title: Ex vivo MR spectroscopic measure differentiates tumor from treatment effects in GBM.
abstract: The motivation of this study was to address the urgent clinical problem related to the inability of magnetic resonance (MR) imaging measures to differentiate tumor progression from treatment effects in patients with glioblastoma multiforme (GBM). While contrast enhancement on MR imaging (MRI) is routinely used for assessment of tumor burden, therapy response, and progression-free survival in GBM, it is well known that changes in enhancement following treatment are nonspecific to tumor. To address this issue, the objective of this study was to investigate whether MR spectroscopy can provide improved biomarker surrogates for tumor following treatment. High-resolution metabolic profiles of tissue samples obtained from patients with GBM were directly correlated with their pathological assessment to determine metabolic markers that correspond to pathological indications of tumor or treatment effects. Acquisition of tissue samples with image guidance enabled the association of ex vivo biochemical and pathological properties of the tissue samples with in vivo MR anatomical and structural properties derived from presurgical MR images. Using this approach, we found that metabolic concentration levels of [Myo-inositol/total choline (MCI)] in tissue samples are able to differentiate tumor from nontumor and treatment-induced reactive astrocytosis with high significance (P < .001) in newly diagnosed and recurrent GBM. The MCI index has a sensitivity of 93% to tumor in recurrent GBM and delineates the contribution of cellularity that originates from tumor and astrocytic proliferation following treatment. Low levels of MCI for tumor were associated with a reduced apparent diffusion coefficient and elevated choline-N-acetyl-aspartate index derived from in vivo MR images.
authors.affiliation: Department of Radiology and Biomedical Imaging, 1700 4th Street, Byers Hall, Suite 301, San Francisco, CA 94143-2532, USA. radhika.srinivasan@radiology.ucsf.edu
authors.forename: Radhika
authors.initials: R
authors.lastname: Srinivasan
authors.forename: Joanna J
authors.initials: JJ
authors.lastname: Phillips
authors.forename: Scott R
authors.initials: SR
authors.lastname: Vandenberg
authors.forename: Mei-Yin C
authors.initials: MY
authors.lastname: Polley
authors.forename: Gabriela
authors.initials: G
authors.lastname: Bourne
authors.forename: Alvin
authors.initials: A
authors.lastname: Au
authors.forename: Andrea
authors.initials: A
authors.lastname: Pirzkall
authors.forename: Soonmee
authors.initials: S
authors.lastname: Cha
authors.forename: Susan M
authors.initials: SM
authors.lastname: Chang
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Nelson
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D005909:Glioblastoma / Q000175:diagnosis* / Q000378:metabolism*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007294:Inositol / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D038361:Neuronavigation / Q000295:instrumentation / Q000379:methods; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D007294:Inositol; D002794:Choline