In vivo 3D microvascular imaging without contrast agents

C. H. Leow, N. L. Bush, A. Stanziola, M. Braga, A. Shah, J. Hernández-Gil, N. J. Long, E. O. Aboagye, J. C. Bamber and M.X. Tang, “3D microvascular imaging using high frame rate ultrasound and ASAP without contrast agents: development and initial in vivo evaluation on non-tumour and tumour models

IEEE Transactions on Ultrasonics Ferroelectrics and Frequency Control PP(99):1-1

DOI: 10.1109/TUFFC.2019.2906434


C.H. Leow, A. Stanziola and M-X. Tang are with the Department of Bioengineering, Imperial College London, United Kingdom. (e-mail:

N.L.Bush, A. Shah and J.C. Bamber are with the Joint Department of Physics and Cancer Research UK Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, United Kingdom.

M. Braga, J. Hernández-Gil, N. J. Long and E.O. Aboagye are with the Comprehensive Cancer Imaging Centre, Department of Surgery & Cancer, United Kingdom.

J. Hernández-Gil and N. J. Long are also with the Department of Chemistry, Imperial College London, United Kingdom.


Three-dimensional imaging is valuable to non-invasively assess angiogenesis given the complex 3D architecture of vascular networks. The emergence of high frame rate (HFR) ultrasound, which can produce thousands of images per second, has inspired novel signal processing techniques and their applications in structural and functional imaging of blood vessels. Although highly sensitive vascular mapping has been demonstrated using ultrafast Doppler, the detectability of microvasculature from the background noise may be hindered by the low signal to noise ratio (SNR) particularly in deeper region and without the use of contrast agents. We have recently demonstrated a coherence-based technique, acoustic sub-aperture imaging (ASAP), for super-contrast vascular imaging and illustrated the contrast improvement using HFR contrast-enhanced ultrasound. In this work, we provide a feasibility study for microvascular imaging using ASAP without contrast agents, and extend its capability from 2D to volumetric vascular mapping. Using an ultrasound research system and a pre-clinical probe, we demonstrated the improved visibility of microvascular mapping using ASAP in comparison to ultrafast Power Doppler (PD) on a mouse kidney, liver and tumour without contrast agent injection. The SNR of ASAP images improves in average by 10dB when compared to PD. Besides, directional velocity mappings were also demonstrated by combining ASAP with the phase information extracted from lag-1 autocorrelation. Three-dimensional vascular and velocity mapping of the mouse kidney, liver and tumour were demonstrated by stacking the ASAP images acquired using 2D ultrasound imaging and a trigger-controlled linear translation stage. The 3D results depicted clear micro-vasculature morphologies and functional information in terms of flow direction and velocity in two non-tumour models and a tumour model. In conclusion, we have demonstrated a new 3D in vivo ultrasound micro-vascular imaging technique with significantly improved SNR over existing ultrafast Doppler.

Supporting Bodies:

This work is funded by the CRUK Multidisciplinary Project Award (C53470/A22353). C.H Leow would like to acknowledge NVIDIA Corporation for the donation of Titan XP GPU used in this research.

Fig: Volume render presentation of 3D microvascular images of a non-tumour kidney (left), liver (middle), and tumour (right) mouse model.