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A team comprising iRCM (CEA-Jacob) and NeuroSpin (CEA-Joliot) researchers analyzed the consequences of irradiation on brain development and neurogenesis in a preclinical model. That work, published in
Radiation Research, lays a path for the use of diffusion imaging for the early detection of neurological abnormalities resulting from different types of stress.
The diagnostic or therapeutic use of ionizing radiation can cause untoward and irreversible consequences for the brain, notably during its development. Furthermore, radiosensitivity is under the influence of certain genetic factors. Epidemiological studies have shown long-term cerebral lesions following in utero radiation exposure, which may occur because of medical interventions like radiation therapy or nuclear accidents like those at Chernobyl or Fukushima. Complications including growth retardation, microcephaly and intellectual disabilities have also been associated with such exposure. Radiosensitivity is dose and age-dependent, with children aged less than seven years more susceptible to serious neurological consequences.
Importantly, such epidemiological studies on radiation exposure are difficult to deploy, and all the more so in the in utero setting. In vitro and in vivo preclinical models however can contribute greatly to a better understanding of early radiation-induced biological processes.
Morphological, metabolic and functional studies can be performed in vivo, non-invasively and longitudinally in animals or humans thanks to magnetic resonance imaging (MRI). For example, microstructural and morphological brain alterations due to radiation exposure have been demonstrated using structural (sMRI) and notably diffusion MRI (dMRI). This latter, although not needed for all cerebral lesions, gives researchers the ability to study the microscopic movement of water molecules, which lends exquisite information on the microstructure of brain tissues.
Considering these possibilities, it would be of great interest to identify imaging markers for cerebral modifications due to low or high-dose irradiation in pertinent preclinical models.
With that goal in mind, researchers from UMR1274 (IRCM/CEA-Jacob) in partnership with NeuroSpin (CEA-Joliot) studied the consequences of in utero (during embryonic development) exposure to radiation on brain development and neurogenesis in a murine model. In their work, published in Radiation Research, the researchers first showed that irradiation causes behavioral alterations in in utero-exposed adult mice. They also reported the development of microcephaly and cerebral microstructure alterations (including myelination profile changes) in the irradiated mouse embryos.
Thereafter, the team analyzed sMRI and dMRI images from adult mice irradiated during their embryonic development, comparing them to those of a control group. They observed volumetric modifications, i.e., significant cerebral atrophy, in the in utero-irradiated mice. Also, the S-index, a dMRI biomarker sensitive to microstructure alterations, diminished significantly in the experimental group.
By correlating the results obtained from the various analyses (histology and imaging), the researchers were able to report sMRI evidence of long-term microcephaly induced by irradiation. Furthermore, the dMRI data revealed cerebral microstructure damage in adult mice exposed to ionizing radiation during their intrauterine development, resulting in behavioral alterations.
The CEA team thus developed a noninvasive sMRI/dMRI approach to detect and characterize radiation-induced neuropathological impairments in a preclinical irradiation model.
The employed MRI markers coupled with a 3D map of the brain enabled an illustration of the sensitivities of specific cerebral structures to ionizing radiation as a function of the irradiated tissue.
Together, these results create new possibilities for the use of diffusion imaging to quickly detect consequential neurological abnormalities caused by various forms of stress (irradiation, genotoxins, etc.) and perhaps thus provide better care to the affected patients.
To learn more about diffusion MRI (information in French):
Médiathèque - Fonctionnement de l'IRM de diffusion (cea.fr)
Diffusion MRI is a medical technology that uses a coefficient of diffusion of the water within a tissue to create an image of this latter. Normal water diffusion within the cerebral tissues is constrained by the various physiological structures therein. Thus, any damage to those structures will result in changes to the diffusion.
Noninvasive Assessment of Neurodevelopmental Disorders after In Utero Irradiation in Mice: An In Vivo Anatomical and Diffusion MRI Study I Radiation Research
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.