3D Super-Resolution US Imaging of Rabbit Lymph Node Vasculature in Vivo by Using Microbubbles

Abstract

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).

A clinically aligned experimental approach for quantitative characterization of patient-specific cardiovascular models

“…Recent advances in Doppler techniques such as ultrafast Doppler and super resolution Doppler should be able to improve significantly the sensitivity of this technique, reducing the need to increase gains. 25,26 This limitation can be overcome by reorienting the transducer with respect to the replica when measurements are required along the entire circumference of the vessel. Nevertheless, for the purpose of characterization, experimental measurements show that the flow inside the replicas match the CFD analysis.…”

Super-resolution Ultrasound Imaging

“…This method was implemented in vivo by Ackermann and Schmitz (2016). Alternatively, multiple lower-volume bolus injections can be performed to improve the duration of the desired bubble concentration as implemented in Errico et al (2015) and Zhu et al (2019). Additionally, destructionÀreplenishment sequences can be performed after contrast injection to capture the reperfusion of microbubbles into a region before their signals overlap, as in Opacic et al (2018).…”

“…Third, microbubble positions need to be accumulated for a long time, up to several minutes, to attain the capillary level. Reconstructing a volume through plane-by-plane imaging as in Errico et al (2015), Lin et al (2017b) or Zhu et al (2019) is difficult to transfer successfully to the clinic. Indeed, it could make ultrasound imaging even more user dependent, as the plane will have to be chosen and preserved for an extended time to avoid trading off the underlying resolution.…”

“…Accurate identification and quantification of metastatic lymph nodes remain essential for prognosis and treatment planning in cancer patients (Grills et al 2003). Recently, super-resolution of the micro-vasculature of rabbit popliteal lymph nodes has been performed (Zhu et al 2019) (Fig. 7).…”

Short Acquisition Time Super-Resolution Ultrasound Microvessel Imaging via Microbubble Separation

“…Contrast MBs can be considered as acoustic point scatterers, since they are substantially smaller than the typical ultrasound wavelength, but also provide strong acoustic backscatter, permitting the application of signal processing methods that can overcome the inherent compromise between ultrasound frequency and attenuation. ULM has been shown by numerous research groups [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] to break the diffraction limit of conventional ultrasound, resulting in an approximately tenfold improvement in imaging resolution while maintaining imaging penetration depth. Furthermore, as an ultrasound-based imaging modality, ULM is safe, non-invasive, low-cost, and lacks ionizing radiation, thereby promising great clinical significance by providing capillary-level imaging resolution at acoustic-level imaging penetrations.…”