Advanced Ultrasonic Evaluation of Sentinel Lymph Nodes

描述（由申请人提供）：滨江研究所、夏威夷大学和Kuakini医学中心以及国家科学研究中心（巴黎，法国）提议继续研究、改进和扩展新型定量超声方法的使用，以区分癌症患者的含癌和无癌淋巴结。淋巴结转移癌的检测对于准确的分期、预后和治疗计划至关重要。我们的总体目标是显著减少现有组织病理学方法在25%至30%的解剖淋巴结和50%的微转移淋巴结中检测转移的不可接受的失败。为了实现这一目标，我们建议开发定量成像方法，在病理实验室使用高频超声，以确定区域的解剖节点，保证仔细的组织学检查。我们已经朝着这个目标取得了令人兴奋的进展，通过开发一种灵敏和特异的超声成像方法，具有良好的空间分辨率的淋巴结转移性疾病。我们的研究结果显示了在广泛的癌症类型的淋巴结中检测癌症的显着能力，并且它们承诺了一种革命性的方法，可以引导病理学家到淋巴结的含癌区域。我们提出的方法所证明的精确定位转移性癌症的能力可能会大大减少当淋巴结包含微转移性疾病时假阴性确定的发生，而使用当前的组织病理学方法很容易忽略微转移性疾病。我们目前的结果基本上验证了我们最初的假设，即所提出的方法可以同时以大约90%的灵敏度和特异性识别解剖的淋巴结的含癌区域。这些发现为我们提出的研究完全实现我们的总体目标提供了鼓励，并且它们表明同时超过95%的灵敏度和特异性实际上是可能的。因此，我们建议获取更多数据，以扩大我们现有的数据库，并彻底验证我们的研究结果。我们还建议研究在检查或手术室中以较低频率应用相同技术用于临床的可行性，以识别需要活检或解剖的淋巴结。此外，我们建议使用甚高频超声显微镜来改进淋巴结中的超声散射模型，并制定能够在病理实验室中常规进行淋巴结评估的低成本超声仪器的工程规范。总之，该项目可以有益于淋巴结评估，用于所有类型癌症的分期，预后和治疗计划，例如，乳腺、结肠直肠、胃、胰腺、肺、甲状腺、前列腺等，以及前哨淋巴结解剖手术，例如，治疗乳腺癌我们正在开发的方法显然可以对术前或术中检查的淋巴结的原位评价、包括前哨淋巴结在内的区域淋巴结的术中评价和切除淋巴结的术后评价产生显著的有益影响。

DESCRIPTION (provided by applicant): Riverside Research Institute, the University of Hawaii and Kuakini Medical Center, and the National Center for Scientific Research (Paris, France) propose to continue to investigate, refine, and expand the use of novel quantitative ultrasound methods for discriminating between cancer-containing and cancer-free lymph nodes of cancer patients. Detection of metastatic cancer in lymph nodes is absolutely crucial for accurate staging, prognosis, and treatment planning. Our overall objective is to reduce markedly the unacceptable failure of existing histopathological methods to detect metastases in 25% to 30% of dissected nodes and 50% in nodes with micrometastases. To achieve this objective, we proposed to develop quantitative imaging methods using high-frequency ultrasound in the pathology laboratory to identify regions of dissected nodes that warrant careful histologic examination. We have made exciting progress toward this objective by developing a sensitive and specific ultrasonic method of imaging metastatic disease present in lymph nodes with fine spatial resolution. Our results have shown a remarkable ability to detect cancer in dissected lymph nodes for a broad range of cancer types, and they promise a revolutionary means of guiding pathologists to cancer-containing regions of dissected lymph nodes. The demonstrated ability of our proposed methods to pinpoint metastatic cancer potentially can reduce the occurrence of false-negative determinations drastically when nodes contain micrometastatic disease, which easily can be overlooked using current histopathology methods. Our current results substantially have validated our original hypothesis that the proposed methods can identify cancer- containing regions of dissected nodes with a simultaneous sensitivity and specificity of approximately 90%. These findings provide encouragement that our proposed studies fully achieve our general objective, and they suggest that a simultaneous sensitivity and specificity exceeding 95% in fact may be possible. Therefore, we propose to acquire additional data to expand our existing database and thoroughly validate our findings. We also propose to investigate the feasibility of applying the same techniques at lower frequencies for clinical use in the examination or operating room to identify nodes that warrant biopsy or dissection. In addition, we propose to improve models for ultrasound scattering in lymph nodes using very-high-frequency ultrasonic microscopy and to formulate engineering specifications for a low-cost ultrasound instrument capable of performing node evaluations routinely in the pathology laboratory. In conclusion, this project can benefit lymph-node evaluations for staging, prognosis, and treatment planning of all types of cancers, e.g., breast, colorectal, gastric, pancreatic, lung, thyroid, prostate, etc., as well as sentinel-node dissection procedures, e.g., for breast cancer. The methods we are developing clearly can have a significant beneficial impact on in situ evaluations of lymph nodes examined prior to or during surgery, intra-operative evaluations of regional nodes including sentinel-nodes, and post-operative evaluations of dissected nodes.