Raman spectroscopy as a non-invasive, transcutaneous tool for characterizing bone health

摘要 骨质疏松症是一种多因素的骨骼疾病，导致骨骼变弱，更容易患上骨质疏松症 骨折。这种疾病的患病率随着年龄的增长而增加，女性被诊断出来的可能性是 年龄相仿的男人。在临床上，骨质疏松症是通过测量骨密度(BMD)来诊断的。 通过双能X射线吸收法。需要额外的指标来增加BMD，以便增加 对骨折风险的敏感性。拉曼光谱是一种测量分子振动的光学技术 模式，产生样本的生化特征。从这个生化特征来看，体内的相对变化 骨矿化和基质被量化，并有助于骨折风险评估。通过在空间上利用 偏移拉曼光谱(SORS)，骨标本可以经皮肤和非侵入性测量， 然而，测量的信号将包含来自软组织和骨骼的光谱峰值。由于两种软组织 而骨骼中含有I型胶原造成谱峰重叠，则必须抑制软组织信号。 为了应对这一挑战，我们开发了一种复杂的算法来去除软组织光谱，称为 《通过同时过约束的基于库的分解的顶层减法》(SOL/TLS)以准确地 描述骨骼健康的特征。我们的团队已经证明，SOR可以在体内测量小鼠的骨骼，并通过 实施SALD/TLS，软组织信号被抑制，可以准确地预测骨骼 生物力学特性。这项提议旨在验证我们的拉曼光谱技术是一种临床前技术， 骨骼评估工具。在这里，我们将专注于将我们的方法转换为人类测量。目标 本项目的主要目的是：1)确定最佳的源-探测器偏移量，以指导放大SOR的设计 人身体手和掌骨可重复经皮测量的光纤束 目的2)论证经皮掌骨SORS测量在诊断中的潜力。 骨质疏松的手部样本。通过完成这些目标，我们将确定拉曼光谱的能力 作为一种临床前工具，用于表征骨骼质量和健康状况，帮助进行骨折风险评估。

Abstract Osteoporosis is a multifactorial bone disease that causes bones to weaken and become more susceptible to fracture. The prevalence of this disease increases with age, and women are twice as likely to be diagnosed than men at comparable ages. Clinically, osteoporosis is diagnosed by measuring bone mineral density (BMD) through dual-energy X-ray absorptiometry. Additional metrics are needed to augment BMD in order to increase the sensitivity for fracture risk. Raman spectroscopy is an optical technique that measures molecule’s vibrational modes, yielding a biochemical signature of the sample. From this biochemical signature, relative changes within the bone mineralization and matrix are quantified and can aid in fracture risk assessment. By utilizing spatially offset Raman spectroscopy (SORS), bone specimens can be measured transcutaneously and noninvasively, however the measured signal will contain spectral peaks from the soft tissue and bone. Since both soft tissue and bone contain type I collagen causing overlapping spectral peaks, the soft tissue signal must be suppressed. To address this challenge, we have developed an intricate algorithm to remove the soft tissue spectra called “top-layer subtraction via simultaneous over-constrained library-based decomposition” (SOLD/TLS) to accurately characterize bone health. Our group has demonstrated that SORS can measure murine bones in vivo, and by implementing SOLD/TLS, the soft tissue signal was suppressed, and that we can accurately predict bone biomechanical properties. This proposal aims to validate our Raman spectroscopy techniques as a preclinical, bone assessment tool. Here, we will focus on translating our methodologies to human measurements. The aims of this project are: Aim 1) Determine optimal source-detector offsets to guide the design of a scaled up SORS optical fiber bundle for reproducible transcutaneous measurements of metacarpals in human cadaver hands and Aim 2) Demonstrate the potential of transcutaneous SORS measurements of metacarpal bones in diagnosing osteoporotic hand samples. By completing these Aims, we will determine Raman spectroscopy’s capability to serve as a preclinical tool for characterizing bone quality and health, to aid in fracture risk assessment.