On the relationship between cellular and hemodynamic properties of the human brain cortex throughout adult lifespan

Establishing baseline MRI biomarkers for normal brain aging is significant and valuable for separating normal changes in the brain structure and function from different neurological diseases. In this paper for the first time we have simultaneously measured a variety of tissue specific contributions defining R2* relaxation of the gradient recalled echo (GRE) MRI signal in human brains of healthy adults (ages 22 to 74 years) and related these measurements to tissue structural and functional properties. This was accomplished by separating tissue (R2_t^*) and extravascular BOLD contributions to the total tissue specific GRE MRI signal decay (R2^*) using an advanced version of previously developed Gradient Echo Plural Contrast Imaging (GEPCI) approach and the acquisition and post-processing methods that allowed the minimization of artifacts related to macroscopic magnetic field inhomogeneities, and physiological fluctuations.Our data (20 healthy subjects) show that in most cortical regions R2_t^* increases with age while tissue hemodynamic parameters, i.e. relative oxygen extraction fraction (OEF_rel), deoxygenated cerebral blood volume (dCBV) and tissue concentration of deoxyhemoglobin (C_deoxy) remain practically constant. We also found the important correlations characterizing the relationships between brain structural and hemodynamic properties in different brain regions. Specifically, thicker cortical regions have lower R2_t^* and these regions have lower OEF.The comparison between GEPCI-derived tissue specific structural and functional metrics and literature information suggests that (a) regions in a brain characterized by higher R2_t^* contain higher concentration of neurons with less developed cellular processes (dendrites, spines, etc.), (b) regions in a brain characterized by lower R2_t^* represent regions with lower concentration of neurons but more developed cellular processes, and (c) the age-related increases in the cortical R2_t^* mostly reflect the age-related increases in the cellular packing density.The baseline GEPCI-based biomarkers obtain herein could serve to help distinguish age-related changes in brain cellular and hemodynamic properties from changes which occur due to the neurodegenerative diseases.