A deep-learning assisted bioluminescence tomography method to enable radiation targeting in rat glioblastoma

Abstract

Objective: A novel solution is required for accurate 3D Bioluminescence Tomography (BLT) based glioblastoma (GBM) targeting. The provided solution should be computationally efficient to support real-time treatment planning, thus reducing the X-ray imaging dose imposed by high-resolution micro cone-beam CT.
Approach: A novel deep-learning approach is developed to enable BLT-based tumor targeting and treatment planning for orthotopic rat GBM models. The proposed framework is trained and validated on a set of realistic Monte Carlo simulations. Finally, the trained deep learning model is tested on a limited set of BLI measurements of real rat GBM models.
Significance: Bioluminescence Imaging (BLI) is a 2D non-invasive optical imaging modality geared toward preclinical cancer research. It can be used to monitor tumor growth in small animal tumor models effectively and without radiation burden. However, the current state-of-the-art does not allow accurate radiation treatment planning using BLI, hence limiting BLI’s value in preclinical radiobiology research. 
Results: The proposed solution can achieve sub-millimeter targeting accuracy on the simulated dataset, with a median dice similarity coefficient (DSC) of 61%. The provided BLT-based planning volume achieves a median encapsulation of more than 97% of the tumor while keeping the median geometrical brain coverage below 4.2%. For the real BLI measurements, the proposed solution provided median geometrical tumor coverage of 95% and a median DSC of 42%. Dose planning using a dedicated small animal treatment planning system indicated good BLT-based treatment planning accuracy compared to ground-truth CT-based planning, where dose-volume metrics for the tumor fall within the limit of agreement for more than 95% of cases.
Conclusion: The combination of flexibility, accuracy, and speed of the deep learning solutions make them a viable option for the BLT reconstruction problem and can provide BLT-based tumor targeting for the rat GBM models.

Multimodal bioimaging across disciplines and scales: challenges, opportunities and breaking down barriers

“…US imaging in the living mouse revealed uptake and adhesion of the agents in vascular structures, but only the combination with ex vivo and in vivo multiphoton imaging allowed determination of the exact location of the attachment of the agents, revealing sites of damage at the molecular level 15,16 . X-ray imaging can also provide valuable structural information and when combined with bioluminescence these modalities can reveal location and function of genetically modified cells or tissues 17 .…”