樊子健，吳麗萍，任有忠，鞠文萍，劉曉藝，王現(xiàn)亮*

膝關(guān)節(jié)軟骨損傷是臨床常見(jiàn)病損，關(guān)節(jié)軟骨損傷后不能再生且自我修復(fù)能力有限，若不及時(shí)診治，最終將發(fā)展為骨性關(guān)節(jié)炎(osteoarthritis，OA)。骨性關(guān)節(jié)炎患者會(huì)出現(xiàn)關(guān)節(jié)疼痛，水腫、活動(dòng)受限及關(guān)節(jié)絞鎖等癥狀，且有較高的致殘率。臨床上常用外科手術(shù)的方法對(duì)軟骨損傷進(jìn)行修復(fù)，因此術(shù)前能正確評(píng)估軟骨損傷范圍及程度十分重要。磁共振成像是膝關(guān)節(jié)軟骨損傷診斷和分級(jí)的最佳影像學(xué)方法。本研究旨在用T2-mapping、三維快速自旋回波脈沖序列(threedimensional fast spin echo cube，3D-FSE-Cube)及常規(guī)序列評(píng)估膝關(guān)節(jié)軟骨損傷敏感度、特異度，以確定三種序列在評(píng)估膝關(guān)節(jié)軟骨損傷分級(jí)以及臨床應(yīng)用的價(jià)值。

1 材料與方法

搜集2016年3月至2016年12月因膝關(guān)節(jié)疼痛等癥狀來(lái)濰坊市人民醫(yī)院住院診治的患者124例，男64例，年齡19～63歲，平均年齡43.4歲；女60例，年齡18～64歲，平均年齡42.3歲，所有患者均接受膝關(guān)節(jié)常規(guī)序列、3D-FSE-Cube序列、T2-mapping序列MR掃描。選取其中符合標(biāo)準(zhǔn)的患者63例，其中男32例，年齡21～63歲，平均年齡42.8歲；女31例，年齡20～63歲，平均年齡41.9歲。納入標(biāo)準(zhǔn)：(1)年齡小于65歲；(2)接受膝關(guān)節(jié)MRI檢查1周內(nèi)行膝關(guān)節(jié)鏡手術(shù)；(3)短期內(nèi)(1～3 d)有明確外傷或明確診斷OA患者，OA患者的診斷采用骨關(guān)節(jié)炎診治指南(中華醫(yī)學(xué)會(huì)骨科學(xué)分會(huì)，2007年)中的診斷標(biāo)準(zhǔn)；(4)患者體重指數(shù)小于30 kg/m2；(5)此前無(wú)膝關(guān)節(jié)手術(shù)史。

1.1 掃描技術(shù)

采用GE 3.0 T Discovery 750 w MR儀及8通道相控膝關(guān)節(jié)線圈，對(duì)124例患者進(jìn)行掃描，掃描序列包括：(1)常規(guī)序列：矢狀面FSE-T1WI (TR 528 ms，TE 20 ms，層厚3.5 cm，間隔1.0 mm，掃描時(shí)間1 min 40 s)、FSE-T2WI (TR 5200 ms，TE 85 ms，層厚3.5 cm，間隔1.0 mm，掃描時(shí)間1 min 49 s)及FS-FSE-PDWI (TR 2046 ms，TE 32 ms，層厚3.5 cm，間隔1.0 mm，掃描時(shí)間2 min 15 s)，冠狀面FS-FSE-PDWI (TR 1756 ms，TE 38 ms，層厚4.0 cm，間隔1.5 mm，掃描時(shí)間1 min 42 s)，橫斷面FS-FSE-PDWI (TR 1722 ms，TE 32 ms，層厚5.0 cm，間隔1.0 mm，掃描時(shí)間1 min6 s)，以上序列的FOV均為18 cm×18 cm，矩陣均為320×256，激勵(lì)次數(shù)均為2；(2)矢狀面T2-mapping序列：采用8回波SE序列掃描，TR 1000 ms，TE 7.6、15.3、22.9、30.5、38.2、45.8、53.4、61.1 ms，層厚4.0 cm，間隔2.0 mm，F(xiàn)OV 16 cm×16 cm，矩陣256×192，激勵(lì)次數(shù)為2，掃描時(shí)間6 min 26 s；(3)矢狀面3D-FSE-Cube序列：TR 1500 ms，TE 28 ms，層厚1.6 cm，間隔0 mm，F(xiàn)OV 18 cm×18 cm，矩陣256×256，激勵(lì)次數(shù)為1，掃描時(shí)間4 min 49 s。

1.2 圖像后處理分析

將原始圖像傳送至GE-ADW 4.6工作站，應(yīng)用Functool 2軟件生成T2-mapping偽彩圖，調(diào)節(jié)上下閾值(色彩范圍為14～144 ms)使正常膝關(guān)節(jié)軟骨顯示為紅、黃色，軟骨損傷顯示為藍(lán)、綠色。由2名經(jīng)驗(yàn)豐富的放射科肌骨影像診斷醫(yī)師觀察分析T2-mapping偽彩圖、 3D-FSE-Cube圖像和常規(guī)序列的圖像，對(duì)膝關(guān)節(jié)股骨內(nèi)、外側(cè)髁，脛骨內(nèi)、外側(cè)平臺(tái)，股骨滑車及髕骨表面的6處軟骨進(jìn)行損傷分級(jí)。2名醫(yī)師獨(dú)立完成分級(jí)診斷，意見(jiàn)不一致時(shí)，討論并達(dá)成統(tǒng)一意見(jiàn)。

對(duì)于軟骨損傷MRI分級(jí)診斷標(biāo)準(zhǔn)采用ICRS分級(jí)[1]，0級(jí)：軟骨表面光滑、未見(jiàn)缺損，軟骨內(nèi)信號(hào)均勻，軟骨下骨未出現(xiàn)異常信號(hào)影；Ⅰ級(jí)：軟骨結(jié)構(gòu)完整，表面光滑、未見(jiàn)缺損，內(nèi)出現(xiàn)局灶性異常信號(hào)影；Ⅱ級(jí)：軟骨表面出現(xiàn)缺損，缺損深度小于全層軟骨厚度的50%；Ⅲ級(jí)：缺損深度大于全層軟骨厚度的50%，但缺損尚未累及全層軟骨；Ⅳ級(jí)：全層軟骨完全缺失，軟骨下骨質(zhì)裸露。同一處軟骨存在不同級(jí)別損傷時(shí)，以最高級(jí)別損傷為準(zhǔn)[2]。

由2名經(jīng)驗(yàn)豐富的骨關(guān)節(jié)外科醫(yī)生共同完成膝關(guān)節(jié)鏡手術(shù)，關(guān)節(jié)鏡下軟骨損傷分級(jí)診斷標(biāo)準(zhǔn)采用Outerbridge[3]分級(jí)：0級(jí)，正常關(guān)節(jié)軟骨；Ⅰ級(jí)，軟骨軟化，表面可見(jiàn)輕度的水泡樣結(jié)構(gòu)，無(wú)裂隙樣潰瘍；Ⅱ級(jí)，軟骨變薄，軟骨輕、中度纖維化或淺表裂隙樣潰瘍，通常表現(xiàn)為縱向“鯊魚(yú)腮”樣改變；Ⅲ級(jí)，軟骨重度纖維化，軟骨部分剝脫，呈“蟹肉樣”改變，無(wú)軟骨下骨暴露；Ⅳ級(jí)，早期骨性關(guān)節(jié)炎，軟骨全層缺失、軟骨下骨暴露。

1.3 統(tǒng)計(jì)學(xué)分析

關(guān)節(jié)鏡診斷結(jié)果作為參考“金標(biāo)準(zhǔn)”，采用SPSS 19.0進(jìn)行數(shù)據(jù)處理和分析，分別計(jì)算T2-mapping、3D-FSE-Cube和常規(guī)序列對(duì)膝關(guān)節(jié)軟骨損傷的敏感度、特異度，用卡方檢驗(yàn)來(lái)比較三種MRI序列之間在評(píng)估膝關(guān)節(jié)軟骨損傷分級(jí)診斷的差異，規(guī)定P＜0.05為差異有統(tǒng)計(jì)學(xué)意義。如果三者比較有統(tǒng)計(jì)學(xué)意義，采用卡方分割法進(jìn)行兩兩比較，校正檢驗(yàn)標(biāo)準(zhǔn)α'=α/[k×(k-1)/2+1] (α為檢驗(yàn)標(biāo)準(zhǔn)，k為樣本量的個(gè)數(shù)，本研究α=0.05，k=3)，規(guī)定P＜0.0125為差異有統(tǒng)計(jì)學(xué)意義。

2 結(jié)果

2.1 T2-mapping、3D-FSE-Cube、常規(guī)序列及關(guān)節(jié)鏡下膝關(guān)節(jié)軟骨損傷的分級(jí)比較

T2-mapping、3D-FSE-Cube、常規(guī)序列及關(guān)節(jié)鏡對(duì)63例患者共378處軟骨(股骨內(nèi)、外側(cè)髁，脛骨內(nèi)、外側(cè)平臺(tái)，股骨髁間滑車及髕骨表面軟骨)進(jìn)行損傷分級(jí)，其中0級(jí)(正常關(guān)節(jié)軟骨)分別為153、168、201、188處，Ⅰ級(jí)損傷分別為106、84、61、76 處，Ⅱ級(jí)損傷分別為60、69、59、58處，Ⅲ級(jí)損傷分別為33、31、35、30處，Ⅳ級(jí)損傷分別為26、26、22、26處(表1)；各級(jí)損傷表現(xiàn)見(jiàn)圖1～4。

2.2 T2-mapping、3D-FSE-Cube和常規(guī)序列對(duì)膝關(guān)節(jié)軟骨損傷的的敏感度及特異度比較

T2-mapping、3D-FSE-Cube、常規(guī)序列對(duì)膝關(guān)節(jié)軟骨各級(jí)損傷的敏感度、特異度見(jiàn)表2。

三種磁共振序列評(píng)估膝關(guān)節(jié)軟骨損傷總的敏感度、特異度及Ⅰ、Ⅱ級(jí)損傷的敏感度差異均有統(tǒng)計(jì)學(xué)意義(P值＜0.05)，Ⅲ、Ⅳ級(jí)損傷的敏感度差異均無(wú)統(tǒng)計(jì)學(xué)意義(P＞0.05；表2)。

T2-mapping序列對(duì)膝關(guān)節(jié)關(guān)節(jié)軟骨Ⅰ級(jí)損傷的敏感度顯著高于3D-FSE-Cube，差異有統(tǒng)計(jì)學(xué)意義(P＜0.0125)，二者在Ⅱ級(jí)損傷的敏感度差異無(wú)統(tǒng)計(jì)學(xué)意義(P＞0.0125)，二者在評(píng)估膝關(guān)節(jié)軟骨損傷總的敏感度、特異度差異均無(wú)統(tǒng)計(jì)學(xué)意義(P值＞0.0125)。T2-mapping與3D-FSE-Cube序列對(duì)膝關(guān)節(jié)軟骨損傷總的敏感度及Ⅰ、Ⅱ級(jí)損傷敏感度均高于常規(guī)序列，而特異度均低于常規(guī)序列，差異均有統(tǒng)計(jì)學(xué)意義(P值均＜0.0125；表3)。

3 討論

膝關(guān)節(jié)軟骨覆蓋于膝關(guān)節(jié)組成骨的表面，屬于透明軟骨，組成成分包括膠原纖維、蛋白多糖和水，具有潤(rùn)滑固定關(guān)節(jié)、減少骨摩擦、緩沖運(yùn)動(dòng)時(shí)的震動(dòng)等作用。膝關(guān)節(jié)軟骨損傷發(fā)病率較高，易導(dǎo)致關(guān)節(jié)疼痛、水腫、活動(dòng)受限及關(guān)節(jié)絞鎖[4]，MRI是其診斷和分級(jí)的最佳影像學(xué)方法。

