Characterization of neurofluid flow using physics-guided enhancement of 4D flow MRI

Cerebrospinal fluid (CSF) plays a diverse role within the skull including cushioning the brain, regulating intracranial pressure, and clearing metabolic waste via the glymphatic system. Disruptions in CSF flow have long been investigated for hydrocephalus-related diseases such as idiopathic normal pressure hydrocephalus (iNPH). Recently, changes in CSF flow have been implicated in neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease. It remains difficult to obtain in vivo measurements of CSF flow which contribute to disease initiation, progression, and treatment. Three-directional phase-contrast MR imaging (4D flow MRI) has been used to measure CSF velocities within the cerebral ventricles. However, there remain challenges in balancing acquisition time, spatiotemporal resolution, and velocity-to-noise ratio. This is complicated by the low velocities and long relaxation times associated with CSF flow. Additionally, flow-derived metrics associated with cellular adaptations and transport rely on near-wall velocities which are poorly resolved and noisy. To address these challenges, we have applied physics-guided neural networks (PGNN) to super-resolve and denoise synthetic 4D flow MRI of CSF flow within the 3rd and 4th ventricles using novel physics-based loss functions. These loss functions are specifically designed to ensure that high-resolution estimations of flow fields are physically consistent and temporarily coherent. We apply these PGNN to various test cases including synthetically generated 4D flow MRI in the cerebral ventricles and vasculature, in vitro 4D flow MRI acquired at two resolutions in 3D printed phantoms of the 3rd and 4th ventricles, and in vivo 4D flow MRI in a healthy subject. Lastly, we apply these physics-guided networks to investigate blood flow through cerebral aneurysms. These techniques can empower larger studies investigating the coupling between arterial blood flow and CSF flow in conditions such as iNPH and AD.