Theranostics 2019; 9(21):6143-6156. doi:10.7150/thno.37284

Research Paper

Automatic Respiratory Gating Hepatic DCEUS-based Dual-phase Multi-parametric Functional Perfusion Imaging using a Derivative Principal Component Analysis

Diya Wang1,2,✉, Guy Cloutier2,3, Yan Fan4, Yanli Hou5, Zhe Su1, Qiang Su5,✉, Mingxi Wan1,✉

1. Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, P. R. China.
2. University of Montreal Hospital Research Center, Montreal, QC, Canada.
3. Department of Radiology, Radio-Oncology and Nuclear Medicine, and Institute of Biomedical Engineering, University of Montreal, Montreal, QC, Canada.
4. Alliance Franco-Chinoise, Montreal, QC, Canada.
5. Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, 1000050, P. R. China.

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Wang D, Cloutier G, Fan Y, Hou Y, Su Z, Su Q, Wan M. Automatic Respiratory Gating Hepatic DCEUS-based Dual-phase Multi-parametric Functional Perfusion Imaging using a Derivative Principal Component Analysis. Theranostics 2019; 9(21):6143-6156. doi:10.7150/thno.37284. Available from

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Purpose: Angiogenesis in liver cancers can be characterized by hepatic functional perfusion imaging (FPI) on the basis of dynamic contrast-enhanced ultrasound (DCEUS). However, accuracy is limited by breathing motion which results in out-of-plane image artifacts. Current hepatic FPI studies do not correct for these artifacts and lack the evaluation of correction accuracy. Thus, a hepatic DCEUS-based dual-phase multi-parametric FPI (DM-FPI) scheme using a derivative principal component analysis (PCA) respiratory gating is proposed to overcome these limitations.

Materials and Methods: By considering severe 3D out-of-plane respiratory motions, the proposed scheme's accuracy was verified with in vitro DCEUS experiments in a flow model mimicking a hepatic vein. The feasibility was further demonstrated by considering in vivo DCEUS measurements in normal rabbit livers, and hepatic cavernous hemangioma and hepatocellular carcinoma in patients. After respiratory kinetics was extracted through PCA of DCEUS sequences under free-breathing condition, dual-phase respiratory gating microbubble kinetics was identified by using a derivative PCA zero-crossing dual-phase detection, respectively. Six dual-phase hemodynamic parameters were estimated from the dual-phase microbubble kinetics and DM-FPI was then reconstructed via color-coding to quantify 2.5D angiogenic hemodynamic distribution for live tumors.

Results: Compared with no respiratory gating, the mean square error of respiratory gating DM-FPI decreased by 1893.9 ± 965.4 (p < 0.05), and mean noise coefficients decreased by 17.5 ± 7.1 (p < 0.05), whereas correlation coefficients improved by 0.4 ± 0.2 (p < 0.01). DM-FPI observably removed severe respiratory motion artifacts on PFI and markedly enhanced the accuracy and robustness both in vitro and in vivo.

Conclusions: DM-FPI precisely characterized and distinguished the heterogeneous angiogenic hemodynamics about perfusion volume, blood flow and flow rate within two anatomical sections in the normal liver, and in benign and malignant hepatic tumors. DCEUS-based DM-FPI scheme might be a useful tool to help clinicians diagnose and provide suitable therapies for liver tumors.

Keywords: contrast-enhanced ultrasound, functional perfusion imaging, respiratory motion, machine learning, principal component analysis