Evaluating the extent of cell death in 3D high frequency ultrasound by registration with whole-mount tumor histopathology
Evaluating the extent of cell death in 3D high frequency ultrasound by registration with whole-mount tumor histopathology
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DOI：
10.1118/1.3459020
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发表时间：
2010-08-01
期刊：
影响因子：
3.8
通讯作者：
Brock, Kristy K.
中科院分区：
文献类型：
--
作者：
Vlad, Roxana M.;Kolios, Michael C.;Brock, Kristy K.
目的：高频超声成像（10-30 MHz）能够在治疗给药后24小时内评估小鼠肿瘤对放疗的反应。这种技术的优点是，图像对比度是由垂死细胞的物理性质的变化产生的。因此，受试者可以在治疗之前和治疗期间多次成像，而不需要注射专门的造影剂。这项研究的动机是需要提供的细胞死亡的体积和定位之间的比较指标，从组织学评估，与体积和定位的细胞死亡替代品，评估为区域增加回声从超声images.Methods：小鼠暴露于辐射剂量为2，4，和8戈伊。使用宽带25 MHz中心频率换能器在暴露于辐射之前和之后24 h从每个肿瘤收集超声图像。放疗后，肿瘤在超声图像中显示出高回声区域，对应于组织学中的细胞死亡区域。超声和组织学图像严格配准。在组织学图像上手动勾画肿瘤和细胞死亡区域。同样，在超声图像上勾画出肿瘤和高回声区域。每组轮廓被转换为一个体积网格，以比较的体积和定位的细胞死亡在组织学和超声images.Results：一个收缩因子为17 +/- 2%，计算从组织学和超声图像中的肿瘤体积的差异进行评估。这用于校正从组织学评估的肿瘤和细胞死亡体积。经校正后，超声和组织学图像评估的细胞死亡体积之间的平均绝对差异为11 +/- 14%，体积重叠为70 +/- 12%.Conclusions：该方法提供了组织学评估的细胞死亡体积与超声图像评估的细胞死亡体积之间的比较指标。在此应用超声成像评估小鼠肿瘤对放疗的早期肿瘤反应的能力。同样，它可以在未来应用于评估超声成像的能力，以评估早期肿瘤对其他癌症治疗方式的反应。这项研究有助于了解超声成像在非侵入性检测细胞死亡方面的能力和局限性。这为未来在临床前和临床应用中使用超声以根据肿瘤对癌症治疗的反应调整治疗提供了基础。(C)2010年美国医学物理学家协会。[DOI：10.1118/1.3459020]
Purpose: High frequency ultrasound imaging, 10-30 MHz, has the capability to assess tumor response to radiotherapy in mouse tumors as early as 24 h after treatment administration. The advantage of this technique is that the image contrast is generated by changes in the physical properties of dying cells. Therefore, a subject can be imaged before and multiple times during the treatment without the requirement of injecting specialized contrast agents. This study is motivated by a need to provide metrics of comparison between the volume and localization of cell death, assessed from histology, with the volume and localization of cell death surrogate, assessed as regions with increased echogeneity from ultrasound images.Methods: The mice were exposed to radiation doses of 2, 4, and 8 Gy. Ultrasound images were collected from each tumor before and 24 h after exposure to radiation using a broadband 25 MHz center frequency transducer. After radiotherapy, tumors exhibited hyperechoic regions in ultrasound images that corresponded to areas of cell death in histology. The ultrasound and histological images were rigidly registered. The tumors and regions of cell death were manually outlined on histological images. Similarly, the tumors and hyperechoic regions were outlined on the ultrasound images. Each set of contours was converted to a volumetric mesh in order to compare the volumes and the localization of cell death in histological and ultrasound images.Results: A shrinkage factor of 17 +/- 2% was calculated from the difference in the tumor volumes evaluated from histological and ultrasound images. This was used to correct the tumor and cell death volumes assessed from histology. After this correction, the average absolute difference between the volume of cell death assessed from ultrasound and histological images was 11 +/- 14% and the volume overlap was 70 +/- 12%.Conclusions: The method provided metrics of comparison between the volume of cell death assessed from histology and that assessed from ultrasound images. It was applied here to evaluate the capability of ultrasound imaging to assess early tumor response to radiotherapy in mouse tumors. Similarly, it can be applied in the future to evaluate the capability of ultrasound imaging to assess early tumor response to other modalities of cancer treatment. The study contributes to an understanding of the capabilities and limitation of ultrasound imaging at noninvasively detecting cell death. This provides a foundation for future developments regarding the use of ultrasound in preclinical and clinical applications to adapt treatments based on tumor response to cancer therapy. (C) 2010 American Association of Physicists in Medicine. [DOI: 10.1118/1.3459020]