Department of Radiology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
Department of Biomedical Engineering, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China.
Neuro Oncol. 2023 Jun 2;25(6):1146-1156. doi: 10.1093/neuonc/noad003.
Gliomas are the most common type of central nervous system tumors in children, and the combination of histological and molecular classification is essential for prognosis and treatment. Here, we proposed a newly developed microstructural mapping technique based on diffusion-time-dependent diffusion MRI td-dMRI theory to quantify tumor cell properties and tested these microstructural markers in identifying histological grade and molecular alteration of H3K27.
This prospective study included 69 pediatric glioma patients aged 6.14 ± 3.25 years old, who underwent td-dMRI with pulsed and oscillating gradient diffusion sequences on a 3T scanner. dMRI data acquired at varying tds were fitted into a 2-compartment microstructural model to obtain intracellular fraction (fin), cell diameter, cellularity, etc. Apparent diffusivity coefficient (ADC) and T1 and T2 relaxation times were also obtained. H&E stained histology was used to validate the estimated microstructural properties.
For histological classification of low- and high-grade pediatric gliomas, the cellularity index achieved the highest area under the receiver-operating-curve (AUC) of 0.911 among all markers, while ADC, T1, and T2 showed AUCs of 0.906, 0.885, and 0.886. For molecular classification of H3K27-altered glioma in 39 midline glioma patients, cell diameter showed the highest discriminant power with an AUC of 0.918, and the combination of cell diameter and extracellular diffusivity further improved AUC to 0.929. The td-dMRI estimated fin correlated well with the histological ground truth with r = 0.7.
The td-dMRI-based microstructural properties outperformed routine MRI measurements in diagnosing pediatric gliomas, and the different microstructural features showed complementary strength in histological and molecular classifications.
神经胶质瘤是儿童中枢神经系统肿瘤中最常见的类型，组织学和分子分类的结合对于预后和治疗至关重要。在这里，我们提出了一种新的基于扩散时间依赖扩散 MRI td-dMRI 理论的微观结构映射技术，用于量化肿瘤细胞特性，并测试这些微观结构标记物在识别组织学分级和 H3K27 分子改变方面的作用。
这项前瞻性研究纳入了 69 名年龄在 6.14±3.25 岁的儿科脑胶质瘤患者，他们在 3T 扫描仪上接受了脉冲和振荡梯度扩散序列的 td-dMRI。在不同 tds 下采集的 dMRI 数据被拟合到一个 2 室微观结构模型中，以获得细胞内分数（fin）、细胞直径、细胞密度等。还获得了表观扩散系数（ADC）和 T1 和 T2 弛豫时间。H&E 染色组织学用于验证估计的微观结构特性。
对于低级别和高级别儿科脑胶质瘤的组织学分类，细胞密度指数在所有标记物中达到了最高的受试者工作特征曲线（AUC）0.911，而 ADC、T1 和 T2 的 AUC 分别为 0.906、0.885 和 0.886。对于 39 例中线胶质瘤患者的 H3K27 改变型胶质瘤的分子分类，细胞直径显示出最高的判别能力，AUC 为 0.918，细胞直径和细胞外扩散的组合进一步将 AUC 提高到 0.929。td-dMRI 估计的 fin 与组织学的真实情况相关性良好，r 值为 0.7。
基于 td-dMRI 的微观结构特性在诊断儿科脑胶质瘤方面优于常规 MRI 测量，并且不同的微观结构特征在组织学和分子分类方面具有互补的优势。
