第二军医大学学报  2019, Vol. 40 Issue (11): 1236-1241   PDF    
多参数磁共振成像在前列腺癌中的诊断价值
王立鹏1, 阳青松1, 张威2, 王振1, 陈玉坤1, 陆建平1     
1. 海军军医大学(第二军医大学)长海医院影像医学科, 上海 200433;
2. 海军军医大学(第二军医大学)长海医院泌尿外科, 上海 200433
摘要: 前列腺癌(PCa)是全球范围内发病率最高的男性恶性肿瘤之一,严重危害着老年男性的身心健康,早期诊断和早期治疗对PCa治疗策略的制定和预后的判断非常关键。目前PCa诊断主要依靠直肠指诊、血清前列腺特异性抗原及经直肠超声引导下穿刺活组织检查。但这些方法的诊断效能均较低。近年来随着功能磁共振成像的推广运用,多参数磁共振成像(mpMRI)成为目前公认的诊断PCa最有效的影像学方法,其不仅能够进行前列腺疾病的鉴别诊断,还能进一步预测PCa病理评分,以及指导后续的靶向穿刺及局部治疗。mpMRI对PCa的精确诊断和后续的个体化治疗意义重大,本文就其在PCa诊断中的研究现状作一综述。
关键词: 多参数磁共振成像    前列腺肿瘤    诊断    磁共振成像    
Diagnostic value of multi-parameter magnetic resonance imaging in prostate cancer
WANG Li-peng1, YANG Qing-song1, ZHANG Wei2, WANG Zhen1, CHEN Yu-kun1, LU Jian-ping1     
1. Department of Radiology, Changhai Hospital, Naval Medical University(Second Military Medical University), Shanghai 200433, China;
2. Department of Urology, Changhai Hospital, Naval Medical University(Second Military Medical University), Shanghai 200433, China
Abstract: Prostate cancer is one of the male malignancies with the highest incidence rate in the world, which seriously endangers the physical and mental health of elderly men. Early diagnosis and treatment are critical for the formulation of treatment strategies and the prognosis of prostate cancer. At present, its diagnosis mainly depends on digital rectal examination, serum prostate-specific antigen and transrectal ultrasound guided biopsy. However, the diagnostic efficiency of these methods is very low. In recent years, with the introduction of functional magnetic resonance imaging, multi-parameter magnetic resonance imaging (mpMRI) is currently recognized as the most effective imaging method for diagnosing prostate cancer. Besides the differential diagnosis of prostate diseases, it could further predict the pathological score of prostate cancer and guide the subsequent targeted biopsy and local treatment. Accurate diagnosis of prostate cancer and subsequent individualized treatment are of great significance. The current status of mpMRI in the diagnosis of prostate cancer is reviewed in this paper.
Key words: multi-parameter magnetic resonance imaging    prostatic neoplasms    diagnosis    magnetic resonance imaging    

前列腺癌(prostate cancer,PCa)是老年男性最常见的恶性肿瘤之一,其发病率与种族、地理位置等因素有关[1]。在欧美国家,PCa的发病率位居男性恶性肿瘤的前2位[1-2]。既往研究显示亚洲国家PCa的发病率较低,但随着我国人口老龄化的加剧、居民饮食结构与生活方式的西化,我国PCa的发病率呈现逐年上升趋势[3]。有数据显示,2015年我国PCa新发病例约60 300例,死亡约26 000例[4];PCa的发病率位居我国男性恶性肿瘤的第6位[5]

前列腺在解剖学上分为4个区域:外周带、移行带、中央带和尿道周围腺体区。外周带PCa的发生比例最高,约占70%[6]。20%的PCa以及绝大多数的良性前列腺增生发生于移行带,1%~5%的PCa发生在中央带,尿道周围腺体区通常不发生PCa[7]

