Introduction

Evaluations of anterior cruciate ligament (ACL)-injured and reconstructed knees have focused mainly on radiographic evaluations, subjective and objective scoring systems, and stability assessed with instruments such as KT-1000 (MEDmetric, San Diego, CA). These modalities are helpful in evaluating the current status and clinical function of each patient. However, they do not provide information on early or subtle changes in adjacent articular cartilage and knee kinematics that may influence treatment plan and long-term prognosis following ligament injuries.

Late complications of ACL injury, such as cartilage degeneration, were considered to be a consequence of long-standing functional deficit of the ACL itself. Contrary to this expectation, several studies reported that several cases resulted in degenerative arthritis, even after ACL-reconstruction surgery.¹^–⁴ These results indicate that initial injury to cartilage and underlying bony architecture may contribute substantially to the long-term outcomes following ACL injuries. Moreover, there needs to be better evaluation of surgical success because knee kinematics or cartilage health may not be restored despite surgical reconstructions. It is important to detect the extent of injury to tissues other than ACL as early as possible to properly guide the patients and obtain satisfactory outcomes. Recent advances in MRI enable physicians to make accurate morphologic assessment on injured structures and to precisely quantify changes in biochemical composition of cartilage and knee kinematics.

Quantitative MRI

MRI techniques have evolved over the past 2 to 3 decades to improve detection of minor changes in morphology of soft tissues as well as bony structures of knee joint. Various sequences, such as fat-suppression techniques, two-dimensional (2D) and three-dimensional (3D) fast spin echo, spoiled gradient-echo, driven equilibrium Fourier transform, dual echo steady state, and balanced steady-state free precession imaging have been used to delineate articular cartilage of knee joint.⁵ Scoring systems were also devised to accommodate these changes in semiquantitative fashion, including whole-organ MRI score (WORMS),⁶ the Boston-Leeds osteoarthritis knee score (BLOKS),⁷ and the knee osteoarthritis scoring system (KOSS).⁸ High sensitivity and specificity have been reported with these techniques.⁹

However, early phenomenon of cartilage breakdown does not always manifest as morphologic change. Earlier events of cartilage degeneration that precede morphologic change are known to be changes in its biochemical composition.¹⁰ Detection of early biochemical changes in cartilage is amenable with the recent development in MRI techniques. This article addresses some of the new advancements in quantitative MRI of articular cartilage and bone injuries. Recent literature and research in delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), T2 mapping, T1ρ mapping, and magnetic resonance spectroscopy imaging (MRSI) on bone marrow edema-like lesions (BMEL) is discussed.

dGEMRIC

Articular cartilage consists of water, chondrocytes, and extracellular matrix composed of collagen fibrils and proteoglycan, which contains negatively charged glycosaminoglycan (GAG) molecules. Decrease in GAG content is known to be an early event of cartilage breakdown.¹⁰ When anions such as gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA)^2- enter a joint, they distribute in cartilage inversely to the amount of GAG (Fig. 1). In other words, the more damaged the articular cartilage is, the higher is the concentration of Gd-DTPA^2- in the area. The gadolinium-enhanced measurement of tissue T1 values (T1Gd or dGEMRIC index) represents the amount of GAG in cartilage. Low T1Gd index is commonly observed in the area of cartilage degeneration.

Fig. 1 (A) Toluidine blue, a cationic dye used to visualize GAG, shows two distinct regions in histologic section: one staining light purple, indicating low GAG, and the other staining dark purple, indicating high GAG concentration. (B) The relative distribution of mobile ions. Due to the GAG’s negative charge, cations are more concentrated in cartilage than in the surrounding synovial fluid and are more concentrated in the high GAG than in the low GAG region. Conversely, the higher GAG, the less concentrated the anions.

Application in ACL Injuries

In an observational longitudinal study, cartilage GAG content after ACL injury was evaluated using dGEMRIC.¹¹ The ACL-injured group (29 subjects) was examined by dGEMRIC at 3 weeks and 2.3 years after injury and compared with a reference cohort (24 normal subjects). T1Gd index was measured at the central weight-bearing portion of lateral and medial femoral cartilage. The healthy reference group showed higher T1Gd value than the ACL-injured group did in both medial and lateral compartments. In the ACL-injured group, the T1Gd index was lower in subjects with concomitant meniscectomy than in subjects without meniscectomy in both medial and lateral compartments. Follow-up dGEMRIC examination in the ACL-injured group showed similar T1Gd values in the medial compartment and minor but significant increase in the lateral compartment. GAG content was lower in the ACL-injured group and more pronounced with associated meniscectomy. T1Gd index was considered to be a useful early biomarker for early posttraumatic osteoarthritis (OA).

In another study, 15 subjects with unilateral ACL injury were examined using dGEMRIC with the contralateral knee used as control.¹² The median time from injury to MRI was 82 days and the median slice of medial compartment was selected for comparison. Index comparisons were made of knee status (ACL-injured vs control group), scan order (ACL-injured first vs control first), and cartilage location (femur vs tibia). There was a significant difference in the mean dGEMRIC indices between injured and uninjured knees (Fig. 2). No significant effects were identified owing to test order or cartilage location.

Fig. 2 T1 maps of the medial compartment of the femur and the tibia with the mean dGEMRIC indices calculated. The blue and red regions denote high and low GAG concentrations, respectively. SD, standard deviation.

Review

Advantages of dGEMRIC

• It is an effective demonstration of GAG changes in cartilage

• It is a well-validated method of measuring GAG level.

Disadvantages of dGEMRIC

• It is time consuming and requires an intravenous injection of gadolinium followed by light exercise for even diffusion of contrast throughout the joint. Although there is no unanimous agreement on the time interval, about 50 to 90 minutes are needed from injection to imaging. Several hours are required to undergo the whole process, which comprises injection, joint exercise, diffusion, and image acquisition.

• It requires a two to three times higher dose of intravenous gadolinium than usual. Intravenous use of gadolinium has been implicated in the rare but fatal condition of nephrogenic systemic fibrosis for patients with renal insufficiency.

T2 mapping

T2 mapping measures interactions between a water molecule and surrounding macromolecules and reflects the collagen component in the cartilage extracellular matrix. Increased interaction between water and collagen decreases T2 values. Therefore, T2 mapping is very sensitive to water and collagen changes in cartilage, which subsequently makes it suitable for early detection of degeneration. It is also sensitive to the orientation of collagen fibrils. Taking zonal variations of collagen orientation in cartilage into account, T2 mapping enables analysis of cartilage in layers. T2 values are barely influenced by GAG content in cartilage.

Application in ACL Injuries

T2 mapping has not been popularized in evaluation of ACL-injured patients. One recent longitudinal study used this technique in part to assess cartilage status of ACL-injured subjects at follow-up.¹³ Forty-two knees with acute, isolated ACL injury underwent MRI at the time of injury and at yearly follow-up with a maximum of 11 years (Figs. 3 and 4). All subjects showed chondral damage at the time of injury. By follow-up years 7 to 11, the risk of cartilage loss for lateral femoral condyle was 50 times baseline, 30 times for patella, and 19 times for medial femoral condyle.

Fig. 3 A patient’s MRI at 22 months after ACL injury. (A) The cartilage-sensitive sequence shows depression of the far posterolateral tibial plateau with cartilage loss. Focal bone formation is seen over the site of impact (arrow). (B) T2 mapping shows prolongation of T2 relaxation times over the far posterolateral tibial plateau (solid arrow) as well as over the central lateral tibial plateau (dashed arrow), an area that was not involved by the initial bone bruise.

Fig. 4 The patient from Fig. 3, 4 years after injury. (A) Morphologic image shows depression of the far posterolateral tibial plateau. (B) T2 mapping shows progressive prolongation of T2 relaxation times over the central tibial plateau (arrow) compared with the study in Fig. 3.

To acquire very short T2 signal from type-I collagen of tendons, ligaments, or menisci, a specific sequence is needed. Ultrashort echo time-enhanced T2* (UTE-T2*) was used in an effort to detect early degeneration of meniscal tissue before surface breakdown.¹⁴ The investigators compared UTE-T2* with histologic findings in 16 cadaveric menisci. UTE-T2* values tended to be lower in histologically normal menisci and higher in torn or degenerated tissues. UTE-T2* values of 10 asymptomatic subjects were compared with ACL-injured subjects with or without meniscal tear. Posteromedial meniscus UTE-T2* values in ACL-injured subjects with medial meniscus tear were 87% higher than in asymptomatic control subjects (P<.001). Posteromedial meniscus UTE-T2* values in ACL-injured subjects without medial meniscus tear were 33% higher than control (P = .001) (Fig. 5). The investigators stated that UTE-T2* mapping is sensitive to subclinical degeneration of meniscal tissue.