磁共振成像对膝关节透明软骨病变的基础及临床应用研究
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摘要
第一部分膝关节软骨MRI序列对比研究
     研究目的
     通过对一组青年志愿者膝关节的MRI检查,探讨MRI显示膝关节软骨的最佳序列。
     材料与方法
     1.研究对象
     选取青年志愿者20例,其中男10例,女10例。无膝关节疼痛症状及其他病史。
     2.MR扫描技术
     使用GE(GE Signa EXCITE HD;GE healthcare,USA)3.0T超导磁共振成像仪。在常规序列扫描的基础上进行膝关节3D-FS-SPGR、FS-GRE、FS-FSE序列矢状位扫描。
     3.影像分析方法
     所有图像均传输到AW4.3工作站及PACS系统进行处理分析。
     所有图像由两位膝关节放射学专家共同阅片,在AW4.3工作站上应用GE公司配置的自带软件分别对3D-FS-SPGR、FS-GRE、FS-FSE序列关节软骨及关节软骨周围的软骨下骨、肌肉、滑液及背景信号进行测量。感兴趣区面积一般设定在4mm~2,每个固定部位重复测量三次,取其平均值。然后通过计算公式分别计算出软骨、软骨下骨、肌肉及滑液的信噪比(SNR)、信噪比效率,并分别计算出软骨与周围组织的对比噪声比(CNR)。
     4.统计学分析
     采用SPSS13.0统计包进行统计分析。
     对3D-FS-SPGR序列、FS-GRE序列、FS-FSE序列所显示的软骨、肌肉、滑液及软骨下骨SNR、SNR效率以及软骨与其他组织的CNR进行统计学分析,方差齐性则采用单因素方差分析(One-way ANOVA)比较各组间的差异,P≤0.05,组间比较存在统计学意义,均数间两两比较采用LSD法;方差不齐,采用非参数秩和检验(Krustal-wallis test)进行比较分析,P≤0.05被认为组间有统计学差异,然后采取多重比较Dunnett's T3法进行两两组间比较。
     结果
     1.正常膝关节软骨MR成像敏感序列比较
     1.1正常膝关节软骨及相邻组织在三种序列上SNR及SNR效率分析
     关节软骨SNR:三种序列SNR测量比较,P=0.000,方差不齐,采用非参数秩和检验进行比较分析,结果P<0.05,组间测量值差异有统计学意义,组间比较3D-FS-SPGR序列与FS-FSE序列、3D-FS-SPGR序列与FS-GRE序列及FS-GRE序列与FS-FSE序列之间存在统计学差异,P<0.05。说明3D-FS-SPGR序列关节软骨的信噪比最高,FS-FSE序列关节软骨信噪比最低;
     软骨下骨SNR:三种序列SNR测量比较,P=0.000,方差不齐,采用非参数秩和检验进行比较分析,P<0.05,组间测量值差异有统计学意义,组间比较3D-FS-SPGR序列与FS-FSE序列、3D-FS-SPGR序列与FS-GRE序列及FS-GRE序列与FS-FSE序列之间存在统计学差异,P<0.05。说明FS-FSE序列软骨下骨信噪比最低,而FS-GRE序列软骨下骨信噪比最高;
     肌肉SNR:三种序列SNR测量比较,P=0.000,方差不齐,采用非参数秩和检验进行比较分析,P<0.05,组间测量值差异有统计学意义,组间比较3D-FS-SPGR序列与FS-FSE序列、3D-FS-SPGR序列与FS-GRE序列及FS-GRE序列与FS-FSE序列之间存在统计学差异,P<0.05。说明3D-FS-SPGR序列肌肉信噪比最高,FS-FSE序列肌肉信噪比最低;
     滑液SNR:三种序列SNR测量比较,P=0.000,方差不齐,采用非参数秩和检验进行比较分析,P<0.05,组间测量值差异有统计学意义,组间比较3D-FS-SPGR序列与FS-FSE序列及FS-GRE序列与FS-FSE序列之间存在统计学差异,P<0.05;而3D-FS-SPGR序列与FS-GRE序列之间不存在统计学差异,P>0.05。说明FS-FSE序列滑液信噪比最高,而FS-GRE序列及3D-FS-SPGR序列滑液信噪比差别不大。
     FS-FSE序列显示滑液明显敏感于其他两序列,而3D-FS-SPGR序列在显示软骨方面强于其他两种序列。
     关节软骨SNR效率:三种序列SNR效率测量比较,P=0.085,方差齐性,P<0.05,组间测量值差异有统计学意义,组间比较3D-FS-SPGR序列与FS-FSE序列、3D-FS-SPGR序列与FS-GRE序列及FS-GRE序列与FS-FSE序列之间存在统计学差异,P<0.05。说明关节软骨在3D-FS-SPGR序列上SNR效率最高,在FS-FSE序列上SNR效率最低;
     软骨下骨SNR效率:三种序列SNR效率测量比较,P=0.000,方差不齐,采用非参数秩和检验进行比较分析,P<0.05,组间测量值差异有统计学意义,组间比较3D-FS-SPGR序列与FS-FSE序列、3D-FS-SPGR序列与FS-GRE序列及FS-GRE序列与FS-FSE序列之间存在统计学差异,P<0.05。说明软骨下骨在FS-FSE序列上SNR效率最低,在FS-GRE序列上SNR效率最高;
     肌肉SNR效率:三种序列SNR测量比较,P=0.000,方差不齐,采用非参数秩和检验进行比较分析,P<0.05,组间测量值差异有统计学意义,组间比较3D-FS-SPGR序列与FS-FSE序列及FS-GRE序列与FS-FSE序列之间存在统计学差异,P<0.05,而3D-FS-SPGR序列与FS-GRE序列之间不存在统计学差异,P>0.05。说明肌肉在FS-FSE序列上SNR效率最低,在3D-FS-SPGR序列及FS-GRE序列上相似,没有明显差别;
     滑液SNR效率:三种序列SNR效率测量比较,P=0.006,方差不齐,采用非参数秩和检验进行比较分析,P<0.05,组间测量值差异有统计学意义,组间比较3D-FS-SPGR序列与FS-FSE序列、3D-FS-SPGR序列与FS-GRE及FS-GRE序列与FS-FSE序列之间存在统计学差异,P<0.05。说明滑液在FS-FSE序列上SNR效率最高,在3D-FS-SPGR序列SNR效率最低。
     由于3D-FS-SPGR序列采集时间长,其各组织SNR效率均会降低。软骨SNR效率在3D-FS-SPGR序列上还是高于其他两序列;滑液SNR效率在3D-FS-SPGR序列上最低,在FS-FSE序列上最高;肌肉SNR效率在3D-FS-SPGR序列上与FS-GRE序列相近;软骨下骨SNR效率在3D-FS-SPGR序列上介于三序列中间。
     1.2正常膝关节软骨与相邻组织对比噪声比分析
     软骨/软骨下骨CNR:三种序列CNR测量比较,P=0.052,方差齐性,P<0.05,组间测量值差异有统计学意义,组间比较3D-FS-SPGR序列与FS-FSE序列、3D-FS-SPGR序列与FS-GRE序列及FS-GRE序列与FS-FSE序列之间存在统计学差异,P<0.05。说明在3D-FS-SPGR序列上软骨/软骨下骨CNR最高,而在FS-FSE序列上其对比噪声比最低:
     软骨/肌肉CNR:三种序列CNR测量比较,P=0.309,方差齐性,P<0.05,组间测量值差异有统计学意义,组间比较3D-FS-SPGR序列与FS-GRE序列及FS-GRE序列与FS-FSE序列之间存在统计学差异,P<0.05;而3D-FS-SPGR序列与FS-FSE序列之间未见明显统计学差异,P>0.05。说明FS-GRE序列上软骨/肌肉对比噪声比最低,而在3D-FS-SPGR序列与FS-FSE序列上未见明显差异;
     软骨/滑液CNR:三种序列CNR测量比较,P=0.005,方差不齐,采用非参数秩和检验进行比较分析,P<0.05,组间测量值差异有统计学意义,组间比较3D-FS-SPGR序列与FS-FSE序列、3D-FS-SPGR序列与FS-GRE序列及FS-GRE序列与FS-FSE序列之间存在统计学差异,P<0.05。说明在FS-FSE序列上软骨/滑液CNR最高,而在FS-GRE序列上最低。
     3D-FS-SPGR序列软骨/骨CNR最高,FSE序列在软骨/骨CNR最低;而FSE序列软骨/滑液CNR最高,GRE序列软骨/滑液CNR最低。
     结论
     在FS-FSE、FS-GRE和3D-FS-SPGR序列上,关节软骨显示为高信号,其中3D-FS-SPGR序列软骨SNR最高,软骨与周围组织的CNR最高,是显示关节软骨的最佳序列。
     第二部分膝关节软骨MR解剖与人体标本对照研究
     研究目的
     1.旨在利用膝关节尸体标本解剖与MR成像敏感序列进行关节软骨厚度测量并对照分析两种测量方法所得软骨厚度的差异;
     2.对膝关节软骨标本特殊染色,分析软骨组织主要成分含量在关节软骨不同位置的差异。
     3.利用3T MR新技术3D-FS-SPGR序列及T2~*GRE多回波序列分别对正常人膝关节软骨厚度及T2~*弛豫时间进行测量,初步确定正常人软骨厚度和T2~*弛豫时间正常值范围。
     1材料
     1.1标本组:选用国人青壮年中等身材无明显关节病变的成年男尸膝关节标本2例(新鲜冷藏),充分解冻的状况下均按常规序列进行MR扫描并进行FS-FSE、FS-GRE、3D-FS-SPGR序列矢状位扫描。复冻后按解剖部位进行矢状位解剖,解剖层厚2cm。
     1.2对照组:20例,同第一部分。
     2实验仪器
     2.1 MR仪器及扫描参数
     使用GE(GE signa VH/I;GE healthcare,Milwaukee,WI,USA)3.0T超导磁共振成像仪。对标本及正常组进行FS-FSE序列、FS-GRE序列及FS-SPGR序列扫描,扫描参数同第一部分。同时对正常组进行T2~*-GRE多回波序列扫描,扫描参数:TR100ms,TE3.6/8.9/14.1/19.4/24.6/29.8/35.1/40.3/45.6/50.8/56.1/61.3/66.6/71.8/77.4/82.3ms,35度翻转角,层厚4.0mm,层间隔0.5mm,FOV:16×16,矩阵:192×160,NEX:1,采集时间:4:46s左右。
     3尸体解剖、取材及组织染色
     3.1尸体解剖及取材
     膝关节以伸直位置于零下三十度状态中,将其取出由解剖教研室专业技术员用电锯进行矢状位解剖,层厚约2cm,解剖完成后立即用清水将标本表面污垢清除,以干布吸水,保持剖面相对干燥,进行照相。用游标卡尺测量固定解剖部位软骨的厚度,最后由专人对关节软骨进行取材,以备组织学分析使用。
     3.2组织学准备
     将关节软骨取材送至病理科,经中性甲醛液固定,石蜡包埋切片后进行维多利亚蓝-丽春红复合特殊染色,染色后在显微镜下观察软骨基质内胶原纤维的情况。
     4.图像处理及分析
     在AW4.3工作站上应用GE公司配置的自带软件对3D-FS-SPGR序列进行重建并对关节软骨厚度进行测量,同时对T2~*GRE多回波序列重建出反映软骨弛豫时间的T2~*map图并在固定位置测量软骨的T2~*弛豫时间。
     5.膝关节标本解剖与MR成像并软骨对照分析
     解剖后膝关节标本进行干燥处理并照相,然后用游标卡尺对软骨固定部位进行测量,并在3D-FS-SPGR序列上于相同部位进行测量,分析并比较关节软骨厚度在解剖与MR成像上的差异性。
     6统计学分析
     采用SPSS13.0统计包进行统计分析。
     正常人关节软骨厚度及T2~*弛豫时间测量结果分析,所有数据均以(均数±标准差)表示。
     结果:
     1.软骨组织学结果
     在镜下观察发现,接近软骨膜的基质丽春红染色较明显,而位于软骨深部的基质红色不明显,但对碱性染料(如维多利亚蓝)有较强的亲和力,不同软骨可有不同的胶原分布模式,表明软骨内纤维的分布方向适应与抵抗软骨通常承受的张力。如在关节软骨内的纤维分布呈现为一系列的哥特式拱形构造模式,有些软骨中可见纤维横向穿越软骨,在软骨的两侧边缘以拱形的方式与软骨膜连接。
     2.软骨解剖测量与MR测量对照
     通过2标本解剖与MR成像对照,两种方法测量的软骨厚度差异性很小,说明在3D-FS-SPGR序列上的测量结果大体反映了关节软骨解剖厚度。
     3.通过对正常人关节软骨厚度及T2~*弛豫时间值分别进行测量,得出一组正常人的测量值范围。
     结论
     1.通过膝关节标本解剖与MR成像测量及对比分析,FS-SPGR序列能够相对真实地反映关节软骨的形态及厚度;
     2.通过膝关节软骨的病理特殊染色,我们发现关节软骨在表层胶原纤维含量相对较多,软骨细胞及其周围基质相对较少,而在关节软骨深层,其胶原纤维含量相对较少,而软骨及软骨周围基质相对较多,说明关节软骨组织成分的分布与软骨的功能相一致。
     3.通过对膝关节正常组软骨厚度测量及T2~*弛豫时间测量,初步得出正常人关节软骨厚度及T2~*弛豫时间正常值范围。
     第三部分MR成像在膝关节软骨病变的临床应用研究
     研究目的
     1.利用3D-FS-SPGR序列对膝关节OA各期软骨厚度进行测量,与正常组进行对比分析,评价OA软骨厚度随病变进展其厚度的改变;
