Restriction spectrum imaging predicts response to bevacizumab in patients with high-grade glioma.
Diffusion-weighted imaging has shown initial promise for evaluating response to bevacizumab in patients with high-grade glioma (HGG). However, it is well recognized that the apparent diffusion coefficient (ADC) is influenced by bevacizumab-induced reductions in edema, which may limit its prognostic value. We demonstrate that an advanced diffusion-weighted imaging technique, restriction spectrum imaging (RSI), improves the evaluation of response to bevacizumab because unlike ADC, RSI is not affected by resolution of edema.



RSI and ADC maps were analyzed for 40 patients with HGG prior to and following initiation of bevacizumab. Volumes of interest were drawn for regions of contrast enhancement (CE) and fluid attenuated inversion recovery (FLAIR) hyperintensity and histogram percentiles within volumes of interest were calculated for ADC 10th percentile (ADC-CE10%, ADC-FLAIR10%) and for RSI 90th percentile (RSI-CE90%, RSI-FLAIR90%). Cox proportional hazard models were used to evaluate the relationship between imaging parameters, progression-free survival (PFS), and overall survival (OS).



An increase in RSI-FLAIR90%following bevacizumab was the strongest predictor of poor PFS (P= .016) and OS (P= .004), whereas decreases in ADC-FLAIR10%showed a weaker association with OS only (P= .041). Within the CE region, increases in RSI-CE90%alone were associated with poorer OS. Correlational analysis revealed that decreases in FLAIR volume were associated with decreases in ADC-FLAIR10%, but not with changes in RSI-FLAIR90%.



RSI is less influenced by changes in edema, conferring an advantage of RSI over ADC for evaluating response to anti-angiogenic therapy in patients with HGG.
Department of Psychiatry, University of California, San Diego, La Jolla, California (C.R.M., A.M.D.), Department of Radiology, University of California, San Diego, La Jolla, California (R.L.D., J.M.K., H.B., N.S.W., A.M.D., N.F.), Department of Radiation Medicine, University of California, San Diego, La Jolla, California (C.R.M., J.A.H.-G., T.M.S., R.K.), Department of Neurosciences, University of California, San Diego, La Jolla, California (D.E.P., A.M.D.), Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, California (C.R.M., A.P.K., K.M.L., T.M.S., P.E., J.M.K., H.B., N.S.W., A.M.D., N.F.).
Carrie R
CR
McDonald
Department of Psychiatry, University of California, San Diego, La Jolla, California (C.R.M., A.M.D.), Department of Radiology, University of California, San Diego, La Jolla, California (R.L.D., J.M.K., H.B., N.S.W., A.M.D., N.F.), Department of Radiation Medicine, University of California, San Diego, La Jolla, California (C.R.M., J.A.H.-G., T.M.S., R.K.), Department of Neurosciences, University of California, San Diego, La Jolla, California (D.E.P., A.M.D.), Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, California (C.R.M., A.P.K., K.M.L., T.M.S., P.E., J.M.K., H.B., N.S.W., A.M.D., N.F.).
Rachel L
RL
Delfanti
Department of Psychiatry, University of California, San Diego, La Jolla, California (C.R.M., A.M.D.), Department of Radiology, University of California, San Diego, La Jolla, California (R.L.D., J.M.K., H.B., N.S.W., A.M.D., N.F.), Department of Radiation Medicine, University of California, San Diego, La Jolla, California (C.R.M., J.A.H.-G., T.M.S., R.K.), Department of Neurosciences, University of California, San Diego, La Jolla, California (D.E.P., A.M.D.), Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, California (C.R.M., A.P.K., K.M.L., T.M.S., P.E., J.M.K., H.B., N.S.W., A.M.D., N.F.).
