Osteoarthritis (OA) of the knee is a prevalent degenerative joint disorder that leads to functional disability and reduced quality of life. Characterized by progressive cartilage degradation, subchondral bone remodeling, and osteophyte formation, OA is a major cause of morbidity worldwide [1]. Conventional diagnostic modalities, particularly radiographs, often detect disease only in advanced stages, showing joint space narrowing and osteophyte formation [2]. Magnetic resonance imaging (MRI) has become indispensable for evaluating cartilage morphology. However, conventional morphological sequences provide limited sensitivity in detecting early biochemical changes [3]. Compositional MRI techniques such as T2 mapping, T1ρ imaging, sodium MRI, and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) enable quantification of cartilage ultrastructure [4]. Among these, T2 mapping is widely used due to its ability to reflect collagen fiber orientation and water content, both critical markers of early degeneration [5]. Regional variations in OA progression are well recognized, with the medial femorotibial compartment being most frequently affected due to biomechanical loading [6]. Assessing compartment-specific changes in T2 values may enhance understanding of disease mechanisms and provide imaging biomarkers for early intervention. This study aims to evaluate regional variations in T2 relaxation times of knee cartilage in osteoarthritis patients compared to controls, and to correlate these findings with Kellgren-Lawrence (KL) radiographic grading.

Study Design And Population This prospective study was conducted at the Barnard Institute of Radiology, Madras Medical College, Chennai, over six months (June-December 2017). A total of 40 subjects were included: 15 clinically and radiographically confirmed OA patients and 25 age-matched controls without OA. Inclusion Criteria ▪ Patients with clinical symptoms of OA and radiographic evidence (KL grading). ▪ Controls referred for knee MRI for non-OA indications and willing to undergo cartilage mapping. Exclusion Criteria ▪ Contraindications to MRI (e.g., pacemakers, metallic implants). ▪ Claustrophobia or orthopnea. Imaging Protocol All imaging was performed on a 3T MRI scanner (MAGNETOM Skyra, Siemens Healthineers) using a 15-channel knee coil. Standard radiographic views included bilateral standing flexion weight-bearing and 30° lateral projections. Sequences Included ▪ Sagittal T1-weighted spin echo ▪ Axial and sagittal fat-suppressed proton density (PD) spin echo ▪ Sagittal PD SPACE ▪ Coronal STIR ▪ Axial, coronal, and sagittal T2 mapping sequences Slice thickness was 3 mm; acquisition time for T2 mapping was approximately 10 minutes. Image Analysis Five cartilage compartments were assessed: ▪ Medial femoral condyle (MFC). ▪ Lateral femoral condyle (LFC). ▪ Medial tibial plateau (MT). ▪ Lateral tibial plateau (LT). ▪ Patella (P). Regions of interest (ROI) were drawn manually on each compartment to extract average T2 relaxation times and cartilage thickness. Radiographs were graded using the Kellgren-Lawrence (KL) scale. Statistical Analysis Data were analyzed using IBM SPSS v23.0. Descriptive statistics were expressed as mean ± standard deviation. Independent sample t-test was applied for group comparisons, and chi-square test for categorical data. A p-value < 0.05 was considered statistically significant.

