Diffusion tensor imaging (DTI) has fundamentally transformed how we interrogate diseases and disorders of the brain in neuropsychiatric illness. DTI and recently developed multi-compartment diffusion weighted imaging (MC-DWI) techniques such as NODDI are formulated upon the assumption of a static neuroglial environment; however, microglial morphology and density are highly dynamic in psychiatric illness and how alterations in microglial density might potentially influence measures of DTI and MC-DWI brain microstructure is unknown. To address this question, DTI and MC-DWI studies of murine brains depleted of microglia were performed, which revealed significant alterations in axonal integrity and fiber tractography in DTI and in commonly used MC-DWI models. With accumulating evidence of the role of microglia in neuropsychiatric illness, our findings uncover the surprising contribution of microglia to measures of axonal integrity and structural connectivity and provide unanticipated insights into the potential influence of microglia in diffusion imaging studies of neuropsychiatric disease.

Microglial Density Alters Measures of Axonal Integrity and Structural Connectivity

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