磁共振T_(1p)、T_2Mapping及DWI定量检测技术诊断腰椎间盘退变的初步研究
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摘要
第一章腰椎间盘退变与Pfirrmann分级研究
目的：
应用3.0TMRI T2WI检查技术,分析节段、性别和年龄与Pfirrmann分级的关系,探讨与腰椎间盘退变有关的生理因素,并为后续定量分析奠定基础。
材料和方法：
病例选择：健康志愿者88例,其中男36,女52,年龄20-76岁,平均(33.5+14.0)岁,纳入标准：无长期体力劳动史、脊柱外伤史、无长期后背痛、腰痛及脊柱畸形。
检查设备及参数：采用多源发射3.0T磁共振(Achieva3.0T TX, Philips),脊柱专用线圈,仰卧位,头先进模式。采用TSE序列采集常规矢状位T2加权像：参数如下TR=3000ms,TE=128ms,FOV=220mm(FH)×201mm(AP)×55mm(RL),层厚5mm,层数11,矩阵448×448,翻转角=90°。
图像处理：由两位有丰富MRI诊断经验的副主任医师以T2WI正中矢状位图像为基础对椎间盘进行Pfirrmann分级,对有分歧者结合改良型Pfirrmann分级系统由两者商议后确定。
统计学方法：采用SPSS15.0软件,分别对腰椎间盘节段、性别、年龄与Pfirrmann分级进行检验：腰椎间盘节段与Pfirrmann分级采用Kruskal-Wallis秩和检验；性别与Pfirrmann分级采用Wilcoxon秩和检验；年龄与Pfirrmann分级检验采用方差分析并进行Spearman相关性检测。方差分析首先进行Levene方差齐性检验,如方差齐则采用单向分类的方差分析(ANOVA),多重比较采用LSD检验；方差不齐则采用Welch检验,多重比较采用Dnnett T3检验；P≤0.05认为有统计学意义
结果：
纳入研究的腰椎间盘节段共440个,包括Pfirrmann Ⅰ级69个、Ⅱ级232个、Ⅲ级90个、Ⅳ级37个、V级12个。正常成年人以Ⅱ级椎间盘最多见约占52%,而Ⅴ级椎间盘最少只占约3%。
不同腰椎间盘节段Pfirrmann等级未见显著性差异(P=0.156)。
不同性别间Pfirrmann等级未见显著性差异(P=0.361)
年龄与Pfirrmann分级关系,随着年龄增加,Pfirrmann等级增加,两者显著正相关(rs=0.668,P=0.000)；本研究观察到除Ⅳ、V级外,不同Pfirrmann等级的平均年龄有显著性差异,等级越高、年龄越大。
结论：
Pfirrmann分级系统作为最常用的腰椎间盘退变的影像学分级方法,对检测椎间盘随年龄的退变具有一定价值,但也存在对早期退变不敏感和主观性影响较大的缺点。
第二章腰椎间盘退变的T1p成像研究
目的：
应用3.OTMRI T1ρ检查技术,分析健康成人腰椎间盘髓核T1ρ值与Pfirrmann分级、腰椎间盘节段、性别、年龄的关系,探讨影响腰椎间盘退变的因素和T1ρ技术在腰椎间盘退变中应用的可行性,为磁共振对腰椎间盘退变的客观评价提供新的技术。
材料和方法：
病例选择：健康志愿者83例,其中男34例,女49例,年龄20-76岁,平均33.9+14.3岁,把志愿者按年龄分为≤35岁(56例)、36岁～50岁(10例),≥51岁(17例)三组。纳入标准：无长期体力劳动史、脊柱外伤史、无长期后背痛、腰痛及脊柱畸形。
检查设备及参数：扫描仪器及常规矢状位T2WI采集同上。T1ρ扫描序列采用3D稳态梯度回波序列,扫描参数：TR=4.85ms,TE=2.39ms,FOV=220mm(FH)×201mm(AP)×55mm(RL),层厚=5mm,层数11,矩阵448×448,翻转角=50。,自旋锁定频率500Hz,自旋锁定时间(Time of spin lock, TSL)分别为0/10/20/30/40ms。
图像处理：由两位有丰富MRI诊断经验的副主任医师以T2WI正中矢状位图像为基础对椎间盘进行Pfirrmann分级,对有分歧者结合改良型Pfirrmann分级系统由两者商议后确定。采用Philips公司提供的后处理软件对数据进行处理得到T1ρ值图,再用ImageJ软件进行手动绘制髓核感兴趣区、伪彩化处理、图像融合和T1ρ值的测定。感兴趣区在T2WI图像绘制,在正中矢状位层面对椎间盘进行三等分,取中间区域作为感兴趣区测量平均值。
统计学方法：统计学方法采用SPSS15.0软件：(1)采用方差分析不同Pfirrmann等级腰椎间盘髓核的T1ρ值差异并进行Spearman相关性检验；使用非参数法构建ROC曲线,计算曲线下面积,以Youden指数最大的切点为诊断界点,并得到此点对应的灵敏度和特异度；(2)采用方差分析不同腰椎间盘节段髓核的T1ρ值差异；(3)分析各节段椎间盘髓核的T1ρ值性别差异,采用独立样本t检验；(4)分析年龄与T1ρ值的相关性,由于年龄不服从正态分布,故采用Spearman相关分析；采用方差分析不同年龄组间的T1ρ值差异。方差分析首先进行Levene方差齐性检验,如方差齐则采用单向分类的方差分析(ANOVA),多重比较采用LSD检验；方差不齐则采用Welch检验,多重比较采用Dnnett T3检验；P≤0.05认为有统计学意义。
结果：
纳入研究的腰椎间盘节段共358个,包括Pfirrmann Ⅰ级50例、Ⅱ级188例、Ⅲ级75例、Ⅳ级37例、V级8例。
T1ρ伪彩图显示正常髓核可分为外周淡黄绿色中值区和核心的橘红色高值区,纤维环除表现为蓝色低值外也夹杂部分中值色。随着退变加重,髓核量值降低、颜色逐渐呈现均匀蓝色；纤维环量值增加。
不同Pfirrmann等级腰椎间盘髓核的T1ρ值：Ⅳ级与V级两者无显著性差异,余各等级间均具有显著性差异。T1ρ值与Pfirrmann分级显著负相关(rs—0.538)。各等级间的参考界值：Ⅰ-Ⅱ级为116.5ms,Ⅱ-Ⅲ级为103.5ms,Ⅲ-Ⅳ级为86.5ms,其诊断不同Pfirrmann等级椎间盘的准确性不高。
不同节段腰椎间盘髓核的T1ρ值,L4/5、L5/S1节段与其余节段均具有显著性差异,但此两者之间无显著性差异。
不同性别各节段腰椎间盘髓核的T1ρ值无显著性异。
年龄与T1ρ值中等负相关(rs=—0.335)；≥51岁组与其它两组存在显著性差异,T1ρ值20-45岁阶段保持相对稳定,在45岁以后则迅速并持续降低。
结论：
T1ρ成像较T2WI对腰椎间盘内组化成分的变化更敏感,可以早期发现并量检测不同程度的腰椎间盘退变,也可监测随年龄增加腰椎间盘变化的过程减少由于诊断经验、主观感受等因素引起的偏差,提高了检查的客观性和司复性。
第三章腰椎间盘退变的T2Mapping成像研究
目的：
应用3.0TMRI T2Mapping检查技术,分析健康成人腰椎间盘髓核的T2值与Pfirrmann分级、腰椎间盘节段、性别、年龄和Tip值的关系,评价并比较两种定量检测技术对腰椎间盘退变的诊断价值。
材料和方法：
病例选择：健康志愿者86例,其中男34例,女52例,年龄20-76岁,平均33.5±14.1岁,把志愿者按年龄分为≤35岁(57例)、36岁～50岁(12例),≥51岁(17例)三组。纳入标准：无长期体力劳动史、脊柱外伤史、无长期后背痛、腰痛及脊柱畸形。嘱患者检查前12小时勿作剧烈运动,扫描前平躺半小时,扫描时间段17：00-22：30
检查设备及参数：扫描仪器及常规矢状位T2WI采集同上。T2Mapping成像参数如下：TR=1162ms,TE=n×20ms,FOV=220mm(FH)×220mm(AP)×25mm(RL),层厚5mm,层数5,矩阵448×448,翻转角=90°,时间12：41。扫描前自动匀场和抑脂技术,为减少呼吸及胃肠蠕动造成的伪影,在椎体前方设置饱和带,以覆盖全部肠道为宜。
图像处理：由两位有丰富MRI诊断经验的副主任医师以T2WI正中矢状位图像为基础对腰椎间盘进行Pfirrmann分级,对有分歧者结合改良型Pfirrmann分级系统由两者商议后确定。采用Philips公司提供的后处理软件对数据进行处理得到T1ρ值和T2Mapping图,再用ImageJ软件进行手动绘制髓核感兴趣区、伪彩化处理、图像融合和定量值的测定。
统计学方法：采用SPSS15.0软件：(1)采用方差分析不同Pfirrmann等级腰椎间盘髓核的T2值差异,进行Spearman相关性检验,构建ROC曲线,计算AUC,并以Youden指数最大的切点为诊断界点,得到此点对应的灵敏度和特异度；(2)采用方差分析不同腰椎间盘节段髓核的T2值差异；(3)分析各节段腰椎间盘髓核的T2值性别差异,采用独立样本t检验；(4)年龄与髓核的T2值进行Spearman相关性检验；采用方差分析不同年龄组髓核的T2值差异；(5)对T2值和T1ρ值进行相关性分析,采用Pearson方法。方差分析首先进行Levene方差齐性检验,如方差齐则采用单向分类的方差分析(ANOVA),多重比较采用LSD检验；方差不齐则采用Welch检验,多重比较采用Dnnett T3检验；P≤0.05认为有统计学意义。
结果：
纳入研究的腰椎间盘节段共420个,包括Pfirrmann I级66例、Ⅱ级225例、Ⅲ级81例、Ⅳ级37例、V级11例。
伪彩图显示正常髓核可分为外周淡黄绿色中值区和核心的橘红色高值区,纤维环表现为蓝色低值。相对于T1ρ图像,T2Mapping髓核核心区量值偏低,不论髓核区还是纤维环区其量值更加均匀；随着髓核T2WI信号的降低,髓核量值逐渐降低,两者变化趋势相同；相对于T1ρ伪彩图,纤维环量值变化幅度较小。
腰椎间盘髓核的T2值随着Pfirrmann等级增加(Ⅰ-Ⅳ级),T2值逐渐减小；除Ⅰ级与Ⅱ级、Ⅳ级与V级外,余各等级间均具有显著性差异；T2值与Pfirrmann分级显著负相关(rs—0.665)。各等级间的参考界值：Ⅱ-Ⅲ级为94.5ms,Ⅲ-Ⅳ级为67.5ms；对不同Pfirrmann等级腰椎间盘退变诊断的准确性较高(AUC>0.8)。
不同节段腰椎间盘髓核的T2值未见显著性差异。
整体上在腰椎间盘各节段,男性髓核的T2值均要高于女性,其中在L1/2及L2/3节段具有显著性差异；在其它各节段差异不显著。
年龄与髓核的T2值中度负相关(rs=—0.492)；三组间均存在显著性差异,髓核的T2值自20岁-45岁缓慢降低,约在45-50岁轻度增高,50-55岁以后迅速降低,并在55岁后维持在较低水平。
T1ρ值与T2值两者具有中度正相关性,1=0.445,P=0.000。
结论：
腰椎间盘髓核的T2值可以定量检测不同程度的退变,也可监测随年龄增加椎间盘变化的过程。相对于Tip值,T2值动态变化范围较小,对早期退变的敏感性弱于Tip技术,对中晚期退变的诊断准确度较高。T2值与T1ρ值的中度正相关可能与髓核PG含量的降低导致了水含量的减少有关。
第四章腰椎间盘退变的弥散加权成像(DW[)研究
目的：
应用3.OTMRI DWI检查技术,分析健康成人腰椎间盘髓核的ADC值与Pfirrmann分级、腰椎间盘节段、性别、年龄的关系,探讨三种定量技术的相关性及其可能的意义,比较三者在腰椎间盘退变诊断中的价值并对其进行综合分析。
材料和方法：
病例选择：健康志愿者42例,其中男16例,女26例,年龄22～63岁,平均38.2±13.9岁,把志愿者按年龄分为≤35岁(22例)、36岁～50岁(9例),≥51岁(11例)三组。纳入标准：无长期体力劳动史、脊柱外伤史、无长期后背痛、腰痛及脊柱畸形。嘱患者检查前12小时勿作剧烈运动,扫描前平躺半小时,扫描时间段17：00-22：30。
检查设备及参数：扫描仪器、T1ρ、T2Mapping扫描参数同上。DWI扫描采用平面回波(EPI)脉冲序列,参数：TR=3000ms,TE=64ms,层厚5mm,扫描层数11,FOV=180mm(FH)×56mm(AP)×65mm(RL),矩阵=288×288,翻转角=90°,b值取Osec/mm2和500sec/mm2。扫描二次常规T2WI图像,首次FOV及矩阵与T1ρ技术一致,二次与DWI技术一致。在椎体前方设置饱和带,以覆盖全部肠道为宜,并在FOV头侧设置水平饱和带。
图像处理：由两位有丰富MRI诊断经验的副主任医师以T2WI正中矢状位图像为基础对腰椎间盘进行Pfirrmann分级,对有分歧者结合改良型Pfirrmann分级系统由两者商议后确定。采用Philips公司提供的后处理软件对数据进行处理得到ADC图,再用ImageJ软件进行手动绘制髓核感兴趣区、伪彩化处理、图像融合和髓核ADC值的测定。感兴趣区的绘制同前。
统计学方法采用SPSS15.0软件：(1)采用方差分析不同Pfirrmann等级椎间盘髓核的ADC值差异,进行Spearman相关性检验,构建ROC曲线,计算AUC,并以Youden指数最大的切点为诊断界点,得到此点对应的灵敏度和特异度；(2)采用方差分析不同节段腰椎间盘髓核的ADC值差异；(3)分析各节段腰椎间盘髓核的ADC值性别差异,采用独立样本t检验；(4)进行年龄与髓核ADC值的Spearman相关性检验,采用方差分析不同年龄组髓核的T2值差异；(5)采用Pearson方法对ADC值与T2值、T1ρ值进行相关性分析。方差分析首先进行Levene方差齐性检验,如方差齐则采用单向分类的方差分析(ANOVA),多重比较采用LSD检验；方差不齐则采用Welch检验,多重比较采用Dnnett T3检验；P≤0.05认为有统计学意义。
结果：
纳入研究的腰椎间盘节段共207个,包括Pfirrmann Ⅰ级19例、Ⅱ级106例、Ⅲ级44例、Ⅳ级29例、V级9例。
ADC伪彩图显示髓核内ADC量值分布与T1ρ、T2Mapping有差异,Ⅱ级椎间盘T1ρ、T2Mapping高值主要位于髓核中心区域,而ADC高值则分布于髓核边缘区域,并且纤维环与髓核的差异性更显著。
不同Pfirrmann等级腰椎间盘髓核的ADC值：除Ⅰ级与Ⅱ级、Ⅳ级与V级外,其余各级间均有显著性差异,虽然部分等级间无统计差异,但随着等级增加,ADC值整体趋势是逐渐减小；ADC值与Pfirrmann分级显著负相关(rs=—0.530)。各等级间的参考界值：Ⅱ-Ⅲ级为1.732×10-3mm2/s,Ⅲ-Ⅳ级为1.587×10-3mm2/s。
腰椎间盘不同节段髓核ADC：L1/2与L2/3、L3/4间具有显著性差异(P=0.014,P=0.050)。
男性与女性各节段髓核的ADC值均未见显著性差异。
年龄与髓核的ADC值中度负相关(rs=—0.422)；≥51岁组与其它两组存在显著性差异；研究ADC值与年龄的趋势图可发现ADC值自20-45岁逐渐降低,约在45-50岁增高,50-60岁再次迅速降低,60岁后轻度抬高。
ADC值与T1ρ值、T2值两者显著正相关性。
结论：
同T1ρ值与T2值类似,髓核的ADC值也与不同程度的腰椎间盘退变相关,并且三者呈显著正相关,但其随年龄的改变却更为复杂。此结果符合腰椎间盘退变的病理变化,即髓核内PG的减少可以导致含水量减少,从而影响水的弥散,证明采用此三种定量方法分析IVDD是可靠的,对于检测IVDD和监测病变进展具有重要价值。
第五章X线导引下针刺诱导兔椎间盘退行性改变的初步研究
目的：
本部分研究X线导引下针刺诱导兔椎间盘退行性改变模型的建立并对椎间盘进行MR定量检测,为MR定量检测技术的深入研究奠定基础。
材料和方法：
选用清洁级健康新西兰大白兔5只,在X线导引下采用穿刺髓核和穿刺软骨终板两种手术方式。分别在穿刺前、穿刺后30分钟、4周及8周进行常规T2WI、T1ρ、T2Mapping成像和CT三维重建,8周对诸椎间盘进行病理学分析。
结果：
造模后30分钟,各椎间盘磁共振信号未见明确异常；4周穿刺髓核组T2WI信号明显降低,高信号区范围缩小；T1ρ技术由于分辨率不足未能成功检测到椎间盘量值的改变；T2Mapping显示高值范围明显缩小；8周髓核变化与4周类似,未见明确退变进展；余各椎间盘(包括正常对照组和穿刺软骨终板组)信号改变不明显。
病理学发现穿刺髓核组的髓核组织发生非常明显的退变,而穿刺软骨终板组发生轻度退变。
结论：
本研究采用X线导引下针刺椎间盘髓核的方式成功建立了兔的椎间盘退变模型,此模型具有操作简单、经济、并发症低、影响因素少等优势,并且证明了T2Mapping技术可用于兔椎间盘退变的检测,为采用动物模型研究磁共振定量技术对IVDD的诊断价值奠定了基础。
全文总结
Pfirrmann等级与三种定量指标的关系：从相关系数看,T2值与Pfirrmann分级相关性最强,可以理解为Pfirrmann分级是以腰椎间盘信号为基础的分级系统,T2WI信号主要反映了组织内含水量,因此与T2值关系更为密切。从准确度讲,对于Ⅱ级以上退变诊断的准确性以T2Mapping技术最高。T2Mapping的ROC曲线显示Ⅱ-Ⅲ级、Ⅳ级-V级的AUC分别为0.865、0.906；高于T1p值(0.720、0.717)和ADC(0.673、0.813)。从检验效能上讲,T2Mapping与DWI技术未能发现Ⅰ级与Ⅱ级的差异,可认为对腰椎间盘早期退变敏感性较低。
Ⅳ级与V级在各定量检测中均未见显著性差异,考虑Pfirrmann分级中,Ⅳ级与V级的区别仅是椎间隙的改变,而无关腰椎间盘信号的改变,两者间定量值可无差异；另一方面也可能是由于V级样本量较小而未能显示两者间的差别,同时正常人中V级比例较低可能说明椎间隙改变往往导致临床症状,这需要在患病人群中进一步统计分析。
由于临床实践上L4/5、L5/S1是最常发生腰椎间盘退变和膨突出的部位,因此T1ρ技术作为唯一可以检测出L4/5、L5/Sl与其它节段不同的方法对早期退变的敏感性应该高于其它方法；综合对Pfirrmann等级的诊断,我们认为T1ρ技术对早期退变的敏感性高于T2Mapping与DWI技术；而对于Ⅱ级以上的中晚期退变诊断的准确性则以T2Mapping技术最高。
研究表明性别对正常人腰椎间盘退变的影响很小。
年龄与腰椎间盘退变的关系：本研究所有检测指标均显示出与年龄相关,因此相对于性别、节段而言,年龄对腰椎间盘退变的作用要更显著。其中以Pfirrmann分级与年龄的相关性最强,而T1ρ值相关性最弱,通过趋势图可以发现,正常人T1ρ值在45岁前比较稳定,这同基础研究显示50岁后髓核的基质很难得到修复相一致,因此可以认为中青年时期腰椎间盘内最显著的变化应该是水含量的丢失。
通过比较定量检测三种技术时间变化曲线,本研究提出二个假说：(1)髓核的ADC值在腰椎间盘退变过程中处于一种波动性变化中,这是由于ADC值所反映的水分子运动与水含量和基质内PG的含量有关,基质内PG具有结合水的能力因此一方面提高髓核内水的含量,另一方面限制水分子的运动。在45岁之前由于PG保持相对稳定,髓核内水含量则处于缓慢减少节段,ADC值同步下降；45-50岁由于自身修复能力的降低,PG出现明显的丢失,对水分子运动限制能力明显减弱,水分子运动活跃,ADC值中运动增加的权重超过水含量丢失的权重,ADC值增加；随着PG进一步丢失,水含量明显降低,水含量丢失的权重超过运动能力增加的权重,ADC值又明显降低。目前研究中ADC值与退变的关系争议较多,本假说对于ADC值进一步研究提供了参考。(2)更为重要的是认为45-50岁是髓核内组织成分发生剧烈变化的时间点,为临床干预、延缓IVDD进展提供重要参考,对本假说进一步证明需要基础研究和更大样本研究的支持。
本研究采用X线导引下针刺椎间盘髓核的方式成功建立了兔的椎间盘退变模型,此模型具有操作简单、经济、并发症低、影响因素少等优势,并且证明了T2Mapping技术可用于兔椎间盘退变的检测,为采用动物模型研究磁共振定量技术对IVDD的诊断价值奠定了基础。
Part I The study of correlation between lumber intervertebral disc degeneration and Pfirrmann grading system
Objective:
(1) To investigate the distribution of disc Pfirrmann grades in healthy volunteers and lay a foundation for further quantitative analyses.(2) To investigate the correlaitons between the degeneration in the lumber spine and the gender, disc level, age and suggest how intervertebral disc degeneration (IVDD) might be affected by physiologic factors.
Materials and Methods:
Subjects:88healthy volunteers (gender:36males,52females; age range=20-76years, mean age=33.5±14.0years) were recruited following approval from Institution Review Broad. Inclusion criteria consisted of:(1) no history of manual labor for a long time;(2) no significant backache within the past6months;(3) no history of spine trauma and deformity.
MR:MR scanning was perfomed3.0T magnetic resonance imaging scanner with dual-source RF transmission(3.0T Achieva TX, Philips) and saggital T2-weighted images were acquired using a fast spin echo sequence with a spine coil for Pfirrmann grading in all patients. The parameters were TR=3000ms, TE=128ms, FOV=220mm(FH)×201mm(AP)×55mm(RL), slice thickness=5mm, matrix=448X448, flip angle=90°, All morphological evaluations were performed by two radiologists in consensus, both with more than10years of experience. All the degenerative discs on T2WI were classified according to the Pfirrmann grading system.
Statistical methods:Statistical analyses were conducted using SPSS15.0software. Disc levels, age and sex of the volunteers and Pfirrmann grades were recorded and used for statistic analyses. We used (1) Kruskal-Wallis test between Pfirrmann grades and disc levels;(2) Wilcoxon test to calculate significant difference between Pfirrmann grades and sex;(3) A one-way analysis of variance (ANOVA) was employed to compare between age and Pfirrmann grades and the Spearman correlation coefficient was determined. Levene test for equality of variances was used to test homogeneity of variances among groups and under an equal condition, the significance of differences were tested using ANOVA with LSD as a post hoc test, otherwise a Dnnett T3test was used. P≤0.05was considered as significance.
Results:
The T2-weighted image-based on Pfirrmann grade classification results were as the following:69disks in grade Ⅰ,232in grade Ⅱ,90in grade Ⅲ,37in grade Ⅳ and12in grade Ⅴ.
No statistically significant difference was observed between the grades (P=0.156)
The difference in Pfirrmann scores between male and female was not obvious and not statistically significant (P=0.361).
There was a significant positive correlation between age and degenerative grade (rs=0.668, P=0.001). The average age of each grade had statistically significant difference, but no difference between grade Ⅳ and grade Ⅴ.
Conclusion:
Pfirrmann grading system is the most common imaging classification method of IVDD but it provides only qualitative data that can be influenced by variable conditions.
Part Ⅱ The study of correlation between lumber intervertebral disc degeneration and T1ρ-weighted imaging
Objective:
(1) To determine whether Tip-weighted imaging is quantitative biomarkers of IVDD and provide new technology for objective evaluation of degenerative discs.(2) To analyze the relationships between Tip and Pfirrmann grades, intervertebral disc levels, gender and age.
Materials and Methods:
Subjects:83healthy volunteers (gender:34males,49females; age range=20-76years, mean age=33.9±14.3years) were recruited following approval from Institution Review Broad. Inclusion criteria consisted of:(1) no history of manual labor for a long time;(2) no significant backache within the past6months;(3) no history of spine trauma and spinal deformity. All volunteers were subdivided into three groups according to age,<35years,36-50years and>51years,
respectively.
MR:Scanners and sagittal T2-weighted images acquisition were the same as mentioned in Part Ⅰ. T1ρ scanning sequence used3D steady gradient echo sequence and parameters were:TR=4.85ms, TE=2.39ms, FOV=220mm(FH)×201mm(AP)×55mm(RL), slice thickness=5mm, matrix=448×448, Flip angle=50°, spin-lock frequency=500Hz, TSLs=0/10/20/30/40ms.
Image processing:All discs were graded according to Pfirrmann grading system. Tip values were calculated on a pixel-by-pixel basis to the exponentially decaying Tip fuction using IDL (Research Systems, Inc, USA) to generate Tip relaxation maps.The color-coded maps were fused with T2WI and ROIs were drawn. Three equally sized rectangular regions were manually subdivided on the middle slices and the center ones were chosen as the areas of interest.
Statistical methods:Statistical analyses were conducted using SPSS15.0software.(1) ANOVA was employed to compare Tip values of different Pfirrmann grades and the Spearman correlation coefficient was determined. Furthermore, in order to determine the T1ρ boundary values between the Pfirrmann classification grades in the nuleus pulposus, receiver operating characteristic (ROC) analyses were perfomed between each grade which were significantly different.(2) ANOVA was employed to compare Tip values of different dick levels.(3) The independent sample t test was used to compare Tip values of different gender at the same disc level.(4) ANOVA was employed to compare between T1ρand age groups and the Spearman correlation coefficient between T1ρ and age was determined. Levene test for equality of variances was used to test homogeneity of variances among groups and under an equal condition, the significance of differences were tested using ANOVA with LSD as a post hoc test, otherwise a Dnnett T3test was used.P<0.05was considered as significant.
