Microendoscopic Electrical Impedance Sensing for Real-time Intraoperative Surgical Margin Assessment

摘要 外科治疗癌症患者的首要目标是清除所有的癌细胞。 从身体内部，以维持器官功能为次要目标。原发病理 衡量手术成功与否的标准是评估被切除者的手术切缘。 手术后的组织标本。这通常包括将组织切成切片并在显微镜下进行 探索这些组织样本的边缘是否存在癌细胞。注意到的癌细胞 切缘代表阳性手术切缘(PSM)，表明癌细胞留在体内 按照程序行事。因此，患有PSM的患者经常暴露在有害的额外程序中 根除残留的癌细胞，包括放射治疗、化学治疗、激素治疗和其他外科治疗； 所有这些疾病都会降低患者的生活质量。没有常规的临床方案 用于在手术过程中评估手术切缘状态。相反，利润率是 通过手术后组织的显微镜评估进行评估，当已经太晚无法提供 额外的手术干预。我们的目标是开发一种能够评估手术切缘的术中设备 状态，以便外科医生可以实时提取额外的组织，并最终降低 PSMS。虽然我们的技术可以应用于大多数癌症手术，但我们正专注于前列腺癌 癌症是男性发病率和死亡率最高的原因，因为患有PSM的患者 这些手术后的复发率比阴性手术的患者高得多 利润率。我们之前已经表明，电阻抗(描述有多容易的属性 电流通过组织)组织对组织的细胞排列很敏感，并且可以 用于区分前列腺癌和良性前列腺组织。我们已经开发了一种柔性内窥镜的原型 在前列腺癌根治术过程中能够对电阻抗组织成像的装置 电阻抗断层扫描(EIT)技术。该设备对边际状态进行焦点测量。 在这里，我们的目标是迈出重要的一步，构建可部署的优化EIT设备 通过腹腔镜术(如前列腺手术)提供一种术中识别阳性的准确方法 手术边缘。我们的目标是开发这种设备，制定术中可视化策略来帮助指导 外科医生，在活体研究中评估该技术，并在术中验证该技术。到了最后 在这个项目中，我们打算开发一种低成本、一次性使用的探测器，它可以部署在多个 中心临床试验，评价该技术对术中手术切缘评估的效果。

ABSTRACT The primary objective of surgical therapy for the treatment of patients with cancer is to remove all cancer cells from within the body, with the secondary objective of maintaining organ function. The primary pathological metric used to rate the success of a surgical procedure is evaluation of the surgical margin of the resected tissue specimen, post-operatively. This typically involves cutting the tissue into sections and microscopically exploring these tissue samples for the presence of cancer cells at the margins. Cancer cells noted at the margins represent Positive Surgical Margins (PSMs) and suggest that cancer cells were left in the body following the procedure. As a result, patients with PSMs are often exposed to noxious additional procedures to eradicate the cancer cells left behind including radiation, chemical, hormonal, and additional surgical therapy; these all have adverse morbidities that decrease a patient's quality of life. No clinical protocols are routinely used to intraoperatively assess surgical margin status during surgical procedures. Instead, margins are evaluated through microscopic assessment of the tissue following the procedure, when it is too late to provide additional surgical intervention. We aim to develop an intraoperative device able to assess surgical margin status so that the surgeons can extract additional tissues in real-time and ultimately decrease the rates of PSMs. While our technology can be applied for most cancer surgeries, we are focusing our efforts on prostate cancer as these are the highest incidence and cause of death for men and because patients with PSMs following these procedures have a much higher rate of recurrence than patients that have negative surgical margins. We have previously shown that the electrical impedance (a property that describes how easily electrical current passes through a tissue) of tissue is sensitive to a tissue's cellular arrangement and can be used to distinguish cancer from benign tissue in prostate. We have developed a prototype flexible endoscopic device capable of imaging the electrical impedance tissue during radical prostatectomy procedures using Electrical Impedance Tomography (EIT) techniques. This device makes focal measurements of margin status. Here we aim to take the significant step of constructing an optimized EIT device that can be deployed laparoscopically (e.g. prostate surgery) to provide an accurate method of intraoperatively identifying positive surgical margins. We aim to develop this device, develop intraoperative visualization strategies to help guide surgeons, evaluate the technology in an in vivo study, and validate the technology intraoperatively. By the end of this program we intend to have developed a low-cost, single use probe that can be deployed in a multi- center clinical trial to evaluate the efficacy of this technology for intraoperative surgical margin assessment.