Quantitative endoscopic imaging and structured light delivery for controlled drug

描述(申请人提供)：晚期卵巢癌是美国最致命的妇科恶性肿瘤。由于早期疾病通常没有症状，大多数卵巢癌病例直到疾病扩散到许多远处部位后才被诊断出来，这些部位被称为腹膜微转移。尽管在手术、放疗和化疗方面有所改善，但这种转移性疾病的五年存活率只有43%。因此，一个主要的挑战与移除数十或数百个转移性肿瘤结节的困难有关。在这里，我们提出了一种全新的基于近红外光直接触发的卟啉-磷脂掺杂(PoPD)脂质体的药物控制释放系统。荧光内窥镜可以利用荧光对比剂的高敏感性和特异性以及内窥镜的高分辨率。光动力诊断(PDD)包括使用光敏剂(例如，基于卟啉的化合物)，这种光敏剂特异性地聚集在癌症组织中，因为外源荧光对比剂已经显示出检测恶性肿瘤的前景。然而，活组织中强烈的组织吸收和散射会扭曲原始荧光信号，混淆 真正的荧光对比。为了解决这个问题，我们提出了一种定量的内窥镜方法，通过应用空间频域成像来获得增强的微转移可视化的绝对荧光浓度。我们将开发一种基于柔性光纤的双通道内窥镜系统，允许定量荧光成像和自适应光束整形，用于将光诱导药物(PoPD)输送到任何大小和形状的肿瘤。该系统将能够在只做锁孔切开的情况下插入到腹腔中，这在临床上已经是例行公事。该系统利用高灵敏度的CCD摄像机和带有数字微镜装置的空间频率调制方案，对药物分布、光触发药物释放和自适应光传输进行定量荧光成像，以优化微转移的治疗。我们期望我们的新的照明和药物释放策略将针对微转移的空间分布提供多种多样的光剂量和形状的调整，以实现高阿霉素沉积，以最小的副作用摧毁微转移。这种治疗将允许使用较低剂量的阿霉素，同时实现更具体的药物输送，以摧毁微转移并提高存活率。

DESCRIPTION (provided by applicant): Advanced ovarian cancer is the most lethal gynecologic malignancy in the United States. Since the early stage disease is generally without symptoms, the majority of ovarian cancer cases are not diagnosed until after the disease has spread to numerous distant sites, known as micrometastases, in the abdominal cavity. Although improvements in surgery, radiation and chemotherapy, the five-year survival rate for the metastatic disease is only 43%. Thus, a major challenge relates to difficulties in removing the dozens or hundreds metastatic tumor nodules within the abdominal cavity. Here, we propose a fundamentally new controlled drug release system based on porphyrin-phospholipid doped (PoPD) liposomes, triggered directly by near infrared (NIR) light. Fluorescence endoscopy can utilize the high sensitivity and specificity of fluorescence contrast and high resolution of endoscopy. Photodynamic diagnosis (PDD) involves using photosensitizers (e.g. porphyrin-based compounds) that specifically accumulate in the cancerous tissue as exogenous fluorescent contrast has demonstrated promise for detecting malignancies. However, strong tissue absorption and scattering in living tissue distorts raw fluorescence signal, confounding the true fluorescence contrast. To address this issue, we propose a quantitative endoscopic approach by applying spatial frequency domain imaging to obtain absolute fluorescence concentration for enhanced visualization of micrometastases. We will develop a flexible fiber based dual-channel endoscopy system that allows both quantitative fluorescence imaging and adaptive beam-shaping for light-induced drug (PoPD) delivery to tumors of any size and shape. The system will be able to be inserted into the abdominal cavity with only a keyhole incision being made, which is already routinely done in the clinic. The system utilizes a highly sensitive CCD camera and spatial frequency modulation scheme with a digital micro-mirror device for quantitative fluorescence imaging of drug distribution, light-triggered drug release and adaptive light delivery for optimized treatment of micrometastases. We expect that our novel illumination and drug release strategy will provide versatile adjustment of light dose and shape with respect to spatial distribution of micrometastasis to achieve high doxorubicin deposition to destroy micrometastasis with minimal side effects to the surrounding tissues. This treatment will permit lower doxorubicin doses to be administered while simultaneously achieving more specific drug delivery in order to destroy the micrometastases and improve survival rates.