基于mDixon-Quant定量参数术前无创预测胰腺导管腺癌病理分化及Ki-67表达的研究

分享到微信朋友圈

• 特别关注 •

陈坤阮志兵石仕晗陈慧淋文凤徐茂丽唐戈雅

Cite this article as: CHEN K, RUAN Z B, SHI S H, et al. Non-invasive preoperative prediction of histological differentiation and Ki-67 expression level in pancreatic ductal adenocarcinoma based on mDixon-Quant sequence[J]. Chin J Magn Reson Imaging, 2025, 16(5): 30-36.本文引用格式：陈坤, 阮志兵, 石仕晗, 等. 基于mDixon-Quant定量参数术前无创预测胰腺导管腺癌病理分化及Ki-67表达的研究[J]. 磁共振成像, 2025, 16(5): 30-36. DOI:10.12015/issn.1674-8034.2025.05.005.

摘要

[摘要] 目的探讨基于mDixon-Quant序列衍生的定量参数值术前预测胰腺导管腺癌（pancreatic ductal adenocarcinoma, PDAC）病理分化程度及Ki-67表达水平的可行性及价值。材料与方法 回顾性分析经病理证实的57例PDAC患者的临床、影像及病理资料。按照病理分化程度分为高分化组30例，低分化组27例。分析两组的临床基线资料（年龄、性别、腹痛、黄疸、术前CA19-9水平等）、常规影像学特征（部位、形态、边界、肿瘤长短径、胰管有无扩张、血管侵犯等）、定量参数（水相值、脂相值、T2^*值、R2^*值及脂肪分数）。按照1∶1的比例收集病例组与对照组正常胰腺的定量参数值进行对照。同时对31例病例按照Ki-67表达水平将其分为高表达组（Ki-67≥50%）和低表达组（Ki-67<50%）。使用组内相关系数（intra-class correlation coefficient, ICC）评估观察者间评价的一致性；采用Mann-Whitney U检验、t检验或χ²检验比较不同分化组间各参数的差异，绘制受试者工作特征（receiver operating characteristic, ROC）曲线并计算曲线下面积（area under the curve, AUC）评价各指标的预测效能；采用DeLong检验比较各AUC之间的效能差异。结果 PDAC高分化组与低分化组之间年龄差异有统计学意义，低分化组年龄小于高分化组（P=0.006）；性别、症状、术前CA19-9水平、肿块形态、部位、有无胰管扩张等差异均无统计学意义（P>0.05）。脂相值、T2^*值、R2^*值及脂肪分数在健康胰腺组与PDAC组、PDAC病灶与胰腺正常区域组间差异均具有统计学意义（P<0.05）；高低分化组的T2^*和R2^*值差异有统计学意义（P<0.05），与高分化组相比，低分化组的T2^*值更高[（58.92±7.84）ms vs.（47.87±6.76）ms]，R2^*值更低[17.73（15.62，19.77）s^-1 vs. 21.57（19.65，24.69）s^-1]；T2^*、R2^*值预测病理分化程度的AUC分别为0.866和0.827，敏感度和特异度分别为77.8%、74.1%和80.0%、83.3%；T2^*、R2^*值两者联合预测病理分化程度的AUC为0.863；Ki-67高表达组与低表达组的T2^*、R2^*值差异有统计学意义（P<0.05），高表达组的T2^*值较低表达组的更高[（55.57±8.77）ms vs.（49.23±6.09）ms]，R2^*值更低[18.48（16.45，22.05）s^-1 vs. 20.87（19.56，22.03）s^-1]。T2^*、R2^*值预测Ki-67表达水平的AUC分别为0.727和0.662，敏感度和特异度分别为71.4%、64.7%和64.3%、70.6%；T2^*、R2^*值两者联合预测Ki-67表达水平的AUC为0.752。与单一参数相比，T2^*、R2^*值两者联合对于PDAC病理分化及Ki-67表达的预测效能差异并无统计学意义。结论 mDixon-Quant序列各定量参数值中，T2^*、R2^*值对PDAC病理分化程度及Ki-67表达水平有较好的预测价值，除水相值外，各定量参数均可有效区分PDAC病灶与胰腺正常区域。

