Washington University in St. Louis, Department of Biomedical Engineering, Optical Imaging Laboratory, One Brookings Drive, St. Louis, Missouri 63130, United States.
J Biomed Opt. 2017 Apr 1;22(4):41004. doi: 10.1117/1.JBO.22.4.041004.
Circulating tumor cell (CTC) clusters, arising from multicellular groupings in a primary tumor, greatly elevate the metastatic potential of cancer compared with single CTCs. High-throughput detection and quantification of CTC clusters are important for understanding the tumor metastatic process and improving cancer therapy. Here, we applied a linear-array-based photoacoustic tomography (LA-PAT) system and improved the image reconstruction for label-free high-throughput CTC cluster detection and quantification <italic<in vivo</italic<. The feasibility was first demonstrated by imaging CTC cluster <italic<ex vivo</italic<. The relationship between the contrast-to-noise ratios (CNRs) and the number of cells in melanoma tumor cell clusters was investigated and verified. Melanoma CTC clusters with a minimum of four cells could be detected, and the number of cells could be computed from the CNR. Finally, we demonstrated imaging of injected melanoma CTC clusters in rats <italic<in vivo</italic<. Similarly, the number of cells in the melanoma CTC clusters could be quantified. The data showed that larger CTC clusters had faster clearance rates in the bloodstream, which agreed with the literature. The results demonstrated the capability of LA-PAT to detect and quantify melanoma CTC clusters <italic<in vivo</italic< and showed its potential for tumor metastasis study and cancer therapy.
循环肿瘤细胞（CTC）簇起源于原发性肿瘤中的多细胞聚集，与单个 CTC 相比，大大提高了癌症的转移潜力。高通量检测和定量 CTC 簇对于理解肿瘤转移过程和改善癌症治疗非常重要。在这里，我们应用了基于线性阵列的光声断层扫描（LA-PAT）系统，并改进了图像重建，用于无标记的高通量 CTC 簇检测和定量<italic<体内</italic<。首先通过对 CTC 簇的<italic<离体</italic<成像证明了其可行性。研究并验证了黑素瘤肿瘤细胞簇的对比噪声比（CNR）与细胞数量之间的关系。可以检测到至少有四个细胞的黑素瘤 CTC 簇，并且可以根据 CNR 计算出细胞数量。最后，我们证明了在大鼠<italic<体内</italic<注射黑素瘤 CTC 簇的成像。同样，可以对黑素瘤 CTC 簇中的细胞数量进行定量。数据表明，较大的 CTC 簇在血液中具有更快的清除率，这与文献一致。结果表明 LA-PAT 具有检测和定量<italic<体内</italic<黑素瘤 CTC 簇的能力，并显示了其在肿瘤转移研究和癌症治疗中的潜力。
