title: Volumetric relationship between 2-hydroxyglutarate and FLAIR hyperintensity has potential implications for radiotherapy planning of mutant IDH glioma patients.
abstract: Gliomas with mutant isocitrate dehydrogenase (IDH) produce high levels of 2-hydroxyglutarate (2HG) that can be quantitatively measured by 3D magnetic resonance spectroscopic imaging (MRSI). Current glioma MRI primarily relies upon fluid-attenuated inversion recovery (FLAIR) hyperintensity for treatment planning, although this lacks specificity for tumor cells. Here, we investigated the relationship between 2HG and FLAIR in mutant IDH glioma patients to determine whether 2HG mapping is valuable for radiotherapy planning.
  
  
  
  Seventeen patients with mutant IDH1 gliomas were imaged by 3 T MRI. A 3D MRSI sequence was employed to specifically image 2HG. FLAIR imaging was performed using standard clinical protocol. Regions of interest (ROIs) were determined for FLAIR and optimally thresholded 2HG hyperintensities. The overlap, displacement, and volumes of 2HG and FLAIR ROIs were calculated.
  
  
  
  In 8 of 17 (47%) patients, the 2HG volume was larger than FLAIR volume. Across the entire cohort, the mean volume of 2HG was 35.3 cc (range, 5.3-92.7 cc), while the mean volume of FLAIR was 35.8 cc (range, 6.3-140.8 cc). FLAIR and 2HG ROIs had mean overlap of 0.28 (Dice coefficients range, 0.03-0.57) and mean displacement of 12.2 mm (range, 3.2-23.5 mm) between their centers of mass.
  
  
  
