Objectives: This exploratory preclinical study aimed to compare the correlations of apparent diffusion coefficient (ADC) and native T1 mapping histogram features with tumor cell proliferation, microvessel density (MVD), and extracellular matrix composition in neuroblastoma xenografts.Methods: Neuroblastoma xenografts (n= 42) were established by subcutaneously injecting threeMYCN-amplified/non-amplified human neuroblastoma cell lines (IMR-32, SK-N-BE(2), and SH-SY5Y;n= 14 per group) into female immunodeficient BALB/c-nude mice. Once tumors reached a diameter within the range of 12–15 mm, native T1 mapping and diffusion-weighted imaging were performed using a 3.0T clinical MRI scanner. Tumor cell proliferation and MVD were assessed via immunohistochemical Ki-67 staining and CD31 staining, respectively. Collagen fibers were visualized using Masson staining to calculate the collagen volume fraction (CVF). Pearson correlation coefficients with false discovery rate (FDR) correction were used to evaluate their associations.Results: Significant negative correlations were observed between Ki-67 expression and multiple ADC values after FDR correction, including ADC10Percentile(r= −0.397, adjustedp= 0.032), ADC90Percentile(r= −0.394, adjustedp= 0.032), ADCmaximum(r= −0.362, adjustedp= 0.048), ADCmean(r= −0.421, adjustedp= 0.032), ADCmedian(r= −0.422, adjustedp= 0.032), ADCminimum(r= −0.390, adjustedp= 0.032), and ADCrootmeansquared(r= −0.419, adjustedp= 0.032). In contrast, multiple T1 mapping features showed significant positive correlations with CVF (adjustedp< 0.05).Conclusions: ADC and T1 mapping provide complementary insights into tumor proliferation and extracellular matrix composition in neuroblastoma. These preclinical findings support further research to validate their potential clinical utility.
目的：本探索性临床前研究旨在比较神经母细胞瘤异种移植模型中表观扩散系数（ADC）与原生T1 mapping直方图特征与肿瘤细胞增殖、微血管密度（MVD）及细胞外基质成分的相关性。 方法：通过皮下注射三种MYCN扩增/非扩增的人神经母细胞瘤细胞系（IMR-32、SK-N-BE(2)和SH-SY5Y，每组n=14）至雌性免疫缺陷BALB/c裸鼠体内，建立神经母细胞瘤异种移植模型（n=42）。当肿瘤直径达到12-15mm范围时，使用3.0T临床MRI扫描仪进行原生T1 mapping和扩散加权成像。分别通过免疫组化Ki-67染色和CD31染色评估肿瘤细胞增殖和MVD。采用Masson染色可视化胶原纤维并计算胶原体积分数（CVF）。使用经错误发现率（FDR）校正的皮尔逊相关系数评估各参数间的关联性。 结果：经FDR校正后，Ki-67表达与多个ADC值呈显著负相关，包括ADC10百分位数（r=-0.397，校正p=0.032）、ADC90百分位数（r=-0.394，校正p=0.032）、ADC最大值（r=-0.362，校正p=0.048）、ADC平均值（r=-0.421，校正p=0.032）、ADC中位数（r=-0.422，校正p=0.032）、ADC最小值（r=-0.390，校正p=0.032）及ADC均方根（r=-0.419，校正p=0.032）。相比之下，多个T1 mapping特征与CVF呈显著正相关（校正p<0.05）。 结论：ADC与T1 mapping能为神经母细胞瘤的肿瘤增殖和细胞外基质成分提供互补性信息。这些临床前发现支持开展进一步研究以验证其潜在的临床应用价值。
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