In vivo palpation of anisotropic human brain tissue using MRI

The mechanical stiffness of brain parenchyma varies across physiological states and pathophysiological conditions, such as during normal and abnormal development, in degenerative diseases and disorders, like Alzheimer's disease and traumatic brain injury (TBI), neuronal activation, and sleep via the glymphatic brain waste clearance mechanism. Despite its biological and clinical importance, relatively few techniques exist to measure and map mechanical properties of brain tissue non-invasively and in vivo . MR elastography (MRE) is an established method that has been widely used to estimate tissue stiffness in the liver by applying mechanical waves using an external tamper and measuring their resulting deformations. However, applying MRE in the brain is more challenging due to the skull and cerebrospinal fluid (CSF), which impede mechanical wave propagation, and tissue mechanical anisotropy, which requires a 4 ^th -order tensor description. In this study, we propose using the intrinsic deformation of brain tissue caused by periodic cardiac pulsation to measure the 4 ^th -order stiffness tensor throughout the brain while simultaneously estimating the 2 ^nd -order diffusion tensor in each voxel throughout the cardiac cycle, which we use as a priori information in the reconstruction of the stiffness tensor. While the DTI-derived mean diffusivity (MD) appears uniform throughout brain parenchyma, stiffness maps obtained at about 1 Hz (i.e., at the fundamental cardiac frequency) show contrast within gray matter, and within white matter pathways such as along the corpus callosum, internal capsule, corona radiata, etc. Generally, stiffness differences at internal tissue boundaries are expected to lead to local stress concentration, which may predispose tissues to damage in TBI. Therefore, our novel tamperless MRE method has the potential to not only identify such interfaces, but assess changes in tissue stiffness there that might occur following injury.