     2.利用软骨敏感序列对病变显示并与关节镜对照,通过各序列对软骨病变显示的特异性、敏感性等指标评价其在软骨病变诊断实际应用中的优越性;
     3.利用T2~*GRE多回波序列对膝关节OA各期软骨弛豫时间进行测量,与正常组软骨T2~*弛豫时间测量值对比,评价OA患者病变进程与T2~*弛豫时间变化的相关性;同时对急性损伤组T2~*弛豫时间进行分析,评价早期软骨损伤T2~*弛豫时间的改变。
     4.利用T2~*GRE多回波序列对膝关节软骨病变弛豫时间进行测量,评价软骨病变的进程;同时对急性损伤进行评价,目的是通过T2~*弛豫时间值伪彩图能够发现软骨损伤的隐匿性病变。
     材料与方法
     研究对象
     1病变组:入选标准:选取2006年6月~2008年1月在南方医院就诊具有膝关节疼痛及功能障碍等症状的患者,MR检查未进行关节镜检查,无膝关节手术病史;如有外伤病史,X线需排除明显膝部骨折症状。外伤患者以外伤时间周期进行分期,2个月内划入急性损伤期,2个月后划入慢性损伤期。因慢性期创伤性OA与退变性OA发病机理一致,所以在分组过程中将两者一并考虑。
     按照上述标准,有62例患者纳入本研究并进行关节软骨厚度测量,男27例,女35,年龄19~65岁,平均年龄36.8岁。
     62例中有36例MR检查后行关节镜检查,男19例,女17例,年龄21-61岁,平均年龄43.5岁。
     62例中有56例同时进行T2~*弛豫时间值测量,男25例,女31例,平均年龄36.4岁。
     2.病例入选标准及分期
     我们结合WOMAC骨关节炎指数评分及K-L放射学诊断标准将膝关节OA患者分为轻、中、重三组。
     3.按软骨损伤程度分级
     Ⅰ级:软骨完整;Ⅱ级:局限性软骨缺失无骨暴露;Ⅲ级:软骨破坏有骨暴露,软骨下骨完整无异常信号;Ⅳ级:软骨全层缺失,关节面下骨内有异常信号。
     这种分期以软骨损伤程度进行分期,有助于关节镜检查与MR检查所得结果进行对照,区别于上述以临床症状所进行的分组。
     仪器
     同第二部分
     图像处理及分析
     图像处理及测量同第一部分
     软骨病变损伤程度的诊断:术前由3位具有膝关节病变诊断经验的放射科教授分别对各显示软骨的序列进行阅片,然后再共同阅片。根据各序列中透明软骨影像表现做出诊断并对软骨病变进行分级。关节镜分级由临床关节镜专家分级,影像分级与关节镜分级采用双盲法。
     统计学分析
     采用SPSS13.0统计包进行统计分析。
     3D-FS-SPGR序列测量软骨厚度及T2~*GRE多回波序列测量软骨T2~*弛豫时间值,分析比较正常组与病变各组之间的差异性。方差齐性则采用单因素方差分析(One-way ANOVA)分别比较各组间的差异,P≤0.05进行均数间两两比较的LSD法;方差不齐,采用非参数秩和检验(Krustal-wallis test)进行比较分析,P≤0.05被认为组间有统计学差异,然后采取多重比较Dunnett's T3法进行两两组间比较。
     同时考虑到体重(kg)、身高(m)、BMI(体重/身高~2,kg/m~2)、年龄及性别对关节软骨厚度及软骨弛豫时间测量的影响,在病变组与对照组之间同时采用了非参数相关性检验(Spearman's检验)来分析相关因素对关节软骨的影响,P≤0.05被认为有统计学差异。
     软骨损伤程度的分析:以关节镜为金标准,利用敏感度、特异度、阳性预测值、阴性预测值及kappa系数等指标进行统计分析。
     结果
     1.OA病变各组与正常组关节软骨厚度测量结果对比
     通过对膝关节OA病变各组软骨厚度的测量并与正常组对比,轻度OA组关节软骨区域其厚度与正常组之间不存在统计学差异,而重度OA组大部分软骨区域其软骨厚度与正常组比较存在统计学差异。另外,软骨厚度的改变可能受到多方面因素的影响,如性别、年龄、体重及BMI等与软骨厚度改变之间存在负相关。
     2.OA病变各组T2~*弛豫时间测量与正常组对比
     通过对膝关节OA病变各组软骨T2~*弛豫时间测量并与正常组对比,轻度OA组大部分关节软骨区域其T2~*弛豫时间测量与正常组之间存在统计学差异,而重度OA组大部分软骨区域其T2~*弛豫时间测量其与正常组比较基本不存在统计学差异。软骨T2~*弛豫时间变化与年龄、体重及身高之间存在关联,T2~*弛豫时间变化可能受到多方面的影响。
     3.软骨病变在三种序列上的影像表现
     在MR各序列中,FS-FSE序列软骨缺损处积液为明显的高信号,正常软骨亦呈明显的高信号;FS-3D-SPGR序列上软骨缺损处积液呈低信号,周围正常软骨呈高信号,软骨缺损处或软骨内部损伤处呈低信号;FS-GRE序列软骨缺损处液体呈低信号,其周围正常软骨呈高信号,软骨损伤处呈稍低信号或与正常软骨相似的信号。
     4.FS-GRE、FS-FSE及3D-FS-SPGR序列对关节软骨病变的评价
     在MR各序列图像中,36名患者共288个软骨面中,关节镜检查共发现21名患者32处不同程度的病变。3D-FS-SPGR序列显示软骨病变效果最好,其病变敏感度99.2%,特异度94.4%,均高于FS-GRE序列、FS-FSE序列。3D-FS-SPGR序列的kappa值0.937>0.75,其在显示软骨病变方面与关节镜发现病变方面有极好的一致性。
     5.T2~*弛豫时间对关节软骨病变的评价
     利用T2~*弛豫时间测量及T2~* map图像对关节软骨病变进行分析是本论文研究的另一个重点。通过对关节软骨OA病变T2~*弛豫时间值测量研究发现:膝关节OA患者其关节软骨T2~*弛豫时间测量值因发病时间长短、发病轻重程度不同而不同。在OA患者早期常发现其软骨信号可见局限增高的现象,而在中晚期,其软骨信号与周围正常软骨信号一致或者低于周围正常软骨信号。在急性损伤期软骨信号在损伤处呈高T2~*弛豫时间值,而在损伤慢性期软骨T2~*弛豫时间降低至周围正常软骨水平或低于周围正常软骨水平。
     结论
     3.1通过关节软骨OA组与对照组厚度测量对比分析:发现关节软骨负重面大部分区域随着OA病情的加重,其软骨厚度变薄,软骨厚度改变除OA病变严重程度影响外,可能还受到体重、年龄及性别等因素的影响。
     3.2通过三种序列对软骨病变诊断并与关节镜对照,发现3D-FS-SPGR序列对病变的特异性及敏感性均高于其他两序列,而且3D-FS-SPGR表现了与关节镜病变诊断较高的一致性。
     3.3通过关节软骨OA组与对照组T2~*弛豫时间测量对比分析:发现关节软骨在正常组与OA组之间存在差异性。这种差异主要发生在轻度OA病变组与正常组之间,说明OA病变早期关节软骨形态改变不大,而主要是软骨组织结构及成分的改变。
     3.4通过关节软骨急性损伤与对照组T2~*弛豫时间测量对比分析:本组损伤病变以股骨内侧髁软骨负重面及髌骨病变为主。同时T2~*弛豫时间测量能够发现关节镜所不能发现的一些早期病变或软骨内在性病变。
Part 1:Comparative study of MR sequences on articular cartilage in the knee
     Objective
     A group of young healthy volunteers were performed with MRI to explore the best magnetic resonance(MR) sequence showing articular cartilage in the knee.
     Materials and Methods
     1.Subjects
     20 healthy young volunteers were selected for MRI study of articular cartilage in their knees,including 10 cases male and 10 cases female.All the volunteers had no symptoms of knee pain,neither any other medical records of knee joint disease.
     2.MR scanning
     All images were acquired with a 3.0-T MR imaging unit(GE Signa EXCITE HD; GE healthcare,USA).After routine MR sequence scanning,sagittal imaging were performed with 3D-FS-SPGR sequence,FS-GRE sequence and FS-FSE sequence.
     3.MR images analysis
     All images were transported into the AW4.3 workstation and PACS system to be analyzed.
     All the images were co-checked by two radiologists.In the AW4.3 workstation, the signal intensity of subcartilage bone tissue,muscle,fluid surrounding the articular cartilage and background were detected in 3D-FS-SPGR sequence,FS-GRE sequence and FSE sequence,respectively.The area of region of interest(ROI) was about 4mm~2. and Every ROI was detected repeatedly for three times and the average signal intensity was calculated.The SNR,SNR efficiency(SNR divided by the square root of the imaging time) for cartilage,subcartilage bone tissue,muscle and fluid surrounding the articular cartilage were calculated,respectively.Then contrast-to-noise ratio(CNR) of cartilage to the surrounding tissues was also acquired.
     4.Statistical analysis
     All the data were expressed as Mean±SD and statistical software SPSS 13.0 was used.One-way ANOVA was used to evaluate the differences of SNR,SNR efficiency and CNR between the different MR sequences in cartilage,subcartilage bone tissue, muscle and fluid surrounding the articular cartilage.If equal variances assumed, Least-significant Difference(LSD) test was applied,otherwise Kruskal-Wallis test or/and Dunnett's T3 test was used.P≤0.05 was considered to indicate significant difference.
     Results
     1.Sensitive MR sequence for articular cartilage in normal knee
     1.1 Analysis of SNR and SNR efficiency for the normal articular cartilage in the knee and its surrounding tissues
     SNR values of cartilage,subcartilage bone and muscle were significant different among three MR sequences,including 3D-FS-SPGR sequence,FS-GRE sequence and FSE sequence(P<0.05).There was significant difference in SNR of fluid between FS-FSE sequence and FS-GRE sequence,or FS-FSE sequence and 3D-FS-SPGR sequence(P<0.05).However,there were not significant difference between 3D-FS-SPGR sequence and FS-GRE sequence(P=0.776).Thus as to showing fluid,FS-FSE sequence was more sensitive than the other two,while 3D-FS-SPGR sequence was best to show cartilage.