T2-mapping成像是一種通過(guò)描述組織橫向磁化衰減來(lái)反映組織特性的技術(shù)，一般采用多層面多回波SE序列，通過(guò)測(cè)量不同回波時(shí)間信號(hào)強(qiáng)度獲取T2加權(quán)原始圖像，經(jīng)工作站后處理生成不同的灰階或色階的偽彩圖[5]，多應(yīng)用于軟骨病變的檢測(cè)，能夠敏感發(fā)現(xiàn)軟骨內(nèi)水和膠原含量以及膠原排列結(jié)構(gòu)等組織成分的變化。以往T2-mapping用于定量評(píng)價(jià)未見(jiàn)明顯肉眼形態(tài)改變的關(guān)節(jié)軟骨早期損傷，利用T2-mapping偽彩圖從結(jié)構(gòu)成像直接觀察軟骨損傷報(bào)道不多，但也有相關(guān)學(xué)者對(duì)該方法進(jìn)行了研究。相關(guān)研究表明，當(dāng)軟骨損傷時(shí)，關(guān)節(jié)軟骨內(nèi)膠原和蛋白多糖含量減少、水含量增加，T2值增加，使T2-mapping偽彩圖上的色階增高[6-7]。王鶴翔等[7]對(duì)膝關(guān)節(jié)脛骨平臺(tái)軟骨退變研究發(fā)現(xiàn)，T2-mapping偽彩圖可以敏感顯示軟骨損傷，但無(wú)法評(píng)價(jià)軟骨損傷的程度，提出改變閾值可能對(duì)評(píng)價(jià)軟骨損傷程度有一定幫助。崔倩[8]在對(duì)髕軟骨損傷研究中發(fā)現(xiàn)，將T2-mapping偽彩圖、FS-FSE-PDWI和關(guān)節(jié)鏡分級(jí)進(jìn)行對(duì)照分析發(fā)現(xiàn)，在T2-mapping偽彩圖上，通過(guò)調(diào)節(jié)閾值可以較好顯示軟骨缺損程度，可用于評(píng)價(jià)髕軟骨損傷的程度，T2-mapping偽彩圖與關(guān)節(jié)鏡評(píng)價(jià)髕軟骨損傷的相關(guān)性優(yōu)于FS-FSE-PDWI與關(guān)節(jié)鏡檢查的相關(guān)性，但二者評(píng)價(jià)髕軟骨損傷的程度無(wú)顯著差異。本組結(jié)果表明T2-mapping序列對(duì)膝關(guān)節(jié)軟骨Ⅰ級(jí)損傷的敏感度顯著高于3D-FSE-Cube (P=0.008)及常規(guī)序列(P＜0.001)，對(duì)Ⅱ級(jí)損傷的敏感性高于常規(guī)序列(P=0.004)，可見(jiàn)T2-mapping序列評(píng)估膝關(guān)節(jié)軟骨早期損傷的敏感性較高，這與以往學(xué)者認(rèn)為T2-mapping序列可以檢測(cè)軟骨中水和膠原含量等生化結(jié)構(gòu)的變化，更早地發(fā)現(xiàn)膝關(guān)節(jié)軟骨損傷的觀點(diǎn)相一致[9-10]。

