Association between ageing, brain chemistry and white matter volume revealed with complementary MRI and FTIR brain imaging.

Magnetic resonance imaging (MRI) is the gold standard method to study brain anatomy in vivo. Using MRI, subtle alterations to white matter structures in the brain are observed prior to cognitive decline associated with the ageing process, and neurodegenerative diseases such as Alzheimer's disease. Detection of such alterations provides hope for early clinical diagnosis. While MRI is essential to detect subtle alterations to brain structure in vivo, the technique is less suited to study and image the distribution of biochemical markers within specific brain structures. Consequently, the chemical changes that drive, or are associated with MRI-detectable alterations to white matter are not well understood. Herein, we describe (to the best of our knowledge) the first application of a complementary imaging approach that incorporates in vivo MRI with ex vivo Fourier transform infrared (FTIR) spectroscopic imaging on the same brain tissue. The combined workflow is used to detect and associate markers of altered biochemistry (FTIR) with anatomical changes to brain white matter (MRI). We have applied this combination of techniques to the senescence accelerated murine prone strain 8 (SAMP8) mouse model (n = 6 animals in each group, analysed across two ageing time points, 6 and 12 months). The results have demonstrated alterations to lipid composition and markers of disturbed metabolism during ageing are associated with loss of white matter volume.

Characterization of Ionic and Lipid Gradients within Corpus Callosum White Matter after Diffuse Traumatic Brain Injury in the Rat.

There is increased recognition of the effects of diffuse traumatic brain injury (dTBI), which can initiate yet unknown biochemical cascades, resulting in delayed secondary brain degeneration and long-term neurological sequela. There is limited availability of therapies that minimize the effect of secondary brain damage on the quality of life of people who have suffered TBI, many of which were otherwise healthy adults. Understanding the cascade of biochemical events initiated in specific brain regions in the acute phase of dTBI and how this spreads into adjacent brain structures may provide the necessary insight into drive development of improved therapies. In this study, we have used direct biochemical imaging techniques (Fourier transform infrared spectroscopic imaging) and elemental mapping (X-ray fluorescence microscopy) to characterize biochemical and elemental alterations that occur in corpus callosum white matter in the acute phase of dTBI. The results provide direct visualization of differential biochemical and ionic changes that occur in the highly vulnerable medial corpus callosum white matter relative to the less vulnerable lateral regions of the corpus callosum. Specifically, the results suggest that altered ionic gradients manifest within mechanically damaged medial corpus callosum, potentially spreading to and inducing lipid alterations to white matter structures in lateral brain regions.