Toward optimization of in vivo super‐resolution ultrasound imaging using size‐selected microbubble contrast agents

Abstract

Purpose Microvascular processes play key roles in many diseases including diabetes. Improved understanding of the microvascular changes involved in disease development could offer crucial insight into the relationship of these changes to disease pathogenesis. Super-resolution ultrasound (SR-US) imaging has showed the potential to visualize microvascular detail down to the capillary level (i.e., subwavelength resolution) but optimization is still necessary. The purpose of this study was to investigate in vivo SR-US imaging of skeletal muscle microvascularity using microbubble (MB) contrast agents of various size and concentration while evaluating different ultrasound (US) system level parameters such as imaging frame rate and image acquisition length. Methods An US system equipped with a linear array transducer was used in a harmonic imaging mode at low transmit power. C57BL/6J mice fed a normal diet were used in this study. An assortment of size-selected MB contrast agents (1–2 μm, 3–4 μm, and 5–8 μm in diameter) were slowly infused in the tail vein at various doses (1.25 × 107, 2.5 × 107 or 5 × 107 MBs). US image data was collected before MB injection and thereafter for 10 min at 30 frames per sec (fps). The US transducer was fixed throughout and between each imaging period to help capture microvascular patterns along the same image plane. An adaptive SR-US image processing technique was implemented using custom Matlab software. Results Experimental findings illustrate the use of larger MB results in better SR-US images in terms of skeletal muscle microvascular detail. A dose of 2.5 × 107 MBs resulted in SR-US images with optimal spatial resolution. An US imaging rate of at least 20 fps and image acquisition length of at least 8 min also resulted in SR-US images with pronounced microvascular detail. Conclusions This study indicates that MB size and dose and US system imaging rate and data acquisition length have significant impact on the quality of in vivo SR-US images of skeletal muscle microvascularity.

Super-resolution Ultrasound Imaging

“…There is an inherent compromise between the SNR of the signal and the localization precision. This has been highlighted in studies such as Desailly et al (2015), Ghosh et al (2017), Lin et al (2017a) and Espindola et al (2018). Exploration of the impact of SNR, specifically in relation to depth and aberration effects, is greatly needed.…”

“…In Foiret et al (2017), the coherence factor, the ratio of coherent intensity to incoherent intensity (Mallart and Fink 1994), was applied to CPS images to improve the SNR of echoes from individual microbubbles. Ghosh et al (2017) and Lin et al (2017b) have reported that selecting a population of larger microbubbles improves the SNR from individual microbubbles. Finally, because of the challenge of separating bubble signals from noise in images using just spatial information, Song et al (2017) proposed to denoise the microbubble signal in a spatiotemporal domain using a nonlocal means filter to improve the separation of microbubble "tracks" from random background noise that does not resemble any feature or pattern.…”

“…This means detecting microbubbles in microvessels at depth can be challenging. Strategies to improve the sensitivity of contrast agents at depth are being investigated for super-resolution imaging, for example, the use of larger microbubbles (Ghosh et al 2017;Lin et al 2017b) and the use of adaptive multifocus methods, which combine the high frame rates of plane wave imaging with the increased bubble detection sensitivity of focused beams (Espindola et al 2018).…”

Accomplishments and challenges in stem cell imaging in vivo

“…Although US does not provide accurate absolute MB concentration, it does provide accurate relative difference in MB concentration between adjacent tissues within the same imaged field. Recently introduced sub-voxel resolution with MB suggests that an accurate MB count can potentially be provided over the entire field of view [33,34]. In addition to the same challenges as US, PAI also suffers from light attenuation that is different for each spectral wavelength.…”

Characterization of Placental Microvasculature Using Superb Microvascular Imaging

“…Microvascular processes play an important role in many diseases, such as diabetes . An improved understanding of these changes has the potential for providing novel insight into characterizing their relationship with developing pathologic conditions as a guide to more effective therapies . In 2016, Machado et al described a novel Superb Microvascular Imaging (SMI; Canon Medical Systems, Tustin, CA) technique for the assessment of thyroid vascularity.…”