  Our results indicate that for a substantial number of patients, the 2HG volumetric assessment of tumor burden is more extensive than FLAIR volume. In addition, there is only partial overlap and asymmetric displacement between the centers of FLAIR and 2HG ROIs. These results may have important implications for radiotherapy planning of IDH mutant glioma.
authors.affiliation: Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (K.J.-K., W.B., B.R.R., O.C.A.); Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (F.L., D.P.C.); Department of Neurosurgery, Charité Medical University, Berlin, Germany (F.L.); High Field MR Center, Department of Biomedical Imaging and Image-Guided Therapy, Medical University Vienna, Vienna, Austria (W.B.); Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (O.R., G.R.G.); Pappas Center of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (E.G., A.S.C., T.T.B.); Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (J.U., H.A.S.).
authors.forename: Kourosh
authors.initials: K
authors.lastname: Jafari-Khouzani
authors.affiliation: Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (K.J.-K., W.B., B.R.R., O.C.A.); Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (F.L., D.P.C.); Department of Neurosurgery, Charité Medical University, Berlin, Germany (F.L.); High Field MR Center, Department of Biomedical Imaging and Image-Guided Therapy, Medical University Vienna, Vienna, Austria (W.B.); Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (O.R., G.R.G.); Pappas Center of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (E.G., A.S.C., T.T.B.); Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (J.U., H.A.S.).
authors.forename: Franziska
authors.initials: F
authors.lastname: Loebel
authors.affiliation: Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (K.J.-K., W.B., B.R.R., O.C.A.); Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (F.L., D.P.C.); Department of Neurosurgery, Charité Medical University, Berlin, Germany (F.L.); High Field MR Center, Department of Biomedical Imaging and Image-Guided Therapy, Medical University Vienna, Vienna, Austria (W.B.); Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (O.R., G.R.G.); Pappas Center of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (E.G., A.S.C., T.T.B.); Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (J.U., H.A.S.).
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bogner
authors.affiliation: Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (K.J.-K., W.B., B.R.R., O.C.A.); Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (F.L., D.P.C.); Department of Neurosurgery, Charité Medical University, Berlin, Germany (F.L.); High Field MR Center, Department of Biomedical Imaging and Image-Guided Therapy, Medical University Vienna, Vienna, Austria (W.B.); Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (O.R., G.R.G.); Pappas Center of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (E.G., A.S.C., T.T.B.); Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (J.U., H.A.S.).
authors.forename: Otto
authors.initials: O
authors.lastname: Rapalino
authors.affiliation: Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (K.J.-K., W.B., B.R.R., O.C.A.); Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (F.L., D.P.C.); Department of Neurosurgery, Charité Medical University, Berlin, Germany (F.L.); High Field MR Center, Department of Biomedical Imaging and Image-Guided Therapy, Medical University Vienna, Vienna, Austria (W.B.); Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (O.R., G.R.G.); Pappas Center of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (E.G., A.S.C., T.T.B.); Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (J.U., H.A.S.).
authors.forename: Gilberto R
authors.initials: GR
authors.lastname: Gonzalez
authors.affiliation: Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (K.J.-K., W.B., B.R.R., O.C.A.); Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (F.L., D.P.C.); Department of Neurosurgery, Charité Medical University, Berlin, Germany (F.L.); High Field MR Center, Department of Biomedical Imaging and Image-Guided Therapy, Medical University Vienna, Vienna, Austria (W.B.); Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (O.R., G.R.G.); Pappas Center of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (E.G., A.S.C., T.T.B.); Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (J.U., H.A.S.).
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Gerstner
authors.affiliation: Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (K.J.-K., W.B., B.R.R., O.C.A.); Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (F.L., D.P.C.); Department of Neurosurgery, Charité Medical University, Berlin, Germany (F.L.); High Field MR Center, Department of Biomedical Imaging and Image-Guided Therapy, Medical University Vienna, Vienna, Austria (W.B.); Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (O.R., G.R.G.); Pappas Center of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (E.G., A.S.C., T.T.B.); Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (J.U., H.A.S.).
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Chi
authors.affiliation: Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (K.J.-K., W.B., B.R.R., O.C.A.); Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (F.L., D.P.C.); Department of Neurosurgery, Charité Medical University, Berlin, Germany (F.L.); High Field MR Center, Department of Biomedical Imaging and Image-Guided Therapy, Medical University Vienna, Vienna, Austria (W.B.); Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (O.R., G.R.G.); Pappas Center of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (E.G., A.S.C., T.T.B.); Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (J.U., H.A.S.).
authors.forename: Tracy T
authors.initials: TT
authors.lastname: Batchelor
authors.affiliation: Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (K.J.-K., W.B., B.R.R., O.C.A.); Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (F.L., D.P.C.); Department of Neurosurgery, Charité Medical University, Berlin, Germany (F.L.); High Field MR Center, Department of Biomedical Imaging and Image-Guided Therapy, Medical University Vienna, Vienna, Austria (W.B.); Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (O.R., G.R.G.); Pappas Center of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (E.G., A.S.C., T.T.B.); Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (J.U., H.A.S.).
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Rosen
authors.affiliation: Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (K.J.-K., W.B., B.R.R., O.C.A.); Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (F.L., D.P.C.); Department of Neurosurgery, Charité Medical University, Berlin, Germany (F.L.); High Field MR Center, Department of Biomedical Imaging and Image-Guided Therapy, Medical University Vienna, Vienna, Austria (W.B.); Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (O.R., G.R.G.); Pappas Center of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (E.G., A.S.C., T.T.B.); Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (J.U., H.A.S.).
authors.forename: Jan
authors.initials: J
authors.lastname: Unkelbach
authors.affiliation: Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (K.J.-K., W.B., B.R.R., O.C.A.); Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (F.L., D.P.C.); Department of Neurosurgery, Charité Medical University, Berlin, Germany (F.L.); High Field MR Center, Department of Biomedical Imaging and Image-Guided Therapy, Medical University Vienna, Vienna, Austria (W.B.); Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (O.R., G.R.G.); Pappas Center of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (E.G., A.S.C., T.T.B.); Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (J.U., H.A.S.).
authors.forename: Helen A
authors.initials: HA
authors.lastname: Shih
authors.affiliation: Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (K.J.-K., W.B., B.R.R., O.C.A.); Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (F.L., D.P.C.); Department of Neurosurgery, Charité Medical University, Berlin, Germany (F.L.); High Field MR Center, Department of Biomedical Imaging and Image-Guided Therapy, Medical University Vienna, Vienna, Austria (W.B.); Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (O.R., G.R.G.); Pappas Center of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (E.G., A.S.C., T.T.B.); Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (J.U., H.A.S.).
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Cahill
authors.affiliation: Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (K.J.-K., W.B., B.R.R., O.C.A.); Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (F.L., D.P.C.); Department of Neurosurgery, Charité Medical University, Berlin, Germany (F.L.); High Field MR Center, Department of Biomedical Imaging and Image-Guided Therapy, Medical University Vienna, Vienna, Austria (W.B.); Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (O.R., G.R.G.); Pappas Center of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (E.G., A.S.C., T.T.B.); Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (J.U., H.A.S.).
authors.forename: Ovidiu C
authors.initials: OC
authors.lastname: Andronesi
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging* / Q000378:metabolism; D005977:Glutarates / Q000378:metabolism*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D055815:Young Adult
chemical_list: D005977:Glutarates; C019417:alpha-hydroxyglutarate; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
keywords: 2-hydroxyglutarate (2HG); glioma; isocitrate dehydrogenase (IDH) mutation; magnetic resonance spectroscopic imaging (MRSI); radiotherapy