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基于腹部CT体成分分析结合扩散峰度成像术前预测T3~T4期直肠癌肿瘤出芽级别的价值
陈安良 张钦和 李文豪 谢素玲 王秀林 王洪凯 孙祎楠 魏强 刘爱连

Cite this article as: CHEN A L, ZHANG Q H, LI W H, et al. The value of preoperative prediction of tumor budding grade in stage T3-T4 rectal cancer based on abdominal CT body composition analysis combined with diffusion kurtosis imaging technique[J]. Chin J Magn Reson Imaging, 2026, 17(9): 16-24.本文引用格式:陈安良, 张钦和, 李文豪, 等. 基于腹部CT体成分分析结合扩散峰度成像术前预测T3~T4期直肠癌肿瘤出芽级别的价值[J]. 磁共振成像, 2026, 17(9): 16-24. DOI:10.12015/issn.1674-8034.2026.09.003.


[摘要] 目的 探讨腹部CT体成分分析结合磁共振扩散峰度成像(diffusion kurtosis imaging, DKI)术前预测T3~T4期直肠癌肿瘤出芽(tumor budding, TB)级别的价值。材料与方法 回顾性分析89例术前行盆腔3.0 T MR及全腹CT检查并经手术病理证实的T3~T4期直肠腺癌患者资料,依据术后病理TB级别分为TB中低级别组(52例)、TB高级别组(37例)。两名观察者分别测量两组病灶的DKI定量参数值,包括各向异性分数(fractional anisotropy, FA)值、平均扩散系数(mean diffusivity, MD)值、平均扩散峰度(mean kurtosis, MK)值。使用TotalSegmentator工具自动分割全腹CT L3水平皮下脂肪、内脏脂肪、肌肉。使用Python编程语言编写皮下脂肪面积(subcutaneous fat area, SFA)、内脏脂肪面积(visceral fat area, VFA)、肌肉面积(muscle area, MA)计算程序,并计算VFA与SFA比值(VFA/SFA)、SFA与标准体质量(standard body weight, SBW)比值(SFA/SBW)、VFA与SBW比值(VFA/SBW)、MA与SBW比值(MA/SBW)、VFA与SFA差值(VFA-SFA)。使用组内相关系数(intra-class correlation coefficient, ICC)检验两名观察者间DKI各参数值测量一致性。采用独立样本t检验或Mann-Whitney U检验对组间DKI参数及体成分指标进行差异性比较。通过多因素logistic回归分析筛选出独立风险预测因子,并据此建立联合预测模型。利用受试者工作特征(receiver operating characteristic, ROC)曲线对各独立风险预测因子及联合预测模型的诊断效能进行评估。通过DeLong检验比较单一变量及联合预测模型的诊断效能差异,同时应用McNemar检验分析其敏感度及特异度差异。结果 DKI定量参数值在两名观察者间的测量一致性良好。TB高级别组MK、VFA、VFA/SBW值分别为0.938(0.891,1.019)、[150.620(107.685,199.840)] cm2、2.490(1.730,3.210),高于TB中低级别组0.776(0.685,0.878)、[117.205(72.067,169.762)] cm2、2.115(1.242,2.650);TB高级别组MD值为(1.113±0.105)μm2/ms,低于TB中低级别组(1.347±0.257)μm2/ms;上述参数两组间差异均具有统计学意义(P<0.05)。而两组在FA、SFA、MA、VFA/SFA、SFA/SBW、MA/SBW、VFA-SFA指标上差异未呈现出统计学意义(P>0.05)。经多因素logistic回归模型分析,MK值[比值比:4.104,95%置信区间(confidence interval, CI):2.223~7.578]和VFA/SBW值[比值比:2.335(95% CI:1.300~4.195)]是预测TB级别的独立风险预测因子(P<0.05)。MK、VFA/SBW值及两者的联合预测模型预测TB级别的曲线下面积(area under the curve, AUC)分别为0.838、0.627及0.886,敏感度分别为91.89%、72.97%及81.08%,特异度分别为67.31%、50.00%及80.77%。联合预测模型诊断效能优于VFA/SBW,且特异度优于MK、VFA/SBW,差异有统计学意义(P<0.05)。结论 对于T3~T4期直肠癌患者,DKI可以有效地预测TB级别,体成分分析亦可初步对TB风险进行分层,两者结合可明显提高对TB级别预测的准确性,为术前预测TB风险级别提供了宿主与肿瘤局部结合更全面的信息。
[Abstract] Objective This study aims to investigate the value of abdominal CT body composition analysis combined with diffusion kurtosis imaging (DKI) for the preoperative prediction of tumor budding (TB) grade in patients with T3 to T4 rectal cancer.Materials and Methods A retrospective analysis was conducted on data from 89 patients diagnosed with T3 to T4 rectal adenocarcinoma, confirmed by postoperative pathology. All patients underwent pelvic 3.0 T MRI and whole abdominal CT examinations prior to surgery. Based on the pathological results, the TB grade was categorized into two groups: a low-intermediate grade TB group (52 cases) and a high grade TB group (37 cases). Two observers measured the quantitative parameters of DKI in the lesions of both groups, including fractional anisotropy (FA) value, mean diffusivity (MD) value, and mean kurtosis (MK) value. The TotalSegmentator tool was utilized to automatically segment subcutaneous fat, visceral fat, and muscle at the L3 level of the abdominal CT scans. Python software facilitated the automatic calculation of subcutaneous fat area (SFA), visceral fat area (VFA), and muscle area (MA). The ratios of VFA to SFA (VFA/SFA), SFA to standard body weight (SBW) (SFA/SBW), VFA to SBW (VFA/SBW), MA to SBW (MA/SBW), and the difference between VFA and SFA (VFA-SFA) were calculated. The consistency of DKI parameters assessed by two observers was evaluated using the intra-class correlation coefficient (ICC). To examine the differences in DKI parameters and body composition indicators across the groups, either a Mann-Whitney U test or an independent sample t-test was utilized. A multivariate logistic regression analysis was performed to determine independent risk factors, which facilitated the creation of a combined prediction model based on these factors. The diagnostic performance of each individual risk factor, as well as the combined prediction model, was evaluated through the receiver operating characteristic (ROC) curve. To compare the diagnostic efficacy between the individual variables and the combined model, the DeLong test was employed, whereas the McNemar test was used to assess differences in sensitivity and specificity.Results The consistency of the DKI quantitative parameters measured by the two observers was good, with ICC values exceeding 0.75. In the high grade TB group, the MK, VFA, and VFA/SBW values were 0.938 (0.891, 1.019), [150.620 (107.685, 199.840)] cm2, and 2.490 (1.730, 3.210), respectively, significantly surpassing those in the low-intermediate grade TB group, which had values of 0.776 (0.685, 0.878), [117.205 (72.067, 169.762)] cm2, and 2.115 (1.242, 2.650). The MD value in the high grade TB group was (1.113 ± 0.105) μm2/ms, which was lower than that in the low-intermediate grade TB group (1.347 ± 0.257) μm²/ms. The differences between the two groups for all the aforementioned parameters were statistically significant (P < 0.05). The results of multivariate logistic regression analysis indicated that the MK value [odds ratio: 4.104, 95% confidence interval (CI): 2.223 to 7.578] and the VFA/SBW value [odds ratio: 2.335 (95% CI: 1.300 to 4.195)] were independent risk predictors for TB grade (P < 0.05). The area under the curve (AUC) for predicting TB grade based on the MK and VFA/SBW values, as well as their combined prediction model, were 0.838, 0.627, and 0.886, respectively. The sensitivity of these models was 91.89%, 72.97%, and 81.08%, respectively, while the specificity was 67.31%, 50.00%, and 80.77%, respectively. The diagnostic efficacy of the combined prediction model was superior to that of VFA/SBW alone, and its specificity exceeded that of both MK and VFA/SBW, with statistically significant differences (P < 0.05).Conclusions For patients with T3 to T4 rectal cancer, DKI has been shown to effectively predict TB grade. Additionally, body composition analysis serves to preliminarily stratify the risk of TB. The integration of these two modalities significantly enhances the accuracy of predicting TB grade, thereby providing more comprehensive insights into the interplay between host factors and local tumor characteristics for preoperative TB risk assessment.
[关键词] 直肠癌;肿瘤出芽;体成分分析;定量计算机断层扫描;磁共振成像;扩散峰度成像
[Keywords] rectal cancer;tumor budding;body composition analysis;quantitative computed tomography;magnetic resonance imaging;diffusion kurtosis imaging

陈安良 1, 2, 3   张钦和 1, 2, 3   李文豪 1   谢素玲 4   王秀林 5   王洪凯 2, 6   孙祎楠 6   魏强 1   刘爱连 1, 2, 3*  

