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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(1rho)) provide a unique magnetic resonance imaging contrast in vivo. Due to the specificity of T(1rho) to water-protein interactions, the T(1rho) 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(1rho) 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(1rho) to alterations in neuronal density, adiabatic T(1rho) 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(1rho) maps in the different areas of the brain of aphakia mouse suggested variation of the (1)H(2)O rotational correlation times, tau(c). This suggests tau(c) to be a sensitive indicator for neuronal loss during neurological disorders. The results manifest significant dependencies of the T(1rho) relaxations on the cell densities in the SNc, suggesting T(1rho) MRI method as a candidate for detection of neuronal loss in neurological disorders.
Microdialysis is a well validated sampling technique that can be used for pharmacokinetic studies of oncological drugs targeting the central nervous system. This technique has also been applied to evaluate tumor metabolism and identify pharmacodynamic biomarkers of drug activity. Despite the potential utility of microdialysis for therapeutic discovery, variability in tumor size and location hamper routine use of microdialysis as a preclinical tool. Quantitative validation of microdialysis membrane location relative to radiographically evident tumor regions could facilitate rigorous preclinical studies. However, a widely accessible standardized workflow for preclinical catheter placement and validation is needed.
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