Noninvasive quantification of ketamine-induced structural plasticity in mice using multishell diffusion weighted imaging

Motivation: To monitor treatment, we need noninvasive quantitation of the microstructural changes known to accompany rapid-acting antidepressant therapy. Goal(s): Our goal was to develop a noninvasive biomarker of the structural plasticity induced by rapid-acting antidepressants. Approach: Neurite orientation dispersion and density imaging (NODDI) was assessed before and after treating male and female mice with ketamine, with or without opioid blockade. Results: Ketamine induced alterations of orientation dispersion index (ODI) and neurite density index (NDI) in brain regions involved in mood regulation and reward processing, particularly in females. Curiously, opioid blockade induced trendwise increases in NDI and ODI across multiple brain regions, independent of ketamine. Impact: Our preliminary results indicate that multishell diffusion MRI tracks the brain microstructural changes known to be induced by ketamine and related rapid-acting antidepressants, enabling a noninvasive quantitative biomarker that could be used to track individual patient response to antidepressant therapy.