ABSTRACT The purpose is to evaluate the feasibility of imaging mouse brain with high resolution ultrasound (HiRes US), and generation of mouse brain tumor (glioma) model under HiRes US guided implantation of glioma cells. Normal mouse brain was imaged with 30 MHz HiRes US in six pups and ten adult nude mice. Glioma model was developed by injecting human glioma cells (5 × 105), U-87MG-luc, under HiRes US guidance, in three pups and five adult mice. Bioluminescence imaging, magnetic resonance imaging, and HiRes US were used for in vivo tumor imaging. In addition, brain imaging ex vivo with HiRes US were also performed in three tumor bearing and five normal brains. The brain parenchyma was seen as a homogeneous low echo on HiRes US without locoregional echo differences. An inverted U shaped linear echo structure (fissure) differentiated the telencephalon from the diencephalon. Bilaterally budding structure at the base of the skull represented the trigeminal nerve. The inserted needle, used to implant the glioma cells, was seen as a high linear echogenic reflection. Brain tumor on ex vivo HiRes US was well demarcated, homogeneous and hyperechoic compared to the surrounding healthy brain. In conclusion, imaging the brain with HiRes US in small animal model like mouse is possible and convenient. Real-time guiding is possible to perform any intervention from tumor implantation to percutaneous therapeutic procedures. Ex vivo, HiRes US is extremely useful to study the detailed anatomical features.
Cite this paper
nullB. Kwak, J. Geschwind, P. Rao, S. Ota, R. Loffroy, M. Lin, S. Ganapathy-Kanniappan, R. Kunjithapatham, M. Buijs, L. Syed, E. Liapi, V. Chacko and M. Vali, "High-Resolution Ultrasound in Research of Mouse Orthotopic Glioma and Ultrasound-Guided Cell Implant," Advances in Molecular Imaging, Vol. 1 No. 2, 2011, pp. 24-32. doi: 10.4236/ami.2011.12004.
 L. Zhang, X. Xu, C. Hu, et al., “A High-Frequency, High Frame Rate Duplex Ultrasound Linear Array Imaging System for Small Animal Imaging,” IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, Vol. 57, No. 12, 2010, pp. 1548-1557.
M. E. Loveless, X. Li, J. Huamani, et al., “A Method for Assessing the Microvasculature in a Murine Tumor Model Using Contrast-Enhanced Ultrasonography,” Journal of Ultrasound in Medicine, Vol. 27, No. 12, 2008, pp. 1699-1709.
M. Saar, C. K?rbel, V. Jung, et al., “Experimental Or-thotopic Prostate Tumor in Nude Mice: Techniques for Local Cell Inoculation and Three-Dimensional Ultrasound Monitoring,” Urologic Oncology, 2010 (in Print).
M. W. Laschke, C. K?rbel, J. Rudzitis-Auth, et al., “High-Resolution Ultrasound Imaging: A Novel Tech-nique for the Noninvasive in Vivo Analysis of Endome-triotic Lesion and Cyst Formation in Small Animal Mod-els,” American Journal of Pathology, Vol. 176, No. 2, 2010, pp. 585-593. doi:10.2353/ajpath.2010.090617
N. Hozumi, R. Yamashita, C. K. Lee, et al., “Time-Fre- quency Analysis for Pulse Driven Ultrasonic Microscopy for Biological Tissue Characterization,” Ultrasonics, Vol. 42, No. 1-9, 2004, pp. 717-722.
K. Shung, J. Cannata, M. Q. Zhou, et al., “High Fre-quency Ultrasound: A New Frontier for Ultrasound,” Conference Proceedings—IEEE Engineering in Medicine and Biology Society, 2009, pp. 1953-1955.
J. Mamou, O. Aristizábal, R. H. Silverman, et al., “40-MHz Ultrasound Imaging with Chirps and Annular Arrays,” Conference Proceedings—IEEE Engineering in Medicine and Biology Society, 2008, pp. 2518-2521.
Q. Xie, R. Thompson, K. Hardy, et al., “A Highly Inva-sive Human Glioblastoma Pre-Clinical Model for Testing Therapeutics,” Journal of Translational Medicine, Vol. 6, 2008, pp. 77-90. doi:10.1186/1479-5876-6-77
Y. K. Hong, D. S. Chung, Y. A. Joe, et al., “Efficient Inhibition of in Vivo Human Malignant Glioma Growth and Angiogenesis by Interferon-Beta Treatment at Early Stage of Tumor Development,” Clinical Cancer Research, Vol. 6, 2000, pp. 3354-3360.
J. J. Verhoeff, L. J. Stalpers, A. W. Coumou, et al., “Ex-perimental Iodine-125 Seed Irradiation of Intracerebral Brain Tumors in Nude Mice,” Radiation Oncology, Vol. 2, 2007, pp. 38-45. doi:10.1186/1748-717X-2-38
S. Sirsi, J. Feshitan, J. Kwan, et al., “Effect of Microbub-ble Size on Fundamental Mode High Frequency Ultra-sound Imaging in Mice,” Ultrasound in Medicine and Bi-ology, Vol. 36, No. 6, 2010, pp. 935-948.
A. Stokvis, J. W. Van Neck, C. F. Van Dijke, et al., “High-Resolution Ultrasonography of the Cutaneous Nerve Branches in the Hand and Wrist,” Journal of Hand Surgery (European Volume), Vol. 34, No. 6, 2009, pp. 766-771.
D. Purger, T. McNutt, P. Achanta, et al., “A Histolo-gy-Based Atlas of the C57BL/6J Mouse Brain Deforma-bly Registered to in Vivo MRI for Localized Radiation And Surgical Targeting,” Physics in Medicine and Biology, Vol. 54, No. 24, 2009, pp. 7315-7327.
E. B. Dinca, J. N. Sarkaria, M. A. Schroeder, et al., “Bi-oluminescence Monitoring of Intracranial Glioblastoma Xenograft: Response to Primary and Salvage Temozolo-mide Therapy,” Journal of Neurosurgery, Vol. 107, No. 3, 2007, pp. 610-616. doi:10.3171/JNS-07/09/0610