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These fixation\u2010induced changes likely also affect myelin density measurements produced by quantitative magnetization transfer and myelin water imaging. In this work, we evaluate these myelin\u2010sensitive MRI methods for fixation\u2010induced biases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We perform quantitative magnetization transfer, myelin water imaging, and deuterium oxide\u2010exchanged zero TE imaging on unfixed human spinal cord tissue at 9.4 Tesla and repeat these measurements after 1 day and 31 days of formalin fixation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The quantitative magnetization\u2010transfer bound pool fraction increased by 30.7% \u00b1 21.1% after 1 day of fixation and by 42.6% \u00b1 33.9% after 31 days of fixation. Myelin water fraction increased by 39.7% \u00b1 15.5% and 37.0% \u00b1 15.9% at these same time points, and mean T\n                      <jats:sub>2<\/jats:sub>\n                      of the myelin water pool nearly doubled. Reference\u2010normalized deuterium oxide\u2010exchanged zero TE signal intensity increased by 8.17% \u00b1 6.03% after 31 days of fixation but did not change significantly after 1 day of fixation. After fixation, specimen cross\u2010sectional area decreased by approximately 5%; after correction for shrinkage, changes in deuterium oxide\u2010exchanged zero TE intensity were nearly eliminated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Bound pool fraction and myelin water fraction are significantly increased by formalin fixation, whereas deuterium oxide\u2010exchanged zero TE intensity is minimally affected. Changes in quantitative magnetization transfer and myelin water imaging may be due in part to delamination and formation of vacuoles in the myelin sheath. Deuterium oxide\u2010exchanged signal intensity may be altered by fixation\u2010induced changes in myelin lipid solid\u2010state\n                      <jats:sup>1<\/jats:sup>\n                      H T\n                      <jats:sub>1<\/jats:sub>\n                      . We urge caution in the comparison of these measurements across subjects or specimens in different states, especially unfixed versus fixed tissue.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mrm.27821","type":"journal-article","created":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T10:03:32Z","timestamp":1558692212000},"page":"1504-1517","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Formalin tissue fixation biases myelin\u2010sensitive MRI"],"prefix":"10.1002","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7877-4813","authenticated-orcid":false,"given":"Alan C.","family":"Seifert","sequence":"first","affiliation":[{"name":"Translational and Molecular Imaging Institute Icahn School of Medicine at Mount Sinai New York NY"},{"name":"Department of Radiology Icahn School of Medicine at Mount Sinai New York NY"},{"name":"Graduate School of Biomedical Sciences 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