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，变得更容易受到 骨折这种疾病的患病率随着年龄的增长而增加，女性被诊断的可能性是男性的两倍。 年龄相仿的男性。临床上，骨质疏松症的诊断是通过测量骨矿物质密度（BMD） 通过双能X线吸收法需要额外的指标来增加BMD， 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，产生样品的生化特征。从这个生化特征来看， 骨矿化和基质被量化，并且可以帮助骨折风险评估。在空间上利用 偏移拉曼光谱（SORS），可以对骨样本进行透射和非侵入性测量， 然而，所测量的信号将包含来自软组织和骨骼的谱峰。因为软组织 并且骨包含I型胶原，导致重叠的光谱峰，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 “通过同时基于过约束库的分解进行顶层减法”（SOLD/TLS）， 表征骨骼健康。我们的研究小组已经证明，SORS可以测量小鼠体内的骨骼， 实施SOLD/TLS，软组织信号被抑制，我们可以准确地预测骨 生物力学性能该提案旨在验证我们的拉曼光谱技术作为临床前， 骨评估工具。在这里，我们将专注于将我们的方法转化为人类测量。目标 目标1）确定最佳的源-探测器偏移量，以指导按比例放大的SORS的设计 用于人尸体手掌骨的可重复经皮测量的光纤束， 目的2）探讨经皮掌骨SORS测量在掌骨骨折诊断中的应用价值 手工标本。通过完成这些目标，我们将确定拉曼光谱的能力， 作为表征骨骼质量和健康的临床前工具，以帮助骨折风险评估。

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.