The invention relates to systems and methods for assessing blood flow in single or multiple vessels and segments, for assessing vascular health, for conducting clinical trials, for screening therapeutic interventions for effect, for assessing risk factors, for evaluating intracranial pressure and for analyzing the results in a defined manner. The invention enables direct monitoring of therapies, substances and devices on blood vessels, especially those of the cerebral vasculature. Relevant blood flow parameters include mean flow velocity, systolic acceleration, and pulsatility index. Measurement and analysis of these parameters, and others, provides details regarding the vascular health of individual and multiple vessels and a global analysis of an individual's overall vascular health. The invention can track the onset, progression and treatment efficacy in an individual experiencing increased intracranial pressure, or can help identify underlying vulnerabilities of the vascular system to normal pressures, associated with and manifested as hydrocphalus or dementia.