Bioluminescence Tomography–Guided Radiation Therapy for Preclinical Research

Zhang, Bin; Wang, Ken Kang Hsin; Yu, Jingjing; Eslami, Sohrab; Iordachita, Iulian; Reyes, Juvenal; Malek, Reem; Tran, Phuoc T.; Patterson, Michael S.; Wong, John W.

doi:10.1016/j.ijrobp.2015.11.039

Cited by 48 publications

(53 citation statements)

References 48 publications

(57 reference statements)

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“…48,49 Recently, some advances were reported on motion management 33 and beam gating, 50 as well as progress in imaging, e.g. bioluminescence, 51,52 optical imaging and dualenergy CT. 53 These techniques, fully integrated in the novel precision irradiation cabinets, will be required to allow sophisticated radiation research that can be translated to the human level.…”

Section: Advances In Small Animal Irradiationmentioning

confidence: 99%

Tumour and normal tissue radiobiology in mouse models: how close are mice to mini-humans?

Koontz¹,

Verhaegen²,

Ruysscher³

2017

BJR

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Animal modelling is essential to the study of radiobiology and the advancement of clinical radiation oncology by providing preclinical data. Mouse models in particular have been highly utilized in the study of both tumour and normal tissue radiobiology because of their cost effectiveness and versatility. Technology has significantly advanced in preclinical radiation techniques to allow highly conformal image-guided irradiation of small animals in an effort to mimic human treatment capabilities. However, the biological and physical limitations of animal modelling should be recognized and considered when interpreting preclinical radiotherapy (RT) studies. Murine tumour and normal tissue radioresponse has been shown to vary from human cellular and molecular pathways. Small animal irradiation techniques utilize different anatomical boundaries and may have different physical properties than human RT. This review addresses the difference between the human condition and mouse models and discusses possible strategies for future refinement of murine models of cancer and radiation for the benefit of both basic radiobiology and clinical translation.

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Section: Advances In Small Animal Irradiationmentioning

confidence: 99%

Tumour and normal tissue radiobiology in mouse models: how close are mice to mini-humans?

Koontz¹,

Verhaegen²,

Ruysscher³

2017

BJR

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“…This error results from multiple sources, including distortions arising from the image formation processes, the digitisation of the target, errors consequent to the registration process as well as the operator bias inherent to the use of trained operators prescribing the centre of rotation manually. Although the centre of the conical arc treatment did not perfectly align with the centre of the target, the 0.6 mm targeting accuracy was comparable with a 3D offset of 1 mm reported in a similar study using BLI as an imaging tool [32]. Therefore, automated image-guided isocentre definition has the potential to further increase the mechanical accuracy of MR-IGRT.…”

Section: Discussionmentioning

confidence: 59%

An efficient and robust MRI-guided radiotherapy planning approach for targeting abdominal organs and tumours in the mouse

Kersemans¹,

Beech²,

Gilchrist³

et al. 2017

PLoS ONE

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IntroductionPreclinical CT-guided radiotherapy platforms are increasingly used but the CT images are characterized by poor soft tissue contrast. The aim of this study was to develop a robust and accurate method of MRI-guided radiotherapy (MR-IGRT) delivery to abdominal targets in the mouse.MethodsA multimodality cradle was developed for providing subject immobilisation and its performance was evaluated. Whilst CT was still used for dose calculations, target identification was based on MRI. Each step of the radiotherapy planning procedure was validated initially in vitro using BANG gel dosimeters. Subsequently, MR-IGRT of normal adrenal glands with a size-matched collimated beam was performed. Additionally, the SK-N-SH neuroblastoma xenograft model and the transgenic KPC model of pancreatic ductal adenocarcinoma were used to demonstrate the applicability of our methods for the accurate delivery of radiation to CT-invisible abdominal tumours.ResultsThe BANG gel phantoms demonstrated a targeting efficiency error of 0.56 ± 0.18 mm. The in vivo stability tests of body motion during MR-IGRT and the associated cradle transfer showed that the residual body movements are within this MR-IGRT targeting error. Accurate MR-IGRT of the normal adrenal glands with a size-matched collimated beam was confirmed by γH2AX staining. Regression in tumour volume was observed almost immediately post MR-IGRT in the neuroblastoma model, further demonstrating accuracy of x-ray delivery. Finally, MR-IGRT in the KPC model facilitated precise contouring and comparison of different treatment plans and radiotherapy dose distributions not only to the intra-abdominal tumour but also to the organs at risk.ConclusionThis is, to our knowledge, the first study to demonstrate preclinical MR-IGRT in intra-abdominal organs. The proposed MR-IGRT method presents a state-of-the-art solution to enabling robust, accurate and efficient targeting of extracranial organs in the mouse and can operate with a sufficiently high throughput to allow fractionated treatments to be given.

