膝关节关节软骨的三维构建

目的:构建膝关节关节软骨的三维模型,为开展膝关节数字医学研究进行模型构建的探索。方法:人体成年新鲜膝关节标本1例,行CT、MRI扫描,利用三维重建软件Mimics及逆向工程软件Geomagic对图像进行三维重建及图像配准,构建膝关节骨、关节软骨结构。结果:利用Mimics 10.01软件构建关节软骨的三维模型,并形成骨-关节软骨复合模型,导入Geomagic软件中与CT构建的骨三维模型相配准,再次导入CT影像中进行逐层微修饰,验证关节软骨分割效果。最终建立具有骨、关节软骨的三维膝关节模型。结论:三维图像重建技术与图像配准技术可将CT、MRI图像两者结合起来,发挥其各自优势,构建出形态较好的膝关节三维模型。     

应用高分辨率显微CT进行大鼠周围神经微血管三维可视化研究

目的 探讨采用高分辨率显微CT（Micro-CT）研究大鼠周围神经微血管三维构筑的可行性,比较两种不同的造影剂对成像效果的影响。
方法 SD大鼠40只,随机分为2组,分别灌注明胶-氧化铅和Microfil,取大鼠两侧坐骨神经行Micro-CT扫描,同时设定电压30kVP、功率40W作为
成像时的最佳能量参数。将扫描得到的断层图像转变为Dicom格式输出至个人电脑,利用Mimics 10.0软件对其进行三维重建。结果 将灌注不同
造影剂后得到的标本图片分别从大体和三维两个方面进行对照,发明明胶-氧化铅的造影效果明显优于Microfil;Micro-CT在扫描重建时呈现出低
耗时、低变化以及高清晰度的特点。结论 Microfil 在灌注微血管造影时存在者灌注压力要求高、成像质量差等缺点,而传统的明胶-氧化铅在
微血管造影上仍有其独到的优越性;Micro-CT不失为一种研究大鼠周围神经微血管三维构筑的好方法。     

3.0 T MRI上正常成人膝关节软骨体积的定量测量及其临床意义

目的：提供正常成人膝关节关节软骨总体积的参考值,研究膝关节各部分软骨体积所占总体积的比重,探讨软骨体积与年龄、性别、身高、体重的关系.方法：选取无关节外伤及手术史、无膝关节痛的健康志愿者140例,分为7个年龄组,在3.0 T MR上使用水激发3D-MEDIC扫描序列对膝关节进行矢状位重复扫描.所获图像使用半自动软件OsiriX进行膝关节软骨的体积测量及三维重建.结果：膝关节软骨总体积的平均值为（18.16±4.36）cm^3,其中,股骨软骨体积最大,髌骨及胫骨外侧髁次之,胫骨内侧髁最小,所占平均比重分别为（58.1±3.3）%、（18.7±2.0）%、（13.3±1.8）%及（10.0±1.9）%,其中以胫骨内侧髁比重变化程度最大（CV=19%）.男性软骨平均体积大于女性,分别为（21.62±3.63）cm^3和（14.70±2.83）cm^3.膝关节软骨总体积大小以及各部分软骨体积与年龄的增长没有明显相关性（P＞0.05）.膝关节软骨总体积与身高及体重呈正相关（P＜0.001）.结论：关节软骨体积与年龄没有明显关系,与身高及体重呈正相关,因此在评估膝关节软骨病损的体积改变时需结合性别、身高及体重等因素综合评价.     

