Raman Tomography of Musculoskeletal Tissue

描述（由申请人提供）：我们将开发拉曼断层扫描，这是一种非侵入性平台技术，用于从活体动物和人类受试者中恢复空间和光谱信息。拉曼断层扫描将提供皮肤以下1厘米深度的骨质量测量。可用的质量指标将包括矿物/基质比、矿物结晶度、碳酸盐/磷酸盐比和胶原-纤维交联状态。该技术只需要一台连续波激光器、一台成像光谱仪和CCD探测器。将使用两个专门设计的光纤探头，提供形状和分布的激光来激发光谱，以及50个或更多的收集光纤阵列来恢复光谱。在组织光学测量的指导下，将开发用于快速深层组织光谱的环/盘探针。同样，将开发用于恢复光谱图像的层析探针。经过验证的化学计量学和层析成像信号恢复算法的改进版本将用于恢复光谱和骨质量指标。我们将研究信号采集时间、深度穿透和空间/频谱细节之间的权衡。优化后的探针将用于野生型小鼠和IV型成骨不全模型brtl的骨折愈合研究。研究将在8周组织再生期的4个时间点对麻醉的活体小鼠和动物切除的肢体进行。切除的肢体可以通过直接测量解剖、切片组织来验证。猪模型将被用作人类受试者的模型，因为皮肤和肌腱光学的相似性，允许进行尸体胫骨和桡骨远端组织的拉曼断层扫描。最后，我们将演示应用于人类受试者使用关节成形术患者的骨组织暴露在手术中，允许测量验证。虽然这个项目的重点是骨组织，但这项技术是广泛适用的。

DESCRIPTION (provided by applicant): We will develop Raman tomography, a non-invasive platform technology, for the recovery of spatial and spectral information from live animals and human subjects. Raman tomography will provide measurements of bone quality at depths of up to 1 cm below the skin. Available quality indicators will include mineral/matrix ratio, mineral crystallinity and carbonate/phosphate ratio and collagen-fibril cross-link state. The technology requires only a CW laser, an imaging spectrograph and CCD detector. Two specially designed fiber optic probes that provide shaped and distributed laser light to excite spectra and an array of 50 or more collection fibers to recover spectra will be used. Guided by tissue optics measurements, a ring/disk probe will be developed for rapid, deep tissue spectroscopy. Similarly, a tomographic probe will be developed for recovery of spectroscopic images. Modified versions of proven chemometric and tomographic signal recovery algorithms will be used to recover spectra and bone quality indicators. We will investigate trade-offs among signal acquisition time, depth penetration and spatial/spectral detail. Optimized probes will be used to study fracture healing in wild type mice and brtl, a model of osteogenesis imperfecta type IV.. Studies will be performed on live anaesthetized mice and on excised limbs from animals sacrificed at four time points in the eight week tissue regeneration period. Excised limbs allow validation by direct measurement of dissected, sectioned tissue. Porcine models will be used as models for human subjects, because of similarities of skin and tendon optics, allowing progression to Raman tomography of cadaveric tibial and distal radius tissue. Finally, we will demonstrate application to human subjects using arthroplasty patients whose bone tissue is exposed during surgery, allowing measurement validation. Although the focus of this project is on bone tissue, the technology is broadly applicable. Relevance to public health: Raman tomography provides new information for assessment of bone quality and fracture risk unavailable by DEXA or micro-MRI. The instruments used are small, safe and non-invasive, requiring only that a laser light be shined on the subject's skin. The technology is also readily adapted to measurement of other important health indicators, including presence and extent of atherosclerotic plaque and levels of serum cholesterol.