Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, Tennessee, 37232, USA.
Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, 37232, USA.
J Magn Reson Imaging. 2024 Feb;59(2):575-584. doi: 10.1002/jmri.28774. Epub 2023 May 23.
Breast cancer treatment response evaluation using the response evaluation criteria in solid tumors (RECIST) guidelines, based on tumor volume changes, has limitations, prompting interest in novel imaging markers for accurate therapeutic effect determination.
To use MRI-measured cell size as a new imaging biomarker for assessing chemotherapy response in breast cancer.
Longitudinal; animal model.
Triple-negative human breast cancer cell (MDA-MB-231) pellets (4 groups, n = 7) treated with dimethyl sulfoxide (DMSO) or 10 nM of paclitaxel for 24, 48, and 96 hours, and 29 mice with MDA-MB-231 tumors in right hind limbs treated with paclitaxel (n = 16) or DMSO (n = 13) twice weekly for 3 weeks.
FIELD STRENGTH/SEQUENCE: Oscillating gradient spin echo and pulsed gradient spin echo sequences at 4.7 T.
MDA-MB-231 cells were analyzed using flowcytometry and light microscopy to assess cell cycle phases and cell size distribution. MDA-MB-231 cell pellets were MR imaged. Mice were imaged weekly, with 9, 6, and 14 being sacrificed for histology after MRI at weeks 1, 2, and 3, respectively. Microstructural parameters of tumors/cell pellets were derived by fitting diffusion MRI data to a biophysical model.
One-way ANOVA compared cell sizes and MR-derived parameters between treated and control samples. Repeated measures 2-way ANOVA with Bonferroni post-tests compared temporal changes in MR-derived parameters. A P-value <0.05 was considered statistically significant.
In vitro experiments showed that the mean MR-derived cell sizes of paclitaxel-treated cells increased significantly with a 24-hours treatment and decreased (P = 0.06) with a 96-hour treatment. For in vivo xenograft experiments, the paclitaxel-treated tumors showed significant decreases in cell size at later weeks. MRI observations were supported by flowcytometry, light microscopy, and histology.
MR-derived cell size may characterize the cell shrinkage during treatment-induced apoptosis, and may potentially provide new insights into the assessment of therapeutic response.
2 TECHNICAL EFFICACY STAGE: 4.
基于肿瘤体积变化的实体瘤反应评估标准（RECIST）在评估乳腺癌治疗反应方面存在局限性，因此人们对新的成像标志物用于准确评估治疗效果产生了兴趣。
使用 MRI 测量的细胞大小作为评估乳腺癌化疗反应的新的成像生物标志物。
纵向；动物模型。
用二甲基亚砜（DMSO）或 10 nM 紫杉醇处理的四阴性人乳腺癌细胞（MDA-MB-231）球（4 组，n=7），分别处理 24、48 和 96 小时；29 只右侧后肢带有 MDA-MB-231 肿瘤的小鼠，每周两次接受紫杉醇（n=16）或 DMSO（n=13）治疗 3 周。
磁场强度/序列：4.7T 下的振荡梯度回波和脉冲梯度回波序列。
使用流式细胞术和相差显微镜分析 MDA-MB-231 细胞，以评估细胞周期阶段和细胞大小分布。对 MDA-MB-231 细胞球进行 MRI 成像。每周对小鼠进行成像，分别在第 1、2 和 3 周的 MRI 后，第 9、6 和 14 天处死进行组织学检查。通过将扩散 MRI 数据拟合到生物物理模型来获得肿瘤/细胞球的微结构参数。
单向方差分析比较处理组和对照组的细胞大小和 MRI 衍生参数。重复测量 2 方式方差分析，结合 Bonferroni 事后检验比较 MRI 衍生参数的时间变化。P 值<0.05 被认为具有统计学意义。
体外实验表明，紫杉醇处理 24 小时后细胞的平均 MRI 衍生细胞大小显著增加，96 小时后减小（P=0.06）。对于体内异种移植实验，紫杉醇治疗的肿瘤在后期周显示出细胞大小的显著减小。MRI 观察结果得到了流式细胞术、相差显微镜和组织学的支持。
MRI 衍生的细胞大小可以描述治疗诱导细胞凋亡过程中的细胞收缩，并且可能为评估治疗反应提供新的见解。
2 技术功效阶段：4
