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dGEMRIC 和 T2 成像与实验性羊 FAIR 模型中的组织学软骨退变相关吗?

Do dGEMRIC and T2 Imaging Correlate With Histologic Cartilage Degeneration in an Experimental Ovine FAI Model?

机构信息

F. Schmaranzer, E. F. Liechti, M. Tannast, Department of Orthopaedic Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland L. Arendt, K. Nuss, B. von Rechenberg, M. Tannast, Musculoskeletal Research Unit (MSRU), Equine Hospital, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland P. R. Kircher, Department of Small Animals, Division of Diagnostic Imaging, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland.

出版信息

Clin Orthop Relat Res. 2019 May;477(5):990-1003. doi: 10.1097/CORR.0000000000000593.

Abstract

BACKGROUND

Biochemical MRI of hip cartilage such as delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 mapping is increasingly used to judge cartilage quality in the assessment of femoroacetabular impingement (FAI). The current evidence is sparse about which of these techniques yields a stronger correlation with histologic cartilage degeneration because of the difficulty in validating biochemical MRI techniques against histology in the clinical setting. Recently, an experimental ovine FAI model was established that induces chondrolabral damage and offers a validated platform to address these limitations.

QUESTIONS/PURPOSES: In a sheep model, we asked: (1) Do dGEMRIC and/or T2 values of acetabular and femoral cartilage correlate with histologic cartilage degeneration as assessed with the Mankin score? (2) Do simultaneously measured dGEMRIC and T2 values correlate in an experimental ovine FAI model?

METHODS

We performed an experimental pilot study on five female Swiss Alpine sheep (10 hips) that underwent postmortem MRI, including biochemical cartilage sequences, after a staged FAI correction had been performed on one side. No surgery was performed on the contralateral side, which served as a healthy control. In these sheep, an extraarticular intertrochanteric varus osteotomy was performed to rotate the naturally aspherical ovine femoral head into the acetabulum to induce cam-type FAI and chondrolabral damage comparable to human beings. After a 70-day ambulation period, femoral osteochondroplasty was performed and all sheep were euthanized after a total observation period of 210 days. Before they were euthanized, the sheep received a contrast agent and roamed and walked for at least 45 minutes. Hips were prepared to fit in a knee coil and MRI was performed at 3 T including a three-dimensional (3-D) dGEMRIC sequence, a two-dimensional (2-D) radial T2 mapping sequence, and a 2-D radial proton density-weighted sequence for morphologic cartilage assessment. Using specifically developed software, the 3-D dGEMRIC images and T2 maps were coregistered on the 2-D morphologic radial images. This enabled us to simultaneously measure dGEMRIC and T2 values using the identical regions of interest. dGEMRIC and T2 values of the acetabular and femoral cartilage were measured circumferentially using anatomic landmarks. After MRI, bone-cartilage samples were taken from the acetabulum and the femur and stained with toluidine blue for assessment of the histologic cartilage degeneration using the Mankin score, which was assessed in consensus by two observers. Spearman's rank correlation coefficient was used to (1) correlate dGEMRIC values and T2 values with the histologic Mankin score of femoroacetabular cartilage; and to (2) correlate dGEMRIC values and T2 values of femoroacetabular cartilage.

RESULTS

A moderate to fair correlation between overall dGEMRIC values of the acetabular cartilage (R = -0.430; p = 0.003) and the femoral cartilage (R = -0.334; p = 0.003) versus the histologic Mankin score was found. A moderate correlation (R = -0.515; p = 0.010) was found among peripheral dGEMRIC values of the acetabulum, the superior femoral cartilage (R = -0.500; p = 0.034), and the histologic Mankin score, respectively. No correlation between overall and regional femoroacetabular T2 values and the histologic Mankin scores was found. No correlation between overall and regional femoroacetabular dGEMRIC values and T2 values was found.

CONCLUSIONS

In this recently established sheep model, we found dGEMRIC values correlated well with histologic evidence of cartilage degeneration in the hip. This combination of a robust animal model and an accurate imaging technique appears to offer a noninvasive means to study the natural course of FAI and to compare the effectiveness of potential surgical options to treat it.

