrated the equivalency of i.c. delivery of carboplatin in combination with X-irradiation with either 6 MV photons or synchrotron X-rays.
- Published
- 2012
- Full Text
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35. Monochromatic minibeams radiotherapy: from healthy tissue-sparing effect studies toward first experimental glioma bearing rats therapy.
- Author
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Deman P, Vautrin M, Edouard M, Stupar V, Bobyk L, Farion R, Elleaume H, Rémy C, Barbier EL, Estève F, and Adam JF
- Subjects
- Animals, Blood Volume radiation effects, Brain Neoplasms blood supply, Brain Neoplasms mortality, Brain Neoplasms pathology, Cranial Irradiation instrumentation, Feasibility Studies, Glioma blood supply, Glioma mortality, Glioma pathology, Magnetic Resonance Imaging, Male, Models, Animal, Organ Sparing Treatments instrumentation, Organs at Risk, Radiotherapy methods, Radiotherapy Dosage, Rats, Rats, Inbred F344, Survival Analysis, Synchrotrons instrumentation, Brain Neoplasms radiotherapy, Cranial Irradiation methods, Glioma radiotherapy, Organ Sparing Treatments methods
- Abstract
Purpose: 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., Methods and Materials: 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 incidences (54 Gy prescribed dose in a 5 × 5 × 4.8 mm(3) volume centered in the right hemisphere), respectively. Magnetic resonance imaging (MRI) follow-up was performed over 1 year. T2-weighted (T2w) images, apparent diffusion coefficient (ADC), and blood vessel permeability maps were acquired. F98 tumor bearing rats were also irradiated with interleaved minibeams to achieve a homogeneous dose of 54 Gy delivered to an 8 × 8 × 7.8 mm(3) volume centered on the tumor. Anatomic and functional MRI follow-up was performed every 10 days after irradiation. T2w images, ADC, and perfusion maps were acquired., Results: All healthy rats were euthanized 1 year after irradiation without any clinical alteration visible by simple examination. T2w and ADC measurements remain stable for the single incidence irradiation group. Localized Gd-DOTA permeability, however, was observed 9 months after irradiation for the interleaved incidences group. The survival time of irradiated glioma bearing rats was significantly longer than that of untreated animals (49 ± 12.5 days versus 23.3 ± 2 days, p < 0.001). The tumoral cerebral blood flow and blood volume tend to decrease after irradiation., Conclusions: This study demonstrates the sparing effect of minibeams on healthy tissue. The increased life span achieved for irradiated glioma bearing rats was similar to the one obtained with other radiotherapy techniques. This experimental tumor therapy study shows the feasibility of using X-ray minibeams with high doses in brain tumor radiotherapy., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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36. Monochromatic minibeam radiotherapy: theoretical and experimental dosimetry for preclinical treatment plans.
- Author
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Deman P, Vautrin M, Stupar V, Barbier EL, Elleaume H, Esteve F, and Adam JF
- Subjects
- Animals, Glioma radiotherapy, Male, Radiometry, Rats, Monte Carlo Method, Radiosurgery methods, Radiotherapy Planning, Computer-Assisted methods
- 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).
- Published
- 2011
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37. [Comments on the review entitled "Radiobiological features of anticancer treatments involving synchrotron radiation: outcome and perspectives"].
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Elleaume H, Rousseau J, Adam JF, and Estève F
- Subjects
- Antineoplastic Agents administration & dosage, Antineoplastic Agents radiation effects, Cisplatin administration & dosage, Cisplatin radiation effects, Combined Modality Therapy methods, Dose-Response Relationship, Radiation, Humans, Monte Carlo Method, Neoplasms drug therapy, Radiation Tolerance, Radiotherapy Dosage, Relative Biological Effectiveness, Treatment Outcome, Neoplasms radiotherapy, Synchrotrons
- Published
- 2011
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38. Dosimetry protocol for the forthcoming clinical trials in synchrotron stereotactic radiation therapy (SSRT).