1 大连医科大学附属第一医院放射科,大连 116011

2 大连市医学影像人工智能工程技术研究中心,大连 116011

3 辽宁省超极化磁共振专业技术创新中心,大连 116011

4 大连医科大学附属第一医院病理科,大连 116011

5 大连医科大学附属第一医院干细胞临床研究机构,大连 116011

6 大连理工大学医学部,大连 116011

通信作者:刘爱连,E-mail:cjr.liuailian@vip.163.com

作者贡献声明::刘爱连设计本研究的方案,对稿件重要内容进行了修改,获得了大连医科大学附属第一医院院内基金项目资助;陈安良起草和撰写稿件,获取、分析及解释本研究的数据;张钦和、李文豪、谢素玲、王秀林、王洪凯、孙祎楠、魏强获取、分析或解释本研究的数据,对稿件重要内容进行了修改,张钦和获得了辽宁省科技计划联合计划项目资助;全体作者都同意发表最后的修改稿,同意对本研究的所有方面负责,确保本研究的准确性和诚信。


基金项目: 辽宁省科技计划联合计划项目 2025-MSLH-199 大连医科大学附属第一医院院内基金项目 2019HZ007
收稿日期:2025-12-04
接受日期:2026-03-15
中图分类号:R814.42  R445.2  R737.37 
文献标识码:A
DOI: 10.12015/issn.1674-8034.2026.09.003
本文引用格式:陈安良, 张钦和, 李文豪, 等. 基于腹部CT体成分分析结合扩散峰度成像术前预测T3~T4期直肠癌肿瘤出芽级别的价值[J]. 磁共振成像, 2026, 17(9): 16-24. DOI:10.12015/issn.1674-8034.2026.09.003.

0 引言

       2022年国家癌症中心公布的恶性肿瘤统计数据显示,结直肠癌的患病率位居各类肿瘤第二位,其致死率在恶性肿瘤中位列第四[1],仅2022年中国新增结直肠癌病例51.7万例[2]。肿瘤出芽(tumor budding, TB)已被证实与肿瘤的侵袭性、转移潜能和不良预后密切相关[3]。T3~T4期直肠癌病灶累及肠壁全层至周围脂肪组织或侵犯邻近器官,治疗策略通常是新辅助治疗结合手术治疗[4]。然而,即使在接受完全根治性手术后,同一分期的直肠癌患者预后也会不同,有研究表明,高级别TB的T3~T4期直肠癌患者从新辅助治疗中获益有限,且为更差的肿瘤退缩分级及生存率的有力预测因子[5, 6, 7]。高级别肿瘤出芽作为直肠癌“高危”特征之一,强化新辅助治疗策略是合理的探索方向,如使用全程新辅助治疗模式、采用更强效的化疗方案,可能有助于克服其内在的治疗抵抗性;相反,对于低级别肿瘤出芽且其他临床病理特征良好的患者,则存在降阶梯治疗的可能性,减少治疗相关的长期毒性,对于达到临床完全缓解的患者,甚至可以考虑采用“等待观察”的非手术管理策略,以实现器官功能保留[8]。因此,如何在术前有效筛查,并对不同TB风险人群实施差异化干预,是临床管理中亟待解决的问题。

       体成分分析作为一种定量评估人体组成的重要方法,能够客观反映个体全身健康状况,在疾病风险评估、营养状况评价及运动医学等领域具有重要应用价值[9]。随着影像学及人工智能技术的进步,使基于影像学方法精准高效的体成分分析用于评估宿主营养及代谢表征成为可能[10, 11, 12]。目前,该技术已被用于直肠癌围手术期指标评估、并发症预测及预后分析等相关研究[13, 14, 15]

       当前,TB的确诊通常需依赖手术后的病理学检查。鉴于此,利用术前影像学技术对TB分级进行非侵入性判定具有显著的临床应用价值。已有基于MR功能成像、定量成像[16, 17, 18]、分子影像[19, 20]以及相关影像组学特征分析[21, 22, 23]、深度学习算法[24, 25, 26]等研究用于术前评估直肠癌TB级别,但仅限于肿瘤局部特征,未考虑宿主的全身状态。扩散峰度成像(diffusion kurtosis imaging, DKI)能反映微观结构的复杂性[27, 28, 29],在预测直肠癌预后风险因素、新辅助治疗疗效[30, 31, 32]等方面显示出很好的价值。本研究旨在探索基于腹部CT体成分分析结合DKI预测T3~T4期直肠癌TB级别的价值。