软骨下骨量变化与软骨退变的相关性

背景：关节软骨与软骨下骨在骨关节炎病变进程中的相互作用机制目前尚未完全阐明。软骨下骨量改变在骨关节炎病理进程中亦发挥重要作用。 目的：分析2种手术方式及2种蛋白酶诱导建立兔膝关节骨关节炎动物模型的效果,以及软骨下骨量变化与关节软骨退变的相关性。 方法：32只新西兰大白兔随机分为4组：Hulth模型组、前交叉韧带切断模型组、Ⅱ型胶原蛋白酶组及木瓜蛋白酶组,每组8只,右膝关节造模,左膝关节作为自身对照。造模后0,4,8周行DXA扫描,8周行MRI扫描后处死实验动物,取双侧膝关节制作病理组织学切片,比较各组膝关节影像学表现、大体形态及病理变化,并采用Mankin评分进行定量分析。 结果与结论：造模后0,4,8周实验侧膝关节骨密度进行性降低,骨量降低程度Hulth模型组>前交叉韧带切断模型组>Ⅱ型胶原蛋白酶组>木瓜蛋白酶组。MRI显示实验侧股骨内外髁关节软骨厚度变薄,厚度Hulth模型组<前交叉韧带切断模型组<Ⅱ型胶原蛋白酶组<木瓜蛋白酶组。大体标本、组织切片观察及Mankin评分显示手术建模组骨关节炎程度较药物组重,Hulth模型组病变最重,木瓜蛋白酶组最轻。结果说明关节内手术及关节腔内注射蛋白酶均能建立骨关节炎动物模型;手术造模可复制出中晚期骨关节炎,药物诱导可产生骨关节炎早期改变。骨关节炎病变严重程度与软骨下骨骨密度呈负相关;关节软骨退变和软骨下骨改变相互关联,病变进行性发展。     

伊班膦酸钠干预骨关节炎模型大鼠丝裂原活化蛋白激酶信号通路的变化

背景:丝裂原活化蛋白激酶信号通路参与成骨细胞与破骨细胞的分化,与软骨下骨重建过程密切相关,在骨关节炎的发生发展中起重要作用。双膦酸盐作为骨吸收抑制剂,主要用于骨质疏松的治疗。目的:探讨伊班膦酸钠对大鼠骨关节炎的治疗效果,以及其对丝裂原活化蛋白激酶信号通路的影响。方法:实验方案经南华大学附属第一医院动物实验伦理委员会批准。30只雌性SD大鼠随机分为假手术组、模型组、治疗组。模型组和治疗组行双侧去卵巢及前交叉韧带切断术,假手术组大鼠只切除卵巢周围与卵巢大小相仿的脂肪组织,切开双侧膝关节腔,但不切断前交叉韧带。术后1周,治疗组予以腹腔注射伊班膦酸钠10μg/kg,模型组予以腹腔注射等量生理盐水,假手术组不作干预。12周以后,处死实验动物,进行关节软骨的组织形态学观察及Mankin评分,软骨下骨的Micro-CT扫描及骨组织显微结构定量分析,检测丝裂原活化蛋白激酶信号通路中细胞外信号调节蛋白激酶(ERK1)和c-Jun氨基酸末端激酶(JNK)的mRNA表达量及蛋白表达水平。结果与结论:①模型组软骨结构明显破坏,Mankin评分较假手术组明显增高,而治疗组的Mankin评分较模型组显著降低(P<0.01);②与假手术组比较,模型组中的骨密度、骨体积分数、骨小梁数量降低,骨小梁分离度显著增高(P<0.01);与模型组相比,治疗组的骨密度、骨体积分数、骨小梁数量增加,骨小梁分离度明显下降(P<0.01);③模型组中的ERK1、JNK mRNA表达和蛋白表达较假手术组明显增加(P<0.05,P<0.01);与模型组相比,治疗组中的ERK1、JNK mRNA表达和蛋白表达显著降低(P<0.05);④结果说明,伊班膦酸钠可能通过抑制ERK1、JNK丝裂原活化蛋白激酶信号通路的表达改善膝骨关节炎大鼠的软骨下骨的微结构,抑制软骨的退变。     

