18F-FDG PET/CT在骨感染中應(yīng)用的研究進(jìn)展

劉思為， 石洪成

復(fù)旦大學(xué)附屬中山醫(yī)院核醫(yī)學(xué)科，上海 200032

·綜述·

18F-FDGPET/CT在骨感染中應(yīng)用的研究進(jìn)展

劉思為， 石洪成*

復(fù)旦大學(xué)附屬中山醫(yī)院核醫(yī)學(xué)科，上海 200032

部分類型骨感染具有病程長、治療困難、預(yù)后差等特點(diǎn)，早期而準(zhǔn)確的診斷非常重要，傳統(tǒng)影像學(xué)檢查對其診斷效果不佳。18F-FDG PET/CT是功能顯像的一種，逐漸被廣泛應(yīng)用于感染性疾病的臨床診治。本文就18F-FDG PET/CT在骨感染的診斷、療效評估等方面的應(yīng)用加以綜述。

PET/CT；骨髓炎；脊柱炎；人工關(guān)節(jié)感染

骨感染可以發(fā)生在任何年齡段。血源性、軟組織感染以及創(chuàng)傷或手術(shù)后感染較為常見。骨感染最常見的致病菌為金黃色葡萄球菌。骨感染后常診斷困難、病程遷延、治療復(fù)雜、預(yù)后較差，早期而準(zhǔn)確的診斷能減少不必要的治療措施、改善患者的預(yù)后，節(jié)約時(shí)間和經(jīng)濟(jì)成本。近年來，功能代謝顯像技術(shù)應(yīng)用逐漸廣泛，18F-FDG PET/CT作為最新的影像學(xué)檢查方法，融合了解剖結(jié)構(gòu)顯像與功能代謝顯像技術(shù)，能反映人體內(nèi)葡萄糖的代謝情況。研究[1-2]表明，18F-FDG PET/CT可用于骨感染的診斷和療效評估。因此，本文對18F-FDG PET/CT在慢性骨髓炎、糖尿病足骨髓炎、化膿性脊柱炎及人工關(guān)節(jié)感染中的應(yīng)用作一綜述。

1 慢性骨髓炎

骨髓炎是由微生物感染引起的伴有骨組織破壞的炎性反應(yīng)，可累及骨髓、骨質(zhì)、骨膜及周圍軟組織。骨髓炎根據(jù)病程可分為急性、亞急性和慢性[3]。對于急性骨髓炎，MRI和骨顯像都有較好的靈敏度[2,4]，結(jié)合臨床表現(xiàn)和實(shí)驗(yàn)室檢查可以明確診斷。而對于慢性骨髓炎，由于骨骼正常的解剖結(jié)構(gòu)和生理功能發(fā)生改變，常規(guī)影像及實(shí)驗(yàn)室檢查診斷的準(zhǔn)確度較差。CT和MRI是診斷慢性骨髓炎的常用方法，但其診斷的靈敏度和特異度一般，不易與術(shù)后改變鑒別，也無法避免金屬假體的影響；骨顯像的靈敏度為82.7%，特異度僅為44.6%；白細(xì)胞顯像的靈敏度和特異度分別為74.2%、88.1%[5]，但由于過程復(fù)雜，國內(nèi)開展較少。

Meta分析[5]結(jié)果顯示，18F-FDG PET和PET/CT診斷慢性骨髓炎的靈敏度和特異度分別為92.3%、92.0%，優(yōu)于其他影像學(xué)檢查。Wenter等[6]納入215例患者，發(fā)現(xiàn)PET/CT的靈敏度、特異度、陽性預(yù)測值(PPV)、陰性預(yù)測值(NPV)、準(zhǔn)確度分別是88%、76%、76%、89%、82%，相比單獨(dú)PET檢查更準(zhǔn)確。而聯(lián)合PET/CT和MRI對骨髓炎診斷的準(zhǔn)確度可達(dá)100%[7]。也有研究[8]報(bào)道，PET/CT早期動(dòng)態(tài)顯像與常規(guī)顯像對骨髓炎的診斷效果相仿。

