A New Platform for Biomechanical Imaging Based on Brillouin Scattering

基于布里渊散射的生物力学成像新平台

• 批准号: EP/M028739/1
• 负责人: Francesca Palombo
• 金额: $ 14.64万
• 依托单位: UNIVERSITY OF EXETER
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FM028739%2F1
• 关键词: New; Platform; Biomechanical; Imaging; Based

Mechanical changes in body tissues are widely associated with diverse clinical problems including many of the serious complications of diabetes, atherosclerosis and cancer, but their microstructural bases are poorly understood. In large blood vessels, stiffness is linked to increased risk of cardiovascular mortality - although the contribution of the stiffness from individual tissue constituents to this risk is unknown. Understanding the mechanisms linking stiffness to structure is limited by our ability to measure mechanical properties on length-scales which allow the relationships with tissue structure and composition to be established. BLS microscopy has the potential to fill this void, as demonstrated in a recent publication (Palombo, Madami, Stone and Fioretto, Analyst, 2014, 139, 729-733) where mechanical maps of structure and elasticity were generated based on Brillouin peaks corresponding to specific tissue components. New techniques of imaging the chemical composition of cells and tissues are making a major impact in many fields of biology and medicine. This proposal is concerned with the development of Brillouin light scattering (BLS) imaging, a new method for microscopic imaging of mechanical properties. The mechanical properties of the connective tissues, cartilage or blood vessels are central to their physiological function and changes in mechanical function are implicated in diseases ranging from diabetes to osteoarthritis. BLS imaging therefore offers the prospect of directly imaging a functionally important property, both in tissues and single constituents e.g. collagen and elastin fibres, whose biomechanics probed at multiple frequencies are almost completely unexplored, which will open a new window on tissue mechanics and offers the prospect of developing new diagnostic techniques.The principle of the approach is to detect the change in frequency of inelastically scattered light arising from the generation of sound waves in the sample. Calculation of the speed of the wave provides a measure of the mechanical properties of the material. Preliminary studies have used confocal BLS microscopy to produce Brillouin frequency maps of an epithelial tissue, which can be combined with Raman micro-spectroscopic maps of chemical composition (Palombo et al. Analyst 2014). Complementary studies have investigated Brillouin scattering in collagen and elastin, the fibrous proteins of the extracellular matrix, and their relationships to fibre micromechanics (Palombo et al. J R Soc Interface, asap).This work provides the basis for the proposed investigations. The methodology will be applicable to many problems of connective tissue physiology and pathology, but the immediate aim will be to investigate the mechanics of extracellular protein fibres - collagens, elastin, proteoglycans - and the effects of physiological and pathological conditions. These changes are widely associated with diverse clinical problems including many of the serious complications of osteoarthritis and diabetes, but their microstructural bases are poorly understood. The project will require construction of a system that will enable biomechanical imaging through Brillouin scattering with a Virtually Imaged Phase Array (VIPA) spectrometer. This will enable us to develop a significantly faster and more versatile technology for the analysis of fibres (and tissues) and to define functionally significant changes which can, in the longer term, become targets for monitoring or therapeutic intervention.

身体组织中的机械变化与各种临床问题广泛相关，包括糖尿病、动脉粥样硬化和癌症的许多严重并发症，但对其微观结构基础知之甚少。在大血管中，硬度与心血管死亡风险增加有关-尽管个体组织成分的硬度对这种风险的贡献尚不清楚。理解连接刚度与结构的机制受到我们在长度尺度上测量机械性能的能力的限制，这使得能够建立与组织结构和组成的关系。BLS显微术具有填补该空白的潜力，如在最近的出版物（Palombo，Madami，Stone和Fioretto，Analyst，2014，139，729-733）中所证明的，其中基于对应于特定组织组分的布里渊峰生成结构和弹性的机械图。细胞和组织化学成分成像的新技术正在生物学和医学的许多领域产生重大影响。该建议涉及布里渊光散射（BLS）成像，一种新的方法，用于力学性能的显微成像的发展。结缔组织、软骨或血管的机械性能对其生理功能至关重要，并且机械功能的变化与从糖尿病到骨关节炎的疾病有关。因此，BLS成像提供了直接成像组织和单一成分（例如胶原和弹性蛋白纤维）中的功能重要性质的前景，其在多个频率下探测的生物力学几乎完全未被探索，该方法的原理是通过检测非弹性散射的频率变化，从而为组织力学的研究开辟了一个新的窗口，并为发展新的诊断技术提供了前景由样品中声波的产生而产生的光。波的速度的计算提供了材料的机械性能的测量。初步研究已经使用共焦BLS显微镜来产生上皮组织的布里渊频率图，其可以与化学组成的拉曼显微光谱图组合（Palombo等人，Analyst 2014）。补充研究已经研究了胶原蛋白和弹性蛋白中的布里渊散射，细胞外基质的纤维蛋白质，以及它们与纤维微观力学的关系（Palombo等人，J R Soc Interface，asap）。这项工作为拟议的研究提供了基础。该方法将适用于结缔组织生理学和病理学的许多问题，但直接的目标将是研究细胞外蛋白质纤维-胶原蛋白，弹性蛋白，蛋白多糖-和生理和病理条件的影响的力学。这些变化与各种临床问题广泛相关，包括骨关节炎和糖尿病的许多严重并发症，但其微观结构基础知之甚少。该项目将需要建造一个系统，该系统将通过布里渊散射与虚拟成像相控阵（VIPA）光谱仪实现生物力学成像。这将使我们能够开发出一种更快、更通用的技术来分析纤维（和组织），并确定功能上的重大变化，从长远来看，这些变化可以成为监测或治疗干预的目标。

项目成果

Viscoelastic properties of biopolymer hydrogels determined by Brillouin spectroscopy: A probe of tissue micromechanics.

• DOI: 10.1126/sciadv.abc1937
• 发表时间: 2020-10
• 期刊: Science advances
• 影响因子: 13.6
• 作者: Bailey M;Alunni-Cardinali M;Correa N;Caponi S;Holsgrove T;Barr H;Stone N;Winlove CP;Fioretto D;Palombo F
• 通讯作者: Palombo F

Applications of Brillouin light scattering within the biological environment

布里渊光散射在生物环境中的应用

• 发表时间: 2022
• 作者: Bailey Michelle Louise

Preparation of Extracellular Matrix Protein Fibers for Brillouin Spectroscopy.

• DOI: 10.3791/54648
• 发表时间: 2016-09-15
• 期刊: Journal of visualized experiments : JoVE
• 作者: Edginton RS;Mattana S;Caponi S;Fioretto D;Green E;Winlove CP;Palombo F
• 通讯作者: Palombo F

Brillouin-Raman microspectroscopy for the morpho-mechanical imaging of human lamellar bone.

• DOI: 10.1098/rsif.2021.0642
• 发表时间: 2022-03
• 期刊: Journal of the Royal Society, Interface
• 作者: Alunni Cardinali M;Di Michele A;Mattarelli M;Caponi S;Govoni M;Dallari D;Brogini S;Masia F;Borri P;Langbein W;Palombo F;Morresi A;Fioretto D
• 通讯作者: Fioretto D

Monitoring the refractive index of tissue models using light scattering spectroscopy

使用光散射光谱监测组织模型的折射率

• DOI: 10.48550/arxiv.2009.02274
• 发表时间: 2020
• 作者: Bailey M