title: Longitudinal restriction spectrum imaging is resistant to pseudoresponse in patients with high-grade gliomas treated with bevacizumab.
abstract: OBJECTIVE
  Antiangiogenic therapies, such as bevacizumab, decrease contrast enhancement and FLAIR hyperintensity in patients with high-grade gliomas in a manner that may not correlate with actual tumor response. This study evaluated the ability of an advanced DWI technique, restriction spectrum imaging, to improve conspicuity within regions of restricted diffusion compared with ADC in patients treated with bevacizumab and to demonstrate that unlike ADC, restriction spectrum imaging is less affected by bevacizumab-induced reductions in FLAIR hyperintensity.
  
  
  METHODS
  Restriction spectrum imaging cellularity maps and DWI were available for 12 patients with recurrent high-grade gliomas at baseline and following initiation of bevacizumab. VOIs were drawn for regions of restricted diffusion, surrounding FLAIR hyperintensity, and normal-appearing white matter; and intensity values within regions of restricted diffusion and FLAIR hyperintensity were normalized to normal-appearing white matter. Normalized values were compared between restriction spectrum imaging cellularity maps and ADC at baseline and on treatment by using repeated-measures ANOVA.
  
  
  RESULTS
  All patients exhibited decreases in contrast enhancement and FLAIR hyperintensity following treatment. Normalized intensity values were higher on restriction spectrum imaging cellularity maps compared with ADC in regions of restricted diffusion, whereas intensity values were higher on ADC compared with restriction spectrum imaging cellularity maps in regions of FLAIR hyperintensity. Bevacizumab-induced decreases in FLAIR hyperintensity had a greater effect on ADC than on the restriction spectrum imaging cellularity maps, with the relative sensitivity of ADC to changes in FLAIR hyperintensity being >20 times higher than that on restriction spectrum imaging cellularity maps.
  
  
  CONCLUSIONS
  Restriction spectrum imaging is less influenced by reductions in FLAIR hyperintensity compared with ADC, which may confer an advantage of restriction spectrum imaging over ADC for interpreting tumor response on imaging following antiangiogenic therapy.
authors.affiliation: School of Medicine, University of California, San Diego, La Jolla, CA.
authors.forename: Pranay
authors.initials: P
authors.lastname: Kothari
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, CA.|Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, CA.
authors.forename: Nathan S
authors.initials: NS
authors.lastname: White
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, CA.|Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, CA.
authors.forename: Nikdokht
authors.initials: N
authors.lastname: Farid
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, CA.
authors.forename: Romy
authors.initials: R
authors.lastname: Chung
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, CA.|Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, CA.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Kuperman
authors.affiliation: Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, CA.
authors.forename: Holly M
authors.initials: HM
authors.lastname: Girard
authors.affiliation: GE Healthcare.
authors.forename: Ajit
authors.initials: A
authors.lastname: Shankaranarayanan
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, CA.|Translational Neuro-Oncology Laboratories, Moores Cancer Center, UC San Diego, La Jolla, CA, 92093.
authors.forename: Santosh
authors.initials: S
authors.lastname: Kesari
authors.affiliation: Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, CA.|Department of Psychiatry, University of California, San Diego, La Jolla, CA.
authors.forename: Carrie R
authors.initials: CR
authors.lastname: McDonald
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, CA.|Department of Neurosciences, University of California, San Diego, La Jolla, CA.|Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, CA.|Department of Psychiatry, University of California, San Diego, La Jolla, CA.
authors.forename: Anders M
authors.initials: AM
authors.lastname: Dale
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab