Optical property measurement in human abscess cavities for photodynamic therapy treatment planning

项目摘要/摘要 深部组织脓肿尽管有发展，但仍是发病率、死亡率和住院时间的常见原因 影像引导下经皮引流配合抗菌治疗。脓肿抽吸物有 已被证明含有多种ESKAPE物种，这是一组抗药性细菌。光动力学 光动力疗法(Pdt)是一种有效的疗法，它通过产生活性氧来发挥抗微生物的作用。 对抗抗生素耐药菌株，不会导致获得性耐药性。光动力疗法可以补充目前的 在引流后对脓腔进行消毒，从而有可能取代抗生素的护理标准。 亚甲蓝(MB)光动力疗法治疗脓肿的安全性和可行性的一期临床试验 龋齿正在进行中(ClinicalTrails.gov标识符：NCT02240498)。这种疗法的疗效取决于 光通量速率、通量和光敏剂浓度。然而，光吸收和散射 人类脓肿腔内的脓肿壁和微生物对MB的摄取还没有被量化。这 由于缺乏光学特性数据，因此无法进行脓肿光动力疗法的治疗前计划，从而减少了治疗。 此外，它还具有良好的药效，并增加了导致热损伤的高注量率的风险。 这项研究的目的是严格计划在脓肿腔PDT治疗中的投光剂量。 使用光学光谱学测量人体脓肿壁的光学特性和MB摄取 系统。针对患者的具体测量将允许设计实现目标光的治疗计划 在更大比例的脓肿壁中进行剂量，并最大限度地减少光学功率和热损伤的风险。这 将为严格的二期临床试验奠定基础，最终目标是减少脓肿复发 以及术后干预，减少或消除对抗生素的依赖。 目标1.开发和验证用于评估光学特性的光学光谱学系统 空腔的边界。将设计和制造一种基于光纤束的光学探头。这 探测器将用于执行空间分辨漫反射和荧光光谱，以 提取光学性质和MB浓度。精确度将在组织模拟模型中进行评估。 目的2.测量人体脓肿壁的光学性质和亚甲基蓝摄取率。光学 脓肿壁的测量将在15名参与第一阶段临床试验的受试者中进行。 审判。这些测量将在甲基溴滴注和抽吸之前和之后进行。 目的3.优化临床PDT治疗深部组织脓肿的治疗方案。被测光学 这些属性以及受试者的CT图像将被用于为每个患者生成回溯性治疗计划 参与主体。这些治疗方案将与固定的光剂量和散射器进行比较 在母体阶段1试验中提供的浓度。

PROJECT SUMMARY/ABSTRACT Deep tissue abscesses remain a common cause of morbidity, mortality, and hospital stay despite development of image-guided percutaneous drainage accompanied by antimicrobial treatment. Abscess aspirates have been shown to contain multiple ESKAPE species, a group of antibiotic-resistant bacteria. Photodynamic therapy (PDT), which exerts antimicrobial activity through generation of reactive oxygen species, is efficacious against antibiotic-resistant strains and does not lead to acquired resistance. PDT could complement the current standard of care by sterilizing the abscess cavity following drainage, thereby potentially replacing antibiotics. A Phase 1 clinical trial to establish the safety and feasibility of methylene blue (MB) PDT of abscess cavities is ongoing (ClinicalTrails.gov identifier: NCT02240498). The efficacy of this treatment is dependent on optical fluence rate, fluence, and photosensitizer concentration. However, optical absorption and scattering of the abscess wall and microbial uptake of MB within human abscess cavities have not been quantified. This lack of optical property data precludes pre-treatment planning for abscess PDT, which reduces treatment efficacy and increases the risk of high fluence rates that would cause thermal damage. The objective of this study is to rigorously plan the delivered light dose during PDT of abscess cavities by measuring abscess wall optical properties and MB uptake in human subjects, using an optical spectroscopy system. Patient-specific measurements will allow for design of treatment plans that achieve the target light dose in a larger proportion of the abscess wall, and minimize optical power and risk of thermal damage. This will lay the foundation for a rigorous Phase 2 clinical trial, with the ultimate goal of reducing abscess recurrence and post-procedure intervention, and decreasing or eliminating reliance on antibiotics. Aim 1. Develop and validate an optical spectroscopy system for assessment of optical properties at the boundary of a hollow cavity. A fiber bundle-based optical probe will be designed and fabricated. This probe will be used to perform spatially-resolved diffuse reflectance and fluorescence spectroscopy to extract optical properties and MB concentration. Accuracy will be assessed in tissue-simulating phantoms. Aim 2. Measure abscess wall optical properties and methylene blue uptake in humans. Optical measurements of abscess walls will be made in 15 subjects participating in the described Phase 1 clinical trial. These measurements will be made prior to and following MB instillation and aspiration. Aim 3. Optimize treatment plans for clinical PDT of deep tissue abscesses. Measured optical properties, along with subject CT images, will be used to generate retrospective treatment plans for each participating subject. These treatment plans will be compared to the fixed light dose and scatterer concentration delivered in the parent Phase 1 trial.