Contrast-enhanced CT facilitates rapid, non-destructive assessment of cartilage and bone properties of the human metacarpal B.A. Lakin, D.J. Ellis, J.S.

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Contrast-enhanced CT facilitates rapid, non-destructive assessment of cartilage and bone properties of the human metacarpal B.A. Lakin, D.J. Ellis, J.S. Shelofsky, J.D. Freedman, M.W. Grinstaff, B.D. Snyder Osteoarthritis and Cartilage Volume 23, Issue 12, Pages 2158-2166 (December 2015) DOI: 10.1016/j.joca.2015.05.033 Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions

Fig. 1 Representative color maps from a central, sagittal, CECT slice for the metacarpal sample with a) the highest GAG content and b) the lowest GAG content, as well as the corresponding Safranin-O stained histological section. Color scale bar indicates corresponding CECT attenuation in Hounsfield Units (HU) for all CECT color maps. The distribution of the CA4+ contrast agent (top row in a & b) more clearly matches the distribution of the Safranin-O stain than does that of Ioxaglate (bottom row in a & b) for both samples. For easier comparison with the corresponding histological sections, the middle column displays a magnified image of region indicated by the red box on the full-size color maps. Osteoarthritis and Cartilage 2015 23, 2158-2166DOI: (10.1016/j.joca.2015.05.033) Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions

Fig. 2 Correlations for human metacarpal cartilage samples: CECT Attenuation (HU) vs a) GAG Content (% of cartilage wet mass) and b) mean Ip value (a measure of red pixel density from Safranin-O stained histological sections that is indicative of GAG). c) GAG content (■) and axial rigidity (□, GAG content multiplied by cartilage thickness) vs indentation equilibrium modulus (E); and d) CECT attenuation vs E. For CECT attenuations, unfilled data points indicate the Ioxaglate data, while filled data points represent the CA4+ data. All correlations were strong (R2 ≥ 0.70) and significant (P < 0.05), except for the correlations involving Ioxaglate (R2 ≤ 0.24, P > 0.05). Osteoarthritis and Cartilage 2015 23, 2158-2166DOI: (10.1016/j.joca.2015.05.033) Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions

Fig. 3 (a) A significant positive correlation between subchondral bone plate mineral density (SBP BMD) and SBP thickness. Representative sagittal μCT slices reflecting the SBP BMD vs SBP relationship for a sample with b) thick and c) thin SBP is shown. The region within the red box has been magnified to highlight this positive correlation. Osteoarthritis and Cartilage 2015 23, 2158-2166DOI: (10.1016/j.joca.2015.05.033) Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions

Fig. 4 Correlations between the subchondral trabecular network properties and GAG content: a) bone volume fraction (■, %BV/TV) vs GAG content and structural model index (□, SMI) vs GAG Content, b) Trabecular Number (Tb.N) vs GAG content, c) Trabecular Thickness (Tb.Th) vs GAG content, and d) Trabecular Spacing (Tb.Sp) vs GAG content. As GAG content declines, the %BV/TV decreases, SMI increases (transitioning from plate to rod-like trabeculae), Tb.N decreases, Tb.Th decreases and Tb.Sp increases. All correlations were significant (P < 0.05). Osteoarthritis and Cartilage 2015 23, 2158-2166DOI: (10.1016/j.joca.2015.05.033) Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions

Fig. 5 Representative CT images for a sample with a) the highest GAG content and b) the lowest GAG content. From a two-dimensional (2D) μCT scan (III, IV), one can construct (I, II) a three-dimensional (3D) CECT color map (CA4+ enhanced CT scan shown), and (V, VI) a 3D reconstruction of the subchondral trabecular network. Unlike histology, which only permits 2D sectioning along one plane and is both time-consuming and destructive, CECT enables rapid, facile, non-destructive (I, II) 3D color maps indicative of cartilage GAG content and compressive stiffness, and (V, VI) the subchondral trabecular network, which can be visually sectioned in real-time in one to three planes simultaneously. Color scale bar indicates corresponding CECT attenuation in Hounsfield Units (HU) for all CECT color maps. Osteoarthritis and Cartilage 2015 23, 2158-2166DOI: (10.1016/j.joca.2015.05.033) Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions