Wang Xiaoyan, Zhang Yan, Cheng Jingliang, Lin Liangjie, Hu Ying, Wang Anfei, Zhang Yong, Wang Ruhua, Li Ying, Zhang Kun, Zhang Wenhua
Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Clinical and Technical Support, Philips Healthcare, Beijing, China.
Front Oncol. 2025 Mar 5;15:1498691. doi: 10.3389/fonc.2025.1498691. eCollection 2025.
This study aims to investigate the feasibility of cellular microstructural mapping by the diffusion MRI (IMPULSED, imaging microstructural parameters using limited spectrally edited diffusion) of breast tumors, and further to evaluate whether the MRI-derived microstructural features is associated with the prognostic factors in breast cancer.
This prospective study collected 232 patients with suspected breast tumors from March to August 2023. The IMPULSED MRI scan included acquisitions of diffusion MRI using both pulsed (PGSE) and oscillating (OGSE) gradient spin echo with the oscillating frequencies up to 33 Hz. The OGSE and PGSE data were fitted by the IMPUSLED method using a two-compartment model to estimate mean cell diameter ( ), intracellular fraction ( ), extracellular diffusivity ( ), and cellularity index ( /d) within breast tumor lesions. The apparent diffusion coefficients (ADCs) were calculated from the conventional diffusion weighted imaging, PGSE, and OGSE (17 Hz and 33 Hz) sequences (ADC, ADC, ADC, and ADC). The independent samples test was used to compare the , , , cellularity index, and ADC values between benign and malignant breast tumors, and between breast cancer subgroups with different risk factors. The receiver operating characteristic (ROC) curve was used to access the diagnostic performance.
213 patients were finally included and divided into malignant (n=130) and benign (n=83) groups according to the histopathological results. The (15.74 ± 2.68 . 14.28 ± 4.65 μm, p<0.001), (0.346 ± 0.125 . 0.279 ± 0.212, p<0.001) and cellularity index (21.19 ± 39.54 . 19.38 ± 14.87 ×10-3 um, p<0.005) values of malignant lesions were significantly higher than those of benign lesions, and the (2.119 ± 0.395 . 2.378 ± 0.332 um/ms, p<0.001) and ADC (0.877 ± 0.148 . 1.453 ± 0.356 um/ms, p<0.001) of malignant lesions were significantly lower than those of benign lesions. For differentiation between benign and malignant breast lesions, ADC showed the highest AUC of 0.951 with the sensitivity of 80.49% and specificity of 98.28%. The combination of , , , and cellularity for differentiation between benign and malignant breast lesions showed AUC of 0.787 (sensitivity = 70.73%, and specificity = 77.86%), and the combination of IMPULSED-derived parameters with ADCs by PGSE and OGSE further improve the AUC to 0.897 (sensitivity = 81.93%, and specificity = 81.54%). The values of HER-2(+) tumors were significantly lower than those of HER-2(-) tumors (0.313 ± 0.100 . 0.371 ± 0.137, p=0.015), and the ADC ADC and ADC values of HER-2(+) tumors were significantly higher than those of HER-2(-) tumors (ADC: 0.929 ± 0.115 . 0.855 ± 0.197 um/ms, p=0.023; ADC: 1.373 ± 0.306 . 1.242 ± 0.301 um/s, p =0.025; ADC: 2.042 ± 0.545 . 1.811 ± 0.392 um/s, p = 0.008). The (0.377 ± 0.136 . 0.300 ± 0.917, p=0.001) and cellularity index (27.22 ± 12.02 . 21.66 ± 7.76 ×10 um, p=0.007) values of PR(+) tumors were significantly higher than those of PR(-) tumor. The ADC values of PR(+) tumors were significantly lower than those of PR(-) tumors(1.227 ± 0.299 . 1.404 ± 0.294 um/s, p =0.002).The ADC and values of ER(+) tumors were significantly lower than those of ER(-) tumors (ADC: 1.258 ± 0.313 . 1.400 ± 0.273 um/s, p = 0.029; : 2.070 ± 0.405 . 2.281 ± 0.331 um/ms, p=0.011). For differentiation between ER(+) and ER(-), the ADC and showed AUCs of 0.643 (sensitivity = 76.67%, and specificity = 47.06%) and 0.646 (sensitivity = 80.0%, and specificity = 45.98%), and the combination of and ADC showed AUCs of 0.663 (sensitivity =93.33%, specificity = 36.78%). For differentiation of PR(+) and PR(-), the ADC, , and cellularity index showed AUCs of 0.666 (sensitivity = 68.18%, and specificity = 61.97%), 0.697 (sensitivity = 77.27%, and specificity = 60.27%) and 0.661 (sensitivity = 68.18%, and specificity = 61.64%), respectively, and their combination showed AUCs of 0.729 (sensitivity =72.73%, specificity = 65.75%). For differentiation of HER-2(+) and HER-2(-), the ADC, ADC, and ADC, and showed AUCs of 0.625 (sensitivity = 59.42%, specificity = 63.04%), 0.632 (sensitivity = 43.66%, and specificity = 84.78%), 0.664 (sensitivity = 47.95%, and specificity = 82.67%) and 0.650 (sensitivity = 77.46%, and specificity = 56.52%), respectively, and their combination showed AUCs of 0.693 (sensitivity = 69.57%, specificity = 64.79%) of HER-2(+) and HER-2(-).
