MEMS Based Intraoperative Photoacoustic Imaging

描述（由申请人提供）：保乳手术或乳房肿瘤切除术是诊断为早期浸润性乳腺癌患者最常见的外科手术。明确的肿瘤边缘和完整的手术切除肿瘤是预防局部复发和提高无病生存率的关键。目前，还没有准确的方法来在术前或术中识别肿瘤边缘。大约20%至30%的接受肿块切除术的患者由于存在阳性肿瘤边缘而需要额外的手术来切除任何剩余的肿瘤。为了开发一种灵敏的检测乳腺组织中肿瘤边缘的方法，我们提出设计一种肿瘤靶向纳米颗粒成像探针，并使用基于微机电系统（MEMS）的光声断层成像（PAT）实现术中成像。本研究的目的是：1）开发一种基于MEMS的双频光声断层扫描系统，用于术中肿瘤成像; 2）使用体模和体内实验验证和优化nanoprobe-MEMS-PAT系统; 3）评估体内nanoprobe-MEMS-PAT引导切除小鼠乳腺肿瘤的有效性。开发一种灵敏、高分辨率的基于MEMS的术中光声成像系统，对于在手术过程中确定肿瘤边缘、预防肿瘤复发并因此提高乳腺癌患者的生存率具有巨大潜力。 公共卫生相关性：本研究的目的是开发一种新的光声成像方法，将肿瘤靶向光学成像探头与基于先进微机电系统（MEMS）的光声成像仪器相结合，用于检测乳腺癌和在保乳手术中勾画肿瘤边界。在这项研究中，我们将使用尿激酶纤溶酶原激活物受体（uPAR）靶向的近红外（NIR）染料标记的纳米粒子，以提供成像探针到乳腺肿瘤。肿瘤的位置和深度将使用光声断层扫描进行检测。这项研究的成功为我们提供了一种新型的光声成像仪器，以解决保乳手术后预防肿瘤复发的迫切需要，并最终提高乳腺癌患者的生存率。

DESCRIPTION (provided by applicant): Breast-conserving surgery, or lumpectomy, is the most common surgical procedure for patients diagnosed with an early stage of invasive breast cancer. Clearly defined tumor margins and complete surgical removal of tumors are critical for preventing local recurrence and increasing disease-free survival. Currently, there is no accurate method to identify tumor margins pre- or intra-operatively. About 20% to 30% of the patients who undergo lumpectomy require additional surgery to excise any remaining tumors due to the presence of positive tumor margins. To develop a sensitive approach for detecting tumor margins in breast tissues, we propose to engineer a tumor targeted nanoparticle imaging probe and to realize the intraoperative imaging using microelectromechanical systems (MEMS) based photoacoustic tomography (PAT). The objectives of this proposed study are: 1) To develop a MEMS based dual-frequency photoacoustic tomography system for intraoperative tumor imaging; 2) To validate and optimize the nanoprobe-MEMS-PAT system using phantom and in vivo experiments; and 3) To evaluate the efficacy of in vivo nanoprobe-MEMS-PAT guided resection of mouse mammary tumors. The development of a sensitive and high resolution miniaturized MEMS based intraoperative photoacoustic imaging system should have great potential for determining tumor margins during surgery, preventing tumor recurrence and therefore, increasing the survival rate of breast cancer patients. PUBLIC HEALTH RELEVANCE: The objective of this proposed study is to develop a novel photoacoustic imaging approach that combines tumor targeted optical imaging probes with advanced microelectromechanical systems (MEMS) based photoacoustic imaging instrumentation for the detection of breast cancer and for outlining the tumor border during breast conserving surgery. In this study, we will use urokinase plasminogen activator receptor (uPAR) targeted near infrared (NIR) dye-labeled nanoparticles to deliver the imaging probes into breast tumors. The location and depth of the tumors will be detected using photoacoustic tomography. Success in this proposed study should provide us with a novel photoacoustic imaging instrument to address the urgent need for preventing tumor recurrence after breast conserving surgery and ultimately, to improve the survival rate of breast cancer patients.