title: Restriction Spectrum Imaging Improves Risk Stratification in Patients with Glioblastoma.
abstract: OBJECTIVE
  ADC as a marker of tumor cellularity has been promising for evaluating the response to therapy in patients with glioblastoma but does not successfully stratify patients according to outcomes, especially in the upfront setting. Here we investigate whether restriction spectrum imaging, an advanced diffusion imaging model, performed after an operation but before radiation therapy, could improve risk stratification in patients with newly diagnosed glioblastoma relative to ADC.
  
  
  METHODS
  Pre-radiation therapy diffusion-weighted and structural imaging of 40 patients with glioblastoma were examined retrospectively. Restriction spectrum imaging and ADC-based hypercellularity volume fraction (restriction spectrum imaging-FLAIR volume fraction, restriction spectrum imaging-contrast-enhanced volume fraction, ADC-FLAIR volume fraction, ADC-contrast-enhanced volume fraction) and intensities (restriction spectrum imaging-FLAIR 90th percentile, restriction spectrum imaging-contrast-enhanced 90th percentile, ADC-FLAIR 10th percentile, ADC-contrast-enhanced 10th percentile) within the contrast-enhanced and FLAIR hyperintensity VOIs were calculated. The association of diffusion imaging metrics, contrast-enhanced volume, and FLAIR hyperintensity volume with progression-free survival and overall survival was evaluated by using Cox proportional hazards models.
  
  
  RESULTS
  Among the diffusion metrics, restriction spectrum imaging-FLAIR volume fraction was the strongest prognostic metric of progression-free survival (P= .036) and overall survival (P= .007) in a multivariate Cox proportional hazards analysis, with higher values indicating earlier progression and shorter survival. Restriction spectrum imaging-FLAIR 90th percentile was also associated with overall survival (P= .043), with higher intensities, indicating shorter survival. None of the ADC metrics were associated with progression-free survival/overall survival. Contrast-enhanced volume exhibited a trend toward significance for overall survival (P= .063).
  
