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、开发一种新的紧凑型太赫兹（THz）成像设备并将其转化为临床实践，用于在乳房保护手术期间准确评估阳性乳腺癌边缘（即，肿瘤切除术）。在保乳手术（BCS）中，外科医生试图切除恶性组织，周围是健康组织。在手术切除肿瘤后，将标本提交病理学进行评估，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的时间才能确定结果。令人惊讶的是，目前病理分析表明约40-50%的时间肿瘤边缘呈阳性[Dillon 2007; Fleming 2004; Jacobs 2008; Waljee 2008]，因此需要患者接受手术再切除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能够在术中评估边缘时提供准确的性能，从而消除目前使用的程序的许多缺点，并最终降低医疗成本。虽然初步报告表明，太赫兹辐射产生的图像应用于乳房标本可以准确地区分乳腺癌和正常的纤维腺体和脂肪组织，（具有比X射线成像大得多的特异性），在所提出的努力中进行的挑战是进一步研究使用THz成像来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），这将允许紧凑和低成本的太赫兹成像，从而最大限度地提高其转化为临床实践的潜力。该提案解释了我们实现这一最终目标的计划。 具体而言，我们的目标是进一步开发现有的设备，该设备对切除的乳房标本进行线扫描，创建病变边缘的2D表面图。开发将包括太赫兹-组织相互作用建模，为正常（脂肪/脂肪，纤维/腺体）和恶性组织创建组织模拟体模，成像体模，最后是乳房标本。切下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，并使用几种不同的技术分析结果。我们还将获得类似标本的THz光谱，并分析这些已知过度表达蛋白质和其他潜在癌症生物标志物的特征。最后，我们将描述我们计划如何将这种太赫兹成像技术转化为未来的临床应用。 公共卫生相关性：我们建议研究一种技术，该技术将使外科医生能够在实时和术中环境中检测癌组织边缘;在许多情况下，由于剩余恶性组织的术后组织病理学确定而消除重复手术的需要（即，“正边缘”）。重复手术对患者和医疗提供者来说都是巨大的财政，时间和情感成本，减少对它们的需求对人类来说是一个明确而直接的好处。

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.