Advances in CT Functional Imaging and Artificial Intelligence for Assessing Esophageal Varices in Cirrhosis
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摘要:
肝硬化相关门脉高压引起的食管静脉曲张（EV），并由此导致的上消化道出血是最常见的并发症之一。内窥镜检查是诊断静脉曲张的“金标准”，但其属于侵入性检查，患者依从性较差，并且不便在短期内随访复查，在一定程度上限制了低出血风险患者中的应用。因此，临床上需寻找一种无创影像学方法，以准确诊断食管静脉曲张、评估其曲张程度，并预测潜在的出血风险。近年来，CT功能成像及人工智能新技术在食管静脉曲张的应用研究逐渐成为热点，二者相结合可能为有效诊断门静脉高压和食管静脉曲张提供新的策略。本文旨在对CT在食管静脉曲张诊断中的研究现状和进展进行综述，以期为临床诊断和治疗提供帮助。
Abstract:Esophageal varices (EV), which result from portal hypertension associated with cirrhosis, along with the consequent upper gastrointestinal bleeding, represent one of the most prevalent complications. Endoscopy is regarded as the "gold standard" for diagnosing varices; however, its invasive nature, coupled with poor patient compliance and the inconvenience of short-term follow-up, restricts its use in patients at low risk of bleeding. Consequently, there is a pressing need to identify a noninvasive imaging method that can accurately diagnose EV, evaluate their severity, and predict the risk of potential bleeding. In recent years, research focusing on the application of computed tomography (CT) functional imaging and novel artificial intelligence techniques in the context of EV has gained significant attention. The integration of these approaches may offer a new strategy for the effective diagnosis of portal hypertension and esophageal varices. This article aims to review the current research status and advancements in the use of CT for diagnosing EV, with the goal of assisting clinical diagnosis and treatment.
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继发性下肢淋巴水肿是指后天性淋巴回流受阻，淋巴液淤滞在组织间隙中导致下肢淋巴源性肿胀，多继发于腹、盆腔恶性肿瘤根治性切除和/或放化疗后，在癌症幸存者中发生率高达22％[1]。患者的生活质量下降，频繁发作蜂窝组织炎、淋巴管炎、静脉炎等并发症，罕见情况下会诱发血管内皮瘤或淋巴管瘤等恶性肿瘤[2]。本病治疗方式的选择与疾病的严重程度相关，主要有保守治疗、吸脂术、淋巴静脉吻合术等[3]。根据2016版国际淋巴学会共识[4]，评价下肢淋巴水肿严重程度依据患肢体积增大的百分比。
目前临床上广泛采用多径线测量法，该法简便易行，但受患者体型及测量者主观因素影响较大[5]。因此，寻找一种客观且重复性好的量化工具是临床应用的一项基本需求。
CT可量化分析脏器体积及脂肪含量，已广泛用于神经肌肉病、骨科创伤等肢体的体积测量[6-9]，但目前尚无将CT应用于淋巴水肿的报道。因此，本文旨在探讨CT在继发性下肢淋巴水肿的应用价值。
1. 材料与方法
1.1 一般资料
本研究通过首都医科大学附属北京世纪坛医院医院伦理委员会批准，分析2019年6月至2020年1月因继发性下肢淋巴水肿入我院的患者。