圖1 女，29歲，膝關(guān)節(jié)外傷。A～D分別為其髕軟骨矢狀面T2-mapping偽彩圖、3D-FSE-Cube-T2WI、FS-FSE-PDWI及關(guān)節(jié)鏡圖；A：可見(jiàn)髕軟骨結(jié)構(gòu)連續(xù)完整，表面光滑，厚度均勻，大部分區(qū)域呈現(xiàn)紅黃色色階(正常軟骨)，局部區(qū)域見(jiàn)斑片狀綠色色階(黑箭)；B：可見(jiàn)髕軟骨結(jié)構(gòu)連續(xù)完整，表面光滑，內(nèi)未見(jiàn)明顯異常高信號(hào)；C：可見(jiàn)髕軟骨結(jié)構(gòu)連續(xù)完整，表面光滑，內(nèi)未見(jiàn)明顯異常高信號(hào)；D：關(guān)節(jié)鏡下可見(jiàn)髕軟骨局部軟化，表面出現(xiàn)輕度的水泡樣結(jié)構(gòu)(黑箭)，為軟骨Ⅰ級(jí)損傷 圖2 男，36歲，膝關(guān)節(jié)外傷。A～D分別為其髕軟骨矢狀面T2-mapping偽彩圖、3D-FSE-Cube-T2WI、FS-FSE-PDWI及關(guān)節(jié)鏡圖。A：見(jiàn)髕軟骨表面紅黃色色階部分缺損，缺損深度小于全層軟骨厚度的50% (白箭)；B：見(jiàn)軟骨表面局部缺損，缺損深度小于全層軟骨厚度的50%；C：僅見(jiàn)軟骨表面模糊(白箭)；D：可見(jiàn)軟骨變薄，中度度纖維化(黑箭)，為軟骨Ⅱ級(jí)損傷Fig. 1 A twenty-nine years old female patient with knee joint trauma. Fig A—D were sagittal T2-mapping artificial color of patellar cartilage, 3D-FSECube-T2WI, FS-FSE-PDWI and arthroscopy findings of her knee joint, respectively. A: The patellar cartilage was intact, with uniform thickness and smooth surface, most part of it was red or yellow (normal cartilage), a little was patchy green (black arrow). B: The patellar cartilage was intact, with smooth surface and no abnormal high signal. C: The patellar cartilage was intact, with smooth surface and no abnormal high signal. D: Arthroscopy showed that the local patellar cartilage was softened and its surface was slightly vesicular (black arrow), the cartilage injury was diagnosed as gradeⅠ. Fig. 2 A thirtysix years old male with knee joint trauma. Fig A—D were the patellar cartilage sagittal T2-mapping artificial color, 3D-FSE-Cube-T2WI, FS-FSE-PDWI and arthroscopy findings of his knee joint, respectively. A: The red and yellow surface of patellar cartilage was partly defect, the defect depth was less than 50% of the thickness of articular cartilage (black arrow). B: The patellar cartilage surface was defect, the defect depth was less than 50% of the thickness of articular cartilage (white arrow). C: The surface of patellar cartilage was obscure (white arrow). D: Arthroscopic cartilage was thin and moderate fibrosis (black arrow), the cartilage injury was diagnosed as grade Ⅱ.

表1 三種MR序列與關(guān)節(jié)鏡下膝關(guān)節(jié)各級(jí)軟骨損傷數(shù)目Tab. 1 The number of knee each grade of cartilage injury in three MR sequence and arthroscopy

表2 三種MR序列評(píng)估膝關(guān)節(jié)軟骨損傷的的敏感度及特異度比較Tab.2 Comparison of sensitivity or specificity among three MR sequences in knee cartilage injury

圖3 男，40歲，膝關(guān)節(jié)外傷。A～D分別為其股骨外側(cè)髁軟骨矢狀面T2-mapping偽彩圖、3D-FSE-Cube-T2WI、FS-FSE-PDWI及關(guān)節(jié)鏡圖。A：見(jiàn)紅黃色色階部分缺損(黑箭)，缺損深度大于全層軟骨厚度的50%，缺損區(qū)見(jiàn)積液綠色色階，軟骨下骨質(zhì)內(nèi)見(jiàn)斑片狀深綠色色階；B、C：可見(jiàn)軟骨局部部分缺損(白箭)，缺損深度大于全層軟骨厚度的50%，軟骨下骨質(zhì)內(nèi)見(jiàn)斑片狀高信號(hào)；D：可見(jiàn)軟骨重度纖維化，軟骨部分剝脫(黑箭)，為軟骨Ⅲ級(jí)損傷 圖4 女，56歲，骨性關(guān)節(jié)炎。A～D分別為其股骨外側(cè)髁軟骨矢狀面T2-mapping偽彩圖、3D-FSE-Cube-T2WI、FS-FSEPDWI及關(guān)節(jié)鏡圖。A：見(jiàn)股骨外側(cè)髁軟骨局部紅黃色色階全層缺失(黑箭)，代之以綠色色階；B、C：可見(jiàn)股骨外側(cè)髁軟骨局部全層缺失(白箭)，軟骨下骨質(zhì)見(jiàn)斑片狀高信號(hào)；D：可見(jiàn)軟骨全層缺失、軟骨下骨暴露(黑箭)，為軟骨Ⅳ級(jí)損傷Fig. 3 A forty years old male with knee joint trauma. Fig A—D were the femoral lateral condyle cartilage sagittal T2-mapping artificial color, 3D-FSECube-T2WI, FS-FSE-PDWI and arthroscopy findings of his knee joint, respectively. A: The red and yellow surface of femoral lateral condyle cartilage was mostly defect (black arrow), the defect depth was more than 50% of the thickness of articular cartilage. The subchondral bone of defect area was patchy dark green. B, C: Showed the femoral lateral condyle cartilage was almost defect (white arrow), the defect depth was more than 50% of the thickness of articular cartilage, the subchondral bone of defect area has patchy high signal. D: Arthroscopic cartilage was severe fibrosis and stripped partly (black arrow), the cartilage injury was diagnosed as grade Ⅲ. Fig. 4 A fifty-six years old female twitch osteoarthritis. Fig A—D were the femoral lateral condyle cartilage sagittal T2-mapping artificial color, 3D-FSE-Cube-T2WI, FS-FSE-PDWI and arthroscopy findings of his knee joint, respectively. A: The red and yellow surface of femoral lateral condyle cartilage was missing and replaced by green color (black arrow). B, C: Showed the femoral lateral condyle cartilage was striped completely (white arrow), the subchondral bone of defect area has patchy high signal. D: Arthroscopic cartilage was striped completely and the subchondral bone exposed (black arrow), the cartilage injury was diagnosed as grade Ⅳ.

