Unprecedented high-spatial resolution was achieved in ultrasound imaging by breaking the fundamental limitation with the operating ultrasound wavelength

Kang Kim – kangkim@upmc.edu
Qiyang Chen – qic41@pitt.edu
Jaesok Yu – jaesok.yu@ece.gatech.edu
Roderick J Tan – tanrj@upmc.edu
University of Pittsburgh
3550 Terrace St, room 623, Pittsburgh, PA 15261

Popular version of paper 2aBA8; 4aBAa7
Presented Tuesday & Thursday morning, May 14 & 16, 2019
177th ASA Meeting, Louisville, KY

US imaging is one of the most favored imaging modalities in clinics in general because of its real-time display, safety, noninvasiveness, portability and affordability. One major disadvantage of ultrasound imaging is its limited spatial resolution that is fundamentally governed by the wavelength of the operating ultrasound. We developed a new super-resolution imaging algorithm that can achieve super high-spatial resolution beyond such limitation called acoustic diffraction limit.
The concept of the super resolution that bypasses a physical limit for the maximum resolution of traditional optical imaging was originally introduced in microscopy imaging community and later developed into a ground-breaking technology of the nano-dimension microscopy imaging, for which the Nobel Prize in Chemistry was awarded in 2014. In brief, microscopy super resolution imaging technology is based on randomly repeated blinking process of the fluorophores in response to the light source of the microscopy. In recent years, the concept has been translated into ultrasound imaging community. The random blinking process that requires for achieving super resolution using ultrasound is provided by flowing microbubbles in blood vessels which randomly oscillate in response to the ultrasound pressure from the imaging transducer. The maximum spatial resolution in super resolution microscopy technology is in the range of tens of nanometers (10-9 m) that allows to visualize the pathways of individual molecules inside living cells, while ultrasound super resolution imaging can achieve a spatial resolution in the range of tens of micrometers (10-6 m) when using a typical clinical ultrasound imaging transducer of a few MHz center frequency. However, due to the large imaging depth of ultrasound up to several centimeters, ultrasound super resolution imaging technology is practically very useful in imaging human subject with greater details of microvasculature which is of critical importance for many diseases.
Figure 1

Traditional contrast enhanced ultrasound (CEU) imaging technologies using microbubbles provide superior contrast of vasculatures, effectively suppressing the surrounding tissue signals, but the spatial resolution remains to the acoustic diffraction limit. In recent years, to overcome such limitation with CEU, several approaches have been made to overcome such limitation by employing super resolution concept, however requiring a long scan time, which hinders the technology from being wide spread. The major contribution from my laboratory is to drastically shorten the scan time of super resolution imaging using deconvolution algorithm for microbubble center localization, as well as to compensate artifacts due to physiological motions using block matching based motion correction and spatio-temporal-interframe-correlation based data re-alignment, so that the technology can be used in vivo for diverse applications. In brief, a novel approach of ultrafast ultrasound imaging, rigid motion compensation, tissue signal suppressor and deconvolution based deblurring has been developed for both high spatial and temporal resolution.

Video 1

The developed technology was applied in imaging microvasculature change which is a critical feature during disease development and progress. Vasa vasorum that is network of small blood vessels that supply the walls of large blood vessels and often multiplies and infiltrates into atherosclerotic plaque were identified in rabbit model.

Microvascular rarefaction is a key signature of acute kidney injury that often progress into chronic kidney diseases and eventual kidney failure. Microvessels in mouse acute kidney injury model were successfully identified and quantitatively analyzed.

Figure 3

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