Micro-imaging of brain cancer radiotherapy using phase-contrast computed tomography

Publication date: Available online 7 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): G.E. Barbone, A. Bravin, P. Romanelli, A. Mittone, D. Bucci, T. Gaaβ, G. Le Duc, S. Auweter, M. Reiser, M.J. Kraiger, M. Hrabě de Angelis, G. Battaglia, P. Coan
PurposeExperimental neuroimaging provides a wide range of methods for the visualization of brain anatomical morphology down to sub-cellular detail. Still, each technique-specific detection mechanism presents compromises between achievable field-of-view size, spatial resolution or nervous-tissue sensitivity, leading e.g. to partial sample coverage, unresolved morphological structure or sparse labeling of neuronal populations, and often also to obligatory sample dissections or other sample-invasive manipulations. X-ray Phase Contrast CT (PCI-CT) is an experimental imaging methodology, which simultaneously provides micrometric spatial resolution, high soft-tissue sensitivity and ex-vivo full-organ rodent brain coverage without any need for sample dissection, staining/labeling or contrast agent injection. In this work, we explore the benefits and limitations of PCI-CT use for the in-vitro imaging of normal and cancerous brain neuro-morphology after in-vivo treatment with synchrotron-generated X-ray Microbeam Radiation Therapy (MRT), a spatially fractionated experimental high-dose radiosurgery. The goals are the visualization of MRT treatment effects on nervous tissue, and qualitative comparison of results to histology and high-field MRI.MethodsMRT was administered in-vivo to the brain of both healthy and cancer-bearing rats. Forty-five days post-treatment, brain organs were dissected out and imaged ex-vivo via propagation-based PCI-CT.ResultsPCI-CT visualizes brain anatomy and micro-vasculature in 3D, and distinguishes cancerous tissue morphology, necrosis, and intra-tumor accumulation of iron and calcium deposits. Moreover, PCI-CT detects the effects of MRT throughout treatment target areas, e.g. the formation of micrometer-thick radiation-induced tissue ablations. Observed neuro-structures were confirmed by histology and immunohistochemistry, and related to micro-MRI data.ConclusionsPCI-CT enables a unique 3D neuroimaging approach for ex-vivo studies on small animal models, in that it concurrently delivers high-resolution insight on local brain tissue morphology in both normal and cancerous micro-milieu, localizes radiosurgical damage, and highlights deep micro-vasculature. This method could assist experimental small-animal neurology studies in the post-mortem evaluation of neuropathology or treatment effects.

Teaser

Experimental X-ray Phase Contrast micro-CT provides ex-vivo 3D representations of post-mortem brain tissue and glioblastoma tumor anatomy of high sensitivity and resolution without the need for extensive sample preparation. This imaging technique proved suitable for a follow-up study of a spatially fractionated radiotherapy technique, X-ray Microbeam Radiation Therapy. We detect 50μm-thick ablations on healthy and tumor tissue, arising from locally-delivered ultra-high-dose X-ray microbeams, as well as calcium and iron accumulation within necrotic tumor tissue.


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