目前PCa的诊断主要依靠临床症状、直肠指诊、血清前列腺特异性抗原(prostate-specific antigen,PSA)检测、经直肠超声(transrectal ultrasound,TRUS)引导的系统穿刺活组织检查等,但这些方法对PCa诊断的灵敏度和特异度仍有待提高。早期PCa缺乏特异性的临床症状,如尿频、尿急、夜尿等症状也可出现在包括良性前列腺增生在内的很多疾病中。直肠指诊的结果主观性较强,对PCa的检出并不敏感,同时仅有约50%直肠指诊怀疑PCa的患者最终被确诊为PCa[8]。PSA为临床常用的PCa筛查及动态随访监测指标,其灵敏度较高但特异度不足,在良性前列腺增生及前列腺炎患者中也可见PSA升高;同时,约25%的PCa患者血清PSA水平低于4.0 ng/mL(正常男性PSA水平低于4.0 ng/mL)[9-10]。当直肠指诊或PSA结果怀疑PCa时,通常会推荐患者行TRUS引导下前列腺穿刺活组织检查,这是目前PCa诊断的金标准,但标准的12点系统穿刺法由于超声分辨率及取样问题往往存在较高的假阴性率[11-12]。近年发表于N Engl J Med 的一项多中心实验研究结果显示,对于疑似PCa患者,磁共振成像(magnetic resonance imaging,MRI)引导的靶向穿刺在风险评估上的作用优于系统穿刺法[13]

MRI可以提供相较于TRUS更加精确的前列腺分区解剖及PCa的病变情况,并且对PCa的检测、分期及随访具有重要意义。多参数磁共振成像(multi-parameter magnetic resonance imaging,mpMRI)通常包括形态学的T2加权像(T2-weighted imaging,T2WI)、功能学的扩散加权成像(diffusion-weighted imaging,DWI)及动态对比增强成像(dynamic contrast-enhanced imaging,DCEI),还可包括磁共振波谱成像(magnetic resonance spectroscopic imaging,MRSI)。mpMRI通过将结构和功能成像技术结合起来,使MRI在前列腺成像上的应用价值得到进一步提升[7, 14-16]。有报道认为,mpMRI对PCa诊断的特异度高达90%,阴性预测值约为85%[7]

1 前列腺的MRI

目前,通常采用1.5 T和3.0 T场强的MRI做PCa的常规检测,也有报道采用7 T场强对前列腺进行成像[17]。前列腺MRI的获得一般采用盆腔相控阵线圈,但直肠内线圈能够更好地提升信噪比[18]。根据我院经验,3.0 T场强的图像质量明显好于1.5 T,同时3.0 T MRI可以不使用直肠内线圈。

1.1 形态学MRI(T1WI和T2WI序列)

在T1WI上,前列腺呈均质中等信号,无法清楚显示分区,因此T1WI主要用于观察前列腺的轮廓及穿刺后出血的情况,同时,T1WI有助于骨转移的判断。

在T2WI上,正常的前列腺外周带表现为高信号,移行带、中央带和尿道周围腺体区呈低T2混杂信号,前列腺各区在T2WI上容易区分[19]。当外周带出现T2低信号改变时需考虑PCa,但这一表现不具有特异性,前列腺上皮内瘤变、出血、腺体萎缩及放射治疗后改变、前列腺炎症性改变等均可有类似信号表现。位于中央腺体的PCa由于其信号与间质型前列腺增生类似,其诊断难度较大[20]

1.2 DWI

DWI序列用于检测组织中水分子扩散运动的受限程度。由于组织中细胞膜的完整性及细胞密度与组织中水分子的扩散程度呈负相关,测量水分子的扩散程度可以提供组织结构的信息以鉴别良恶性[7, 19]。在正常前列腺组织,水分子扩散相对自由,在高b值(扩散敏感系数)DWI序列上表现为低信号。在恶性组织,细胞密度增加、间质更为致密,细胞外空间减少,水分子扩散受限,DWI序列上表现为高信号[21]。在生物体中,通常用表观扩散系数(apparent diffusion coefficient,ADC)来定量反映组织内水分子的扩散受限程度。ADC图的绘制需要至少2个b值。研究证实,在ADC图上PCa较周围健康的前列腺组织显示出更低的ADC值,当ADC图显示外周带高信号背景中出现低信号区时,应当考虑PCa[16]。但目前对于b值的选取并未达成共识,通常认为高b值如1 500 s/mm2和2 000 s/mm2对于PCa的诊断较佳[22-23]。同时也有研究表明ADC值和PCa的病理分级存在一定的相关性,可用于病理Gleason评分的预测,指导临床治疗及预后判断[24]

有研究认为,在含有血管的器官中,由于血液灌注的存在,常规DWI的单指数衰减模型并不能很好地反映扩散信号,因而尝试应用双指数信号衰减的体素内不相干运动(intravoxel incoherent motion,IVIM)成像来描述灌注情况[25]。但应用IVIM模型得到的灌注分数在评估PCa上的应用目前尚不成熟,诊断价值有限[25]