- Author
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Prezado Y, Vautrin M, Martínez-Rovira I, Bravin A, Estève F, Elleaume H, Berkvens P, and Adam JF
- Subjects
- Humans, Radiosurgery instrumentation, Radiotherapy Dosage, Scattering, Radiation, Water, Clinical Trials as Topic methods, Clinical Trials as Topic trends, Radiometry methods, Radiosurgery methods, Synchrotrons
- Abstract
Purpose: 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%., Methods: 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., Results: 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., Conclusions: 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.
- Published
- 2011
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39. [Synchroton radiotherapy].
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Deman P, Edouard M, Besse S, Vautrin M, Elleaume H, Adam JF, and Estève F
- Subjects
- Animals, Humans, Radiotherapy methods, Stereotaxic Techniques, Brain Neoplasms radiotherapy, Synchrotrons
- 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., (Copyright (c) 2010 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)
- Published
- 2010
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40. Efficacy of intracerebral delivery of cisplatin in combination with photon irradiation for treatment of brain tumors.
- Author
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Rousseau J, Barth RF, Fernandez M, Adam JF, Balosso J, Estève F, and Elleaume H
- Subjects
- Animals, Brain Neoplasms mortality, Brain Neoplasms pathology, Combined Modality Therapy, Disease Models, Animal, Dose-Response Relationship, Radiation, Drug Delivery Systems methods, Glioma mortality, Glioma pathology, Male, Particle Accelerators, Rats, Rats, Inbred F344, Survival Analysis, Synchrotrons, Antineoplastic Agents administration & dosage, Brain Neoplasms therapy, Cisplatin administration & dosage, Glioma drug therapy, Photons therapeutic use, Radiotherapy methods
- Abstract
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. by CED at a flow rate of 0.5 microl/min. On the following day the animals were irradiated with a single 15 Gy dose of X-rays, administered by a linear accelerator (LINAC) or 78.8 keV synchrotron X-rays at the European Synchrotron Radiation Facility (ESRF). Untreated controls had a mean survival time (MST) + or - standard error of 24 + or - 1 days compared to >59 + or - 13 days for rats that received cisplatin alone with 13% of the latter surviving >200 days. Rats that received cisplatin in combination with either 6 MV (LINAC) or 78.8 keV (synchrotron) X-rays had almost identical MSTs of >75 + or - 18 and >74 + or - 19 days, respectively with 17 and 18% long-term survivors. Microscopic examination of the brains of long-term surviving rats revealed an absence of viable tumor cells and cystic areas at the presumptive site of the tumor. Our data demonstrate that i.c. CED of cisplatin in combination with external X-irradiation significantly enhanced the survival of F98 glioma-bearing rats. This was independent of the X-ray beam energy and probably was not due to the production of Auger electrons as we previously had postulated. Our data provide strong support for the approach of concomitantly administering platinum-based chemotherapy in combination with radiotherapy for the treatment of brain tumors. Since a conventional LINAC can be used as the radiation source, this should significantly broaden the clinical applicability of this approach compared to synchrotron radiotherapy, which could only be carried out at a very small number of specialized facilities.
- Published
- 2010
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41. Treatment plans optimization for contrast-enhanced synchrotron stereotactic radiotherapy.