急性创伤后2周软骨下骨未发生明显力学变化

背景：既往研究主要集中于退行性软骨损伤及软骨下骨的修复机制,而对于急性创伤后软骨下骨的组织、形态研究比较少。 目的：观察软骨急性损伤后软骨下骨的早期组织形态学、分子生物、生物力学的变化。 方法：健康成年新西兰兔24只,建立股骨头软骨缺损模型,分别收集模后即刻、造模后4,7,14 d兔股骨头软骨及软骨下骨标本,大体观察造模后兔股骨头软骨及软骨形态变化,番红-固绿染色观察软骨及软骨下骨形态变化、免疫组织化学法测定骨转换标志物骨保护素/核因子κB受体活化因子配体的表达、Micro-CT扫描分析软骨下骨超微结构改变、力学检测法评估软骨下骨机械强度变化。 结果与结论：大体粗测可见股骨头缺损模型于造模后7 d出现软骨缺损面积扩大,深度增加及退变表现,利用染色法观测进一步证实了造模后7 d其软骨厚度降低,软骨下骨骨小梁吸收。免疫组织化学及免疫荧光检测发现,造模后7-14 d软骨下骨中骨保护素表达明显减少,核因子κB受体活化因子配体表达量显著增加,骨保护素/核因子κB受体活化因子配体比值降低,提示骨转化减弱甚至逆转。采用Micro-CT分析发现造模后7-14 d软骨下骨的骨小梁数量增加,骨小梁数目及间距减小,通透性降低。抗压力学试验分析抗压强度和弹性模量未见统计学差异。结果提示,软骨损伤后软骨下骨可在早期造模后7 d后即发生显著组织形态变化和骨转换能力的下调,从而导致软骨进一步破坏;造模后2周内未见软骨下骨从在明显力学改变,基于此的修复手段可为软骨损伤修复提供治疗靶点。     

长骨类骨折内固定系统刚度和应力分布规律

目的 了解由间质液流动而产生的流动电势在关节软骨中的分布规律，获得一定的软骨电特性。方法 将流体控制方程与静电理论结合，建立软骨二维微元模型，通过有限元法计算在一定压力下微元内产生的稳态流动电势。结果 在长度为5 μm处关节软骨微孔隙模型中的流动电势约为38.4 μV，外压和Zeta电势对软骨模型的流动电势影响比较大，并且呈线性增长的关系。流动电势随离子数浓度的增加而减小，但浓度对软骨流动电势影响有所不同。当离子数浓度较低时，流动电势对离子数浓度依赖较大；当离子数浓度较高时，离子数浓度对流动电势的影响很小。结论 研究结果为利用电流、电场、电磁场刺激等方法对软骨细胞的分化增殖、关节软骨疾病防治和治疗、组织工程化软骨研制以及关节软骨损伤修复提供重要的理论依据。     

模拟微重力对大鼠关节软骨力学特性的影响

目的基于大鼠尾吊实验,研究模拟微重力对关节软骨组织力学特性的影响。方法通过14 d的尾吊实验建立模拟微重力作用的大鼠模型,获得12块后肢大腿骨关节处软骨样本,运用高频超声测量技术获取大鼠关节软骨特定位置因自由膨胀引起的组织应变,基于三相模型估计软骨组织的轴向弹性模量,并比较尾吊组和对照组大鼠关节软骨的力学特性。结果尾吊组大鼠后肢特定测量位置处软骨厚度的平均值略小于对照组,但差异不显著;尾吊组大鼠特定位置关节软骨组织的平均轴向弹性模量为(5.05±2.98)MPa,小于对照组((6.31±3.37)MPa),两者存在着显著差异(P<0.05)。结论微重力环境会影响关节软骨组织的力学特性,本研究结果为人类长期的太空活动提供参考信息。     

医用臭氧对骨关节炎关节软骨作用的病理-磁共振成像实验研究

目的 通过病理-磁共振成像(MRI)对照研究,评价医用臭氧对骨关节炎动物模型的关节软骨的修复作用.方法 新西兰大白兔36只,分为正常对照组、模型对照组、10mg/L臭氧关节腔内注射组、30mg/L臭氧关节腔内注射组、10mg/L臭氧自血回输组、30mg/L臭氧自血回输组,每组6只兔.采用Ⅱ型胶原蛋白酶关节腔内注射法诱导骨关节炎模型,造模4周后进行臭氧干预.比较各组关节软骨的MRI表现,测量其关节软骨的平均厚度及信号强度,与病理学改变对照分析,并对MRI表现与Mankin评分进行直线相关及回归分析.结果 模型对照组、各臭氧干预组的膝关节软骨平均厚度及信号强度较正常对照组变薄和降低(均P<0.05).病理结果显示关节软骨表面粗糙,裂隙形成并基质失染,模型对照及臭氧干预各组的Mankin评分均高于正常对照组(均P<0.05),而模型组与各臭氧干预组间的关节软骨平均厚度、信号强度及Mankin评分差异均无统计学意义(均P>0.05).关节软骨平均厚度与信号强度呈正的直线相关(r=0.561,P=0.000);关节软骨平均厚度及信号强度与Mankin评分呈负的直线相关(r=-0.727、-0.590,均P=0.000);关节软骨平均厚度与Mankin评分存在线性回归关系(Y=18.582-0.035X,R~2=0.528).结论 关节软骨损伤的MRI表现与病理有较好的相关性,中低浓度的医用臭氧经关节腔内注射及自血回输对骨关节炎动物模型的关节软骨可能均无修复作用.     

