d2946ab09fb21892800c464a1a1ca593 pmc_28524099.pdf 05de3ad38ad876b58faa79a75cc474291a4b48c7 pmc_28524099.pdf 6261a44d9b531c639c9cc93553d5b8f8414e4c5a34c21bbe1ff8d64201117059 pmc_28524099.pdf Title: Metabolomics of Therapy Response in Preclinical Glioblastoma: A Multi-Slice MRSI-Based Volumetric Analysis for Noninvasive Assessment of Temozolomide Treatment Subject: 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 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 system activation in response to treatment could contribute to the responding patterns detected. Keywords: glioma; GL261; orthotopic tumors; therapy response; TMZ; immune response; nosological images Author: Nuria Arias-Ramos, Laura Ferrer-Font, Silvia Lope-Piedrafita, Victor Mocioiu, Margarida Julià-Sapé, Martí Pumarola, Carles Arús and Ana Paula Candiota Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.15 CreationDate: Thu May 18 11:43:06 2017 CEST ModDate: Thu May 18 11:43:06 2017 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 29 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 15485427 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- NOLISI+URWPalladioL-Ital Type 1 Custom yes yes no 115 0 SLYQQZ+URWPalladioL-Bold Type 1 Custom yes yes no 116 0 ICWMHX+VnURWPalladioL-Bold Type 1 Custom yes yes no 117 0 IEZEJT+URWPalladioL-Roma Type 1 Custom yes yes no 118 0 NQWDWO+VnURWPalladioL Type 1 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Title: ぃぬちびびどてどっちぴどはの〠はて〠ごきず〭ごひづちぴづつ〠きどっづ〠ちてぴづひ〠ごげぉ〠ぃちぬっふぬちぴどはの〠ちのつ〠ぅぶはぬふぴどはの〠はて〠ごげぉ〠ざちぬふづび〠 Item: Title: えどびぴはばちぴとはぬはでべ〠げづびふぬぴび〠 Item: Title: ぁ〠ぐはびびどぢぬづ〠ぅへばぬちのちぴどはの〠てはひ〠ぴとづ〠ぃべっぬどっちぬ〠ごげぉ〠あづとちぶどはひ〺〠ごきず〠ごとづひちばべ〠ごひどででづひどので〠ぉねねふのづ〠げづびばはのびづ〠どの〠えはびぴ〠 Item: Title: きちぴづひどちぬび〠ちのつ〠きづぴとはつび〠 Children: Item: Title: ぇが〲〶〱〠ぃづぬぬび〠 Item: Title: ぐひづっぬどのどっちぬ〠ぇぬどはぢぬちびぴはねち〠きはつづぬ〠てはひ〠どの〠ぶどぶは〠こぴふつどづび〠 Item: Title: ぁのどねちぬ〠ごひづちぴねづのぴ〠ぷどぴと〠ごづねはぺはぬはねどつづ〠 Item: Title: ぉの〠ぶどぶは〠きげぉ〠ちのつ〠きげこぉ〠こぴふつどづび〠 Children: Item: Title: いちぴち〠ぁっぱふどびどぴどはの〠 Item: Title: きげぉ〠ちのつ〠きげこぉ〠ぐひはっづびびどので〠ちのつ〠ぐはびぴ〠ぐひはっづびびどので〠 Item: Title: ごふねはひ〠げづびばはのつどので〠ぉのつづへ〠〨ごげぉ〩〠ぃちぬっふぬちぴどはのび〠 Item: Title: えどびぴはばちぴとはぬはでべ〠こぴふつどづび〠 Item: Title: こぴちぴどびぴどっちぬ〠ぁのちぬべびどび〠 Item: Title: ぃはのっぬふびどはのび〠 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: OVNEXW+EURM10 FontSubset: true FirstChar: 22 LastChar: 22 FontDescriptor: FontName: OVNEXW+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: NOLISI+URWPalladioL-Ital 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