Results:
The T2-weighted image-based on Pfirrmann grade classification results were as the following:50disks in grade Ⅰ,188in grade Ⅱ,75in grade Ⅲ,37in grade Ⅳ and8in grade Ⅴ.
Color-coded T1ρmap displayed normal nucleus pulposus could be divided into peripheral low values and core high values areas and fiber annulus showed lowest values. With the reduction of T2WI signal, nucleus pulposus values gradually were lower and values of fiber annulus increased.
Tip values were statistically significantly different when comparing between every grade, but not when comparing between grades Ⅲ and Ⅴ. T1ρ was significant negative correlation with Pfirrmann grade (rs=-0.538). ROC analyses illustrate the Tip cut-off value between grade Ⅰ and Ⅱ was116.5ms, which corresponded to a sensitivity, specificity, and area under the curve (AUC) of70%,53.2%and0.623respectively. The cut-off value, sensitivity, specificity, and AUC between grade Ⅱ and Ⅲ were103.5ms,67.6%,66.7%,0.720respectively, and those between grades Ⅲ and Ⅳ were86.5ms,60%,75.5%and0.717respectively.
T1ρ values were statistically significantly different when comparing between every level, but not when comparing between L4/5and L5/S1.
The difference in T1ρ values between male and female in the nuleus pulposus of every level was small and not statistically significant.
T1ρ values decreased significantly with increasing age and this correlation with age was moderate negatice (rs=-0.335). The T1ρ values remained relatively stable during20-45years and rapidly and continuously reduced after45years.
Conclusion:
Tip reflects changes in IVD composition, with comparably high spatial resolution. T1ρ imaging technique is more sensitive to molecular modification than T2WI and can be potentially used as a clinical tool to detect early IVDD and longitudinal followup. The method can create a reliable quantitative scale, as the result, the accuracy and repeatability of measurements are better than Pfirrmann grading system.
ParⅢ The study of correlationship between lumber intervertebral disc degeneration with T2Mapping imaging
Objective:
(1) To determine the associations between T2and Pfirrmann grades, intervertebral disc levels, gender and age.(2) To assess, compare and correlate T1ρ and T2relaxation time.
Materials and Methods:
Subject:86healthy volunteers (gender:34males,52females; age range=20-76years, mean age=33.5±14.1years) were recruited following approval from Institution Review Broad. Inclusion criteria consisted of:(1) no history of manual labor for a long time;(2) no significant backache within the past6months;(3) no history of spine trauma and spinal deformity. All volunteers were subdivided into three groups according to age,≤35years,36-50years and≥51years respectively. Volunteers were investigated in the afternoon (5-10PM) and did not exercise strenuously and laid down about half an hour before scan.
MR:Scanners and sagittal T2-weighted images acquisition were the same as the mentioned in Part I and T2Mapping parameters were:TR=1162ms, TE=n×20ms, FOV=220mm(FH)×201mm(AP)×25mm(RL), slice thickness=5mm, matrix=448×448, Flip angle=90°. To reduce the artifacts caused by respiratory and gastrointestinal moving, the saturation band was set in front of the vertebral bodies and automatic shimming and fat suppression techniques were applied.
Image processing:All discs were scored according to Pfirrmann grading system. T2values were calculated on a pixel-by-pixel basis to generate T2relaxation map. The color-coded maps were fused with T2WI and ROIs were drawn.
Statistical methods:Statistical analyses were conducted using SPSS15.0software.(1) ANOVA was employed to compare T2values of different Pfirrmann grades and the Spearman correlation coefficient was determined. Furthermore, in order to determine the T2boundary values between the Pfirrmann classification grades in the nuleus pulposus, ROC analyses was perfomed between each grade which were significantly different.(2) ANOVA was employed to compare T2values of different disc levels.(3) The independent sample t test was used to compare T2values of different gender at the same disc level.(4) ANOVA was employed to compare between T2values and age groups and the Spearman correlation coefficient between T2and age was determined.(5) The Pearson correlation coefficient was determined between T1ρ and T2values. Levene test for equality of variances was used to test homogeneity of variances among groups and under an equal condition, the significance of differences were tested using ANOVA with LSD as a post hoc test, otherwise a Dnnett T3test was used.P≤0.05was considered as significant.
Results:
The T2-weighted image-based on Pfirrmann grade classification results were as the following:66disks in grade Ⅰ,225in grade Ⅱ,81in grade Ⅲ,37in grade Ⅳ and11in grade Ⅴ.
Color-coded maps displayed normal nucleus pulposus could be divided into peripheral low values and core high values area and the fiber annulus were lowest. Comparing with the T1ρ, the high values were lower and the values of nucleus pulposus and fiber annulus were more uniform. With the reduction of T2WI signal, the values of pulposus gradually were lower and fiber annulus changes were less significance than T1ρ.
T2values were significantly different when comparing between every grade, but not when comparing grade Ⅰ with Ⅱ and grade Ⅳ with Ⅴ. T2values was significant negative correlation with Pfirrmann grades (rs=-0.665). ROC analyses illustrated the T2cut-off value between grade Ⅱ and Ⅲ was94.5ms, which corresponded to a sensitivity, specificity, and AUC of84.9%,71.6%and0.865respectively. The cut-off value, sensitivity, specificity, and AUC between grade Ⅲ and Ⅳ were67.5ms,75.3%,91.9%and0.906respectively.
T2values were not significantly different when comparing between every level.
Overall in all intervertebral disc level, T2values of male were higher than female's, even there was significant difference between L1/2and L2/3.
T2values decreased significantly with increasing age and this correlation with age was moderate negative (rs=-0.492). T2values during20-45years decreased slowly and increased slightly during45-50years, then the values fell rapidly again and stayed low stage after55years.
T2values was moderate positive correlation with T1ρ value(r=0.445).
Conclusion:
The method of T2Mapping seems to be able to characterize different degrees of disc degeneration quantitatively and become a promising method for longitudinal followup. T2Mapping can monitor the changes in tissue composition and is less sensitive for early IVDD than T1ρ, on the other hand, T2Mapping demonstrate higher degree of accuracy for late stage. The moderate positive correlation between Tip and T2can suggest the decrease of PG content in nucleus pulposus lead to the water loss.
PartIV The study of correlationship between intervertebral disc degeneration with diffusion weighted imaging
Objective:
(1) To determine the associations between ADC values and Pfirrmann grades, intervertebral discs levels, gender and age.(2) To assess, compare and correlate quantitative Tip, T2relaxation time and ADC values and finish the comprehensive analyses for the three quantitative methods.
Materials and Methods:
Subjects:42healthy volunteers (gender:16males,26females; age range=22-63years, mean age=38.2±12years) were recruited following approval from Institution Review Broad. Inclusion criteria consisted of:(1) no history of manual labor for a long time;(2) no significant backache within the past6months;(3) no history of spine trauma and spinal deformity. All volunteers were subdivided into three groups according to age,≤35years,36～50years,≥51years respectively. Volunteers were investigated in the afternoon (5～10PM) and did not exercise strenuously and laid down about half an hour before scan.
MR:MR instrument, Tip and T2Mapping scan parameters were the same as the mentioned in Part1-3. DWI parameters were:TR=3000ms, TE=64ms, FOV=180mm(FH)×56mm(AP)×65mm(RL), slice thickness=5mm, matrix=288×288, flip angle=90°, b values=Osec/mm2and500sec/mm2. Fov and acquisition matrix of T2WI were the same as the ones of T1ρ and DWI, respectively.
Image processing:All discs were scored according to Pfirrmann grading system. ADC values were calculated on a pixel-by-pixel basis using the scanner software. The color-coded ADC maps by using ImageJ software. At last the color-coded maps were fused with convention T2WI and ROIs were drawn.
Statistical methods:Statistical analyses were conducted using SPSS15.0software.(1) ANOVA was employed to compare ADC values of different Pfirrmann grades and the Spearman correlation coefficient was determined. Furthermore, in order to determine the ADC boundary values between the Pfirrmann classification grades in the nuleus pulposus, ROC analyses were perfomed between each grade which were significantly different.(2) ANOVA was employed to compare ADC values of different dick levels.(3) The independent sample t test was used to compare ADC values from different gender of the same level.(4) ANOVA was employed to compare ADC values and age groups and the Spearman correlation coefficient between ADC and age was determined.(5) The Pearson correlation coefficients were determined between ADC with T2and T1ρ respectively. Levene test for equality of variances was used to test homogeneity of variances among groups and under an equal condition, the significance of differences were tested using ANOVA with LSD as a post hoc test, otherwise a Dnnett T3test was used.P≤0.05was considered as significant.
Results:
The T2-weighted image-based on Pfirrmann grade classification results were as the following:19disks in grade Ⅰ,106in grade Ⅱ,44in grade Ⅲ,29in grade Ⅳ and9in grade Ⅴ.
Color-coded maps displayed normal nucleus pulposus could be divided into core low values and peripheral high values areas and fiber annulus were black which indicated extremely low values, as the result, the difference between nucleus pulposus and fiber annulus was more significant than other two kinds of color-coded maps. Comparing with the Tip and T2Mapping, the distribution of high values were different that laid on the peripheral area.
ADC values were no significantly different when comparing between grade Ⅰ and Ⅱ, grade Ⅲ and Ⅳ. ADC was significant negative correlation with Pfirrmann grade (rs=-0.530). ROC analyses between each grade illustrated the ADC cut-off value between grade Ⅱ and Ⅲ was1.732×10-3mm2/s, which corresponded to a sensitivity, specificity, and AUC of50%,81.8%and0.673respectively. The cut-off value, sensitivity, specificity, and AUC between grade Ⅲ and Ⅳ were1.582×10-3mm2/s,64.1%,89.7%and0.813respectively.
ADC values were statistically significantly different when L1/2comparing with L2/3and L3/4(P=0.014, P=0.050).
No statistically significant difference was found between men and women in each disc level.
ADC values decreased significantly with increasing age and this correlation with age was moderate negative (rs=-0.422). ADC values during20-45years decreased slowly and increased dramatically during45-50years, then the values fell rapidly again after50years.
ADC values were significant positive correlation with T1ρ and T2values.
Conclusion:
The method of DWI seems to be also able to characterize different degrees of disc degeneration quantitatively and ADC values are significant positive correlation with T1ρ and T2, which can reflect the changes in tissue composition. T1ρ, T2and DWI are the promising methods for detecting early early and longitudinal followup ofIVDD.
Part V A novel rabbit model of disc degeneration by needle puncture under X-ray guidance
Objective:
To establish a reproducible rabbit model of disc degeneration by needle puncture using X-ray guidance, then determine whether MR quantitative technology can evaluate the disc degeneration of rabbits.
Materials and methods:
Five SP healthy New Zealand white rabbits were used in this study under the Insitutional Animal Care Use Committee approval. Nucleus pulposus and cartilage endplates were destructed respectively through anular puncture under X-ray guidance. The IVDD was evaluated using MR T2WI, T1ρ and T2Mapping techniques at the time points of pre-puncture, after30minutes,4weeks and8weeks. Pathological changes of the intervertebral discs were analyzed after8weeks.
Results:
T2WI and CT:After30minutes, MR and CT failed to find changes of intervertebral disc. On the contrary, after4and8weeks, signal intensity of the punctured discs decreased. Other disc levels intensity had not different with control group.
Tip technology did not provide enough spatial resolution to detect the values changes of nucleus pulpous. T2Mapping showed values of nucleus pulposus were significant low after4and8weeks in the nuclers pulposus of punctured discs and the values of other discs remains no change.
Conclusion:
Nucleus pulposus destructed approach by needle puncture using X-ray guidance can result in a convenient, less-invasive, reproducible and cost-effective rabbit model of disc degeneration and be a useful choice for studying disc degeneration. T2Mapping can quantantatively evaluate the rabbit IVDD, on the contray, T1ρ technique is unable to detect the degeration in our experiment and more research investigation is required.
Summary
The relationship between Pfirrmann grades and three quantitative techniques: According to correlation coefficients, T2values had the strongest correlation with Pfirrmann grading, which can be resulted from Pfirrmann grading system based on disc signals of T2WI is closely correlated with water content in the nucleus pulposus. T2Mapping and DWI failed to discover the differences of grades I and II and it suggests the both techniques are less sensitive for early degeneration than T1ρ.
Three kinds of quantitative values were not significantly different between grades IV and V. Two reasons can lead to the result:First, according to Pfirrmann grading system, the difference between grades Ⅳ and Ⅴ is only the space of the intervertebral disc, regardless of the signal changes. Second, it also may be due to the small sample size of grade V. Furthmore, the narrow space of intervertebral disc may be closely correlated with clinical symptoms since the low incidence of grede V in healthy adult populations.
The relationship between disc levels and three quantitative techniques:Only T1ρ technology could identify the difference of L4/5and L5/S1from other levels with lower incidience of disc heniation.
So we consider T1ρ is more sensitive for early degeneration and T2Mapping demonstrate higher degree of accuracy for late stage.
Gender has little impact on the normal human intervertebral disc degeneration.
The relationship between age and three quantitative techniques:All three methods showed moderate or significant age-associated changes but Tip values showed the weakest correlation and remained stable younger than45years old, which was consistant with fundamental research that nucleus pulposus matrix was hard to be repaired older than50years. So we think the most significant change in nucleus pulposus should be the loss of water content young and middle-aged populations. Hypothesis:Comparing three value curves of age-associated changes, ADC values fluctuated during45-50years old. We suggest ADC values are closely correlated with water and PG cotent. One one hand, PG attracted the water; on the other hand, PG restricts Brown motion of water molecules. Before45years old, PG remains stable and water gradually loses, which lead to ADC values decrease. During45-50years old, PG content diminishes dramatically and can not restrict the motion of water, as the result, ADC values increase although water content lose continually. After50years old, the loss of water dominates and ADC values decrease again. So studying the correlation between DWI and IVDD, more factors need to be considered. We think it is more important to note the tissue composition changes dramatically at the45-50years old stage and the finding can provide the evidence to support clinical intervention for delaying IVDD.
We can induce a convenient, less-invasive, reproducible and cost-effective rabbit model of disc degeneration and T2Mapping is a promising method for investigating IVDD of rabbit model.
目的：
应用3.0TMRI T2WI检查技术,分析节段、性别和年龄与Pfirrmann分级的关系,探讨与腰椎间盘退变有关的生理因素,并为后续定量分析奠定基础。
材料和方法：
病例选择：健康志愿者88例,其中男36,女52,年龄20-76岁,平均(33.5+14.0)岁,纳入标准：无长期体力劳动史、脊柱外伤史、无长期后背痛、腰痛及脊柱畸形。
检查设备及参数：采用多源发射3.0T磁共振(Achieva3.0T TX, Philips),脊柱专用线圈,仰卧位,头先进模式。采用TSE序列采集常规矢状位T2加权像：参数如下TR=3000ms,TE=128ms,FOV=220mm(FH)×201mm(AP)×55mm(RL),层厚5mm,层数11,矩阵448×448,翻转角=90°。
图像处理：由两位有丰富MRI诊断经验的副主任医师以T2WI正中矢状位图像为基础对椎间盘进行Pfirrmann分级,对有分歧者结合改良型Pfirrmann分级系统由两者商议后确定。
统计学方法：采用SPSS15.0软件,分别对腰椎间盘节段、性别、年龄与Pfirrmann分级进行检验：腰椎间盘节段与Pfirrmann分级采用Kruskal-Wallis秩和检验；性别与Pfirrmann分级采用Wilcoxon秩和检验；年龄与Pfirrmann分级检验采用方差分析并进行Spearman相关性检测。方差分析首先进行Levene方差齐性检验,如方差齐则采用单向分类的方差分析(ANOVA),多重比较采用LSD检验；方差不齐则采用Welch检验,多重比较采用Dnnett T3检验；P≤0.05认为有统计学意义
结果：
纳入研究的腰椎间盘节段共440个,包括Pfirrmann Ⅰ级69个、Ⅱ级232个、Ⅲ级90个、Ⅳ级37个、V级12个。正常成年人以Ⅱ级椎间盘最多见约占52%,而Ⅴ级椎间盘最少只占约3%。
不同腰椎间盘节段Pfirrmann等级未见显著性差异(P=0.156)。
不同性别间Pfirrmann等级未见显著性差异(P=0.361)
年龄与Pfirrmann分级关系,随着年龄增加,Pfirrmann等级增加,两者显著正相关(rs=0.668,P=0.000)；本研究观察到除Ⅳ、V级外,不同Pfirrmann等级的平均年龄有显著性差异,等级越高、年龄越大。
结论：
Pfirrmann分级系统作为最常用的腰椎间盘退变的影像学分级方法,对检测椎间盘随年龄的退变具有一定价值,但也存在对早期退变不敏感和主观性影响较大的缺点。
第二章腰椎间盘退变的T1p成像研究
目的：
应用3.OTMRI T1ρ检查技术,分析健康成人腰椎间盘髓核T1ρ值与Pfirrmann分级、腰椎间盘节段、性别、年龄的关系,探讨影响腰椎间盘退变的因素和T1ρ技术在腰椎间盘退变中应用的可行性,为磁共振对腰椎间盘退变的客观评价提供新的技术。
材料和方法：
病例选择：健康志愿者83例,其中男34例,女49例,年龄20-76岁,平均33.9+14.3岁,把志愿者按年龄分为≤35岁(56例)、36岁～50岁(10例),≥51岁(17例)三组。纳入标准：无长期体力劳动史、脊柱外伤史、无长期后背痛、腰痛及脊柱畸形。
检查设备及参数：扫描仪器及常规矢状位T2WI采集同上。T1ρ扫描序列采用3D稳态梯度回波序列,扫描参数：TR=4.85ms,TE=2.39ms,FOV=220mm(FH)×201mm(AP)×55mm(RL),层厚=5mm,层数11,矩阵448×448,翻转角=50。,自旋锁定频率500Hz,自旋锁定时间(Time of spin lock, TSL)分别为0/10/20/30/40ms。
图像处理：由两位有丰富MRI诊断经验的副主任医师以T2WI正中矢状位图像为基础对椎间盘进行Pfirrmann分级,对有分歧者结合改良型Pfirrmann分级系统由两者商议后确定。采用Philips公司提供的后处理软件对数据进行处理得到T1ρ值图,再用ImageJ软件进行手动绘制髓核感兴趣区、伪彩化处理、图像融合和T1ρ值的测定。感兴趣区在T2WI图像绘制,在正中矢状位层面对椎间盘进行三等分,取中间区域作为感兴趣区测量平均值。
统计学方法：统计学方法采用SPSS15.0软件：(1)采用方差分析不同Pfirrmann等级腰椎间盘髓核的T1ρ值差异并进行Spearman相关性检验；使用非参数法构建ROC曲线,计算曲线下面积,以Youden指数最大的切点为诊断界点,并得到此点对应的灵敏度和特异度；(2)采用方差分析不同腰椎间盘节段髓核的T1ρ值差异；(3)分析各节段椎间盘髓核的T1ρ值性别差异,采用独立样本t检验；(4)分析年龄与T1ρ值的相关性,由于年龄不服从正态分布,故采用Spearman相关分析；采用方差分析不同年龄组间的T1ρ值差异。方差分析首先进行Levene方差齐性检验,如方差齐则采用单向分类的方差分析(ANOVA),多重比较采用LSD检验；方差不齐则采用Welch检验,多重比较采用Dnnett T3检验；P≤0.05认为有统计学意义。
结果：
纳入研究的腰椎间盘节段共358个,包括Pfirrmann Ⅰ级50例、Ⅱ级188例、Ⅲ级75例、Ⅳ级37例、V级8例。
T1ρ伪彩图显示正常髓核可分为外周淡黄绿色中值区和核心的橘红色高值区,纤维环除表现为蓝色低值外也夹杂部分中值色。随着退变加重,髓核量值降低、颜色逐渐呈现均匀蓝色；纤维环量值增加。
不同Pfirrmann等级腰椎间盘髓核的T1ρ值：Ⅳ级与V级两者无显著性差异,余各等级间均具有显著性差异。T1ρ值与Pfirrmann分级显著负相关(rs—0.538)。各等级间的参考界值：Ⅰ-Ⅱ级为116.5ms,Ⅱ-Ⅲ级为103.5ms,Ⅲ-Ⅳ级为86.5ms,其诊断不同Pfirrmann等级椎间盘的准确性不高。
不同节段腰椎间盘髓核的T1ρ值,L4/5、L5/S1节段与其余节段均具有显著性差异,但此两者之间无显著性差异。
不同性别各节段腰椎间盘髓核的T1ρ值无显著性异。
年龄与T1ρ值中等负相关(rs=—0.335)；≥51岁组与其它两组存在显著性差异,T1ρ值20-45岁阶段保持相对稳定,在45岁以后则迅速并持续降低。
结论：
T1ρ成像较T2WI对腰椎间盘内组化成分的变化更敏感,可以早期发现并量检测不同程度的腰椎间盘退变,也可监测随年龄增加腰椎间盘变化的过程减少由于诊断经验、主观感受等因素引起的偏差,提高了检查的客观性和司复性。
第三章腰椎间盘退变的T2Mapping成像研究
目的：
应用3.0TMRI T2Mapping检查技术,分析健康成人腰椎间盘髓核的T2值与Pfirrmann分级、腰椎间盘节段、性别、年龄和Tip值的关系,评价并比较两种定量检测技术对腰椎间盘退变的诊断价值。
材料和方法：
病例选择：健康志愿者86例,其中男34例,女52例,年龄20-76岁,平均33.5±14.1岁,把志愿者按年龄分为≤35岁(57例)、36岁～50岁(12例),≥51岁(17例)三组。纳入标准：无长期体力劳动史、脊柱外伤史、无长期后背痛、腰痛及脊柱畸形。嘱患者检查前12小时勿作剧烈运动,扫描前平躺半小时,扫描时间段17：00-22：30
检查设备及参数：扫描仪器及常规矢状位T2WI采集同上。T2Mapping成像参数如下：TR=1162ms,TE=n×20ms,FOV=220mm(FH)×220mm(AP)×25mm(RL),层厚5mm,层数5,矩阵448×448,翻转角=90°,时间12：41。扫描前自动匀场和抑脂技术,为减少呼吸及胃肠蠕动造成的伪影,在椎体前方设置饱和带,以覆盖全部肠道为宜。
图像处理：由两位有丰富MRI诊断经验的副主任医师以T2WI正中矢状位图像为基础对腰椎间盘进行Pfirrmann分级,对有分歧者结合改良型Pfirrmann分级系统由两者商议后确定。采用Philips公司提供的后处理软件对数据进行处理得到T1ρ值和T2Mapping图,再用ImageJ软件进行手动绘制髓核感兴趣区、伪彩化处理、图像融合和定量值的测定。
统计学方法：采用SPSS15.0软件：(1)采用方差分析不同Pfirrmann等级腰椎间盘髓核的T2值差异,进行Spearman相关性检验,构建ROC曲线,计算AUC,并以Youden指数最大的切点为诊断界点,得到此点对应的灵敏度和特异度；(2)采用方差分析不同腰椎间盘节段髓核的T2值差异；(3)分析各节段腰椎间盘髓核的T2值性别差异,采用独立样本t检验；(4)年龄与髓核的T2值进行Spearman相关性检验；采用方差分析不同年龄组髓核的T2值差异；(5)对T2值和T1ρ值进行相关性分析,采用Pearson方法。方差分析首先进行Levene方差齐性检验,如方差齐则采用单向分类的方差分析(ANOVA),多重比较采用LSD检验；方差不齐则采用Welch检验,多重比较采用Dnnett T3检验；P≤0.05认为有统计学意义。
结果：
纳入研究的腰椎间盘节段共420个,包括Pfirrmann I级66例、Ⅱ级225例、Ⅲ级81例、Ⅳ级37例、V级11例。
伪彩图显示正常髓核可分为外周淡黄绿色中值区和核心的橘红色高值区,纤维环表现为蓝色低值。相对于T1ρ图像,T2Mapping髓核核心区量值偏低,不论髓核区还是纤维环区其量值更加均匀；随着髓核T2WI信号的降低,髓核量值逐渐降低,两者变化趋势相同；相对于T1ρ伪彩图,纤维环量值变化幅度较小。
腰椎间盘髓核的T2值随着Pfirrmann等级增加(Ⅰ-Ⅳ级),T2值逐渐减小；除Ⅰ级与Ⅱ级、Ⅳ级与V级外,余各等级间均具有显著性差异；T2值与Pfirrmann分级显著负相关(rs—0.665)。各等级间的参考界值：Ⅱ-Ⅲ级为94.5ms,Ⅲ-Ⅳ级为67.5ms；对不同Pfirrmann等级腰椎间盘退变诊断的准确性较高(AUC>0.8)。
不同节段腰椎间盘髓核的T2值未见显著性差异。
整体上在腰椎间盘各节段,男性髓核的T2值均要高于女性,其中在L1/2及L2/3节段具有显著性差异；在其它各节段差异不显著。
年龄与髓核的T2值中度负相关(rs=—0.492)；三组间均存在显著性差异,髓核的T2值自20岁-45岁缓慢降低,约在45-50岁轻度增高,50-55岁以后迅速降低,并在55岁后维持在较低水平。
T1ρ值与T2值两者具有中度正相关性,1=0.445,P=0.000。
结论：
腰椎间盘髓核的T2值可以定量检测不同程度的退变,也可监测随年龄增加椎间盘变化的过程。相对于Tip值,T2值动态变化范围较小,对早期退变的敏感性弱于Tip技术,对中晚期退变的诊断准确度较高。T2值与T1ρ值的中度正相关可能与髓核PG含量的降低导致了水含量的减少有关。
第四章腰椎间盘退变的弥散加权成像(DW[)研究
目的：
应用3.OTMRI DWI检查技术,分析健康成人腰椎间盘髓核的ADC值与Pfirrmann分级、腰椎间盘节段、性别、年龄的关系,探讨三种定量技术的相关性及其可能的意义,比较三者在腰椎间盘退变诊断中的价值并对其进行综合分析。
材料和方法：
病例选择：健康志愿者42例,其中男16例,女26例,年龄22～63岁,平均38.2±13.9岁,把志愿者按年龄分为≤35岁(22例)、36岁～50岁(9例),≥51岁(11例)三组。纳入标准：无长期体力劳动史、脊柱外伤史、无长期后背痛、腰痛及脊柱畸形。嘱患者检查前12小时勿作剧烈运动,扫描前平躺半小时,扫描时间段17：00-22：30。
检查设备及参数：扫描仪器、T1ρ、T2Mapping扫描参数同上。DWI扫描采用平面回波(EPI)脉冲序列,参数：TR=3000ms,TE=64ms,层厚5mm,扫描层数11,FOV=180mm(FH)×56mm(AP)×65mm(RL),矩阵=288×288,翻转角=90°,b值取Osec/mm2和500sec/mm2。扫描二次常规T2WI图像,首次FOV及矩阵与T1ρ技术一致,二次与DWI技术一致。在椎体前方设置饱和带,以覆盖全部肠道为宜,并在FOV头侧设置水平饱和带。
图像处理：由两位有丰富MRI诊断经验的副主任医师以T2WI正中矢状位图像为基础对腰椎间盘进行Pfirrmann分级,对有分歧者结合改良型Pfirrmann分级系统由两者商议后确定。采用Philips公司提供的后处理软件对数据进行处理得到ADC图,再用ImageJ软件进行手动绘制髓核感兴趣区、伪彩化处理、图像融合和髓核ADC值的测定。感兴趣区的绘制同前。
统计学方法采用SPSS15.0软件：(1)采用方差分析不同Pfirrmann等级椎间盘髓核的ADC值差异,进行Spearman相关性检验,构建ROC曲线,计算AUC,并以Youden指数最大的切点为诊断界点,得到此点对应的灵敏度和特异度；(2)采用方差分析不同节段腰椎间盘髓核的ADC值差异；(3)分析各节段腰椎间盘髓核的ADC值性别差异,采用独立样本t检验；(4)进行年龄与髓核ADC值的Spearman相关性检验,采用方差分析不同年龄组髓核的T2值差异；(5)采用Pearson方法对ADC值与T2值、T1ρ值进行相关性分析。方差分析首先进行Levene方差齐性检验,如方差齐则采用单向分类的方差分析(ANOVA),多重比较采用LSD检验；方差不齐则采用Welch检验,多重比较采用Dnnett T3检验；P≤0.05认为有统计学意义。
结果：
纳入研究的腰椎间盘节段共207个,包括Pfirrmann Ⅰ级19例、Ⅱ级106例、Ⅲ级44例、Ⅳ级29例、V级9例。