[Abstract] Objective To investigate the feasibility and clinical value of quantitative parameters derived from the mDixon-Quant sequence in preoperative non-invasive prediction of histological differentiation grade and Ki-67 expression level in patients with pancreatic ductal adenocarcinoma (PDAC).Materials and Methods A retrospective analysis was conducted on the clinical, radiological, and a cohort of 57 cases exhibiting pathologically confirmed PDAC. According to the histological differentiation degree, 57 patients were divided into well-differentiated group (n = 30) and poorly differentiated group (n = 27). The basic clinical data of the two groups (age, gender, abdominal pain, jaundice, preoperative CA19-9 level, etc.), conventional imaging features (location, morphology, boundary, long and short diameters of the tumor, whether there is dilation of the pancreatic duct, vascular invasion, etc.) and quantitative parameters [water phase value, fat phase value, T2^* value, R2^* value and fat fraction (FF)] were analyzed. The quantitative parameter values of healthy pancreases were collected for normal control according to the ratio of the case group to the normal group (1∶1). At the same time, 31 cases with Ki-67 expression level results were analyzed, and they were divided into high expression (Ki-67 ≥ 50%) and low expression groups (Ki-67 < 50%). The intra-class correlation coefficient (ICC) was used to evaluate the repeatability. The Mann-Whitney U test, t test or χ² test was used to compare the differences of various parameters between the two groups. The receiver operating characteristic (ROC) curve was drawn and the area under the curve (AUC) was calculated to evaluate the predictive efficacy of relevant indicators. The efficacy of different AUCs was compared by employing the DeLong test.Results A statistically significant age disparity was observed between the well-differentiated and poorly differentiated subgroups. Patients with poorly differentiated demonstrated a modestly younger compared to the well-differentiated cohort (P = 0.006). However, there were no statistically significant differences in gender, symptoms, CA19-9 level, mass morphology, location, and whether there was dilation of the pancreatic duct, etc. Except for the water phase value, there were statistically significant differences between the healthy pancreas group and the PDAC group, as well as between the patient's lesion and the normal pancreatic area (P < 0.05). Furthermore, the well-differentiated and poorly differentiated cohorts demonstrated significantly divergent T2^* and R2^* parameters (P < 0.05). Compared with the well-differentiated group, the T2^* value of the poorly differentiated group was higher [(58.92 ± 7.84) ms vs. (47.87 ± 6.76) ms]; and the R2^* value was lower [17.73 (15.62, 19.77) s^-1 vs. 21.57 (19.65, 24.69) s^-1]. The AUCs of the T2^* and R2^* values for predicting the histological differentiation degree were 0.866 and 0.827, respectively. The sensitivity and specificity of T2^* were 77.8% and 74.1%, respectively, while those of R2^* were 80.0% and 83.3%, respectively. The combined diagnostic AUC of T2^* and R2^* values predicted pathological differentiation grade was 0.863.There were statistically significant differences in the T2^* and R2^* values between the high and the low Ki-67 expression group (P < 0.05). The T2^* value of the high expression group was higher than that of the low expression group [(55.57 ± 8.77) ms vs. (49.23 ± 6.09) ms], and the R2^* value was lower [18.48 (16.45, 22.05) s^-1 vs. 20.87 (19.56, 22.03) s^-1]. The AUCs of the T2^* and R2^* values for predicting the Ki-67 expression level were 0.727 and 0.662, respectively. The sensitivity and specificity of T2^* were 71.4% and 64.7%, respectively, while those of R2^* were 64.3% and 70.6%, respectively. The combined diagnostic AUC of T2^* and R2^* values predicted Ki-67 expression level was 0.752. Compared with individual parameters, the combined use of T2^* and R2^* values showed no statistically significant difference in predictive efficacy for both pathological differentiation and Ki-67 expression level in PDAC.Conclusions The T2^* and R2^* values have good predictive value for the pathological differentiation degree of PDAC and the expression level of Ki-67 among the quantitative parameters of the mDixon-Quant sequence; except for the water phase value, each quantitative parameter can effectively distinguish between the PDAC lesion and the normal pancreatic area.

[关键词] 胰腺导管腺癌；磁共振成像；魔镜成像；病理分化；Ki-67

[Keywords] pancreatic ductal adenocarcinoma；magnetic resonance imaging；mDixon-Quant；histological differentiation；Ki-67

作者信息

陈坤 ¹ 阮志兵 ^1* 石仕晗 ² 陈慧淋 ¹ 文凤 ² 徐茂丽 ¹ 唐戈雅 ¹

¹ 贵州医科大学附属医院影像科，贵阳　550004

² 贵州医科大学，贵阳　550001

通信作者：阮志兵，E-mail: 1368105787@qq.com

作者贡献声明：阮志兵设计本研究的方案，对稿件重要内容进行了修改，获得了贵州省基础研究计划（自然科学）面上项目及贵州医科大学附属医院博士科研启动基金项目的支持；陈坤起草和撰写稿件，获取、分析和解释本研究的数据；石仕晗、陈慧淋、文凤、徐茂丽、唐戈雅获取、分析或解释本研究的数据，对稿件重要内容进行了修改；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。

出版信息

基金项目： 2025年贵州省基础研究计划（自然科学）面上项目黔科合基础MS〔2025〕437 贵州医科大学附属医院博士科研启动基金项目 gyfybsky-2024-49

收稿日期：2025-02-28

接受日期：2025-05-10

中图分类号：R445.2 R735.9

文献标识码：A

DOI: 10.12015/issn.1674-8034.2025.05.005

本文引用格式：陈坤, 阮志兵, 石仕晗, 等. 基于mDixon-Quant定量参数术前无创预测胰腺导管腺癌病理分化及Ki-67表达的研究[J]. 磁共振成像, 2025, 16(5): 30-36. DOI:10.12015/issn.1674-8034.2025.05.005.

正文

0 引言

胰腺导管腺癌（pancreatic ductal adenocarcinoma, PDAC）是一种致死率极高的恶性肿瘤，具有起病隐匿、易发生局部血管侵犯及转移、化疗耐药、术后复发率高、预后差等特点，5年生存率约为10%^[¹^,²^,³^]，近年来发病率与死亡率呈逐年上升趋势，已成为威胁全球民众健康且加剧癌症负担的癌症之一^[⁴^,⁵^]。手术切除是治愈PDAC的唯一机会，然而有机会接受手术的患者并不多^[⁶^]。研究表明PDAC的病理分化程度与手术方法选择、疗效及预后密切相关，目前评估PDAC病理分化的方法与金标准是术后组织病理学检查^[⁷^,⁸^]。Ki-67是反映肿瘤细胞增殖情况的常用免疫标志物之一，与癌症的发生、发展以及耐药性密切相关^[⁹^,¹⁰^]，Ki-67高表达往往提示预后不良并且拥有更高的病理分级^[¹¹^,¹²^]，目前评估Ki‐67表达水平只能通过术后病理免疫组化获得。术后病理评价PDAC病理分化与Ki‐67表达存在有创、操作烦琐、假阴性、滞后性与不良并发症等缺陷，且不适用于无法手术的患者，无法为患者诊疗决策提供及时快速的支撑。因此，寻找一种术前无创、快速、全面、准确及时的技术手段评估PDAC病理分化程度及其Ki‐67表达水平，进而辅助临床精准诊疗决策具有重要的临床价值。