1 材料与方法

1.1 研究对象

       本研究遵守《赫尔辛基宣言》,经大连医科大学附属第一医院伦理委员会批准,免除受试者知情同意,批准文号:PJ-KS-KY-2019-49、PJ-KS-KY-2025-607。回顾性分析2015年9月至2025年7月期间在本院接受GE 3.0 T MRI检查,于一周内行手术切除且经病理证实为T3~T4期原发性直肠腺癌(术后病理包含TB信息)的患者96例。纳入标准:(1)患者具备完整的临床、实验室资料;(2)MRI扫描序列涵盖扩散加权成像(diffusion weighted imaging, DWI)、DKI、动态对比增强MRI(dynamic contrast-enhanced MRI, DCE-MRI)序列;(3)术前两周内行全腹CT检查。排除标准:(1)DKI图像拟合度差或伪影重(4例);(2)术前接受新辅助治疗或靶向治疗(3例)。最终89例患者入组。

1.2 扫描方法及技术参数

       采用3.0 T MRI系统(GE Signa HDxt, USA)实施盆腔MRI扫描。配置8通道腹部线圈,嘱受检者在检查前4小时禁食水以保持肠道清洁。扫描序列包括轴位DWI(b值为0、600 s/mm2)、DKI(b值为0、1000、2000 s/mm2,扫描方向数为15个)、DCE-MRI序列,扫描方案见表1

       采用单源双能CT(GE Revolution, GE Healthcare, USA)行全腹CT平扫。患者空腹6小时,于检查前20 min饮温开水800~1000 mL。扫描范围为自膈顶部至耻骨联合,扫描方案如下。管电压及管电流:(1)80 kVp和140 kVp瞬时切换,190~445 mA;(2)120 kVp,自动mA;(3)80 kVp,自动mA。余扫描及重建参数一致:螺距0.992∶1,矩阵512×512,旋转时间0.5 s/rot,探测器宽度80 mm,扫描与重建层厚及层间距均为5 mm,图像重建选用标准算法。

表1  MRI扫描序列及技术参数
Tab.1  MRI scanning sequence and technical parameters

1.3 临床及病理资料

       记录患者年龄、性别、体质指数(body mass index, BMI)、便血、肠癌家族史;计算标准体质量(standard body weight, SBW),其中男性标准体质量(kg)=[身高(cm)-80]×0.7,女性标准体质量(kg)=[身高(cm)-70]×0.6;癌胚抗原(carcinoembryonic antigen, CEA)水平、糖类抗原(carbohydrate antigen 19-9, CA19-9)水平;血细胞计数(中性粒细胞、淋巴细胞、单核细胞、血小板)。计算血液炎症指数:中性粒细胞/淋巴细胞比值(the neutrophil to lymphocyte ratio, NLR)、单核细胞/淋巴细胞比值(the monocyte to lymphocyte ratio, MLR)、血小板/淋巴细胞比值(the platelet to lymphocyte ratio, PLR)、血小板/单核细胞比值(the platelet to monocyte ratio, PMR);计算系统免疫炎症指数(systemic immune-inflammation index, SII),SII=血小板计数(×109 /L)×中性粒细胞计数(×109 /L)/淋巴细胞计数(×109 /L)。记录常规MRI评估指标,包括淋巴结转移、壁外血管侵犯、直肠系膜筋膜状态。

       采集术后病理资料,包括淋巴结转移、远处转移、病理大体分型、分化程度、脉管侵犯、神经侵犯。按照国际肿瘤出芽共识会议(International Tumor Budding Consensus Conference, ITBCC)标准对直肠癌TB进行量化评估,报告20倍物镜视野下,肿瘤浸润前沿TB最密集的区域(热点区)的出芽数目,依据出芽计数分为TB低级别(0~4个出芽)、TB中级别(5~9个出芽)和TB高级别(≥10个出芽)。

