J. van Tiel

Clinically applied CT arthrography to measure the sulphated glycosaminoglycan content of cartilage

OBJECTIVE Similar to delayed gadolinium enhanced MRI of cartilage, it might be possible to image cartilage quality using CT arthrography (CTa). This study assessed the potential of CTa as a clinically applicable tool to evaluate cartilage quality in terms of sulphated glycosaminoglycan content (sGAG) and structural composition of the extra-cellular matrix (ECM). METHODS Eleven human cadaveric knee joints were scanned on a clinical CT scanner. Of each knee joint, a regular non-contrast CT (ncCT) and an ioxaglate injected CTa scan were performed. Mean X-ray attenuation of both scans was compared to identify contrast influx in seven anatomical regions of interest (ROIs). All ROIs were rescanned with contrast-enhanced μCT, which served as the reference standard for sGAG content. Mean X-ray attenuation from both ncCT and CTa were correlated with μCT results and analyzed with linear regression. Additionally, residual values from the linear fit between ncCT and μCT were used as a covariate measure to identify the influence of structural composition of cartilage ECM on contrast diffusion into cartilage in CTa scans. RESULTS CTa resulted in higher X-ray attenuation in cartilage compared to ncCT scans for all anatomical regions. Furthermore, CTa correlated excellent with reference μCT values (sGAG) (R=0.86; R(2)=0.73; P<0.0001). When corrected for structural composition of cartilage ECM, this correlation improved substantially (R=0.95; R(2)=0.90; P<0.0001). CONCLUSIONS Contrast diffusion into articular cartilage detected with CTa correlates with sGAG content and to a lesser extent with structural composition of cartilage ECM. CTa may be clinically applicable to quantitatively measure the quality of articular cartilage.

CT arthrography of the human knee to measure cartilage quality with low radiation dose

OBJECTIVE Recently, CT arthrography (CTa) was introduced as a non-destructive technique to quantitatively measure cartilage quality in human knees. This study investigated whether this is also possible using lower radiation dose CT protocols. Furthermore, we studied the ability of (lower radiation) CTa to distinguish between local sulphated glycosaminoglycan (sGAG) content differences. DESIGN Of ten human cadaveric knee joints, six CT scans using different radiation doses (81.33-8.13 mGy) were acquired after intra-articular ioxaglate injection. The capability of CTa to measure overall cartilage quality was determined in seven anatomical regions of interest (ROIs), using equilibrium partitioning of an ionic contrast agent using (EPIC)-microCT (μCT) as reference standard for sGAG content. To test the capability of CTa to spatially distinguish between local differences in sGAG content, we calculated the percentage of pixels incorrectly predicted as having high or low sGAG content by the different CTa protocols. RESULTS Low radiation dose CTa correlated well with EPIC-μCT in large ROIs (R = 0.78; R(2) = 0.61; P < 0.0001). CTa can also distinguish between high and low sGAG content within a single slice. However, the percentage of incorrectly predicted quality pixels increases (from 35% to 41%) when less radiation is used. This makes is hard or even impossible to differentiate between spatial differences in sGAG content in the lowest radiation scans. CONCLUSIONS CTa acquired using low radiation exposure, comparable to a regular knee CT, is able to measure overall cartilage quality. Spatial sGAG distribution can also be determined using CTa, however for this purpose a higher radiation dose is necessary. Nevertheless, radiation dose reduction makes CTa suitable for quantitative analysis of cartilage in clinical research.

Micro- and nano-mechanics of osteoarthritic cartilage: The effects of tonicity and disease severity.

The present study aims to discover the contribution of glycosaminoglycans (GAGs) and collagen fibers to the mechanical properties of the osteoarthritic (OA) cartilage tissue. We used nanoindentation experiments to understand the mechanical behavior of mild and severe osteoarthritic cartilage at micro- and nano-scale at different swelling conditions. Contrast enhanced micro-computed tomography (EPIC-μCT) was used to confirm that mild OA specimens had significantly higher GAGs content compared to severe OA specimens. In micro-scale, the semi-equilibrium modulus of mild OA specimens significantly dropped after immersion in a hypertonic solution and at nano-scale, the histograms of the measured elastic modulus revealed three to four components. Comparing the peaks with those observed for healthy cartilage in a previous study indicated that the first and third peaks represent the mechanical properties of GAGs and the collagen network. The third peak shows considerably stiffer elastic modulus for mild OA samples as compared to the severe OA samples in isotonic conditions. Furthermore, this peak clearly dropped when the tonicity increased, indicating the loss of collagen (pre-) stress in the shrunk specimen. Our observations support the association of the third peak with the collagen network. However, our results did not provide any direct evidence to support the association of the first peak with GAGs. For severe OA specimens, the peak associated with the collagen network did not drop when the tonicity increased, indicating a change in the response of OA cartilage to hypertonicity, likely collagen damage, as the disease progresses to its latest stages.

419 CT ARTHROGRAPHY OF THE KNEE TO MEASURE CARTILAGE QUALITY WITH LOW RADIATION EXPOSURE

Introduction Novel imaging techniques which measure cartila ge quality in terms of the sulphated glycosaminoglycan (sGAG) content a re valuable in osteoarthritis (OA) research. An example of such an imaging technique is in vivo μCT arthrography in small animals . Recently, we showed that CT arthrography (CTa) performed on a clinical CT system using human cadaveric knees is also capable of measuring cartilage quality in terms of the sGAG content . Because of the relatively high radiation dose (~2 m Sv per scan) of the CTa protocol compared to a standard CT of the k nee (~0.2 mSv per scan), the radiation exposure must be decreased bef ore CTa can be used in a clinical research setting. Therefore, the firs t aim of this study was to assess the effect of radiation dose reduction on th e capability of CTa to measure overall cartilage quality. Second, we deter mined the capability of CTa to assess local cartilage quality within a s ingle slice and the effect of radiation dose reduction on this assessme nt.