Region-by-region analysis of PET, MRI, and histology in en bloc-resected oligodendrogliomas reveals intra-tumoral heterogeneity.
Region-by-region analysis of PET, MRI, and histology in en bloc-resected oligodendrogliomas reveals intra-tumoral heterogeneity.
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DOI：
10.1007/s00259-018-4107-z
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发表时间：
2019-03
影响因子：
9.1
通讯作者：
Smits A
中科院分区：
文献类型：
--
作者：
Roodakker KR;Alhuseinalkhudhur A;Al-Jaff M;Georganaki M;Zetterling M;Berntsson SG;Danfors T;Strand R;Edqvist PH;Dimberg A;Larsson EM;Smits A
少突胶质细胞瘤在影像表现上是异质性肿瘤，需要更深入地了解肿瘤的组织病理学特征与成像参数的关系。我们使用PET-MRI-组织学联合配准，目的是研究肿瘤内11C-蛋氨酸(MET)摄取与肿瘤灌注和相应区域组织学细胞标记物的蛋白表达的关系。对覆盖整个切除肿瘤的四个肿瘤的连续组织切片进行了IDH1突变蛋白(肿瘤细胞)、Ki67(增殖细胞)和CD34(血管)抗体的免疫组织化学染色。开发了基于解剖标志的软件，用于后续组织学图像的联合配准，这些图像覆盖在相应的MET PET扫描和MRI灌注图上。在整个肿瘤体积上选择感兴趣区(ROI)，覆盖热点区域、热点邻近区域和肿瘤边界与浸润区。在ROI中测量肿瘤与正常组织的MET摄取比值(T/N)和平均相对脑血容量(RCBV)，并对相应区域组织细胞标志物的蛋白表达进行定量。计算MET摄取、rCBV和定量蛋白表达之间的统计相关性。在4例少突胶质细胞瘤中，共有84个感兴趣区。在所有肿瘤中，MET摄取与肿瘤细胞密度显著相关(p <； 0.05)。在2例肿瘤中，MET与增殖细胞密度和血管细胞密度相关。MET摄取与rCBV、rCBV与组织学细胞标志物无显著相关性。MET在热点、热点外和浸润性肿瘤边缘的摄取一致反映了肿瘤细胞密度。MET摄取与血管密度和增殖细胞密度之间的相关性在浸润性肿瘤边缘不那么严格，可能更容易受到肿瘤周围较大血管引起的伪影的影响。尽管基于有限数量的样本，但这项研究提供了MET作为肿瘤细胞密度指标的组织学证据，以及在少突胶质瘤中rCBV和组织细胞标志物之间缺乏统计学上的显著相关性。本文的在线版本(10.1007/s00259-0184107-z)包含向授权用户提供的补充材料。
Oligodendrogliomas are heterogeneous tumors in terms of imaging appearance, and a deeper understanding of the histopathological tumor characteristics in correlation to imaging parameters is needed. We used PET-to-MRI-to-histology co-registration with the aim of studying intra-tumoral 11C-methionine (MET) uptake in relation to tumor perfusion and the protein expression of histological cell markers in corresponding areas. Consecutive histological sections of four tumors covering the entire en bloc-removed tumor were immunostained with antibodies against IDH1-mutated protein (tumor cells), Ki67 (proliferating cells), and CD34 (blood vessels). Software was developed for anatomical landmarks-based co-registration of subsequent histological images, which were overlaid on corresponding MET PET scans and MRI perfusion maps. Regions of interest (ROIs) on PET were selected throughout the entire tumor volume, covering hot spot areas, areas adjacent to hot spots, and tumor borders with infiltrating zone. Tumor-to-normal tissue (T/N) ratios of MET uptake and mean relative cerebral blood volume (rCBV) were measured in the ROIs and protein expression of histological cell markers was quantified in corresponding regions. Statistical correlations were calculated between MET uptake, rCBV, and quantified protein expression. A total of 84 ROIs were selected in four oligodendrogliomas. A significant correlation (p < 0.05) between MET uptake and tumor cell density was demonstrated in all tumors separately. In two tumors, MET correlated with the density of proliferating cells and vessel cell density. There were no significant correlations between MET uptake and rCBV, and between rCBV and histological cell markers. The MET uptake in hot spots, outside hotspots, and in infiltrating tumor edges unanimously reflects tumor cell density. The correlation between MET uptake and vessel density and density of proliferating cells is less stringent in infiltrating tumor edges and is probably more susceptible to artifacts caused by larger blood vessels surrounding the tumor. Although based on a limited number of samples, this study provides histological proof for MET as an indicator of tumor cell density and for the lack of statistically significant correlations between rCBV and histological cell markers in oligodendrogliomas. The online version of this article (10.1007/s00259-018-4107-z) contains supplementary material, which is available to authorized users.
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影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
DOI：
10.1007/s00259-001-0690-4
发表时间：
2002-02-01
影响因子：
9.1
作者：
Chung, JK;Kim, YK;Lee, MC
通讯作者：
Lee, MC
影响因子：
5.6
作者：
Chan, ASY;Leung, SY;Chung, LP
通讯作者：
Chung, LP
影响因子：
2
作者：
Bette, Stefanie;Gempt, Jens;Ringel, Florian
通讯作者：
Ringel, Florian
影响因子：
2.6
作者：
Friedman, S. N.;Bambrough, P. J.;Hoggard, N.
通讯作者：
Hoggard, N.