This study demonstrated the feasibility of using texture analysis to characterize the spatial distribution of T2 values in articular cartilage in OA patients and controls. Entropy and ASM showed significant differences between mild OA patients and controls, demonstrating that these parameters may be able to differentiate osteoarthritic from healthy cartilage. The mean T2 values, their SD, and their entropy were greater in OA patients than in controls, indicating that the T2 values in osteoarthritic cartilage are not only elevated, but also more heterogeneous than those in healthy cartilage. Over 9 months, the SD and entropy of cartilage T2 significantly (P < 0.05) decreased in OA patients, while no significant changes were evident in cartilage thickness or volume. The longitudinal results demonstrate that changes in texture parameters of cartilage T2 may precede morphological changes in thickness and volume in the progression of OA.
The results of this study are consistent with those of previous studies, which have reported elevated T2
values in OA cartilage6,7
, and increased entropy and decreased ASM of cartilage T2
values in OA subjects compared to controls20
relaxation time in cartilage has been associated with many factors including the mobility of water21
(which is affected by the breakdown of the extracellular matrix), water content22
, and collagen fiber orientation23
. Both in vitro24
and in vivo
have observed differences in T2
values from the deep to superficial layers of cartilage. Characterizing the heterogeneity of T2
values (using SD and texture analysis) provides a means to quantify their distribution. SD, which evaluates the deviation of T2
values from their mean, characterizes the spread of T2
values, while GLCM texture measures examine the differences in neighboring T2
pixel values. Together, these measurements can be used to quantify the distribution of cartilage T2
values on both a global and focal scale, which is essential, given the heterogeneity of biochemical changes that occur in osteoarthritic cartilage. Based on the cross-sectional data, the mean, SD, and entropy of cartilage T2
values were elevated in OA subjects as compared to controls. The increases in mean cartilage T2
suggest that the mobility of water is elevated in osteoarthritic cartilage; the increases in SD and entropy suggest that the changes to the extracellular matrix are both globally and spatially heterogeneous throughout the degenerated cartilage.
Longitudinally, the SD and entropy of cartilage T2 significantly decreased in OA patients. There were no significant changes in mean, SD, ASM or entropy of cartilage T2 in controls. The mechanisms responsible for the longitudinal decreases of cartilage T2 entropy are difficult to isolate in an in vivo imaging study. These longitudinal results were unexpected; however, we speculate that decreased entropy of cartilage T2 in OA patients over 9 months is related to swelling of cartilage in the early stages of OA, or short-term changes in disease progression. For example, illustrates the progression of cartilage degeneration in an OA patient from baseline to 9 months. At baseline, the cartilage signal is inhomogeneous, and at 12 months, a cartilage defect (which has a more homogeneous signal) has developed. The changes in intensity and spatial distribution of pixel values are evidenced by decreased entropy of cartilage T2. These results demonstrate that changes in cartilage T2 are heterogeneous during the evolution of OA.
Fig. 4 Sagittal T2-weighted FSE images (top row) and cartilage T2 maps overlayed on T2-weighted FSE images (bottom row) of an OA patient at baseline and 9 months. At baseline, the cartilage signal at the posterior lateral tibia (arrow) is inhomogeneous (a) and (more ...)
The goal of this study was to establish a method that can be used to quantify and compare the distribution of T2 pixels in osteoarthritic and healthy cartilages. Since GLCM texture analysis yields a numerical result, it facilitates a simple means for comparison between subject groups. The short-term changes in the spatial distribution of cartilage T2 values motivate a long-term follow-up study. A further study with a larger patient cohort, and multiple follow-up durations (such as the Osteoarthritis Initiative) is therefore clearly warranted, and would be essential to understand the time-course of T2 changes in OA. There were no significant cross-sectional differences or longitudinal changes in cartilage thickness or volume in OA patients and controls. This may be because the time-course of cartilage volume and thickness changes are slower than changes in mean, SD, and texture of cartilage T2 in OA.
The limitations of this pilot study include a small subject sample size (8 OA patients and 10 controls), short follow-up duration (9 months) and the use of two echo times in calculating the T2
map. While additional echo times would increase the accuracy of cartilage T2
and texture quantification, two echo times were used due to constraints in imaging duration. Due to the limited spatial resolution of the T2
mapping sequence, only approximately 3–4 pixels spanned the cartilage thickness28–30
. Increased spatial resolution would decrease partial volume effects at the cartilage–bone surface and would improve the accuracy of the texture analysis particularly perpendicular to the cartilage surface. Because the patient's knee cannot be in an identical position during the baseline and follow-up scans, registration of these scans would ensure that the same region of cartilage is evaluated at both visits. Therefore, improved registration and segmentation techniques would increase the accuracy of cartilage volume, thickness, and T2
measurements. Another limitation to this study is the fact that the OA patients had a significantly greater mean BMI than controls. The excess fat tissue in the knee may affect the signal received by the coils, and may affect the calculated T2
values. Future studies should be designed to include both age and BMI-matched patients and controls.
In this study, the orientation of the texture analysis was performed with respect to the imaging plane, rather than with respect to bone surface. Therefore, 0° may not be considered parallel to the bone surface, especially given the curvature of the femoral condyles. Future studies will define the texture analysis coordinates with respect to the bone surface – 0° will be parallel to the bone surface, while 90° will be perpendicular. This could be accomplished by flattening out the cartilage, thereby facilitating texture analysis at a greater pixel offset in the horizontal plane31
A recent study by Qazi et al
quantified the homogeneity of cartilage signal from T1
-weighted knee images obtained on a 0.18 T scanner. This study calculated first order entropy of cartilage using a histogram-based method, and demonstrated a significant difference in cartilage entropy between mild OA patients and healthy controls. Though both studies evaluate the pixel distribution of OA cartilage, the field strength, thus the contrast-to-noise, resolution and other factors are different between our study and the above-mentioned study, which makes direct comparison difficult. Perhaps, future studies could combine histogram and co-occurrence-based measurements to investigate their collective sensitivity to cartilage degeneration.
In summary, the results show that OA patients have higher and more heterogeneous cartilage T2 values than healthy controls. Over 9 months, the SD and entropy of T2 values decreased in OA patients, which may reflect the change of heterogeneity in cartilage structure in the evolution of OA. The T2 quantification sequence, number of echoes, fitting routine, and impact of noise are all factors, which may affect the calculation of texture parameters. While we have established the feasibility of using texture measures to quantify regional heterogeneity in cartilage T2, the time-course and evolution of these measures are likely to be complex; therefore, further studies examining texture analysis in a larger cohort are warranted.