CLINICAL RELEVANCE

This translational study supports the continuing use of dGEMRIC as a biomarker for prearthritic cartilage degeneration with the ultimate goal to identify patients who will benefit most from corrective FAI surgery. The value of T2 imaging of hip cartilage warrants further investigation.

摘要

背景

髋关节软骨的生化 MRI 技术,如延迟钆增强 MRI(dGEMRIC)和 T2 映射,越来越多地用于评估髋关节撞击症(FAI)中的软骨质量。由于在临床环境中验证生化 MRI 技术与组织学之间存在困难,目前关于这些技术中哪一种与组织学软骨退变的相关性更强的证据还很有限。最近,建立了一种实验性羊 FAI 模型,该模型可诱导软骨-半月板损伤,并为解决这些局限性提供了经过验证的平台。

问题/目的:在绵羊模型中,我们提出以下问题:(1)髋臼和股骨软骨的 dGEMRIC 和/或 T2 值是否与组织学软骨退变的 Mankin 评分相关?(2)在实验性羊 FAI 模型中,同时测量的 dGEMRIC 和 T2 值是否相关?

方法

我们对 5 只雌性瑞士阿尔卑斯羊(10 只髋关节)进行了一项实验性初步研究,在一侧进行了分期 FAI 矫正后,对这些羊进行了尸体 MRI 检查,包括生化软骨序列。对侧髋关节未进行手术,作为健康对照。在这些羊中,进行了关节外转子间内翻截骨术,以使自然非球形的羊股骨头旋转到髋臼中,从而诱发类似于人类的凸轮型 FAI 和软骨-半月板损伤。在 70 天的步行期后,进行了股骨骨软骨切除术,所有羊在总共 210 天的观察期后被安乐死。在安乐死前,羊接受了造影剂,并在至少 45 分钟的时间内四处走动和行走。将羊的髋部准备好放入膝关节线圈中,并在 3T 磁共振成像仪上进行检查,包括三维(3D)dGEMRIC 序列、二维(2D)径向 T2 映射序列和二维径向质子密度加权序列,以评估形态学软骨。使用专门开发的软件,将 3D dGEMRIC 图像和 T2 图谱与 2D 形态学径向图像进行了配准。这使我们能够使用相同的感兴趣区域同时测量 dGEMRIC 和 T2 值。使用解剖学标志,在髋臼和股骨周围测量 dGEMRIC 和 T2 值。在 MRI 后,从髋臼和股骨取出骨软骨样本,并使用甲苯胺蓝染色评估组织学软骨退变的 Mankin 评分,由两名观察者进行共识评估。使用 Spearman 秩相关系数来(1)dGEMRIC 值和 T2 值与髋关节软骨的组织学 Mankin 评分相关;以及(2)髋关节软骨的 dGEMRIC 值和 T2 值相关。

结果

发现髋臼软骨(R = -0.430;p = 0.003)和股骨软骨(R = -0.334;p = 0.003)的整体 dGEMRIC 值与组织学 Mankin 评分之间存在中度至适度的相关性。发现髋臼周围的 dGEMRIC 值(R = -0.515;p = 0.010)、上股骨软骨(R = -0.500;p = 0.034)与组织学 Mankin 评分之间存在中度相关性。未发现整体和区域髋关节 T2 值与组织学 Mankin 评分之间存在相关性。未发现整体和区域髋关节 dGEMRIC 值与 T2 值之间存在相关性。

结论

在这个最近建立的绵羊模型中,我们发现 dGEMRIC 值与髋关节软骨的组织学退变证据密切相关。这种强大的动物模型和准确的成像技术的结合,似乎为研究 FAI 的自然病程并比较潜在手术治疗方案的有效性提供了一种非侵入性的方法。

临床意义

这项转化研究支持将 dGEMRIC 继续作为关节炎前软骨退变的生物标志物,最终目标是确定最受益于 FAI 矫正手术的患者。髋关节软骨 T2 成像的价值值得进一步研究。

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