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Bioluminescence Tomography-Guided Radiation Therapy for Glioblastoma in Vivo

Z Deng1*, X Xu1 , e Kim1 , Z Belcaid1 , T Garzon-Muvdi1 , A Luksik1 , R Maxwell1 , I Iordachita2 , J Yu3 , M Lim1 , J Wong1 , K Wang1 , (1) Johns Hopkins University School of Medicine, Baltimore, MD, (2) Johns Hopkins University, Baltimore, MD, (3) Shaanxi Normal University, Shanxi, China

Presentations

(Sunday, 7/29/2018) 2:05 PM - 3:00 PM

Room: Karl Dean Ballroom B1

Purpose: Tremendous effort has been devoted to study radiation therapy(RT) for glioblastoma(GBM) in pre-clinical setting. CBCT-guided small animal radiation research platform(SARRP) is a widely-used platform, but it is limited by low soft tissue imaging contrast. Alternatively, we innovated a 3D bioluminescence tomography(BLT) for RT guidance. GBM growth curve was established to provide target volume for BLT-guided RT. Brain optical property(absorption coefficient μa) were optimized to estimate the GBM center of mass(CoM) reconstructed by BLT. These two together provide BLT-guided RT for GBM.

Methods: Bioluminescent GBM cells were injected into mouse left striatum. Contrast-enhanced CBCT/MRI were used to establish GBM growth curve and equivalent sphere as approximated gross target volume(GTV). For BLT, mice were first subject to multispectral bioluminescence imaging(Fig 1), followed by SARRP CBCT imaging and BLT reconstruction. SARRP CBCT image was acquired to generate anatomic mesh for BLT reconstruction and RT planning. To reduce the uncertainty of the μa toward BLT targeting accuracy, we optimized μa by minimizing the distance between the CoMs of BLT reconstruction and contrast-CBCT/MRI imaged GBM. The residual uncertainty of BLT localization and approximated GTV are combined to generate the estimated target volume(ETV). We will irradiate GBM with multiple-arc delivery by localizing GBM with BLT-reconstructed CoM and ETV, followed by pathological staining for validation.

Results: The GBM growth can be fitted and converted to equivalent spherical radius(Fig 2). Fig 3 illustrates BLT reconstructed CoM compared to contrast-CBCT. The optimized μa decreased along with the tumor growth, likely due to tumor necrosis(Fig 4a). Deviation between CoMs of BLT reconstruction and contrast-CBCT/MRI imaged GBM is approximately 1.3mm(Fig 4b). ETV volume vs. tumor growth, an example of applying BLT CoM and ETV for GBM coverage(Fig 5), and RT planning(Fig 6) are shown.

Conclusion: Our study demonstrates the BLT-guided RT and provides an innovative platform to support GBM-RT research.

Funding Support, Disclosures, and Conflict of Interest: John Wong and Iulian Iordachita receive royalty payment from a licensing agreement between Xstrahl Ltd. and Johns Hopkins University.

Keywords

Image Guidance, Radiation Therapy, Optical Tomography

Taxonomy

IM- Optical : Optical computed tomography

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