mDixon-Quant是一种基于化学位移编码的水脂分离技术，一次成像可同时生成水相图、脂相图、T2^*图、R2^*图和脂肪分数（fat fraction, FF）图等多组图像，并且成像时间极短^[¹³^,¹⁴^]，已应用于分析慢性肾病患者肾脏损害程度^[¹⁵^]、判断宫颈鳞癌的分化程度^[¹⁶^]、乳腺癌的诊断及预后判断^[¹⁷^]、前列腺癌的淋巴结及骨转移评估^[¹⁸^]、直肠癌Ki-67表达水平评价^[¹⁹^]等，mDixon-Quant对于肿瘤的生物学行为，如病理分化程度及Ki-67表达水平等有较好的预测价值。因此，本研究首次探讨通过mDixon-Quant序列衍生的定量参数值术前无创预测PDAC病理分化程度及其Ki-67表达水平的可行性及临床价值，为PDAC患者的精准诊疗提供新的支撑。

1 材料与方法

1.1 研究对象

本研究遵守《赫尔辛基宣言》，经贵州医科大学附属医院伦理审查委员会批准，批准文号：2024伦审第（512）号，免除受试者知情同意。回顾性分析2022年1月至2025年1月在贵州医科大学附属医院经手术病理证实的PDAC患者的临床、影像及病理资料。纳入标准：（1）经手术切除且病理证实为PDAC，依据病理结果将中-高分化定义为高分化组，低分化定义为低分化组；（2）在术前两周内完成MRI检查（包含mDixon-Quant序列）；（3）MRI检查前未进行放化疗等抗肿瘤治疗；（4）临床诊疗资料完整。排除标准：（1）合并有其他部位原发恶性肿瘤；（2）图像质量达不到研究要求；（3）肿瘤较小（肿瘤直径≤5 mm）无法准确测值。经严格筛选后，最终共有57例符合标准的PDAC病例纳入研究分析。收集所有患者的临床基线资料信息（年龄、性别、临床症状、CA19-9水平等）、病理分化程度与Ki-67表达水平，以及一般影像学特征（肿块部位、形态、边界、肿块长短径、胰管有无扩张、有无血管侵犯等）。同期按照1∶1的比例收集对照组，对照组纳入标准：（1）同期收集年龄、性别大致匹配的以非胰腺病变就诊住院患者；（2）既往无胰腺相关疾病病史，临床无胰腺疾病相关症状及异常实验室检查；（3）完成MRI检查（包含mDixon-Quant序列）及图像质量达到研究要求；（4）影像学表现胰腺未见异常。

1.2 MRI检查方法

MRI检查采用3.0 T MRI扫描仪（Elition，Philips，荷兰），使用配套的32通道相控阵腹部线圈。所有患者检查前均禁食6~8 h，并在影像科技师指导下进行屏气和均匀呼吸训练。定位：仰卧位、头先进，中心对准线圈中心与剑突下2~3 cm，扫描范围为上腹部，包括胰腺及十二指肠壶腹部。扫描序列包括：轴位T1WI（TR 1.15 ms，TE 133 ms，FOV 360 mm×309 mm，矩阵256×171，层厚6.0 mm，层间距1.0 mm）、T2WI（TR 2105 ms，TE 100 ms，FOV 380 mm×380 mm，矩阵252×252，层厚6.0 mm，层间距1.0 mm）、扩散加权成像（diffusion-weighted imaging, DWI；b=800 s/mm²，TR 2900 ms，TE 64 ms，FOV 380mm×380 mm，矩阵256×256，层厚6.0 mm，层间距4.0 mm）、mDixon-Quant（TR 5.7 ms，TE 0.99 ms，梯度回波6，矩阵320×200，FOV 400 mm×350 mm，层厚6.0 mm，层间距-3 mm）。增强扫描对比剂为Gd-DTPA（江苏恒瑞，中国），静脉注射，注射速率为2 mL/s，注射剂量为0.2 mL/kg。

1.3 组织病理学分析

所有患者均经过手术获取大体标本，由病理科技师对取材组织进行脱水、切片、染色、制片等操作。Ki‐67表达水平按热点区阳性细胞所占百分比表示。由于目前在PDAC中尚没有确定Ki-67指数分组的最佳临界值，所以根据既往研究^[²⁰^,²¹^]选择50%作为临界值将其分为高表达组（Ki-67≥50%）和低表达组（Ki-67<50%）。本研究最终纳入31例有Ki-67表达水平的PDAC患者。所有组织切片均由两名病理科诊断医师（分别具有7年和15年的诊断经验）在双盲的情况下独立阅片，意见不同时，经协商达成一致。

1.4 图像分析

将所有纳入研究的扫描数据传输到Philips后处理工作站。在MRI平扫和增强扫描的图像中记录病灶部位（胰头颈、钩突、胰体、胰尾等）、形态（团块状、不规则、结节状）、病灶长径与短径、病灶边界（清楚/不清楚）、有无胰管扩张、有无血管侵犯等。参照MRI常规平扫、增强及DWI图像，在mDixon-Quant的水相图上，绘制感兴趣区（region of interest, ROI），尽量避开胰腺导管、血管、囊变、出血坏死区等。将ROI复制到脂肪相、T2^*、R2^*及FF参数图上，得到水相值、脂相值、T2^*、R2^*值及FF。同时在同一患者的胰腺正常区域勾画ROI，记录其各定量参数值。另外，在正常对照组中重复上述操作，得到对照组健康胰腺的上述各参数定量值。所有图像由两名高级职称的腹部影像诊断医师在双盲的情况下独立分析，意见不同时，经协商达成一致。两名医师独立勾画ROI以测试观察者间的可重复性，其中1名医师间隔1个月后进行第2次ROI勾画以测试观察者内可重复性。典型病例见图1, 2。

