Using multi-modality measurements to investigate intracranial pressure waveform morphology in patients with normal pressure hydrocephalus

The dynamic environment of the cranial vault relies on normal brain pulsatility to maintain homeostasis. Small deviations in pressure or flow of either blood or cerebrospinal fluid (CSF) can drastically alter normal brain function. This thesis will investigate alterations in brain pulsatility in normal pressure hydrocephalus (NPH) patients; however, many of the conclusions/analysis methods have a broader impact and can be applied to other neurologic conditions, including traumatic brain injury and subarachnoid hemorrhage. Invasive intracranial pressure (ICP) monitoring and noninvasive Phase-contrast MRI (PC-MRI) will be used to measure brain pulsatility for this thesis, which is divided into three sections with three specific aims. Study 1: It is commonly accepted that there is some degree of CSF dysfunction in NPH. The first study investigates the stroke volume, latency, and variability changes that occur in the cerebral aqueduct and prepontine cistern of NPH patients and age-matched controls. Results show significant alterations in all aspects of CSF dynamics, which suggests decrease cisternal buffering, decreased compliance, and increased variability in the NPH cohort. Study 2: Differentiating shunt responders and non-responders has been a cornerstone of NPH research for over 50 years. Several aspects of ICP monitoring have been investigated as possible prognostic tests for NPH; however, results remain inconsistent and inaccurate. The advanced morphological analysis techniques used in this study show higher accuracy than traditional ICP analysis. These features, once further validated, could replace existing methods for more expensive, less accurate shunt selections. Study 3: Changes in pressure and flow dominate regulation of the internal dynamic environment of the brain; despite the physical relationship between the two phenomena, little is known about their impact on one another. Using CSF flow measured by PC-MRI, regional and individual ICP metrics that correlate with CSF flow were easily identified. This is a first step toward a better understanding of the characteristic peaks of the ICP pulse pressure waveform. Conclusion: The aforementioned studies reveal that modest changes in brain pulsatility can be detected in NPH patients. Although it is unlikely that these changes are the sole reason for the symptoms of NPH, these studies make important advances in understanding the pathoetiology of NPH. These discoveries need further investigation, but have the potential to change the way NPH is diagnosed and treated in the future.