Multispectral quantification of tissue types in a RIF-1 tumor model with histological validation. Part I

Multispectral quantification of tissue types in a RIF-1 tumor model with histological validation. Part I
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DOI:
10.1002/mrm.21161
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发表时间:
2007-03-01
影响因子:
3.3
通讯作者:
Helmer, Karl G.
Helmer, Karl G.
中科院分区:
医学3区
文献类型:
--
作者:
Henning, Erica C.;Azuma, Chieko;Helmer, Karl G.

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治疗效果的准确评估受到肿瘤内和肿瘤间异质性的混淆。为了解决这个问题,我们采用了多光谱(MS)分析,使用表观扩散系数(ADC),T-2,质子密度(M-0),和k均值(KM)聚类算法,以确定多个隔间内的活性和坏死组织在辐射诱导的纤维肉瘤(RIF-1)肿瘤模型接受单剂量(1000 cGy)放疗。通过苏木精-伊红(H&E)染色和缺氧诱导因子-1 α(HIF-1 α)免疫组织化学进行组织学验证,实现KM方法的优化。最佳KM方法被确定为双特征(ADC,T-2)和四簇(活组织和坏死组织各两簇)分割。存活组织(r = 0.94,P < 0.01)和坏死组织(r = 0.69,P = 0.07)的KM体积估计值与它们的H&E对应物高度相关。HIF-1 α免疫组化显示HIF-1 α表达的强度倾向于集中在坏死周围区域,支持将活组织细分为氧合良好和缺氧区域。由于坏死和缺氧都与治疗反应差和患者生存率降低有关,因此用这种方法定量坏死程度和缺氧严重程度的能力可能有助于规划和修改治疗方案。
Accurate assessments of therapeutic efficacy are confounded by intra- and intertumor heterogeneity. To address this issue we employed multispectral (MS) analysis using the apparent diffusion coefficient (ADC), T-2, proton density (M-0), and k-means (KM) clustering algorithm to identify multiple compartments within both viable and necrotic tissue in a radiation-induced fibrosarcoma (RIF-1) tumor model receiving single-dose (1000 cGy) radiotherapy. Optimization of the KM method was achieved through histological validation by hematoxylin-eosin (H&E) staining and hypoxia-inducible factor-1 alpha (HIF-1 alpha) immunohistochemistry. The optimum KM method was determined to be a two-feature (ADC, T-2) and four-cluster (two clusters each of viable tissue and necrosis) segmentation. KM volume estimates for both viable (r = 0.94, P < 0.01) and necrotic (r = 0.69, P = 0.07) tissue were highly correlated with their H&E counterparts. HIF-1 alpha immunohistochemistry showed that the intensity of HIF-1 alpha expression tended to be concentrated in perinecrotic regions, supporting the subdivision of the viable tissue into well-oxygenated and hypoxic regions. Since both necrosis and hypoxia have been implicated in poor treatment response and reduced patient survival, the ability to quantify the degree of necrosis and the severity of hypoxia with this method may aid in the planning and modification of treatment regimens.