總之，PET/CT在慢性骨髓炎診斷中有一定應(yīng)用價(jià)值，但其診斷標(biāo)準(zhǔn)和適用范圍等尚需進(jìn)一步的研究。目前慢性骨髓炎的首選檢查方法仍是MRI，對于MRI不能明確診斷的患者，建議補(bǔ)充PET/CT檢查。

2 糖尿病足骨髓炎

足部感染是糖尿病患者常見的并發(fā)癥，常繼發(fā)于頑固性潰瘍，感染侵犯骨組織可進(jìn)展為骨髓炎，治療困難，甚至可能需截肢[9]?；顧z雖為診斷的金標(biāo)準(zhǔn)，但無法應(yīng)用于全部病例，病史、臨床表現(xiàn)、實(shí)驗(yàn)室檢查、影像學(xué)檢查都不易在病變早期準(zhǔn)確地診斷糖尿病足骨髓炎[2]。

MRI是糖尿病足骨髓炎常用的檢查方法，但糖尿病其他的并發(fā)癥如神經(jīng)性骨關(guān)節(jié)炎、應(yīng)激反應(yīng)等可使MRI結(jié)果呈假陽性[10]。同位素顯像中，白細(xì)胞顯像應(yīng)用較廣泛，99Tc-WBC診斷的靈敏度為86%～93%、特異度為80%～98%，111In-WBC診斷的靈敏度為72%～100%、特異度為67%～100%[4]。白細(xì)胞顯像還可以評估糖尿病足骨髓炎的療效，其靈敏度和特異度分別為100%、91.5%[11]。

一項(xiàng)Meta分析[10]對比18F-FDG PET和PET/CT與其他影像學(xué)檢查的診斷效果，結(jié)果顯示，18F-FDG PET和PET/CT診斷的靈敏度為74%、特異度為91%，并可以有效鑒別糖尿病足骨髓炎、軟組織感染、夏科氏關(guān)節(jié)炎，由于PET/CT具有較好的特異度，使其診斷的準(zhǔn)確度高于CT、MRI、骨顯像或白細(xì)胞顯像；且PET/CT診斷的準(zhǔn)確度和對感染灶的定位優(yōu)于單獨(dú)PET檢查。此外，Yang等[12]研究發(fā)現(xiàn)，輕微的血糖升高不會(huì)影響PET/CT的診斷結(jié)果，所以PET/CT可以應(yīng)用于糖尿病足的診斷。但是，F(xiàn)amiliari等[13]納入13例患者，得到白細(xì)胞顯像的準(zhǔn)確度為92%，而PET/CT只有54%，認(rèn)為PET/CT不能取代白細(xì)胞顯像。

我們認(rèn)為，18F-FDG PET/CT對于糖尿病足骨髓炎的早期診斷有一定意義，作為補(bǔ)充檢查有助于鑒別診斷和明確感染的范圍，指導(dǎo)進(jìn)一步的治療。但相關(guān)研究的具體診斷方法不一致，缺乏統(tǒng)一的陽性標(biāo)準(zhǔn)，仍需要進(jìn)一步的研究。

