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Journal of Southern Medical University logoLink to Journal of Southern Medical University
. 2022 Jun 20;42(6):922–928. [Article in Chinese] doi: 10.12122/j.issn.1673-4254.2022.06.17

微血流成像能准确鉴别和诊断胆囊息肉样病变

Differential diagnosis of gallbladder polypoid lesions by micro-flow imaging

朱 连华 1, 韩 鹏 1, 姜 波 1, 李 楠 1, 费 翔 1,*
PMCID: PMC9257369  PMID: 35790444

Abstract

目的

探讨微血流成像（MFI）评价胆囊息肉样病变血流灌注特征及鉴别诊断的价值。

方法

回顾性分析73例胆囊息肉样病变患者的临床资料和超声图像，根据病理结果分为肿瘤性息肉组（n=24）和非肿瘤性息肉组（n=49）。所有患者在胆囊切除术前均行常规超声、MFI和超声造影（CEUS）检查。比较彩色多普勒血流成像（CDFI）和MFI评价胆囊息肉样病变血流灌注特征的差异。运用加权Kappa一致性检验评估CDFI和MFI观察血流灌注特征与CEUS的一致性，并评价MFI在胆囊息肉样病变中的诊断效能。

结果

MFI和CDFI在评价胆囊息肉样病变血流灌注特征方面差异具有统计学意义（χ2=37.684，P < 0.001），MFI较CDFI能更准确显示息肉内血流灌注特征。CDFI和MFI对胆囊息肉样病变血流灌注特征评价与CEUS的一致性分别为0.118和0.816。MFI鉴别诊断肿瘤性息肉和非肿瘤性息肉的敏感性、特异性和准确性分别为75.00%、93.88%和87.67%。

结论

MFI显示息肉的血流灌注特征与CEUS具有较好的一致性，其能准确鉴别诊断肿瘤性息肉和非肿瘤性息肉，为胆囊息肉样病变患者选择合适的治疗方式提供新的超声诊断依据。

Keywords: 超声检查, 微血流成像, 胆囊息肉样病变

胆囊息肉样病变是临床最常见的胆道疾病之一，影响我国人群健康[1, 2]。胆囊肿瘤性息肉具有恶性或恶变潜能，需要行胆囊切除术[3]。因此准确鉴别胆囊息肉样病变的性质对于患者选择合适的治疗方式至关重要。超声是胆囊息肉样病变检查的最常用方法，通过评价息肉最大径、数量、回声等来鉴别其性质，但诊断准确性有待进一步提高[4-6]。胆囊息肉样病变血流灌注特征与其性质密切相关，常用彩色多普勒血流成像（CDFI）来评价息肉的血流灌注[7-9]。然而，由于息肉内血管纤细及血流缓慢，CDFI往往不能观察到其内血流灌注特征[10, 11]。超声造影（CEUS）能实时反映胆囊息肉样病变微循环灌注特征，在鉴别胆囊息肉样病变性质方面具有重要价值[12, 13]。然而CEUS检查具有耗时长，费用高等不利因素，影响其临床应用。微血流成像（MFI）是新的高分辨血流超声成像技术，其能在未使用超声造影剂的条件下准确评价微血管和低速血流，提高肝脏局灶性病变鉴别诊断的准确性[14-16]，但尚未有关胆囊息肉样病变MFI应用的研究。本研究将比较CDFI、MFI与CEUS评价胆囊息肉样病变血流灌注特征的一致性，旨在研究MFI评价胆囊息肉样病变血流灌注特征及鉴别诊断的价值。

1. 资料和方法

1.1. 研究对象

选取2021年1月~2021年7月因胆囊息肉样病变在解放军总医院第一医学中心就诊的患者。所有患者均于胆囊切除术前行常规超声、MFI和CEUS检查。纳入标准：（1）胆囊壁上非活动性局灶性隆起性病变；（2）胆囊局灶性病变的最大径≥1.0 cm；（3）胆囊切除术在超声检查结束后4周内；（4）病理证实为肿瘤性或非肿瘤性胆囊息肉样病变。排除标准：（1）存在CEUS检查禁忌症，如小于18岁、对造影剂过敏的患者等；（2）患者合并有其他腹部恶性肿瘤；（3）因结石等影响超声图像显示不满意。本研究被解放军总医院伦理委员会批准（审批号：S2022-006-01）。

