Michael Albro

Raman Spectroscopic Diagnostics of Intervertebral Disk Degeneration

PROJECT DESCRIPTION
The intervertebral disk (IVD) is a specialized connective tissue situated in between adjacent vertebrae to function as a cushion-like shock absorber. The composition and structure of the IVD is optimized for its mechanical performance, consisting of an inner proteoglycan-rich nucleus pulposus (NP), which pressurizes in response to mechanical compressive loading, and an outer collagen-rich fibrocartilage annulus fibrosus (AF), which restricts NP lateral expansion, allowing for the maintenance of its load-bearing pressurized state. Degenerative disk disease—one of the leading causes of disability in the adult population—is associated with compositional/structural changes to the IVD, such as NP herniation or proteoglycan loss. While an assortment of promising degenerative therapies are emerging for potential use in patients (e.g. injectable hydrogels, biologics), clinical translation is hindered by limitations in current state-of-the-art imaging platforms to monitor the composition of the IVD and thus establish the efficacy of emerging therapies in mitigating or restoring IVD compositional health.

Recently, the Albro Lab has developed a novel arthroscopic Raman needle probe for performing the first-ever in vivo diagnostics of the composition of musculoskeletal connective tissues. Recent work has established the capability of the platform to: 1) generate Raman-derived ECM specific biomarkers, which can predict 80% of the variation of proteoglycan content and 70% of the variation of elastic modulus of articular cartilage ex vivo over a range of degenerative states, and 2) acquire Raman ECM biomarkers in vivo of the articular cartilage of a live sheep during knee arthroscopy. Together, these characterizations serve as strong support with the capability of our Raman probe platform to serve as a clinical tool for monitoring connective tissue degeneration and restoration.

In the current project, we aim to examine the capability of advancing this novel technology towards diagnosing IVD degeneration and monitoring its response to emerging treatments. To this end, the ability of our Raman probe to monitor IVD composition will be assessed in ex vivo degenerative model systems, including bovine IVDs of varying age and IVDs subjected to enzymatic degeneration.

LABORATORY MENTOR
Erik Ersland

RESEARCH GOALS
– Evaluate the capability of our Raman spectroscopic platform, as a nondestructive, label-free measurement, to quantify the relative contribution of key biochemical constituents of IVDs for determining tissue composition and predicting functional material properties. The platform will be applied to bovine IVDs subjected to varying degrees of enzymatic (trypsin) degeneration and bovine IVDs from a range of animal ages (2 month, 1 year, 3 year, 10 year), where degeneration is more prominent for older age animals.
– Analyze IVDs for Raman-derived biomarkers, mechanical properties (aggregate modulus, fluid permeability), and biochemical composition.
– Test the hypothesis that Raman-derived biomarkers can predict the variability of IVD composition and material properties with an R2 >0.7.

LEARNING GOALS
– Learn an extensive array of interdisciplinary skills including harvesting tissue, Raman spectroscopic measurements and data analysis, mechanical testing, biochemical analysis of GAG assay, and histology preparation.
– Improve critical thinking and problem-solving skills.
– Enhance presentation and science communication skills by performing monthly research presentation in the Albro Lab’s project meeting.

Learn more about Assistant Professor Michael Albro on his  faculty page.