Raman spectroscopy probes for assisting stereotactic breast biopsy needle placeme

描述(申请人提供)：对于乳房X光检查发现的不可触及的乳房病变，采用俯卧式活检台并由影像引导的立体定向大芯针活检，现已被接受为开放式外科活检术的替代方法。与以前的微创技术，如细针抽吸相比，切除了足够的组织，以实现可靠的病理。据报道，诊断的手术确认率为95%，该方法被认为是手术活检的安全替代方法，前提是在随后的正常乳腺组织诊断中进行后续的针吸活检或手术活检。正常的诊断可能意味着漏掉了乳房X光检查上看到的原始病变。抽样不足是针吸活组织检查后诊断正常的主要原因。这种情况发生在2%到10%的手术中。针本身可能模糊病变的图像，或者由于致密的乳房组织而难以看到病变，或者由于立体定向靶向装置的压缩伪影，病变可能从其预期位置移动。在活检针的组织采集孔处实时检测目标病变的方法可以减少采样不足的发生，并有可能加快整个过程。为此，提出了一种光纤拉曼光谱探头，通过活检针展开。拉曼光谱是一种特别好的病变检测候选方法，因为它对通常与此类病变相关的微钙化非常敏感。X光乳房X光检查是在乳腺癌最早、最可治愈的阶段发现未触及的乳腺癌的标准程序。微钙化是钙盐的小而固体的沉积物，通常与癌症病变有关，它强烈地吸收X射线，因此在乳房X光照片上显示为高对比度的阴影。他们的存在可能导致转诊为立体定向针吸活组织检查。在拉曼光谱学中，这些微钙化由从组织散射的近红外光的光谱中的强、尖锐、容易区分的峰来指示。由于组织的化学成分，该光谱还包含更宽的峰。这些峰值的幅度发生更细微的变化，可以直接表明癌症的存在或不存在。拉曼光谱的这种诊断能力已经在小型、体外、临床研究中得到了证明。侧视拉曼针状探针还没有在体内得到证实。在第一阶段，将设计、制造一种实用的拉曼针探头，并在大芯针活检的体外乳腺组织芯上进行测试。在第二阶段，将建立一个具有实时分析能力的完整诊断系统，并在立体定向穿刺针活检过程中进行体内测试。如果成功，第二阶段的仪器将被证明可以减少组织采样不足的发生，并充分提高采样效率，以减少这些程序所需的总体时间，节省后续活组织检查程序的成本和随之而来的患者痛苦。与公众健康相关：该项目将开发一种光纤拉曼光谱探头，该探头将部署在立体定向乳腺活检针的内部，以实时指示组织采集孔是否已正确定位在先前通过乳房X光检查发现的微钙化和/或可疑组织旁边。该系统应减少取回已知微钙化点所需的活检样本数量，并最大限度地减少潜在的“遗漏”，即未能取回微钙化点和正常组织的病理报告。其结果应该是减少手术时间和病人的痛苦。

DESCRIPTION (provided by applicant): Stereotactic, large-core, needle biopsy using a prone biopsy table and guided by imaging, is now accepted as an alternative to open surgical biopsy for non-palpable breast lesions discovered by mammography. Compared to previous minimally-invasive techniques, such as fine needle aspiration, sufficient tissue is removed to allow for reliable pathology. Surgical confirmation rates of 95% for diagnosis have been reported and the method is considered a safe alternative to surgical biopsy provided that follow- up needle biopsies or surgical biopsies are performed in the case of a subsequent normal breast tissue diagnosis. A normal diagnosis may mean that the original lesion seen on mammography was missed. Inadequate sampling is the primary reason for a normal breast tissue diagnosis following needle biopsies. This occurs in 2 to 10% of procedures. The needle itself may obscure the image of the lesion or the lesion may be difficult to see because of dense breast tissue or the lesion may move from its expected position due to compression artifacts of the stereotactic targeting apparatus. A means of detecting the target lesions, in real time, at the tissue acquisition aperture of the biopsy needle could reduce the occurrence of inadequate sampling and potentially speed up the overall procedure. A fiberoptic Raman spectroscopy probe, deployed through the biopsy needle, is proposed for this purpose. Raman spectroscopy is a particularly good candidate for lesion detection because it is highly sensitive to microcalcifications which are often associated with such lesions. X-ray mammography is the standard procedure for detecting non-palpable breast cancers at their earliest, most-curable stage. Microcalcifications are small, solid deposits of calcium salts, often associated with cancerous lesions, which strongly absorb x-rays and thus show up as high-contrast shadows on mammograms. Their presence may result in a referral for a stereotactic needle biopsy. In Raman spectroscopy these microcalcifications are indicated by strong, sharp, easily distinguished peaks in the optical spectrum of near-infrared light scattered from the tissue. This spectrum also contains broader peaks due to the chemical constituents of tissue. More subtle shifts in the amplitudes of these peaks can indicate the presence or absence of cancer directly. This diagnostic ability of Raman spectroscopy has already been demonstrated in small, ex-vivo, clinical studies. Side-looking Raman needle probes have yet to be demonstrated in-vivo. In Phase I a practical Raman needle probe will be designed, built and tested on ex-vivo breast tissue cores from large-core needle biopsies. In Phase II a full diagnostic system with real-time analysis capability will be built and tested, in-vivo, during stereotactic needle biopsy procedures. If successful, the Phase II instrument will be shown to reduce the occurrence of inadequate tissue sampling and improve the efficiency of sampling sufficiently to reduce the overall time required by these procedures, saving the cost of subsequent biopsy procedures and the attendant patient distress. PUBLIC HEALTH RELEVANCE: This program will develop a fiberoptic Raman spectroscopy probe which will be deployed inside of a stereotactic breast biopsy needle to indicate, in real time, when the tissue acquisition aperture has been correctly positioned next to microcalcifications and/or suspicious tissue which has been previously found through mammography. This system should reduce the number of biopsy samples necessary to retrieve known microcalcifications and minimize potential "misses", defined as a failure to retrieve microcalcifications coupled with a pathology report of normal tissue. The result should be a reduction of both procedure time and patient distress.