Measuring Cerebral Blood Flow in a Mouse Model of Alzheimer's Disease

Abstract

Mild traumatic brain injuries (mTBIs), which are defined by an absence of overt structural damage in the brain have been associated with an increased risk of Alzheimer's Disease when sustained multiple times over an interval. Within mTBI, indirect evidence suggests that persistent post-concussive symptoms may be linked to reduced cerebral blood flow (CBF), of which deficits have been observed in cases of Alzheimer's Disease.

Diffuse correlation spectroscopy (DCS) is a non-invasive optical method that uses near-infrared light to measure fluctuations in intensity that are caused by moving red blood cells that can be used to measure cerebral blood flow (CBF) in C57bl/6 mice. This dissertation will adapt this novel protocol to a mouse model of Alzheimer’s Disease (3xTg). This strain will be utilized due to its accelerated AD pathology and the presence of literature that have observed impairments in CVR, CBF, among other biomarkers of Alzheimer’s Disease and traumatic brain injury. Given the smaller size of the 3xTg mice compared to C57bl/6, the DCS optical sensor must be modified. Herein, the design of a smaller sensor is detailed, along with a series of validation tests, which include measurements on a liquid phantom with known flow properties and on a pilot cohort of four 6–7-month-old 3xTg mice (2 males, 2 females). This data provides the foundational work to characterize the feasibility of DCS as a technique to monitor CBF and CVR in 3xTg mice for future experiments.