Longitudinal Study of Irradiation-Induced Brain Microstructural Alterations With S-Index, a Diffusion MRI Biomarker, and MR Spectroscopy

Purpose: Radiation therapy is widely used for the treatment of brain tumors, but it may lead to severe cognitive impairments. Previous studies have shown that ionizing irradiation induces demyelination, blood-brain barrier alterations, and impaired neurogenesis in animal models. Hence, noninvasive and sensitive biomarkers of irradiation injury are needed to investigate these effects in patients and improve radiation therapy protocols.

Methods and materials: The heads of 3-month-old male C57BL/6RJ mice (15 control mice and 15 irradiated mice) were exposed to radiation doses of 3 fractions of 5 Gy from a ⁶⁰Co source with a medical irradiator. A longitudinal study was performed to investigate cranial irradiation-induced (3 fractions of 5 Gy) microstructural tissue alterations using water diffusion magnetic resonance imaging and magnetic resonance spectroscopy in different areas of the mouse brain (cortex, thalamus, striatum, olfactory bulbs [OBs], hippocampus, and subventricular zone [SVZ]). In addition to the quantification of standard non-Gaussian diffusion parameters, apparent diffusion coefficient (ADC₀) and kurtosis (K), we evaluated a new composite diffusion metric, designated the S-index (ie, "signature index").

Results: We observed a significant decrease in the S-index in the SVZ from 1 month to 8 months after brain irradiation (P < .05). An interesting finding was that, along with a decrease in taurine levels (up to -15% at 2 months, P < .01), a delayed S-index drop was observed in the OBs from 4 months after irradiation and maintained until the end of our experiment (P < .0001). These observations suggest that S-index variations revealed the irradiation-induced decline of neurogenesis that was further confirmed by a decrease in neural stem cells in the SVZ and in newborn neurons in the OBs of irradiated animals.

Conclusions: This study demonstrates that diffusion magnetic resonance imaging, especially through the S-index approach, is a relevant imaging modality to monitor brain irradiation injury and probe microstructural changes underlying irradiation-induced cognitive deficits.