Metabolomics of therapy response in preclinical glioblastoma: A multi-slice MRSI-based volumetric analysis for noninvasive assessment of temozolomide treatment

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Abstract

© 2017 by the authors. Licensee MDPI, Basel, Switzerland. Glioblastoma (GBM) is themost common aggressive primary brain tumor in adults, with a short survival time even after aggressive therapy. Non-invasive surrogate biomarkers of therapy response may be relevant for improving patient survival. Previous work produced such biomarkers in preclinical GBM using semi-supervised source extraction and single-slice Magnetic Resonance Spectroscopic Imaging (MRSI). Nevertheless, GBMs are heterogeneous and single-slice studies could prevent obtaining relevant information. The purpose of this work was to evaluate whether a multi-sliceMRSI approach, acquiring consecutive grids across the tumor, is feasible for preclinical models and may produce additional insight into therapy response. Nosological images were analyzed pixel-by-pixel and a relative responding volume, the Tumor Responding Index (TRI), was defined to quantify response. Heterogeneous response levels were observed and treated animals were ascribed to three arbitrary predefined groups: high response (HR, n = 2), TRI = 68.2 ± 2.8%, intermediate response (IR, n = 6), TRI = 41.1 ± 4.2% and low response (LR, n = 2), TRI = 13.4 ± 14.3%, producing therapy response categorization which had not been fully registered in single-slice studies. Results agreed with the multi-slice approach being feasible and producing an inverse correlation between TRI and Ki67 immunostaining. Additionally, ca. 7-day oscillations of TRI were observed, suggesting that host immune systemactivation in response to treatment could contribute to the responding patterns detected.
Original languageEnglish
Article number20
JournalMetabolites
Volume7
DOIs
Publication statusPublished - 1 Jun 2017

Keywords

  • GL261
  • Glioma
  • Immune response
  • Nosological images
  • Orthotopic tumors
  • TMZ
  • Therapy response

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