Raman spectroscopic measurement of bone composition has shown promise as a medical diagnostic by measuring the
molecular composition of the bone mineral and matrix. We previously demonstrated proof-of-principle transcutaneous
Raman spectroscopy bone measurements in human cadavers. In this paper, we discuss further optimization of the
instrumental configuration for efficient collection of bone signal using contact fiber-optic probe designs. To optimize
collection of Raman signal through overlaying soft tissue, novel geometrically-accurate tissue phantoms were prepared.
MRI and CT images of the human cadaveric specimens were used to create solid tissue phantoms with accurate
geometric dimensions. In these tissue phantoms, optical properties can be varied systematically. Raman spectra of the
prepared tissue phantoms were used to optimize the positions of the fibers in the fiber optic system, and the laser
illumination sequence in the measurements. Three fiber optic probes were developed and tested with both novel tissue
phantoms and human cadaveric specimens. The contact fiber optic probes were developed for arthroscopic
measurements of joints, for transcutaneous measurements of bone in situ, and for contact measurements of exposed
bone. By coupling the fiber optic probe to an imaging spectrograph, spectra were collected simultaneously at many
positions on the tissue. Furthermore, spectra were collected with several different excitation laser patterns to enhance the
effective spatial resolution of the measurements. Finally, a series of improvements were made in the data preprocessing
to improve the recovered spectral signal. Together, these modifications improve signal-to-noise and spatial resolution.