Yu Jingjing, Zhang Bin, Iordachita Iulian I, Reyes Juvenal, Lu Zhihao, Brock Malcolm V, Patterson Michael S, Wong John W, Wang Ken Kang-Hsin
Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland 21231 and School of Physics and Information Technology, Shaanxi Normal University, Shaanxi 710119, China.
Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland 21231.
Med Phys. 2016 May;43(5):2619. doi: 10.1118/1.4947481.
To overcome the limitation of CT/cone-beam CT (CBCT) in guiding radiation for soft tissue targets, the authors developed a spectrally resolved bioluminescence tomography (BLT) system for the small animal radiation research platform. The authors systematically assessed the performance of the BLT system in terms of target localization and the ability to resolve two neighboring sources in simulations, tissue-mimicking phantom, and in vivo environments.
Multispectral measurements acquired in a single projection were used for the BLT reconstruction. The incomplete variables truncated conjugate gradient algorithm with an iterative permissible region shrinking strategy was employed as the optimization scheme to reconstruct source distributions. Simulation studies were conducted for single spherical sources with sizes from 0.5 to 3 mm radius at depth of 3-12 mm. The same configuration was also applied for the double source simulation with source separations varying from 3 to 9 mm. Experiments were performed in a standalone BLT/CBCT system. Two self-illuminated sources with 3 and 4.7 mm separations placed inside a tissue-mimicking phantom were chosen as the test cases. Live mice implanted with single-source at 6 and 9 mm depth, two sources at 3 and 5 mm separation at depth of 5 mm, or three sources in the abdomen were also used to illustrate the localization capability of the BLT system for multiple targets in vivo.
For simulation study, approximate 1 mm accuracy can be achieved at localizing center of mass (CoM) for single-source and grouped CoM for double source cases. For the case of 1.5 mm radius source, a common tumor size used in preclinical study, their simulation shows that for all the source separations considered, except for the 3 mm separation at 9 and 12 mm depth, the two neighboring sources can be resolved at depths from 3 to 12 mm. Phantom experiments illustrated that 2D bioluminescence imaging failed to distinguish two sources, but BLT can provide 3D source localization with approximately 1 mm accuracy. The in vivo results are encouraging that 1 and 1.7 mm accuracy can be attained for the single-source case at 6 and 9 mm depth, respectively. For the 2 sources in vivo study, both sources can be distinguished at 3 and 5 mm separations, and approximately 1 mm localization accuracy can also be achieved.
This study demonstrated that their multispectral BLT/CBCT system could be potentially applied to localize and resolve multiple sources at wide range of source sizes, depths, and separations. The average accuracy of localizing CoM for single-source and grouped CoM for double sources is approximately 1 mm except deep-seated target. The information provided in this study can be instructive to devise treatment margins for BLT-guided irradiation. These results also suggest that the 3D BLT system could guide radiation for the situation with multiple targets, such as metastatic tumor models.
为克服CT/锥形束CT（CBCT）在引导软组织靶点放疗方面的局限性，作者开发了一种用于小动物放疗研究平台的光谱分辨生物发光断层扫描（BLT）系统。作者在模拟、仿组织体模和体内环境中，系统地评估了BLT系统在靶点定位以及分辨两个相邻光源方面的性能。
在单次投影中获取的多光谱测量数据用于BLT重建。采用带有迭代允许区域收缩策略的不完全变量截断共轭梯度算法作为优化方案来重建光源分布。对半径为0.5至3mm、深度为3 - 12mm的单个球形光源进行了模拟研究。相同配置也应用于双光源模拟，光源间距从3至9mm不等。实验在独立的BLT/CBCT系统中进行。选择两个间距分别为3和4.7mm、置于仿组织体模内的自发光光源作为测试案例。还使用了在6和9mm深度植入单光源、在5mm深度植入两个间距为3和5mm的光源或在腹部植入三个光源的活体小鼠，以说明BLT系统在体内对多个靶点的定位能力。
对于模拟研究，在单光源情况下定位质心（CoM）以及双光源情况下定位组合CoM时，可实现约1mm的精度。对于1.5mm半径的光源（临床前研究中常用的肿瘤大小），模拟表明，对于所有考虑的光源间距，除了9和12mm深度处3mm的间距外，在3至12mm深度处两个相邻光源均可分辨。体模实验表明，二维生物发光成像无法区分两个光源，但BLT能够以约1mm的精度提供三维光源定位。体内结果令人鼓舞，在6和9mm深度的单光源情况下，分别可达到1和1.7mm的精度。对于体内双光源研究，在3和5mm的间距下两个光源均可区分，并且也可实现约1mm的定位精度。
本研究表明，他们的多光谱BLT/CBCT系统可潜在地应用于在广泛的光源大小、深度和间距范围内定位和分辨多个光源。除深部靶点外，单光源定位CoM和双光源定位组合CoM的平均精度约为1mm。本研究提供的信息可为设计BLT引导放疗的治疗边界提供指导。这些结果还表明，三维BLT系统可用于指导多靶点情况（如转移性肿瘤模型）的放疗。