- Author
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Edouard M, Broggio D, Prezado Y, Estève F, Elleaume H, and Adam JF
- Subjects
- Computer Simulation, Humans, Algorithms, Brain Neoplasms surgery, Models, Biological, Radiosurgery methods, Surgery, Computer-Assisted methods, Synchrotrons
- Abstract
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 energy x-rays on the high-Z atoms (characteristic x-rays, photoelectrons, and Auger electrons), produces a localized dose enhancement in the tumor. Iodine-enhanced SSRT with systemic injections of iodinated contrast agents has been successfully developed in the past six years in the team, and is currently being transferred to clinical trials. The purpose of this work is to study the impact on the SSRT treatment of the contrast agent type, the beam quality, the irradiation geometry, and the beam weighting for defining an optimized SSRT treatment plan., Methods: Theoretical dosimetry was performed using the MCNPX particle transport code. The simulated geometry was an idealized phantom representing a human head. A virtual target was positioned in the central part of the phantom or off-centered by 4 cm. The authors investigated the dosimetric characteristics of SSRT for various contrast agents: Iodine, gadolinium, and gold; and for different beam qualities: Monochromatic x-ray beams from a synchrotron source (30-120 keV), polychromatic x-ray beams from an x-ray tube (80, 120, and 180 kVp), and a 6 MV x-ray beam from a linear accelerator. Three irradiation geometries were studied: One arc or three noncoplanar arcs dynamic arc therapy, and an irradiation with a finite number of beams. The resulting dose enhancements, beam profiles, and histograms dose volumes were compared for iodine-enhanced SSRT. An attempt to optimize the irradiation scheme by weighing the finite x-ray beams was performed. Finally, the optimization was studied on patient specific 3D CT data after contrast agent infusion., Results: It was demonstrated in this study that an 80 keV beam energy was a good compromise for treating human brain tumors with iodine-enhanced SSRT, resulting in a still high dose enhancement factor (about 2) and a superior bone sparing in comparison with lower energy x-rays. This beam could easily be produced at the European Synchrotron Radiation Facility medical beamline. Moreover, there was a significant diminution of dose delivered to the bone when using monochromatic x-rays rather than polychromatic x-rays from a conventional tube. The data showed that iodine SSRT exhibits a superior sparing of brain healthy tissue in comparison to high energy treatment. The beam weighting optimization significantly improved the treatment plans for off-centered tumors, when compared to nonweighted irradiations., Conclusions: This study demonstrated the feasibility of realistic clinical plans for low energy monochromatic x-rays contrast-enhanced radiotherapy, suitable for the first clinical trials on brain metastasis with a homogeneous iodine uptake.
- Published
- 2010
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42. Long-term post-operative cognitive decline in the elderly: the effects of anesthesia type, apolipoprotein E genotype, and clinical antecedents.
- Author
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Ancelin ML, de Roquefeuil G, Scali J, Bonnel F, Adam JF, Cheminal JC, Cristol JP, Dupuy AM, Carrière I, and Ritchie K
- Subjects
- Aged, Aged, 80 and over, Anesthesia, Conduction adverse effects, Anesthesia, General adverse effects, Arthroplasty, Replacement, Attention physiology, Choice Behavior physiology, Cognition physiology, Cognition Disorders genetics, Female, Humans, Language, Male, Memory physiology, Mental Processes physiology, Neuropsychological Tests, Postoperative Complications genetics, Socioeconomic Factors, Space Perception physiology, Surveys and Questionnaires, Visual Perception physiology, Anesthesia adverse effects, Apolipoproteins E genetics, Cognition Disorders etiology, Cognition Disorders psychology, Postoperative Complications psychology
- Abstract
Cognitive dysfunction in the elderly commonly observed following anesthesia has been attributed to age-related neuronal changes exacerbated by pharmacotoxic effects. However, the extent to which these changes may persist following recovery from surgery is still largely unknown. This study investigates the long-term effects of anesthesia on cognitive functioning after orthopedic surgery in 270 elderly patients over the age of 65 who completed a computerized cognitive battery before and 8 days, 4 and 13 months after surgery. Their performance was compared to those of 310 elderly controls who completed the same neuropsychiatric evaluation at baseline and one-year interval. Multivariate analyses adjusted for socio-demographic variables, depressive symptomatology, vascular pathology as well as baseline cognitive performance. We found early and transient post-operative decline in reaction time and constructional praxis. With regard to long-term changes we observed improvement compared to controls in most verbal tasks (probably due to learning effects). On the other hand, a clear dissociation effect was observed for several areas of visuospatial functioning which persisted up to the 13-month follow-up. This specific pattern of visuospatial deficit was found to be independent of apolipoprotein E genotype and closely resembles what has recently been termed vascular mild cognitive impairment, in turn associated with subtle sub-cortical vascular changes. The observation of only minor differences between persons operated by general and regional anesthesia makes it difficult to attribute these changes directly to the anesthetic agents themselves, suggesting that cognitive dysfunction may be attributable at least in part to peri-operative conditions, notably stress and glucocorticoid exposure.
