CAREER: Photoacoustic-Brillouin microscopy for multimodal mechanical imaging of tumor growth

职业：用于肿瘤生长多模态机械成像的光声布里渊显微镜

• 批准号: 2339278
• 负责人: Jitao Zhang
• 金额: $ 50.21万
• 依托单位: Wayne State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-07-01 至 2029-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2339278&HistoricalAwards=false
• 关键词: CAREER; Photoacoustic; Brillouin; microscopy; multimodal

Tumor tissues are usually harder than surrounding healthy tissues, leading to a different microenvironment for cancer cells inside. Since the behaviors and functions of cells are regulated by physical cues from their microenvironment, emerging research has suggested that the altered mechanics of tumor tissue plays a crucial role in the progression of metastatic cancers. To understand the relationship between the properties of the microenvironment and tumor growth, it is essential to quantify these mechanical properties with high spatial resolution in three dimensions. However, existing mechanical testing tools are mostly contact-based and invasive, making such measurement highly challenging. This Faculty Early Career Development (CAREER) project aims to address the current technical challenge by developing an optical technology named photoacoustic-Brillouin microscopy (PABM), which can measure the mechanical properties of cancer cells and their microenvironment in a non-contact, non-invasive, and high-resolution manner. In concert with the research goal, this project will develop educational modules to promote the dissemination of the innovative Brillouin technology and to stimulate a lasting interest in biophotonics for high school, undergraduate, and graduate students.Confocal Brillouin microscopy has been recently demonstrated as a promising non-contact mechanical testing tool. However, due to the lack of knowledge on refractive index and density of the sample under test, existing Brillouin microscopy is mostly used to estimate the relative mechanical change, rather than to provide an absolute measurement of mechanical modulus, making it inapplicable for heterogeneous tumor microenvironment, benchmarking, and comparison across studies. In this project, a novel optical technique named PABM will be developed based on the colocalized excitation of scattered Brillouin light and time-resolved photoacoustic signals. In addition to directly quantifying mechanical modulus, the PABM can provide complementary contrast mechanisms, including stiffness, optical absorption, and acoustic speed. This capability will enable a comprehensive understanding of heterogeneous processes in tumor growth. Taken together, the PABM addresses a significant gap in current cancer research methodologies. The new data and insights gained from this technology holds a unique potential to advance a wide range of research in both biophotonics and cancer diseases.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

肿瘤组织通常比周围的健康组织更硬，导致内部癌细胞的微环境不同。由于细胞的行为和功能受到微环境物理信号的调节，新兴研究表明，肿瘤组织力学的改变在转移性癌症的进展中发挥着至关重要的作用。为了了解微环境特性与肿瘤生长之间的关系，必须在三个维度上以高空间分辨率量化这些机械特性。然而，现有的机械测试工具大多是接触式和侵入式的，使得这种测量极具挑战性。该教师早期职业发展（CAREER）项目旨在通过开发一种名为光声布里渊显微镜（PABM）的光学技术来解决当前的技术挑战，该技术可以在非接触式、非接触式的环境中测量癌细胞及其微环境的机械特性。侵入式、高分辨率的方式。与研究目标相一致，该项目将开发教育模块，以促进创新布里渊技术的传播，并激发高中生、本科生和研究生对生物光子学的持久兴趣。共焦布里渊显微镜最近被证明是一种有前途的技术非接触式机械测试工具。然而，由于缺乏对待测样品的折射率和密度的了解，现有的布里渊显微镜大多用于估计相对机械变化，而不是提供机械模量的绝对测量，使其不适用于异质肿瘤微环境、基准测试和研究之间的比较。在该项目中，将基于散射布里渊光和时间分辨光声信号的共定位激发开发一种名为 PABM 的新型光学技术。除了直接量化机械模量之外，PABM 还可以提供补充对比机制，包括刚度、光吸收和声速。这种能力将使人们能够全面了解肿瘤生长的异质过程。总而言之，PABM 解决了当前癌症研究方法中的一个重大差距。从这项技术中获得的新数据和见解具有独特的潜力，可以推动生物光子学和癌症疾病的广泛研究。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响进行评估，被认为值得支持审查标准。