ADC伪彩图显示髓核内ADC量值分布与T1ρ、T2Mapping有差异,Ⅱ级椎间盘T1ρ、T2Mapping高值主要位于髓核中心区域,而ADC高值则分布于髓核边缘区域,并且纤维环与髓核的差异性更显著。
不同Pfirrmann等级腰椎间盘髓核的ADC值：除Ⅰ级与Ⅱ级、Ⅳ级与V级外,其余各级间均有显著性差异,虽然部分等级间无统计差异,但随着等级增加,ADC值整体趋势是逐渐减小；ADC值与Pfirrmann分级显著负相关(rs=—0.530)。各等级间的参考界值：Ⅱ-Ⅲ级为1.732×10-3mm2/s,Ⅲ-Ⅳ级为1.587×10-3mm2/s。
腰椎间盘不同节段髓核ADC：L1/2与L2/3、L3/4间具有显著性差异(P=0.014,P=0.050)。
男性与女性各节段髓核的ADC值均未见显著性差异。
年龄与髓核的ADC值中度负相关(rs=—0.422)；≥51岁组与其它两组存在显著性差异；研究ADC值与年龄的趋势图可发现ADC值自20-45岁逐渐降低,约在45-50岁增高,50-60岁再次迅速降低,60岁后轻度抬高。
ADC值与T1ρ值、T2值两者显著正相关性。
结论：
同T1ρ值与T2值类似,髓核的ADC值也与不同程度的腰椎间盘退变相关,并且三者呈显著正相关,但其随年龄的改变却更为复杂。此结果符合腰椎间盘退变的病理变化,即髓核内PG的减少可以导致含水量减少,从而影响水的弥散,证明采用此三种定量方法分析IVDD是可靠的,对于检测IVDD和监测病变进展具有重要价值。
第五章X线导引下针刺诱导兔椎间盘退行性改变的初步研究
目的：
本部分研究X线导引下针刺诱导兔椎间盘退行性改变模型的建立并对椎间盘进行MR定量检测,为MR定量检测技术的深入研究奠定基础。
材料和方法：
选用清洁级健康新西兰大白兔5只,在X线导引下采用穿刺髓核和穿刺软骨终板两种手术方式。分别在穿刺前、穿刺后30分钟、4周及8周进行常规T2WI、T1ρ、T2Mapping成像和CT三维重建,8周对诸椎间盘进行病理学分析。
结果：
造模后30分钟,各椎间盘磁共振信号未见明确异常；4周穿刺髓核组T2WI信号明显降低,高信号区范围缩小；T1ρ技术由于分辨率不足未能成功检测到椎间盘量值的改变；T2Mapping显示高值范围明显缩小；8周髓核变化与4周类似,未见明确退变进展；余各椎间盘(包括正常对照组和穿刺软骨终板组)信号改变不明显。
病理学发现穿刺髓核组的髓核组织发生非常明显的退变,而穿刺软骨终板组发生轻度退变。
结论：
本研究采用X线导引下针刺椎间盘髓核的方式成功建立了兔的椎间盘退变模型,此模型具有操作简单、经济、并发症低、影响因素少等优势,并且证明了T2Mapping技术可用于兔椎间盘退变的检测,为采用动物模型研究磁共振定量技术对IVDD的诊断价值奠定了基础。
全文总结
Pfirrmann等级与三种定量指标的关系：从相关系数看,T2值与Pfirrmann分级相关性最强,可以理解为Pfirrmann分级是以腰椎间盘信号为基础的分级系统,T2WI信号主要反映了组织内含水量,因此与T2值关系更为密切。从准确度讲,对于Ⅱ级以上退变诊断的准确性以T2Mapping技术最高。T2Mapping的ROC曲线显示Ⅱ-Ⅲ级、Ⅳ级-V级的AUC分别为0.865、0.906；高于T1p值(0.720、0.717)和ADC(0.673、0.813)。从检验效能上讲,T2Mapping与DWI技术未能发现Ⅰ级与Ⅱ级的差异,可认为对腰椎间盘早期退变敏感性较低。
Ⅳ级与V级在各定量检测中均未见显著性差异,考虑Pfirrmann分级中,Ⅳ级与V级的区别仅是椎间隙的改变,而无关腰椎间盘信号的改变,两者间定量值可无差异；另一方面也可能是由于V级样本量较小而未能显示两者间的差别,同时正常人中V级比例较低可能说明椎间隙改变往往导致临床症状,这需要在患病人群中进一步统计分析。
由于临床实践上L4/5、L5/S1是最常发生腰椎间盘退变和膨突出的部位,因此T1ρ技术作为唯一可以检测出L4/5、L5/Sl与其它节段不同的方法对早期退变的敏感性应该高于其它方法；综合对Pfirrmann等级的诊断,我们认为T1ρ技术对早期退变的敏感性高于T2Mapping与DWI技术；而对于Ⅱ级以上的中晚期退变诊断的准确性则以T2Mapping技术最高。
研究表明性别对正常人腰椎间盘退变的影响很小。
年龄与腰椎间盘退变的关系：本研究所有检测指标均显示出与年龄相关,因此相对于性别、节段而言,年龄对腰椎间盘退变的作用要更显著。其中以Pfirrmann分级与年龄的相关性最强,而T1ρ值相关性最弱,通过趋势图可以发现,正常人T1ρ值在45岁前比较稳定,这同基础研究显示50岁后髓核的基质很难得到修复相一致,因此可以认为中青年时期腰椎间盘内最显著的变化应该是水含量的丢失。
通过比较定量检测三种技术时间变化曲线,本研究提出二个假说：(1)髓核的ADC值在腰椎间盘退变过程中处于一种波动性变化中,这是由于ADC值所反映的水分子运动与水含量和基质内PG的含量有关,基质内PG具有结合水的能力因此一方面提高髓核内水的含量,另一方面限制水分子的运动。在45岁之前由于PG保持相对稳定,髓核内水含量则处于缓慢减少节段,ADC值同步下降；45-50岁由于自身修复能力的降低,PG出现明显的丢失,对水分子运动限制能力明显减弱,水分子运动活跃,ADC值中运动增加的权重超过水含量丢失的权重,ADC值增加；随着PG进一步丢失,水含量明显降低,水含量丢失的权重超过运动能力增加的权重,ADC值又明显降低。目前研究中ADC值与退变的关系争议较多,本假说对于ADC值进一步研究提供了参考。(2)更为重要的是认为45-50岁是髓核内组织成分发生剧烈变化的时间点,为临床干预、延缓IVDD进展提供重要参考,对本假说进一步证明需要基础研究和更大样本研究的支持。
本研究采用X线导引下针刺椎间盘髓核的方式成功建立了兔的椎间盘退变模型,此模型具有操作简单、经济、并发症低、影响因素少等优势,并且证明了T2Mapping技术可用于兔椎间盘退变的检测,为采用动物模型研究磁共振定量技术对IVDD的诊断价值奠定了基础。
Part I The study of correlation between lumber intervertebral disc degeneration and Pfirrmann grading system
Objective:
(1) To investigate the distribution of disc Pfirrmann grades in healthy volunteers and lay a foundation for further quantitative analyses.(2) To investigate the correlaitons between the degeneration in the lumber spine and the gender, disc level, age and suggest how intervertebral disc degeneration (IVDD) might be affected by physiologic factors.
Materials and Methods:
Subjects:88healthy volunteers (gender:36males,52females; age range=20-76years, mean age=33.5±14.0years) were recruited following approval from Institution Review Broad. Inclusion criteria consisted of:(1) no history of manual labor for a long time;(2) no significant backache within the past6months;(3) no history of spine trauma and deformity.
MR:MR scanning was perfomed3.0T magnetic resonance imaging scanner with dual-source RF transmission(3.0T Achieva TX, Philips) and saggital T2-weighted images were acquired using a fast spin echo sequence with a spine coil for Pfirrmann grading in all patients. The parameters were TR=3000ms, TE=128ms, FOV=220mm(FH)×201mm(AP)×55mm(RL), slice thickness=5mm, matrix=448X448, flip angle=90°, All morphological evaluations were performed by two radiologists in consensus, both with more than10years of experience. All the degenerative discs on T2WI were classified according to the Pfirrmann grading system.
Statistical methods:Statistical analyses were conducted using SPSS15.0software. Disc levels, age and sex of the volunteers and Pfirrmann grades were recorded and used for statistic analyses. We used (1) Kruskal-Wallis test between Pfirrmann grades and disc levels;(2) Wilcoxon test to calculate significant difference between Pfirrmann grades and sex;(3) A one-way analysis of variance (ANOVA) was employed to compare between age and Pfirrmann grades and the Spearman correlation coefficient was determined. Levene test for equality of variances was used to test homogeneity of variances among groups and under an equal condition, the significance of differences were tested using ANOVA with LSD as a post hoc test, otherwise a Dnnett T3test was used. P≤0.05was considered as significance.
Results:
The T2-weighted image-based on Pfirrmann grade classification results were as the following:69disks in grade Ⅰ,232in grade Ⅱ,90in grade Ⅲ,37in grade Ⅳ and12in grade Ⅴ.
No statistically significant difference was observed between the grades (P=0.156)
The difference in Pfirrmann scores between male and female was not obvious and not statistically significant (P=0.361).
There was a significant positive correlation between age and degenerative grade (rs=0.668, P=0.001). The average age of each grade had statistically significant difference, but no difference between grade Ⅳ and grade Ⅴ.
Conclusion:
Pfirrmann grading system is the most common imaging classification method of IVDD but it provides only qualitative data that can be influenced by variable conditions.
Part Ⅱ The study of correlation between lumber intervertebral disc degeneration and T1ρ-weighted imaging
Objective:
(1) To determine whether Tip-weighted imaging is quantitative biomarkers of IVDD and provide new technology for objective evaluation of degenerative discs.(2) To analyze the relationships between Tip and Pfirrmann grades, intervertebral disc levels, gender and age.
Materials and Methods:
Subjects:83healthy volunteers (gender:34males,49females; age range=20-76years, mean age=33.9±14.3years) were recruited following approval from Institution Review Broad. Inclusion criteria consisted of:(1) no history of manual labor for a long time;(2) no significant backache within the past6months;(3) no history of spine trauma and spinal deformity. All volunteers were subdivided into three groups according to age,<35years,36-50years and>51years,
respectively.
MR:Scanners and sagittal T2-weighted images acquisition were the same as mentioned in Part Ⅰ. T1ρ scanning sequence used3D steady gradient echo sequence and parameters were:TR=4.85ms, TE=2.39ms, FOV=220mm(FH)×201mm(AP)×55mm(RL), slice thickness=5mm, matrix=448×448, Flip angle=50°, spin-lock frequency=500Hz, TSLs=0/10/20/30/40ms.
Image processing:All discs were graded according to Pfirrmann grading system. Tip values were calculated on a pixel-by-pixel basis to the exponentially decaying Tip fuction using IDL (Research Systems, Inc, USA) to generate Tip relaxation maps.The color-coded maps were fused with T2WI and ROIs were drawn. Three equally sized rectangular regions were manually subdivided on the middle slices and the center ones were chosen as the areas of interest.
Statistical methods:Statistical analyses were conducted using SPSS15.0software.(1) ANOVA was employed to compare Tip values of different Pfirrmann grades and the Spearman correlation coefficient was determined. Furthermore, in order to determine the T1ρ boundary values between the Pfirrmann classification grades in the nuleus pulposus, receiver operating characteristic (ROC) analyses were perfomed between each grade which were significantly different.(2) ANOVA was employed to compare Tip values of different dick levels.(3) The independent sample t test was used to compare Tip values of different gender at the same disc level.(4) ANOVA was employed to compare between T1ρand age groups and the Spearman correlation coefficient between T1ρ and age was determined. Levene test for equality of variances was used to test homogeneity of variances among groups and under an equal condition, the significance of differences were tested using ANOVA with LSD as a post hoc test, otherwise a Dnnett T3test was used.P<0.05was considered as significant.
Results:
The T2-weighted image-based on Pfirrmann grade classification results were as the following:50disks in grade Ⅰ,188in grade Ⅱ,75in grade Ⅲ,37in grade Ⅳ and8in grade Ⅴ.
Color-coded T1ρmap displayed normal nucleus pulposus could be divided into peripheral low values and core high values areas and fiber annulus showed lowest values. With the reduction of T2WI signal, nucleus pulposus values gradually were lower and values of fiber annulus increased.
Tip values were statistically significantly different when comparing between every grade, but not when comparing between grades Ⅲ and Ⅴ. T1ρ was significant negative correlation with Pfirrmann grade (rs=-0.538). ROC analyses illustrate the Tip cut-off value between grade Ⅰ and Ⅱ was116.5ms, which corresponded to a sensitivity, specificity, and area under the curve (AUC) of70%,53.2%and0.623respectively. The cut-off value, sensitivity, specificity, and AUC between grade Ⅱ and Ⅲ were103.5ms,67.6%,66.7%,0.720respectively, and those between grades Ⅲ and Ⅳ were86.5ms,60%,75.5%and0.717respectively.
T1ρ values were statistically significantly different when comparing between every level, but not when comparing between L4/5and L5/S1.
The difference in T1ρ values between male and female in the nuleus pulposus of every level was small and not statistically significant.
T1ρ values decreased significantly with increasing age and this correlation with age was moderate negatice (rs=-0.335). The T1ρ values remained relatively stable during20-45years and rapidly and continuously reduced after45years.
Conclusion:
Tip reflects changes in IVD composition, with comparably high spatial resolution. T1ρ imaging technique is more sensitive to molecular modification than T2WI and can be potentially used as a clinical tool to detect early IVDD and longitudinal followup. The method can create a reliable quantitative scale, as the result, the accuracy and repeatability of measurements are better than Pfirrmann grading system.
ParⅢ The study of correlationship between lumber intervertebral disc degeneration with T2Mapping imaging
Objective:
(1) To determine the associations between T2and Pfirrmann grades, intervertebral disc levels, gender and age.(2) To assess, compare and correlate T1ρ and T2relaxation time.
Materials and Methods:
Subject:86healthy volunteers (gender:34males,52females; age range=20-76years, mean age=33.5±14.1years) were recruited following approval from Institution Review Broad. Inclusion criteria consisted of:(1) no history of manual labor for a long time;(2) no significant backache within the past6months;(3) no history of spine trauma and spinal deformity. All volunteers were subdivided into three groups according to age,≤35years,36-50years and≥51years respectively. Volunteers were investigated in the afternoon (5-10PM) and did not exercise strenuously and laid down about half an hour before scan.
MR:Scanners and sagittal T2-weighted images acquisition were the same as the mentioned in Part I and T2Mapping parameters were:TR=1162ms, TE=n×20ms, FOV=220mm(FH)×201mm(AP)×25mm(RL), slice thickness=5mm, matrix=448×448, Flip angle=90°. To reduce the artifacts caused by respiratory and gastrointestinal moving, the saturation band was set in front of the vertebral bodies and automatic shimming and fat suppression techniques were applied.
Image processing:All discs were scored according to Pfirrmann grading system. T2values were calculated on a pixel-by-pixel basis to generate T2relaxation map. The color-coded maps were fused with T2WI and ROIs were drawn.
Statistical methods:Statistical analyses were conducted using SPSS15.0software.(1) ANOVA was employed to compare T2values of different Pfirrmann grades and the Spearman correlation coefficient was determined. Furthermore, in order to determine the T2boundary values between the Pfirrmann classification grades in the nuleus pulposus, ROC analyses was perfomed between each grade which were significantly different.(2) ANOVA was employed to compare T2values of different disc levels.(3) The independent sample t test was used to compare T2values of different gender at the same disc level.(4) ANOVA was employed to compare between T2values and age groups and the Spearman correlation coefficient between T2and age was determined.(5) The Pearson correlation coefficient was determined between T1ρ and T2values. Levene test for equality of variances was used to test homogeneity of variances among groups and under an equal condition, the significance of differences were tested using ANOVA with LSD as a post hoc test, otherwise a Dnnett T3test was used.P≤0.05was considered as significant.
Results:
The T2-weighted image-based on Pfirrmann grade classification results were as the following:66disks in grade Ⅰ,225in grade Ⅱ,81in grade Ⅲ,37in grade Ⅳ and11in grade Ⅴ.
Color-coded maps displayed normal nucleus pulposus could be divided into peripheral low values and core high values area and the fiber annulus were lowest. Comparing with the T1ρ, the high values were lower and the values of nucleus pulposus and fiber annulus were more uniform. With the reduction of T2WI signal, the values of pulposus gradually were lower and fiber annulus changes were less significance than T1ρ.
T2values were significantly different when comparing between every grade, but not when comparing grade Ⅰ with Ⅱ and grade Ⅳ with Ⅴ. T2values was significant negative correlation with Pfirrmann grades (rs=-0.665). ROC analyses illustrated the T2cut-off value between grade Ⅱ and Ⅲ was94.5ms, which corresponded to a sensitivity, specificity, and AUC of84.9%,71.6%and0.865respectively. The cut-off value, sensitivity, specificity, and AUC between grade Ⅲ and Ⅳ were67.5ms,75.3%,91.9%and0.906respectively.
T2values were not significantly different when comparing between every level.
Overall in all intervertebral disc level, T2values of male were higher than female's, even there was significant difference between L1/2and L2/3.
T2values decreased significantly with increasing age and this correlation with age was moderate negative (rs=-0.492). T2values during20-45years decreased slowly and increased slightly during45-50years, then the values fell rapidly again and stayed low stage after55years.
T2values was moderate positive correlation with T1ρ value(r=0.445).
Conclusion:
The method of T2Mapping seems to be able to characterize different degrees of disc degeneration quantitatively and become a promising method for longitudinal followup. T2Mapping can monitor the changes in tissue composition and is less sensitive for early IVDD than T1ρ, on the other hand, T2Mapping demonstrate higher degree of accuracy for late stage. The moderate positive correlation between Tip and T2can suggest the decrease of PG content in nucleus pulposus lead to the water loss.
PartIV The study of correlationship between intervertebral disc degeneration with diffusion weighted imaging
Objective:
(1) To determine the associations between ADC values and Pfirrmann grades, intervertebral discs levels, gender and age.(2) To assess, compare and correlate quantitative Tip, T2relaxation time and ADC values and finish the comprehensive analyses for the three quantitative methods.
Materials and Methods:
Subjects:42healthy volunteers (gender:16males,26females; age range=22-63years, mean age=38.2±12years) were recruited following approval from Institution Review Broad. Inclusion criteria consisted of:(1) no history of manual labor for a long time;(2) no significant backache within the past6months;(3) no history of spine trauma and spinal deformity. All volunteers were subdivided into three groups according to age,≤35years,36～50years,≥51years respectively. Volunteers were investigated in the afternoon (5～10PM) and did not exercise strenuously and laid down about half an hour before scan.
MR:MR instrument, Tip and T2Mapping scan parameters were the same as the mentioned in Part1-3. DWI parameters were:TR=3000ms, TE=64ms, FOV=180mm(FH)×56mm(AP)×65mm(RL), slice thickness=5mm, matrix=288×288, flip angle=90°, b values=Osec/mm2and500sec/mm2. Fov and acquisition matrix of T2WI were the same as the ones of T1ρ and DWI, respectively.
Image processing:All discs were scored according to Pfirrmann grading system. ADC values were calculated on a pixel-by-pixel basis using the scanner software. The color-coded ADC maps by using ImageJ software. At last the color-coded maps were fused with convention T2WI and ROIs were drawn.
Statistical methods:Statistical analyses were conducted using SPSS15.0software.(1) ANOVA was employed to compare ADC values of different Pfirrmann grades and the Spearman correlation coefficient was determined. Furthermore, in order to determine the ADC boundary values between the Pfirrmann classification grades in the nuleus pulposus, ROC analyses were perfomed between each grade which were significantly different.(2) ANOVA was employed to compare ADC values of different dick levels.(3) The independent sample t test was used to compare ADC values from different gender of the same level.(4) ANOVA was employed to compare ADC values and age groups and the Spearman correlation coefficient between ADC and age was determined.(5) The Pearson correlation coefficients were determined between ADC with T2and T1ρ respectively. Levene test for equality of variances was used to test homogeneity of variances among groups and under an equal condition, the significance of differences were tested using ANOVA with LSD as a post hoc test, otherwise a Dnnett T3test was used.P≤0.05was considered as significant.
Results:
The T2-weighted image-based on Pfirrmann grade classification results were as the following:19disks in grade Ⅰ,106in grade Ⅱ,44in grade Ⅲ,29in grade Ⅳ and9in grade Ⅴ.
Color-coded maps displayed normal nucleus pulposus could be divided into core low values and peripheral high values areas and fiber annulus were black which indicated extremely low values, as the result, the difference between nucleus pulposus and fiber annulus was more significant than other two kinds of color-coded maps. Comparing with the Tip and T2Mapping, the distribution of high values were different that laid on the peripheral area.
ADC values were no significantly different when comparing between grade Ⅰ and Ⅱ, grade Ⅲ and Ⅳ. ADC was significant negative correlation with Pfirrmann grade (rs=-0.530). ROC analyses between each grade illustrated the ADC cut-off value between grade Ⅱ and Ⅲ was1.732×10-3mm2/s, which corresponded to a sensitivity, specificity, and AUC of50%,81.8%and0.673respectively. The cut-off value, sensitivity, specificity, and AUC between grade Ⅲ and Ⅳ were1.582×10-3mm2/s,64.1%,89.7%and0.813respectively.
ADC values were statistically significantly different when L1/2comparing with L2/3and L3/4(P=0.014, P=0.050).
No statistically significant difference was found between men and women in each disc level.
ADC values decreased significantly with increasing age and this correlation with age was moderate negative (rs=-0.422). ADC values during20-45years decreased slowly and increased dramatically during45-50years, then the values fell rapidly again after50years.
ADC values were significant positive correlation with T1ρ and T2values.
Conclusion:
The method of DWI seems to be also able to characterize different degrees of disc degeneration quantitatively and ADC values are significant positive correlation with T1ρ and T2, which can reflect the changes in tissue composition. T1ρ, T2and DWI are the promising methods for detecting early early and longitudinal followup ofIVDD.
Part V A novel rabbit model of disc degeneration by needle puncture under X-ray guidance
Objective:
To establish a reproducible rabbit model of disc degeneration by needle puncture using X-ray guidance, then determine whether MR quantitative technology can evaluate the disc degeneration of rabbits.
Materials and methods:
Five SP healthy New Zealand white rabbits were used in this study under the Insitutional Animal Care Use Committee approval. Nucleus pulposus and cartilage endplates were destructed respectively through anular puncture under X-ray guidance. The IVDD was evaluated using MR T2WI, T1ρ and T2Mapping techniques at the time points of pre-puncture, after30minutes,4weeks and8weeks. Pathological changes of the intervertebral discs were analyzed after8weeks.
Results:
T2WI and CT:After30minutes, MR and CT failed to find changes of intervertebral disc. On the contrary, after4and8weeks, signal intensity of the punctured discs decreased. Other disc levels intensity had not different with control group.
Tip technology did not provide enough spatial resolution to detect the values changes of nucleus pulpous. T2Mapping showed values of nucleus pulposus were significant low after4and8weeks in the nuclers pulposus of punctured discs and the values of other discs remains no change.
Conclusion:
Nucleus pulposus destructed approach by needle puncture using X-ray guidance can result in a convenient, less-invasive, reproducible and cost-effective rabbit model of disc degeneration and be a useful choice for studying disc degeneration. T2Mapping can quantantatively evaluate the rabbit IVDD, on the contray, T1ρ technique is unable to detect the degeration in our experiment and more research investigation is required.
Summary
The relationship between Pfirrmann grades and three quantitative techniques: According to correlation coefficients, T2values had the strongest correlation with Pfirrmann grading, which can be resulted from Pfirrmann grading system based on disc signals of T2WI is closely correlated with water content in the nucleus pulposus. T2Mapping and DWI failed to discover the differences of grades I and II and it suggests the both techniques are less sensitive for early degeneration than T1ρ.
Three kinds of quantitative values were not significantly different between grades IV and V. Two reasons can lead to the result:First, according to Pfirrmann grading system, the difference between grades Ⅳ and Ⅴ is only the space of the intervertebral disc, regardless of the signal changes. Second, it also may be due to the small sample size of grade V. Furthmore, the narrow space of intervertebral disc may be closely correlated with clinical symptoms since the low incidence of grede V in healthy adult populations.
The relationship between disc levels and three quantitative techniques:Only T1ρ technology could identify the difference of L4/5and L5/S1from other levels with lower incidience of disc heniation.