1.4 图像处理与数据测量

       将DWI和DKI序列影像导入AW 4.6工作站后,由两名腹部MRI诊断医师[分别具备5年(观察者1,主治医师)和11年(观察者2,副主任医师)诊断经验]采用Functool处理系统进行图像分析,生成表观扩散系数(apparent diffusion coefficient, ADC)、各向异性分数(fractional anisotropy, FA)、平均扩散系数(mean diffusivity, MD)、平均扩散峰度(mean kurtosis, MK)图。选择肿瘤实质的最大截面,基于DWI高信号区域、ADC低信号区域以及DCE-MRI(灌注期相10)显著强化区域,对应DKI图拟合最佳区域内放置3个类圆形感兴趣区(region of interest, ROI),其直径需大于肿瘤最大径或厚度1/3,同时规避坏死、囊变及肠腔结构。测量并记录DKI各参数值(图1),取平均值用于后续统计分析。

       选择L3水平全腹CT的横截面为ROI,使用开源自动分割工具TotalSegmentator(https://github.com/wasserth/TotalSegmentator)对图像中的皮下脂肪、内脏脂肪、肌肉进行自动分割(图1)。使用Python 3.9编程语言编写皮下脂肪面积(subcutaneous fat area, SFA)、内脏脂肪面积(visceral fat area, VFA)、肌肉面积(muscle area, MA)计算程序,并计算VFA与SFA比值(VFA/SFA)、SFA与SBW比值(SFA/SBW)、VFA与SBW比值(VFA/SBW)、MA与SBW比值(MA/SBW)、VFA与SFA差值(VFA-SFA)。体成分分析分割与面积计算流程如图2所示。

图1  男,64岁,BMI为20.83 kg/m2,SBW为68.60 kg,直肠腺癌低级别肿瘤出芽患者,分期为T3N0M0。1A:DWI示直肠下段环壁增厚伴局部隆起的高信号灶,最大层面大小约27.2 mm×22.9 mm;1B:ADC图示病灶呈低信号;1C:DCE-MRI示病灶明显强化;1D~1F:DKI后处理图像,FA、MD、MK平均值分别为0.200、1.347 μm2/ms、0.794;1G:L3水平CT体成分分割图,皮下脂肪(蓝色)、内脏脂肪(黄色)、肌肉(红色)区域面积分别为59.69 cm2、99.18 cm2、115.78 cm2;1H:病理图(HE ×200)示肿瘤浸润前沿处小于4个芽。BMI:身体质量指数;SBW:标准体质量;DWI:扩散加权成像;ADC:表观扩散系数;DCE-MRI:动态对比增强磁共振成像;DKI:扩散峰度成像;FA:各向异性分数;MD:平均扩散系数;MK:平均扩散峰度。
Fig. 1  A 64-year-old male patient with a BMI of 20.83 kg/m2 and a SBW of 68.60 kg, diagnosed with low-grade tumor budding in rectal adenocarcinoma, classified as T3N0M0. 1A: DWI reveals thickening of the lower rectal wall, accompanied by a locally protruding high-signal lesion, with the largest dimensions measuring approximately 27.2 mm × 22.9 mm; 1B: ADC map shows low signal intensity; 1C: DCE-MRI demonstrates significant enhancement of the lesion; 1D-1F: DKI post-processing maps indicate average values of FA, MD, and MK of 0.200, 1.347 μm2/ms, and 0.794, respectively; 1G: The CT body composition segmentation map at the L3 level, depicting subcutaneous fat (blue area), visceral fat (yellow area), and muscle (red area) areas measuring 59.69 cm2, 99.18 cm2, and 115.78 cm2, respectively; 1H: The pathological image (HE ×200) reveals fewer than four buds at the forefront of tumor infiltration. BMI: body mass index; SBW: standard body weight; DWI: diffusion weighted imaging; ADC: apparent diffusion coefficient; DCE-MRI: dynamic contrast-enhanced MRI; DKI: diffusion kurtosis imaging; FA: fractional anisotropy; MD: mean diffusivity; MK: mean kurtosis.
图2  全腹平扫CT体成分分析分割与面积计算流程图。SFA:皮下脂肪面积;VFA:内脏脂肪面积、MA:肌肉面积。
Fig. 2  Flowchart of body composition analysis segmentation and area calculation for abdominal plain scan CT. SFA: subcutaneous fat area; VFA: visceral fat area; MA: muscle area.