Demographic Distribution The study population (n=40) included 20 males and 20 females, with a mean age of 38 ± 14 years. Among OA patients (n=15), the mean age was higher (52.3 ± 11.2 years) compared to controls (31.4 ± 9.7 years). Table 1: Age and gender distribution of participants Group Mean Age (years) ± SD Male (n) Female (n) OA patients 52.3 ± 11.2 5 10 Controls 31.4 ± 9.7 15 10 T2 Relaxation Times By Compartment Significant differences in T2 values were observed between OA patients and controls across all five compartments (Table 2). Table 2: Mean T2 relaxation times (ms) in OA vs controls Compartment OA Patients (n=15) Controls (n=25) p-value Medial femoral condyle (MFC) 39.3 ± 11.1 28.1 ± 2.4 <0.001 Lateral femoral condyle (LFC) 34.2 ± 6.9 27.4 ± 3.0 <0.001 Medial tibial plateau (MT) 41.5 ± 9.4 27.0 ± 2.3 <0.001 Lateral tibial plateau (LT) 35.5 ± 5.7 27.4 ± 2.5 <0.001 Patella (P) 34.0 ± 6.7 27.2 ± 2.6 <0.01 Table 3: Mean T2 values by KL grade KL Grade Number of Patients Mean T2 Value (ms) ± SD 1 3 29.6 ± 2.1 2 4 32.6 ± 3.3 3 5 39.3 ± 4.5 4 3 45.7 ± 6.2 Figure 2 would depict a rising trend in mean T2 values from KL 1 through KL 4, demonstrating a direct correlation between disease severity and T2 prolongation. Cartilage Thickness No statistically significant differences were noted in cartilage thickness between OA patients and controls (p > 0.05). Table 4: Mean cartilage thickness (mm) in OA vs controls Compartment OA Patients (n=15) Controls (n=25) p-value MFC 1.55 ± 0.49 1.62 ± 0.26 0.41 LFC 1.70 ± 0.52 1.59 ± 0.23 0.36 MT 1.50 ± 0.39 1.63 ± 0.21 0.28 LT 1.81 ± 0.51 1.61 ± 0.22 0.24 Patella 1.96 ± 0.62 2.11 ± 0.27 0.30 Overall Findings 1. T2 values were consistently elevated in OA compared to controls. 2. Medial compartments demonstrated the greatest elevation in T2 values, reflecting the known biomechanical vulnerability of the medial compartment. 3. Cartilage thickness measurements were not reliable indicators of early OA. 4. T2 mapping showed a positive correlation with KL scores, establishing its value as a progression marker.

This study highlights the clinical relevance of regional variations in T2 relaxation times in osteoarthritic cartilage. Several key insights emerge: 1. Sensitivity of T2 Mapping in Early OA: The ability of T2 mapping to detect subtle biochemical changes before morphological cartilage thinning emphasizes its superiority over conventional MRI and radiography. The observed elevation of T2 values in mild OA cases (KL grade 1–2) supports prior findings by Mosher et al. [5] and Dunn et al. [8], who demonstrated similar trends in early disease detection. 2. Regional Variations and Biomechanical Load: Our findings that medial compartments (MFC, MT) had higher T2 values are consistent with the biomechanical loading patterns of the knee joint. Increased stress on the medial compartment accelerates collagen matrix disorganization and water influx, reflected as prolonged T2 relaxation times. Similar compartment-specific findings have been reported by Apprich et al. [10]. 3. Correlation with Disease Severity: T2 mapping values increased with KL grades, reinforcing its role as a biomarker for disease progression. This direct correlation suggests that T2 mapping could be integrated into longitudinal monitoring of OA patients, aiding in both clinical evaluation and therapeutic trials. 4. Lack of Cartilage Thickness Differences: Interestingly, no significant variation in cartilage thickness was noted between OA and controls. This may be attributed to compensatory cartilage swelling in early OA, where increased water content masks true volumetric loss. This highlights why morphological measures alone are insufficient in early disease evaluation. 5. Clinical Implications: Incorporating T2 mapping into standard MRI protocols may provide clinicians with a non-invasive, quantitative, and reproducible marker for evaluating cartilage health. It is particularly useful for: ▪ Identifying early biochemical degeneration. ▪ Monitoring post-intervention cartilage repair (e.g., after chondroplasty or cell-based therapies). ▪ Stratifying patients for disease-modifying OA drugs (DMOADs) in clinical trials. 6. Study Limitations ▪ Lack of arthroscopic correlation as a gold standard. ▪ Influence of magic angle effect on T2 values. ▪ Small sample size limiting generalizability. ▪ Only five compartments assessed, while zonal analysis (superficial vs deep) could provide richer insights.

The present study confirms that T2 mapping using 3T MRI is a powerful imaging biomarker for detecting early and regional biochemical alterations in knee osteoarthritis. Unlike cartilage thickness, which remains relatively stable across disease stages, T2 relaxation times rise progressively, correlating strongly with KL grades and reflecting underlying collagen network disorganization and water content changes (11,12). The regional predominance of medial compartment involvement observed in our study aligns with biomechanical vulnerability and clinical patterns of disease progression. This reinforces the importance of compartmental analysis rather than global cartilage assessment. By integrating T2 mapping into clinical and research protocols, radiologists and orthopedic specialists can: ▪ Detect OA earlier. ▪ Track disease progression objectively. ▪ Monitor treatment response more effectively. Future studies with larger cohorts, arthroscopic validation, and combined use of multiple compositional MRI techniques (e.g., T1ρ, dGEMRIC) may further enhance the role of MRI in OA management.

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