Deciphering spatially distinct immune microenvironments in glioblastoma using ferumoxytol and gadolinium-enhanced and FLAIR hyperintense MRI phenotypes.

Autor:	Stoller J; Department of Diagnostic Radiology, Oregon Health and Science University, Portland, Oregon, USA., Kersch CN; Department of Radiation Medicine, Oregon Health and Science University, Portland, Oregon, USA., Muldoon LL; Department of Neurology, Oregon Health and Science University, Portland, Oregon, USA., Ambady P; Department of Oncology, Providence Hospital, Portland, Oregon, USA., Harrington CA; Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon, USA.; Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA., Fu R; School of Public Health, Oregon Health & Science University-Portland State University, Portland, Oregon, USA., Raslan AM; Department of Neurosurgery, Oregon Health and Science University, Portland, Oregon, USA., Dogan A; Department of Neurosurgery, Oregon Health and Science University, Portland, Oregon, USA., Neuwelt EA; Department of Neurology, Oregon Health and Science University, Portland, Oregon, USA.; Department of Neurosurgery, Oregon Health and Science University, Portland, Oregon, USA.; Department of Veterans Affairs Medical Center, Portland, Oregon, USA., Barajas RF Jr; Department of Diagnostic Radiology, Oregon Health and Science University, Portland, Oregon, USA.; Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA.; Advanced Imaging Research Center, Oregon Health and Science University, Portland, Oregon, USA.
Jazyk:	angličtina
Zdroj:	Neuro-oncology advances [Neurooncol Adv] 2023 Nov 08; Vol. 5 (1), pp. vdad148. Date of Electronic Publication: 2023 Nov 08 (Print Publication: 2023).
DOI:	10.1093/noajnl/vdad148
Abstrakt:	Background: MRI with gadolinium (Gd)-contrast agents is used to assess glioblastoma treatment response but does not specifically reveal heterogeneous biology or immune microenvironmental composition. Ferumoxytol (Fe) contrast is an iron nanoparticle that localizes glioblastoma macrophages and microglia. Therefore, we hypothesized that the use of Fe contrast improves upon standard Gd-based T1-weighted and T2/FLAIR analysis by specifically delineating immune processes. Methods: In this, HIPAA-compliant institutional review board-approved prospective study, stereotactic biopsy samples were acquired from patients with treatment-naïve and recurrent glioblastoma based on MR imaging phenotypes; Gd and Fe T1 enhancement (Gd+, Fe+) or not (Gd-, Fe-), as well as T2-Flair hyperintensity (FLAIR+, FLAIR-). Analysis of genetic expression was performed with RNA microarrays. Imaging and genomic expression patterns were compared using false discovery rate statistics. Results: MR imaging phenotypes defined a variety of immune pathways and Hallmark gene sets. Gene set enrichment analysis demonstrated that Gd+, Fe+, and FLAIR+ features were individually correlated with the same 7 immune process gene sets. Fe+ tissue showed the greatest degree of immune Hallmark gene sets compared to Gd+ or Flair+ tissues and had statistically elevated M2 polarized macrophages, among others. Importantly, the FLAIR+ Gd+ and Fe- imaging phenotypes did not demonstrate expression of immune Hallmark gene sets. Conclusions: Our study demonstrates the potential of Fe and Gd-enhanced MRI phenotypes to reveal spatially distinct immune processes within glioblastoma. Fe improves upon the standard of care Gd enhancement by specifically localizing glioblastoma-associated inflammatory processes, providing valuable insights into tumor biology. Competing Interests: Neither any authors nor their immediate family have a financial relationship with a commercial organization that may have a direct or indirect interest in this content. (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu