Quantitative Bioluminescence Tomography-Guided Conformal Irradiation for Preclinical Radiation Research

Xu, X. Frank; Deng, Zijian; Dehghani, Hamid; Iordachita, Iulian; Lim, Michael; Wong, John W.; Wang, Ken Kang Hsin

doi:10.1016/j.ijrobp.2021.08.010

Cited by 15 publications

(30 citation statements)

References 46 publications

(93 reference statements)

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“…Two BLT systems in a similar configuration and equal performance were utilized in this study. The first one is an in-house BLT system 18 consisting of an optical assembly, a thermostatic system, a transportable mouse bed, and a mobile cart. The optical assembly is driven by a motorized linear stage to dock onto the mouse bed for imaging.…”

Section: Methodsmentioning

confidence: 99%

“…Details of both systems utilized in this work, together with system characterization and evaluation have been outlined previously. 18 , 21 , 23 …”

Section: Methodsmentioning

confidence: 99%

“…BLT in areas of research such as oncology has shown to be of benefit as a tool allowing high-contrast image-guided radiation therapy. 18 , 19 Specifically, to advance image-guided irradiation for soft tissue targeting and treatment assessment, a unique multimodal system has been developed combining BLT with x-ray cone-beam CT (CBCT) for preclinical radiation research. The system has been verified using an orthotopic glioblastoma (GBM) model 18 , 20 and orthotopic pancreatic ductal adenocarcinoma (PDAC) model, 21 with accuracies of tumor location recovery of

and 2 mm, respectively.…”

Section: Introductionmentioning

confidence: 99%

“… 18 , 19 Specifically, to advance image-guided irradiation for soft tissue targeting and treatment assessment, a unique multimodal system has been developed combining BLT with x-ray cone-beam CT (CBCT) for preclinical radiation research. The system has been verified using an orthotopic glioblastoma (GBM) model 18 , 20 and orthotopic pancreatic ductal adenocarcinoma (PDAC) model, 21 with accuracies of tumor location recovery of

and 2 mm, respectively. Limitations, however, exist from the need for a trial-and-error approach for optimizing the unknown optical parameters of the tissue, based on structural a-priori knowledge from the CBCT.…”

Section: Introductionmentioning

confidence: 99%

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Quantitative molecular bioluminescence tomography

Bentley

Deng

et al. 2022

J. Biomed. Opt.

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. Significance: Bioluminescence imaging and tomography (BLT) are used to study biologically relevant activity, typically within a mouse model. A major limitation is that the underlying optical properties of the volume are unknown, leading to the use of a “best” estimate approach often compromising quantitative accuracy. Aim: An optimization algorithm is presented that localizes the spatial distribution of bioluminescence by simultaneously recovering the optical properties and location of bioluminescence source from the same set of surface measurements. Approach: Measured data, using implanted self-illuminating sources as well as an orthotopic glioblastoma mouse model, are employed to recover three-dimensional spatial distribution of the bioluminescence source using a multi-parameter optimization algorithm. Results: The proposed algorithm is able to recover the size and location of the bioluminescence source while accounting for tissue attenuation. Localization accuracies of are obtained in all cases, which is similar if not better than current “gold standard” methods that predict optical properties using a different imaging modality. Conclusions: Application of this approach, using in-vivo experimental data has shown that quantitative BLT is possible without the need for any prior knowledge about optical parameters, paving the way toward quantitative molecular imaging of exogenous and indigenous biological tumor functionality.

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Section: Methodsmentioning

confidence: 99%

“…Details of both systems utilized in this work, together with system characterization and evaluation have been outlined previously. 18 , 21 , 23 …”

Section: Methodsmentioning

confidence: 99%

and 2 mm, respectively.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Quantitative molecular bioluminescence tomography

Bentley

Deng

et al. 2022

J. Biomed. Opt.

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“…Moreover, the importance of the domain geometry and imaging subject position on the measured bioluminescence fluence was studied, and an image reconstruction algorithm based on the spectral derivative (SD) of the measured spectral data was proposed to overcome the measurement noise from the surface of the imaging subject to the CCD (7). For the spectral-derivative method, the ratio of the BLIs at adjacent wavelengths was used as input data for the source reconstruction, as bioluminescence at similar wavelengths encounters a near-identical system response (25).…”

mentioning

confidence: 99%

Multispectral Differential Reconstruction Strategy for Bioluminescence Tomography

Chu

Guo

et al. 2022

Front. Oncol.

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Bioluminescence tomography (BLT) is a promising in vivo molecular imaging tool that allows non-invasive monitoring of physiological and pathological processes at the cellular and molecular levels. However, the accuracy of the BLT reconstruction is significantly affected by the forward modeling errors in the simplified photon propagation model, the measurement noise in data acquisition, and the inherent ill-posedness of the inverse problem. In this paper, we present a new multispectral differential strategy (MDS) on the basis of analyzing the errors generated from the simplification from radiative transfer equation (RTE) to diffusion approximation and data acquisition of the imaging system. Through rigorous theoretical analysis, we learn that spectral differential not only can eliminate the errors caused by the approximation of RTE and imaging system measurement noise but also can further increase the constraint condition and decrease the condition number of system matrix for reconstruction compared with traditional multispectral (TM) reconstruction strategy. In forward simulations, energy differences and cosine similarity of the measured surface light energy calculated by Monte Carlo (MC) and diffusion equation (DE) showed that MDS can reduce the systematic errors in the process of light transmission. In addition, in inverse simulations and in vivo experiments, the results demonstrated that MDS was able to alleviate the ill-posedness of the inverse problem of BLT. Thus, the MDS method had superior location accuracy, morphology recovery capability, and image contrast capability in the source reconstruction as compared with the TM method and spectral derivative (SD) method. In vivo experiments verified the practicability and effectiveness of the proposed method.

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Characterization of a commercial bioluminescence tomography‐guided system for pre‐clinical radiation research

Xu,

Deng,

Sforza

et al. 2023

Medical Physics

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BackgroundWidely 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.PurposeTo 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.MethodsMuriGlo 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.ResultsThe 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.ConclusionsThis 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.

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Quantitative Bioluminescence Tomography-Guided Conformal Irradiation for Preclinical Radiation Research

Cited by 15 publications

References 46 publications

Quantitative molecular bioluminescence tomography

Quantitative molecular bioluminescence tomography

Multispectral Differential Reconstruction Strategy for Bioluminescence Tomography

Characterization of a commercial bioluminescence tomography‐guided system for pre‐clinical radiation research

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