OPG／RANKL在大鼠骨关节炎模型中的表达及意义

目的：检测骨保护素（OPG）和核因子Kβ受体活化因子配体（RANKL）在大鼠骨关节炎（OA）模型软骨下骨中的表达,探讨其与OA软骨下骨病变的关系及意义。方法：36只大鼠分两组。模型组行右膝前交叉韧带＋内侧副韧带横断术造模,对照组仅切开关节囊。术后2,6,8周取两组膝关节标本,观察外观、Mankin评分和骨形态计量参数变化,并检测软骨下骨中OPG和RANKL含量及其比值。结果：模型组软骨Mankin评分随时间逐渐增加（P〈0．01）;骨形态计量学显示造模后2周骨量降低,6、8周增加（P〈0．05）;模型组OPG含量由低变高,RANKL含量则由高变低,其比值逐渐增加（P〈0．01）。结论：OPG、RANKL在OA软骨下骨异常重建中起着重要作用。由此推测,在OA早期对其调控可能抑制异常骨重建,将是治疗OA的一种潜在有效方法。     

Method for Segmentation of Knee Articular Cartilages Based on Contrast-Enhanced CT Images

Segmentation of contrast-enhanced computed tomography (CECT) images enables quantitative evaluation of morphology of articular cartilage as well as the significance of the lesions. Unfortunately, automatic segmentation methods for CECT images are currently lacking. Here, we introduce a semiautomated technique to segment articular cartilage from in vivo CECT images of human knee. The segmented cartilage geometries of nine knee joints, imaged using a clinical CT-scanner with an intra-articular contrast agent, were compared with manual segmentations from CT and magnetic resonance (MR) images. The Dice similarity coefficients (DSCs) between semiautomatic and manual CT segmentations were 0.79–0.83 and sensitivity and specificity values were also high (0.76–0.86). When comparing semiautomatic and manual CT segmentations, mean cartilage thicknesses agreed well (intraclass correlation coefficient?=?0.85–0.93); the difference in thickness (mean?±?SD) was 0.27?±?0.03 mm. Differences in DSC, when MR segmentations were compared with manual and semiautomated CT segmentations, were statistically insignificant. Similarly, differences in volume were not statistically significant between manual and semiautomatic CT segmentations. Semiautomation decreased the segmentation time from 450?±?190 to 42?±?10 min per joint. The results reveal that the proposed technique is fast and reliable for segmentation of cartilage. Importantly, this is the first study presenting semiautomated segmentation of cartilage from CECT images of human knee joint with minimal user interaction.     

Diffusion coefficients of articular cartilage for different CT and MRI contrast agents

In contrast enhanced magnetic resonance imaging (MRI) and computed tomography (CT), the equilibrium distribution of anionic contrast agent is expected to reflect the fixed charged density (FCD) of articular cartilage. Diffusion is mainly responsible for the transport of contrast agents into cartilage. In osteoarthritis, cartilage composition changes at early stages of disease, and solute diffusion is most likely affected. Thus, investigation of contrast agent diffusion could enable new methods for imaging of cartilage composition. The aim of this study was to determine the diffusion coefficient of four contrast agents (ioxaglate, gadopentetate, iodide, gadodiamide) in bovine articular cartilage. The contrast agents were different in molecular size and charge. In peripheral quantitative CT experiments, penetration of contrast agent into the tissue was allowed either through the articular surface or through deep cartilage. To determine diffusion coefficients, a finite element model based on Fick's law was fitted to experimental data. Diffusion through articular surface was faster than through deep cartilage with every contrast agent. Iodide, being of atomic size, diffused into the cartilage significantly faster (q < 0.05) than the other three contrast agents, for either transport direction. The diffusion coefficients of all clinical contrast agents (ioxaglate, gadopentetate and gadodiamide) were relatively low (142.8–253.7 μm²/s). In clinical diagnostics, such slow diffusion may not reach equilibrium and this jeopardizes the determination of FCD by standard methods. However, differences between diffusion through articular surface and deep cartilage, that are characterized by different tissue composition, suggest that diffusion coefficients may correlate with cartilage composition. Present method could therefore enable image-based assessment of cartilage composition by determination of diffusion coefficients within cartilage tissue.     

