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，用于在外科乳腺保乳手术(即肿块切除术)中准确评估阳性乳腺癌边缘。在保乳手术(BCS)中，外科医生试图切除周围有健康组织的恶性组织。在手术切除肿瘤后，标本被提交给病理学进行评估，以确定边缘是否没有恶性组织。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，病理分析目前显示约40%-50%的肿瘤边缘呈阳性[Dillon 2007；Fleming 2004；Jacobs 2008；Waljee 2008]，因此需要患者接受再次手术切除额外的乳房组织。我们在这份提案中解释了拟议的实时太赫兹成像方法如何潜在地在评估术中边缘方面提供准确的性能，从而消除了当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，应用于乳腺标本的THz辐射产生的图像可以准确区分乳腺癌和正常纤维腺组织和脂肪组织(比X光成像具有更高的特异性)，但拟议工作中面临的挑战是进一步研究使用THz成像在术中评估肿瘤边缘的性能，以及开发(使用频域技术)能够实现紧凑和低成本THz成像的技术，从而最大限度地将其转化为临床实践。该提案解释了我们实现这一最终目标的计划。具体地说，我们的目标是进一步开发一种现有的设备，对切除的乳房样本执行行扫描，创建病变边缘的2D表面地图。开发将包括模拟太赫兹与组织的相互作用，为正常组织(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。对切除的乳腺组织薄样的太赫兹图像将与组织图像进行比较，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，并分析这些已知的过度表达蛋白质和其他潜在的癌症生物标记物的特征。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，使外科医生能够实时和在术中环境中检测癌组织边缘；在许多情况下，消除了由于术后组织病理学确定残留的恶性组织(即“阳性边缘”)而再次手术的需要。重复手术对患者和医疗提供者来说都会带来巨大的财政、时间和情感成本，减少对它们的需求对人类来说是明显和直接的好处。

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.