Longitudinal study of radiation-induced brain microstructural alterations with S-index, a Diffusion MRI biomarker, and MR Spectroscopy

Publication date: Available online 2 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): E.A. Pérès, O. Etienne, A. Grigis, F. Boumezbeur, F.D. Boussin, D. Le Bihan
PurposeRadiotherapy is widely used for the treatment of brain tumors but it may lead to severe cognitive impairments. Previous studies have shown that ionizing radiation induces demyelination, blood-brain barrier alterations and impaired neurogenesis in animal models. Hence, non-invasive and sensitive biomarkers of radiation injury are needed to investigate these effects in patients and improve radiotherapy protocols.Methods and MaterialsThe heads of 3-months old male C57BL/6RJ mice (CTL: n=15; IR: n=15) were exposed to radiation doses of 3x5Gy from a ⁶⁰Co source with a medical irradiator. A longitudinal study was performed to investigate cranial radiation-induced (3x5Gy) microstructural tissue alterations using water diffusion MRI (dMRI) and MR Spectroscopy (MRS) in different areas of the mouse brain (cortex, thalamus, striatum, olfactory bulbs (OB), hippocampus and the subventricular zone (SVZ)). In addition to the quantification of standard non-Gaussian diffusion parameters, ADC0 (Apparent Diffusion Coefficient) and K (Kurtosis), we evaluated a new composite diffusion metric, designated as S-index.ResultsWe observed a significant decrease in S-index in the SVZ, from 1 month to 8 months after brain radiation (p<0.05). Interestingly, along with a decrease in Taurine (up to -15% at 2 months, p<0.01), a delayed S-index drop was also observed in the OB from 4 months after irradiation and maintained until the end of our experiment (p<0.0001). These observations suggest that S-index variations revealed the radiation-induced decline of neurogenesis that was further confirmed by a decrease of neural stem cells in the SVZ and of newborn neurons in the OB of irradiated animals.ConclusionsThis study demonstrates that dMRI, especially through the S-index approach, is a relevant imaging modality to monitor brain radiation injury and probe microstructural changes underlying radiation-induced cognitive deficits.

Teaser

Cancer patients frequently suffer from cognitive impairments following brain radiotherapy. To monitor radiation-induced microstructural tissue damage, especially in neurogenic areas, we have investigated the potential of diffusion MRI and MR spectroscopy. The diffusion S-index calculated from diffusion MRI signal acquired at two optimized values of diffusion-weighting appeared as the most sensitive biomarker revealing subtle brain tissue alterations induced by ionizing radiation.


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