ABSTRACT: The Network Modification (NeMo) Tool uses a library of brain connectivity maps from normal subjects to quantify the amount of structural connectivity loss caused by focal brain lesions. We hypothesized that the Network Modification Tool could predict remote brain tissue loss caused by poststroke loss of connectivity.Baseline and follow-up MRIs (10.7±7.5 months apart) from 26 patients with acute ischemic stroke (age, 74.6±14.1 years, initial National Institutes of Health Stroke Scale, 3.1±3.1) were collected. Lesion masks derived from diffusion-weighted images were superimposed on the Network Modification Tool's connectivity maps, and regional structural connectivity losses were estimated via the Change in Connectivity (ChaCo) score (ie, the percentage of tracks connecting to a given region that pass through the lesion mask). ChaCo scores were correlated with subsequent atrophy.Stroke lesions' size and location varied, but they were more frequent in the left hemisphere. ChaCo scores, generally higher in regions near stroke lesions, reflected this lateralization and heterogeneity. ChaCo scores were highest in the postcentral and precentral gyri, insula, middle cingulate, thalami, putamen, caudate nuclei, and pallidum. Moderate, significant partial correlations were found between baseline ChaCo scores and measures of subsequent tissue loss (r=0.43, P=4.6×10(-9); r=0.61, P=1.4×10(-18)), correcting for the time between scans.ChaCo scores varied, but the most affected regions included those with sensorimotor, perception, learning, and memory functions. Correlations between baseline ChaCo and subsequent tissue loss suggest that the Network Modification Tool could be used to identify regions most susceptible to remote degeneration from acute infarcts.