表3 三種磁共振序列評(píng)估膝關(guān)節(jié)軟骨損傷的敏感度及特異度的兩兩比較Tab. 3 Pairwise comparison of sensitivity or specificity among three MR sequences in evaluating knee joint cartilage injury

本研究中筆者還發(fā)現(xiàn)T2-mapping序列特異度低于常規(guī)序列，可能原因：T2-mapping成像技術(shù)T2值易受主磁場(chǎng)均勻程度、磁化率改變、魔角效應(yīng)、化學(xué)位移、軟骨與關(guān)節(jié)液界面所致的部分容積效應(yīng)等因素的影響[11-14]，使正常關(guān)節(jié)軟骨出現(xiàn)損傷的假象，從而造成假陽(yáng)性。

3D-FSE-Cube是目前新研發(fā)的一項(xiàng)具有各向同性以寬回波鏈采集的三維(three dimensional，3D)快速自旋回波(fast spin echo，F(xiàn)SE)及并行成像的技術(shù)[15]，該技術(shù)對(duì)診斷軟骨損傷具有獨(dú)特優(yōu)勢(shì)[16]：(1) 3D-FSE -Cub序列所獲得的圖像提高了軟骨和滑液的信噪比及軟骨與軟骨下骨皮質(zhì)的對(duì)比噪聲比，使軟骨呈現(xiàn)中等信號(hào)，關(guān)節(jié)液呈現(xiàn)高信號(hào)，可較清晰地顯示軟骨損傷的深度，診斷軟骨損傷的敏感度大大提高。(2)具備各向同性以及無(wú)間距容積掃描，可獲得無(wú)間隔的連續(xù)薄層圖像，避免部分容積效應(yīng)對(duì)軟骨損傷分級(jí)帶來(lái)的影響，明顯減少軟骨損傷漏診的可能性。(3)所得圖像顯示軟骨的空間分辨率較高，可清晰地顯示出軟骨內(nèi)的病灶。3D-FSE-Cube亦存在不足之處，在長(zhǎng)回波鏈晚期進(jìn)行高空間分辨率采集時(shí)，導(dǎo)致圖像清晰度下降，使正常關(guān)節(jié)軟骨表面出現(xiàn)損傷的假象，故診斷軟骨損傷的特異度減低。Kijowski等[17]在3D-FSE- Cube與常規(guī)序列評(píng)估膝關(guān)節(jié)病變對(duì)比研究中發(fā)現(xiàn)，對(duì)軟骨損傷進(jìn)行評(píng)估時(shí)，前者較后者有較高的敏感度，差異有統(tǒng)計(jì)學(xué)意義，而特異度卻較后者低，差異有統(tǒng)計(jì)學(xué)意義，與本組研究得出的3D-FSE-Cube序列的敏感度較高，但特異度較低的結(jié)論相一致。

總之，在膝關(guān)節(jié)軟骨損傷分級(jí)診斷方面，T2-mapping和3D-FSE-Cube序列的敏感度較常規(guī)序列高，常規(guī)序列的特異度高于T2-mapping和3D-FSECube序列。T2-mapping序列可以發(fā)現(xiàn)無(wú)明顯形態(tài)學(xué)改變的膝關(guān)節(jié)軟骨早期損傷，為臨床早期診治提供重要參考依據(jù)。

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