title: Investigation of the diffusion abnormality index as a new imaging biomarker for early assessment of brain tumor response to radiation therapy.
abstract: BACKGROUND
  Diffusion MRI, although having the potential to be a biomarker for early assessment of tumor response to therapy, could be confounded by edema and necrosis in or near the brain tumors. This study aimed to develop and investigate the ability of the diffusion abnormality index (DAI) to be a new imaging biomarker for early assessment of brain metastasis response to radiation therapy (RT).
  
  
  METHODS
  Patients with either radiosensitive or radioresistant brain metastases that were treated by whole brain RT alone or combined with bortezomib as a radiation sensitizer had diffusion-weighted (DW) MRI pre-RT and 2 weeks (2W) after starting RT. A patient-specific diffusion abnormality probability function (DAProF) was created to account for abnormal low and high apparent diffusion coefficients differently, reflecting respective high cellularity and edema/necrosis. The DAI of a lesion was then calculated by the integral of DAProF-weighted tumor apparent diffusion coefficient histogram. The changes in DAI from pre-RT to 2W were evaluated for differentiating the responsive, stable, and progressive tumors and compared with the changes in gross tumor volume and conventional diffusion metrics during the same time interval.
  
  
  RESULTS
  In lesions treated with whole brain RT, the DAI performed the best among all metrics in predicting the posttreatment response of brain metastases to RT. In lesions treated with whole brain RT + bortezomib, although DAI was the best predictor, the performance of all metrics worsened compared with the first group.
  
  
  CONCLUSIONS
  The ability of DAI for early assessment of brain metastasis response to RT depends upon treatment regimes.
authors: Corresponding author: Yue Cao, PhD, Department of Radiation Oncology, University of Michigan, 519 W William St, Ann Arbor, MI 48103. yuecao@umich.edu.
authors: Reza
authors: R
authors: Farjam
authors: Christina I
authors: CI
authors: Tsien
authors: Felix Y
authors: FY
authors: Feng
authors: Diana
authors: D
authors: Gomez-Hassan
authors: James A
authors: JA
authors: Hayman
authors: Theodore S
authors: TS
authors: Lawrence
authors: Yue
authors: Y
authors: Cao
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D001932:Brain Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000532:radiotherapy*; D059248:Chemoradiotherapy; D016371:Cranial Irradiation; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000175:diagnosis / Q000188:drug therapy / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D011719:Pyrazines / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D001897:Boronic Acids; D011719:Pyrazines; D011838:Radiation-Sensitizing Agents; D000069286:Bortezomib
keywords: DW-MRI; cancer; diffusion abnormality index; imaging biomarker