We proposed to develop quantitative magnetic resonance (MR) methods of imaging cerebral blood flow (CBF) and blood volume (CBV) using combinations of magnitude- and phase-based blood and tissue signals. Quantitative CBV and CBF imaging in the human brain is of significant importance in the evaluation of a number of disease processes, especially those involving longitudinal measurements within and across subjects. Also, it is fundamental in understanding the relationship of brain function to brain metabolism in the normal brain. Compared with the quantitative method of positron emission tomography (PET), MR utilizing bolus administration of gadolinium (Gd), contrast agents has potential advantages of high spatial resolution, high signal- to-signal ratio (SNR), no ionizing radiation, high availability, and lower costs. However, the ability of MR methods to quantitate CBF and CBV has not yet been fully realized. While the magnetic susceptibility effect of bolus Gd injection on change in relaxation rate (deltaR2 or delta R*2 signals) is often used for MR perfusion imaging, these signals are likely dependent on other factors in addition to tissue GD concentration, such as compartmentation (e.g., hematocrit). CBV and CBF quantitations also require measurement of the Gd arterial input function (AIF), where temporal and spatial resolution, SNR, signal linearity with respect to concentration, and response over a wide range of doses and concentrations (dose dynamic range) are critical. We plan to utilize phase shift (delta-phi) signals in conjunction with deltaR2 and deltaR*2 to quantitate CBV and CBF. In model systems, the delta-phi signal is linear and has high SNR and dose dynamic range. As the first Aim, these signal mechanisms will be analyzed theoretically and experimentally in blood and tissue. In the second Aim, signal- concentrations relations will be experimentally determined in blood and tissue. Finally, the validity of quantitative MR CBV and CBF measurements obtained with different signal combinations will be tested against PET in baboons with normal and physiologically-altered flow.
