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We first derived a biophysical model of neurite beading, and we show that the beaded morphology allows a larger volume to be encompassed within an equivalent surface area and is, therefore, a consequence of osmotic imbalance after ischemia. The DWI experiment simulated within the model revealed that intracellular ADC decreased by 79% in beaded neurites compared with the unbeaded form. To validate the model experimentally, excised rat sciatic nerves were subjected to stretching, which induced beading but did not cause a bulk shift of water into the axon (i.e., swelling). Beading-induced changes in cell-membrane morphology were sufficient to significantly hinder water mobility and thereby decrease ADC, and the experimental measurements were in excellent agreement with the simulated values. This is a demonstration that neurite beading accurately captures the diffusion changes measured in vivo. The results significantly advance the specificity of DWI in ischemia and other acute neurological injuries and will greatly aid the development of treatment strategies to monitor and repair damaged brain in both clinical and experimental settings.<\/jats:p>","DOI":"10.1073\/pnas.1004841107","type":"journal-article","created":{"date-parts":[[2010,7,26]],"date-time":"2010-07-26T23:41:37Z","timestamp":1280187697000},"page":"14472-14477","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":241,"title":["Neurite beading is sufficient to decrease the apparent diffusion coefficient after ischemic stroke"],"prefix":"10.1073","volume":"107","author":[{"given":"Matthew D.","family":"Budde","sequence":"first","affiliation":[{"name":"Radiology and Imaging Sciences, Clinical Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A.","family":"Frank","sequence":"additional","affiliation":[{"name":"Radiology and Imaging Sciences, Clinical Center, and"},{"name":"Intramural Research Program, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,7,26]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"423","article-title":"Diffusion-weighted MR imaging of acute stroke: Correlation with T2-weighted and magnetic susceptibility-enhanced MR imaging in cats","volume":"11","author":"Moseley ME","year":"1990","unstructured":"ME Moseley, et al., Diffusion-weighted MR imaging of acute stroke: Correlation with T2-weighted and magnetic susceptibility-enhanced MR imaging in cats. 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