3 化膿性脊柱炎

化膿性脊柱炎一般由血行感染引起，好發(fā)于腰椎，病灶可累及椎弓、椎體及椎間盤?；撔约怪纂m然臨床上較少見，但病情嚴(yán)重，若轉(zhuǎn)為慢性，則終身難愈。MRI是診斷化膿性脊柱炎的常用方法，對椎體、椎管內(nèi)及周圍軟組織的病灶都很敏感[14]。相比MRI，18F-FDG PET/CT具有更好的診斷效果。文獻(xiàn)[15-17]報(bào)道，PET/CT診斷化膿性脊柱炎的準(zhǔn)確度為84%～96%，而MRI則為72%～81%，此外，PET/CT還可以發(fā)現(xiàn)MRI不能顯示的病灶[18]。Fuster等研究[17]發(fā)現(xiàn)，PET/CT診斷化膿性脊柱炎的靈敏度較MRI稍差(83%vs94%)，但特異度更好(88%vs38%)，認(rèn)為PET/CT應(yīng)作為化膿性脊柱炎的首選檢查方法 。Smids等[15]研究發(fā)現(xiàn)，在化膿性脊柱炎發(fā)病2周內(nèi)，PET/CT的診斷準(zhǔn)確度優(yōu)于MRI(97%vs58%)，而在2周后，兩者準(zhǔn)確度接近(94%vs82%)，說明PET/CT在早期診斷方面更具有優(yōu)勢。

研究[19-21]結(jié)果顯示，18F-FDG PET/CT還可以用以評估化膿性脊柱炎的療效。Riccio等[20]發(fā)現(xiàn)，經(jīng)抗感染無效的病例表現(xiàn)為椎骨和軟組織中FDG攝取持續(xù)增強(qiáng)；而治療有效的表現(xiàn)為FDG攝取增強(qiáng)僅局限在受損的椎間盤邊緣，該組患者在停止治療6～8周后未見復(fù)發(fā)；但是，最大標(biāo)準(zhǔn)攝取值(SUVmax)不能作為診斷感染的依據(jù)。Niccoli等[21]納入15例化膿性脊柱炎患者，在治療前、后(間隔6周)行MRI和PET/CT檢查，評估治療效果，顯示PET/CT的準(zhǔn)確度為100%，而MRI僅為53%。同時(shí)，PET/CT對化膿性脊柱炎病灶的定位也優(yōu)于MRI，有助于明確手術(shù)治療的范圍[22]。

雖然有研究[4]認(rèn)為，脊柱退化性病變和脊柱內(nèi)假體會(huì)導(dǎo)致FDG攝取增強(qiáng)，而且PET/CT不易鑒別脊柱炎癥和腫瘤，因此不適用于脊柱感染的診斷，但18F-FDG PET/CT對化膿性脊柱炎的早期診斷、治療方案的制定和療效評估具有積極意義。

4 人工關(guān)節(jié)感染

隨著接受關(guān)節(jié)置換術(shù)患者的逐年增多，人工關(guān)節(jié)感染作為關(guān)節(jié)術(shù)后的嚴(yán)重并發(fā)癥，越來越受到人們的重視[23]。人工關(guān)節(jié)感染在首次術(shù)后的發(fā)病率約為2%，再次術(shù)后約為5%。臨床工作中最重要的是將感染與假體無菌性松動(dòng)進(jìn)行鑒別。無菌性松動(dòng)是由人體的自身免疫反應(yīng)導(dǎo)致，治療方式為一期翻修術(shù)，而人工關(guān)節(jié)感染不僅手術(shù)方式更為復(fù)雜，還需要持續(xù)的抗感染治療。人工關(guān)節(jié)感染臨床癥狀隱蔽，與無菌性松動(dòng)的影像表現(xiàn)相似，鑒別困難[24]。

同位素顯像在人工關(guān)節(jié)感染的診斷中應(yīng)用廣泛，骨顯像的準(zhǔn)確度為50%～70%，67Ga顯像的準(zhǔn)確度為60%～80%。白細(xì)胞顯像是同位素顯像中的“金標(biāo)準(zhǔn)”，其準(zhǔn)確度為90%；近30年的相關(guān)研究證實(shí)了白細(xì)胞顯像具有較高的靈敏度和特異度[25]。