点击查看大图

图1 女，72岁，病理证实为高分化胰腺导管腺癌。1A~1G：分别为DWI（b=800 s/mm²）、ADC、水相、脂相、T2^*相、R2^*相及FF图，其ROI水相值、脂相值、T2^*、R2^*及FF分别为：1 055.4、49.27、44.71 ms、22.57 s^-1、2.65%；1H：Ki-67免疫组化（×100）示低表达，Ki-67表达约10%。DWI：扩散加权成像；ADC：表观扩散系数；FF：脂肪分数；ROI：感兴趣区。
Fig. 1 A 72-year-old female patient with pathologically confirmed well-differentiated pancreatic ductal adenocarcinoma. 1A-1G: DWI map (b = 800 s/mm²), ADC map, Water map, Fat map, T2^* map, R2^* map and FF map, respectively, the values of ROI are as follows: water value of 1 055.4, fat value of 49.27, T2^* value of 44.71 ms, R2^* value of 22.57 s^-1, and FF value of 2.65%; 1H: Ki-67 immunohistochemistry (× 100) show low Ki-67 expression, with approximately 10%. DWI: diffusion-weighted imaging; ADC: apparent diffusion coefficient; FF: fat fraction; ROI: region of interest.

点击查看大图

图2 女，46岁，病理证实为低分化胰腺导管腺癌。2A~2G：分别为DWI（b=800 s/mm²）、ADC、水相、脂相、T2^*相、R2^*相及FF图，其ROI水相值、脂相值、T2^*、R2^*及FF分别为：1 255.46、56.57、78.45 ms、13.81 s^-1、2.44%；2H：Ki-67免疫组化（×100）示Ki-67高表达，Ki-67表达约70%。DWI：扩散加权成像；ADC：表观扩散系数；FF：脂肪分数；ROI：感兴趣区。
Fig. 2 A 46-year-old female patient with pathologically confirmed poorly differentiated pancreatic ductal adenocarcinoma. 2A-2G: DWI map (b = 800 s/mm²), ADC map, Water map, Fat map, T2^* map, R2^* map and FF map, respectively, the values of ROI are as follows: water value of 1 255.46, fat value of 56.57, T2^* value of 78.45 ms, R2^* value of 13.81 s^-1, and FF value of 2.44%; 2H: Ki-67 immunohistochemistry (× 100) show high Ki-67 expression, with approximately 70%. DWI: diffusion-weighted imaging; ADC: apparent diffusion coefficient; FF: fat fraction; ROI: region of interest.

1.5 统计学分析

采用SPSS Statistics 26（IBM，美国）软件进行统计学分析，对计量资料进行正态性检验，若数据符合正态分布以均数±标准差表示，组间比较采用t检验，否则以中位数M（P25，P75）表示，组间比较采用Mann-Whitney U检验。分类变量用频数表示，组间比较采用χ²检验。组内相关系数（intra-class correlation coefficient, ICC）用于评估两个观察者内和观察者间的一致性，若一致性良好（ICC>0.75），取两位观察者测量的平均值进行后续分析。绘制受试者工作特征（receiver operating characteristic, ROC）曲线并计算曲线下面积（area under the curve, AUC）评价各指标的诊断效能，最后获得各指标的敏感度、特异度以及最佳截断值，采用DeLong检验比较各AUC之间的差异。P<0.05认为差异具有统计学意义。

2 结果

2.1 受试者入组情况

本研究最终共纳入57例PDAC患者（男27例，女30例）。高分化组30例，年龄47~82（64.87±8.94）岁，低分化组27例，年龄23~77（56.56±12.77）岁；Ki-67高表达组14例，年龄35~82（58.00±12.98）岁，Ki-67低表达组17例，年龄47~76（62.65±8.54）岁；正常对照组57例（男27例，女30例），年龄18~78（48.47±17.66）岁。

2.2 一般资料统计结果

测得的各参数定量值组间和组内ICC值在0.84~0.96之间。低分化组年龄小于高分化组[（56.56±12.77）岁vs.（64.87±8.94）岁]（P=0.006），其余临床基线资料、影像基本特征、CA19-9水平等差异均无统计学意义，详见表1。

点击查看表格

表1 高低分化组PDAC患者临床基线资料和常规影像特征比较
Tab. 1 Comparison of clinical baseline characteristics and conventional imaging features between the well-differentiated and poorly differentiated groups

2.3 mDixon-Quant定量影像学参数统计分析结果

各影像参数除水相值外，脂相值、T2^*值、R2^*值及FF在PDAC患者与对照组间、PDAC患者病灶与其胰腺正常区域间差异具有统计学意义（均P<0.001），详见表2, 3。

不同分化程度组之间（表4），病灶的T2^*值与R2^*值差异存在统计学意义（P<0.001），与高分化组相比，低分化组的T2^*值更高[（58.92±7.84）ms vs.（47.87±6.76）ms]，R2^*值更低[17.73（15.62，19.77）s^-1 vs. 21.57（19.65，24.69）s^-1]，其余影像参数差异均无统计学意义（P>0.05）；两组胰腺正常区域之间差异均无统计意义（P>0.05）。

Ki-67高表达组与低表达组之间的T2^*值与R2^*值差异存在统计学意义（P值分别为0.025、0.032），高表达组的T2^*值较低表达组的更高[（55.57±8.77）ms vs.（49.23±6.09）ms]，R2^*值更低[18.48（16.45，22.05）s^-1 vs. 20.87（19.56，22.03）s^-1]，其余影像参数差异均无统计学意义（P>0.05），详见表5。

点击查看表格

表2 PDAC病灶与对照组的mDixon-Quant定量影像学参数比较
Tab. 2 Comparison of imaging parameters of PDAC lesions and control groups