     SNR efficiency of cartilage,subcartilage bone and fluid were significantly different among three MR sequences(P<0.05).But as to the SNR efficiency of muscle,except that no difference was found between FS-GRE sequence and 3D-FS-SPGR sequence(P>0.05),others were significantly different(P<0.01).Since 3D-FS-SPGR sequence having a long scanning time,the SNR efficiency in various tissues would be decreased,but the SNR efficiency of cartilage was still higher than those in other two sequences.SNR efficiency of fluid in 3D-FS-SPGR sequence was lowest among three sequences.In muscle,it was close to that in FS-GRE sequence. But as to the subcartilage bone,it was in the medium among three sequences.
     1.2 Analysis of CNR for the normal articular cartilage in the knee and its surrounding tissues
     Significant differences of the CNR as for cartilage to subcartilage bone,and cartilage to fluid,could be found among the three sequences(P<0.05).Except for those between 3D-FS-SPGR sequence and FS-FSE sequence,others were obviously different(P<0.05) in CNR of cartilage to muscle.CNR of cartilage to bone in 3D-FS-SPGR sequence was the highest,while as to FS-FSE sequence,it was the lowest.In addition,CNR of cartilage to fluid in FS-FSE sequence was the highest, while as to FS-GRE sequence,the lowest.
     Conclusion
     Articular cartilage was shown as high signal intensity among the three sequences, including 3D-FS-SPGR sequence,FS-GRE sequence and FSE sequence.And 3D-FS-SPGR sequence was the best to show the articular cartilage,due to the highest SNR values and CNR of cartilage to surrounding tissues.
     Part 2:The comparison between MR anatomy and the body specimen of the articular cartilage in the knee
     Objective
     1.To compare and evaluate the differences of the articular cartilage thickness, detected by two different methods:direct detection from corpse sample and from MR imaging with the sensitive sequences;
     2.To analyze and evaluate the location of different elements of cartilage in articular genus by means of special staining for the articular cartilage in the knee;
     3.To examine the cartilage thickness and T2~*relaxation time of the normal articular genus,by using the new 3T MR technology:3D-FS-SPGR sequence and T2~*GRE multiple echo sequence.
     1 Materials
     1.1 Sample group:The fresh articular genu samples from two normal adult young male corpses,medium stature,from the local country,were obtained(keeping fresh in a cold preservation).Under the situation that defrosted well,MRI scanning was carried on these 2 cases according to the routine MR sequences.After defrosting,the knees were dissected longitudinally at a thickness of 2cm each.
     1.2 Control group:20 cases,same as that in Part 1.
     2 Experimental instruments
     2.1 The MR instrument and scan parameters
     All images were acquired with a 3.0-T MR imaging unit(GE signa VH/I;GE healthcare,Milwaukee,WI,USA).Sagittal MR scan was administrated in all the specimens following various MR sequences,including FS-FSE sequence,FS-GRE sequence,FS-SPGR sequence,having the same scanning parameters as those in part 1, and also following T2~*GRE multiple echo sequence at the same time.
     3 Corpse patellae dissection and histological processing
     3.1 Corpse patellae dissection
     The corpse patellae were preserved below -30℃,keeping in a stretching position. After being taken out and defrosted,they were dissected longitudinally using electronic saw by a professional technician in the department of anatomy.Each layer has a thickness of 2cm.Clean water was used to keep their surfaces clear and an absorbing cloth to keep them dry.Then screen following the anatomical position. Finally,the articular cartilage was acquired by a professor for the preparation of histological examination.
     3.2 histological processing
     The articular cartilage specimens were sent to the department of pathology in Nanfang University.Routine procedures of neutral formalin fixation,alcohol dehydration,paraffin embedding and slicing were then completed.Subsequently,the slices were stained with a compound dyes,Victorial blue and Ponceau red.After xylene clearing,they were mounted with neutral gum for visualizing the collagen fibres in the cartilage matrix.
     4.MR images analysis
     In the AW4.3 workstation,the images of 3D-FS-SPGR sequence were remodified, and the thickness of articular cartilage was examined.At the same time,T2~*map of articular cartilage was also remodified according to T2~*GRE multiple echo sequence, and T2~*relaxation time of articular cartilage was detected in T2~*map.
     5.Comparative analysis of articular cartilage between corpse sample and MR imaging
     Post-dissected specimens of articular genus were kept dry and photoed.The thickness of articular cartilage in some local region was examined with sliding caliper. And that in the same region of MR images was also examined.Then the differences between anatomical specimens and MRI were evaluated.
     6.Statistical analysis
     All the data were expressed as Mean±SD and statistical soft SPSS 13.0 was used. One-way ANOVA was used to evaluate the differences of articular cartilage thickness and T2~*relaxation time in the normal volunteers.If equal variances assumed, Least-significant Difference(LSD) test was applied,otherwise Kruskal-Wallis test or/and Dunnett's T3 test was used.P≤0.05 was considered to indicate significant difference.
     Results