1.2. 仪器与方法

本研究中使用飞利浦EPIQ7超声诊断仪，C5-1凸阵探头，频率为1~5 MHz，配有MFI及CEUS模式。检查前患者禁食8 h以上，患者于仰卧位或左侧卧位完成常规超声、MFI和CEUS检查。常规超声完整扫查胆囊，发现局灶性病变时，调节至合适图像，测量息肉的大小。分别采用CDFI和MFI观察息肉内血流灌注特征，壁滤波频率不超过50 Hz，调节取样框大小、血流速度和增益，使临近肝脏组织出现血流信号而无伪影。最后调节至CEUS模式，机械指数低于0.1，静脉注射1.5 mL Bracco公司的SonoVue，同时启动计时器，并保存动态图像。

1.3. 图像分析

根据病理结果，胆囊息肉样病变分为肿瘤性息肉和非肿瘤性息肉组。所有超声图像均由2名分别具有5年和15年腹部超声经验的医师分析，若两者不一致，则由两名医师讨论后确定。根据血流灌注特征分为Ⅰ-Ⅵ级：Ⅰ级，无血流信号；Ⅱ级，点状血流信号；Ⅲ级，线状血流信号；Ⅳ级，环状血流信号；Ⅴ级，分支状血流信号；Ⅵ级，不规则血流信号[7]。比较CDFI、MFI显示息肉的血流灌注特征能力，并评价与CEUS的一致性。

1.4. 统计学方法

应用SPSS26.0完成统计学分析。应用加权Kappa检验分析CDFI、MFI分别与CEUS的一致性。计量资料的正态性检验应用Kolmogorov-Smirnov法，正态分布以均数±标准差表示。计数资料比较采用卡方检验。P < 0.05为差异具有统计学意义。绘制受试者工作特征（ROC）曲线，分析MFI诊断肿瘤性息肉的敏感性、特异性、阳性预测值、阴性预测值及准确性。

2. 结果

2.1. 临床资料特征分析

73例胆囊息肉样病变患者中，肿瘤性息肉患者24例，非肿瘤性息肉患者49例。肿瘤性息肉包括腺瘤性息肉18例，胆囊癌6例，最大径范围为1.0~3.3 cm（表 1）。非肿瘤性息肉最大径范围为1.0~3.7 cm，包括胆固醇性息肉33例，胆囊腺肌症16例（表 1）。

1.

胆囊息肉样病变的一般情况

General characteristics of the patients with gallbladder polypoid lesions (Mean±SD)

Gallbladder polypoid lesions n Age (year) Maximum size (cm)
Cholesterol polyp 33 41.15±11.40 (24-64) 1.29±0.22 (1.0-1.7)
Adenomyosis 16 46.31±11.47 (24-66) 1.56±0.67 (1.0-3.7)
Adenomatous polyp 18 48.11±15.78 (19-72) 1.43±0.30 (1.0-2.1)
Gallbladder carcinoma 6 56.00±11.54 (41-71) 2.28±0.79 (1.4-3.3)
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2.2. 胆囊息肉样病变的血流灌注特征

MFI和CDFI在评价胆囊息肉样病变血流灌注特征方面差异具有统计学意义（χ2=37.684，P < 0.001，表 2）。在CDFI图像上，46例胆囊息肉样病变未见血流信号，而MFI图像上仅6例胆囊息肉样病变无血流信号。在40例CDFI示其内未见血流信号，而MFI可见血流信号的胆囊息肉样病变中，胆囊癌1例，腺瘤性息肉5例，胆囊腺肌症15例，胆固醇性息肉19例。

2.

对比CDFI与MFI评价胆囊息肉样病变的血流灌注特征

Comparison of blood flow characteristics of gallbladder polypoid lesions by CDFI and MFI

CDFI MFI Total
Grade Ⅰ Grade Ⅱ Grade Ⅲ Grade Ⅳ Grade Ⅴ Grade Ⅵ
Grade Ⅰ 6 10 9 15 4 2 46
Grade Ⅱ 0 3 7 0 6 2 18
Grade Ⅲ 0 0 2 0 2 0 4
Grade Ⅴ 0 0 0 0 2 0 2
Grade Ⅵ 0 0 0 0 0 3 3
Total 6 13 18 15 14 7 73
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在6例胆囊癌中，MFI图像中Ⅵ级血流灌注特征5例，Ⅲ级血流灌注特征1例；CDFI图像中Ⅵ级血流灌注特征仅2例，Ⅱ级血流灌注特征3例，剩余1例胆囊癌中未发现血流灌注（图 1）。18例腺瘤性息肉中，MFI图像中仅有1例未发现血流灌注，11例为Ⅴ级血流灌注特征；CDFI图像上6例未发现血流灌注，8例为Ⅱ级血流灌注特征（图 2）。16例胆囊腺肌症中，MFI图像中15例为Ⅳ级血流灌注特征，仅1例未发现血流灌注；而CDFI图像上全部胆囊腺肌症未发现血流灌注（图 3）。33例胆固醇性息肉中，MFI图像上26例为Ⅱ~Ⅲ级血流灌注特征，4例未发现血流灌注；而CDFI图像上23例未发现血流灌注，其余10例为Ⅱ~Ⅲ级血流灌注特征（图 4）。

1.