1.5 统计学分析

       采用SPSSAU 25.0及MedCalc 15.2.2进行统计学分析。对于分类变量,采用卡方检验或Fisher确切概率法进行分析。通过组内相关系数(intra-class correlation coefficient, ICC)评估两名观察者所测DKI参数的一致性(ICC≤0.40表示一致性较差,0.40<ICC<0.75表示一致性中等,ICC≥0.75表示一致性良好),后续统计采用两者测量结果的平均值。对于定量数据,通过Shapiro-Wilk检验其正态性。符合正态分布的数据采用均数±标准差描述,组间比较采用独立样本t检验;非正态分布数据则以中位数(25%分位数,75%分位数)表示,采用Mann-Whitney U检验进行组间差异分析,对于组间差异具有统计学意义的指标,进行单因素logistic回归分析,并使用多因素logistic回归筛选独立风险预测因子,并构建由这些因子组成的联合预测模型。采用受试者工作特征(receiver operating characteristic, ROC)曲线评估独立风险预测因子及联合预测模型的诊断效能,计算曲线下面积(area under the curve, AUC),并依据最大约登指数确定最佳阈值及其对应的敏感度与特异度。通过DeLong检验比较独立风险预测因子及联合预测模型的诊断效能差异,采用McNemar检验比较其敏感度和特异度差异。以P<0.05为差异具有统计学意义。

2 结果

2.1 患者一般资料

       本研究共纳入89例患者,其中TB中低级别组52例,TB高级别组37例。两组患者临床及病理资料比较见表2。BMI、SII在两组间差异存在统计学意义(P<0.05),而其他临床、病理指标在两组间差异未见统计学意义(P>0.05)。

表2  两组患者临床及病理指标比较
Tab. 2  Comparison of clinical and pathological data of the two groups of patients

2.2 两组DKI各参数值两名观察者间一致性检验

       对两名观察者测得的DKI各参数值进行一致性检验结果显示,FA、MD和MK值在两名观察者间一致性良好(ICC>0.75),如表3所示。

表3  两组患者DKI定量参数值两名观察者一致性比较
Tab. 3  Consistency comparison of quantitative parameters of DKI between the two groups of patients by two observers

2.3 两组DKI各参数值的差异性分析

       TB高级别组MD值低于中低级别组,MK值高于中低级别组,两组间差异均存在统计学意义(P<0.05);而两组间FA值差异无统计学意义(P>0.05)。详见表4

表4  两组DKI各定量参数值差异性比较结果
Tab. 4  Comparison of the differences in quantitative parameters of DKI between the two groups

2.4 两组体成分分析参数的差异性分析

       TB高级别组VFA、VFA/SBW值高于中低级别组,两组间差异具有统计学意义(P<0.05);而两组间SFA、MA、VFA/SFA、SFA/SBW、MA/SBW、VFA-SFA值差异未见统计学意义(P>0.05),如表5所示。

表5  两组体成分分析各参数值差异性比较结果
Tab. 5  Comparison of the differences in quantitative parameters of body composition analysis between the two groups

2.5 两组定量参数单因素及多因素logistic回归分析

       对两组差异存在统计学意义的临床、血液炎性指标、DKI定量参数、体成分参数进行单因素logistic回归分析及多因素logistic回归分析,采用forward向前法筛选独立预测因子。结果显示,MK值[比值比:4.104,95%置信区间(confidence interval, CI):2.223~7.578]和VFA/SBW值[比值比:2.335(95% CI:1.300~4.195)]是预测TB等级的独立风险预测因子(P<0.05),如表6所示。

表6  两组定量参数logistic回归分析
Tab. 6  Logistic regression analysis of quantitative parameters between the two groups

2.6 两组MK、VFA/SBW及其联合预测模型诊断效能比较

       MK、VFA/SBW及其联合预测模型评估直肠癌不同TB级别的AUC值分别为0.838、0.627及0.886(表7图3)。DeLong检验示联合预测模型AUC优于VFA/SBW,差异具有统计学意义(P<0.001),与MK差异无统计学意义(P=0.111)(表8)。McNemar检验示联合预测模型特异度较MK、VFA/SBW提升(P<0.05),MK、VFA/SBW与联合预测模型间特异度、敏感度差异无统计学意义(P>0.05)。

