Visualization of the protective ability of a free radical trapping compound against rat C6 and F98 gliomas with diffusion tensor fiber tractography.
OBJECTIVE
To apply fiber tractography to assess the effect of a possible antiglioma drug, phenyl N-tert-butyl nitrone (PBN), on glioma-affected neuronal fibers. The fiber tractography method was able to differentiate between different tumor types, such as the C6 and F98 rat glioma models.


METHODS
C6 or F98 cells were intracranially injected into the cortex of male Fischer 344 rats. PBN treatment was initiated before or after cell implantation. Tumor growth was monitored with diffusion tensor imaging (DTI) and fiber tractography using diffusion-weighting gradients in 30 noncolinear directions.


RESULTS
Although proton density-weighted (PDw) and T2-weighted (T2w) images did not show any difference between C6 and F98 gliomas without edema, the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps were able to discriminate between these two tumor models. Fiber tractography was used to visualize C6 glioma-induced ischemia of tumor-surrounding tissues, whereas F98 glioma was found to infiltrate and penetrate into the corpus callosum (CC). During glioma growth, neuronal fibers were found to disappear at the border regions between the tumor and surrounding tissues. PBN treatment was shown to inhibit glioma growth with accompanying changes in the surrounding tissue.


CONCLUSIONS
By noninvasively monitoring the degree of neuronal fiber integrity and connectivity with the use of neuronal fiber tractography, we were able to evaluate the protective effect of PBN against invasive glioma growth in rat brains. PBN provided protection of the neuronal fibers against tumor-induced ischemia and tumor invasion.
Asanuma
Taketoshi
T
Small Animal MRI Facility, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
Doblas
Sabrina
S
Tesiram
Yasvir A
YA
Saunders
Debra
D
Cranford
Rebecca
R
Yasui
Hironobu
H
Inanami
Osamu
O
Smith
Nataliya
N
Floyd
Robert A
RA
Kotake
Yashige
Y
Towner
Rheal A
RA
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D045744:Cell Line, Tumor; D003497:Cyclic N-Oxides / Q000008:administration & dosage*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D016166:Free Radical Scavengers / Q000008:administration & dosage; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology*; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D021621:Imaging, Three-Dimensional / Q000379:methods; D009412:Nerve Fibers / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000970:Antineoplastic Agents; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; C029217:phenyl-N-tert-butylnitrone