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Here, we investigated very late (&gt;9 years) effects of adjuvant high\u2010dose chemotherapy on brain white and gray matter in primary breast cancer survivors (\n                    <jats:italic>n<\/jats:italic>\n                    = 17) with multimodal magnetic resonance imaging (MRI). A group of breast cancer survivors who did not receive chemotherapy was scanned for comparison (\n                    <jats:italic>n<\/jats:italic>\n                    = 15). Neuropsychological tests demonstrated cognitive impairments in the chemotherapy group. Diffusion tensor imaging (DTI) with tract\u2010based spatial statistics showed that chemotherapy was associated with focal changes in DTI values indicative for reduced white matter integrity. Single voxel proton MR spectroscopy (1H\u2010MRS) in the left centrum semiovale (white matter) showed a reduction of\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acetylasparate\/creatine indicative of axonal injury. Voxel\u2010based morphometry demonstrated a reduction of gray matter volume that overlapped with fMRI hypoactivation (as reported in a previous publication) in posterior parietal areas and colocalized with DTI abnormalities. Also, DTI correlated with 1H\u2010MRS only in the chemotherapy group. These results converge to suggest that high\u2010dose adjuvant chemotherapy for breast cancer is associated with long\u2010term injury to white matter, presumably reflecting a combination of axonal degeneration and demyelination, and damage to gray matter with associated functional deficits. Hormonal treatment with tamoxifen may also have contributed to the observed effects, although results from other studies indicate that it is unlikely that tamoxifen is solely or largely responsible. Using this multimodality approach we provide for the first time insight into the neural substrate underlying cognitive impairments following systemic administration of cytotoxic agents many years after treatment. Hum Brain Mapp, 2012. \u00a9 2011 Wiley Periodicals, Inc.\n                  <\/jats:p>","DOI":"10.1002\/hbm.21422","type":"journal-article","created":{"date-parts":[[2011,9,27]],"date-time":"2011-09-27T17:01:37Z","timestamp":1317142897000},"page":"2971-2983","source":"Crossref","is-referenced-by-count":231,"title":["Late effects of high\u2010dose adjuvant chemotherapy on white and gray matter in breast cancer survivors: Converging results from multimodal magnetic resonance imaging"],"prefix":"10.1002","volume":"33","author":[{"given":"Michiel B.","family":"de Ruiter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liesbeth","family":"Reneman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem","family":"Boogerd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dick 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