入组标准：①继发性下肢淋巴水肿诊断明确，如继发于直肠癌、宫颈癌、子宫内膜癌等恶性肿瘤，治疗后患者出现单侧下肢淋巴水肿；②下肢 CT成像资料完整；③签署知情同意书。排除标准：①其它原因导致的下肢淋巴水肿，如血栓、心衰、肝肾功能不全，代谢性下肢水肿；②肿瘤复发和/或转移者。
1.2 CT成像检查及测量法
所有检查均在GE Revolution CT完成，扫描范围自盆腔至双足。扫描参数：管电压80/140 kVp切换，自动管电流调节模式100～200 mA，噪声指数为12，Asir比例设置为40％，球管旋转时间0.5 s，螺距0.992︰1，探测器宽8 cm，矩阵512×512，SFOV 50 cm，层厚与层间隔设置为5 mm。
所得原始数据均以2.5 mm层厚、2.5 mm层间隔进行重建，所得CT图像均导入GE AW 4.7工作站，使用感兴趣体积工具，设定CT阈值范围为 -200至1000。
大腿测量范围上缘起自会阴水平，下缘达膝关节间隙水平，小腿测量范围以膝关节间隙水平以下至脚踝水平为准，全下肢测量范围以会阴水平以下至脚踝水平为准（图1）。分别记录双侧大腿、小腿及全下肢体积数据，计算（患侧大腿体积 - 健侧大腿体积）/健侧大腿体积、（患侧小腿体积 - 健侧小腿体积）/健侧小腿体积、（患侧全下肢体积 - 健侧全下肢体积）/健侧全下肢体积的百分比结果，并参照2016版国际淋巴协会共识[5]将所得结果进行分级。
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图 1 CT双下肢冠状面图像，大腿测量范围由会阴水平至膝关节间隙水平，小腿测量范围由膝关节间隙水平至脚踝水平，全下肢测量范围由会阴水平至脚踝水平Figure 1. CT imaging of both lower extre- mities. The measurement range of thigh is from perineum to knee, the measurement range of calf is from knee to ankle, and the measurement range of whole lower extremity is from perineum to ankle1.3 临床多径线测量法
由具有5年以上肢体测量经验的临床医师测量入组患者双侧下肢，分别记录患侧与健侧踝、小腿下1/3、小腿中1/2、小腿上1/3、膝、大腿下1/3、大腿中1/2、大腿上1/3、大腿根部的周径，以及相邻周径层面之间的长度距离（图2），采用圆锥体计算公式得出分段体积，将相应分段的体积相加计算为总体积。分别计算（患侧大腿体积 - 健侧大腿体积）/健侧大腿体积、（患侧小腿体积 - 健侧小腿体积）/健侧小腿体积、（患侧全下肢体积 - 健侧全下肢体积）/健侧全下肢体积的百分比结果，并参照2016版国际淋巴协会共识[5]将所得结果进行分级。
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图 2 临床多径线测量法的双下肢病例展示图，黑线为临床医师选取的下肢截面，从下到上依次为踝、小腿下1/3、小腿中1/2、小腿上1/3、膝、大腿下1/3、大腿中1/2、大腿上1/3及大腿根部Figure 2. The image of clinical multiple-circumference for both lower extre-mities. The black line is the cross section selected by the clinician. From bottom to top, it is ankle, lower 1/3 of calf, 1/2 of calf, and upper 1/3 of calf, Knee, lower 1/3 of thigh, 1/2 of thigh, upper 1/3 of thigh, and the root of thigh1.4 统计学分析
所有数据采用SPSS 25.0版软件进行统计分析，分别计算临床双下肢多径线测量法及CT双下肢体积测量法所得双侧大腿、小腿及全下肢体积的平均数及标准差。
采用配对t检验分别比较两种方法测量同一部位体积之间的差异，采用Kappa方法分析CT全下肢淋巴水肿分级与临床全下肢淋巴水肿分级之间的一致性。
2. 结果
2.1 患者一般资料
最终入组患者38例，女/男，34/4例，年龄范围32～71岁，中位年龄（51±10）岁，病程中位年限（3±7）年。主要临床表现为单侧下肢肿胀、皮肤粗糙，其中继发于子宫内膜癌7例，宫颈癌22例，卵巢癌4例，腹股沟肿瘤3例，阴茎癌1例，下肢皮肤病变1例。
2.2 测量结果
临床双下肢多径线测量法与CT双下肢体积测量法所得双侧大腿、小腿及全下肢体积的结果详见表1和表2。基于2016版国际淋巴协会共识，依临床与CT所得患侧比健侧全下肢、大腿及小腿体积增大的百分比值分别进行分级诊断，结果如表3。