图3  MK、VFA/SBW及其联合预测模型预测TB级别的ROC曲线图。MK为平均扩散峰度;VFA为内脏脂肪面积;SBW为标准体质量;VFA/SBW:VFA与SBW比值;TB为肿瘤出芽;ROC为受试者工作特征。
Fig. 3  The ROC curves of MK, VFA/SBW and the combined prediction model for predicting the TB level. MK: mean kurtosis; VFA: visceral fat area; SBW: standard body weight; VFA/SBW: ratio of VFA to SBW; TB: tumor budding; ROC: receiver operating characteristic.
表7  两组MK、VFA/SBW及联合预测模型诊断效能分析
Tab. 7  Comparison of diagnosis efficacy of MK, VFA/SBW and the combined prediction model between the two groups
表8  各参数值及联合模型诊断效能比较DeLong检验结果
Tab. 8  DeLong test results of the diagnostic efficiency between two groups

3 讨论

       本研究主要应用腹部CT体成分分析联合DKI技术预测T3~T4期直肠癌TB级别,并建立联合预测模型,结果发现TB高级别组MK、VFA、VFA/SBW值高于中低级别组,而MD值低于中低级别组。其中MK及VFA/SBW为独立风险预测因子,由两者建立的联合预测模型AUC显著高于VFA/SBW,且联合预测模型较单独MK、VFA/SBW的特异度均显著提高。首次尝试用体成分分析联合DKI技术评估T3~T4期直肠癌TB级别,为术前识别TB高风险人群及制订个体化治疗方案提供了宿主结合肿瘤共同评估的新视角。

3.1 直肠癌TB定义与T3~T4期直肠癌TB不同级别临床诊疗意义

       TB是指在肿瘤浸润前沿(肿瘤-间质界面)出现的由不超过4个肿瘤细胞构成的离散细胞簇。这一概念着重强调了TB细胞在形态学上的特征,反映了肿瘤的上皮-间质转化(epithelial-mesenchymal transition, EMT)过程,是侵袭性和转移潜能的标志[3, 33, 34]。TB与直肠癌新辅助治疗疗效、手术范围选择及辅助治疗策略密切相关,美国癌症联合委员会(American Joint Committee on Cancer, AJCC)、国际抗癌联盟(Union for International Cancer Control, UICC)癌症分期指南以及中国结直肠癌诊疗规范已将其列为直肠癌的附加预后因素[4, 35]。对于错配修复基因功能完整或微卫星高度不稳定性表达患者,推荐使用免疫治疗,且治疗有效[36]。因此,对于错配修复基因功能缺陷或微卫星稳定性表达患者的T3~T4期直肠癌患者应术前接受新辅助治疗[4],但有研究表明无论是否进行新辅助治疗,TB阳性均与较低的5年总生存率和无病生存率显著相关,且高级别TB可显著增加5年疾病复发风险和远处转移风险,提示此类人群从新辅助治疗中受益有限[5, 37, 38]。另有一项研究表明,高级别TB与新辅助放化疗后较差的退缩分级显著相关,对于术前T3~T4期患者低级别TB治疗后T分期降期效果明显优于高级别TB[7]。所以,TB不仅是一个形态学指标,更反映了肿瘤内在的侵袭性和治疗抵抗潜能。在新辅助治疗时代,TB作为局部晚期直肠癌一个不可或缺的预后病理学标志物,高级别TB与较差的病理学治疗反应、更高的病理分期以及显著缩短的生存期独立相关,在识别新辅助治疗后高危复发患者、指导辅助治疗决策中具有潜在的临床价值,因此对于T3~T4期直肠癌患者的临床评估应充分考虑TB的影响。然而,TB作为术后病理学特征,无法更好地为术前治疗方案提供帮助,且在实际病理评估中面临重复性和标准化的挑战[39]。因此,术前通过无创手段预测直肠癌TB级别,有助于临床对高级别TB患者进行个体化管理,如适当扩大淋巴结清扫范围、调整新辅助治疗方案、加强对异时性远处转移的监控等。

