Label-Free Visualization of Early Cancer Hepatic Micrometastasis and Intraoperative Image-Guided Surgery by Photoacoustic Imaging
Label-Free Visualization of Early Cancer Hepatic Micrometastasis and Intraoperative Image-Guided Surgery by Photoacoustic Imaging
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DOI：
10.2967/jnumed.119.233155
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发表时间：
2020-07-01
影响因子：
9.3
通讯作者：
Nie, Liming
中科院分区：
文献类型：
--
作者：
Yu, Qian;Huang, Shanshan;Nie, Liming
癌症微转移的早期诊断和治疗对传统的影像技术提出了极大的挑战。本研究的目的是评价光声成像(PAI)在黑色素瘤肝脏微转移的早期发现和在术中指导下辅助肿瘤切除的作用。方法：按厦门大学动物研究伦理委员会批准的方案进行体内实验。首先，建立了小鼠B16黑色素瘤肝转移模型(n=10)，以研究B16黑色素瘤在体内的微转移发展。接下来，用可扩展的PAI仪器、超声波、9.4-T高分辨率磁共振成像、PET/CT和生物发光成像对小鼠进行成像。用线性最小二乘法对680~850 nm光学波长的PAI扫描图像进行光谱分离，以区分不同的成分。用双尾配对检验确定不同模式之间信号背景比的差异。通过组织学检查对诊断结果进行评价。被诊断为肝癌的患者的切除肝脏样本也被检查以确定肿瘤的边界。转移性黑色素瘤的手术切除是由便携式PAI系统在体内精确引导的。结果：PAI能够在体内检测到大约400微米深至7毫米的转移--这个大小比超声波和MRI所能检测到的要小。术后第8天(4.2±-0.2，n=6)和第14天(9.2+/-0.4，n=5)肿瘤/肝脏比值明显高于正电子发射计算机断层扫描(PET/CT，分别为1.8+/-0.1，n=5和4.5+/-0.2，P<；0.001)。功能性PAI显示肿瘤生长过程中血氧饱和度的动态变化。L的体外检测下限约为219个/亩。我们使用便携式PAI系统成功地完成了术中PAI引导的活体手术。结论：我们的研究结果为无创检测微转移和指导术中切除提供了一种快速有效的辅助临床影像应用。
The detection of cancer micrometastasis for early diagnosis and treatment poses a great challenge for conventional imaging techniques. The aim of our study was to evaluate the performance of photoacoustic imaging (PAI) in detecting hepatic micrometastases from melanoma at a very early stage and in aiding tumor resection by intraoperative guidance. Methods: In vivo studies were performed by following protocols approved by the Ethical Committee for Animal Research at Xiamen University. First, a mouse model of B16 melanoma metastatic to the liver (n = 10) was established to study the development of micrometastases in vivo. Next, the mice were imaged by a scalable PAI instrument, ultrasound, 9.4-T high-resolution MRI, PET/CT, and bioluminescence imaging. PAI scans acquired with optical wavelengths of 680-850 nm were kept spectrally unmixed by using a linear least-squares method to differentiate various components. Differences in signal-to-background ratios among different modalities were determined with the 2-tailed paired test. The diagnostic results were assessed with histologic examination. Excised liver samples from patients diagnosed with hepatic cancer were also examined to identify the tumor boundaries. Surgical removal of metastatic melanoma was precisely guided in vivo by the portable PAI system. Results: PAI was able to detect metastases as small as approximately 400 mu m at a depth of up to 7 mm in vivo-a size that is smaller than can be detected with ultrasound and MRI. The tumor-to-liver ratio for PAI at 8 d (4.2 +/- 0.2, n = 6) and 14 d (9.2 +/- 0.4, n = 5) was significantly higher than for PET/CT (1.8 +/- 0.1, n = 5, and 4.5 +/- 0.2, n = 5, respectively; P < 0.001 for both). Functional PAI revealed dynamic oxygen saturation changes during tumor growth. The limit of detection was approximately 219 cells/mu L in vitro. We successfully performed intraoperative PAI-guided surgery in vivo using the portable PAI system. Conclusion: Our findings offer a rapid and effective complementary clinical imaging application to noninvasively detect micrometastases and guide intraoperative resection.