点击查看表格

表3 PDAC病灶及其胰腺正常区域的mDixon-Quant定量影像学参数比较
Tab. 3 Comparison of imaging parameters of PDAC lesions and normal pancreas of patients

点击查看表格

表4 高分化组与低分化组病灶及其胰腺正常区域的mDixon-Quant定量影像学参数比
Tab. 4 Comparison of imaging parameters of lesions and normal pancreas of patients between the well-differentiated and poorly differentiated groups

点击查看表格

表5 Ki-67高表达组与低表达组的mDixon-Quant定量影像学参数比较
Tab. 5 Comparison of imaging parameters between the Ki-67 high and low expression groups

2.4 ROC曲线分析结果

ROC曲线显示T2^*、R2^*值预测PDAC病理分化程度的AUC分别为0.866、0.827；两者联合预测病理分化程度的AUC为0.863，详见表6、图3A。T2^*、R2^*值预测PDAC Ki-67表达水平的AUC分别为0.727、0.662；两者联合预测Ki-67表达水平的AUC为0.752，详见表7、图3B。

经DeLong检验，T2^*与R2^*值及两者联合对预测PDAC病理分化程度的效能差异均无统计学意义（P值分别为0.287、0.833和0.164）；T2^*与R2^*值及两者联合对预测PDAC Ki-67表达的效能差异均无统计学意义（P值分别为0.282、0.685和0.384）。

点击查看大图

图3 T2^*与R2^*值预测胰腺导管腺癌病理分化程度（3A）及Ki-67表达水平（3B）的ROC曲线。
Fig. 3 The receiver operating characteristic (ROC) curve of each image parameter value predicting histopathological differentiation (3A) and Ki-67 expression level (3B) in pancreatic ductal adenocarcinoma (PDAC).

点击查看表格

表6 T2^*、R2^*值及两者联合预测病理分化程度的受试者工作特征曲线分析结果
Tab. 6 Receiver operating characteristic curve analysis results of T2, R2 values and their combination in predicting pathological differentiation grade

点击查看表格

表7 T2^*、R2^*值及两者联合预测Ki-67表达水平的受试者工作特征曲线分析结果
Tab. 7 Receiver operating characteristic curve analysis results of T2, R2 values and their combination in predicting Ki-67 expression level

3 讨论

本研究首次采用mDixon-Quant定量参数对PDAC病理分化程度及Ki-67表达进行预测，发现了mDixon-Quan参数T2^*值和R2^*值对PDAC病理分化程度及Ki-67表达有较好的预测价值，PDAC患者病灶区与胰腺正常区域、PDAC患者与健康胰腺之间脂相值、T2^*、R2^*值及FF差异均具有统计学意义，有望为PDAC临床精准诊疗决策提供新的技术支撑及理论见解。

3.1 高低分化组之间临床基线资料比较

本研究发现，高低分化组之间临床基线资料比较除年龄差异存在统计学意义，其余临床基线资料比较差异均无统计学意义，低分化PDAC患者年龄较高分化组稍低（P=0.006），与既往研究显示年轻化PDAC患者的临床病理特征、治疗及预后等与晚发型胰腺导管腺癌（later-onset pancreatic adenocarcinoma, LOPAC）患者有所不同结论一致^[²²^]，但与大多数相关研究^[²³^,²⁴^]显示的PDAC患者不同病理分化程度之间不存在年龄差异的研究结果不同，推断可能跟纳入的研究样本有关，检索文献^[²⁵^,²⁶^]发现本研究符合早发型胰腺导管腺癌（early-onset pancreatic adenocarcinoma, EOPAC）的相关研究结论，这更符合恶性肿瘤相关年龄的流行病学特点，提示年龄较低患者的恶性程度更高，预后更差，因此在临床类似患者管理中应增加关注度。

3.2 mDixon-Quant各参数值与PDAC病理分级的关系

mDixon-Quant是一种水脂分离技术，一次成像可在极短的时间内同时生成水相图、脂相图、T2^*和R2^*图及FF等多组图像^[¹³^,¹⁴^,²⁷^]，可通过各个图像生成的定量参数值对组织微环境及代谢情况进行评价。目前，mDixon-Quant已应用于肝脏^[²⁸^]、慢性肾病^[¹⁵^]、乳腺癌^[¹⁷^]、子宫内膜癌^[²⁹^]、前列腺癌^[¹⁸^,³⁰^,³¹^]、直肠癌^[³²^]等疾病评价中。本研究发现，PDAC患者与对照组之间、病灶与其胰腺正常区域之间脂相值、T2^*和R2^*值以及FF均存在差异，并且在高分化组和低分化组之间T2^*和R2^*值间差异更具有统计学上的显著性。既往研究显示，恶性肿瘤的脂肪代谢发生改变，往往伴随着更多的脂肪消耗^[³³^,³⁴^]，并且与其生物学行为有关。尽管在本研究中，高分化组与低分化组之间脂相值并无差异（P=0.284），但低分化组整体水平较高分化组有所下降，这与刘扶摇等^[³⁵^]发现PDAC淋巴结转移组的脂相值较非转移组有所减低的研究结果一致。T2^*值是在不消除磁场均匀性和周围磁性材料的影响下得到有效横向弛豫时间，其受到各种顺磁性物质的含量、质子密度、含水量和水分子的运动状态等因素的影响。本研究显示低分化组T2^*值较高分化组升高，推测可能是由于PDAC中低分化肿瘤细胞增殖更活跃，代谢旺盛，脂肪大量消耗，含水量相对增加，最终导致T2^*值升高，符合不同恶性程度肿瘤的生物学特性差异。R2^*值与T2^*值存在倒数关系（R2^*=1000/T2^*），在本研究中，低分化组T2^*值较高分化组升高，R2^*值变化与之呈相反趋势，这与之前的研究结果一致^[¹⁷^,³⁵^,³⁶^]。