     1.Cartilage histology
     With the microscope,it was found that collage fibre was rich at the periphery of the articular cartilage,while the cartilage matrix was less and the chondrocytes were immature at this site.However,in the center of the articular cartilage,collage fibre was less,while the cartilage matrix increased and chondrocytes became mature.The running diversity of collagenous fibres resulted in the differences of MR images.
     2.Comparison between cartilage anatomy and MR imaging
     The differences of cartilage thickness detected with these two methods were not obvious,which demonstrated the examination in MRI according to 3D-FS-SPGR sequence could represent the actual cartilage thickness of articular genus.
     3.A range of detecting data for cartilage thickness and T2~* relaxation time for the normal group could be obtained.
     Conclusion
     1.By comparing cartilage anatomy and MR imaging,3D-FS-SPGR sequence could represent the actual morphology and cartilage thickness of articular genus.
     2.By means of special staining for the articular cartilage in the knee,collage fibre was rich at the periphery of the articular cartilage,while the cartilage matrix was less. and the chondrocytes were immature at this site.However,in the center of the articular cartilage,collage fibre was less,while the cartilage matrix increased and chondrocytes became mature.This indicated the distribution of tissue elements in the articular cartilage was related with its function.
     3.A range detecting data of cartilage thickness and T2~*relaxation time for the normal group could be obtained.
     Part 3 The clinical application of MR imaging on the disease of articular cartilage in the knee
     Objective
     1.The cartilage thickness at various phases of OA in the articular genus is to be detected by using MR 3D-FS-SPGR sequence.And its changes during the pathological progress of OA are also evaluated after being compared with those in the normal group;
     2.By comparing with the showing from anthroscope,the specificity and sensitivity of imaging cartilage are to be evaluated with some sensitive MR sequences for cartilage, and the preponderance of MRI in diagnosing the disease of articular cartilage is also to be estimated;
     3.By the detection of T2~* relaxation time for cartilage in knee OA of various phases and in normal group through T2~*GRE multiple echo sequence,the correlation of T2~* relaxation time changes with the development of pathological changes of OA patients is to be estimated.And through the analysis of T2~* relaxation time for that in acute OA,the changes of T2~* relaxation time are examined at the early time of cartilage injury.
     4.By the detection ofT2~* relaxation time for the pathological articular cartilage in the knee through T2~* GRE multiple echo sequence with multi-echoes,the progress of cartilage pathology was analyzed,in order to find the concealed pathological changes in cartilage injury as early as possible.
     Material and Method
     Subjects
     1.Selected criterion:The subjects were selected from the outpatients of Nanfang Hospital ranged in the period between the June in 2006 and the January in 2008, having the symptoms of knee pain or functional impairment in their knees.All the cases had no history of arthroscopy and surgery in either knee.If the patients had a history of trauma,it was necessary that no signs of bone fracture in the knee would be shown from X-ray.According to the emergent time of trauma,these cases were classified into two stages.If the trauma happened within two months,it was in the acute period.However,the contrary was in the chronic period.Since having the similar pathogenesis,the chronic trauma-induced osteoarthritis would be incorporated into the degenerative osteoarthritis as one group.
     62 cases with the above criterion were included and their articular cartilage thickness was detected in this research.Among of them,27 cases were male and 35 cases female,which ranged in age between 19 and 65 years,with an average age of 37 years.36 cases of them performed with arthroscopy and surgery in knee after MRI examination,including 19 males and 17 females,which ranged in age between 21 and 61 years,with an average age of 44 years.
     56 of 62 cases carried on the measure of T2~*relaxation time,including 25 males and 31 females,with an average age of 36 years old.
     2.Classification of cases
     According to the OA index made by WOMAC and K-L radiological diagnosis standard,the cases with OA in the knee could be further classified into gentle, medium and serious injury groups.
     3.Grading standard according to the cartilage injury
     GradeⅠ:The cartilage is intact;GradeⅡ:The cartilage is lack in local area but the bone at this site is not exposed;GradeⅢ:The cartilage is broken with exposed subcartilage bone tissue,but it is integrate with no abnormal signals;GradeⅣ:The whole layer of cartilage is loss,and the bone underlying the articular surface has the abnormal signals.
     Unlike the classification based on the clinical symptoms,this grading standard is accord with the degree of cartilage injury,which helps to compare the MR images with those from anthroscope.
     Instruments
     It is same as part 2.
     Image processing
     The image processing is same as part 1.
     Estimation of the cartilage injury:Before the surgery,the images based on the sensitive MR sequences for cartilage were checked by three professors of radiology. Then the injury of articular cartilage and its grading are estimated from MRI.On the other hand,its grading from the anthroscope was judged by the clinical specialists of anthroscope.Both MRI and anthroseope grading were based on the double-blinded principle.
