Nuclear Medicine Unit, Ente Ospedaliero Ospedali Galliera, Genoa, Italy.
Neuroradiology Unit, IRCCS Istituto Giannina Gaslini, via G. Gaslini 5, 16147, Genoa, Italy.
Eur J Nucl Med Mol Imaging. 2019 Jul;46(8):1685-1694. doi: 10.1007/s00259-019-04333-4. Epub 2019 Apr 27.
The aim of this study was to investigate MRI-derived diffusion weighted imaging (DWI), H-MR spectroscopy (H-MRS) and arterial spin labeling (ASL) perfusion imaging in comparison with F-dihydroxyphenylalanine (DOPA) PET with respect to diagnostic evaluation of pediatric diffuse midline gliomas (DMG) H3K27M-mutant and wild-type.
We retrospectively analyzed 22 pediatric patients with DMG histologically proved and molecularly classified as H3K27M-mutant (12 subjects) and wild-type (10 subjects) who underwent DWI, H-MRS, and ASL performed within 2 weeks of F-DOPA PET. DWI-derived relative minimum apparent diffusion coefficient (rADC min), H-MRS data [choline/N-acetylaspartate (Cho/NAA), choline/creatine (Cho/Cr), and presence of lactate] and relative ASL-derived cerebral blood flow max (rCBF max) were compared with F-DOPA uptake Tumor/Normal tissue (T/N) and Tumor/Striatum (T/S) ratios, and correlated with histological and molecular features of DMG. Statistics included Pearson's chi-square and Mann-Whitney U tests, Spearman's rank correlation and receiver operating characteristic (ROC) analysis.
The highest degrees of correlation among different techniques were found between T/S, rADC min and Cho/NAA ratio (p < 0.01), and between rCBF max and rADC min (p < 0.01). Significant differences between histologically classified low- and high-grade DMG, independently of H3K27M-mutation, were found among all imaging techniques (p ≤ 0.02). Significant differences in terms of rCBF max, rADC min, Cho/NAA and F-DOPA uptake were also found between molecularly classified mutant and wild-type DMG (p ≤ 0.02), even though wild-type DMG included low-grade astrocytomas, not present among mutant DMG. When comparing only histologically defined high-grade mutant and wild-type DMG, only the F-DOPA PET data T/S demonstrated statistically significant differences independently of histology (p < 0.003). ROC analysis demonstrated that T/S ratio was the best parameter for differentiating mutant from wild-type DMG (AUC 0.94, p < 0.001).
Advanced MRI and F-DOPA PET characteristics of DMG depend on histological features; however, F-DOPA PET-T/S was the only parameter able to discriminate H3K27M-mutant from wild-type DMG independently of histology.
本研究旨在比较磁共振弥散加权成像(DWI)、质子磁共振波谱(H-MRS)和动脉自旋标记(ASL)灌注成像与 F-二羟苯丙氨酸(DOPA)PET 对儿科弥漫中线胶质瘤(DMG)H3K27M 突变型和野生型的诊断评估。
我们回顾性分析了 22 例经组织学证实且分子学分类为 H3K27M 突变型(12 例)和野生型(10 例)的儿科 DMG 患者,这些患者在 F-DOPA PET 检查前 2 周内接受了 DWI、H-MRS 和 ASL 检查。DWI 衍生的相对最小表观弥散系数(rADC min)、H-MRS 数据[胆碱/N-乙酰天冬氨酸(Cho/NAA)、胆碱/肌酸(Cho/Cr)和乳酸的存在]和相对 ASL 衍生的最大脑血流(rCBF max)与 F-DOPA 摄取的肿瘤/正常组织(T/N)和肿瘤/纹状体(T/S)比值进行比较,并与 DMG 的组织学和分子特征相关联。统计学分析包括 Pearson's chi-square 和 Mann-Whitney U 检验、Spearman 秩相关和受试者工作特征(ROC)分析。
不同技术之间相关性最高的是 T/S、rADC min 和 Cho/NAA 比值(p<0.01),以及 rCBF max 和 rADC min(p<0.01)。在组织学分类的低级别和高级别 DMG 中,独立于 H3K27M 突变,所有成像技术之间都存在显著差异(p≤0.02)。在分子学分类的突变型和野生型 DMG 中,rCBF max、rADC min、Cho/NAA 和 F-DOPA 摄取也存在显著差异(p≤0.02),尽管野生型 DMG 包括低级别星形细胞瘤,而突变型 DMG 中没有。当仅比较组织学定义的高级别突变型和野生型 DMG 时,只有 F-DOPA PET 的 T/S 独立于组织学显示出统计学显著差异(p<0.003)。ROC 分析表明,T/S 比值是区分突变型和野生型 DMG 的最佳参数(AUC 0.94,p<0.001)。
DMG 的高级 MRI 和 F-DOPA PET 特征取决于组织学特征;然而,F-DOPA PET-T/S 是唯一能够独立于组织学区分 H3K27M 突变型和野生型 DMG 的参数。