In vivo imaging in a murine model of glioblastoma

Sarah C. Jost, John E. Wanebo, Sheng Kwei Song, Michael R. Chicoine, Keith M. Rich, Thomas A. Woolsey, Jason S. Lewis, Robert H. Mach, Jinbin Xu, Joel R. Garbow

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

OBJECTIVE: To use in vivo imaging methods in mice to quantify intracranial glioma growth, to correlate images and histopathological findings, to explore tumor marker specificity, to assess effects on cortical function, and to monitor effects of chemotherapy. METHODS: Mice with DBT glioma cell tumors implanted intracranially were imaged serially with a 4.7-T small-animal magnetic resonance imaging (MRI) scanner. MRI tumor volumes were measured and correlated with postmortem histological findings. Different nonspecific and specific positron emission tomography radiopharmaceuticals, [18F]2-fluoro-2-deoxy-d-glucose, [18F]3′-deoxy-3′-fluorothymidine, or [11C]RHM-I, a σ2-receptor ligand, were visualized with microPET (CTI-Concorde MicroSystems LLC, Knoxville, TN). Intrinsic optical signals were imaged serially during contralateral whisker stimulation to study the impact of tumor growth on cortical function. Other groups of mice were imaged serially with MRI after one or two doses of the antimitotic N,N′-bis(2-chloroethyl)-N-nitrosourea (BCNU). RESULTS: MRI and histological tumor volumes were highly correlated (r2 = 0.85). Significant binding of [11C]RHM-I was observed in growing tumors. Over time, tumors reduced and displaced (P # 0.001) whisker-activated intrinsic optical signals but did not change intrinsic optical signals in the contralateral hemisphere. Tumor growth was delayed 7 days after a single dose of BCNU and 18 days after two doses of BCNU. Mean tumor volume 15 days after DBT implantation was significantly smaller for treated mice (1- and 2-dose BCNU) compared with controls (P = 0.0026). CONCLUSION: Mouse MRI, positron emission tomography, and optical imaging provide quantitative and qualitative in vivo assessments of intracranial tumors that correlate directly with tumor histological findings. The combined imaging approach provides powerful multimodality assessments of tumor progression, effects on brain function, and responses to therapy.

Original languageEnglish
Pages (from-to)360-370
Number of pages11
JournalNeurosurgery
Volume60
Issue number2
DOIs
StatePublished - Feb 2007

Keywords

  • Glioma
  • Magnetic resonance imaging
  • Optical imaging
  • Positron emission tomography
  • Therapeutic response

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