Ultrasound imaging is the most widely used method for visualising and quantifying blood flow in medical practice, but existing techniques have various limitations in terms of imaging sensitivity, field of view, flow angle dependence, and imaging depth. In this study, we developed an ultrasound imaging velocimetry approach capable of visualising and quantifying dynamic flow, by combining high-frame-rate plane wave ultrasound imaging, microbubble contrast agents, pulse inversion contrast imaging and speckle image tracking algorithms. The system was initially evaluated in vitro on both straight and carotid-mimicking vessels with steady and pulsatile flows and in vivo in the rabbit aorta. Colour and spectral Doppler measurements were also made. Initial flow mapping results were compared with theoretical prediction and reference Doppler measurements and indicate the potential of the new system as a highly sensitive, accurate, angle-independent and full field-of-view velocity mapping tool capable of tracking and quantifying fast and dynamic flows.

Photo-activated localization microscopy (PALM) has revolutionized the field of fluorescence microscopy by breaking the diffraction limit in spatial resolution. In this study, “acoustic wave sparsely activated localization microscopy (AWSALM),” an acoustic counterpart of PALM, is developed to super-resolve structures which cannot be resolved by conventional B-mode imaging. AWSALM utilizes acoustic waves to sparsely and stochastically activate decafluorobutane nanodroplets by acoustic vaporization and to simultaneously deactivate the existing vaporized nanodroplets via acoustic destruction. In this method, activation, imaging, and deactivation are all performed using acoustic waves. Experimental results show that sub-wavelength micro-structures not resolvable by standard B-mode ultrasound images can be separated by AWSALM. This technique is flow independent and does not require a low concentration of contrast agents, as is required by current ultrasound super resolution techniques. Acoustic activation and deactivation can be controlled by adjusting the acoustic pressure, which remains well within the FDA approved safety range. In conclusion, this study shows the promise of a flow and contrast agent concentration independent super-resolution ultrasound technique which has potential to be faster and go beyond vascular imaging.

he lymphatic system plays an important role in human circulatory and immune homeostasis. Peripheral lymph nodes (LNs) are regional hubs that receive interstitial fluid as well as circulating blood. They contain large numbers of immune cells and the complex internal architecture of LNs constitutes an interface between the cellular and molecular constituents of lymph and blood. Cellular debris is filtered and primary immune responses can be generated in LNs to pathogens (1). LN blood vessels are highly specialized for facilitating T-cell entry to the node (2). The spatial distribution of surface area for exchange of fluid with blood vessels in LNs determines the amount of local fluid movement, and it is therefore important to quantify the three-dimensional distribution of LN blood vessels. In patients with cancer, tumor cells can also traffic through lymphatic channels to regional LNs (3). Recent studies have demonstrated that metastatic cells migrate toward and into LN blood vessels (4,5). Malignant processes are associated with both angiogenesis and lymphangiogenesis (6). LNs may even act as a permissive niche to support the proliferation of metastatic cells and promote movement to distant sites (7). The accurate identification and quantification of metastatic LNs remains essential for prognosis and treatment planning (8).

High frame rate 3-D ultrasound imaging technology combined with super-resolution processing method can visualize 3-D microvascular structures by overcoming the diffraction limited resolution in every spatial direction. However, 3-D superresolution ultrasound imaging using a full 2-D array requires a system with large number of independent channels, the design of which might be impractical due to the high cost, complexity, and volume of data produced.In this study, a 2-D sparse array was designed and fabricated with 512 elements chosen from a density-tapered 2-D spiral layout. High frame rate volumetric imaging was performed using two synchronized ULA-OP 256 research scanners. Volumetric images were constructed by coherently compounding 9-angle plane waves acquired in 3 milliseconds at a pulse repetition frequency of 3000 Hz. To allow microbubbles sufficient time to move between consequent compounded volumetric frames, a 7millisecond delay was introduced after each volume acquisition. This reduced the effective volume acquisition speed to 100 Hz and the total acquired data size by 3.3-fold. Localization-based 3-D super-resolution images of two touching sub-wavelength tubes were generated from 6000 volumes acquired in 60 seconds. In conclusion, this work demonstrates the feasibility of 3D superresolution imaging and super-resolved velocity mapping using a customized 2D sparse array transducer.

In this study, a technique for high-frame-rate ultrasound imaging velocimetry (UIV) is extended first to provide more robust quantitative flow velocity mapping using ensemble correlation of images without coherent compounding, and second to generate spatio-temporal wall shear stress (WSS) distribution. A simulation model, which couples the ultrasound simulator with analytical flow solution, was implemented to evaluate its accuracy. It is shown that the proposed approach can reduce errors in velocity estimation by up to 10-fold in comparison with the coherent correlation approach. Mean errors (ME) of 3.2% and 8.6% were estimated under a steady flow condition, while 3.0% and 10.6% were found under a pulsatile condition for the velocity and wall shear rate (WSR) measurement, respectively. Appropriate filter parameters were selected to constrain the velocity profiles before WSR estimations and the effects of incorrect wall tracking were quantified under a controlled environment. Although accurate wall tracking is found to be critical in WSR measurement (as a 200 µm deviation from the wall may yield up to a 60% error), this can be mitigated by HFR imaging (of up to 10 kHz) with contrast agents, which allow for improved differentiation of the wall-fluid boundaries. In vitro investigations on two carotid bifurcation phantoms, normal and diseased, were conducted, and their relative differences in terms of the flow patterns and WSR distribution were demonstrated. It is shown that high-frame-rate UIV technique can be a non-invasive tool to measure quantitatively the spatio-temporal velocity and WSS distribution.