Evaluation of radial distribution of cartilage degeneration and necessity of pre-contrast measurements using radial dGEMRIC in adults with acetabular dysplasia

Hip osteoarthritis (OA) is one of the major causes of musculoskeletal disability among adults[1]. One of the common anatomical predisposing factors for hip OA, acetabular dysplasia (AD), is seen not only in young patients but also in elderly patients[2]. A shallow acetabulum results in statically elevated contact pressure, reduced contact area, and joint instability, and OA tends to develop much earlier in the population with AD than in those with normal acetabular architecture[3, 4]. Hip preserving procedures are desirable solutions especially for young or active patients with AD[5]. They have been widely performed and are accounted as extremely effective treatments for patients without significant secondary OA[6, 7]. However, the reliability of these procedures in patients with secondary OA remains undefined[5, 6, 8]. The level of articular cartilage degeneration is the most important factor affecting the postoperative results[9]. Due to the unreliability of preoperative radiographic measurements, preoperative magnetic resonance imaging (MRI) is needed to assess the cartilage status in these patients[10].

Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) is a minimally invasive technique to assess the biochemical properties of articular cartilage. The intravenously injected anionic contrast agent gadopentetate (Gd-DTPA^2-) distributes in cartilage inversely to the concentration of negatively charged glycosaminoglycans (GAGs). GAGs provide cartilage with its compressive stiffness and are lost early during development of OA[11]. The dGEMRIC technique has been shown to be useful for assessing cartilage integrity in dysplastic hips by using coronal T1 mapping sequences[10, 12]. The radial dGEMRIC is obtained by radial reformation from a 3D data set using dual flip angle T1 mapping sequence. Compared to conventional coronal T1 mapping, the radial dGEMRIC provides radial reformatted slices rotating from anterior to posterior perpendicular to the acetabular rim, allowing evaluation of the cartilage status in various radial regions of the entire hip joint. Distribution of the T1 dGEMRIC values measured using radial dGEMRIC have been found to be unique in different sub-groups of femoroacetabular impingement (FAI)[13]. These patterns of cartilage degeneration, reflected by the radial dGEMRIC index, have not yet been fully investigated on dysplastic hips at different stages of secondary OA.

Currently, post-contrast T1 relaxation time (T1_Gd) is commonly used as the dGEMRIC index to determine the relative GAG levels within articular cartilage[10, 12–14]. An inherent assumption behind this is that pre-contrast T1 relaxation time (T1_pre) does not vary significantly with the health status of cartilage. However, T1_pre values can vary greatly in reparative cartilage and in the native cartilage with fibrillation or edema, compared to normal hyaline cartilage[15, 16]. The difference between the relaxation rates (ΔR1= 1/T1_Gd - 1/T1_pre) showed a better correlation with biopsy-determined GAG content in transplanted cartilage than either T1_pre or T1_Gd[16]. In native cartilage, a high correlation between T1_Gd and ΔR1 was observed in the weight-bearing region of hip and knee joints in asymptomatic volunteers and OA patients[17–19]. The relationship between T1_Gd and ΔR1 on radial T1 mapping has not been reported.

Based on the above-mentioned findings, we hypothesized that: radial dGEMRIC would depict different patterns of articular cartilage degeneration in dysplastic hips at different stages of secondary OA; and that pre-contrast imaging is unnecessary for radial dGEMRIC in hips at any stage of secondary OA. The aims of this current study were to investigate, first, the radial distribution of cartilage degeneration using radial dGEMRIC indices, and second, the correlations between radial T1_Gd and ΔR1 in dysplastic hips at different stages of secondary OA.

In this study, different patterns of T1_Gd were shown in various radial sub-regions of dyplastic hip joints in pace with the aggravation of secondary OA. In studies performed on healthy asymptomatic volunteers, T1_Gd values were reported as 570 ± 90 ms on coronal T1 mapping by Kim et al.[12], and the mean value of T1_Gd ranged from 553.9 to 629.4 ms on radial T1 mapping according to Bittersohl et al.[25]. Using the values of healthy asymptomatic volunteers as the normal standard[12, 25], hips without radiographic OA in the present study showed a normal mean value of T1_Gd (538 ~ 624 ms) in the radial sub-regions from anterior to posterosuperior and a mildly decreased T1_Gd value (mean, 502 ms) in the posterior, with a higher T1_Gd value toward the superior sub-regions. In hips with mild radiographic OA a significant decrease in T1_Gd was detected in the radial sub-regions from anterosuperior to superior, compared to the hips without radiographic OA. In the hips with moderate to severe radiographic OA, a significant overall decrease in T1_Gd was found compared to those without radiographic OA. The patterns of cartilage degeneration in this series accorded well with the general understanding of cartilage damage in the hip with dysplasia. Previous arthroscopic and radiographic studies have indicated that there is a high prevalence of cartilage lesions in the anterosuperior and superoanterior regions[26, 27], and early degenerative processes in dysplastic hips originate at the watershed zone between the acetabular labrum and the acetabular cartilage[28]. Recently, another study using radial dGEMRIC to evaluate cartilage degeneration in hip dysplasia was published by Domayer et al.[14]. Radial dGEMRIC showed an increased T1 in the weight-bearing areas of the acetabulum when the dGEMRIC index was more than 500 ms and a globally decreased T1 when the dGEMRIC index was less than 500 ms. Those findings corresponded to ours in the subgroups without radiographic OA and with moderate to severe radiographic OA.