So we consider T1ρ is more sensitive for early degeneration and T2Mapping demonstrate higher degree of accuracy for late stage.
Gender has little impact on the normal human intervertebral disc degeneration.
The relationship between age and three quantitative techniques:All three methods showed moderate or significant age-associated changes but Tip values showed the weakest correlation and remained stable younger than45years old, which was consistant with fundamental research that nucleus pulposus matrix was hard to be repaired older than50years. So we think the most significant change in nucleus pulposus should be the loss of water content young and middle-aged populations. Hypothesis:Comparing three value curves of age-associated changes, ADC values fluctuated during45-50years old. We suggest ADC values are closely correlated with water and PG cotent. One one hand, PG attracted the water; on the other hand, PG restricts Brown motion of water molecules. Before45years old, PG remains stable and water gradually loses, which lead to ADC values decrease. During45-50years old, PG content diminishes dramatically and can not restrict the motion of water, as the result, ADC values increase although water content lose continually. After50years old, the loss of water dominates and ADC values decrease again. So studying the correlation between DWI and IVDD, more factors need to be considered. We think it is more important to note the tissue composition changes dramatically at the45-50years old stage and the finding can provide the evidence to support clinical intervention for delaying IVDD.
We can induce a convenient, less-invasive, reproducible and cost-effective rabbit model of disc degeneration and T2Mapping is a promising method for investigating IVDD of rabbit model.
引文
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[1]Watanabe A, Benneker LM, Boesch C et al. Classification of intervertebral disk degeneration with axial T2 mapping [J]. AJR,2007,189(4):936-942.
[2]Stelzeneder D, Welsch GH, Kovacs BK, et al. Quantitative T2 evaluation at 3.0T compared to morphological grading of the lumbar intervertebral disc:a standardized evaluation approach in patients with low back pain [J]. Eur J Radiol,2012,81(2):324-330.
[3]Jazini E, Sharan AD, Morse LJ, et al. Alterations in T2 relaxation magnetic resonance imaging of the ovine intervertebral disc due to nonenzymatic glycation [J]. Spine,2012,37(4):E209-215.
[4]Wang C, Auerbach JD, Witschey WR, et al. Advances in magnetic resonance imaging for the assessment of degenerative disc disease of the lumbar spine [J]. Semin Spine Surg,2007,19(2):65-71.
[5]Marinelli NL, Haughton VM, Anderson PA, et al. T2 relaxation times correlated with stage of lumbar intervertebral disk degeneration and patient age [J]. Am J Neuroradiology,2010,31(7):1278-1282.
[6]Karakida O, Ueda H, Ueda M, et al. Diurnal T2 value changes in the lumba intervertebral Discs [J]. Clin Radiol,2003,58(5):389-392.
[7]Stelzeneder D, Kovacs BK, Goed S, et al. Effect of short-term unloading on T2 relaxation time in the lumbar tervertebral disc—in vivo magnetic resonance imaging study at 3.0 tesla [J]. Spine,2012,12(3):257-264.
[8]Hoppe S, Quirbach S, Mamisch TC, et al. Axial T2* mapping in intervertebral discs:a new technique for assessment of intervertebral disc degeneration [J]. Eur Radiol,2012,22(9):2013-2019.
[9]Welsch GH, Trattnig S, Paternostro-Sluga T, et al. Parametric T2 and T2* mapping techniques to visualize intervertebral disc degeneration in patients with low back pain:initial results on the clinical use of 3.0 Tesla MRI [J]. Skeletal Radiology,2011,40(5):543-551.
[10]Watanabe A, Benneker LM, Boesch C, et al. Classification of intervertebral disk degeneration with axial T2 mapping [J]. Am J Roentgenol,2007, 189(4):936-942.
[11]Perry J, Haughton V, Anderson PA, et al. The value of T2 relaxation times to characterize lumbar intervertebral disks:preliminary results [J]. Am J Neuroradiol,2006,27(2):337-342.
[12]Takashima H, Takebayashi T, Yoshimoto M, et al. Correlation between T2 relaxation time and intervertebral disk degeneration [J]. Skeletal Radiol,2012, 41(2):163-167.
[1]Niinimaki J, Korkiakoski A, Ojala O, et al, Association between visual degeneration of intervertebral discs and the apparent diffusion coefficient [J]. Magn Reson Imaging.2009,27(5):641-647.
[2]Chiu E J,Newitt DC, Segal MR,et al.Magnetic resonance imaging measurement of relaxation and water diffusion in the human lumbar intervertebral disc under compression in vitro [J]. Spine,2001, 26(19):437-444.
[3]俎金燕.椎间盘退变的磁共振成像研究[D].上海：第二军医大学,2011.
[4]Antoniou J, Demers CN, Beaudoin G, et al. Apparent diffusion coefficient of intervertebral discs related to matrix composition and integrity [J]. Magn Reson Imaging,2004,22(7):963-972
[5]Kealey SM, Aho RT, Delong D, et al. Assessment of Apparent Diffusion Coefficient in Normal and Degenerated Intervertebral Lumbar Disks:Initial Experience [J]. Neuroradiology,2005,235(2):569-574.
[6]张娅,陈建宇,蒋新华,等.MRI表观弥散系数与腰椎间盘退变分级的相关性[J].中国医学影像技术,2011,27(6)：1264-1267.
[7]李跃华,孙万驹,赵振国,等.L1-4椎间盘ADC值、腰动脉血供与椎间盘退变程度的相关性分析[J].第二军医大学学报,2010,31(2)：169-172.
[8]邓绍强.弥散加权ADC值定量评价退变椎间盘蛋白多糖和胶原蛋白含量 的实验研究[D].南充：川北医学院,2009.
[9]方元.MRS、T2Map、DWI多种方法对腰椎间盘退变评价的相关性研究[D].石家庄：河北医科大学,2009.
[10]陈雄.探讨表观弥散系数评价腰椎间盘病变的应用价值[D].青岛：青岛大学,2011.
[11]王娟,周义成,夏黎明,等.使用ADC值评估正常及退变椎间盘的初步研究[J].医学影像学杂志,2006,16(10)：1093-1096.
[12]李颖,常英娟,魏光全,等.青年健康志愿者腰椎间盘水扩散：活体、无创测量[J].实用放射学杂志,2006,22(11)：1369-1371.
[13]董辉.正常及退变腰椎间盘DTI及ADC值联合应用对比评价[D].郑州：郑州大学,2010.
[14]陈耀康.正常成人腰椎间盘ADC值的初步测定[D].南充：川北医学院,2011.
[1]Zhou H, Hou S, Shang W, et al. A new in vivo animal model to create intervertebral disc degeneration characterized by MRI, radiography, CT/discogram, biochemistry, and histology [J]. Spine,2007,32(8):864-872.
[2]Hsieh AH, Hwang D, Ryan DA, et al. Degenerative anular changes induced by puncture are associated with insufficiency of disc biomechanical function [J]. Spine,2009,34(10):998-1005.
[3]王鹏,徐海孺,骆国钢,等.经皮穿刺纤维环法诱导兔腰椎间盘退变模型[J].浙江中西医结合杂志,2009,19(11)：668-670.
[4]Elliott DM, Yerramalli CS, Beckstein JC, et al. The effect of relative needle diameter in puncture and sham injection animal models of degeneration [J]. Spine,2008,33(6):588-596.
[5]Korecki CL, Costi JJ, Iatridis JC, et al. Needle puncture injury affects intervertebral disc mechanics and biology in an organ culture model [J]. Spine, 2008,33(3):235-241.
[6]Keorochana G, Johnson JS, Taghavi CE, et al. The effect of needle size inducing degeneration in the rat caudal disc:evaluation using radiograph, magnetic resonance imaging, histology, and immunohistochemistry [J]. Spine, 2010,10(11):1014-1023.
[7]Michalek AJ, Funabashi KL, Iatridis JC, et al. Needle puncture injury of the rat intervertebral disc affects torsional and compressive biomechanics differently [J]. Eur Spine J,2010,19(12):2110-2116.
[8]Masuda K, Aota Y, Muehleman C, et al. A novel rabbit model of mild, reproducible disc degeneration by an anulus needle puncture:correlation between the degree of disc injury and radiological and histological appearances of disc degeneration [J]. Spine,2005,30(1):5-14.
[9]Sobajima S, Kompel JF, Kim JS, et al. A slowly progressive and reproducible animal model of intervertebral disc degeneration characterized by MRI, X-Ray, and histology [J]. Spine,2005,30(1):15-24.
[10]Kong MH, Do DH, Miyazaki M, et al. Rabbit model for in vivo study of intervertebral disc degeneration and regeneration [J]. J Korean Neurosurg Soc, 2008,44(5):327-333.
[1]Stewart WF, Ricci JA, Chee E, et al. Lost productive time and cost due to common pain conditions in the US workforce [J]. JAMA,2003, 290(18):2443-2454.
[2]Kallewaard JW, Terheggen MA, Groen GJ, et al. Discogenic low back pain [J]. Pain Pract,2010,10(6):560-579.
[3]Zuo J, Joseph GB, Li X, et al. In vivo intervertebral disc characterization using magnetic resonance spectroscopy and Tip imaging [J]. Spine,2012, 37(3):214-221.
[4]Witschey WR, Borthakur A, Elliott MA,et al. Tlrho-prepared balanced gradient echo for rapid 3D Tlrho MRI [J]. J Magn Reson Imaging,2008, 28(3):744-54.
[5]周智洋,单鸿,李占军等.家猪体外胰蛋白酶消化关节软骨：7.0T MR T1p加权成像与量化分析[J].中国组织工程研究与临床康复,2009,13(37)：7221-7225.
[6]康立丽,路世龙,胡志等.MR图像T2定量分析的单指数、多指数方法分析与探讨[J].实用放射学杂志,2012,28(5)：763-766.
[7]Blumenkrantz G, Li X, Han ET, et al. A feasibility study of in vivo T1ρ imaging of the intervertebral disc [J]. Magn Reson Imaging,2006, 24(8):1001-1017.
[8]Johannessen W, Auerbach JD, Wheaton AJ, et al. Assessment of human disc degeneration and proteoglycan content using Tip-weighted magnetic resonance imaging [J]. Spine,2006,31(11):1253-1257.
[9]Nguyen AM, Johannessen W, Yoder JH, et al. In vivo intervertebral disc characterization using magnetic resonance spectroscopy and T1ρimaging [J]. J Bone Joint Surg Am,2008,90(4):796-802.
[10]Wang C, Witschey W, Elliott MA, et al. Measurement of intervertebral disc pressure with T1ρMRI [J]. Magn Reson Med,2010,64(6):1721-1727.
[11]Borthakur A, Maurer PM, Fenty M, et al. T1ρ magnetic resonance imaging and discography pressure as novel biomarkers for disc degeneration and low back pain [J]. Spine,2011,36(25):2190-2196.
[12]Johannessen W, Elliott DM. Effects of degeneration on the biphasic material properties of human nucleus pulposus in confined compression [J]. Spine, 2005,30(24):E724-729.
[13]Blumenkrantz G, Zuo J, Li X, et al. In vivo 3.0-Tesla magnetic resonance T1ρ and T2 relaxation mapping in subjects with intervertebral disc degeneration and clinical symptoms [J]. Magn Reson Med,2010,63(5):1193-1200.
[14]Auerbach JD, Johannessen W, Borthakur A, et al. In vivo quantification of human lumbar disc degeneration using T1ρ-weighted magnetic resonance imaging [J]. Eur Spine J,2006,15 (Suppl 3):S338-344.
[15]Zobel BB, Vadala G, Del Vescovo R, et al. T1ρ magnetic resonance imaging quantification of early lumbar intervertebral disc degeneration in healthy young adults [J]. Spine,2012,37(14):1224-1230.
[16]Wang C, Auerbach JD, Witschey WR, et al. Advances in magnetic resonance imaging for the assessment of degenerative disc disease of the lumbar spine [J]. Semin Spine Surg,2007,19(2):65-71.
[17]Marinelli NL, Haughton VM, Anderson PA, et al. T2 relaxation times correlated with stage of lumbar intervertebral disk degeneration and patient age [J]. Am J Neuroradiology,2010,31(7):1278-1282.
[18]Watanabe A, Benneker LM, Boesch C et al. Classification of intervertebral disk degeneration with axial T2 mapping [J]. AJR,2007,189(4):936-942.
[19]Perry J, Haughton V, Anderson PA, et al. The value of T2 relaxation times to characterize lumbar intervertebral disks:preliminary results [J]. Am J Neuroradiol,2006,27(2):337-342.
[20]Takashima H, Takebayashi T, Yoshimoto M, et al. Correlation between T2 relaxation time and intervertebral disk degeneration [J]. Skeletal Radiol,2012, 41(2):163-167.
[21]Jazini E, Sharan AD, Morse LJ, et al. Alterations in T2 relaxation magnetic resonance imaging of the ovine intervertebral disc due to nonenzymatic glycation [J]. Spine.2012 37(4):E209-215.
[22]Stelzeneder D, Welsch GH, Kovacs BK, et al. Quantitative T2 evaluation at 3.0T compared to morphological grading of the lumbar intervertebral disc:a standardized evaluation approach in patients with low back pain [J]. Eur J Radiol,2012,81(2):324-330.
[23]Karakida O, Ueda H, Ueda M, et al. Diurnal T2 value changes in the lumba intervertebral Discs [J]. Clin Radiol,2003,58(5):389-392.
