RESUMO
BACKGROUND: Widely used Cone-beam computed tomography (CBCT)-guided irradiators have limitations in localizing soft tissue targets growing in a low-contrast environment. This hinders small animal irradiators achieving precise focal irradiation. PURPOSE: To advance image-guidance for soft tissue targeting, we developed a commercial-grade bioluminescence tomography-guided system (BLT, MuriGlo) for pre-clinical radiation research. We characterized the system performance and demonstrated its capability in target localization. We expect this study can provide a comprehensive guideline for the community in utilizing the BLT system for radiation studies. METHODS: MuriGlo consists of four mirrors, filters, lens, and charge-coupled device (CCD) camera, enabling a compact imaging platform and multi-projection and multi-spectral BLT. A newly developed mouse bed allows animals imaged in MuriGlo and transferred to a small animal radiation research platform (SARRP) for CBCT imaging and BLT-guided irradiation. Methods and tools were developed to evaluate the CCD response linearity, minimal detectable signal, focusing, spatial resolution, distortion, and uniformity. A transparent polycarbonate plate covering the middle of the mouse bed was used to support and image animals from underneath the bed. We investigated its effect on 2D Bioluminescence images and 3D BLT reconstruction accuracy, and studied its dosimetric impact along with the rest of mouse bed. A method based on pinhole camera model was developed to map multi-projection bioluminescence images to the object surface generated from CBCT image. The mapped bioluminescence images were used as the input data for the optical reconstruction. To account for free space light propagation from object surface to optical detector, a spectral derivative (SD) method was implemented for BLT reconstruction. We assessed the use of the SD data (ratio imaging of adjacent wavelength) in mitigating out of focusing and non-uniformity seen in the images. A mouse phantom was used to validate the data mapping. The phantom and an in vivo glioblastoma model were utilized to demonstrate the accuracy of the BLT target localization. RESULTS: The CCD response shows good linearity with < 0.6% residual from a linear fit. The minimal detectable level is 972 counts for 10 × 10 binning. The focal plane position is within the range of 13-18 mm above the mouse bed. The spatial resolution of 2D optical imaging is < 0.3 mm at Rayleigh criterion. Within the region of interest, the image uniformity is within 5% variation, and image shift due to distortion is within 0.3 mm. The transparent plate caused < 6% light attenuation. The use of the SD imaging data can effectively mitigate out of focusing, image non-uniformity, and the plate attenuation, to support accurate multi-spectral BLT reconstruction. There is < 0.5% attenuation on dose delivery caused by the bed. The accuracy of data mapping from the 2D bioluminescence images to CBCT image is within 0.7 mm. Our phantom test shows the BLT system can localize a bioluminescent target within 1 mm with an optimal threshold and only 0.2 mm deviation was observed for the case with and without a transparent plate. The same localization accuracy can be maintained for the in vivo GBM model. CONCLUSIONS: This work is the first systematic study in characterizing the commercial BLT-guided system. The information and methods developed will be useful for the community to utilize the imaging system for image-guided radiation research.
RESUMO
PURPOSE: The goal of this work was to develop and test a cylindrical tissue-equivalent quality assurance (QA) phantom for micro computed tomography (microCT) image-guided small animal irradiators that overcomes deficiencies of existing phantoms due to its mouse-like dimensions and composition. METHODS: The 8.6-cm-long and 2.4-cm-diameter phantom was three-dimensionally (3D) printed out of Somos NeXt plastic on a stereolithography (SLA) printer. The modular phantom consisted of four sections: (a) CT number evaluation section, (b) spatial resolution with slanted edge (for the assessment of longitudinal resolution) and targeting section, (c) spatial resolution with hole pattern (for the assessment of radial direction) section, and (d) uniformity and geometry section. A Python-based graphical user interface (GUI) was developed for automated analysis of microCT images and evaluated CT number consistency, longitudinal and radial modulation transfer function (MTF), image uniformity, noise, and geometric accuracy. The phantom was placed at the imaging isocenter and scanned with the small animal radiation research platform (SARRP) in the pancake geometry (long axis of the phantom perpendicular to the axis of rotation) with a variety of imaging protocols. Tube voltage was set to 60 and 70 kV, tube current was set to 0.5 and 1.2 mA, voxel size was set to 200 and 275 µm, imaging times of 1, 2, and 4 min were used, and frame rates of 6 and 12 frames per second (fps) were used. The phantom was also scanned in the standard (long axis of the phantom parallel to the axis of rotation) orientation. The quality of microCT images was analyzed and compared to recommendations presented in our previous work that was derived from a multi-institutional study. Additionally, a targeting accuracy test with a film placed in the phantom was performed. MicroCT imaging of the phantom was also simulated in a modified version of the EGSnrc/DOSXYZnrc code. Images of the resolution section with the hole pattern were acquired experimentally as well as simulated in both the pancake and the standard imaging geometries. The radial spatial resolution of the experimental and simulated images was evaluated and compared to experimental data. RESULTS: For the centered phantom images acquired in the pancake geometry, all imaging protocols passed the spatial resolution criterion in the radial direction (>1.5 lp/mm @ 0.2 MTF), the geometric accuracy criterion (<200 µm), and the noise criterion (<55 HU). Only the imaging protocol with 200-µm voxel size passed the criterion for spatial resolution in the longitudinal direction (>1.5 lp/mm @ 0.2 MTF). The 70-kV tube voltage dataset failed the bone CT number consistency test (<55 HU). Due to cupping artifacts, none of the imaging protocols passed the uniformity test of <55 HU. When the phantom was scanned in the standard imaging geometry, image uniformity and longitudinal MTF were satisfactory; however, the CT number consistency failed the recommended limit. A targeting accuracy of 282 and 251 µm along the x- and z-direction was observed. Monte Carlo simulations confirmed that the radial spatial resolution for images acquired in the pancake geometry was higher than the one acquired in the standard geometry. CONCLUSIONS: The new 3D-printed phantom presents a useful tool for microCT image analysis as it closely mimics a mouse. In order to image mouse-sized animals with acceptable image quality, the standard protocol with a 200-µm voxel size should be chosen and cupping artifacts need to be resolved.
