Theranostics 2017; 7(15):3745-3758. doi:10.7150/thno.20329

Research Paper

Quantitative Three-Dimensional Dynamic Contrast-Enhanced Ultrasound Imaging: First-In-Human Pilot Study in Patients with Liver Metastases

Ahmed El Kaffas1*, Rosa Maria Silveira Sigrist1*, George Fisher2, Sunitha Bachawal1, Joy Liau1, Huaijun Wang1, Alexander Karanany1, Isabelle Durot1, Jarrett Rosenberg1, Dimitre Hristov3, Jürgen K. Willmann1✉

1. Department of Radiology, Molecular Imaging Program at Stanford, School of Medicine, Stanford University, Stanford, CA
2. Department of Medicine, Division of Oncology, School of Medicine, Stanford University, Stanford, CA
3. Department of Radiation Oncology, School of Medicine, Stanford University, Stanford, CA
*These authors contributed equally to this work.


Purpose: To perform a clinical assessment of quantitative three-dimensional (3D) dynamic contrast-enhanced ultrasound (DCE-US) feasibility and repeatability in patients with liver metastasis, and to evaluate the extent of quantitative perfusion parameter sampling errors in 2D compared to 3D DCE-US imaging.

Materials and Methods: Twenty consecutive 3D DCE-US scans of liver metastases were performed in 11 patients (45% women; mean age, 54.5 years; range, 48-60 years; 55% men; mean age, 57.6 years; range, 47-68 years). Pairs of repeated disruption-replenishment and bolus DCE-US images were acquired to determine repeatability of parameters. Disruption-replenishment was carried out by infusing 0.9 mL of microbubbles (Definity; Latheus Medical Imaging) diluted in 35.1 mL of saline over 8 min. Bolus consisted of intravenous injection of 0.2 mL microbubbles. Volumes-of-interest (VOI) and regions-or-interest (ROI) were segmented by two different readers in images to extract 3D and 2D perfusion parameters, respectively. Disruption-replenishment parameters were: relative blood volume (rBV), relative blood flow (rBF). Bolus parameters included: time-to-peak (TP), peak enhancement (PE), area-under-the-curve (AUC), and mean-transit-time (MTT).

Results: Clinical feasibility and repeatability of 3D DCE-US using both the destruction-replenishment and bolus technique was demonstrated. The repeatability of 3D measurements between pairs of repeated acquisitions was assessed with the concordance correlation coefficient (CCC), and found to be excellent for all parameters (CCC > 0.80), except for the TP (0.74) and MTT (0.30) parameters. The CCC between readers was found to be excellent (CCC > 0.80) for all parameters except for TP (0.71) and MTT (0.52). There was a large Coefficient of Variation (COV) in intra-tumor measurements for 2D parameters (0.18-0.52). Same-tumor measurements made in 3D were significantly different (P = 0.001) than measurements made in 2D; a percent difference of up to 86% was observed between measurements made in 2D compared to 3D in the same tumor.

Conclusions: 3D DCE-US imaging of liver metastases with a matrix array transducer is feasible and repeatable in the clinic. Results support 3D instead of 2D DCE US imaging to minimize sampling errors due to tumor heterogeneity.

Keywords: Ultrasound, contrast-enhanced, three-dimensional (3D), cancer

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How to cite this article:
El Kaffas A, Sigrist RMS, Fisher G, Bachawal S, Liau J, Wang H, Karanany A, Durot I, Rosenberg J, Hristov D, Willmann JK. Quantitative Three-Dimensional Dynamic Contrast-Enhanced Ultrasound Imaging: First-In-Human Pilot Study in Patients with Liver Metastases. Theranostics 2017; 7(15):3745-3758. doi:10.7150/thno.20329. Available from