To compare adiabatic $$$T_{1\rho}$$$, adiabatic $$$T_{2\rho}$$$ and $$$T_2$$$ relaxation times of articular cartilage (AC) between subjects with and without early signs of osteoarthritis.A total of 30 subjects (age range: 50-70 y) were selected from the OKOA (Oulu Knee Osteoarthritis Study) cohort, including 15 patients with pre- and early radiographic OA (KL=1,2) and confirmed clinical symptoms, and 15 asymptomatic volunteers, matched for age and sex. WOMAC questionnaire $$$^1$$$ was filled out by each subject. Patients and volunteers underwent 3T knee MRI (Siemens Skyra) with six different sequences (Fig.1). The clinical MR images were evaluated using MOAKS $$$^2$$$, and $$$AdT_{1\rho}$$$, $$$AdT_{2\rho}$$$ $$$^3$$$ and $$$T_2$$$ were determined in 36 manually segmented cartilage subregions in lateral and medial central condyles (Fig.2) and compared between the two groups. Finally, the study participants were divided into groups based on (i) the severity of symptoms (WOMAC average visual analogue score ≤ 1 mm and > 1 mm), (ii) the depth of cartilage defects (none, partial-thickness and full-thickness lesions), (iii) the presence of bone marrow lesions (BML), (iv) the presence of osteophytes, and (v) the presence of meniscus tears. Differences in relaxation times between the groups were tested for each cartilage subregion with non-parametric Mann-Whitney or Kruskal-Wallis tests.

Significantly longer $$$AdT_{1\rho}$$$, $$$AdT_{2\rho}$$$ and $$$T_2$$$ were found in several ROIs with group indicating OA progression by different division methods (Fig.3-4). Moreover, in most ROIs for which the differences did not reach statistical significance, a trend of increasing relaxation times was observed along with OA signs. When comparing patients and volunteers, $$$AdT_{1\rho}$$$, $$$AdT_{2\rho}$$$ and $$$T_2$$$ times were significantly longer in patient group in one, two and two ROIs, respectively (Fig.3-5). Considering the prevalence of well-established OA hallmarks such as focal lesions, the overlap between volunteer and patient groups was apparent. The differences in $$$AdT_{1\rho}$$$ were predominant after dividing the subjects according to OA symptoms (Fig.5), with relaxation time of the symptomatic group significantly increased in eight different cartilage subregions and in the bulk medial femur. Significantly longer $$$AdT_{1\rho}$$$ was also associated with the presence of osteophytes, bone marrow lesions and meniscal tears. No significant differences in $$$AdT_{1\rho}$$$ were associated with AC lesions. Significantly elevated $$$AdT_{2\rho}$$$ and $$$T_2$$$ were associated with each of the considered OA signs in at least one ROI. The most prominent differences in $$$AdT_{2\rho}$$$ were observed with group division by the presence of osteophytes; significantly increased values in the osteophyte group were observed in five different ROIs and in the bulk medial femur (Fig.5). Significantly lower $$$T_2$$$ was found in one ROI of lateral condyle (superficial aCF) associated with the presence of meniscus tear.

ROIs presenting significant differences in relaxation times were mostly found in femoral cartilage subregions (Fig.5). Some subregions showed significant elongation of all three quantitative MRI parameters (e.g. medial deep PT ROI for OA symptomatic group), but more frequently the significant differences in $$$AdT_{1\rho}$$$, $$$AdT_{2\rho}$$$ and $$$T_2$$$ were in different ROIs, particularly in the lateral compartment.

Increased $$$AdT_{1\rho}$$$ and $$$AdT_{2\rho}$$$ times of articular cartilage were associated with different clinical signs of early OA. Earlier preclinical studies have shown the superior sensitivity of $$$AdT_{1\rho}$$$, $$$AdT_{2\rho}$$$ in detecting early OA changes as compared to established quantitative MRI parameters $$$^{4-6}$$$. In this study, with respect to $$$T_2$$$, $$$AdT_{1\rho}$$$ was more related to physical symptoms whilst $$$AdT_{2\rho}$$$ was more related to bone marrow lesions and osteophytes. Furthermore, the different associations of quantitative MRI parameters to various OA signs found in different ROIs may depend on different effective relaxation mechanisms. Therefore, the novel rotating frame techniques may provide complementary information regarding changes in cartilage tissue and OA progression.

The association of $$$AdT_{1\rho}$$$ and $$$AdT_{2\rho}$$$ with cartilage lesion severity was weaker as compared with the other OA signs, suggesting that the link between morphological and subtle biochemical changes may not be always obvious in cartilage, particularly in early OA stages $$$^7$$$. Finally the overlap between volunteer and patient groups is most probably imputable to the current limitations of the OA diagnostics, which relies on subjective physical examinations and plain radiographs.

$$$AdT_{1\rho}$$$ and $$$AdT_{2\rho}$$$ of articular cartilage are associated with different clinical signs of early OA, and more related respectively to OA symptoms and structural changes as compared to $$$T_2$$$. Based on these findings, $$$AdT_{1\rho}$$$ and $$$AdT_{2\rho}$$$ have considerable potential as tools for OA diagnosis and in vivo research.