  
  CONCLUSIONS
  Restriction spectrum imaging-derived cellularity in FLAIR hyperintensity regions may be a more robust prognostic marker than ADC and conventional imaging for early progression and poorer survival in patients with glioblastoma. However, future studies with larger samples are needed to explore its predictive ability.
authors.affiliation: From the Multimodal Imaging Laboratory (A.P.K., K.M.L., T.M.S., J.M.K., H.B., P.E., A.S., A.M.D., N.F., C.R.M., N.S.W.).
authors.forename: A P
authors.identifier: http://orcid.org/0000-0003-0193-2494
authors.initials: AP
authors.lastname: Krishnan
authors.affiliation: Departments of Radiation Medicine (R.K., T.M.S., J.A.H.-G., C.R.M.).
authors.forename: R
authors.identifier: http://orcid.org/0000-0001-6918-0589
authors.initials: R
authors.lastname: Karunamuni
authors.affiliation: From the Multimodal Imaging Laboratory (A.P.K., K.M.L., T.M.S., J.M.K., H.B., P.E., A.S., A.M.D., N.F., C.R.M., N.S.W.).
authors.forename: K M
authors.identifier: http://orcid.org/0000-0002-7994-5028
authors.initials: KM
authors.lastname: Leyden
authors.affiliation: From the Multimodal Imaging Laboratory (A.P.K., K.M.L., T.M.S., J.M.K., H.B., P.E., A.S., A.M.D., N.F., C.R.M., N.S.W.).|Departments of Radiation Medicine (R.K., T.M.S., J.A.H.-G., C.R.M.).
authors.forename: T M
authors.identifier: http://orcid.org/0000-0002-4089-7399
authors.initials: TM
authors.lastname: Seibert
authors.affiliation: Radiology (R.L.D., J.M.K., H.B., A.M.D., N.F., N.S.W.).
authors.forename: R L
authors.identifier: http://orcid.org/0000-0002-2373-5419
authors.initials: RL
authors.lastname: Delfanti
authors.affiliation: Radiology (R.L.D., J.M.K., H.B., A.M.D., N.F., N.S.W.).
authors.forename: J M
authors.identifier: http://orcid.org/0000-0002-7890-4785
authors.initials: JM
authors.lastname: Kuperman
authors.affiliation: From the Multimodal Imaging Laboratory (A.P.K., K.M.L., T.M.S., J.M.K., H.B., P.E., A.S., A.M.D., N.F., C.R.M., N.S.W.).|Radiology (R.L.D., J.M.K., H.B., A.M.D., N.F., N.S.W.).
authors.forename: H
authors.identifier: http://orcid.org/0000-0003-1486-4128
authors.initials: H
authors.lastname: Bartsch
authors.affiliation: From the Multimodal Imaging Laboratory (A.P.K., K.M.L., T.M.S., J.M.K., H.B., P.E., A.S., A.M.D., N.F., C.R.M., N.S.W.).
authors.forename: P
authors.identifier: http://orcid.org/0000-0003-1717-240X
authors.initials: P
authors.lastname: Elbe
authors.affiliation: From the Multimodal Imaging Laboratory (A.P.K., K.M.L., T.M.S., J.M.K., H.B., P.E., A.S., A.M.D., N.F., C.R.M., N.S.W.).
authors.forename: A
authors.identifier: http://orcid.org/0000-0002-6126-2966
authors.initials: A
authors.lastname: Srikant
authors.affiliation: From the Multimodal Imaging Laboratory (A.P.K., K.M.L., T.M.S., J.M.K., H.B., P.E., A.S., A.M.D., N.F., C.R.M., N.S.W.).|Radiology (R.L.D., J.M.K., H.B., A.M.D., N.F., N.S.W.).|Neurosciences (A.M.D., D.E.P.).
authors.forename: A M
authors.initials: AM
authors.lastname: Dale
authors.affiliation: Department of Translational Neuro-Oncology and Neurotherapeutics (S.K.), John Wayne Cancer Institute and Pacific Neuroscience Institute at Providence Saint John's Health Center, Santa Monica, California.
authors.forename: S
authors.identifier: http://orcid.org/0000-0003-3772-6000
authors.initials: S
authors.lastname: Kesari
authors.affiliation: Neurosciences (A.M.D., D.E.P.).
authors.forename: D E
authors.identifier: http://orcid.org/0000-0001-6006-0126
authors.initials: DE
authors.lastname: Piccioni
authors.affiliation: Departments of Radiation Medicine (R.K., T.M.S., J.A.H.-G., C.R.M.).
authors.forename: J A
authors.identifier: http://orcid.org/0000-0001-8222-606X
authors.initials: JA
authors.lastname: Hattangadi-Gluth
authors.affiliation: From the Multimodal Imaging Laboratory (A.P.K., K.M.L., T.M.S., J.M.K., H.B., P.E., A.S., A.M.D., N.F., C.R.M., N.S.W.).|Radiology (R.L.D., J.M.K., H.B., A.M.D., N.F., N.S.W.).
authors.forename: N
authors.identifier: http://orcid.org/0000-0002-0876-1934
authors.initials: N
authors.lastname: Farid
authors.affiliation: From the Multimodal Imaging Laboratory (A.P.K., K.M.L., T.M.S., J.M.K., H.B., P.E., A.S., A.M.D., N.F., C.R.M., N.S.W.).|Departments of Radiation Medicine (R.K., T.M.S., J.A.H.-G., C.R.M.).|Psychiatry (C.R.M.), University of California, San Diego, La Jolla, California.
authors.forename: C R
authors.identifier: http://orcid.org/0000-0002-0721-5640
authors.initials: CR
authors.lastname: McDonald
authors.affiliation: From the Multimodal Imaging Laboratory (A.P.K., K.M.L., T.M.S., J.M.K., H.B., P.E., A.S., A.M.D., N.F., C.R.M., N.S.W.) nswhite@ucsd.edu.|Radiology (R.L.D., J.M.K., H.B., A.M.D., N.F., N.S.W.).
authors.forename: N S
authors.identifier: http://orcid.org/0000-0003-4564-2237
authors.initials: NS
authors.lastname: White
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000145:classification / Q000000981:diagnostic imaging* / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000145:classification / Q000000981:diagnostic imaging* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies