Temperature-Modulated Bioluminescence Tomography

描述（由申请人提供）：我们于2002年发明的生物发光层析成像（BLT）是一种快速发展的小动物光学分子成像方式。最先进的结果表明，在有利的情况下或具有强大的先验知识，BLT确实可以产生有价值的层析信息。然而，这一领域的主要挑战仍然是，稳定和提高目前的BLT性能是非常可取的，但却极其困难。最近有报道称，生物发光光谱受到温度的显著影响，我们认为这是将不适定BLT问题转化为适定环境的一个重要机会。具体来说，通过聚焦超声加热，可以以局部可控的方式精确地扰动小鼠体内的生物发光源分布。由此产生的外部捕获光信号的差异仅与加热区域中的源参数有关。我们的假设是，这种生物发光的温度依赖性可以用于BLT重建，以获得更好的图像质量。我们的总体目标是开发用于小鼠研究的温度调节生物发光断层扫描（TBT）。三个具体目标是：(1)建立聚焦超声阵列的原型，每次在活体小鼠中加热一个小体积感兴趣（VOI）；(2)开发BLT算法，根据加热前后测量的生物发光数据重建底层源分布；(3)在数值模拟和模拟实验中评估TBT技术，并在小鼠研究中应用和验证它。当这个项目完成后，我们将建立第一个TBT系统，并证明其在体内的有效性和实用性。这一成功将是BLT领域向前迈出的重要一步。由于生物发光成像已被用于几乎所有人类疾病的小鼠模型，因此我们提出的TBT技术在小鼠研究和分子医学的发展中具有普遍、重要和直接的适用性。生物发光断层扫描（BLT）是我们在2002年发明的，它可以定位和量化生物发光源，用于小动物和许多人类疾病模型的研究。本项目将通过聚焦超声加热诱导小鼠体表生物发光信号变化，显著提高BLT技术的准确性和鲁棒性。我们的技术将在小鼠研究中具有普遍、重要和直接的适用性，并促进分子医学的发展。

DESCRIPTION (provided by applicant): Bioluminescence tomography (BLT) we invented in 2002 is a rapidly developing optical molecular imaging modality for small animal imaging. The state-of-the art results have indicated that BLT can indeed produce valuable tomographic information in favorable cases or with strong prior knowledge. However, the primary challenge in this area remains that it is highly desirable but extremely difficult to stabilize and improve the current BLT performance. It has been recently reported that bioluminescent spectra are significantly affected by temperature, which we recognize as a major opportunity to transform the ill-posed BLT problem into a well-posed setting. Specifically, with focused ultrasound heating, a bioluminescent source distribution in a mouse can be precisely perturbed in a local and controllable fashion. The resultant difference in the externally captured optical signals is solely related to the source parameters in the heated region. Our hypothesis is that this temperature dependence of the bioluminescence can be utilized in the BLT reconstruction for superior image quality. Our overall goal is to develop temperature-modulated bioluminescence tomography (TBT) for mouse studies. The three specific aims are to (1) prototype a focused ultrasound array to heat one small volume of interest (VOI) each time in a living mouse, (2) develop a BLT algorithm to reconstruct an underlying source distribution based on the bioluminescent data measured before and after heating, (3) evaluate the TBT technology in numerical simulation and phantom experiments, as well as apply and validate it in mouse studies. Upon the completion of this project, we will have built the first TBT system and demonstrated its in vivo validity and utility. This success will represent a major step forward in the field of BLT. Since bioluminescent imaging has been used in almost all the mouse models of human diseases, our proposed TBT technology shall have a general, important and immediate applicability in mouse studies, and for development of molecular medicine. Bioluminescence tomography (BLT) invented by us in 2002 is to localize and quantify bioluminescent sources in studies of small animals as many human disease models. This project will improve significantly the accuracy and robustness of the BLT techniques by means of focused ultrasound heating to induce bioluminescent signal changes on the mouse body surface. Our technology shall have a general, important and immediate applicability in mouse studies, and facilitate the development of molecular medicine.