Contrast-enhanced micro-computed tomography of compartment and time-dependent changes in femoral cartilage and subchondral plate in a murine model of osteoarthritis

A lack of understanding of the mechanisms underlying osteoarthritis (OA) progression limits the development of effective long-term treatments. Quantitatively tracking spatiotemporal patterns of cartilage and bone degeneration is critical for assessment of more appropriately targeted OA therapies. In this study, we use contrast-enhanced micro-computed tomography (μCT) to establish a timeline of subchondral plate (SCP) and cartilage changes in the murine femur after destabilization of the medial meniscus (DMM). We performed DMM or sham surgery in 10–12-week-old male C57Bl/6J mice. Femora were imaged using μCT after 0, 2, 4, or 8 weeks. Cartilage-optimized scans were performed after immersion in contrast agent CA4+. Bone mineral density distribution (BMDD), cartilage attenuation, SCP, and cartilage thickness and volume were measured, including lateral and medial femoral condyle and patellar groove compartments. As early as 2 weeks post-DMM, cartilage thickness significantly increased and cartilage attenuation, SCP volume, and BMDD mean significantly decreased. Trends in cartilage and SCP metrics within each joint compartment reflected those seen in global measurements, and both BMDD and SCP thickness were consistently greater in the lateral and medial condyles than the patellar groove. Sham surgery also resulted in significant changes to SCP and cartilage metrics, highlighting a potential limitation of using surgical models to study tissue morphology or composition changes during OA progression. Contrast-enhanced μCT analysis is an effective tool to monitor changes in morphology and composition of cartilage, and when combined with bone-optimized μCT, can be used to assess the progression of degenerative changes after joint injury.     

Topographical variations in articular cartilage and subchondral bone of the normal rat knee are age-related

In osteoarthritis animal models the rat knee is one of the most frequently investigated joint. However, it is unknown whether topographical variations in articular cartilage and subchondral bone of the normal rat knee exist and how they are linked or influenced by growth and maturation. Detailed knowledge is needed in order to allow interpretation and facilitate comparability of published osteoarthritis studies. For the first time, the present study maps topographical variations in cartilage thickness, cartilage compressive properties and subchondral bone microarchitecture between the medial and lateral tibial compartment of normal growing rat knees (7 vs. 13 weeks). Thickness and compressive properties (aggregate modulus) of cartilage were determined and the subchondral bone was analyzed by micro-computed tomography. We found that articular cartilage thickness is initially homogenous in both compartments, but then differentiates during growth and maturation resulting in greater cartilage thickness in the medial compartment in the 13-week-old animals. Cartilage compressive properties did not vary between the two sites independently of age. In both age-groups, subchondral plate thickness as well as trabecular bone volume ratio and trabecular thickness were greater in the medial compartment. While a high porosity of subchondral bone plate with a high topographical variation (medial/lateral) could be observed in the 7-week-old animals, the porosity was reduced and was accompanied by a reversion in topographical variation when reaching maturity. Our findings highlight that there is a considerable topographical variation in articular cartilage and subchondral bone within the normal rat knee in relation to the developmental status.     