The decrease of T1_Gd value in the posterior sub-region in hips without OA and with mild OA detected in the current study is not an unexpected finding. Knowledge of normal variations of GAG content within different regions of the hip joint is critical for defining the “abnormal” T1_Gd and should be taken into consideration. GAG content was revealed to be higher in the weight-bearing portions of the hip joint with a gradual decrease toward the inferior regions[29, 30]. Correspondingly, radial T1_Gd shows a zonal variation in adult asymptomatic hip joints, with higher values toward the superior regions and the lowest value noted in the posterior[25]. Further efforts are needed to establish the ideal zonal cutoff value of T1_Gd for distinguishing abnormal cartilage from normal.

Whether T1_Gd gives information comparable to ΔR1 is one of the central issues in dGEMRIC. Watanabe et al. showed that ΔR1 had a better correlation with biopsy-determined GAG content in transplanted cartilage than either T1_pre or T1_Gd alone[16]. In native articular cartilage, ΔR1 was equally effective as T1_Gd for both OA and healthy subjects[17–19]. According to the study performed on FAI patients by Bittersohl et al., the correlation between ΔR1 and T1_Gd within the weight-bearing region of the hip joint was −0.95 in a study cohort with Tönnis grade 0, -0.89 in Tönnis grade 1 and −0.88 in asymptomatic volunteers[19]. Li et al. compared the ability of ΔR1 and T1_Gd to differentiate patients with knee OA from healthy subjects[17]. In their study, ΔR1 and T1_Gd were found to be highly correlated (r = −0.96) and almost identical in terms of effect sizes and areas under receiver operating characteristic curves. Williams et al. also reported a high correlation (r = −0.87 ~ −0.96) between ΔR1 and T1_Gd in knee joints with and without symptoms[18]. Another study found that T1_pre values were only minimally different in early cartilage degeneration[31]. Our study showed good consistence with those previous studies. No significant difference of T1_pre was detected in any radial sub-regions except the superoanterior and posterior in hips with radiographic OA, compared to those without. Radial ΔR1 was observed to have similar patterns of radial distribution and a high inverse linear correlation with radial T1_Gd (r = −0.869 ~ −0.944) in all 3 subgroups. Correlation coefficients between ΔR1 and T1_Gd noted by the present study were in accordance with those (r = −0.87 ~ −0.96) noted by previous studies[17–19]. Considering the logistical costs in terms of time and effort to acquire T1_pre measurements, the results of the present study support that the current practice of measuring T1_Gd is adequate for assessing native cartilage in AD patients using radial dGEMRIC.

The radial dGEMRIC index, with the potential to reflect cartilage status in the entire hip joint, should be effective and helpful for preoperative evaluation in adult AD patients. The different patterns of T1_Gd in various radial sub-regions shown in this current study indicate that the articular cartilage from anterior to superior and posterior is vulnerable to degenerative processes, and therefore evaluation of cartilage status in these sub-regions is critical for predicting the postoperative effects in cases with early stages of secondary OA. In contrast, significant overall cartilage damage with advanced OA presages a poor postoperative outcome.

The main limitation of the present study was the lack of a healthy control group, for ethical reasons, and therefore the normal zonal variations of dGEMRIC indices are not available. It may not be accurate enough to define “abnormal” radial T1_Gd using the reported normal range of T1_Gd value measured on coronal T1 mapping as the normal standard, particularly for the inferior sub-regions. For the same reason, subgroup comparisons were only performed between hips with radiographic OA and those without instead of healthy asymptomatic hips. It is possible that the decrease in T1_Gd in hips with radiographic OA was underestimated. However, values of radial T1_Gd in hips without radiographic OA in this study were found to be comparable with those in healthy volunteers reported by a previous study[25]. So we believe the issue should have a minimal impact on our conclusion on subgroup comparisons. Future studies should involve healthy asymptomatic volunteers to establish the normal range of radial T1_Gd and the best cutoff values for distinguishing abnormal cartilage from normal. In addition, the present study included a relatively inhomogeneous cohort with wide age range (14 to 54 years) and therefore, age related primary OA may be the potential cofounding. Statistically, bilateral observations in part of the study samples may be not strict although no significant correlations (p = 0.122 ~ 0.994) of the radial indices were detected between two hips in the same patient. As in previous studies as described by Kim et al. and Bittersohl et al.[12, 25], differentiation between acetabular and femoral cartilage was not possible for the ROI analysis on a 1.5 T scanner because of the limitation of spatial resolution. Joint fluid as well as Gd-DTPA^2- in the synovial fluid may have altered the T1 value.

Different patterns of cartilage degeneration were detected in dysplastic hips at different stages of secondary OA by radial dGEMRIC indices, with a significant decline of cartilage function in the radial sub-regions from anterosuperior to superior in those with mild radiographic OA, and overall cartilage damage in those with moderate to severe radiographic OA. Because of the high correlations between ΔR1 and T1_Gd, pre-contrast measurements seem unnecessary for radial dGEMRIC regardless of the severity of OA. With the ability to reflect cartilage status in the entire hip joint, radial dGEMRIC seems to be a more useful technique than conventional coronal imaging for preoperative evaluation in AD patients at an early stage of secondary OA.