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

项目总结/摘要 深部组织脓肿仍然是发病、死亡和住院的常见原因， 影像引导下经皮穿刺引流并辅以抗菌治疗。脓肿抽吸物 已被证明含有多种ESKAPE物种，一组耐药细菌。光动力 光动力疗法（PDT）通过产生活性氧来发挥抗微生物活性， 针对耐药菌株，并且不导致获得性耐药性。PDT可以补充目前 通过在引流后对脓肿腔进行消毒，从而可能替代抗生素。 确定亚甲蓝（MB）PDT治疗脓肿的安全性和可行性的I期临床试验 腔正在进行中（ClinicalTrails.gov标识符：NCT 02240498）。这种治疗的效果取决于 光学注量率、注量和光敏剂浓度。然而，光吸收和散射的 脓肿壁和人体脓肿腔内MB的微生物摄取尚未定量。这 光学特性数据的缺乏妨碍了脓肿PDT的治疗前计划，这减少了治疗 有效性，并增加了高注量率的风险，这将导致热损伤。 本研究的目的是严格计划在脓肿腔PDT过程中的光剂量， 使用光谱学测量人类受试者中的脓肿壁光学性质和MB摄取 系统患者特定的测量将允许设计实现目标光的治疗计划 剂量在脓肿壁的较大比例，并尽量减少光功率和热损伤的风险。这 将为严格的2期临床试验奠定基础，最终目标是减少脓肿复发 和术后干预，以及减少或消除对抗生素的依赖。 目标1.开发和验证光学光谱系统，用于评估 一个空洞的边界。设计并制作了一种基于光纤光栅的光学探头。这 探针将用于执行空间分辨漫反射和荧光光谱， 提取光学性质和MB浓度。将在组织模拟体模中评估准确度。 目标二。测量人体脓肿壁光学特性和亚甲蓝摄取。光学 将在参与所述1期临床试验的15名受试者中进行脓肿壁测量， 审判这些测量将在MB滴注和抽吸前后进行。 目标3：优化临床PDT治疗深部组织脓肿的治疗方案。测定光电 属性，沿着受试者CT图像，将用于为每个患者生成回顾性治疗计划。 参与主体。这些治疗计划将与固定的光剂量和散射体进行比较 在母I期试验中递送的浓度。

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.