1.3 DCEI

基于组织内在对比度的磁共振平扫对有些病变并不能很好地显示。DCEI是一种通过静脉注射对比剂评价组织血管特征的功能成像方法。通过外源对比剂的应用,在肿瘤定性方面,由于肿瘤区域较周围健康组织有更丰富的血液供应,因而肿瘤区域通常出现早期强化。而这种强化与微血管密度、灌注及血管通透性的变化也有密切关系[26]。同时,用信号时间曲线可对组织进行半定量分析,任一体素的信号时间曲线显示的是对比剂的摄取速率,可以反映组织内的血管性质。通过DCEI的信号时间曲线可以确定半定量参数,如初始斜率(initial slope)、达峰时间(time-to-peak,TTP)、最大信号强度(maximum signal enhancement)、流出斜率(wash-out slope)及特定时间曲线下面积(area under the curve after a specified time,AUCtime[27]。通过示踪动力模型确定的定量参数可用于评估药代动力学特征,包括转运常数(transfer constant,Ktrans)、血管外细胞外容积(extravascular extracellular volume,Ve)和速率常数(Kep[27]。DCEI有助于外周带前列腺疾病的良恶性鉴别,而对于中央带前列腺良性疾病和PCa的鉴别价值不大。与正常的前列腺外周带相比,PCa的DCEI表现为早期更高的强化峰值、更早的流出及明显升高的Ktrans、Kep和Ve[28]。有研究显示DCEI对PCa诊断的灵敏度和特异度分别为69%~95%和80%~90%[27]。最近一项研究提出,以扩展Tofts模型和Lawrence-Lee延迟模型来进行图像后处理,较其他定量参数能更好地鉴别PCa[29]

1.4 MRSI

MRSI是指通过化学移位现象测定物质成分,反映组织细胞代谢情况的成像技术。正常的前列腺上皮细胞分泌大量的枸橼酸盐(citrate,Cit)到前列腺液中,在正常或增生的前列腺组织,Cit含量为8 000~15 000 nmol/g,而在PCa组织,其含量通常降至500 nmol/g以下[30]。恶性前列腺细胞中锌的含量同样明显降低,目前认为Cit与锌含量的降低是鉴别PCa与正常前列腺及良性前列腺增生的重要标志[30]。也有研究发现由于磷脂代谢的改变,PCa组织中胆碱成分含量增加[31]

MRSI除了可以观察到代谢产物共振强度的变化,还可以确定代谢产物的绝对及相对浓度。通常可以计算代谢产物峰值下面积,记作代谢物比值,也叫相对浓度。通过将数学曲线拟合到实验峰并计算曲线下面积可以得到峰值积分。绝对浓度的获得更为复杂,需要设定参考浓度、校正弛豫时间等[7]。目前,有关前列腺中代谢产物绝对浓度的研究较少。

近年来,动态核极化(dynamic nuclear polarization,DNP)技术已被用于获得体内13C光谱[32]。注入的超极化13C可以通过磁共振波谱监测标记的底物。13C-丙酮酸在许多实验中被广泛使用,因为它的季碳有一个相对较长的T1弛豫,并且在关键代谢途径(包括糖酵解和三羧酸循环)中处于中心位置。Nelson等[33]于2013年第1次在人类PCa中进行了体内超极化13C-丙酮酸的研究,证明了超极化13C-丙酮酸代谢成像的可行性和安全性。该研究表明与非癌性组织相比,PCa区域13C-乳酸盐/13C-丙酮酸盐的比值增加。

虽然有关MRSI应用的研究很多,但它并未被作为主流的磁共振检查手段用于前列腺的常规评估[7]。在由美国放射学会(American College of Radiology,ACR)和欧洲泌尿生殖放射学会(European Society of Urogenital Radiology,ESUR)共同出版的前列腺影像报告与数据系统(prostate imaging reporting and data system,PI-RADS)2.0版本中,已将MRSI从mpMRI方案中去除[34-35]。因为MRSI对扫描设备及扫描技师专业水平的要求均较高,同时前列腺MRSI过长的检查时间及烦琐的后处理也限制了其临床应用。