Collagen fibre arrangement in the tibial plateau articular cartilage of man and other mammalian species

Experimental animal models are frequently used to study articular cartilage, but the relevance to man remains problematic. In this study animal models were compared by examination of the collagen fibre arrangement in the medial tibial plateau of human, cow, pig, dog, sheep, rabbit and rat specimens. 24 cartilage samples from each species were prepared and maximum cartilage thickness in the central tibial plateau measured. Samples were fixed, dehydrated, freeze-fractured and imaged by scanning electron microscopy (SEM). At low magnification, 2 different arrangements of collagen fibres were observed: leaf-like (human, pig, dog) and columnar (cow, sheep, rabbit, rat). The porcine collagen structure was the most similar to that of man. This arrangement was consistent from the radial to the upper zones. Under higher magnification at the surface of the leaves, the collagen was more randomly oriented, whereas the columns consisted of parallel collagen fibrils. The maximum thickness of cartilage did not correlate with the type of collagen arrangement but was correlated with the body weight of the species ( r =0.785). When using animal models for investigating human articular cartilage function or pathology, the differences in arrangement of collagen fibres in tibial plateau cartilage between laboratory animals should be considered especially if morphological evaluation is planned.     

Contrast agent enhanced pQCT of articular cartilage

The delayed gadolinium enhanced MRI of cartilage (dGEMRIC) technique is the only non-invasive means to estimate proteoglycan (PG) content in articular cartilage. In dGEMRIC, the anionic paramagnetic contrast agent gadopentetate distributes in inverse relation to negatively charged PGs, leading to a linear relation between T1,Gd and spatial PG content in tissue. In the present study, for the first time, contrast agent enhanced peripheral quantitative computed tomography (pQCT) was applied, analogously to dGEMRIC, for the quantitative detection of spatial PG content in cartilage. The suitability of two anionic radiographic contrast agents, gadopentetate and ioxaglate, to detect enzymatically induced PG depletion in articular cartilage was investigated. First, the interrelationships of x-ray absorption, as measured with pQCT, and the contrast agent solution concentration were investigated. Optimal contrast agent concentrations for the following experiments were selected. Second, diffusion rates for both contrast agents were investigated in intact (n=3) and trypsin-degraded (n=3) bovine patellar cartilage. The contrast agent concentration of the cartilaginous layer was measured prior to and 2-27 h after immersion. Optimal immersion time for the further experiments was selected. Third, the suitability of gadopentetate and ioxaglate enhanced pQCT to detect the enzymatically induced specific PG depletion was investigated by determining the contrast agent concentrations and uronic acid and water contents in digested and intact osteochondral samples (n=16). After trypsin-induced PG loss (-70%, p<0.05) the penetration of gadopentetate and ioxaglate increased (p<0.05) by 34% and 48%, respectively. Gadopentetate and ioxaglate concentrations both showed strong correlation (r=-0.95, r=-0.94, p<0.01, respectively) with the uronic acid content. To conclude, contrast agent enhanced pQCT provides a technique to quantify PG content in normal and experimentally degraded articular cartilage in vitro. As high resolution imaging of e.g. the knee joint is possible with pQCT, the present technique may be further developed for in vivo quantification of PG depletion in osteoarthritic cartilage. However, careful in vitro and in vivo characterization of diffusion mechanics and optimal contrast agent concentrations are needed before diagnostic applications are feasible.     

Effects of Aging And Dietary Restriction On The Structural Integrity of Rat Articular Cartilage

The objectives of this study were to investigate the effects of aging and diet restriction on the biomechanical properties of articular cartilage, using a well-controlled rat model (Fischer 344). This animal model is recommended by the National Institute of Aging specifically to study aging and diet issues. The intrinsic biomechanical properties of articular cartilage were obtained using a creep indentation approach. The ages chosen (6, 12, 18, 24 months of age) correspond to approximate human ages of 20 to 80 years old. The diet regimen employed in this study used either an ad libitum fed group or a group fed 60% of the mean food intake of the ad libitum group. The results demonstrate that, unlike bone, rat articular cartilage biomechanical properties are not affected in a discernible manner by diet restriction, despite the fact that diet-restricted animals were significantly lighter in terms of body weight. Age effects on biomechanical properties are found only at 6 and 12 months probably due to developmental reasons, but not at later ages. It appears that aging and diet restriction have profoundly different effects on articular cartilage and bone. Another significant result of this study was to establish the rat as a suitable animal model to study cartilage biomechanical properties. Thus, the rat can be added to the list of animals that can be used to study structure-function and pathophysiological relationships in articular cartilage. © 2000 Biomedical Engineering Society. PAC00: 8714Ee, 8715La, 8719Rr     

