Home Comparison of T1ρ, dGEMRIC, and Quantitative T2 MRI in Preoperative ACL Rupture Patients
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Comparison of T1ρ, dGEMRIC, and Quantitative T2 MRI in Preoperative ACL Rupture Patients

Rationale and Objectives

T1ρ, inversion recovery sequence with a gadolinium contrast agent (dGEMRIC), and T2 mapping have shown sensitivity toward different osteoarthritic-associated compositional changes after joint injury, but have not been studied concomitantly in vivo. We hypothesized that these magnetic resonance imaging sequences can be used to measure early glycosaminoglycan (GAG) losses and collagen disruption in cartilage of anterior cruciate ligament (ACL) rupture patients.

Materials and Methods

Thirteen acute ACL rupture patients were each imaged during a 4-hour presurgery workup to acquire a fast-spin-echo-based T1ρ sequence, a multi-echo spin-echo T2 sequence, and T1-weighted dGEMRIC an average of 55.7 days after injury. After acquisition, the three sequences’ relaxation times were analytically compared.

Results

Site-specific differences were evinced, but nonsignificant differences in mean relaxation time between layers of the same region and sequence were observed (analysis of variance, P < .05). Spearman’s correlation coefficients of 0.542 (T1ρ vs. T2, P < .05), −0.026 (T1ρ vs. dGEMRIC, P = .585) and −0.095 (T2 vs. dGEMRIC, P < .05) were found.

Conclusion

No appreciable focal GAG loss was detected by dGEMRIC, and T2 was generally elevated in the early acute phase of blunt trauma injury. In contrast, both general and focal elevations in T1ρ relaxation times were identified, indicating an acute increase in unbound water in the matrix after blunt trauma, and show that patient-specific cartilage changes occur within otherwise healthy, young patients. Further investigation into each sequence’s long-term significance is warranted to help clinicians decide which sequence(s) will be the most useful for osteoarthritis prognosis given the challenge of concomitantly acquiring all three in a busy clinical setting.

Introduction

Articular cartilage injuries that lead to posttraumatic osteoarthritis include injury-induced cell death, matrix degradation, cartilage fissures, and alterations in cartilage material and mechanical properties . One of the most common joint injuries with damage to articular surfaces in the absence of osteochondral fractures or overt articular surface injury is in the knee with an acute anterior cruciate ligament (ACL) tear. At the time of knee arthroscopy, visible evidence of cartilage injury is not observed in the majority of cases . Morphologic changes in cartilage are less likely to be observed in the first year after ACL reconstruction, compared to imaging sessions observed years after injury, when a patient is closer to osteoarthritis (OA) development . However, within 15 years of injury, a large percentage of patients show evidence of structural abnormalities associated with knee OA on conventional radiographs, morphologic magnetic resonance imaging (MRI), or arthroscopy . The ability to detect these changes early in the process of developing posttraumatic osteoarthritis (ie, imaging biomarkers) would be a significant advance as it increases the possibility of intervention before significant joint deterioration.

Emerging quantitative cartilage imaging techniques including T1ρ, T2 mapping, and delayed gadolinium enhanced MRI of cartilage (dGEMRIC) are more promising than morphological sequences in acute injury assessment. Evidence in the literature indicates that each of these imaging sequences probes different biologic markers of cartilage degeneration. Researchers have been working to define what each of these quantitative sequences measures. T2 mapping correlates predominately with cartilage hydration and collagen content . T1ρ is a relaxation measurement that probes the rate of exchange between protons of free water and those from water associated with macromolecules in the cartilage’s extracellular matrix, giving rise to longer relaxation times where components of the extracellular matrix, especially proteoglycans (PGs), are disrupted . dGEMRIC measures T1 relaxation changes after an intravenous injection of a charged gadolinium-based contrast agent to directly measure the fixed charge density arising from glycosaminoglycan chains of PG .

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Materials and methods

Inclusion Criteria and Subjects

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Table 1

Acute ACL Rupture Patient Demographics

ACL Patient Gender Age Height (m) Weight (kg) BMI Knee Imaged BC Injury to Preoperative Scan (weeks) 1 F 19 1.89 84.0 24.4 Left Yes 1.6 2 F 20 1.70 71.2 24.9 Right No 1.3 3 M 28 1.73 101.0 33.7 Left Yes 4.4 4 M 25 1.98 122. 5 30.4 Right Yes 19.0 5 F 22 1.70 64.0 22.5 Left Yes 8.3 6 F 18 1.78 77.1 24.3 Left Yes 5.9 7 M 29 1.73 66.0 22.4 Left Yes 11.1 8 M 24 1.78 92.4 27.5 Left Yes 4.1 9 M 22 1.78 74.0 25.8 Right No 1.3 10 F 23 1.70 120.00 41.50 Left Yes 19.4 11 F 20 1.72 70.00 23.70 Left Yes 1.0 12 M 25 1.78 95.90 30.30 Left Yes 17.1 13 M 22 1.78 100.00 31.60 Left Yes 8.9 Average – 23.2 1.76 84.6 27.9 – – 8.0

ACL, anterior cruciate ligament; BC, bone contusion; BMI, body mass index; F, female; M, male.

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Imaging

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Figure 1, Patient 6's presurgery, same-day imaging study of cartilage-specific T1ρ, T1-weighted inversion recovery sequence with a gadolinium contrast agent (dGEMRIC), and T2 magnetic resonance imaging 3.1 weeks after the initial anterior cruciate ligament injury. A bone contusion and more focal elevations are present in the T1ρ panel ( left ). T2 relaxation times are globally elevated compared to the T1ρ map, reaffirming that increased fluid content (T2 relaxation times increase) shortly after injury is occurring on a whole-joint level, whereas T1ρ is also affected by proteoglycan content and thus displays different relaxation patterns. GAG, glycosaminoglycan; Gd, gadolinium.

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Image Postprocessing

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Figure 2, (a) Automated image co-registration is achieved by feature-based sulcus location along an objective bone-cartilage-interface (BCI) with anthropometric scaling to posterior condyle radius for inter-knee comparisons in the 20-ms T1ρ image of anterior cruciate ligament patient 6. (b) Each location of the cartilage examined ( orange ) was subdivided into smaller regions, as shown in the same patient's inversion recovery sequence with a gadolinium contrast agent (dGEMRIC) image. Relaxation times within each subdivision's radial and transitional cartilage zones were averaged and reported for each patient's dataset.

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Data Analysis

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Results

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Figure 3, Whole region average (and standard deviation) for each patient's (as well as all patients combined) 1.0 mm (approximately radial) and 1.5 mm (approximately transitional) cartilage layers for T1ρ, T2, and inversion recovery sequence with a gadolinium contrast agent (dGEMRIC) relaxation times by each region examined (averaged 20% to 80% in the patella and tibial plateau, 0° to 50° in the posterior portion of the lateral femoral condyle as defined in Fig 2 b).

Figure 4, Relaxation times incremented into subregions and averaged across all patients at both cartilage depths demonstrate differing degrees of site-specific spatial variation across all three sequences.

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Figure 5, Spearman's correlation coefficients ( r ) are shown for T1ρ compared to T2, T1ρ compared to inversion recovery sequence with a gadolinium contrast agent (dGEMRIC), and T2 compared to dGEMRIC relaxation times (*significant correlation, P < .05). Correlation values were computed by combining both layers' subregion (averaged every 10° or 10%) data by patella, femur, tibia, and overall combined regions. The correlation values for each layer's comparisons (r 1.0 = correlation value for 1.0-mm layer, r 1.5 = correlation value for 1.5-mm layer) are also shown in the lower portion of each box.

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Discussion

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Figure 6, Closer examination of one patient's subregion relaxation times demonstrates how each sequence's relaxation times vary across regions. Note in the T2 fat-saturated image that increased signal in the femur (superior to the sulcus, between the two arrows ) and the posterior aspect of the tibial plateau ( single arrow ) indicate bone contusions; there are significant elevations in T1ρ and T2 relaxation times near these bone contusions (0° to −25° femur, 80 to 100 tibia displayed in graphs at right). Fluid signal (near the −40° reference) trapped between the meniscus and the femoral condyle precludes overlying sulcus cartilage from meaningful analysis.

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Conclusion

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