Exploring the asynchronous changes of articular cartilage and osteochondral junction in knee osteoarthritis based on T2 mapping and ultrashort echo time imaging: a pilot study

Introduction

Knee osteoarthritis (KOA) is the most common chronic degenerative joint disease, predominantly affecting middle-aged and older adults, with a global age-standardised prevalence of about 4.3% in 2020 and an expected increase of 74.9% by 2050 (1,2). The pathological features of this disease are primarily progressive articular cartilage (AC) degeneration, accompanied by subchondral bone (SB) sclerosis, ultimately leading to joint destruction, instability, and disability (3). Consequently, understanding the pathogenesis of KOA, particularly the initiating factors, is crucial for early diagnosis, clinical prevention, and effective management of disease progression.

Magnetic resonance imaging (MRI) enables noninvasive diagnosis of KOA at an earlier stage and has become the preferred imaging diagnostic method (4). Apart from utilizing conventional MRI sequences for a qualitative evaluation of degraded AC and adjacent soft tissues, diverse quantitative techniques, such as T2 mapping, T2* mapping, and T1ρ relaxation time measurements, have been extensively employed in the investigation of AC and the osteochondral junction (OCJ) (5-7). T2 mapping technology exhibits high sensitivity to cartilage matrix lesions, enabling the detection of cartilage abnormalities and reflecting early alterations in extracellular matrix water and collagen content before the occurrence of morphological changes in the cartilage (8,9). Ultrashort echo time (UTE) imaging technology has demonstrated effectiveness in visualizing the OCJ with a short transverse relaxation time and can be integrated with T2* mapping for quantitative analysis (7,10). A normal OCJ appears as a thin, linear structure with a high signal intensity on UTE images. To investigate the origin of high-intensity signals observed in the cartilage region on UTE images, Bae et al. (10) conducted a study in which human patellar cartilage samples were categorized into distinct groups and subjected to UTE imaging; histological validation was also performed. The findings revealed that only areas containing deep layers of uncalcified cartilage or regions with calcified cartilage exhibited linear high-signal intensities on the corresponding UTE images. This indicates that UTE is an imaging modality that can be used to evaluate the OCJ. UTE studies of ex vivo samples from humans and animals have demonstrated that a bright OCJ signal line is visible in normal joints, with T2* values gradually increasing from the OCJ towards the superficial cartilage. Additionally, a significant positive correlation has been observed between T2* values and the cartilage degeneration MRI Osteoarthritis Knee Score (MOAKS) (11-13).

Numerous studies have investigated the pathogenesis and early progression of KOA, yet controversy persists regarding the precise asynchronous alterations occurring among the AC, calcified cartilage, and SB. Generally, it is believed that there is a complex interaction between the AC and SB during the occurrence and progression of early KOA (3,14). All along, most researchers have concurred that the earliest pathological changes in the early stages of KOA are degradation of the surface cartilage matrix, metabolic disorders of chondrocytes, and loss of proteoglycans. As the disease advances, these pathological changes propagate from the superficial to deeper layers, encompassing the calcified cartilage and SB regions. Consequently, the surface of the SB becomes unprotected, rendering it susceptible to direct abnormal stress, ultimately leading to the aberrant reconstruction of the SB (15,16). However, some researchers argue that alterations in the OCJ may precede those in the AC (17-19). The OCJ, as the main functional barrier between the non-calcified cartilage layer and the SB, is susceptible to damage due to aging, SB lesions, and other factors. Following damage to OCJ, a cascade of intricate biochemical molecular crosstalk mechanisms becomes activated, encompassing numerous signal transduction pathways such as TGF-β/Smad, Wnt/β-Catenin, and mitogen-activated protein kinase. The activation of these signaling pathways collectively contributes to AC degeneration, extracellular matrix degradation, and decreased chondrocyte load-bearing capacity by increasing the porosity of SB and blood vessels, disrupting chondrocyte gene expression and protein synthesis regulation, or inducing chondrocyte phenotypic alterations (18,19).

Previous studies have demonstrated that early cartilage degeneration is associated with increased T2 values and decreased T2* values. Specifically, superficial cartilage exhibits significantly higher T2 values compared to deep cartilage (20,21). Notably, T2 values vary across different regions of the knee joint, potentially influenced by factors such as age, sex, and body mass index (BMI) (22). Nevertheless, there is a paucity of studies utilizing these quantitative MRI techniques to assess the sequential changes occurring in the AC and OCJ in patients with KOA.

The primary objective of this study was to investigate the sequential order of pathophysiological changes in the AC and OCJ in early osteoarthritis, based on quantitative MRI-derived T2 values of AC and UTE-T2* values of the OCJ in the knee joint. The secondary objectives were to explore the influence of age and sex on quantitative MRI metrics in healthy knee joints, as well as the correlation between cartilage T2 values and OCJ T2* values. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-24-1492/rc).

Methods

Subjects

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the local Institutional Review Board of Tianjin Hospital (Medical Ethics Review No. 159 in 2023), and written informed consent was obtained from all individual participants. This was a prospective, observational study conducted at Tianjin University Tianjin Hospital from July 2023 to March 2024.

The patients with early KOA and healthy volunteers without knee pain symptoms in the past 6 months were included in the study. All participants were between 20 and 65 years with a BMI <30 kg/m². Among them, knees with early OA were defined as having knee pain symptoms and had undergone standing radiographs of the knees in the past 3 months, showing Kellgren-Lawrence (KL) (23) grades 1 to 2. The exclusion criteria for patients with early KOA were as follows: (I) a history of knee trauma or surgery; (II) suffering from rheumatoid arthritis, hematological malignancies, bone metastases, or metabolic bone diseases; (III) Lequesne index (24) >4; and (IV) poor MRI image quality. Lequesne index serves as a calculation method for the severity of KOA, with higher scores indicating more severe disease progression and functional impairment. Specifically, a score ranging from 1 to 4 is categorized as mild. The exclusion criteria for healthy knee joints were as follows: (I) the presence of any evidence of any knee joint abnormalities on MRI; and (II) poor MRI image quality.

To ensure that the included knees were in the early stages of OA, the cartilage signal and morphology were evaluated using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) (25) post-MRI. Knees with a WORMS cartilage score of >2 were excluded. The KL grading and WORMS cartilage scoring were performed by two experienced radiologists (Reader A and Reader B with 9 and 12 years of musculoskeletal imaging diagnosis experience, respectively) based on the conventional MRI images. In cases of disagreement, a consensus was reached. Figure 1 outlines the flowchart of the exclusion criteria.

Figure 1 The flowchart of inclusion and exclusion criteria for the study subjects. MRI, magnetic resonance imaging; OA, osteoarthritis; WORMS, Whole-Organ Magnetic Resonance Imaging Score.

To investigate the potential influence of age and sex on the quantitative MRI values of the AC and OCJ, we stratified healthy knees into two sex groups and three distinct age cohorts: group 1: 20–35 years; group 2: 36–50 years; and group 3: 51–65 years.

Data acquisition

All MRI scans were performed using a 3.0T scanner (Ingenia CX, Philips Healthcare, Best, The Netherlands). The subjects were positioned in a supine posture with a knee flexion angle of 30° and feet first. We used an eight-channel knee joint surface flexible coil and aligned its positioning line to the inferior margin of the patella. All scanning sequences, except for three-dimensional water-selective (3D WATS) and UTE imaging, were conducted using turbo spin echo (TSE). These include T1-weighted imaging (T1WI), T2-weighted imaging with spectral attenuation with inversion recovery (T2WI SPAIR), proton density-weighted imaging with SPAIR (PDWI SPAIR), and T2 mapping. To accentuate the OCJ with a short T2 relaxation time and minimize the interference from tissues exhibiting a long transverse relaxation time during UTE imaging, we used dual-echo UTE (dUTE) imaging, where a subtraction image is obtained by subtracting the free-decay signal of the second echo (with an echo time of 2.9 ms) from the free-decay signal of the first echo (with an echo time of 0.2 ms) (Figure 2). Moreover, short hard-pulse excitation and radial sampling were employed to shorten the scan time. Table 1 details the specific scanning parameters utilized for each sequence.

Figure 2 Regions of interest selection. UTE subtraction images obtained from knee joint samples of a healthy individual (A,B) and an early-stage OA patient (C,D). Image (A) depicts the OCJ of a healthy knee joint, manifesting as a continuous high-signal linear zone. The corresponding manually delineated ROI is presented by the green circle in (B). In contrast, image (C) illustrates thinning of the femoral OCJ in an early KOA patient, accompanied by partial defects in the high-signal region (indicated by the arrow), with the corresponding manually delineated ROI displayed by green circle in (D). KOA, knee osteoarthritis; OA, osteoarthritis; OCJ, osteochondral junction; ROI, region of interest; UTE, ultrashort echo time.

After all the above qualitative and quantitative MRI images were obtained, they were transferred to the image and information management software (IntelliSpacePorta, version 9.0, Philips Medical Systems Nederland B.V., The Netherlands) for quantitative values measurement. Conventional sequences were used to score the cartilage according to WORMS to exclude non-early stage patients. Given that AC and the OCJ exhibit high signal intensity on 3D WATS and UTE subtraction images, respectively, in this study, 3D WATS and UTE subtraction images were utilized to determine the location, extent, and thickness of AC and the OCJ. The thickness of the high signal intensity regions was taken as the thickness of either the AC or the OCJ. Additionally, T2 mapping and UTE-T2* mapping images were employed to measure the T2 values of AC and the T2* values of the OCJ, respectively. To mitigate the impact of regional variations in knee joint cartilage on quantitative MRI metrics, we performed manual segmentation of each knee joint into six distinct regions of interest (ROIs): the medial femoral condyle (MFC), lateral femoral condyle (LFC), medial tibial plateau (MTP), lateral tibial plateau (LTP), patellar region, and trochlear region. During the manual segmentation of ROIs, the anterior and posterior boundaries of the tibiofemoral joint cartilage and the OCJ were aligned with the anterior and posterior margins of the tibial plateau, respectively. The ROI for the femoral trochlea region was defined as the remaining unmarked anterior portion of the femur. For the patellar region, the ROI included the AC and OCJ adjacent to the patella at the patellofemoral joint. Given the thin nature of the OCJ, in instances where the boundary between the OCJ and the SB was indistinct, the ROI was either appropriately reduced in scope or excluded from segmentation to ensure precision and reliability.

T2 and UTE-T2* values were directly obtained using the T2 imaging and T2* imaging software on the Philips workstation where T2 and T2* maps are independently generated from multiple echo images through single-exponential pixel-by-pixel fitting of T2 and T2*. The representative fitting curves are shown in Figure 3. This process followed image registration to ensure anatomical correspondence between images acquired from different sequences. Initially, the AC was outlined on the 3D WATS image and subsequently copied to the corresponding position on the T2 maps for the quantification of T2 values. Similarly, the OCJ was sketched on the UTE subtraction image and replicated onto UTE-T2* maps to assess the T2* values (Figure 4). During ROI delineation, joint effusion and meniscus were avoided, and the entire cartilage or OCJ in the image was included as much as possible. The ROI was manually segmented on the slice showing the thickest cartilage, as well as the preceding and subsequent two slices. The average values of the cartilage in the corresponding regions were then obtained for statistical analysis to minimize measurement errors in the data. Furthermore, the segmentation of the ROI and measurement of quantitative MRI values were performed independently by two experienced musculoskeletal radiologists (Reader A and Reader B) to analyze inter-observer consistency.

Figure 3 The representative fitting curves for T2 mapping (A) and UTE-T2* mapping (B). Curve fitting was performed using the exponential decay formula for signal intensity, SI =S0 × exp (–TE/T2), in conjunction with the Levenberg-Marquardt algorithm to calculate the T2 or T2* values. The R² values for both fitting curves (A and B) were 0.99. SI, signal intensity; TE, echo time; UTE, ultrashort echo time.

Figure 4 T2 and T2* value measurement. The 3D WATS image (A), T2 map (B), UTE subtraction image (C) and UTE-T2* map (D) derived from an early OA knee joint sample. The manual selection of irregular ROIs, indicated by a green circle, corresponds to high signal intensity profiles. The region of high signal intensity in (A) indicates the extent of the articular cartilage, ranging from the articular surface to the tidemark, with the corresponding average T2 values measured and displayed in (B) (area: 79.8 mm², mean: 66.3 ms at femur; area: 68.7 mm², mean: 55.9 ms at tibia). The line of high signal intensity in (C) represents the OCJ region, and the corresponding T2* values are measured and displayed in (D) (area: 57.6 mm², mean: 10.1 ms at femur; area: 42.8 mm², mean: 19.76 ms at tibia). 3D WATS, three-dimensional water-selective; OA, osteoarthritis; OCJ, osteochondral junction; ROI, region of interest; UTE, ultrashort echo time.

Statistical analysis

All statistical analyses were conducted using SPSS (version 22.0; IBM Corp., Armonk, NY, USA) and R v. 4.4.1 (www.r-project.org). Continuous variables were expressed as means ± standard deviation or medians (25th quartile, 75th quartile). The chi-square test was used to determine significant differences in gender and side distribution between the healthy group and the KOA group.

The intraclass correlation coefficient (ICC) was used to assess the interobserver consistency for AC T2 values and OCJ T2* values. Strength of agreement was categorized as follows: poor (ICC: <0.50), moderate (ICC: 0.50–0.74), good (ICC: 0.75–0.9), and excellent (ICC: greater than 0.9) (26).

Before performing the analysis of variance and correlation, the Shapiro-Wilk test was conducted for each dataset. Differences between the healthy group and the KOA group were analyzed through analysis of covariance controlling for age. Furthermore, to assess the diagnostic efficiency of the quantitative MRI values in identifying cartilage and OCJ lesions in different regions of the knee, receiver operating characteristic (ROC) curve analysis and DeLong test were conducted.

The T2 and T2* values of all three age groups were compared using Kruskal-Wallis and Dunn tests. The Mann-Whitney U test was used to assess whether there were statistical differences between the two sex groups. Spearman’s correlation analysis was conducted to evaluate the correlation between all measured T2 and T2* values as well as the correlation between quantitative MRI values and the Lequesne index in all patients. P values <0.05 were considered statistically significant.

Results

Ultimately, 34 normal knee joints from 27 healthy volunteers and 42 knee joints from 34 patients with early OA were included in the study. Table 2 presents the baseline characteristics of the study participants.

Reliability assessment of T2 value and T2* value

The inter-observer agreement was excellent for both AC T2 value with an ICC of 0.94 [95% confidence interval (CI): 0.81–0.98] and OCJ T2* value with an ICC of 0.94 (95% CI: 0.72–0.96).

Comparison of T2 and T2* value between early KOA and healthy group

The AC T2 values were significantly higher in the early KOA group for MFC (P<0.001), MTP (P=0.04), patellar region (P<0.001), and trochlear region (P=0.01) relative to those in the healthy control groups. However, there was no significant difference between T2 values in LFC (P=0.59) and LTP (P=0.10) as shown in Figure 5. The T2 values for each region in the healthy group and the early KOA group are presented in Table 3.

Figure 5 Comparison of articular cartilage T2 values (A) and OCJ T2* values (B) between healthy group and early KOA group. Asterisks indicate a significant difference between the two groups. ns indicates no statistically significant difference between the two groups; KOA, knee osteoarthritis; LFC, lateral femoral condyle; LTP, lateral tibial plateau; MFC, medial femoral condyle; MTP, medial tibial plateau; OCJ, osteochondral junction.

For the OCJ T2* values, the early KOA group in each of the six regions measured exhibited some degree of elevation compared to the healthy group as shown in Figure 4. However, the difference of OCJ T2* value in LFC (P=0.16) was not statistically significant. The median T2* value of KOA group in MFC (P<0.001) showed the greatest increase, followed by MTP (P<0.001), LTP (P=0.01), patellar (P=0.03) and trochlear (P=0.01). The UTE-T2* values for each region in the healthy group and the early KOA group are presented in Table 3.

ROC curve analysis of T2 mapping and UTE-T2* mapping for early degeneration of cartilage

Figure 6 shows the ROC curve for diagnosing cartilage degeneration by T2 mapping and OCJ lesion by UTE-T2* mapping in early KOA. In the patellar region specifically, the area under the curve (AUC) for diagnosing early KOA using AC T2 values (AUC =0.78, P<0.001) was higher than that using OCJ UTE-T2* values (AUC =0.64, P=0.04). This difference was confirmed to be statistically significant by the Delong test (P=0.04). In contrast, no significant difference in AUC was observed between the two imaging modalities in the remaining five regions at the 0.05 significance level.

Figure 6 ROC curve for diagnosing articular cartilage degeneration using T2 mapping and OCJ lesions using UTE-T2* mapping in early KOA. In the context of diagnosing early articular cartilage degeneration in KOA, the AUC for the MFC was 0.78 (P<0.001), with a cut-off value of 59.16 ms. For the LFC, the AUC was 0.53 (P=0.64), with a cut-off value of 68.02 ms. In the patellar region, the AUC was 0.78 (P<0.001), with a cut-off value of 55.98 ms. In the MTP, the AUC was 0.65 (P=0.02), accompanied by a cut-off value of 36.51 ms. The AUC for the LTP was 0.57 (P=0.27), with a corresponding cut-off value of 36.44 ms. Lastly, for the femoral trochlear region, the AUC was 0.66 (P=0.01), with a cut-off value of 55.54 ms. In the diagnosis of early KOA OCJ lesions, UTE-T2* mapping yielded an AUC of 0.77 (P<0.001) with a cut-off value of 9.55 ms at the MFC, an AUC of 0.59 (P=0.17) with a cut-off value of 10.32 ms at the LFC, an AUC of 0.64 (P=0.04) with a cut-off value of 20.00 ms at the patellar region, an AUC of 0.75 (P<0.001) with a cut-off value of 16.05 ms at the MTP, an AUC of 0.66 (P=0.01) with a cut-off value of 8.00 ms at the LTP, and an AUC of 0.66 (P=0.01) with a cut-off value of 17.50 ms at the femoral trochlear region. Only in the patellar, the AUC for diagnosing early KOA using cartilage T2 values was higher than that using OCJ UTE-T2* values and this difference was confirmed to be statistically significant by the Delong test (P=0.04). AUC, area under the curve; KOA, knee osteoarthritis; LFC, lateral femoral condyle; LTP, lateral tibial plateau; MFC, medial femoral condyle; MTP, medial tibial plateau; OCJ, osteochondral junction; ROC, receiver operating characteristic; UTE, ultrashort echo time.

Age and sex differences in AC T2 value and OCJ T2* value

Figures 7,8 show a comparison of the quantitative MR values between different age groups in six distinct regions of healthy knees. Apart from the statistically significant difference in T2 values observed between group 1 and group 2 in the trochlear region, there were no discernible variations in T2 values among the various age groups in the remaining regions. Specifically, in the trochlear region, the T2 value of group 2 (57.1, 51.1–63.2 ms) was significantly higher than that of group 1 (50.9, 46.2–54.4 ms, P=0.02).

Figure 7 Comparison of articular cartilage T2 values among three age groups. For group 1 (comprising individuals aged 20–35 years), group 2 (36–50 years), and group 3 (51–65 years), the respective number of knees was 13, 11, and 10. In MFC, LFC, Patellar, MTP, and LTP, there were no significant differences in T2 values among age groups. However, T2 values in the trochlear region were significantly higher in group 2 (57.1, 51.1–63.2 ms) than in group 1 (50.9, 46.2–54.4 ms, P=0.02). Asterisk (*) indicates a significant difference between the two groups. LFC, lateral femoral condyle; LTP, lateral tibial plateau; MFC, medial femoral condyle; MTP, medial tibial plateau.

Figure 8 Comparison of OCJ T2* values among three age groups. For group 1 (comprising individuals aged 20–35 years), group 2 (36–50 years), and group 3 (51–65 years), the respective number of knees was 13, 11, and 10. The OCJ T2* value of group 1 (11.2, 7.2–17.9 ms) was higher than those of group 2 (4.7, 3.8–6.8 ms, P=0.007) only in LTP. Asterisk (*) indicates a significant difference between the two groups. LFC, lateral femoral condyle; LTP, lateral tibial plateau; MFC, medial femoral condyle; MTP, medial tibial plateau; OCJ, osteochondral junction.

For UTE-T2* mapping, the OCJ T2* value of group 1 (11.2, 7.2–17.9 ms) was higher than those of group 2 (4.7, 3.8–6.8 ms, P=0.007) in LTP. However, no significant differences in T2* values were observed among different age groups in other regions (Figure 8).

Table 4 shows a sex-specific comparison of T2 and T2* values in healthy knees. The cartilage T2 values were significantly higher in females than in males only in MFC (52.5, 46.7–54.9 ms vs. 40.9, 37.8–46.0 ms, P=0.003) and MTP (36.3, 35.7–43.7 ms vs. 34.0, 31.0–37.3 ms, P=0.02). No significant differences were seen in the T2 values and T2* values between the sexes in any other ROIs.

Correlation analysis

Spearman’s correlation analysis showed a weak positive correlation between AC T2 values and OCJ T2* values in the 912 regional ROIs (r=0.30, P<0.001).

Only the cartilage T2 values of the MFC (r=0.33, P=0.03) and trochlear regions (r=0.33, P=0.03) exhibited a positive correlation, albeit a weak one, with the Lequesne index. In LFC (P=0.65), patellar (P=0.25), MTP (P=0.88) and LTP (P=0.65), the Spearman’s correlation coefficient between AC T2 values and Lequesne index was 0.67, 0.18, 0.24 and 0.07, respectively.

For the correlation between OCJ T2* values and Lequesne index, no significant correlation was found irrespective of whether they were examined in MFC (r=0.02, P=0.88), LFC (r=0.19, P=0.20), patellar (r=0.02, P=0.94), MTP (r=0.07, P=0.63), LTP (r=0.25, P=0.10), or trochlear regions (r=−0.17, P=0.26).

Discussion

This study quantitatively and non-invasively evaluated early-stage AC and OCJ lesions in patients with KOA using T2 and UTE-T2* mapping techniques, respectively. In the early stage of KOA, compared with normal knees, both the T2 values of the AC and the UTE-T2* values of the OCJ increased in the MFC, MTP, patellar, and trochlear regions, while no changes were observed in the LFC. Additionally, there was an approximate 43% increase in the LTP OCJ T2* value, whereas no statistically significant difference was observed in the T2 value of the lateral tibial cartilage compared to the healthy group. This preliminary study indicates the presence of pathophysiological alterations in both AC and the OCJ during the early stages of KOA.

Early diagnosis and prevention of KOA requires careful monitoring of changes in the AC and OCJ, particularly alterations in the UTE-T2* values of the OCJ at the medial tibiofemoral joint. Although no changes in OCJ UTE-T2* values were detected in the LFC in the early stage of KOA, the OCJ plays a crucial role in transporting nutrients from the SB to the avascular cartilage, thereby maintaining homeostasis and function of the entire knee joint. Changes in cartilage composition and structure commence during the early stages of OA, highlighting the critical importance of early diagnosis and intervention in KOA.

Osteoarthritis is influenced by both biochemical signals and biomechanical factors. Any alterations in the tissues of the OCJ can compromise its barrier and transport functions, ultimately contributing to the initiation and progression of OA. In case of microstructural damage in SB, prostaglandins and growth factors released from osteoblasts can affect the AC (27). Bellido et al.’s research indicates that increased SB resorption in individuals with osteoporosis and OA may exacerbate cartilage damage (28). Variations in SB density or stiffness can predispose the overlying AC to degeneration (29). The study conducted by Davis et al. (18) using animal models of medial tibial OA to assess the early mechanical changes, suggests that stiffening of the deep zone of the AC and a decrease in SB stiffness may precede cartilage degeneration in OA progression.

T2 values can reflect subtle changes in the water content and orientation of collagen fibers within the knee cartilage, which serve as signals of cartilage degradation and correlate with the severity of osteoarthritis (9,30). Previous studies have demonstrated that the median T2 value of AC in the healthy knee is approximately 50 ms and increases with the degree of cartilage degeneration (31,32). Consistent with the findings of Soellner et al. (32) who compared the T2 relaxation time of knee AC with intraoperative results, our findings also revealed a 5% to 26% increase in the AC T2 values in specific regions during the early stages of KOA. Furthermore, the T2 mapping technique exhibited good diagnostic efficiency in distinguishing between normal and early degenerative hyaline AC.

The T2* relaxation time provides significant insight into local magnetic field inhomogeneity, potentially offering a more sensitive measure of tissue composition changes than did the T2 relaxation time (33,34). Therefore, UTE-T2* mapping of deep cartilage has great potential for early diagnosis and prediction of future KOA. Chu et al. (35) measured the T2* values of the deep cartilage in the central MFC and the anterior MFC of normal knees using three- Dimensional Double-Echo Steady-State (DESS) UTE technique, with results of 9.9±0.3 and 11.9±0.3 ms, respectively. Williams et al. (36) conducted in vivo studies and reported that the T2* value of the deep cartilage of the patella was 15.1±0.4 ms, and they also found an increase in the UTE-T2* values of the deep cartilage in the medial femoral and medial tibial in patients who underwent anterior cruciate ligament reconstruction within two years, exhibiting evidence of cartilage degeneration. Notably, this elevation was also observed in patients without medial cartilage or meniscal degeneration.

However, the UTE-T2* values are largely dependent on the choice of scanning parameters, particularly the first TE. For instance, Titchenal et al. (37) measured the UTE-T2* values of normal deep knee cartilage to be within the range of 10–20 ms using a 3D UTE sequence with 8 echoes and a first TE of 0.032 ms at a 3T magnetic field. In contrast, in a similar study by Chu et al. (35), they observed UTE-T2* values of deep knee cartilage below 10 ms when employing a UTE sequence with 11 echoes and a first TE of 0.6 ms.

The feasibility study results of Mackay et al. (7) in assessing the OCJ using UTE imaging are similar to ours, they observed that knees with pain symptoms exhibited an increased mean T2 value in the medial tibial cartilage, a reduction in the high-signal-intensity lines in the medial and lateral OCJ regions, and the peak signal intensity ratio in the medial tibia was significantly lower than that in asymptomatic volunteers, while no such difference was noted in the lateral tibia. This observation suggests that UTE-T2* mapping exhibits sensitivity to compositional alterations within the OCJ.

Although no significant alterations were noted in the T2 values of the AC in LFC and LTP, nor in the T2* values of the lateral femoral OCJ in the present study, there was a tendency towards an increase. Moreover, a positive correlation was found between the AC T2 value and the Lequesne index in MFC. This may potentially be ascribed to the comparatively infrequent manifestation of lateral compartment narrowing in tibiofemoral osteoarthritis as compared to the medial compartment (38).

The elevations of AC T2 values and OCJ T2* values in the KOA group of could be attributed either to normal physiological changes associated with aging or to biochemical alterations due to mild cartilage degeneration. However, when examining the influence of age on quantitative MRI indices, we did not find a significant increase in T2 or T2* values with advancing age. Therefore, the significant elevations in cartilage T2 values and OCJ T2* values observed in this study are likely due to the disruption of collagen fibers and an increase in mobile water protons in the early stages of cartilage and OCJ degeneration (39). Furthermore, the lack of observed differences in quantitative MRI indices among different age groups may be attributed to the inclusion of normal volunteers with cartilage pathology rather than normal cartilage, after strictly excluding risk factors for KOA, and who exhibit no symptoms or radiological signs of KOA. Despite these findings, there are still some inconsistencies in the literature regarding age-related changes in MRI indices (40).

Our study also did not reveal a significant impact of sex on OCJ T2* values in normal knees, whereas in females, the cartilage T2 values of medial MTP and MFC were significantly higher than those in males. This is consistent with the higher prevalence of KOA among women (41). This finding underscores the importance of understanding the impact of sex on cartilage T2 values. Regarding the influence of age on quantitative metrics, no clear pattern was observed in this study, which may be attributed to the relatively small sample size.

