Co-registered photoacoustic and ultrasound imaging for non-invasive ovarian can

描述(申请人提供)：我们建议开发一种新的经阴道成像设备，使用共同注册的光声和超声技术，用于卵巢癌和原位异常的双模式非侵入性检测和定性。光声技术为深达3-4厘米的病变提供超声(US)分辨率的肿瘤血管生成和肿瘤缺氧的光学对比。通过这种非侵入性成像方式，能够对卵巢早期血管生成变化和肿瘤缺氧进行成像，将极大地加强对卵巢癌风险女性的护理。我们对正常、异常和恶性卵巢组织的体外成像数据表明，与正常卵巢组织相比，恶性肿瘤和异常卵巢组织有显著不同的血管生成。我们已经开发了一个联合注册的光声和US系统的原型，这使得我们能够验证这样的假设，即这种新的成像设备将改进目前对早期卵巢癌和卵巢异常的非侵入性诊断的临床实践，并将指导高危卵巢癌患者的手术干预。在这个建议中，我们将1)开发一种经阴道光声/超声探头和系统，适合于体内双模式无创检测和鉴定卵巢；2)通过比较成像结果与组织病理学、微血管密度计数和分布以及平均光吸收，确定正常、异常和癌变卵巢组织的体外特征；3)评估原型探头用于预防性卵巢切除术患者的体内成像；4)监测一组高危绝经前妇女在月经周期中的功能和形态参数的周期性变化，以确定可能与恶性过程相关的血管生成变化不同的周期性变化。大约60名患者将被招募参加AIM 2的体外研究，这将使我们能够验证拟议技术的初步敏感性和特异性。目标3将招募大约40名患者进行体内研究，这将使我们能够评估该技术并验证体外结果。大约20到25名绝经前高危患者将被招募参加AIM 4的活体研究，这将使我们能够评估这项新技术在绝经前人群中的有效性。该项目的成功完成将提供一种改善目前临床实践的手段：它将提供必要的技术，以提高确定是否存在癌症的能力，并避免相当数量的妇女接受手术。 公共卫生意义：在这个项目中，将开发一种新的经阴道成像设备，优化用于卵巢癌检测和诊断，并通过体外和体内临床研究进行验证。我们将研究具有正常、异常和恶性卵巢组织的绝经前和绝经后妇女的卵巢，试图提供一种更具成本效益和更准确的诊断技术，以帮助医生和患者确定是否需要手术。目前的技术(超声、CT、MRI、PET、CA125和体检)提供的数据不足以确定卵巢是否必须切除或可能是癌的；因此，需要更好的方法来确定卵巢组织是恶性的还是良性的。该项目的成功完成将为改善目前的临床实践提供一种手段；它将为提高卵巢癌的早期检测提供必要的技术；它将是避免大多数卵巢正常患者手术的有效手段。这也是一种相对便宜的技术，如果准确的话，将大大降低医疗成本，并为妇女提供更好的癌症风险确定，从而提高她们的生活质量。

DESCRIPTION (provided by applicant): We propose to develop a new transvaginal imaging device using co-registered photoacoustic and ultrasound technique for dual-modality non-invasive detection and characterization of ovarian cancer and abnormality in situ. The photoacoustic technique provides optical contrast of tumor angiogenesis and tumor hypoxia with ultrasound (US) resolution for deeply seated lesions of up to 3-4 cm. The ability to image early angiogenesis changes as well as tumor hypoxia in the ovary with this non-invasive imaging modality would greatly enhance the care for women at risk for ovarian cancer. Data obtained from our ex vivo imaging of normal, abnormal and malignant ovarian tissue have demonstrated that there is a significantly different angiogenic formation when malignant cancers and abnormal ovarian tissues are compared to normal ovarian tissues. We have developed a prototype co- registered photoacoustic and US system, which allows us to validate the hypothesis that this new imaging device will improve the current clinical practice for non-invasive diagnosis of early stage ovarian cancers and ovarian abnormality and will guide surgical intervention of high-risk ovarian cancer patients. In this proposal, we will 1) develop a transvaginal photoacoustic/US probe and system suitable for in vivo dual-modality non-invasive detection and characterization of the ovary; 2) characterize normal, abnormal and cancerous ovarian tissue ex vivo by comparing imaging results with histopathology and microvessel density counts and distributions as well as average optical absorption; 3) evaluate the prototype probe for in vivo imaging of patients who are scheduled for prophylactic oophorectomy; 4) monitor a group of high-risk premenopausal women during their menstrual cycles to determine the cyclic changes in functional and morphological parameters that may differ from angiogenesis changes associated with the malignant process. Approximately 60 patients will be recruited for the ex vivo study in Aim 2, which will allow us to validate the initial sensitivity and specificity of the proposed technique. Approximately 40 patients will be recruited for the in vivo study in Aim 3, which will allow us to evaluate the technique and validate the ex vivo results. Approximately 20 to 25 premenopausal high- risk patients will be recruited for the in vivo study in Aim 4, which will allow us to assess the efficacy of this new technique within a premenopausal population. The successful completion of the project will provide a means to improve the current clinical practice: it will provide necessary technology to improve the ability to determine if a cancer is present and to avoid surgery in a substantial number of women. PUBLIC HEALTH RELEVANCE: In this project, a new transvaginal imaging device optimized for ovarian cancer detection and diagnosis will be developed and validated from ex vivo and in vivo clinical studies. We will study ovaries from both premenopausal and postmenopausal women with normal, abnormal and malignant ovarian tissue in an attempt to provide a more cost effective and accurate diagnostic technique to aid doctors and patients in determining the need for surgery. Current technologies (ultrasound, CT, MRI, PET, CA125 and physical exam) provide insufficient data to determine whether an ovary must be removed or is likely cancerous; therefore, a better method is needed to determine if ovarian tissue is malignant or benign. The successful completion of the project will provide a means to improve the current clinical practice; it will provide necessary technology to improve early ovarian cancer detection; and it will be an effective means to avoid surgery in most patients with a normal ovary. It is also a relatively inexpensive technology and, if accurate, would substantially reduce medical costs and provide women with a better determination of their risk of cancer and thus improve their quality of life.