Ultrasound Super-Resolution Imaging for the Differential Diagnosis of Thyroid Nodules: A Pilot Study

Objective: Ultrasound imaging provides a fast and safe examination of thyroid nodules. Recently, the introduction of superresolution imaging technique shows the capability of breaking the Ultrasound diffraction limit in imaging the micro-vessels. The aim of this study was to evaluate its feasibility and value for the differentiation of thyroid nodules. Methods: In this study, B-mode, contrast-enhanced ultrasound, and color Doppler flow imaging examinations were performed on thyroid nodules in 24 patients. Super-resolution imaging was performed to visualize the microvasculature with finer details. Microvascular flow rate (MFR) and micro-vessel density (MVD) within thyroid nodules were computed. The MFR and MVD were used to differentiate the benign and malignant thyroid nodules with pathological results as a gold standard. Results: Super-resolution imaging (SRI) technique can be successfully applied on human thyroid nodules to visualize the microvasculature with finer details and obtain the useful clinical information MVD and MFR to help differential diagnosis. The results suggested that the mean value of the MFR within benign thyroid nodule was 16.76 ± 6.82 mm/s whereas that within malignant thyroid was 9.86 ± 4.54 mm/s. The mean value of the MVD within benign thyroid was 0.78 while the value for malignant thyroid region was 0.59. MFR and MVD within the benign thyroid nodules were significantly higher than those within the malignant thyroid nodules respectively (p < 0.01). Conclusions: This study demonstrates the feasibility of ultrasound super-resolution imaging to show micro-vessels of human thyroid nodules via a clinical ultrasound platform. The important imaging markers, such as MVD and MFR, can be derived from SRI to provide more useful clinical information. It has the potential to be a new tool for aiding differential diagnosis of thyroid nodules

Acoustic wave sparsely activated localization microscopy (AWSALM): super-resolution ultrasound imaging using acoustic activation and deactivation of nanodroplets

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

3D in Vitro Ultrasound Super-Resolution Imaging Using a Clinical System

© 2018 IEEE. Assessment of complex and disordered tumour vasculature requires full 3D visualization. Ultrasound super-resolution techniques are able to image microvascular structure and flow beyond the diffraction limit. Existing demonstrations have been predominantly 2D, where the elevational resolution remains restricted to around the millimeter range, while 3D demonstrations have either used mechanical scanning, or have required customized or state-of-the-art research systems to achieve true super-resolution in the third dimension. In this study, 3D super-resolution and velocity tracking is demonstrated in vitro using an ultrasound imaging system currently available in the clinic. This was performed at 1.25 MHz transmit frequency, with a frame rate of 54 Hz in contrast enhanced imaging mode. Three-dimensional super-resolved volumetric imaging of a twisted micro-vessel phantom was demonstrated at 3.5 cm depth, where between 66-70% of localizations where estimated to fall within the vessel internal diameter. Demonstration of 3D ultrasound super-resolution using a system currently available in the clinic demonstrates a fast route for clinical translation and application. In the future, 3D localization using microbubble signal onset could allow considerably improved microvascular visualization to aid early disease detection, diagnosis, and intervention for micro-vascular related diseases like cancer

3-D Motion Correction for Volumetric Super-Resolution Ultrasound Imaging

© 2018 IEEE. Motion during image acquisition can cause image degradation in all medical imaging modalities. This is particularly relevant in 2-D ultrasound imaging, since out-of-plane motion can only be compensated for movements smaller than elevational beamwidth of the transducer. Localization based super-resolution imaging creates even a more challenging motion correction task due to the requirement of a high number of acquisitions to form a single super-resolved frame. In this study, an extension of two-stage motion correction method is proposed for 3-D motion correction. Motion estimation was performed on high volumetric rate ultrasound acquisitions with a handheld probe. The capability of the proposed method was demonstrated with a 3-D microvascular flow simulation to compensate for handheld probe motion. Results showed that two-stage motion correction method reduced the average localization error from 136 to 18 μm