2 mpMRI在PCa诊断中的应用

传统的PCa诊断方法仍存在缺陷,易导致过度诊治及漏诊。mpMRI的出现成为解决这些问题的宝贵工具。使用mpMRI可以减少不必要的活组织检查、减少穿刺点的数量、避免假阴性结果,还可以筛选出低风险的患者从而进行监测。

2.1 mpMRI对PCa的诊断

2012年,ESUR发布指南,将前列腺MRI作为PI-RADS的一部分[27]。2014年,由ACR和ESUR共同出版的PI-RADS v2.0中建议对PCa进行mpMRI检查和PI-RADS评分[34-35]

de Rooij等[36]对mpMRI的诊断效能进行了meta分析,结果显示mpMRI具有很高的灵敏度和特异度。Hamoen等[37]认为基于mpMRI结果的PI-RADS评分对PCa的诊断具有很高的准确性。已有研究基于mpMRI参数并结合血清PSA,应用统计学方程来确定PCa的风险评分[38]

2.2 mpMRI在靶向穿刺中的应用

临床通常会建议在前列腺穿刺前进行mpMRI检查。MRI具有很高的阴性预测值,这意味着对那些极有可能穿刺阴性的患者可以推迟穿刺,而选择PSA随访。MRI有助于检测和定位前列腺的可疑区域,以便进行靶向活组织检查,这样可以减少取样误差,也更加有助于肿瘤的分级。

目前有3种不同的方式利用mpMRI数据来进行前列腺靶向穿刺,即认知融合(cognitive fusion)、TRUS-MRI融合和MRI-MRI融合。认知融合是指医师在TRUS引导下穿刺时,参考MRI进行穿刺。TRUS-MRI融合是指使用专用软件和硬件根据储存的磁共振图像及实时TRUS情况进行穿刺。MRI-MRI融合是在MRI台架内根据实时关联的磁共振图像进行穿刺。大量研究表明,应用MRI靶向穿刺对PCa的检出率明显高于TRUS引导[39-40],但有关3种靶向穿刺方法的比较研究相对较少。MRI引导的靶向穿刺需要的穿刺点更少,同时能够减少无意义癌的检出,这可以减少穿刺相关并发症的发生及避免过度诊治。一项名为前列腺MRI研究(prostate MR imaging study,PROMIS)的项目通过前瞻性队列研究方法对准备穿刺患者mpMRI的阴性预测值和阳性预测值进行了评估,结果提示患者mpMRI结果为阴性,可以推迟穿刺而进行影像学随访[40],这与Kumar等[41]的研究结论一致。

mpMRI在PSA水平升高而前期前列腺活组织检查阴性的患者中同样发挥重要作用。Girometti等[42]对PSA值处于灰区(4~10 ng/mL),而前期前列腺穿刺阴性的患者进行了mpMRI检查,其中癌症的患病率为19.2%,阴性预测值为100%。Abd-Alazeez等[43]对活组织检查阴性而PSA水平升高患者的mpMRI准确性进行了评估,其灵敏度为76%~100%,阴性预测值为79%~100%。

2018年Kasivisvanathan等[13]进行的一项多中心、随机研究表明,对临床怀疑PCa的患者首先进行MRI检查,对MRI提示PCa的患者进行MRI引导下的靶向穿刺可以有效提高临床有意义癌的检出率,并减少对临床无意义癌的过度诊治。这或将成为PCa诊断的新流程。

3 小结

综上所述,mpMRI可以早期发现具有临床意义的PCa,并能够提高穿刺活组织检查的准确性。对PSA水平升高、前期活组织检查阴性的患者行mpMRI检查,已被写入美国国家综合癌症网络(National Comprehensive Cancer Network,NCCN)指南、美国泌尿外科协会(American Urological Association,AUA)指南和欧洲泌尿外科协会(European Association of Urology,EAU)指南[44-46]。目前指南中并没有推荐在活组织穿刺前应用mpMRI对PCa进行初步评估,但在NCCN指南中增加了脚注来说明mpMRI在穿刺前发挥的作用[44]。基于mpMRI的PI-RADS评分系统的推荐使用,将增加报告的客观性和可靠性,并会促进PCa诊断效能的整体提升[47-48]。随着研究的进一步深入,加之放射组学及分子影像学的不断发展,mpMRI在PCa诊断中的价值将不断提升。

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