3.3 mDixon-Quant各参数值预测肿瘤增殖指数Ki-67的价值

Ki-67表达水平可以反映肿瘤细胞在体内的增殖状态与活性，与肿瘤的病理分级、预后及无病预测期密切相关^[¹⁰^,¹²^,³⁷^]。本研究结果显示，Ki-67高表达病灶T2^*值增高，符合恶性肿瘤的肿瘤细胞增殖活跃特性，肿瘤新生血管密度增加，导致含水量增加，与上述研究^[¹⁰^,¹²^,³⁷^]结果一致。王卓等^[¹⁷^]的研究亦表明在高Ki-67表达组的乳腺癌中T2^*值增高且与肿瘤的分子亚型之间存在相关性，但是在一项关于直肠癌Ki-67表达的研究^[¹⁹^]中发现高表达组的T2^*值较低表达组的稍低，但差异没有统计学意义（P=0.086），这提示在不同肿瘤之间，肿瘤异质性导致肿瘤的微环境有所不同，因此各参数对于不同肿瘤的敏感性会有所不同，有待进一步研究分析总结。

3.4 不足与展望

本研究仍然有一些局限性：第一，本研究为单中心回顾性分析研究，可能存在潜在选择偏倚风险，并且没有外部验证队列，基于单中心数据构建的模型可能存在泛化能力受限的问题；第二，纳入研究的患者必须经过手术获得组织病理学结果，并通过免疫组化获得Ki-67表达水平，最终纳入研究的病例数较少，未来需要扩大样本量进一步研究；第三，通过手动描绘ROI测量各参数值可能存在一定的主观误差，未来可借助人工智能及机器学习等手段减小误差，确保ROI同质化；第四，研究发现，PDAC患者胰腺正常区域各参数值均较正常对照组有所变化，提示PDAC的高侵袭性及其继发性改变导致所谓的正常区域胰腺组织已出现了病理变化，未来可通过技术手段从肿瘤中心向外周逐渐扩展（如扩大1 mm、2 mm、5 mm等），测量各参数值以验证上述病理变化的机制。

4 结论

综上所述，mDixon-Quant序列衍生的定量参数值可术前无创预测PDAC病理分化程度及Ki-67表达水平，为术前评价PDAC的生物学行为提供了新的无创可行技术手段，T2*和R2*值可以作为预测PDAC病理分化程度的独立预测因素，脂相值、T2*、R2*值及FF均可有效区分肿瘤病灶与胰腺正常区域，为PDAC精准诊断提供了新的影像支撑。未来将进一步扩大研究样本量，进行多中心大样本分析，并着重于验证和优化该技术，以便促进其在临床实践中的推广应用，助力临床个性化诊疗决策。

参考文献

[1]

SIEGEL R L, GIAQUINTO A N, JEMAL A. Cancer statistics, 2024[J]. CA A Cancer J Clin, 2024, 74(1): 12-49. DOI: 10.3322/caac.21820.

[2]

HALBROOK C J, LYSSIOTIS C A, DI MAGLIANO M P, et al. Pancreatic cancer: advances and challenges[J]. Cell, 2023, 186(8): 1729-1754. DOI: 10.1016/j.cell.2023.02.014.

[3]

SHERMAN M H, BEATTY G L. Tumor microenvironment in pancreatic cancer pathogenesis and therapeutic resistance[J]. Annu Rev Pathol, 2023, 18: 123-148. DOI: 10.1146/annurev-pathmechdis-031621-024600.

[4]

HUANG J J, LOK V, NGAI C H, et al. Worldwide burden of, risk factors for, and trends in pancreatic cancer[J]. Gastroenterology, 2021, 160(3): 744-754. DOI: 10.1053/j.gastro.2020.10.007.

[5]

郑荣寿, 陈茹, 韩冰峰, 等. 2022年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2024, 46(3): 221-231. DOI: 10.3760/cma.j.cn112152-20240119-00035.

ZHENG R S, CHEN R, HAN B F, et al. Cancer incidence and mortality in China, 2022[J]. Chin J Oncol, 2024, 46(3): 221-231. DOI: 10.3760/cma.j.cn112152-20240119-00035.

[6]

STROBEL O, NEOPTOLEMOS J, JÄGER D, et al. Optimizing the outcomes of pancreatic cancer surgery[J]. Nat Rev Clin Oncol, 2018, 16(1): 11-26. DOI: 10.1038/s41571-018-0112-1.

[7]

CHANG S F, LIU Y H, LIANG Y X, et al. Biological risk based on preoperative serum CA19-9 and histological grade predicts prognosis and improves accuracy of classification in patients with pancreatic ductal adenocarcinoma[J/OL]. Cancer Rep (Hoboken), 2023, 6(12): e1911 [2025-02-01]. https://pubmed.ncbi.nlm.nih.gov/37827990/. DOI: 10.1002/cnr2.1911.

[8]

KARUNAKARAN M, BARRETO S G. Surgery for pancreatic cancer: current controversies and challenges[J]. Future Oncol, 2021, 17(36): 5135-5162. DOI: 10.2217/fon-2021-0533.

[9]

UXA S, CASTILLO-BINDER P, KOHLER R, et al. Ki-67 gene expression[J]. Cell Death Differ, 2021, 28(12): 3357-3370. DOI: 10.1038/s41418-021-00823-x.

[10]

PERGOLINI I, CRIPPA S, PAGNANELLI M, et al. Prognostic impact of Ki-67 proliferative index in resectable pancreatic ductal adenocarcinoma[J]. BJS Open, 2019, 3(5): 646-655. DOI: 10.1002/bjs5.50175.

