Systematic calibration of an integrated x‐ray and optical tomography system for preclinical radiation research

Abstract

Purpose: The cone beam computed tomography (CBCT) guided small animal radiation research platform (SARRP) has been developed for focal tumor irradiation, allowing laboratory researchers to test basic biological hypotheses that can modify radiotherapy outcomes in ways that were not feasible previously. CBCT provides excellent bone to soft tissue contrast, but is incapable of differentiating tumors from surrounding soft tissue. Bioluminescence tomography (BLT), in contrast, allows direct visualization of even subpalpable tumors and quantitative evaluation of tumor response. Integration of BLT with CBCT offers complementary image information, with CBCT delineating anatomic structures and BLT differentiating luminescent tumors. This study is to develop a systematic method to calibrate an integrated CBCT and BLT imaging system which can be adopted onboard the SARRP to guide focal tumor irradiation. Methods: The integrated imaging system consists of CBCT, diffuse optical tomography (DOT), and BLT. The anatomy acquired from CBCT and optical properties acquired from DOT serve as a priori information for the subsequent BLT reconstruction. Phantoms were designed and procedures were developed to calibrate the CBCT, DOT/BLT, and the entire integrated system. Geometrical calibration was performed to calibrate the CBCT system. Flat field correction was performed to correct the nonuniform response of the optical imaging system. Absolute emittance calibration was performed to convert the camera readout to the emittance at the phantom or animal surface, which enabled the direct reconstruction of the bioluminescence source strength. Phantom and mouse imaging were performed to validate the calibration. Results: All calibration procedures were successfully performed. Both CBCT of a thin wire and a euthanized mouse revealed no spatial artifact, validating the accuracy of the CBCT calibration. The absolute emittance calibration was validated with a 650 nm laser source, resulting in a 3.0% difference between simulated and measured signal. The calibration of the entire system was confirmed through the CBCT and BLT reconstruction of a bioluminescence source placed inside a tissue-simulating optical phantom. Using a spatial region constraint, the source position was reconstructed with less than 1 mm error and the source strength reconstructed with less than 24% error. Conclusions: A practical and systematic method has been developed to calibrate an integrated x-ray and optical tomography imaging system, including the respective CBCT and optical tomography system calibration and the geometrical calibration of the entire system. The method can be modified and adopted to calibrate CBCT and optical tomography systems that are operated independently or hybrid x-ray and optical tomography imaging systems. C 2015 American Association of Physicists in Medicine. [http://dx

Bioluminescence Tomography–Guided Radiation Therapy for Preclinical Research

“…We recently developed a standalone CBCT/BLT system (28) for calibration method and algorithm development. In this study, we introduce an online BLT-SARRP system to demonstrate BLT-guided radiation for the first time.…”

“…In this study, we introduce an online BLT-SARRP system to demonstrate BLT-guided radiation for the first time. Compared with the earlier work from Yang et al (28), this paper integrates multispectral BLT (25, 29), the IVTCG method (30) and permissible source region (31) developed by our group and collaborators to enable fast and accurate CoM reconstruction. Furthermore, the new algorithm enables better conformality of the reconstructed source distributions without a predefined region of interest (see Figure 2 vs.…”

“…In this study, CCD counts per unit time per pixel area were chosen as the measurement quantity at the boundary and were not linked to absolute emittance. Further study to calibrate CCD counts to absolute emittance at the boundary is warranted (28). The optical and reconstruction parameters used in this study are listed in the Supplementary Table e1.…”

“…We had built an integrated CBCT and BLT system in a standalone configuration (28) for calibration method and reconstruction algorithm development. In this study, we introduced an online BLT/CBCT system for the SARRP and a significantly improved BLT algorithm.…”

The changing paradigm of tumour response to irradiation

“…140 Modern small animal irradiators, which provide small defined focused beams and an ability to target the tumour from different angles have reduced concerns about normal tissue exposure and have largely obviated the need to use subcutaneous transplantation sites. [141][142][143][144] These current technologies are allowing investigation of treatment strategies not previously possible in small animals. They provide opportunities to test different approaches with the attending possible differences in the critical parameters affecting tumour treatment response, particularly those related with the microenvironment.…”