Detection of neuronal loss using T_1ρ MRI assessment of ¹H₂O spin dynamics in the aphakia mouse

The loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) is well characterized in Parkinson's disease (PD). Recent developments in magnetic resonance imaging (MRI) techniques have provided the opportunity to evaluate for changes in cellular density. Longitudinal relaxation measurements in the rotating frame (T_1ρ) provide a unique magnetic resonance imaging contrast in vivo. Due to the specificity of T_1ρ to water-protein interactions, the T_1ρ MRI method has strong potential to be used as a non-invasive method for quantification of neuronal density in the brain. Recently introduced adiabatic T_1ρ magnetic resonance imaging mapping methods provide a tool to assess molecular motional regimes with high sensitivity due to utilization of an effective magnetic field sweep during adiabatic pulses. In this work, to investigate the sensitivity of T_1ρ to alterations in neuronal density, adiabatic T_1ρ MRI measurements were employed in vivo on Pitx3-homeobox gene-deficient aphakia mice in which the deficit of DA neurons in the SNc is well established. The theoretical analysis of T_1ρ maps in the different areas of the brain of aphakia mouse suggested variation of the ¹H₂O rotational correlation times, τ_c. This suggests τ_c to be a sensitive indicator for neuronal loss during neurological disorders. The results manifest significant dependencies of the T_1ρ relaxations on the cell densities in the SNc, suggesting T_1ρ MRI method as a candidate for detection of neuronal loss in neurological disorders.