[11]

LUCHINI C, PANTANOWITZ L, ADSAY V, et al. Ki-67 assessment of pancreatic neuroendocrine neoplasms: Systematic review and meta-analysis of manual vs. digital pathology scoring[J]. Mod Pathol, 2022, 35(6): 712-720. DOI: 10.1038/s41379-022-01055-1.

[12]

LIANG Y X, SHENG G N, GUO Y, et al. Prognostic significance of grade of malignancy based on histopathological differentiation and Ki-67 in pancreatic ductal adenocarcinoma[J]. Cancer Biol Med, 2024, 21(5): 416-432. DOI: 10.20892/j.issn.2095-3941.2023.0363.

[13]

YU F Y, HE B, CHEN L, et al. Intermuscular fat content in young Chinese men with newly diagnosed type 2 diabetes: based on MR mDIXON-quant quantitative technique[J/OL]. Front Endocrinol (Lausanne), 2021, 12: 536018 [2025-02-01]. https://pubmed.ncbi.nlm.nih.gov/33868161/. DOI: 10.3389/fendo.2021.536018.

[14]

WEISS S, NEJAD-DAVARANI S, EGGERS H, et al. A novel and rapid approach to estimate patient-specific distortions based on mDIXON MRI[J/OL]. Phys Med Biol, 2019, 64(15): 155002 [2025-02-01]. https://iopscience.iop.org/article/10.1088/1361-6560/ab2b0a. DOI: 10.1088/1361-6560/ab2b0a.

[15]

WANG Y, JU Y, AN Q, et al. mDIXON-Quant for differentiation of renal damage degree in patients with chronic kidney disease[J/OL]. Front Endocrinol (Lausanne), 2023, 14: 1187042 [2025-02-03]. https://pubmed.ncbi.nlm.nih.gov/37547308/. DOI: 10.3389/fendo.2023.1187042.

[16]

MENG X, TIAN S, MA C, et al. APTw combined with mDixon-Quant imaging to distinguish the differentiation degree of cervical squamous carcinoma[J/OL]. Front Oncol, 2023, 13: 1105867 [2025-02-03]. https://www.frontiersin.org/articles/10.3389/fonc.2023.1105867/full. DOI: 10.3389/fonc.2023.1105867.

[17]

王卓, 吴祺, 宁宁, 等. mDixon-Quant技术在乳腺浸润性导管癌诊断与预后评估中的价值研究[J]. 磁共振成像, 2023, 14(3): 65-71. DOI: 10.12015/issn.1674-8034.2023.03.012.

WANG Z, WU Q, NING N, et al. Study on the value of mDixon-Quant technique in the diagnosis and prognosis evaluation of invasive ductal breast cancer[J]. Chin J Magn Reson Imag, 2023, 14(3): 65-71. DOI: 10.12015/issn.1674-8034.2023.03.012.

[18]

QIN C, GOLDBERG O, KAKAR G, et al. MRI fat fraction imaging of nodal and bone metastases in prostate cancer[J]. Eur Radiol, 2023, 33(8): 5851-5855. DOI: 10.1007/s00330-023-09527-x.

[19]

赵雅迪, 李伟兰, 宋健, 等. IVIM、mDixon-Quant多参数定量成像联合血细胞参数评估直肠癌Ki-67表达水平的研究[J]. 磁共振成像, 2024, 15(8): 145-151. DOI: 10.12015/issn.1674-8034.2024.08.022.

ZHAO Y D, LI W L, SONG J, et al. IVIM, m Dixon-Quant multiparameter quantitative imaging combined with blood cell parameters to assess Ki-67 expression levels in rectal cancer[J]. Chin J Magn Reson Imag, 2024, 15(8): 145-151. DOI: 10.12015/issn.1674-8034.2024.08.022.

[20]

LI Q, SONG Z H, LI X J, et al. Development of a CT radiomics nomogram for preoperative prediction of Ki-67 index in pancreatic ductal adenocarcinoma: a two-center retrospective study[J]. Eur Radiol, 2024, 34(5): 2934-2943. DOI: 10.1007/s00330-023-10393-w.

[21]

ZHU X F, CAO Y S, JU X P, et al. Personalized designs of adjuvant radiotherapy for pancreatic cancer based on molecular profiles[J]. Cancer Sci, 2021, 112(1): 287-295. DOI: 10.1111/cas.14486.

[22]

LAPELUSA M, SHEN C, ARHIN N D, et al. Trends in the incidence and treatment of early-onset pancreatic cancer[J/OL]. Cancers (Basel), 2022, 14(2): 283 [2025-02-03]. https://pubmed.ncbi.nlm.nih.gov/35053447/. DOI: 10.3390/cancers14020283.

[23]

徐茂丽, 阮志兵, 刘欢, 等. 基于增强CT影像组学预测胰腺导管腺癌病理分化程度的研究[J]. 医学影像学杂志, 2023, 33(10): 1830-1835.

XU M L, RUAN Z B, LIU H, et al. Prediction of pathological differentiation degree of pancreatic ductal adenocarcinoma based on enhanced CT radiomics[J]. J Med Imag, 2023, 33(10): 1830-1835.

[24]

庄雨, 陈杰, 李静燕, 等. 多参数MRI影像组学模型预测胰腺导管腺癌病理分化程度的价值[J]. 临床放射学杂志, 2023, 42(11): 1768-1773. DOI: 10.13437/j.cnki.jcr.2023.11.015.

ZHUANG Y, CHEN J, LI J Y, et al. Value of multiparameter MRI radiomics model in predicting the pathological diferentiation of pancreatic ductal adenocarcinoma[J]. J Clin Radiol, 2023, 42(11): 1768-1773. DOI: 10.13437/j.cnki.jcr.2023.11.015.