關(guān)于18F-FDG PET診斷人工關(guān)節(jié)感染的研究結(jié)果差異較大，對其能否取代白細(xì)胞顯像也有爭議[24, 26]。Love等[27]認(rèn)為，白細(xì)胞顯像診斷的準(zhǔn)確度高于PET(95%vs71%)。Pill等[28]的研究中，PET診斷的靈敏度和特異度分別為95%、93%，而白細(xì)胞顯像則分別為50%、95.1% 。Yue等[23]認(rèn)為，18F-FDG PET/CT尚不能取代白細(xì)胞顯像。但是，Basu等[29]納入221例患者，PET診斷人工髖關(guān)節(jié)的靈敏度和特異度分別為81.8%、93.1%，診斷膝關(guān)節(jié)感染的靈敏度和特異度94.7%、88.2%；白細(xì)胞顯像分別為38.5%、95.7%，33.3%、88.5%。結(jié)果說明PET對髖關(guān)節(jié)感染的靈敏度高于白細(xì)胞顯像，其他數(shù)據(jù)兩者相似。Kumar等[30]對42例髖關(guān)節(jié)置換術(shù)后可疑感染的患者進(jìn)行了研究，結(jié)果顯示PET/CT診斷的靈敏度、特異度、準(zhǔn)確度分別為93.7%、92.3%、92.8% 。Shemesh等[31]報(bào)道，PET/CT可以幫助鑒別術(shù)后的感染性不愈合、非感染性不愈合、軟組織感染和慢性骨髓炎，其特異度可達(dá)100%。Chatziioannou等[32]在動(dòng)物模型上證明，PET/CT可以用來監(jiān)測人工關(guān)節(jié)感染抗感染治療的療效 。

因此，Kwee等[33]認(rèn)為，Yue等[23]的綜述參考文獻(xiàn)時(shí)間較早，不能代表目前的診斷水平，且PET/CT的性能要優(yōu)于單獨(dú)PET，所以PET/CT的診斷價(jià)值在該文中被低估了。因此，18F-FDG PET/CT在人工關(guān)節(jié)感染的診斷和療效評估中有較好的潛在應(yīng)用價(jià)值。目前有關(guān)PET/CT在人工關(guān)節(jié)感染中應(yīng)用的研究較少，PET/CT對人工關(guān)節(jié)感染的診斷效能還需要進(jìn)一步多中心大樣本研究。

綜上所述，部分類型骨感染始終是臨床診斷和治療的難題。致病菌的耐藥性、外科手術(shù)的增加以及偶發(fā)隱匿的深部感染，讓骨感染病情趨于復(fù)雜化和隱匿化。近年來，多項(xiàng)研究表明，18F-FDG PET/CT可用于診斷慢性骨髓炎、糖尿病足骨髓炎、化膿性骨髓炎和人工植入物感染，對于疾病的早期診斷、治療方案的制定、療效的評估都有重要的作用。隨著技術(shù)的進(jìn)步和認(rèn)識(shí)的不斷深入，相信18F-FDG PET/CT在骨感染的診斷與療效評價(jià)中將會(huì)發(fā)揮更大的作用。

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Role of18F-FDG PET/CT in bone infection: recent progress

LIU Si-wei, SHI Hong-cheng*

Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China

Some kinds of bone infection are characterized by long course, treatment difficulty and poor prognosis, so early and accurate diagnosis is very important to them. The diagnosis of such infections are not always obvious by using traditional imaging procedures.18F-FDG PET/CT is a functional imaging procedure that is widely used in the diagnosis of infection. In this paper, the role of18F-FDG PET/CT in the diagnosis and curative effect evaluation of bone infection is reviewed.

PET/CT; osteomyelitis; spondylitis; prosthetic joint infection

2017-02-07接受日期2017-02-27

劉思為, 碩士, 住院醫(yī)師. E-mail: liusw90@126.com

*通信作者(Corresponding author). Tel: 021-64041990-12205, E-mail: shi.hongcheng@zs-hospital.sh.cn

10.12025/j.issn.1008-6358.2017.20170086

R 681.2

A

[本文編輯] 姬靜芳