Coupling Advanced Computational Analyses for Mammography and SHG Imaging for Early Detection of Breast Cancer Tissue Microenvironment Disruptions Accompanying Tumorigenesis

摘要 乳腺癌的微环境在癌症的早期发展中起着关键作用。一个 对肿瘤微环境的更好理解将有助于疾病的早期发现和 开发新的、更有效的疗法。目前对乳房X光检查的放射学解释是 基于识别乳房病变并评估其潜在的恶性和致命性。生物医学 研究界尚未将微环境改变和乳房X光检查的特征联系起来 在肿瘤发生过程中，甚至在肿瘤发生之前，组织动态平衡的丧失。 PI最近使用了一种新颖而强大的计算技术来演示组织 动态平衡的破坏和丧失可以从标准临床中进行定量和客观的评估 乳房X光检查。这些初步发现仅与单一诊断性乳房X光检查有关；拟议的 Area Project将分析之前多年的乳房X光检查的纵向序列，以及 临近诊断年，从而揭示健康乳腺组织微环境的进展 走向混乱的状态。据推测，组织混乱的特征存在于 乳房X光检查数据与组织破坏和组织内稳态的丧失有关 微环境。团队成员将通过成像乳房组织样本来验证这一假设 在细胞水平上表征与肿瘤微环境相关的胶原结构的破坏 伴随肿瘤发生的改变。 该项目的具体目标包括：1)验证乳房X光检查组织破坏 伴随甚至可能先于肿瘤的发展；2)开发一种电子计算机模型 乳腺X线摄影组织环境中的微钙化生长，3)改进计算 我们数据分析的效率，以及4)将乳腺肿瘤微环境的形态特征联系起来 由乳房X光摄影成像到二次谐波产生显微镜成像的细胞尺度的改变。 拟议的研究将促进本科生的教育和职业准备 缅因州唯一的生物医学工程项目，培育了缅因州大学之间日益增长的合作伙伴关系 缅因州，Spectrum Healthcare Partners和缅因州医学研究所，引进两名UMaine教师 用于生物医学研究，并支持两名助理教授的早期职业发展。

Summary The breast tumor microenvironment plays a key role in the early development of cancer. An improved understanding of the tumor microenvironment will support the early detection of disease and the development of novel, more effective therapies. Current radiological interpretation of mammograms is based on identifying breast lesions and assessing their potential malignancy and lethality. The biomedical research community has yet to correlate the mammographic signatures of microenvironment alterations and loss of tissue homeostasis accompanying, or even preceding tumorigenesis. The PI recently used a novel and powerful computational technique to demonstrate that tissue disruption and loss of homeostasis can be quantitatively and objectively assessed from standard clinical mammography. These preliminary findings pertain only to single diagnostic mammograms; the proposed AREA project will analyze longitudinal sequences of mammograms over multiple years prior to, and approaching the year of diagnosis, thus revealing the progression of healthy breast tissue microenvironment towards a disrupted state. It is hypothesized that the tissue disorganization signature present in mammographic data is associated with tissue disruption and loss of tissue homeostasis in the microenvironment. Team members will verify this hypothesis by imaging breast tissue samples to characterize, at the cellular level, disruption of collagen structures associated to tumor microenvironment alterations accompanying tumorigenesis. This project's specific aims include: 1) verifying that mammographic tissue disruption accompanies and perhaps even precedes tumor development; 2) developing an in silico model of microcalcification growth into mammographic breast tissue environment, 3) improving the computational efficiency of our data analysis, and 4) linking morphological features of the breast tumor microenvironment imaged by mammography to cellular-scale alterations imaged by second harmonic generation microscopy. The proposed research will advance the education and career preparation of undergraduates within Maine's only biomedical engineering program, nurture a growing partnership among the University of Maine, Spectrum Healthcare Partners and Maine Medical Research Institute, introduce two UMaine faculty to biomedical research, and support the early career development of two assistant professors.