Poisson Statistical Model of Ultrasound Super-Resolution Imaging Acquisition Time

A number of acoustic super-resolution techniques have recently been developed to visualize microvascular structure and flow beyond the diffraction limit. A crucial aspect of all ultrasound super-resolution (SR) methods using single microbubble localization is time-efficient detection of individual bubble signals. Due to the need for bubbles to circulate through the vasculature during acquisition, slow flows associated with the microcirculation limit the minimum acquisition time needed to obtain adequate spatial information. Here, a model is developed to investigate the combined effects of imaging parameters, bubble signal density, and vascular flow on SR image acquisition time. We find that the estimated minimum time needed for SR increases for slower blood velocities and greater resolution improvement. To improve SR from a resolution of λ10 to λ20 while imaging the microvasculature structure modelled here, the estimated minimum acquisition time increases by a factor of 14. The maximum useful imaging frame rate to provide new spatial information in each image is set by the bubble velocity at low blood flows (< 150 mm/s for a depth of 5 cm) and by the acoustic wave velocity at higher bubble velocities. Furthermore, the image acquisition procedure, transmit frequency, localization precision, and desired super-resolved image contrast, together determine the optimal acquisition time achievable for a fixed flow velocity. Exploring the effects of both system parameters and details of the target vasculature can allow a better choice of acquisition settings and provide improved understanding of the completeness of SR information. © 2019 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works

Acoustic wave sparsely-activated localization microscopy (AWSALM): super-resolution ultrasound imaging using acoustic activation and deactivation of nanodroplets

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

Fast acoustic wave sparsely activated localization microscopy (fast-AWSALM): ultrasound super-resolution using plane-wave activation of nanodroplets

Localization-based ultrasound super-resolution imaging using microbubble contrast agents and phase-change nano-droplets has been developed to visualize microvascular structures beyond the diffraction limit. However, the long data acquisition time makes the clinical translation more challenging. In this study, fast acoustic wave sparsely activated localization microscopy (fast-AWSALM) was developed to achieve super-resolved frames with sub-second temporal resolution, by using low-boiling-point octafluoropropane nanodroplets and high frame rate plane waves for activation, destruction, as well as imaging. Fast-AWSALM was demonstrated on an in vitro microvascular phantom to super-resolve structures that could not be resolved by conventional B-mode imaging. The effects of the temperature and mechanical index on fast-AWSALM was investigated. Experimental results show that sub-wavelength micro-structures as small as 190 lm were resolvable in 200 ms with plane-wave transmission at a center frequency of 3.5 MHz and a pulse repetition frequency of 5000 Hz. This is about a 3.5 fold reduction in point spread function full-width-half-maximum compared to that measured in conventional B-mode, and two orders of magnitude faster than the recently reported AWSALM under a non-flow/very slow flow situations and other localization based methods. Just as in AWSALM, fast-AWSALM does not require flow, as is required by current microbubble based ultrasound super resolution techniques. In conclusion, this study shows the promise of fast-AWSALM, a super-resolution ultrasound technique using nanodroplets, which can generate super-resolution images in milli-seconds and does not require flow

3-D super-resolution ultrasound (SR-US) imaging using a 2-D sparse array with high volumetric imaging rate

Super-resolution ultrasound imaging has been so far achieved in 3-D by mechanically scanning a volume with a linear probe, by co-aligning multiple linear probes, by using multiplexed 3-D clinical ultrasound systems, or by using 3- D ultrasound research systems. In this study, a 2-D sparse array was designed with 512 elements according to a density- tapered 2-D spiral layout and optimized to reduce the sidelobes of the transmitted beam profile. High frame rate volumetric imaging with compounded plane waves was performed using two synchronized ULA-OP256 systems. Localization-based 3-D super-resolution images of two touching sub-wavelength tubes were generated from a 120 second acquisition