The IMPULSED method demonstrates promise for characterizing cellular microstructural features in breast tumors, which may be helpful for prognostic risk evaluation in breast cancer.
本研究旨在探讨通过乳腺肿瘤的扩散磁共振成像（IMPULSED，使用有限频谱编辑扩散成像微观结构参数）进行细胞微观结构映射的可行性，并进一步评估磁共振成像衍生的微观结构特征是否与乳腺癌的预后因素相关。
本前瞻性研究于2023年3月至8月收集了232例疑似乳腺肿瘤患者。IMPULSED磁共振成像扫描包括使用脉冲（PGSE）和振荡（OGSE）梯度自旋回波进行扩散磁共振成像采集，振荡频率高达33Hz。使用两室模型通过IMPUSLED方法对OGSE和PGSE数据进行拟合，以估计乳腺肿瘤病变内的平均细胞直径（ ）、细胞内分数（ ）、细胞外扩散率（ ）和细胞密度指数（ /d）。从传统扩散加权成像、PGSE和OGSE（17Hz和33Hz）序列计算表观扩散系数（ADC）（ADC、ADC、ADC和ADC）。采用独立样本检验比较良性和恶性乳腺肿瘤之间以及具有不同危险因素的乳腺癌亚组之间的 、 、 、细胞密度指数和ADC值。使用受试者操作特征（ROC）曲线评估诊断性能。
最终纳入213例患者，根据组织病理学结果分为恶性（n = 130）和良性（n = 83）组。恶性病变的 （15.74±2.68. 14.28±4.65μm，p<0.001）、 （0.346±0.125. 0.279±0.212，p<0.001）和细胞密度指数（21.19±39.54.19.38±14.87×10-3um，p<0.005）值显著高于良性病变，恶性病变的 （2.119±0.395. 2.378±0.332um/ms，p<0.001）和ADC（0.877±0.148. 1.453±0.356um/ms，p<0.001）显著低于良性病变。对于乳腺良恶性病变的鉴别，ADC显示出最高的AUC为0.951，敏感性为80.49%，特异性为98.28%。 、 、 和细胞密度指数联合用于乳腺良恶性病变鉴别的AUC为0.787（敏感性 = 70.73% , 特异性 = 77.86%），IMPULSED衍生参数与PGSE和OGSE的ADC联合使用可进一步将AUC提高至0.897（敏感性 = 81.93% , 特异性 = 81.54%）。HER-2(+)肿瘤的 值显著低于HER-2(-)肿瘤（0.313±0.100. 0.371±0.137，p = 0.015），HER-2(+)肿瘤的ADC、ADC和ADC值显著高于HER-2(-)肿瘤（ADC：0.929±0.115. 0.855±0.197um/ms，p = 0.023；ADC：1.373±0.306. 1.242±0.301um/s，p = 0.025；ADC：2.042±0.545. 1.811±0.392um/s，p = 0.008）。PR(+)肿瘤的 值（0.377±0.136. 0.300±0.917，p = 0.001）和细胞密度指数（27.22±12.02. 21.66±7.76×10um，p = 0.007）显著高于PR(-)肿瘤。PR(+)肿瘤的ADC值显著低于PR(-)肿瘤（1.227±0.299. 1.404±0.294um/s，p = 0.002）。ER(+)肿瘤的ADC和 值显著低于ER(-)肿瘤（ADC：1.258±0.313. 1.400±0.273um/s，p = 0.029； ：2.070±0.405. 2.281±0.331um/ms，p = 0.011）。对于ER(+)和ER(-)的鉴别，ADC和 显示的AUC分别为0.643（敏感性 = 76.67% , 特异性 = 47.06%）和 0.646（敏感性 = 80.0% , 特异性 = 45.98%）， 和ADC联合显示的AUC为0.663（敏感性 = 93.33% , 特异性 = 36.78%）。对于PR(+)和PR(-)的鉴别，ADC、 和细胞密度指数显示的AUC分别为0.666（敏感性 = 68.18% , 特异性 = 61.97%）、0.697（敏感性 = 77.27% , 特异性 = 60.27%）和0.661（敏感性 = 68.18% , 特异性 = 61.64%），它们联合显示的AUC为0.729（敏感性 = 72.73% , 特异性 = 65.75%）。对于HER-2(+)和HER-2(-)的鉴别，ADC、ADC和ADC以及 显示的AUC分别为0.625（敏感性 = 59.42% , 特异性 = 63.04%）、0.632（敏感性 = 43.66% , 特异性 = 84.78%）、0.664（敏感性 = 47.95% , 特异性 = 82.67%）和0.650（敏感性 = 77.46% , 特异性 = 56.52%），它们联合显示的HER-2(+)和HER-2(-)的AUC为0.693（敏感性 = 69.57% , 特异性 = 64.79%）。
IMPULSED方法在表征乳腺肿瘤细胞微观结构特征方面显示出前景，这可能有助于乳腺癌的预后风险评估。