[24]Stelzeneder D, Kovacs BK, Goed S, et al. Effect of short-term unloading on T2 relaxation time in the lumbar tervertebral disc—in vivo magnetic resonance imaging study at 3.0 tesla [J]. Spine,2012,12(3):257-264.
[25]Hoppe S, Quirbach S, Mamisch TC, et al. Axial T2* mapping in intervertebral discs:a new technique for assessment of intervertebral disc degeneration [J]. Eur Radiol,2012,22(9):2013-2019.
[26]Welsch GH, Trattnig S, Paternostro-Sluga T, et al. Parametric T2 and T2* mapping techniques to visualize intervertebral disc degeneration in patients with low back pain:initial results on the clinical use of 3.0 Tesla MRI [J]. MRI, 2011,40(5):543-551.
[27]Watanabe A, Benneker LM, Boesch C, et al. Classification of intervertebral disk degeneration with axial T2 mapping [J]. Am J Roentgenol,2007, 189(4):936-942.
[28]Wang YX, Zhao F, Griffith JF, et al. Tlrho and T2 relaxation times for lumbar disc degeneration:an in vivo comparative study at 3.0-Tesla MRI [J]. Eur Radiol,2012,23(1):228-234.
[1]Rinkler C, Heuer F, Pedro MT, et al. Influence of low glucose supply on the regulation of gene expression by nucleus pulposus cells and their responsiveness to mechanical loading [J]. J Neurosurg Spine,2010, 13(4):535-542.
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[6]Zhou H, Hou S, Shang W, et al. A new in vivo animal model to create intervertebral disc degeneration characterized by MRI, radiography, CT/discogram, biochemistry, and histology [J]. Spine,2007,32(8):864-872.
[7]Hsieh AH, Hwang D, Ryan DA, et al. Degenerative anular changes induced by puncture are associated with insufficiency of disc biomechanical function [J]. Spine,2009,34(10):998-1005.
[8]Elliott DM, Yerramalli CS, Beckstein JC, et al. The effect of relative needle diameter in puncture and sham injection animal models of degeneration [J]. Spine,2008,33(6):588-596.
[9]Korecki CL, Costi JJ, Iatridis JC, et al. Needle puncture injury affects intervertebral disc mechanics and biology in an organ culture model [J]. Spine, 2008,3(3):235-241.
[10]Keorochana G, Johnson JS, Taghavi CE, et al. The effect of needle size inducing degeneration in the rat caudal disc:evaluation using radiograph, magnetic resonance imaging, histology, and immunohistochemistry [J]. Spine, 2010,10(11):1014-1023.
[11]Michalek AJ, Funabashi KL, Iatridis JC, et al. Needle puncture injury of the rat intervertebral disc affects torsional and compressive biomechanics differently [J]. Eur Spine J,2010,19(12):2110-2116.
[12]Aoki Y, Akeda K, An H, et al. Nerve fiber ingrowth into scar tissue formed following nucleus pulposus extrusion in the rabbit anular-puncture disc degeneration model:effects of depth of puncture [J]. Spine,2006,31(21): 774-780.
[13]Kim KS, Yoon ST, Li J, et al. Disc degeneration in the rabbit:a biochemical and radiological comparison between four disc injury models [J]. Spine,2005, 30(1):33-37.
[14]Masuda K, Aota Y, Muehleman C, et al. A novel rabbit model of mild, reproducible disc degeneration by an anulus needle puncture:correlation between the degree of disc injury and radiological and histological appearances of disc degeneration [J]. Spine,2005,30(1):5-14.
[15]Sobajima S, Kompel JF, Kim JS, et al. A slowly progressive and reproducible animal model of intervertebral disc degeneration characterized by MRI, X-Ray, and histology [J]. Spine,2005,30(1):15-24.
[16]Kong MH, Do DH, Miyazaki M, et al. Rabbit model for in vivo study of intervertebral disc degeneration and regeneration [J]. J Korean Neurosurg Soc, 2008,44(5):327-333.
[17]Michalek AJ, Buckley MR, Bonassar LJ, et al. The effects of needle puncture injury on microscale shear strain in the intervertebral disc annulus fibrosus [J]. Spine J,2010,10(12):1098-1105.
[18]Wang JL, Tsai YC, Wang YH, et al. The leakage pathway and effect of needle gauge on degree of disc injury post anular puncture [J]. Spine,2007,32(17): 1809-1815.
[19]Yang F, Leung VY, Luk KD, et al. Injury-induced sequential transformation of notochordal nucleus pulposus to chondrogenic and fibrocartilaginous phenotype in the mouse [J]. J Pathol,2009,218(1):113-121.
[20]Sobajima S, Shimer AL, Chadderdon RC, et al. Quantitative analysis of gene expression in a rabbit model of intervertebral disc degeneration by real-time polymerase chain reaction [J]. Spine J,2005,5(1):14-23.
[2]Peterson CK, Bolton JE, Wood AR, et al. A cross-sectional study correlating lumbar spine degeneration with disability and pain [J]. Spine,2000, 25(2):218-223.
[3]Pfirrmann CW, Metzdorf A, Zanetti M, et al. Magnetic resonance classification of lumbar intervertebral disc degeneration [J]. Spine,2001, 26(17):1873-1878.
[4]Zuo J, Joseph GB, Li X, et al. In vivo intervertebral disc characterization using magnetic resonance spectroscopy and T1ρ imaging [J]. Spine,2012, 37(3):214-221.
[5]Griffith JF, Wang YX, Antonio GE, et al. Modified Pfirrmann Grading System for Lumbar Intervertebral Disc Degeneration [J]. Spine,2007,32(24):708-712.
[6]Kawaguchi Y, Kanamori M, Ishihara H, et al. The association of lumbar disc disease with vitamin-D receptor gene polymorphism [J]. J Bone Joint Surg Am,2002,84(11):2022-2028.
[7]Siemionow K, An H, Masuda K, et al. The effects of age, sex, ethnicity, and spinal level on the rate of intervertebral disc degeneration [J]. Spine,2011, 36(17):1333-1339.
[8]Adams MA, Roughley PJ. What is intervertebral disc degeneration, and what causes it [J]. Spine,2006,31(18):2151-2161.
[9]吴剑宏,阮狄克.腰椎间盘退变的MRI诊断分级及其临床应用进展[J].中国脊柱脊髓杂志,2010,20(6)：511-515.
[10]俎金燕.椎间盘退变的磁共振成像研究[D].上海：第二军医大学,2011.
[1]周智洋,单鸿,李占军等.家猪体外胰蛋白酶消化关节软骨：7.0TMR T1ρ加权成像与量化分析[J].中国组织工程研究与临床康复,2009,13(37)：7221-7225.
[2]Witschey WR, Borthakur A, Elliott MA,et al. Tlrho-prepared balanced gradient echo for rapid 3D Tlrho MRI [J]. J Magn Reson Imaging,2008, 28(3):744-54.
[3]Johannessen W, Auerbach JD, Wheaton AJ, et al. Assessment of human disc degeneration and proteoglycan content using Tip-weighted magnetic resonance imaging [J]. Spine,2006,31(11):1253-1257.
[4]Zuo J, Joseph GB, Li X, et al. In vivo intervertebral disc characterization using magnetic resonance spectroscopy and T1ρ imaging [J]. Spine,2012, 37(3):214-221.
[5]Wang C, Witschey W, Elliott MA, et al. Measurement of intervertebral disc pressure with T1ρ MRI[J]. Magn Reson Med,2010,64(6):1721-1727.
[6]Borthakur A, Maurer PM, Fenty M, et al. Tip magnetic resonance imaging and discography pressure as novel biomarkers for disc degeneration and low back pain [J]. Spine,2011,36(25):2190-2196.
[7]Nguyen AM, Johannessen W, Yoder JH, et al. In vivo intervertebral disc characterization using magnetic resonance spectroscopy and Tip imaging [J]. J Bone Joint Surg Am,2008,90(4):796-802.
[8]Blumenkrantz G, Zuo J, Li X et al. In vivo 3.0-Tesla magnetic resonance T1ρ and T2 relaxation mapping in subjects with intervertebral disc degeneration and clinical symptoms [J]. Magn Reson Med,2010,63(5):1193-1200.
[9]Auerbach JD, Johannessen W, Borthakur A, et al. In vivo quantification of human lumbar disc degeneration using Tip-weighted magnetic resonance imaging [J]. Eur Spine J,2006,15 (Suppl 3):S338-344.
[10]Zobel BB, Vadala G, Del Vescovo R, et al. Tip magnetic resonance imaging quantification of early lumbar intervertebral disc degeneration in healthy young adults [J]. Spine,2012,37(14):1224-1230.
[11]Siemionow K, An H, Masuda K, et al. The effects of age, sex, ethnicity, and spinal level on the rate of intervertebral disc degeneration [J]. Spine,2011, 36(17):1333-1339.
[12]Blumenkrantz G, Li X, Han ET, et al. A feasibility study of in vivo Tip imaging of the intervertebral disc [J]. Magn Reson Imaging,2006,24(8):1001-1017.
[1]Watanabe A, Benneker LM, Boesch C et al. Classification of intervertebral disk degeneration with axial T2 mapping [J]. AJR,2007,189(4):936-942.
[2]Stelzeneder D, Welsch GH, Kovacs BK, et al. Quantitative T2 evaluation at 3.0T compared to morphological grading of the lumbar intervertebral disc:a standardized evaluation approach in patients with low back pain [J]. Eur J Radiol,2012,81(2):324-330.
[3]Jazini E, Sharan AD, Morse LJ, et al. Alterations in T2 relaxation magnetic resonance imaging of the ovine intervertebral disc due to nonenzymatic glycation [J]. Spine,2012,37(4):E209-215.
[4]Wang C, Auerbach JD, Witschey WR, et al. Advances in magnetic resonance imaging for the assessment of degenerative disc disease of the lumbar spine [J]. Semin Spine Surg,2007,19(2):65-71.
[5]Marinelli NL, Haughton VM, Anderson PA, et al. T2 relaxation times correlated with stage of lumbar intervertebral disk degeneration and patient age [J]. Am J Neuroradiology,2010,31(7):1278-1282.
[6]Karakida O, Ueda H, Ueda M, et al. Diurnal T2 value changes in the lumba intervertebral Discs [J]. Clin Radiol,2003,58(5):389-392.
[7]Stelzeneder D, Kovacs BK, Goed S, et al. Effect of short-term unloading on T2 relaxation time in the lumbar tervertebral disc—in vivo magnetic resonance imaging study at 3.0 tesla [J]. Spine,2012,12(3):257-264.
[8]Hoppe S, Quirbach S, Mamisch TC, et al. Axial T2* mapping in intervertebral discs:a new technique for assessment of intervertebral disc degeneration [J]. Eur Radiol,2012,22(9):2013-2019.
[9]Welsch GH, Trattnig S, Paternostro-Sluga T, et al. Parametric T2 and T2* mapping techniques to visualize intervertebral disc degeneration in patients with low back pain:initial results on the clinical use of 3.0 Tesla MRI [J]. Skeletal Radiology,2011,40(5):543-551.
[10]Watanabe A, Benneker LM, Boesch C, et al. Classification of intervertebral disk degeneration with axial T2 mapping [J]. Am J Roentgenol,2007, 189(4):936-942.
[11]Perry J, Haughton V, Anderson PA, et al. The value of T2 relaxation times to characterize lumbar intervertebral disks:preliminary results [J]. Am J Neuroradiol,2006,27(2):337-342.
[12]Takashima H, Takebayashi T, Yoshimoto M, et al. Correlation between T2 relaxation time and intervertebral disk degeneration [J]. Skeletal Radiol,2012, 41(2):163-167.
[1]Niinimaki J, Korkiakoski A, Ojala O, et al, Association between visual degeneration of intervertebral discs and the apparent diffusion coefficient [J]. Magn Reson Imaging.2009,27(5):641-647.
[2]Chiu E J,Newitt DC, Segal MR,et al.Magnetic resonance imaging measurement of relaxation and water diffusion in the human lumbar intervertebral disc under compression in vitro [J]. Spine,2001, 26(19):437-444.
[3]俎金燕.椎间盘退变的磁共振成像研究[D].上海：第二军医大学,2011.
[4]Antoniou J, Demers CN, Beaudoin G, et al. Apparent diffusion coefficient of intervertebral discs related to matrix composition and integrity [J]. Magn Reson Imaging,2004,22(7):963-972
[5]Kealey SM, Aho RT, Delong D, et al. Assessment of Apparent Diffusion Coefficient in Normal and Degenerated Intervertebral Lumbar Disks:Initial Experience [J]. Neuroradiology,2005,235(2):569-574.
[6]张娅,陈建宇,蒋新华,等.MRI表观弥散系数与腰椎间盘退变分级的相关性[J].中国医学影像技术,2011,27(6)：1264-1267.
[7]李跃华,孙万驹,赵振国,等.L1-4椎间盘ADC值、腰动脉血供与椎间盘退变程度的相关性分析[J].第二军医大学学报,2010,31(2)：169-172.
[8]邓绍强.弥散加权ADC值定量评价退变椎间盘蛋白多糖和胶原蛋白含量 的实验研究[D].南充：川北医学院,2009.
[9]方元.MRS、T2Map、DWI多种方法对腰椎间盘退变评价的相关性研究[D].石家庄：河北医科大学,2009.
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