Anitha P
AP
Krishnan
Department of Psychiatry, University of California, San Diego, La Jolla, California (C.R.M., A.M.D.), Department of Radiology, University of California, San Diego, La Jolla, California (R.L.D., J.M.K., H.B., N.S.W., A.M.D., N.F.), Department of Radiation Medicine, University of California, San Diego, La Jolla, California (C.R.M., J.A.H.-G., T.M.S., R.K.), Department of Neurosciences, University of California, San Diego, La Jolla, California (D.E.P., A.M.D.), Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, California (C.R.M., A.P.K., K.M.L., T.M.S., P.E., J.M.K., H.B., N.S.W., A.M.D., N.F.).
Kelly M
KM
Leyden
Department of Psychiatry, University of California, San Diego, La Jolla, California (C.R.M., A.M.D.), Department of Radiology, University of California, San Diego, La Jolla, California (R.L.D., J.M.K., H.B., N.S.W., A.M.D., N.F.), Department of Radiation Medicine, University of California, San Diego, La Jolla, California (C.R.M., J.A.H.-G., T.M.S., R.K.), Department of Neurosciences, University of California, San Diego, La Jolla, California (D.E.P., A.M.D.), Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, California (C.R.M., A.P.K., K.M.L., T.M.S., P.E., J.M.K., H.B., N.S.W., A.M.D., N.F.).
Jona A
JA
Hattangadi-Gluth
Department of Psychiatry, University of California, San Diego, La Jolla, California (C.R.M., A.M.D.), Department of Radiology, University of California, San Diego, La Jolla, California (R.L.D., J.M.K., H.B., N.S.W., A.M.D., N.F.), Department of Radiation Medicine, University of California, San Diego, La Jolla, California (C.R.M., J.A.H.-G., T.M.S., R.K.), Department of Neurosciences, University of California, San Diego, La Jolla, California (D.E.P., A.M.D.), Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, California (C.R.M., A.P.K., K.M.L., T.M.S., P.E., J.M.K., H.B., N.S.W., A.M.D., N.F.).
Tyler M
TM
Seibert
Department of Psychiatry, University of California, San Diego, La Jolla, California (C.R.M., A.M.D.), Department of Radiology, University of California, San Diego, La Jolla, California (R.L.D., J.M.K., H.B., N.S.W., A.M.D., N.F.), Department of Radiation Medicine, University of California, San Diego, La Jolla, California (C.R.M., J.A.H.-G., T.M.S., R.K.), Department of Neurosciences, University of California, San Diego, La Jolla, California (D.E.P., A.M.D.), Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, California (C.R.M., A.P.K., K.M.L., T.M.S., P.E., J.M.K., H.B., N.S.W., A.M.D., N.F.).
Roshan
R
Karunamuni
Department of Psychiatry, University of California, San Diego, La Jolla, California (C.R.M., A.M.D.), Department of Radiology, University of California, San Diego, La Jolla, California (R.L.D., J.M.K., H.B., N.S.W., A.M.D., N.F.), Department of Radiation Medicine, University of California, San Diego, La Jolla, California (C.R.M., J.A.H.-G., T.M.S., R.K.), Department of Neurosciences, University of California, San Diego, La Jolla, California (D.E.P., A.M.D.), Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, California (C.R.M., A.P.K., K.M.L., T.M.S., P.E., J.M.K., H.B., N.S.W., A.M.D., N.F.).
Pia
P
Elbe
Department of Psychiatry, University of California, San Diego, La Jolla, California (C.R.M., A.M.D.), Department of Radiology, University of California, San Diego, La Jolla, California (R.L.D., J.M.K., H.B., N.S.W., A.M.D., N.F.), Department of Radiation Medicine, University of California, San Diego, La Jolla, California (C.R.M., J.A.H.-G., T.M.S., R.K.), Department of Neurosciences, University of California, San Diego, La Jolla, California (D.E.P., A.M.D.), Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, California (C.R.M., A.P.K., K.M.L., T.M.S., P.E., J.M.K., H.B., N.S.W., A.M.D., N.F.).