     Statistical analysis
     All the data were expressed as Mean±SD and statistical soft SPSS 13.0 was used. One-way ANOVA was used to evaluate the differences of articular cartilage thickness and T2~* relaxation time according to 3D-FS-SPGR and T2~*GRE sequences between the normal volunteers and OA patients.If equal variances assumed,Least-significant Difference(LSD) test was applied,otherwise Kruskal-Wallis test or/and Dunnett's T3 test was used.P≤0.05 was considered to indicate significant difference.
     Given multiple factors affecting articular cartilage thickness and T2~* relaxation time,such as weight,height,body mass index(BMI),age and sex,non-parametric correlation analysis(Spearman's test) was used to evaluate the effects of these factors on the articular cartilage.P≤0.05 was considered to indicate significant difference.
     As to the degree of cartilage injury,the kappa coefficient analysis was used to evaluate the sensitivity and specificity of the three MR sequences,taking the results from anthroscope as a golden standard.
     Result
     1.Comparison of articular cartilage thickness between in the OA cases of various degrees and in the healthy volunteers
     In the gentle OA group,there was no statistical difference of articular cartilage thickness with that in the normal volunteers,while that in a bulk of articular cartilage in serious OA group was significant different from that in the normal volunteers.In addition,multiple factors,such as sex,age,weight and BMI,might affect the thickness of articular cartilage in the knee.
     2.Comparison of T2~* relaxation time in cartilage between various OA groups and healthy volunteers
     In the gentle OA group,the T2~* relaxation time for a bulk of articular cartilage region was obviously different from that in the healthy volunteers.However,there was no statistical difference of T2~* relaxation time in serious OA group,when compared with the healthy volunteers.The change of T2~* relaxation time for cartilage was also associated with the age,weight and height.In addition,other multiple factors might affect it.
     3.The images of cartilage pathological changes in three MR sequences
     In the FS-FSE sequence,the accumulated fluid in the cartilage defection appeared as an obvious high signal,and the cartilage was so as well.In the 3D-FS-SPGR sequence,both the accumulated fluid in the cartilage defection and cartilage defection or injury show as low signal,while the cartilage was in a high signal.In the FS-GRE sequence,the accumulated fluid in the cartilage defection appeared as low signal,and the cartilage was high signal.However,in the site of cartilage injury,slightly low signal or similar signal as the normal cartilage was shown.
     4.Evaluation of the FS-GRE,FS-FSE and 3D-FS-SPGR sequences on the pathological changes of articular cartilage
     In the images of various MR sequences,there were 288 cartilage surfaces in 36 patients.The results of anthroscope indicated that there were 32 cartilage pathological changes in 21 cases.The 3D-FS-SPGR sequence was best to show the pathological changes of cartilage.Its sensitivity arrived at 99.2%and its specificity was 94.4%. Both were higher than other two MR sequences,including FS-GRE and FS-FSE sequences.The kappa value of the 3D-FS-SPGR sequence was 0.937>0.75,which demonstrated the good consistency as the anthroscope when showing the pathological changes of cartilage.
     5.Evaluation of T2~* relaxation time on the pathological changes of articular cartilage According to the different incidence time and degree of OA in the knee,the value of T2~* relaxation time was also different.In the early stage of OA,the cartilage signal displayed a limit increase;while in the mid or late stage,it was similar as or slightly lower than the signal of surrounding normal cartilage.In the acute injury,the cartilage signal in the injury showed a high T2~* relaxation time.However,in the chronic injury period,T2~* relaxation time of cartilage decreased to or below the level of surrounding normal cartilage.
     Conclusion
     3.1 By comparing of articular cartilage thickness between in the OA cases and in the healthy volunteers,the articular cartilage thickness in a bulk of cartilage weigh-loading surface attenuated gradually,following with the aggregated OA disease.Except for the degree of disease,it might be affected by multiple factors, such as weight,age,sex,and so on.
     3.2 The sensitivity and specificity of 3D-FS-SPGR sequence for showing cartilage pathological changes were higher than other two sequences.In addition,it presented a good consistency with the anthroscope in showing the pathological changes of cartilage.
     3.3 The difference of T2~* relaxation time for cartilage was mainly between the gentle OA cases and normal group,which indicated the shape of articular cartilage varied not very much in the early time of OA,while the change of tissue structure and elements was true.
     3.4 In the acute phase of articular cartilage injury,the pathological changes mainly took place in the cartilage weight-loading surface of tibial condyle of femur or in the patella.At the same time,the detection of T2~* relaxation time could detect some earlier pathological change or some native change in the cartilage,which couldn't be found by anthroscope.
引文
1. Kurkijarvi JE, Nissi MJ, Kiviranta I, et al. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 characteristics of human knee articular cartilage:topographical variation and relationships to mechanical properties. Magn Reson Med2004,52(1):41-6.
    