表 1 临床多径线与CT测量患侧肢体体积值Table 1. The volume of the affected side by clinical multiple-circumference and CT部位 不同方法患侧肢体体积/cm3 统计检验 临床多径线 CT t P 全下肢 11308±2373 9984±2217 5.320 0.000 大腿 7122±1847 6515±1455 3.182 0.003 小腿 3973±1162 3462±1078 8.180 0.000 表 2 临床多径线与CT测量健侧肢体体积值Table 2. The volume of the healthy side by clinical multiple-circumference and CT部位 不同方法健侧肢体体积/cm3 统计检验 临床多径线 CT t P 全下肢 8265±1704 7154±1417 5.788 0.000 大腿 5763±1618 4917±1004 3.211 0.003 小腿 2714±562 2174±575 12.056 0.000 表 3 基于临床多径线与CT测量的下肢淋巴水肿分级Table 3. The grading of lower extremity lymphedema by clinical multiple-circumference and CT方法 下肢淋巴水肿分级分布/例 隐匿期 轻度 中度 重度 临床多径线全下肢分级 1 8 11 18 CT全下肢分级 1 6 14 17 临床多径线大腿分级 0 10 19 9 CT大腿分级 0 10 18 10 临床多径线小腿分级 1 10 8 19 CT小腿分级 1 8 10 19 统计学分析显示，CT双下肢体积测量法与临床双下肢多径线测量法对全下肢淋巴水肿分级的一致性非常好（Kappa=0.878），CT全下肢分级与CT大腿、小腿分级的一致性中等（Kappa=0.486/0.511）。
3. 讨论
继发性下肢淋巴水肿作为一种严重影响癌症幸存患者生活质量的慢性疾病，临床治疗目标主要包括减轻患肢沉重与疼痛感、预防患肢感染、改善患肢外观及功能等，但仅从患者主观感受不足以决定治疗方式的选择及评估疗效。本研究引用2016版国际淋巴学会共识制定的客观分级标准，首次将CT双下肢体积测量法与当前临床应用最广泛的多径线测量法进行了对照分析，两种方法分级的一致性非常好。
继发性下肢淋巴水肿的准确分级诊断可有效帮助临床评估与治疗。目前该类疾病公认的分级指标为患侧肢体体积增大百分比，临床常用体积测量方法如排水测量法、多径线测量法等[10-13]均存在不同程度的局限性，不但容易受到测量者主观因素影响，甚至会增加患者感染的风险。
影像学检查是一种无创的可精准量化的评价工具，研究表明，CT可用于液体、脂肪、肌肉等不同密度组织的定量分析中，并可评价靶组织及脏器体积，如肺结节、肝脏等，特别是对下肢肌肉萎缩和脂肪化程度的定量分析，在神经肌肉病、骨科创伤后等疾病的评价中已得到广泛认可[6-9]。因此本研究将CT应用于继发性下肢淋巴水肿患者肢体体积的测量中，根据患肢体积增大百分比进行分级，与临床多径线测量法分级一致的例数共有35/38例，高达92％。
研究结果表明，临床多径线测量法所得全下肢的体积值均大于CT双下肢体积测量法所得全下肢的体积值，这种差异也存在于大腿和小腿的体积测量中。出现这种差异的原因在于CT体积值是基于体素测量得出的精确数据，不受影像医师主观影响，而临床基于圆锥体计算公式的多径线测量法是估值数据，且圆锥体计算公式对不规则形态的淋巴水肿肢体存在一定的计算误差。
本研究中分别以患侧大腿或小腿体积增大百分比作为分级标准时，与全下肢分级结果的一致性中等，尤其在中度和重度组，大腿和小腿分别出现了过低分级和过高分级的情况（表3），这符合继发性下肢淋巴水肿多从远端向近端蔓延的发病趋势，小腿肿胀程度常较大腿为重，因此单独计算大腿或小腿体积变化不能代表全下肢，更不能决定治疗方式。
此外，本研究中CT剂量指数为4.88 mGy，剂量长度乘积范围约421～596 mGy·cm，有效剂量约0.0842～0.1192 mSv，但本研究主要针对恶性肿瘤患者，且辐射剂量远远低于传统的多时相腹腔及盆腔成像，这是因为下肢的转换系数（k=0.0002～0.0110）比腹盆腔低（k=0.0180）[14-16]。
本研究的不足：①本研究对于继发性下肢淋巴水肿患者的分级是基于体积增大百分比，然而，CT图像表明，处于同一分级的患肢组织成分（脂肪、肌肉）比例可能存在明显差异，即患肢体积增大百分比一致，但其内纤维化程度明显不同[17]，因此手术方式和难度存在很大差异，疗效和预后也大相径庭，所以基于体积的分级诊断有一定的局限性，下一步的研究将基于淋巴水肿肢体体积增大的不同组织成分进行精确量化分析与分级评价；②本研究样本量较小，下一步的研究将继续增加淋巴水肿病例数目及类型，不断寻求肢体淋巴水肿分级评价的最佳方法；③本研究未纳入MRI、核医学等影像学研究，期待进一步完善比较影像学研究。
4. 结论
CT双下肢体积测量法可以准确测量淋巴水肿肢体体积并进行分级，指导临床选择最佳治疗方案与评估疗效，对提高癌症幸存者生存质量意义深远。
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