- Published
- 2010
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43. Simulation of dose deposition in stereotactic synchrotron radiation therapy: a fast approach combining Monte Carlo and deterministic algorithms.
- Author
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Smekens F, Freud N, Létang JM, Adam JF, Ferrero C, Elleaume H, Bravin A, Estève F, and Babot D
- Subjects
- Animals, Benchmarking, Head radiation effects, Humans, Radiotherapy Dosage, Rats, Time Factors, Algorithms, Models, Biological, Monte Carlo Method, Radiation Dosage, Radiosurgery instrumentation, Synchrotrons
- Abstract
A hybrid approach, combining deterministic and Monte Carlo (MC) calculations, is proposed to compute the distribution of dose deposited during stereotactic synchrotron radiation therapy treatment. The proposed approach divides the computation into two parts: (i) the dose deposited by primary radiation (coming directly from the incident x-ray beam) is calculated in a deterministic way using ray casting techniques and energy-absorption coefficient tables and (ii) the dose deposited by secondary radiation (Rayleigh and Compton scattering, fluorescence) is computed using a hybrid algorithm combining MC and deterministic calculations. In the MC part, a small number of particle histories are simulated. Every time a scattering or fluorescence event takes place, a splitting mechanism is applied, so that multiple secondary photons are generated with a reduced weight. The secondary events are further processed in a deterministic way, using ray casting techniques. The whole simulation, carried out within the framework of the Monte Carlo code Geant4, is shown to converge towards the same results as the full MC simulation. The speed of convergence is found to depend notably on the splitting multiplicity, which can easily be optimized. To assess the performance of the proposed algorithm, we compare it to state-of-the-art MC simulations, accelerated by the track length estimator technique (TLE), considering a clinically realistic test case. It is found that the hybrid approach is significantly faster than the MC/TLE method. The gain in speed in a test case was about 25 for a constant precision. Therefore, this method appears to be suitable for treatment planning applications.
- Published
- 2009
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44. Intracerebral delivery of 5-iodo-2'-deoxyuridine in combination with synchrotron stereotactic radiation for the therapy of the F98 glioma.
- Author
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Rousseau J, Adam JF, Deman P, Wu TD, Guerquin-Kern JL, Gouget B, Barth RF, Estève F, and Elleaume H
- Subjects
- Animals, Combined Modality Therapy, Male, Rats, Rats, Inbred F344, Synchrotrons, X-Rays, Brain Neoplasms drug therapy, Brain Neoplasms radiotherapy, Glioma drug therapy, Glioma radiotherapy, Idoxuridine administration & dosage, Radiation-Sensitizing Agents therapeutic use
- Abstract
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 radiosentizing agent. IUdR was administered intracerebrally over six days to F98 glioma-bearing rats using Alzet osmotic pumps, beginning seven days after tumor implantation. On the 14th day, a single 15 Gy dose of 50 keV synchrotron X-rays was delivered to the brain. Animals were followed until the time of death and the primary endpoints of this study were the mean and median survival times. The median survival times for irradiation alone, chemotherapy alone or their combination were 44, 32 and 46 days, respectively, compared with 24 days for untreated controls. Each treatment alone significantly increased the rats' survival in comparison with the untreated group. Their combination did not, however, significantly improve survival compared with that of X-irradiation alone or chemotherapy alone. Further studies are required to understand why the combination of chemoradiotherapy was no more effective than X-irradiation alone.
