Early changes measured by CT perfusion imaging in tumor microcirculation following radiosurgery in rat C6 brain gliomas

Laboratory investigation

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Object

In this paper, the authors' aim was to use CT perfusion imaging to evaluate the early changes in tumor microcirculation following radiosurgery in rat C6 brain gliomas.

Methods

C6 glioma cells were inoculated into the right caudate nucleus of 25 Wistar rats using a stereotactic procedure. Tumor-bearing rats were randomly divided into 2 groups (tumor group and treatment group). Rats in the treatment group received maximal doses of 20 Gy delivered by the X-knife unit 16 days postimplantation. Computed tomography perfusion imaging was performed in all rats 3 weeks after tumor implantation prior to death and histopathological analysis.

Results

Hypocellular regions and tumor edema were increased in the treatment group compared with the tumor group. Parameters of CT perfusion imaging including cerebral blood volume (CBV) and mean transit time (MTT) of the tumors as well as the permeability surface area (PSA) product in the tumor-brain districts were decreased in the treatment group compared with the tumor group (p < 0.05). Although microvascular density (MVD) in the periphery of the tumors in the treatment group was higher than that in the normal contralateral brain (p < 0.05), MVD of the tumors in the treatment group was less than that in the tumor group (p < 0.01). There was a positive correlation between cerebral blood flow (CBF) and MVD as well as CBV and MVD in the center and periphery of tumors in both groups (p < 0.05).

Conclusions

A decrease in the perfusion volume of rat C6 brain gliomas was observed during the acute stage following X-knife treatment, and CBF and CBV were positively correlated with MVD of rat C6 brain gliomas. Thus, CT perfusion imaging can be used to evaluate the early changes in tumor microcirculation following radiosurgery.

Abbreviations used in this paper: BBB = blood-brain barrier; CBF = cerebral blood flow; CBV = cerebral blood volume; FOV = field of view; Gd-DTPA = gadopentetate dimeglumine; MTT = mean transit time; MVD = microvessel density; PSA = permeability surface area; ROI = region of interest; TBD = tumor-brain district.

Article Information

Address correspondence to: Ke Xu, M.D., Ph.D.,155 Nanjing North Street, Heping district, Shenyang, Liaoning Province, China 110001. email: kexu@vip.sina.com.

Please include this information when citing this paper: published online February 25, 2011; DOI: 10.3171/2011.1.JNS101513.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Diagram of the study design. Protocol 1: Treatment group (9 rats). Protocol 2: Tumor group (9 rats). All the rats, having grafted tumors as confirmed by MR imaging 14 days after implantation of C6 glioma cells, were assigned randomly to either the tumor group or treatment group. Rats in the treatment group received maximal doses of 20 Gy delivered by the X-knife 2 days later. Computed tomography perfusion imaging was performed in all rats in both groups 21 days after implantation of C6 glioma cells. The rats were then killed, and the brains were rapidly removed for histopathological analysis.

  • View in gallery

    The sets of tissue ROIs shown on the transverse PSA product map (one of the reconstructed CT perfusion images) of a rat C6 glioma following radiosurgery (20 Gy). The ROIs are as follows: 1, center of the tumor ; 2, contralateral normal tissue; 3, periphery of the tumor; 4, tumor-brain districts (TBD).

  • View in gallery

    Histological appearance of a rat C6 brain glioma following radiosurgery (20 Gy). A and B: Photomicrographs of treated (A) and untreated (B) tumors. The treated tumor is less compact, discretely hypocellular (short arrows), and markedly necrotic (long arrows). C and D: Photomicrographs showing capillary endothelium. The treated tumor (C) shows fewer brown-stained vascular tumors (arrows) than untreated tumor (D). H & E (A and B); anti-CD34 staining (C and D). Original magnification × 200 (A and B); × 400 (C and D).

  • View in gallery

    Images of a rat C6 glioma at the early stage after radiosurgery (20 Gy). A and B: Axial T2-weighted (A) and contrast-enhanced T1-weighted (B) MR images with Gd-DTPA showing a hyperintense tumor (arrows) with evident edema compared with the tissue surrounding the tumor. C–F: Reconstructed transverse images of perfusion CT scanning showing a heterogeneous increase in CBF (C), CBV (D), MTT (E), and PSA (F) (arrows) of the treated tumor compared with the surrounding tissue of the tumor and contralateral brain tissue.

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