[25]

RASHAD N, GOUDA A, SABRA E, et al. Early onset pancreatic adenocarcinoma (EOPAC): presentation, clinical course and treatment outcomes in comparison to average onset pancreatic adenocarcinoma (AOPAC): a retrospective cohort study[J/OL]. BMC Cancer, 2024, 24(1): 1289 [2025-02-03]. https://bmccancer.biomedcentral.com/articles/10.1186/s12885-024-12955-7. DOI: 10.1186/s12885-024-12955-7.

[26]

RAMAI D, LANKE G, LAI J, et al. Early- and late-onset pancreatic adenocarcinoma: a population-based comparative study[J]. Pancreatology, 2021, 21(1): 124-129. DOI: 10.1016/j.pan.2020.12.007.

[27]

TANG R, TANG G Y, HUA T, et al. mDIXON-Quant technique diagnostic accuracy for assessing bone mineral density in male adult population[J/OL]. BMC Musculoskelet Disord, 2023, 24(1): 125 [2025-02-03]. https://bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/s12891-023-06225-z. DOI: 10.1186/s12891-023-06225-z.

[28]

CRAFT M L, EDWARDS M, JAIN T P, et al. R2 and R2* MRI assessment of liver iron content in an undifferentiated diagnostic population with hyperferritinaemia, and impact on clinical decision making[J/OL]. Eur J Radiol, 2021, 135: 109473 [2025-02-10]. https://linkinghub.elsevier.com/retrieve/pii/S0720048X2030663X. DOI: 10.1016/j.ejrad.2020.109473.

[29]

马长军, 田士峰, 陈丽华, 等. T2 mapping联合mDixon-Quant多参数成像定量评估子宫内膜癌微卫星不稳定状态的研究[J]. 磁共振成像, 2022, 13(8): 48-54. DOI: 10.12015/issn.1674-8034.2022.08.009.

MA C J, TIAN S F, CHEN L H, et al. Quantitative assessment of microsatellite instability in endometrial cancer by T2 mapping combined with m Dixon-Quant multiparameter imaging[J]. Chin J Magn Reson Imag, 2022, 13(8): 48-54. DOI: 10.12015/issn.1674-8034.2022.08.009.

[30]

LIAO Z H, LIU G Y, MING B, et al. Evaluating prostate cancer bone metastasis using accelerated whole-body isotropic 3D T1-weighted Dixon MRI with compressed SENSE: a feasibility study[J]. Eur Radiol, 2023, 33(3): 1719-1728. DOI: 10.1007/s00330-022-09181-9.

[31]

任雪, 刘爱连, 陈丽华, 等. APT联合mDIXON-Quant成像对前列腺癌和前列腺增生的鉴别诊断价值[J]. 放射学实践, 2023, 38(1): 58-64. DOI: 10.13609/j.cnki.1000-0313.2023.01.011.

REN X, LIU A L, CHEN L H, et al. The value of APT combined with mDIXON-Quant imaging in the differential diagnosis of prostate cancer and benign prostatic hyperplasia[J]. Radiol Pract, 2023, 38(1): 58-64. DOI: 10.13609/j.cnki.1000-0313.2023.01.011.

[32]

PENG Y, LUO Y, HU X M, et al. Quantitative T2*-weighted imaging and reduced field-of-view diffusion-weighted imaging of rectal cancer: correlation of R2* and apparent diffusion coefficient with histopathological prognostic factors[J/OL]. Front Oncol, 2021, 11: 670156 [2025-02-10]. https://www.frontiersin.org/articles/10.3389/fonc.2021.670156/full. DOI: 10.3389/fonc.2021.670156.

[33]

MERINO SALVADOR M, GÓMEZ DE CEDRÓN M, MORENO RUBIO J, et al. Lipid metabolism and lung cancer[J]. Crit Rev Oncol Hematol, 2017, 112: 31-40. DOI: 10.1016/j.critrevonc.2017.02.001.

[34]

HISANAGA S, AOKI T, SHIMAJIRI S, et al. Peritumoral fat content correlates with histological prognostic factors in breast carcinoma: a study using iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL)[J]. Magn Reson Med Sci, 2021, 20(1): 28-33. DOI: 10.2463/mrms.mp.2019-0201.

[35]

刘扶摇, 张京刚, 陈杰, 等. 基于ZOOM-mDixon的T2*/R2*成像术前预测胰腺导管腺癌淋巴结转移的价值[J]. 磁共振成像, 2024, 15(1): 119-124. DOI: 10.12015/issn.1674-8034.2024.01.019.

LIU F Y, ZHANG J G, CHEN J, et al. Value of ZOOM-mDixon-derived T2*/R2* imaging in preoperative predicting lymph node metastasis in pancreatic ductal adenocarcinoma[J]. Chin J Magn Reson Imag, 2024, 15(1): 119-124. DOI: 10.12015/issn.1674-8034.2024.01.019.

[36]

SEO M, RYU J K, JAHNG G H, et al. Estimation of T2* relaxation time of breast cancer: correlation with clinical, imaging and pathological features[J]. Korean J Radiol, 2017, 18(1): 238-248. DOI: 10.3348/kjr.2017.18.1.238.

[37]

QIU Z, XIAO J, ZHENG S, et al. Associations between functional polychlorinated biphenyls in adipose tissues and prognostic biomarkers of breast cancer patients[J/OL]. Environ Res, 2020, 185: 109441 [2025-02-10]. https://linkinghub.elsevier.com/retrieve/pii/S0013935120303340. DOI: 10.1016/j.envres.2020.109441.

上一篇 基于多模型DWI的胰腺癌组织学表征研究：动物-临床联合验证

下一篇 扩散峰度成像定量参数预测胰腺导管腺癌HIF-1α的初步研究