In vivo imaging in a murine model of glioblastoma.
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 sigma2-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).


CONCLUSIONS
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.
Jost
Sarah C
SC
Department of Neurosurgery, Washington University, School of Medicine, St. Louis, Missouri 63110, USA.
Wanebo
John E
JE
Song
Sheng-Kwei
SK
Chicoine
Michael R
MR
Rich
Keith M
KM
Woolsey
Thomas A
TA
Lewis
Jason S
JS
Mach
Robert H
RH
Xu
Jinbin
J
Garbow
Joel R
JR
D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005909:Glioblastoma / Q000175:diagnosis* / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D049268:Positron-Emission Tomography / Q000379:methods; D023041:Xenograft Model Antitumor Assays / Q000379:methods