- Published
- 2009
- Full Text
- View/download PDF
45. Biological equivalent dose studies for dose escalation in the stereotactic synchrotron radiation therapy clinical trials.
- Author
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Prezado Y, Fois G, Edouard M, Nemoz C, Renier M, Requardt H, Estève F, Adam JF, Elleaume H, and Bravin A
- Subjects
- Biophysical Phenomena, Clinical Trials as Topic, Humans, Monte Carlo Method, Phantoms, Imaging, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted, Stereotaxic Techniques, Brain Neoplasms radiotherapy, Synchrotrons statistics & numerical data
- Abstract
Synchrotron radiation is an innovative tool for the treatment of brain tumors. In the stereotactic synchrotron radiation therapy (SSRT) technique a radiation dose enhancement specific to the tumor is obtained. The tumor is loaded with a high atomic number (Z) element and it is irradiated in stereotactic conditions from several entrance angles. The aim of this work was to assess dosimetric properties of the SSRT for preparing clinical trials at the European Synchrotron Radiation Facility (ESRF). To estimate the possible risks, the doses received by the tumor and healthy tissues in the future clinical conditions have been calculated by using Monte Carlo simulations (PENELOPE code). The dose enhancement factors have been determined for different iodine concentrations in the tumor, several tumor positions, tumor sizes, and different beam sizes. A scheme for the dose escalation in the various phases of the clinical trials has been proposed. The biological equivalent doses and the normalized total doses received by the skull have been calculated in order to assure that the tolerance values are not reached.
- Published
- 2009
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46. Heavy element enhanced synchrotron stereotactic radiotherapy as a promising brain tumour treatment.
- Author
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Adam JF, Biston MC, Rousseau J, Boudou C, Charvet AM, Balosso J, Estève F, and Elleaume H
- Subjects
- Animals, Biophysical Phenomena, Biophysics, Contrast Media administration & dosage, Glioma surgery, Humans, Idoxuridine administration & dosage, Iodine administration & dosage, Platinum administration & dosage, Rats, Rats, Inbred F344, Synchrotrons, Brain Neoplasms surgery, Radiosurgery methods
- Abstract
Synchrotron stereotactic radiotherapy (SSR) is a treatment that involves selective accumulation of high-Z elements in tumours followed by stereotactic irradiation, in CT mode, with monochromatic X-rays from a synchrotron source, tuned at an optimal energy. The irradiation geometry, characteristic X-rays, photoelectrons, and Auger electrons generated on high-Z atoms by kilovoltage X-rays produce a localized dose enhancement. Two complimentary SSR approaches have been successfully developed in the past 5 years in our team, and may be promising in high-grade glioma management: iodine-enhanced SSR, with an iodinated contrast agent; and Pt-enhanced SSR; a concomitant radio-chemotherapy treatment with locoregional injection of platinated chemotherapy drugs. The results for iodine-enhanced SSR using contrast agents are presented in this paper. IUdR-enhanced SSR was also tested in this study. Up to 15 Gy, intracarotid infusion of iodine significantly improved the rats' survival compared to irradiation alone. SSR provides the most protracted survivals of F98 glioma-bearing rats. The technique is currently transferred to clinical trials. Iodine-enhanced SSR will be implemented first, because of its simplicity; and pave the way for Pt-enhanced SSR, the most efficient technique, but still needing to be improved in terms of intrinsic toxicity.
- Published
- 2008
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47. Polymer gel dosimetry for synchrotron stereotactic radiotherapy and iodine dose-enhancement measurements.
