title: Synchrotron X ray induced axonal transections in the brain of rats assessed by high-field diffusion tensor imaging tractography.
abstract: Since approximately two thirds of epileptic patients are non-eligible for surgery, local axonal fiber transections might be of particular interest for them. Micrometer to millimeter wide synchrotron-generated X-ray beamlets produced by spatial fractionation of the main beam could generate such fiber disruptions non-invasively. The aim of this work was to optimize irradiation parameters for the induction of fiber transections in the rat brain white matter by exposure to such beamlets. For this purpose, we irradiated cortex and external capsule of normal rats in the antero-posterior direction with a 4 mm×4 mm array of 25 to 1000 µm wide beamlets and entrance doses of 150 Gy to 500 Gy. Axonal fiber responses were assessed with diffusion tensor imaging and fiber tractography; myelin fibers were examined histopathologically. Our study suggests that high radiation doses (500 Gy) are required to interrupt axons and myelin sheaths. However, a radiation dose of 500 Gy delivered by wide minibeams (1000 µm) induced macroscopic brain damage, depicted by a massive loss of matter in fiber tractography maps. With the same radiation dose, the damage induced by thinner microbeams (50 to 100 µm) was limited to their paths. No macroscopic necrosis was observed in the irradiated target while overt transections of myelin were detected histopathologically. Diffusivity values were found to be significantly reduced. A radiation dose ≤ 500 Gy associated with a beamlet size of < 50 µm did not cause visible transections, neither on diffusion maps nor on sections stained for myelin. We conclude that a peak dose of 500 Gy combined with a microbeam width of 100 µm optimally induced axonal transections in the white matter of the brain.
authors: INSERM, U836, Grenoble, France ; Université Joseph Fourier, Grenoble Institut des Neurosciences, UMR-S836, Grenoble, France.
authors: Raphaël
authors: R
authors: Serduc
authors: INSERM, U836, Grenoble, France ; Université Joseph Fourier, Grenoble Institut des Neurosciences, UMR-S836, Grenoble, France ; European Synchrotron Radiation Facility, Grenoble, France ; University of Bern, Bern, Switzerland.
authors: Audrey
authors: A
authors: Bouchet
authors: INSERM, U836, Grenoble, France ; Université Joseph Fourier, Grenoble Institut des Neurosciences, UMR-S836, Grenoble, France.
authors: Benoît
authors: B
authors: Pouyatos
authors: CNRS, CerCo, Toulouse, France ; Université de Toulouse, UPS, Centre de Recherche Cerveau et Cognition, Toulouse, France.
authors: Luc
authors: L
authors: Renaud
authors: European Synchrotron Radiation Facility, Grenoble, France.
authors: Elke
authors: E
authors: Bräuer-Krisch
authors: European Synchrotron Radiation Facility, Grenoble, France.
authors: Géraldine
authors: G
authors: Le Duc
authors: University of Bern, Bern, Switzerland.
authors: Jean A
authors: JA
authors: Laissue
authors: German Cancer Research Center, Heildeberg, Germany.
authors: Stefan
authors: S
authors: Bartzsch
authors: INSERM, U836, Grenoble, France ; Université Joseph Fourier, Grenoble Institut des Neurosciences, UMR-S836, Grenoble, France.
authors: Nicolas
authors: N
authors: Coquery
authors: Service du développement et de la croissance, hôpitaux universitaires de Genève, Genève, Suisse ; Laboratoire d'imagerie fonctionnelle et métabolique, école polytechnique fédérale de Lausanne, Lausanne, Suisse.
authors: Yohan
authors: Y
authors: van de Looij
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology* / Q000528:radiation effects; D001921:Brain / Q000473:pathology* / Q000528:radiation effects; D056324:Diffusion Tensor Imaging / Q000379:methods*; D009186:Myelin Sheath / Q000473:pathology / Q000528:radiation effects; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000528:radiation effects; D011829:Radiation Dosage; D051381:Rats; D017356:Synchrotrons; D014965:X-Rays