Measuring Myelin Repair and Axonal Loss with Diffusion Tensor Imaging

Abstract

DTI is an MR imaging measure of brain tissue integrity and provides an attractive metric for use in neuroprotection clinical trials. The purpose of our study was to use DTI to evaluate the longitudinal changes in brain tissue integrity in a group of patients with MS. Twenty-one patients with MS starting natalizumab were imaged serially for 12 months. Gadolinium-enhancing lesions and 20 regions of interest from normal-appearing white and gray matter brain tissue were followed longitudinally. Average values within each region of interest were derived for FA, λ(∥), λ(⊥), and MD. New T1 black holes were identified at 12 months. Analysis was performed by using mixed-model regression analysis with slope (ie, DTI change per month) as the dependent variable. During 1 year, FA increased in gadolinium-enhancing lesions but decreased in NABT (P < .0001 for both). Changes in FA within gadolinium-enhancing lesions were driven by decreased λ(⊥) (P < .001), and within NABT, by decreased λ(∥) (P < .0001). A higher λ(⊥) within gadolinium-enhancing lesions at baseline predicted conversion to T1 black holes at 12 months. MD was unchanged in both gadolinium-enhancing lesions and NABT. We observed changes in DTI measures during 1 year in both gadolinium-enhancing lesions and NABT. The DTI results may represent possible remyelination within acute lesions and chronic axonal degeneration in NAWM. These results support the use of DTI as a measure of tissue integrity for studies of neuroprotective therapies.