Joshua M
JM
Kuperman
Department of Psychiatry, University of California, San Diego, La Jolla, California (C.R.M., A.M.D.), Department of Radiology, University of California, San Diego, La Jolla, California (R.L.D., J.M.K., H.B., N.S.W., A.M.D., N.F.), Department of Radiation Medicine, University of California, San Diego, La Jolla, California (C.R.M., J.A.H.-G., T.M.S., R.K.), Department of Neurosciences, University of California, San Diego, La Jolla, California (D.E.P., A.M.D.), Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, California (C.R.M., A.P.K., K.M.L., T.M.S., P.E., J.M.K., H.B., N.S.W., A.M.D., N.F.).
Hauke
H
Bartsch
Department of Psychiatry, University of California, San Diego, La Jolla, California (C.R.M., A.M.D.), Department of Radiology, University of California, San Diego, La Jolla, California (R.L.D., J.M.K., H.B., N.S.W., A.M.D., N.F.), Department of Radiation Medicine, University of California, San Diego, La Jolla, California (C.R.M., J.A.H.-G., T.M.S., R.K.), Department of Neurosciences, University of California, San Diego, La Jolla, California (D.E.P., A.M.D.), Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, California (C.R.M., A.P.K., K.M.L., T.M.S., P.E., J.M.K., H.B., N.S.W., A.M.D., N.F.).
David E
DE
Piccioni
Department of Psychiatry, University of California, San Diego, La Jolla, California (C.R.M., A.M.D.), Department of Radiology, University of California, San Diego, La Jolla, California (R.L.D., J.M.K., H.B., N.S.W., A.M.D., N.F.), Department of Radiation Medicine, University of California, San Diego, La Jolla, California (C.R.M., J.A.H.-G., T.M.S., R.K.), Department of Neurosciences, University of California, San Diego, La Jolla, California (D.E.P., A.M.D.), Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, California (C.R.M., A.P.K., K.M.L., T.M.S., P.E., J.M.K., H.B., N.S.W., A.M.D., N.F.).
Nathan S
NS
White
Department of Psychiatry, University of California, San Diego, La Jolla, California (C.R.M., A.M.D.), Department of Radiology, University of California, San Diego, La Jolla, California (R.L.D., J.M.K., H.B., N.S.W., A.M.D., N.F.), Department of Radiation Medicine, University of California, San Diego, La Jolla, California (C.R.M., J.A.H.-G., T.M.S., R.K.), Department of Neurosciences, University of California, San Diego, La Jolla, California (D.E.P., A.M.D.), Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, California (C.R.M., A.P.K., K.M.L., T.M.S., P.E., J.M.K., H.B., N.S.W., A.M.D., N.F.).
Anders M
AM
Dale
Department of Psychiatry, University of California, San Diego, La Jolla, California (C.R.M., A.M.D.), Department of Radiology, University of California, San Diego, La Jolla, California (R.L.D., J.M.K., H.B., N.S.W., A.M.D., N.F.), Department of Radiation Medicine, University of California, San Diego, La Jolla, California (C.R.M., J.A.H.-G., T.M.S., R.K.), Department of Neurosciences, University of California, San Diego, La Jolla, California (D.E.P., A.M.D.), Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, California (C.R.M., A.P.K., K.M.L., T.M.S., P.E., J.M.K., H.B., N.S.W., A.M.D., N.F.).
Nikdokht
N
Farid
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D001929:Brain Edema / Q000150:complications / Q000000981:diagnostic imaging*; D001932:Brain Neoplasms / Q000150:complications / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D003936:Diagnosis, Computer-Assisted; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005910:Glioma / Q000150:complications / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D016019:Survival Analysis
D020533:Angiogenesis Inhibitors; D000068258:Bevacizumab; C512478:EGFR protein, human; D066246:ErbB Receptors
apparent diffusion coefficient; bevacizumab; diffusion-weighted imaging; high-grade glioma; restriction spectrum imaging