Correlative multi-scale cytoarchitecture of the human brain for stratification of ALS patients

This proposal aims to characterise heterogeneity of the disease Amyotrophic Lateral Sclerosis (ALS), an incurable and relentlessly progressive, fatal motor neuron disease, using multi-modal /-scale /- synchrotron X-ray tomography. A key to understanding the disease heterogeneity is linking clinical imaging (MRI) down to variations in the patterns of cytoarchitechture changes in human ALS brains. Through the HOAHub we have developed a protocol whereby human brains with very short post-mortem interval, are collected, undergo diffusion MRI, and are then scanned down to ~1um/voxel on BM18/BM05 (beamtime already awarded). We will take small biopsies from these brains in specific locations of the cortex, relevant for stratifying ALS patient cohorts, prepare them for nano tomography, through paraffin embedding and osmium staining, then scan on ID16A, to provide single cell/axon resolution. All dataset will then all be registered to link single axon to diffusion MRI.