Revealing the biology behind MRI signatures in high grade glioma.
Revealing the biology behind MRI signatures in high grade glioma.
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揭示高级别神经胶质瘤 MRI 特征背后的生物学。
DOI：
10.1101/2023.12.08.23299733
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Plaisier,ChristopherL
中科院分区：
文献类型：
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作者：
Lewis,ErikaM;Mao,Lingchao;Wang,Lujia;Swanson,KristinR;Barajas,RamonF;Li,Jing;Tran,NhanL;Hu,LelandS;Plaisier,ChristopherL
在高级别胶质瘤(HGG)的治疗过程中，常规收集磁共振成像(MRI)测量数据，以确定肿瘤边界并指导手术切除肿瘤。利用空间匹配的MRI和转录本，我们发现了通过MRI测量捕捉到的HGG肿瘤生物学。我们战略性地将空间匹配的组学特征叠加到先前存在的多形性胶质母细胞瘤(GBM)转录图谱上，以增强我们分析的稳健性。我们发现，T1+C测量旨在捕捉血管系统和血脑屏障(BBB)的破坏以及随后的造影剂外渗，也间接揭示免疫细胞的渗透。肿瘤内血管系统和血脑屏障的破坏创造了一个允许的浸润性环境，使抗炎巨噬细胞能够向肿瘤内迁移。这些关系通过组织学和与免疫细胞迁移和增殖相关的基因的丰富而得到验证。此外，T2加权(T2W)和平均扩散率(MD)测量与血管生成相关，并通过组织学和与新生血管相关的基因的丰富来验证。此外，我们建立了一种无偏见的方法，用于在未来的研究中确定MRI测量和肿瘤生物学之间的额外联系，特别是结合新的MRI技术。最后，我们说明了如何使用非侵入性MRI来绘制整个肿瘤的HGG生物学图，这为开发诊断、预后或治疗效果生物标记物以改善患者预后提供了一个平台。
Magnetic resonance imaging (MRI) measurements are routinely collected during the treatment of high-grade gliomas (HGGs) to characterize tumor boundaries and guide surgical tumor resection. Using spatially matched MRI and transcriptomics we discovered HGG tumor biology captured by MRI measurements. We strategically overlaid the spatially matched omics characterizations onto a pre-existing transcriptional map of glioblastoma multiforme (GBM) to enhance the robustness of our analyses. We discovered that T1+C measurements, designed to capture vasculature and blood brain barrier (BBB) breakdown and subsequent contrast extravasation, also indirectly reveal immune cell infiltration. The disruption of the vasculature and BBB within the tumor creates a permissive infiltrative environment that enables the transmigration of anti-inflammatory macrophages into tumors. These relationships were validated through histology and enrichment of genes associated with immune cell transmigration and proliferation. Additionally, T2-weighted (T2W) and mean diffusivity (MD) measurements were associated with angiogenesis and validated using histology and enrichment of genes involved in neovascularization. Furthermore, we establish an unbiased approach for identifying additional linkages between MRI measurements and tumor biology in future studies, particularly with the integration of novel MRI techniques. Lastly, we illustrated how noninvasive MRI can be used to map HGG biology spatially across a tumor, and this provides a platform to develop diagnostics, prognostics, or treatment efficacy biomarkers to improve patient outcomes.