Quantitative Ultrashort Echo Time Magnetization Transfer Imaging of the Osteochondral Junction: An In Vivo Knee Osteoarthritis Study

Abstract

Osteoarthritis (OA) is the most prevalent degenerative joint disorder worldwide, causing significant declines in quality of life. The osteochondral junction (OCJ), a critical structural interface between deep cartilage and subchondral bone, plays an essential role in OA progression but is challenging to assess using conventional magnetic resonance imaging (MRI) due to its short T2 relaxation times. This study aimed to evaluate the utility of ultrashort echo time (UTE) MRI biomarkers, including macromolecular fraction (MMF), magnetization transfer ratio (MTR), and T2*, for in vivo quantification of OCJ changes in knee OA for the first time. Forty-five patients (mean age: 53.8 ± 17.0 years, 50% female) were imaged using 3D UTE-MRI sequences on a 3T clinical MRI scanner. Patients were stratified into two OA groups based on radiographic Kellgren-Lawrence (KL) scores: normal/subtle (KL = 0-1) (n = 21) and mild to moderate (KL = 2-3) (n = 24). Quantitative analysis revealed significantly lower MMF (15.8 ± 1.4% vs. 13.6 ± 1.2%, p < 0.001) and MTR (42.5 ± 2.5% vs. 38.2 ± 2.3%, p < 0.001) in the higher KL 2-3 group, alongside a higher trend in T2* values (19.7 ± 2.6 ms vs. 21.6 ± 3.8 ms, p = 0.06). Moreover, MMF and MTR were significantly negatively correlated with KL grades (r = -0.66 and -0.59; p < 0.001, respectively), while T2* showed a weaker positive correlation (r = 0.26, p = 0.08). Receiver operating characteristic (ROC) analysis demonstrated superior diagnostic accuracy for MMF (AUC = 0.88) and MTR (AUC = 0.86) compared to T2* (AUC = 0.64). These findings highlight UTE-MT techniques (i.e., MMF and MTR) as promising imaging tools for detecting OCJ degeneration in knee OA, with potential implications for earlier and more accurate diagnosis and disease monitoring.

Keywords: macromolecular fraction (MMF); magnetization transfer ratio (MTR); osteoarthritis (OA); osteochondral junction (OCJ); ultrashort echo time (UTE) MRI.

Figure 1

(A) Fat-suppressed T2w-FSE (T2w). (B) Proton-density-weighted FSE (PDw). (C) UTE-T1-weighted (FA = 30°) images of the knee joint for a 38-year-old male with KL = 0. Note that the femoral condyle OCJ (yellow line) and tibial condyle OCJ (blue line) show no signal on conventional clinical MRI images (A,B). On the UTE-T1 image, the OCJ is evident as a region with a higher signal between the subchondral bone and deep cartilage (C). Using the UTE-T1 image, schematic regions of interest were placed in the femoral condyle OCJ (yellow line) and tibial condyle OCJ (blue line) for measurement as shown (D). T2w, T2-weighted; PDw, proton-density-weighted; OCJ, osteochondral junction; UTE-T1, ultrashort echo time-based T1; KL, Kallgren–Lawrence.

Figure 2

Representative fat-suppressed T2w-FSE (T2w) images (a,e,i,m) and corresponding MMF (b,f,j,n), MTR (c,g,k,o), and T2* (d,h,l,p) maps from four participants with varying degrees of KL scores. Top row (a–d): a 23-year-old male with normal cartilage (KL = 0); second row (e–h): a 57-year-old male with subtle cartilage changes (KL = 1); third row (i–l): a 52-year-old female with mild cartilage degeneration (KL = 2); bottom row (m–p): a 70-year-old female with moderate cartilage degeneration (KL = 3). T2w, T2-weighted fast spin echo; MMF, macromolecular fraction; MTR, magnetization transfer ratio.

Figure 3

Box plots of the MMF (A), MTR (B), and T2* (C) measurements for different OA groups. The “Normal/Subtle” OA group includes KL grades 0 and 1, and the “Mild to Moderate” OA group includes KL grades 2 and 3. The edges of the box indicate the first and third IQR percentiles, respectively. The normal/subtle OA group had significantly higher MMF than the mild to moderate OA group (p < 0.001). The normal/subtle OA group had significantly higher MTR than the mild to moderate OA group (p < 0.001). The normal/subtle OA group had lower T2* than the mild to moderate OA group (p = 0.06). KL, Kallgren–Lawrence; OA, osteoarthritis; MMF, macromolecular fraction; MTR, magnetization transfer ratio; IQR, interquartile range.

Figure 4

Pearson’s and Spearman’s correlations between MMF, MTR, and T2* measurements and the KL scores. (A) Spearman’s correlation between MMF values and KL scores; (B) Spearman’s correlation between MTR values and KL scores; (C) Pearson’s correlation between UTE-T2* values and KL scores. The KL scores are negatively correlated with both MMF (r = −0.66, p < 0.001) and MTR (r = −0.59, p < 0.001) and weakly positively correlated with T2* (r = 0.26, p = 0.08), KL, Kallgren–Lawrence; MMF, macromolecular fraction; MTR, magnetization transfer ratio.

Figure 5

ROC curves of quantitative UTE-MRI measurements for distinguishing between subjects with normal/subtle OA findings (KL scores 0 and 1) and those with significant OA findings (KL scores 2 and 3). The areas under the curve (AUC) of MMF (AUC  =  0.88, p < 0.001), followed by MTR (AUC  =  0.86, p < 0.001), were much higher than T2* (AUC  =  0.64, p = 0.08) at a 0.05 significance level. UTE, ultrashort echo time; MMF, macromolecular fraction; MTR, magnetization transfer ratio.