    2. Mevorach D, Menkes CJ. Osteoarthritis and chondroprotection. Isr J Med Sci 1994,30(12):928-31.
    
    3. Minas T, Nehrer S. Current concepts in the treatment of articular cartilage defects.Orthopedics 1997,20(6):525-38.
    
    4. Brittberg M, Lindahl A, Nilsson A, et al. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med,1994,331(14):889-95.
    
    5. Yoshioka H, Stevens K, Genovese M, et al. Articular Cartilage of Knee: Normal Patterns at MR Imaging That Mimic Disease in Healthy Subjects and Patients with Osteoarthritis. Radiology, 2004,231(1):31-8.
    
    6. Faber SC,Eckstein F,Lukasz S, et al. Gender differences in knee joint cartilage thickness, volume and articular surface areas: assessment with quatitative three-dimensional MR imaging. Skeletal Radiol, 2001,30(3): 144-50.
    
    7. Jaramillo D, Villegas-Medina OL, Doty DK, et al. Age-related vascular changes in he epiphysis, physis, and metaphysic: normal findings on gadolinium-enhangced MRI of piglet. AJR,2004,182(2):353-60.
    
    8. Erickson SJ, Waldschmidt JG, Czervionke LE, et al. Hyaline cartilage: truncation artifact as a cause of trilaminal appearance with fat-suppressed three-dimensional spoiled gradient-recalled sequences. Radiology 1996,201(1):260 -4.
    
    9. Frank LR, Brossmann JB, Buxton RB, Resnick D. MR imaging truncation artifacts can create a false laminar appearance in cartilage. AJR Am J Roentgenol 1997,168(2):547-54.
    10. Rubenstein DJ, Kim JK, Henkelman RM. Effects of compression and recovery on bovine articular cartilage: appearance on MR images. Radiology, 1996,201(3):843-50.
    11.Uhl M, Oiling C, Allmann KH, et al. Human articular cartilage: in vitro correlation of MRI and histologic findings. Eur Radiol, 1998, 8(7): 1123-9.
    
    12. Lehner KB, Rechl HP, Gmeinwieser JK, et al. Structure, function, degeneration of bovine hyaline cartilage: assessment with MR imaging in vitro. Radiology,1989, 170(2): 495-9.
    
    13. Chandnani VP, Ho C, Chu P, et al. Knee hyaline cartilage evaluated with MR imaging: a cadaveric study involving multiple imaging sequences and intra-articular injection of gadolinium and saline solution. Radiology,1991,178(2):557-61.
    
    14. Babyn PS, Kim HK, Lemaire C, et al. High-resolution magnetic resonance imaging of normal porcine cartilaginous epiphyseal maturation. J Magn Reson Imaging,1996,6(1):172-9.
    
    15. Rubenstein JD, Kim JK, Morova-Protzner I, et al. Effects of collagen orientation on MR imaging characteristics of bovine articular cartilage. Radiology, 1993,188(1):219-26.
    
    16. Henkelman RM, Stanisz GJ, Kim JK, et al. Anisotropy of NMR properties of tissues. Magn Reson Med, 1994, 32(5):592-601.
    
