Image-Guided Radiotherapy Using a Modified Industrial Micro-CT for Preclinical Applications

Abstract

Purpose/objective: Although 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/materials: A 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.

Results: The 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.

Conclusion: A conventional industrial micro-CT can be easily modified to allow effective small animal IGRT even of critical target volumes such as the brain.

Fig 1. Dosimetric characteristics and reproducibility of the system.

(a) Measured data and fitted curves (S3 Text, Eq. (1)) of depth-dose rates. Mean values of three measurements in various depths using all established collimators (aperture sizes 1–5 mm) are shown. (b) Radial dose profiles of the five collimators in 1 mm depth. (c) Accuracy assessment of the manipulator in the x-y-plane. A quadratic pattern was produced and the distances between the spots were measured. (d) Assessment of center of rotation accuracy. A pentagon pattern (right side) was used to assess the angle accuracy of the CNC arm.

Fig 2. Proof of principle using an orthotopic implant model.

(a) CT scans used to measure tumor depths and example for a plan using 3 irradiation angles (0°, 270° and 315°). (b) Graphical user interface of the planning application with a standard treatment scheme. (c) Dose distribution of a three-beam plan (details shown in b) in the head phantom measured with a Gafchromic film. (d) Treated tumors show extensive necrotic areas (white arrow) after irradiation, which were not present in untreated tumors. (e) Survival plots of irradiated and untreated mice.