3.2 DKI参数预测T3~T4期直肠癌TB级别价值评估

       DKI技术作为DWI的衍生技术,通过引入非高斯分布模型,比常规DWI更能准确反映生物组织及细胞微结构的复杂性和空间异质性特征[27, 40, 41]。MK是量化水分子多向扩散峰度的综合指标,其数值变化直接体现组织微观结构的复杂程度[42]。在本组病例中,高级别TB组的MK值明显高于中低级别组,原因可能为高级别TB细胞异型性显著,形态不规则,胞质丰富且易于融合,同时在EMT过程中,肿瘤细胞失去极性及细胞间连接,转化为间质样细胞,导致肿瘤前沿区域细胞排列紊乱,复杂性增加[43, 44],进而导致MK值升高。MD作为校正后的表观扩散系数,排除了非高斯分布的影响,能够准确表征体素内水分子的平均扩散率[29]。在本组病例中,高级别TB组的MD值显著低于中低级别组,原因可能为EMT驱动肿瘤细胞迁移与增殖,导致高级别TB区域肿瘤细胞排列更为密集,同时EMT过程中产生的相关细胞及蛋白增多[45],进一步使局部肿瘤组织密度升高,细胞外间隙减小,水分子弥散运动受限,引起MD值减低。因此,通过对肿瘤区域进行DKI分析,特别是MK值(AUC=0.838),可在术前有效评估T3~T4期直肠癌TB级别。

3.3 体成分分析预测T3~T4期直肠癌TB级别价值评估

       脂肪组织与多种癌症的发病风险密切相关。作为活跃的内分泌器官,脂肪组织能够分泌瘦素、肿瘤坏死因子α、白介素6等多种脂肪因子,共同参与调控肿瘤的发生、侵袭、血管生成、炎症反应及免疫逃逸等过程[46, 47],继而促进EMT,导致TB数目增加。因此,能够准确进行脂肪定量分析的技术在临床与研究中显得尤为重要,而体成分分析正是其中一种重要方法。此外,腹部CT是直肠癌术前常规检查,图像容易获取和分析,也为相关评估提供了便利。本研究中高级别TB组VFA、VFA/SBW高于中低级别组,而SFA两组间无差异,进一步证明VFA更具生物能量活性[47]。值得注意的是,虽然两组患者的BMI存在统计学差异,但由于BMI仅整合身高与体质量参数,无法区分脂肪与肌肉组织,亦不能反映脂肪组织在体内的具体分布;而单纯的VFA值未能考虑到不同体型个体间的差异。这些局限性导致二者均未能成为预测TB分级的独立风险预测因子。相比之下,VFA/SBW通过体质量标准化处理,有效消除了体型差异对内脏脂肪评估的影响,使其成为判断TB级别的可靠独立风险预测因子。此外,本研究中高级别TB组SII值显著高于中低级别TB组,也提示不同TB分级的直肠癌患者在全身炎症与免疫状态上存在差异,且这种差异可能与内脏脂肪蓄积程度相关。综上,基于全身体成分分析中的VFA及VFA/SBW值,可在术前有效评估患者的全身炎症与免疫状态,从而预测TB级别。

3.4 体成分分析联合DKI技术预测T3~T4期直肠癌TB级别价值评估

       本研究结果显示体成分分析及DKI技术均能够预测T3~T4期直肠癌TB级别,多因素回归分析发现MK、VFA/SBW为独立风险预测因子,提示DKI和体成分分析从不同维度预测T3~T4期直肠癌TB级别。MK主要聚焦于肿瘤局部组织复杂性,而VFA/SBW则反映了全身脂肪分布状态,揭示肿瘤与宿主间的复杂相互作用。由MK及VFA/SBW构建的联合预测模型,其诊断效能虽未显著超越MK值,但特异度较单一变量均得到明显提升。这一优势使得联合预测模型对T3~T4期直肠癌TB分级的预测更为可靠,临床应用价值更高,为T3~T4期直肠癌多模型临床管理提供了可靠的影像学依据。

3.5 局限性

       本研究仍存在以下局限性:(1)本研究ROI主要基于肿瘤最大层面DWI高信号区、ADC低信号区及DCE-MRI明显强化区选取,未采用全肿瘤轮廓勾画方式,可能导致影像特征未能充分反映肿瘤的异质性。(2)本研究未能提取直肠系膜脂肪并进行分析,未来将同时纳入肠系膜脂肪面积/密度等局部指标,探讨其与TB及全身性脂肪指标的相互作用。(3)本研究纳入病例数有限,且VFA和VFA/SBW差异处于统计学意义的边缘,后续研究需进一步扩大样本量,并开展多中心验证各模型的稳健性。

4 结论

       DKI序列的MK值可针对肿瘤内部结构复杂性,实现对不同TB级别的术前无创预测。而基于腹部CT的体成分分析可评估患者全身状态,用于不同TB级别人群的分层。MK与VFA/SBW构建的联合预测模型大大提高了预测的精准度,通过整合肿瘤特征与宿主状态双重维度,为T3~T4期直肠癌不同TB级别的多模型临床管理提供了新的综合依据。

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