    17. Modl JM, Sether LA, Haughton VM, et al. Articular cartilage: correlation of histologic zones with signal intensity at MR imaging. Radiology,1991,181(3):853-5.
    
    18. Mlynarik V, Degrassi A, Toffanin R, et al. Investigation of laminar appearance of articular cartilage by means of magnetic resonance microscopy. Magn Reson Imaging, 1996,14(4):435-42.
    
    19. Akella SVS, Regatte RR, Wheaton AJ, et al. Reduction of residual dipolar interaction in cartilage by spin-lock technique. Magn Reson Med,2004,52(5):1103-1109.
    
    20. Kijowski R, Lu A, Block W, et al. Evaluation of the articular cartilage of the knee joint with vastly undersampled isotropic projection reconstruction steady-state free precession imaging. J Magn Reson Imaging. 2006,24(1): 168-75
    21. Akella SVS, Regatte RR, Wheaton AJ, et al. Reduction of residual dipolar interaction in cartilage by spin-lock technique. Magn Reson Med,2004,52(5):1103-1109.
    
    22. Hodgeson RJ, Carpenter TA, Hall LD. Articular cartilage and osteoarthritis. New York: Raven, 1991.
    
    23. Shapiro EM, Borthakur A, Kaufman JH, et al. Water distribution patterns inside bovine articular as visualized by 1H magnetic resonance imaging. Osteoarthritis Cartilage, 2001,9(6):533-8.
    
    24. Roughley PJ, Lee ER. Cartilage proteoglycans: structure and potential functions.Microsc Res Tech, 1994,28(5):385-97.
    
    25. Wu JZ, Herzog W. Elastic anisotropy of articular cartilage is associated with the microstructures of collagen fibers and chondrocytes, J Biomech, 2002,35(7):931-42.
    
    26. Bauer JS, Krause SJ, Ross CJ, et al. Volumetric Cartilage Measurements of Porcine Knee at 1.5-T and 3.0-T MR Imaging: Evaluation of Precision and Accuracy, Radiology, 2006,241(2):399-406.
    
    27. Roos EM. Joint injury causes knee osteoarthritis in young adults. Curr Opin Rheumatol, 2005,17(2):195-200.
    
    28. Cohen, ZA, McCarthy, DM, Kwak, SD,et al. Knee cartilage topography,thickness,and contact areas from MRI: in-vitro calibration and invivo measurements.Osteoarthritis Cartil. 1999, 7 (1):95-109.
    
    29. Stammberger, T, Eckstein, F., Michaelis, M, et al. Interobserver reproducibility of quantitative cartilagemeasurements: comparison of B-spline snakes and manual segmentation.Magn. Reson. Imaging, 1999b ,17 (7): 1033-1042.
    
    30. Mosher TJ, Dardzinski BJ, Smith MB. Human articular cartilage: influence of aging and early symptomatic degeneration on the spatial variation of T2-preliminary findings at 3 T. Radiology, 2000, 214 (1) : 259-66.
    
    31. Mosher TJ, Smith H, Dardzinski BJ, et al. MR imaging and T2 mapping of femoral cartilage: in vivo determination of the magic angle effect. AJR Am J Roentgenol, 2001,177(3): 665-9.
    
    32. Mosher TJ, Collins CM, Smith HE, et al. Effect ofgender on in vivo cartilage magnetic resonance imaging T2 mapping. J Magn Reson Imaging 2004,19(3):323-8.
    
    33. Trattnig S, Mamisch TC, Welsch GH, et al. Quantitative T2 mapping of matrix-associated autologous chondrocyte transplantation at 3 Tesla an in vivo cross-sectional study. Invest Radiol,2007,42(6):442-8.Vasanawala S, Pauly J,Nishimura D. Linear combination steadystate free precession MRI. Magn Reson Med, 2000,43(l):82-90.
    
    34. Wayne JS, Kraft KA, Shields KJ, et al. MR imaging of normal and matrix-depleted cartilage: correlation with biomechanical function and biochemical composition. Radiology. 2003,228(2):493-9.
    
    35. Dardzinski BJ, Mosher TJ, Li S, et al. Spatial variation of T2 in human articular cartilage. Radiology,1997,205(2):546 -50.
    
    36. Nieminen MT, Rieppo J, Silvennoinen J, et al. Spatial assessment of articular cartilage proteoglycans with Gd-DTPA-Enhanced Tl imaging. Magn Reson Med,2002,48(4):640-8.
    
    37. Nieminen MT, Rieppo J, Toyras J, et al. T2 relaxation reveals spatial collagen architecture in articular cartilage: a comparative quantitative MRI and polarized light microscopic study. Magn Reson Med, 2001,46(3): 487-93.
    
    38. Goodwin DW, Wadghiri YZ, Dunn JF. Micro-imaging of articular cartilage: T2,proton density, and the magic angle effect. Acad Radiol, 1998,5(11):790 -798.
    39. Goodwin DW, Zhu H, Dunn JF. In vitro MR imaging of hyaline cartilage:correlation with scanning electron microscopy. AJR Am J Roentgenol,2000,174(2):405-9.
    
    40. Xia Y, Moody JB, Burton-Wurster N, et al. Quantitative in situ correlation between microscopic MRI andpolarized light microscopy studies of articular cartilage. Osteoarthritis Cartilage, 2001,9(5):393-406.
    
    41. Menezes NM, Gray ML, Hartke JR, Burstein D. T2 and T1rho MRI of articular cartilage system. Magn Reson Med, 2004,51(3):503-9.
    
    42. Nieminen MT, Toyras J, Rieppo J, et al. Quantitative MR microscopy of enzymatically degraded articular cartilage. Magn Reson Med, 2000,43(5):676-81.
    
    43. Lusse S, Claassen H, Gehrke T, et al. Evaluation of water content by spatially resolved transverse relaxation times of human articular cartilage. Magn Reson Imaging, 2000,18(4):423-30.
    
    44. Grunder W, Wagner M, Werner A. MR-microscopic visualization of anisotropic internal cartilage structures using the magic angle technique. Magn Reson Med,1998,39(3):376-82.
    
    45. Rubenstein JD, Kim JK, Morova-Protzner I, et al. Effects of collagen orientation on MR imaging characteristics of bovine articular cartilage. Radiology,1993,188(1): 219-26.
    
    46. Goodwin DW. Visualization of the macroscopic structure of hyaline cartilage with MR imaging. Semin Musculoskelet Radiol, 2001,5(4):305-12
    
    47. Mosher TJ, Liu Y, Yang QX, et al. Age dependency of cartilage magnetic resonance imaging T2 relaxation times in asymptomatic women. Arthritis Rheum, 2004,50(9):2820-8.
    1. Yoshioka H, Stevens K, Genovese M, et al. Articular cartilage of knee, normal patterns at MR imaging that mimic disease in healthy subjects and patients with osteoarthritis. Radiology, 2004,231(1):31-8.
    
