Abstract
Background Variations in lymph node (LN) microcirculation can be indicative of metastasis. The identification and quantification of metastatic LNs remains essential for prognosis and treatment planning, but a reliable noninvasive imaging technique is lacking. Three-dimensional super-resolution (SR) US has shown potential to noninvasively visualize microvascular networks in vivo. Purpose To study the feasibility of three-dimensional SR US imaging of rabbit LN microvascular structure and blood flow by using microbubbles. Materials and Methods In vivo studies were carried out to image popliteal LNs of two healthy male New Zealand white rabbits aged 6-8 weeks. Three-dimensional, high-frame-rate, contrast material-enhanced US was achieved by mechanically scanning with a linear imaging probe. Individual microbubbles were identified, localized, and tracked to form three-dimensional SR images and super-resolved velocity maps. Acoustic subaperture processing was used to improve image contrast and to generate enhanced power Doppler and color Doppler images. Vessel size and blood flow velocity distributions were evaluated and assessed by using Student paired t test. Results SR images revealed microvessels in the rabbit LN, with branches clearly resolved when separated by 30 µm, which is less than half of the acoustic wavelength and not resolvable by using power or color Doppler. The apparent size distribution of most vessels in the SR images was below 80 µm and agrees with micro-CT data, whereas most of those detected with Doppler techniques were larger than 80 µm in the images. The blood flow velocity distribution indicated that most of the blood flow in rabbit popliteal LN was at velocities lower than 5 mm/sec. Conclusion Three-dimensional super-resolution US imaging using microbubbles allows noninvasive nonionizing visualization and quantification of lymph node microvascular structures and blood flow dynamics with resolution below the wave diffraction limit. This technology has potential for studying the physiologic functions of the lymph system and for clinical detection of lymph node metastasis. Published under a CC BY 4.0 license. Online supplemental material is available for this article.
Highlights
Ree-dimensional US has the potential to improve both qualitative inspection and the accuracy of quantitative approaches when imaging the complex architecture of vascular networks
The lymphatic system plays an important role in human movement, and it is important to quantify the circulatory and immune homeostasis
Key Points nn Three-dimensional super-resolution (SR) US imaging with microbubble contrast agents noninvasively visualized rabbit lymph node (LN) microvessels and quantified blood flow dynamics in vivo with a 15-fold improvement in resolution compared with color or power Doppler
Summary
Ree-dimensional US has the potential to improve both qualitative inspection and the accuracy of quantitative approaches when imaging the complex architecture of vascular networks. It can be obtained with mechanical scanning to acquire a stack of two-dimensional SR images [14,22]. SR in all three directions was achieved through the use of two one-dimensional transducer arrays [12,23] or a hemispherical array probe [24]
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