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“…Including other reported sources of setup uncertainty (11), an undesirably large beam aperture >15 mm in diameter, about half of the width of the mouse abdomen, would be required to ensure coverage of a small 3 mm diameter tumor. Bioluminescence tomography (BLT), based on the 2D bioluminescence image measured on the object surface, can reveal the three-dimensional (3D) distribution of the internal bioluminescent sources (12–19). Recently, our group proposed an on-line 3D BLT system to guide SARRP irradiation (19).…”

Section: Introductionmentioning

confidence: 99%

“…Bioluminescence tomography (BLT), based on the 2D bioluminescence image measured on the object surface, can reveal the three-dimensional (3D) distribution of the internal bioluminescent sources (12–19). Recently, our group proposed an on-line 3D BLT system to guide SARRP irradiation (19). …”

Section: Introductionmentioning

confidence: 99%

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Evaluation of On- and Off-Line Bioluminescence Tomography System for Focal Irradiation Guidance

et al. 2016

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In response to the limitations of computed tomography (CT) and cone-beam CT (CBCT) in irradiation guidance, especially for soft-tissue targets without the use of contrast agents, our group developed a solution that implemented bioluminescence tomography (BLT) as the image-guidance modality for preclinical radiation research. However, adding such a system to existing small animal irradiators is no small task. A potential solution is to utilize an off-line BLT system in close proximity to the irradiator, with stable and effective animal transport between the two systems. In this study, we investigated the localization accuracy of an off-line BLT system when used for the small animal radiation research platform (SARRP) and compared the results with those of an on-line system. The CBCT was equipped on both the off-line BLT system and the SARRP, with a distance of 5 m between them. To evaluate the setup error during animal transport between the two systems, the mice underwent CBCT imaging on the SARRP and were then transported to the off-line system for a second CBCT imaging session. The normalized intensity difference of the two images and the corresponding histogram and correlation were computed to evaluate if the transport process perturbed animal positioning. Strong correlation (correlation coefficients >0.95) between the SARRP and the off-line mouse CBCT was observed. The offset of the implanted light source center can be maintained within 0.2 mm during transport. To compare the target localization accuracy using the on-line SARRP BLT and the off-line system, a self-illuminated bioluminescent source was implanted in the abdomen of anesthetized mice. In addition to the application for dose calculation, CBCT imaging was also employed to generate the mesh grid of the imaged mouse for BLT reconstruction. Two scenarios were devised and compared, which involved localization of the luminescence source based on either: 1. on-line SARRP bioluminescence image and CBCT; or 2. off-line bioluminescence image and SARRP CBCT. The first scenario is assumed to have the least setup error, because no animal transport was involved. The second scenario examines if an off-line BLT system, with the mesh generated from the SARRP CBCT, can be used to guide SARRP irradiation when there is minimal target contrast in CBCT. Stability during animal transport between the two systems was maintained. The center of mass (CoM) of the light source reconstructed by the off-line BLT had an offset of 1.0 ± 0.4 mm from the true CoM derived from the SARRP CBCT. These results are comparable to the offset of 1.0 ± 0.2 mm using on-line BLT. With CBCT information provided by the SARRP and effective animal immobilization during transport, these findings support the utilization of an off-line BLT-guided system, in close proximity to the SARRP, for accurate soft-tissue target localization. In addition, a dedicated standalone BLT system for our partner site at the University of Pennsylvania was introduced in this study.

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Bioluminescence Tomography–Guided Radiation Therapy for Preclinical Research

Cited by 48 publications

References 48 publications

Tumour and normal tissue radiobiology in mouse models: how close are mice to mini-humans?

Tumour and normal tissue radiobiology in mouse models: how close are mice to mini-humans?

An efficient and robust MRI-guided radiotherapy planning approach for targeting abdominal organs and tumours in the mouse

Evaluation of On- and Off-Line Bioluminescence Tomography System for Focal Irradiation Guidance

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