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Metabolomics of Therapy Response in Preclinical Glioblastoma: A Multi-Slice MRSI-Based Volumetric Analysis for Noninvasive Assessment of Temozolomide Treatment
Ist Teil von
Metabolites, 2017-05, Vol.7 (2), p.20
Ort / Verlag
Switzerland: MDPI
Erscheinungsjahr
2017
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
Glioblastoma (GBM) is the most 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-slice MRSI 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
(
), was defined to quantify response. Heterogeneous response levels were observed and treated animals were ascribed to three arbitrary predefined groups: high response (HR,
= 2),
= 68.2 ± 2.8%, intermediate response (IR,
= 6),
= 41.1 ± 4.2% and low response (LR,
= 2),
= 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
and Ki67 immunostaining. Additionally, ca. 7-day oscillations of
were observed, suggesting that host immune system activation in response to treatment could contribute to the responding patterns detected.