Terahertz Imaging in Breast Cancer Detection

描述（由申请人提供）：这项拟议研究的总体目标是设计，开发并转化为临床实践一种新的紧凑型太赫兹（THz）成像设备，用于在手术乳房保护手术（即乳房肿瘤切除术）中准确评估阳性乳腺癌边缘。在乳房保护手术（BCS）中，外科医生试图切除周围有健康组织边缘的恶性组织。手术切除肿瘤后，标本提交病理评估，以确定边缘是否清除恶性组织。病理分析通常需要至少一天才能确定结果。令人惊讶的是，目前病理分析显示约40-50%的肿瘤边缘呈阳性[Dillon 2007；弗莱明2004;雅各布斯2008;Waljee 2008]，因此要求患者接受外科再切除手术以去除额外的乳腺组织。我们在本提案中解释了所提出的实时太赫兹成像方法如何在术中评估边缘时提供准确的性能，从而消除了目前使用的程序的许多缺点，并最终降低了医疗成本。虽然初步报告表明，太赫兹辐射对乳腺标本产生的图像可以准确区分乳腺癌与正常纤维腺组织和脂肪组织（比x射线成像具有更高的特异性），但在拟议的努力中所面临的挑战是进一步研究使用太赫兹成像在术中评估肿瘤边缘的性能。以及开发一种技术（使用频域技术），该技术将允许紧凑和低成本的太赫兹成像，从而最大限度地发挥其转化为临床实践的潜力。提案说明了我们实现这一最终目标的计划。具体来说，我们的目标是进一步开发一种现有的设备，对切除的乳房标本进行线扫描，创建病变边缘的二维表面图。开发将包括太赫兹组织相互作用的建模，为正常（脂肪/脂肪，纤维/腺体）和恶性组织创建组织模拟模型，成像模型，最后是乳房标本。切除的乳腺组织薄样本的太赫兹图像将与组织学图像进行比较，并用几种不同的技术对结果进行分析。我们还将获得类似标本的太赫兹光谱，并分析这些已知过表达蛋白和其他潜在癌症生物标志物的特征。最后，我们将描述我们如何计划在未来将这种太赫兹成像技术转化为临床应用。

DESCRIPTION (provided by applicant): The overall goal of this proposed research is to design, develop and translate into clinical practice a new compact terahertz (THz) imaging device for accurately assessing positive breast cancer margins during surgical breast conservation procedures (i.e., lumpectomy). In breast conservation surgery (BCS), the surgeon attempts to remove malignant tissue with a surrounding margin of healthy tissue. After the surgical excision of the tumor, the specimen is submitted to pathology for evaluation to determine if the margins are clear of malignant tissue. Pathological analysis typically requires at least one day before results can be ascertained. Surprisingly, pathologic analysis currently indicates positive tumor margins about 40-50% of the time [Dillon 2007; Fleming 2004; Jacobs 2008; Waljee 2008], thereby requiring that the patient undergo a surgical re- excision procedure to remove additional breast tissue. We explain in this proposal how the proposed real-time terahertz imaging method can potentially provide accurate performance in assessing margins intra-operatively, thus eliminating many of the disadvantages with the currently used procedures, and ultimately decreasing healthcare costs. While preliminary reports have suggested that images produced with THz radiation applied to breast specimens can accurately differentiate between breast carcinoma and normal fibroglandular and adipose tissue (with much greater specificity than x-ray imaging), the challenge undertaken in the proposed effort is to further study the performance of using THz imaging to intra-operatively assess tumor margins, as well as to develop a technology (using frequency domain techniques) which will allow compact and low-cost THz imaging, thus maximizing its potential for translation into clinical practice. The proposal explains our plans for accomplishing this ultimate goal. Specifically, we aim to further develop an existing apparatus that performs line- scanning of excised breast specimens, creating a 2D surface map of lesion margins. Development will consist of modeling THz-tissue interactions, creating tissue-simulated phantoms for normal (fatty/adipose, fibrous/glandular) and malignant tissue, imaging phantoms and finally breast specimens. Terahertz images of excised thin samples of breast tissue will be compared with histological images and the results analyzed with several different techniques. We will also obtain THz spectra of similar specimens and analyze these for signatures of known over-expressed proteins and other potential biomarkers for cancer. Finally, we will describe how we plan to translate this THz imaging technique into clinical use in the future. PUBLIC HEALTH RELEVANCE: We propose investigating a technology that will enable surgeons to detect cancerous tissue margins in real-time and in intraoperational settings; eliminating in many cases the need for repeat surgery due to post-surgical histopathological determination of remaining malignant tissue (i.e., "positive margins"). Repeat surgeries come at significant fiscal, temporal, and emotional cost for both patients and medical providers and reducing the need for them represents a clear and immediate benefit to humanity.