Quantitative imaging of bone–cartilage interactions in ACL-injured patients with PET–MRI

Abstract

Objective: To investigate changes in bone metabolism by PET, as well as spatial relationships between bone metabolism and MRI quantitative markers of early cartilage degradation, in ACL-reconstructed knees. Design: Both knees of 15 participants with unilateral reconstructed ACL tears and unaffected contralateral knees were scanned using a simultaneous 3.0T PET-MRI system following injection of 18F-sodium fluoride(18F-NaF). The maximum pixel standardized uptake value(SUVmax) in the subchondral bone and the average T2 relaxation time in cartilage were measured in each knee in 8 knee compartments. We tested differences in SUVmax and cartilage T2 relaxation times between the ACL-injured knee and the contralateral control knee as well as spatial relationships between these bone and cartilage changes. Results: Significantly increased subchondral bone 18F-NaF SUVmax and cartilage T2 times were observed in the ACL-reconstructed knees (median[inter-quartile-range(IQR)]:5.0[5.8],36.8[3.6]ms) compared to the contralateral knees (median[IQR]:1.9[1.4],34.4[3.8]ms). A spatial relationship between the two markers was also seen. Using the contralateral knee as a control, we observed a significant correlation of r= 0.59 between the difference in subchondral bone SUVmax (between injured and contralateral knees) and the adjacent cartilage T2 (between the two knees)[p<0.001], with a slope of 0.49ms/a.u. This correlation and slope were higher in deep layers (r=0.73,slope=0.60ms/a.u.) of cartilage compared to superficial layers (r=0.40,slope=0.43ms/a.u.). Conclusions: 18F-NaF PET-MR imaging enables detection of increased subchondral bone metabolism in ACL-reconstructed knees and may serve as an important marker of early OA progression. Spatial relationships observed between early OA changes across bone and cartilage support the need to study whole-joint disease mechanisms in OA.

Translation of morphological and functional musculoskeletal imaging

“…also explored correlations between voxel based relaxation time T 1ρ and T 2 in the cartilage with sodium fluoride uptake metrics (slope K i and SUV), showing correlations not only not only in adjacent regions but also in compartments that are not adjoining. Correlations between SUV and cartilage compositional data were also recently shown in ACL subjects …”

“…al., 89 whereby repetitive joint loading causes an initial increase in bone remodeling, that is associated with increased vascular invasion of the deep layers of cartilage, which allows access to the cartilage by chondrolytic enzymes unopposed by inhibitors of the degradative proteinases, that cause a breakdown of the extra-cellular matrix, loss of Simultaneous PET-MRI was also recently used to study cartilage and bone interactions. [91][92][93][94][95] Savic et. al.…”

“…Correlations between SUV and cartilage compositional data were also recently shown in ACL subjects. 93 The ability to simultaneously monitor early changes in bone remodeling and cartilage composition, linked with the assessment of morphological shape changes has the potential to make a tremendous impact of defining OA as a total joint disease. The translation of these tools to the clinic would potentially bring not just advanced diagnosis to the point of patient care, but also open the path for drug discovery and the development of new therapeutic regimes.…”

Applications of PET‐MRI in musculoskeletal disease

“…In a study of mild to moderate OA patients, increases in cartilage T 1ρ relaxation times, which are associated with a loss of cartilage GAG content, were correlated with increased 18 F‐NaF uptake in the adjoining bone as well as reduced uptake in the nonadjoining compartments . In a separate study of patients with unilateral, reconstructed ACL tears, a correlation was observed between increased 18 F‐NaF uptake measures of bone remodeling and increased T 2 values in adjacent cartilage, which is indicative of early collagen matrix breakdown . This correlation was particularly pronounced in the deep layers of cartilage adjacent to the subchondral bone.…”

“…c). Furthermore, in patients with unilateral, reconstructed anterior cruciate ligament (ACL) tears within 10 years of their injury, who have a known increased risk for developing accelerated OA, significantly increased 18 F‐NaF PET uptake was observed in the subchondral bone of ACL‐reconstructed knee joints, compared with their uninjured contralateral knees . As molecular changes often precede changes at the tissue level, these findings suggest increased bone activity detected with 18 F‐NaF PET may serve as a marker for early OA in this population.…”