Abstract
Purpose/ObjectiveAlthough radiotherapy is a key component of cancer treatment, its implementation into pre-clinical in vivo models with relatively small target volumes is frequently omitted either due to technical complexity or expected side effects hampering long-term observational studies. We here demonstrate how an affordable industrial micro-CT can be converted into a small animal IGRT device at very low costs. We also demonstrate the proof of principle for the case of partial brain irradiation of mice carrying orthotopic glioblastoma implants.Methods/MaterialsA commercially available micro-CT originally designed for non-destructive material analysis was used. It consists of a CNC manipulator, a transmission X-ray tube (10–160 kV) and a flat-panel detector, which was used together with custom-made steel collimators (1–5 mm aperture size). For radiation field characterization, an ionization chamber, water-equivalent slab phantoms and radiochromic films were used. A treatment planning tool was implemented using a C++ application. For proof of principle, NOD/SCID/γc−/− mice were orthotopically implanted with U87MG high-grade glioma cells and irradiated using the novel setup.ResultsThe overall symmetry of the radiation field at 150 kV was 1.04±0.02%. The flatness was 4.99±0.63% and the penumbra widths were between 0.14 mm and 0.51 mm. The full width at half maximum (FWHM) ranged from 1.97 to 9.99 mm depending on the collimator aperture size. The dose depth curve along the central axis followed a typical shape of keV photons. Dose rates measured were 10.7 mGy/s in 1 mm and 7.6 mGy/s in 5 mm depth (5 mm collimator aperture size). Treatment of mice with a single dose of 10 Gy was tolerated well and resulted in central tumor necrosis consistent with therapeutic efficacy.ConclusionA conventional industrial micro-CT can be easily modified to allow effective small animal IGRT even of critical target volumes such as the brain.
Highlights
External beam radiotherapy (RT) is a mainstay of cancer treatment
The full width at half maximum (FWHM) ranged from 1.97 to 9.99 mm depending on the collimator aperture size
Modern machines can be employed to treat very small intracerebral lesions in humans, brain tumor xenografts in animals as small as mice will be below the detection limit of on-board positioning CTs or even clinical CT scanners, thereby hampering image-guided RT (IGRT)
Summary
Its implementation into pre-clinical (small) animal models involving small target volumes is frequently omitted due to a high technical complexity associated with multi-angle or multi-planar irradiation to spare healthy tissue [1,2,3,4,5,6,7,8,9]. Modern machines can be employed to treat very small intracerebral lesions in humans, brain tumor xenografts in animals as small as mice will be below the detection limit of on-board positioning (cone-beam) CTs or even clinical CT scanners, thereby hampering image-guided RT (IGRT). Multiple pre-clinical studies employing LINAC-irradiated volumes involve irradiation of the whole brain, which includes high doses to normal tissues such as unaffected brain parts, eyes, nose, throat and mouth [12,13,14,15]
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