- Author
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Boudou C, Troprès I, Rousseau J, Lamalle L, Adam JF, Estève F, and Elleaume H
- Subjects
- Dose-Response Relationship, Radiation, Iodine chemistry, Radiotherapy Dosage, Reproducibility of Results, Sensitivity and Specificity, Synchrotrons, Gels radiation effects, Iodine radiation effects, Polymers radiation effects, Radiometry methods, Radiosurgery methods
- Abstract
Synchrotron stereotactic radiotherapy (SSR) is a radiotherapy technique that makes use of the interactions of monochromatic low energy x-rays with high atomic number (Z) elements. An important dose-enhancement can be obtained if the target volume has been loaded with a sufficient amount of a high-Z element, such as iodine. In this study, we compare experimental dose measurements, obtained with normoxic polymer gel (nPAG), with Monte Carlo computations. Gels were irradiated within an anthropomorphic head phantom and were read out by magnetic resonance imaging. The dose-enhancement due to the presence of iodine in the gel (iodine concentration: 5 and 10 mg ml(-1)) was measured at two radiation energies (35 and 80 keV) and was compared to the calculated factors. nPAG dosimetry was shown to be efficient for measuring the sharp dose gradients produced by SSR. The agreement between 3D gel dosimetry and calculated dose distributions was found to be within 4% of the dose difference criterion and a distance to agreement of 2.1 mm for 80% of the voxels. Polymer gel doped with iodine exhibited higher sensitivity, in good agreement with the calculated iodine-dose enhancement. We demonstrate in this preliminary study that iodine-doped nPAG could be used for measuring in situ dose distributions for iodine-enhanced SSR treatment.
- Published
- 2007
- Full Text
- View/download PDF
48. Prolonged survival of Fischer rats bearing F98 glioma after iodine-enhanced synchrotron stereotactic radiotherapy.
- Author
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Adam JF, Joubert A, Biston MC, Charvet AM, Peoc'h M, Le Bas JF, Balosso J, Estève F, and Elleaume H
- Subjects
- Animals, Blood-Brain Barrier drug effects, Brain Neoplasms metabolism, Brain Neoplasms mortality, Glioma metabolism, Glioma mortality, Iopamidol pharmacokinetics, Male, Mannitol pharmacology, Radiotherapy Dosage, Random Allocation, Rats, Rats, Inbred F344, Synchrotrons, Tomography, X-Ray Computed methods, Blood-Brain Barrier metabolism, Brain Neoplasms radiotherapy, Contrast Media pharmacokinetics, Glioma radiotherapy, Iopamidol analogs & derivatives, Stereotaxic Techniques instrumentation
- Abstract
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
- Published
- 2006
- Full Text
- View/download PDF
49. 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.
- Author
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Adam JF, Biston MC, Joubert A, Charvet AM, Le Bas JF, Estève F, and Elleaume H
- Subjects
- Animals, Blood-Brain Barrier metabolism, Brain Neoplasms diagnostic imaging, Brain Neoplasms surgery, Glioma diagnostic imaging, Glioma surgery, Iodine Radioisotopes administration & dosage, Male, Mannitol administration & dosage, Rats, Rats, Inbred F344, Tomography, X-Ray Computed, Blood-Brain Barrier drug effects, Brain Neoplasms metabolism, Glioma metabolism, Iodine Radioisotopes pharmacokinetics, Synchrotrons
- Abstract
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.
- Published
- 2005
- Full Text
- View/download PDF
50. High-resolution blood-brain barrier permeability and blood volume imaging using quantitative synchrotron radiation computed tomography: study on an F98 rat brain glioma.
- Author
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Adam JF, Nemoz C, Bravin A, Fiedler S, Bayat S, Monfraix S, Berruyer G, Charvet AM, Le Bas JF, Elleaume H, and Estève F
- Subjects
- Animals, Brain blood supply, Cell Line, Tumor, Cerebrovascular Circulation physiology, Diagnostic Imaging methods, Image Processing, Computer-Assisted methods, Rats, Blood-Brain Barrier diagnostic imaging, Brain Neoplasms diagnostic imaging, Glioma diagnostic imaging, Permeability, Synchrotrons, Tomography, X-Ray Computed methods
- Abstract
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.
- Published
- 2005
- Full Text
- View/download PDF
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