Dual Contrast CT Method Enables Diagnostics of Cartilage Injuries and Degeneration Using a Single CT Image

Cartilage injuries may be detected using contrast-enhanced computed tomography (CECT) by observing variations in distribution of anionic contrast agent within cartilage. Currently, clinical CECT enables detection of injuries and related post-traumatic degeneration based on two subsequent CT scans. The first scan allows segmentation of articular surfaces and lesions while the latter scan allows evaluation of tissue properties. Segmentation of articular surfaces from the latter scan is difficult since the contrast agent diffusion diminishes the image contrast at surfaces. We hypothesize that this can be overcome by mixing anionic contrast agent (ioxaglate) with bismuth oxide nanoparticles (BINPs) too large to diffuse into cartilage, inducing a high contrast at the surfaces. Here, a dual contrast method employing this mixture is evaluated by determining the depth-wise X-ray attenuation profiles in intact, enzymatically degraded, and mechanically injured osteochondral samples (n = 3 × 10) using a microCT immediately and at 45 min after immersion in contrast agent. BiNPs were unable to diffuse into cartilage, producing high contrast at articular surfaces. Ioxaglate enabled the detection of enzymatic and mechanical degeneration. In conclusion, the dual contrast method allowed detection of injuries and degeneration simultaneously with accurate cartilage segmentation using a single scan conducted at 45 min after contrast agent administration.     

In vivo morphometry and functional analysis of human articular cartilage with quantitative magnetic resonance imaging--from image to data, from data to theory

Analyses of form-function relationships and disease processes in human articular cartilage necessitate in vivo assessment of cartilage morphology and deformational behavior. MR imaging and advanced digital post-processing techniques have opened novel possibilities for quantitative analysis of cartilage morphology, structure, and function in health and disease. This article reviews work on three-dimensional post-processing of MR image data of articular cartilage, summarizing studies on the accuracy and precision of quantitative analyses in human joints. It presents normative values on cartilage volume, thickness, and joint surface areas in the human knee, and describes the correlation between different joints and joint surfaces as well as their association with gender, body dimensions, and age. The article summarizes ongoing work on functional adaptation of articular cartilage to mechanical loading, analyses of in situ cartilage deformation in intact joints in vivo and in vitro, and the quantitative evaluation of cartilage tissue loss in osteoarthritis. We describe evolving techniques for assessment of the structural/biochemical composition of articular cartilage, and discuss future perspectives of quantitative cartilage imaging in the context of joint mechanics, mechano-adaptation, epidemiology, and osteoarthritis research. Specifically, we show that fat-suppressed gradient echo sequences permit valid analysis of cartilage morphology, both in healthy and severely osteoarthritic joints, as well as highly reproducible measurements (CV%=1 to 3% in the knee, and 2 to 10% in the ankle). Relatively small differences in cartilage morphology exist between both limbs of the same person (approximately 5%), but large differences between individuals (CV% approximately 20%). Men display only slightly thicker cartilage then women (approximately 10%), but significantly larger joint surface areas (approximately 25%), even when accounting for differences in body weight and height. Weight and height represent relatively poor predictors of cartilage thickness (r2 <15%), but muscle cross section areas display more promising correlations (r2 >40%). The level of physical exercise (sportive activity) does not account for interindividual differences in cartilage thickness. The thickness appears to decrease slightly in the elderly--in particular in women, even in the absence of osteoarthritic cartilage lesions. Strenuous physical exercises (e.g., knee bends) cause a 6% patellar cartilage deformation in young individuals, but significantly less deformation in elderly men and women (<3%). The time required for full recovery after exercise (fluid flow back into the matrix) is relatively long (approximately 90 min). Static in situ compression of femoropatellar cartilage with 150% body weight produces large deformations after 4 h (approximately 30% volume change), but only very little deformation during the first minutes of loading. Quantitative analyses of magnetization transfer and proton density hold promise for biochemical evaluation of articular cartilage, and are shown to be related to the deformational behavior of the cartilage. Application of these techniques to larger cohorts of patients in epidemiological and clinical studies will establish the role of quantitative cartilage imaging not only in basic research on form-function relationships of articular cartilage, but also in clinical research and management of osteoarthritis.