1

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胆囊癌血流灌注特征

Blood flow characteristics of gallbladder carcinoma. A: Gallbladder carcinoma on ultrasound image (arrow). B: Dotted blood flow on CDFI image (arrow). C: Irregular blood flow on MFI image (arrow). D: Irregular blood flow on CEUS image (arrow).

2.

2

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腺瘤性息肉血流灌注特征

Blood flow characteristics of adenomatous polyp. A: Adenomatous polyp on ultrasound image (arrow). B: Dotted blood flow on CDFI image (arrow). C: Branch-like blood flow on MFI image (arrow). D: Branch-like blood flow on CEUS image (arrow).

3.

3

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胆囊腺肌症血流灌注特征

Blood flow characteristics of adenomyosis. A: Adenomyosis on ultrasound image (arrow). B: Absent blood flow on CDFI image (arrow). C: Annular blood flow on MFI image (arrow). D: Annular blood flow on CEUS image (arrow).

4.

4

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胆固醇性息肉血流灌注特征

Blood flow characteristics of cholesterol polyp. A: Cholesterol polyp on ultrasound image (arrow). B: Absent blood flow on CDFI image (arrow). C: Single blood flow on MFI image (arrow). D: Single blood flow on CEUS image (arrow).

以CEUS动脉期胆囊息肉样病变的血流灌注特征为“金标准”，比较MFI与CDFI评价息肉内血流灌注特征的能力。CDFI显示血流灌注特征与CEUS相比，Kappa值为0.118（95%CI：0.030-0.207），仅有8例胆囊息肉样病变的CDFI评价血流灌注特征与CEUS一致。MFI显示血流灌注特征与CEUS相比，Kappa值为0.816（95%CI：0.720-0.911），59例胆囊息肉样病变的MFI评价血流灌注特征与CEUS一致。MFI显示胆囊息肉样病变血流灌注特征与CEUS的一致性优于CDFI与CEUS的一致性（Z=8.470，P < 0.001）。

2.3. MFI诊断效能

以Ⅴ-Ⅵ级血流灌注特征提示肿瘤性息肉，以Ⅰ-Ⅳ级血流灌注特征提示非肿瘤性息肉，MFI鉴别诊断肿瘤性息肉和非肿瘤性息肉的敏感性为75.00%，特异性为93.88%，阳性预测值为85.71%，阴性预测值为88.46%，准确性为87.67%，ROC曲线下面积为0.816（图 5A）。以Ⅵ级血流灌注特征提示胆囊癌，MFI鉴别诊断胆囊癌和腺瘤性息肉的敏感性为83.33%，特异性为88.89%，阳性预测值为71.43%，阴性预测值为94.12%，准确性为87.50%，ROC曲线下面积为0.824（图 5B）。

5.

5

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MFI诊断效能的ROC曲线

ROC curve for assessing diagnostic performance of MFI. A: ROC curve analysis of MFI in distinguishing neoplastic polyps from non-neoplastic polyps. B: ROC curve analysis of MFI in distinguishing gallbladder cancer from adenomatous polyps.

3. 讨论

非肿瘤性息肉是临床最常见的息肉，仅需随访观察，而肿瘤性息肉并不少见，其需行胆囊切除术[3, 17]。因此，准确鉴别肿瘤性息肉和非肿瘤性息肉具有重要意义。血流灌注是鉴别胆囊肿瘤性息肉和非肿瘤性息肉的重要特征[12, 18, 19]。由于肿瘤性息肉内血管增生扩张，微血管密度大，毛细血管分布于整个息肉内，故肿瘤性息肉内部血供较非肿瘤性息肉丰富[20, 21]。然而，CDFI难以显示微小血管或低速血流，故其难以准确显示胆囊息肉样病变内血流灌注，影响肿瘤性息肉的鉴别诊断[10, 15]。

