title: Cerebral Perfusion and Gray Matter Changes Associated With Chemotherapy-Induced Peripheral Neuropathy.
abstract: OBJECTIVE
  To investigate the longitudinal relationship between chemotherapy-induced peripheral neuropathy (CIPN) symptoms (sx) and brain perfusion changes in patients with breast cancer. Interaction of CIPN-sx perfusion effects with known chemotherapy-associated gray matter density decrease was also assessed to elucidate the relationship between CIPN and previously reported cancer treatment-related brain structural changes.
  
  
  METHODS
  Patients with breast cancer treated with (n = 24) or without (n = 23) chemotherapy underwent clinical examination and brain magnetic resonance imaging at the following three time points: before treatment (baseline), 1 month after treatment completion, and 1 year after the 1-month assessment. CIPN-sx were evaluated with the self-reported Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity four-item sensory-specific scale. Perfusion and gray matter density were assessed using voxel-based pulsed arterial spin labeling and morphometric analyses and tested for association with CIPN-sx in the patients who received chemotherapy.
  
  
  RESULTS
  Patients who received chemotherapy reported significantly increased CIPN-sx from baseline to 1 month, with partial recovery by 1 year (P < .001). CIPN-sx increase from baseline to 1 month was significantly greater for patients who received chemotherapy compared with those who did not (P = .001). At 1 month, neuroimaging showed that for the group that received chemotherapy, CIPN-sx were positively associated with cerebral perfusion in the right superior frontal gyrus and cingulate gyrus, regions associated with pain processing (P < .001). Longitudinal magnetic resonance imaging analysis in the group receiving chemotherapy indicated that CIPN-sx and associated perfusion changes from baseline to 1 month were also positively correlated with gray matter density change (P < .005).
  
  
  CONCLUSIONS
  Peripheral neuropathy symptoms after systemic chemotherapy for breast cancer are associated with changes in cerebral perfusion and gray matter. The specific mechanisms warrant further investigation given the potential diagnostic and therapeutic implications.
authors.affiliation: Kelly N.H. Nudelman, Brenna C. McDonald, Yang Wang, Dori J. Smith, John D. West, Darren P. O'Neill, Victoria L. Champion, Bryan P. Schneider, and Andrew J. Saykin, Indiana University School of Medicine; Noah R. Zanville and Victoria L. Champion, Indiana University School of Nursing, Indianapolis, IN; and Yang Wang, Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Kelly N H
authors.initials: KN
authors.lastname: Nudelman
authors.affiliation: Kelly N.H. Nudelman, Brenna C. McDonald, Yang Wang, Dori J. Smith, John D. West, Darren P. O'Neill, Victoria L. Champion, Bryan P. Schneider, and Andrew J. Saykin, Indiana University School of Medicine; Noah R. Zanville and Victoria L. Champion, Indiana University School of Nursing, Indianapolis, IN; and Yang Wang, Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Brenna C
authors.initials: BC
authors.lastname: McDonald
authors.affiliation: Kelly N.H. Nudelman, Brenna C. McDonald, Yang Wang, Dori J. Smith, John D. West, Darren P. O'Neill, Victoria L. Champion, Bryan P. Schneider, and Andrew J. Saykin, Indiana University School of Medicine; Noah R. Zanville and Victoria L. Champion, Indiana University School of Nursing, Indianapolis, IN; and Yang Wang, Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Kelly N.H. Nudelman, Brenna C. McDonald, Yang Wang, Dori J. Smith, John D. West, Darren P. O'Neill, Victoria L. Champion, Bryan P. Schneider, and Andrew J. Saykin, Indiana University School of Medicine; Noah R. Zanville and Victoria L. Champion, Indiana University School of Nursing, Indianapolis, IN; and Yang Wang, Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Dori J
authors.initials: DJ
authors.lastname: Smith
authors.affiliation: Kelly N.H. Nudelman, Brenna C. McDonald, Yang Wang, Dori J. Smith, John D. West, Darren P. O'Neill, Victoria L. Champion, Bryan P. Schneider, and Andrew J. Saykin, Indiana University School of Medicine; Noah R. Zanville and Victoria L. Champion, Indiana University School of Nursing, Indianapolis, IN; and Yang Wang, Medical College of Wisconsin, Milwaukee, WI.
authors.forename: John D
authors.initials: JD
authors.lastname: West
authors.affiliation: Kelly N.H. Nudelman, Brenna C. McDonald, Yang Wang, Dori J. Smith, John D. West, Darren P. O'Neill, Victoria L. Champion, Bryan P. Schneider, and Andrew J. Saykin, Indiana University School of Medicine; Noah R. Zanville and Victoria L. Champion, Indiana University School of Nursing, Indianapolis, IN; and Yang Wang, Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Darren P
authors.initials: DP
authors.lastname: O'Neill
authors.affiliation: Kelly N.H. Nudelman, Brenna C. McDonald, Yang Wang, Dori J. Smith, John D. West, Darren P. O'Neill, Victoria L. Champion, Bryan P. Schneider, and Andrew J. Saykin, Indiana University School of Medicine; Noah R. Zanville and Victoria L. Champion, Indiana University School of Nursing, Indianapolis, IN; and Yang Wang, Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Noah R
authors.initials: NR
authors.lastname: Zanville
authors.affiliation: Kelly N.H. Nudelman, Brenna C. McDonald, Yang Wang, Dori J. Smith, John D. West, Darren P. O'Neill, Victoria L. Champion, Bryan P. Schneider, and Andrew J. Saykin, Indiana University School of Medicine; Noah R. Zanville and Victoria L. Champion, Indiana University School of Nursing, Indianapolis, IN; and Yang Wang, Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Champion
authors.affiliation: Kelly N.H. Nudelman, Brenna C. McDonald, Yang Wang, Dori J. Smith, John D. West, Darren P. O'Neill, Victoria L. Champion, Bryan P. Schneider, and Andrew J. Saykin, Indiana University School of Medicine; Noah R. Zanville and Victoria L. Champion, Indiana University School of Nursing, Indianapolis, IN; and Yang Wang, Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Bryan P
authors.initials: BP
authors.lastname: Schneider
authors.affiliation: Kelly N.H. Nudelman, Brenna C. McDonald, Yang Wang, Dori J. Smith, John D. West, Darren P. O'Neill, Victoria L. Champion, Bryan P. Schneider, and Andrew J. Saykin, Indiana University School of Medicine; Noah R. Zanville and Victoria L. Champion, Indiana University School of Nursing, Indianapolis, IN; and Yang Wang, Medical College of Wisconsin, Milwaukee, WI. asaykin@iupui.edu.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Saykin
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005260:Female; D066128:Gray Matter / Q000187:drug effects*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D059906:Neuroimaging; D020258:Neurotoxicity Syndromes / Q000175:diagnosis*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced*; D013113:Spin Labels
chemical_list: D013113:Spin Labels