TY - JOUR
T1 - Metabolomics of therapy response in preclinical glioblastoma
T2 - A multi-slice MRSI-based volumetric analysis for noninvasive assessment of temozolomide treatment
AU - Arias-Ramos, Nuria
AU - Ferrer-Font, Laura
AU - Lope-Piedrafita, Silvia
AU - Mocioiu, Victor
AU - Julià-Sapé, Margarida
AU - Pumarola, Martí
AU - Arús, Carles
AU - Candiota, Ana Paula
N1 - Publisher Copyright:
© 2017 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2017/6
Y1 - 2017/6
N2 - 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.
AB - 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.
KW - GL261
KW - Glioma
KW - Immune response
KW - Nosological images
KW - Orthotopic tumors
KW - Therapy response
KW - TMZ
UR - http://www.scopus.com/inward/record.url?scp=85020900593&partnerID=8YFLogxK
U2 - 10.3390/metabo7020020
DO - 10.3390/metabo7020020
M3 - Artículo
AN - SCOPUS:85020900593
VL - 7
JO - Metabolites
JF - Metabolites
SN - 2218-1989
IS - 2
M1 - 20
ER -