MFI是一种新的高分辨血流超声成像技术，其应用更高级的算法鉴别血流与组织来源的多普勒信号，因此其能在未使用超声造影剂的条件下准确评价微血管和低速血流[22, 23]。与MFI相似的超微血流成像技术能清晰显示直径>100 μm、最低流速0.8 cm/s的低速微小血流，且其联合常规超声有助于胆囊息肉病变的鉴别诊断，但该研究未比较超微血流成像与CDFI在显示胆囊息肉样病变血流灌注中的差异[10]。MFI能显示直径为0.1 mm和流速为1 cm/s的血管[15]，故其较CDFI能发现胆囊息肉样病变中血管更细、流速更低的血流信号。本研究中MFI能发现91.78%的胆囊息肉样病变内血流灌注，而CDFI仅能发现36.99%的胆囊息肉样病变内血流灌注。胆囊癌是胆囊最常见的恶性肿瘤，其内有大量新生血管，肿瘤新生血管生长快，血管壁结构不完整，血管扩张，扭曲，且分布杂乱[24, 25]。因此，胆囊癌MFI图像上多为不规则血流灌注特征，而CDFI图像上多仅显示点状的血流灌注。腺瘤性息肉是常见的肿瘤性息肉，MFI图像上多为分支状血流灌注特征，这是由于腺瘤性息肉的滋养血管自胆囊壁进入息肉内呈分支状改变[26]。然而CDFI图像上腺瘤性息肉多未见血流灌注或点状血流灌注。胆囊腺肌症是胆囊黏膜上皮增生陷入或穿过肥厚肌层所形成的一种非肿瘤性息肉，其黏膜层和浆膜层较肌层血流丰富，CEUS动脉期表现为周边环状等增强，内为低增强[27]。MFI图像上胆囊腺肌症表现为环状血流灌注特征，而CDFI图像上胆囊腺肌症均未见血流灌注。胆固醇性息肉是最常见的胆囊息肉样病变，其内正常动脉逐渐变细，分为更细的血管均匀分布[28]。MFI图像上胆固醇性息肉的典型表现为点状或线状血流灌注，这与胆固醇性息肉血管分布特征相一致，而CDFI图像上多未能发现息肉内血流灌注。

CEUS是纯血池成像，能够观察组织或病灶内血管形态和分布，可作为评价血流灌注的“金标准”[29]。因此，本研究将CDFI、MFI显示的息肉内血流灌注特征与CEUS相比，发现MFI与CEUS的一致性较好，而CDFI与CEUS的一致性较差。MFI与CEUS图像上息肉血流灌注特征相同有59例，而CDFI与CEUS图像上一致的仅有8例。因此，与CDFI相比，MFI能更准确评价胆囊息肉样病变内血流灌注特征，更准确反应息肉内的血管形态，能为肿瘤性息肉和非肿瘤性息肉的鉴别诊断提供更准确的诊断信息。

最大径是鉴别胆囊息肉样病变性质的重要指标，目前临床通常认为最大径达到或超过1.0 cm的胆囊息肉样病变多为肿瘤性息肉，需要行胆囊切除术[17, 30]。然而，临床发现超过1.0 cm的息肉并非全部是肿瘤性息肉[12, 31]。本研究中胆囊息肉样病变的最大径均达到或超过1.0 cm，但仅有32.88%的胆囊息肉样病变为肿瘤性息肉。因此，仅凭息肉的最大径难以准确鉴别其性质。应用MFI评估胆囊息肉样病变的血流灌注特征鉴别诊断肿瘤性息肉和非肿瘤性息肉的敏感性为75.00%，特异性为93.88%，准确性为87.67%，具有较高的诊断效能。

本研究的局限性在于仅分析了MFI与CEUS显示胆囊息肉样病变血流灌注特征的一致性，但MFI显示血流灌注特征与病理标本上微血管密度间的关系将需进一步评价。此外，尽管MFI较CDFI能显示流速更低的血流和更细的血管，但是其仍不能显示内径小于100 μm的血管或流速低于1 cm/s的血流。

综上所述，与CDFI相比，MFI对胆囊息肉样病变内血流灌注特征的显示与CEUS具有较好的一致性，能较准确地反应息肉内血管形态。因此，采用MFI评价息肉血流灌注特征能提高鉴别胆囊息肉样病变性质的能力，从而为胆囊息肉样病变患者选择合适的治疗方式提供更有价值的超声诊断依据。

Biography

朱连华，主治医师，E-mail: zhulianhua27@163.com

Funding Statement

中国超声医师科技新星计划(KJXX2021004)

Contributor Information

朱 连华 (Lianhua ZHU), Email: zhulianhua27@163.com.

费 翔 (Xiang FEI), Email: george301feixiang@163.com.

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