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.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Enabling Bioanalytical and Biophysical Technologies Study Section (EBT)
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Lester, Gayle E
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University of Michigan Ann Arbor
Schools of Arts and Sciences
Ann Arbor
United States
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Demers, Jennifer-Lynn H; Esmonde-White, Francis W L; Esmonde-White, Karen A et al. (2015) Next-generation Raman tomography instrument for non-invasive in vivo bone imaging. Biomed Opt Express 6:793-806
Peterson, Jonathan R; Eboda, Oluwatobi N; Brownley, R Cameron et al. (2015) Effects of aging on osteogenic response and heterotopic ossification following burn injury in mice. Stem Cells Dev 24:205-13
Peterson, Jonathan R; De La Rosa, Sara; Eboda, Oluwatobi et al. (2014) Treatment of heterotopic ossification through remote ATP hydrolysis. Sci Transl Med 6:255ra132
Esmonde-White, Karen A; Esmonde-White, Francis W L; Morris, Michael D et al. (2014) Characterization of biofluids prepared by sessile drop formation. Analyst 139:2734-41
Tchanque-Fossuo, Catherine N; Gong, Bo; Poushanchi, Behdod et al. (2013) Raman spectroscopy demonstrates Amifostine induced preservation of bone mineralization patterns in the irradiated murine mandible. Bone 52:712-717
Kunstar, Aliz; Leferink, Anne M; Okagbare, Paul I et al. (2013) Label-free Raman monitoring of extracellular matrix formation in three-dimensional polymeric scaffolds. J R Soc Interface 10:20130464
Esmonde-White, Karen A; Esmonde-White, Francis W L; Holmes, Crystal M et al. (2013) Alterations to bone mineral composition as an early indication of osteomyelitis in the diabetic foot. Diabetes Care 36:3652-4
Gong, Bo; Oest, Megan E; Mann, Kenneth A et al. (2013) Raman spectroscopy demonstrates prolonged alteration of bone chemical composition following extremity localized irradiation. Bone 57:252-8
Peterson, Jonathan R; Okagbare, Paul I; De La Rosa, Sara et al. (2013) Early detection of burn induced heterotopic ossification using transcutaneous Raman spectroscopy. Bone 54:28-34
Okagbare, Paul I; Morris, Michael D (2012) Polymer-capped fiber-optic Raman probe for non-invasive Raman spectroscopy. Analyst 137:77-81

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