MRI Markers for Detecting Accelerated Alzheimer’s Disease after Neurotrauma

Abstract

AbstractBackgroundA history of traumatic brain injury (TBI) is linked to an earlier onset of Alzheimer’s disease (AD) (Nemetz et al., 1999). Evidence showed that the more severe the injury, the greater risk of developing AD (Johnson et al.,2010). However, systematic evaluation of in vivo MRI markers in the monitoring of AD progression after trauma is lacking. Here, we investigated the performance of various MRI markers in tracking AD progression after neurotrauma in a mouse model of AD. The following MRI sequences were investigated: dynamic contrast‐enhanced (DCE) MRI, Fluid attenuated inversion recovery (FLAIR) MRI, Quantitative Susceptibility Mapping (QSM) and diffusion MRI.Method3xTg‐AD mice (Jackson Laboratory, ME) were bred and maintained at Boston University. Unanesthetized mice were pretreated with a non‐sedating dose of the analgesic buprenorphine (0.2mg/kg, i.p.) prior to TBI. Male and female 3xTg‐AD mice were subjected to left‐lateral closed‐head impact injury at 10‐12 weeks of age as described in our previous work (Tagge et al., 2018). MRI data were acquired at 1 day, 3 days, 1 month and 3 months post TBI. DCE‐MRI was analyzed using in‐house software programmed in Matlab (Mathworks, MA). The volume of white matter hyperintensity was measured using manual contours in ImageJ (NIH). QSM data was analyzed using JHU/KKI QSM Toolbox (Li et al, 2019). Diffusion MRS was analyzed in DSI Studio (http://dsistudio.labsolver.org). Age, gender matched 3xTg‐AD mice without TBI were used as controls.ResultIncreased blood‐brain permeability was detected by DCE‐MRI and changes of white matter susceptibility detected by QSM were observed in the subacute phase (1‐3 days) post TBI. Accelerated development of white matter hyperintensity was observed as early as 1 month post TBI.ConclusionMRI markers provide valuable measures of the integrities of blood‐brain barrier and white matter after neurotrauma in vivo, and have the potential to facilitate the management of neurotrauma subjects with a risk of accelerated AD development.