Conformal laser thermal therapy for epithelial cancer

描述(申请人提供)：尽管绝大多数癌症发生在容易接触到的上皮表面，但对于许多器官系统来说，上皮癌及其前驱疾病的治疗仍然严重不足。治疗这些病变的主要挑战是1)通常肉眼看不到它们，2)它们可能在空间上是不同的，分布在很大的表面积上，3)对邻近的非受累组织的附带损伤可能会导致严重的并发症。这项拟议研究的总体目标是开发一种大大改进的治疗技术--“适形激光疗法”，用于治疗上皮癌及其前驱疾病。我们方法的一个重要组成部分是全面的诊断筛查，它提供了疾病在大片粘膜表面积上的详细分布图。使用这张地图，治疗可以被引导到已知的疾病发源地。然而，与以前的激光治疗不同，我们的方法能够使治疗区域(三维)与病变组织体积相一致，同时将附带损害降至最低。这一创新的方法将筛查与实时方法相结合，根据通过监测局部激光与组织相互作用获得的反馈信号来控制激光治疗量。适形激光治疗将利用三维微结构成像技术和诊断标准，我们已经建立了全面的广泛领域筛查上皮病。R21的目标是开发和测试监测和控制方法。将研究新的高分辨率、横截面成像技术，以动态监测热激发和蛋白质变性的微观后果。为了控制治疗体积，我们将利用水在近红外(1350-1450 nm)吸收的波长依赖性，使用可调谐激光来改变热损伤的深度。R21研究的结果将指导在R33期进行适形激光治疗的临床可行系统和内窥镜探头的构建。该仪器将在活体猪身上进行测试，并将确定这种选择性治疗上皮组织的方法的准确性。虽然我们的研究重点是改进Barrett‘s食道的治疗，但这项技术也将作为一个平台，在各种其他器官系统中进行广泛的上皮治疗，在这些系统中，综合治疗和最小的附带损害至关重要。

DESCRIPTION (provided by applicant): Although the vast majority of cancers arise within readily accessible epithelial surfaces, therapy of epithelial cancers and their precursors remains woefully inadequate for many organ systems. The primary challenges for treating these lesions are 1) oftentimes they are not visible by eye, 2) they may be spatially heterogeneous and distributed over a large surface area, and 3) collateral damage to adjacent, non-involved tissues may cause significant complications. The overall objective of the proposed research is to develop a greatly improved therapeutic technique, 'conformal laser therapy,' for the treatment of epithelial cancers and their precursors. An important component of our approach is comprehensive diagnostic screening, which provides a detailed map of the disease distribution over large mucosal surface areas. Using this map, therapy can be directed to regions known to harbor disease. Unlike prior laser therapies, however, our method has the ability to conform the treatment region (in three-dimensions) to the diseased tissue volume, while minimizing collateral damage. This innovative approach integrates screening with real-time methods for controlling the laser treatment volume based on feedback signals obtained by monitoring local laser- tissue interactions. Conformal laser therapy will leverage 3-dimensional microstructural imaging technology and diagnostic criteria that we have established for comprehensive wide-field screening of epithelial disease. The objective of the R21 is to develop and test methods for monitoring and control. Novel high-resolution, cross-sectional imaging techniques will be investigated for dynamic monitoring of the microscopic consequences of thermal excitation and protein denaturation. In order to control treatment volume, we will exploit the wavelength- dependence of water absorption in the near-infrared (1350-1450 nm), using a tunable laser to vary the depth of thermal injury. Results from the R21 research will guide the construction of a clinically viable system and endoscopic probe for conformal laser therapy during the R33-phase. This instrument will be tested in living swine and the accuracy of this approach for selectively treating epithelial tissues will be determined. Although we focus our research on improving treatment of Barrett's esophagus, this technology will also serve as a platform for wide-field epithelial therapy in a variety of other organ systems where comprehensive treatment and minimal collateral damage are critical.