During the progression of OA, there exists a complex biochemical crosstalk between the cartilage and SB, resulting in mutual influences between the two (42). This finding is consistent with the observed significant correlation between the AC T2 values and the T2* values of the OCJ in this study.

In contrast to previous studies (9,11,32), this research employed 3D WATS rather than T2 mapping technology to acquire images for determining the specific location and extent of the AC. The 3D WATS sequence, based on water-fat separation technology, selectively excites water signals, effectively suppressing the interference of fat signals on cartilage imaging. Additionally, this sequence employs three-dimensional volumetric acquisition technology, significantly reducing partial volume effects and thereby enhancing the signal-to-noise ratio (SNR) and contrast of the images. It enables the acquisition of high-resolution, high-SNR full-thickness cartilage images in a single scan. In contrast, conventional T2 mapping sequences typically utilize two-dimensional imaging techniques and lower spatial resolution (43,44). Furthermore, a study by Zhang et al. (43) has demonstrated that MR cartilage images based on the 3D WATS sequence, combined with automated cartilage segmentation algorithms (such as the NNU-NET model), exhibit high segmentation accuracy (mean dice scores >0.90) in different knee compartments. Therefore, this study selected the 3D WATS images for ROI segmentation to ensure the accuracy and reliability of cartilage quantitative analysis.

Due to the thinness of the OCJ (45) and the prolonged scanning time required to achieve high spatial resolution imaging in quantitative sequences, UTE MRI has primarily been used for the assessment of full-thickness AC in the knee, with rare instances of independent evaluation of the OCJ. In this study, the shortest echo time, 0.2 ms, was employed when performing UTE imaging of the OCJ and a subtraction technique was used to suppress longer T2 signals. By acquiring two echo signals, this method was less susceptible to the effects of magnetic field inhomogeneity, enabling clear visualization of the OCJ. In combination with quantitative imaging, the scan duration for UTE was 5 min 22 s. Additionally, the SPAIR sequence was used to suppress fat signals, effectively eliminating chemical shift artifacts arising from the SB marrow.

However, this study has some limitations. First, as the subjects in our study comprised patients with early-stage KOA and healthy individuals, we did not conduct histopathological validation of the results. Second, due to technological constraints, T2 mapping imaging may be influenced by the magic angle effect, leading to a certain degree of elevation in the T2 values of the hyaline cartilage. Finally, as this study was a preliminary exploration, our observations were limited to the early stages of KOA, and we did not conduct longitudinal follow-ups to determine the ultimate outcomes for these patients. Consequently, in future research, we will enlarge the sample size, broaden the scope of cartilage assessment and incorporate additional quantitative MRI techniques to determine the changes in quantitative MRI biomarkers of cartilage and OCJ in KOA. Concurrently, we will also endeavor to enroll a greater number of young participants to establish MRI normal values and variances for healthy young adults, and to mitigate the impact of age-related factors. Furthermore, it is equally important and necessary to conduct longitudinal studies across all stages of KOA progression, including the early, middle, and late stages, in order to observe the changes in quantitative MRI values of AC and the OCJ.

Conclusions

Early KOA can be identified by T2 mapping imaging of AC and UTE-T2* mapping of the OCJ. The T2 and UTE-T2* values, respectively, provide quantitative and non-invasive measures of the degeneration in the AC and the OCJ during the early stages of KOA. Notably, quantitative MRI biomarkers demonstrate alterations in both the AC and the OCJ in early KOA, with a positive correlation observed between the AC T2 values and the OCJ T2* values.

Acknowledgments

The authors are grateful the supports from Tianjin Medical University, Tianjin University Tianjin Hospital and Philips Healthcare. We would also like to thank the friends who helped us with the creation and revision of the article, as well as Editage for their professional language polishing work on this paper.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-24-1492/rc

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-1492/coif). Z.S. is an employee of Philips healthcare company; however, the corporation had no influence on the design, conduct, or interpretation of the results of this study. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the local Institutional Review Board of Tianjin Hospital (Medical Ethics Review No. 159 in 2023), and written informed consent was taken from all individual participants.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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