Project Summary/Abstract The subarachnoid space (SAS) and dura are critical to brain health, but the vast majority of neuroimaging studies have been concerned solely with the gray matter and white matter of the brain itself. The dura is a thin, tough membrane about 1 mm thick that lies just inside the skull protecting the brain as well as the blood vessels and cerebrospinal fluid (CSF). The paired dural membranes separate to create the dural sinuses, which contain venous blood that drains blood as well as CSF from the brain. The SAS is a variable-thickness space lying just inside the dura and outside the brain and contains CSF, blood vessels, and arachnoid trabeculae, which loosely connect the arachnoid and pia matter. Both structures are thought to provide mechanical protection for the brain and are therefore important in modeling impacts that may lead to traumatic brain injury. As well, these structures are critical for their roles in facilitating adequate blood and CSF flow, which are both critical to brain health. Magnetic resonance imaging (MRI) is the key modality for imaging the brain, and one of the first steps in a conventional neuroimage pipeline is to remove materials outside the brain, including the SAS and dura (in a step called “skull-stripping” or “brain isolation”). This grant aims to radically alter this practice and to recover this conventionally-ignored extra-axial material by providing methods to segment both the SAS and dura and to characterize their geometries in health and disease. Specifically, we will: 1) Develop and carry out a detailed manual delineation protocol for labeling the SAS, the dural sinuses, and the epidural surface using multi-modal images; 2) Develop an automated algorithm to segment the subarachnoid space, dural sinuses, and dura from conventional T1-weighted and T2-weighted MRI; 3) Carry out pilot studies on subjects with normal pressure hydrocephalus and multiple sclerosis as well as normally aging adults. The software implementing these methods will be made freely available to the neuroscience community which will enable a host of new studies involving the quantification of this extra-axial anatomy across many neurological and neurodegenerative diseases.