    2. Goodwin DW. Visualization of the macroscopic structure of hyaline cartilage with MR imaging. Semin Musculoskelet Radiol, 2001,5(4):305-12
    
    3. Mosher TJ, Liu Y, Yang QX, et al. Age dependency of cartilage magnetic resonance imaging T2 relaxation times in asymptomatic women. Arthritis Rheum, 2004,50(9):2820-8.
    
    4. Yoshioka H, Stevens K, Genovese M, et al. Articular Cartilage of Knee: Normal Patterns at MR Imaging That Mimic Disease in Healthy Subjects and Patients with Osteoarthritis. Radiology, 2004,231(1):31-8.
    
    5. Disler DG, McCauley TR, Hospodar PP, et al. Fat-suppressed three-dimensional spoiled gradient-echo MR imaging of hyaline cartilage defects in the knee:comparison with standard MR imaging and arthroscopy. AJR Am J Roentgenol,1996,167(1):127-32.
    
    6. Disler DG. Fat-suppressed three-dimensional spoiled gradient-recalled MR imaging: assessment of articular and physeal hyaline cartilage. AJR Am J Roentgenol, 1997,169(4):1117-23.
    
    7. Recht MP, Piraino DW, Paletta GA, et al. Accuracy of fat-suppressed three-dimensional spoiled gradient-echo FLASH MR imaging in the detection of patellofemoral articular cartilage abnormalities. Radiology, 1996, 198(1):209-212.
    
    8. Nieminen MT, Rieppo J, Toyras J, et al. T2 relaxation reveals spatial collagen architecture in articular cartilage: a comparative quantitative MRI and polarized light microscopic study. Magn Reson Med, 2001,46(3): 487-93.
    9. Goodwin DW, Wadghiri YZ, Dunn JF. Micro-imaging of articular cartilage: T2,proton density, and the magic angle effect. Acad Radiol, 1998,5(11):790 -798.
    
    10. Woertler K, Strothmann M, Tombach B, et al. Detection of articular cartilage lesions: experimental evaluation of low- and high-field-strength MR imaging at 0.18 and 1.0 T. J Magn Reson Imaging, 2000,11(6):678-85.
    
    11. Ahn JM, Kwak SM, Kang HS, et al. Evaluation of patellar cartilage in cadavers with a low-field-strength extremity-only magnet: comparison of MR imaging sequences, with macroscopic findings as the standard. Radiology, 1998,208(1):57-62.
    
    12. Palosaari K, Ojala R, Blanco-Sequeiros R, et al. Fat suppression gradient-echo magnetic resonance imaging of experimental articular cartilage lesions:comparison between phase-contrast method at 0.23T and chemical shift selective method at 1.5T..J Magn Reson Imaging,2003,18(2):225-31
    
    13. David-Vaudey E, Ghosh S, Ries M, et al.T2 relaxation time measurements in osteoarthritis. Magn Reson Imaging, 2004,22(5):673-82
    
    14. Rubenstein JD, Kim JK, Morova-Protzner I, Stanchev PL, Henkelman RM.Effects of collagen orientation on MR imaging characteristics of bovine articular cartilage. Radiology, 1993,88(1):219-226
    
    15. Rubenstein JD, Kim JK, Henkelman RM. Effects of compression and recovery on bovine articular cartilage:appearance on MR images, Radiology 1996,201:843-850
    
    16. Mosher TJ, Dardzinski BJ, Smith MB. Human articular cartilage: influence of aging and early symptomatic degeneration on the spatial variation of T2-preliminary findings at 3 T. Radiology,2000,214(1): 259-66.
    
    17. Mosher TJ, Smith H, Dardzinski BJ, et al. MR imaging and T2 mapping of femoral cartilage: in vivo determination of the magic angle effect. AJR Am J Roentgenol, 2001,177(3): 665-9.
    
    18. Mosher TJ, Collins CM, Smith HE, et al. Effect ofgender on in vivo cartilage magnetic resonance imaging T2 mapping. J Magn Reson Imaging 2004,19(3):323-8.
    
    19. Rubenstein JD, Kim JK, Morova-Protzner I, Stanchev PL, Henkelman RM.Effects of collagen orientation on MR imaging characteristics of bovine articular cartilage. Radiology, 1993 ,188(1):219-226
    
    20. Rubenstein JD, Kim JK, Henkelman RM. Effects of compression and recovery on bovine articular cartilage: appearance on MR images. Radiology 1996;201:843-850
    
    21.Waterton JC, Solloway S, Foster JE, et al. Diurnal variation in the femoral articular cartilage of the knee in young adult humans. Magn Reson Med 2000,43:126-132
    
    22. Panula HE, Hyttinen MM, Arokoski JP, et al. Articular cartilage superficial zone collagen birefringence reduced and cartilage thickness increased before surface fibrillation in experimental osteoarthritis. Ann Rheum Dis, 1998,57:237-45.
    
    23. Venn MF. Variation of chemical composition with age in human femoral head cartilage. Ann Rheum Dis, 1978,37(2):168-74.
    
    24. Grushko G, Schneiderman R, Maroudas A. Some biochemical and biophysical parameters for the study of the pathogenesis of osteoarthritis: a comparison between the processes of ageing and degeneration in human hip cartilage.Connect Tissue Res, 1989,19(2-4): 149-76.
    
    25. Mosher TJ, Chen Q, Smith MB. 1H magnetic resonance spectroscopy of nanomelic chicken cartilage: effect of aggrecan depletion on cartilage T2.Osteoarthritis Cartilage, 2003,11(10):709-15.
    
    26. Fragonas E, Mlynarik V, Jellus V, et al. Correlation between biochemical composition and magnetic resonance appearance of articular cartilage.Osteoarthritis Cartilage, 1998,6(1):24-32.
    
    27. Mlynarik V, Trattnig S, Huber M, et al. The role of relaxation times in monitoring proteoglycan depletion in articular cartilage. J Magn Reson Imaging ,1999,10(4):497-502.
    
    28. Dalla Palma L, Cova M, Pozzi-Mucelli RS. MRI appearance of the articular cartilage in the knee according to age. J Beige Radiol, 1997,80(1): 17-20.
    
    29. Hudelmaier M, Glaser C, Hohe J, et al. Age-related changes in the morphology and deformational behavior of knee joint cartilage. Arthritis Rheum, 2001,44(11):2556-61.
    
    30. Hwang WS, Li B, Jin LH, et al. Collagen fibril structure of normal, aging, and osteoarthritic cartilage. J Pathol, 1992,167(4):425-33.
    
    31. Hollander AP, Pidoux I, Reiner A, et al. Damage to type II collagen in aging and osteoarthritis starts at the articular surface, originates around chondrocytes, and extends into the cartilage with progressive degeneration. J Clin Invest,1995,96(6):2859-69.
    
    32. Nieminen MT, Toyras J, Laasanen MS, et al. Prediction of biomechanical properties of articular cartilage with quantitative magnetic resonance imaging. J Biomech 2004,37(3): 321-8.