β-Radioluminescence Imaging: A Comparative Evaluation with Cerenkov Luminescence Imaging

Abstract

Cerenkov luminescence imaging (CLI) can provide high-resolution images of 18 F-FDG-avid tumors but requires prolonged acquisition times because of low photon sensitivity. In this study, we proposed a new modality, termed β-radioluminescence imaging (β-RLI), which incorporates a scintillator with a γ-rejection strategy for imaging β particles. We performed a comparative evaluation of β-RLI with CLI in both in vitro and in vivo systems. Methods: Using in vitro phantoms, we characterized the photon sensitivity and resolution of CLI and β-RLI. We also conducted a series of in vivo experiments with xenograft mouse models using both amelanotic (A375, UMSCC1-Luc) and melanotic (B16F10-Luc) cell lines. The B16F10 and UMSCC1 cell lines were transfected with the luciferase gene (Luc). CLI was acquired over 300 s, and β-RLI was acquired using two 10-s acquisitions. We correlated 18 F-FDG activities, as assessed by PET, with tumor radiances for both β-RLI and CLI. We also compared tumor signal-to-background ratios (SBRs) between these modalities for amelanotic and melanotic tumors. Results: For in vitro experiments, the photon sensitivity for β-RLI was 560-fold greater than that for CLI. However, the spatial resolution for β-RLI (4.4 mm) was inferior to that of CLI (1.0 mm). For in vivo experiments, correlations between 18 F-FDG activity and tumor radiance were 0.52 (P , 0.01) for β-RLI, 0.81 (P 5 0.01) for amelanotic lesions with CLI, and −0.08 (negative contrast; P 5 0.80) for melanotic lesions with CLI. Nine of 13 melanotic lesions had an SBR less than 1 for CLI, despite an SBR greater than 1 among all lesions for β-RLI. Conclusion: β-RLI can produce functional images of both amelanotic and melanotic tumors in a shorter time frame than CLI. Further engineering developments are needed to realize the full clinical potential of this modality.

Cerenkov luminescence imaging: physics principles and potential applications in biomedical sciences

“…1 It should be noted that recently a technique termed radioluminescence imaging (RLI) has been explored [84, 131], but this method uses the luminescence produced by radioactive sources in scintillating crystals rather than in tissue.…”

Flexible radioluminescence imaging for FDG‐guided surgery

“…Given the strong correlation between CLI signal and 18 F-FDG activity, 3 tumor burden can be monitored during surgical resection. [4][5][6] However, CLI is fundamentally limited by the relatively low photon sensitivity, which necessitates acquisition times on the order of 3-5 min. 1,3,5,7 Radioluminescence imaging (RLI) is an alternative optical imaging strategy, which enhances photon sensitivity by utilizing a scintillator to convert beta particles and gamma rays into optical light.…”

“…1,3,5,7 Radioluminescence imaging (RLI) is an alternative optical imaging strategy, which enhances photon sensitivity by utilizing a scintillator to convert beta particles and gamma rays into optical light. 6,8 This modality has been utilized for imaging 18 F-FDG uptake from single microscopic cells 9,10 and ex vivo atheroscerotic plaques. 11,12 However, background gamma rays from distant organs such as the heart or kidneys can dilute the signal-to-background ratio (SBR) of 18 F-FDGavid tumors in vivo.…”

“…11,12 However, background gamma rays from distant organs such as the heart or kidneys can dilute the signal-to-background ratio (SBR) of 18 F-FDGavid tumors in vivo. 6 Beta-RLI attempts to minimize background gamma rays by incorporating a gamma rejection strategy into the image acquisition process. Each beta-RLI is calculated as the difference of two images: a RLI and a block-RLI, in which a piece of stainless steel is carefully positioned between the scintillator and the object.…”

“…However, beta-RLI assumes a completely static geometry between the two image acquisitions and may produce high background signal if this assumption is not met. 6 In this paper, we investigate an alternative method for RLI, termed flexible RLI (flex-RLI). This method utilizes a flexible scintillator, which can loosely conform to body contours.…”