Ultrasensitive US Microvessel Imaging of Hepatic Microcirculation in the Cirrhotic Rat Liver.

Background Liver microcirculation dysfunction plays a vital role in the occurrence and development of liver diseases, and thus, there is a clinical need for in vivo, noninvasive, and quantitative evaluation of liver microcirculation. Purpose To evaluate the feasibility of ultrasensitive US microvessel imaging (UMI) in the visualization and quantification of hepatic microvessels in healthy and cirrhotic rats. Materials and Methods In vivo studies were performed to image hepatic microvasculature by means of laparotomy in Sprague-Dawley rats (five cirrhotic and five control rats). In vivo conventional power Doppler US and ex vivo micro-CT were performed for comparison. UMI-based quantifications of perfusion, tortuosity, and integrity of microvessels were compared between the control and cirrhotic groups by using the Wilcoxon test. Spearman correlations between quantification parameters and pathologic fibrosis, perfusion function, and hepatic hypoxia were evaluated. Results UMI helped detect minute vessels below the liver capsule, as compared with conventional power Doppler US and micro-CT. With use of UMI, lower perfusion indicated by vessel density (median, 22% [IQR, 20%-28%] vs 41% [IQR, 37%-46%]; P = .008) and fractional moving blood volume (FMBV) (median, 6.4% [IQR, 4.8%-8.6%] vs 13% [IQR, 12%-14%]; P = .008) and higher tortuosity indicated by the sum of angles metric (SOAM) (median, 3.0 [IQR, 2.9-3.0] vs 2.7 [IQR, 2.6-2.9]; P = .008) were demonstrated in the cirrhotic rat group compared with the control group. Vessel density (r = 0.85, P = .003), FMBV (r = 0.86, P = .002), and median SOAM (r = -0.83, P = .003) showed strong correlations with pathologically derived vessel density labeled with dextran. Vessel density (r = -0.81, P = .005) and median SOAM (r = 0.87, P = .001) also showed strong correlations with hepatic tissue hypoxia. Conclusion Contrast-free ultrasensitive US microvessel imaging provided noninvasive in vivo imaging and quantification of hepatic microvessels in cirrhotic rat liver. © RSNA, 2022 Supplemental material is available for this article. See also the editorial by Fetzer in this issue.

Quantitative Shear Wave Speed Assessment for Muscles With the Diagnosis of Taut Bands and/or Myofascial Trigger Points Using Probe Oscillation Shear Wave Elastography: A Pilot Study.

OBJECTIVE: To use probe oscillation shear wave elastography (PROSE) with two vibration sources to generate two shear waves in the imaging plane to quantitatively assess the shear wave speeds (SWSs) of muscles with and without the diagnosis of taut bands (TB) and/or myofascial trigger points (MTrPs). METHODS: Thirty-three patients were scanned with the PROSE technique. Shear waves were generated through continuous vibration of the ultrasound probe, while the shear wave motions were detected using the same probe. SWSs for the sides with and without TBs and/or MTrPs were computed and compared. The pressure pain thresholds (PPTs) were measured as an indicator of maximum pain tolerance of patients. The statistical differences between the SWSs with and without TBs and/or MTrPs with different PPT values were analyzed using the nonparametric Wilcoxon rank-sum test. RESULTS: The mean SWSs for the sides with TBs and/or MTrPs are faster than that of the contralateral side without TBs and/or MTrPs. A significant difference was observed between mean SWSs with and without TBs and/or MTrPs without any information of PPT, with rank-sum test P < .005. Additionally, with the information of PPT, a significant difference was observed between mean SWSs for the sides with and without TBs and/or MTrPs, for PPT values between 0 and 50 N/cm2 (P < .005), but for PPT values between 50 and 90 N/cm2 , it was difficult to differentiate mean SWSs with and without TBs and/or MTrPs. CONCLUSION: Our preliminary results show that SWSs measured from patients had a significant difference between the mean SWSs with and without TBs and/or MTrPs.

Three-Dimensional Ultrasound Localization Microscopy with Bipartite Graph-Based Microbubble Pairing and Kalman-Filtering-Based Tracking on a 256-Channel Verasonics Ultrasound System with a 32 × 32 Matrix Array.

Three-dimensional (3D) ultrasound localization microscopy (ULM) using a 2-D matrix probe and microbubbles (MBs) has been recently proposed to visualize microvasculature beyond the ultrasound diffraction limit in three spatial dimensions. However, 3D ULM suffers from several limitations: (1) high system complexity due to numerous channel counts, (2) complex MB flow dynamics in 3D, and (3) extremely long acquisition time. To reduce the system complexity while maintaining high image quality, we used a sub-aperture process to reduce received channel counts. To address the second issue, a 3D bipartite graph-based method with Kalman filtering-based tracking was used in this study for MB tracking. An MB separation approach was incorporated to separate high concentration MB data into multiple, sparser MB datasets, allowing better MB localization and tracking for a limited acquisition time. The proposed method was first validated in a flow channel phantom, showing improved spatial resolutions compared with the contrasted enhanced power Doppler image. Then the proposed method was evaluated with an in vivo chicken embryo brain dataset. Results showed that the reconstructed 3D super-resolution image achieved a spatial resolution of around 52 µm (smaller than the wavelength of around 200 µm). Microvessels that cannot be resolved clearly using localization only, can be well identified with the tailored 3D pairing and tracking algorithms. To sum up, the feasibility of the 3D ULM is shown, indicating the great possibility in clinical applications.

Changes in spinal cord hemodynamics reflect modulation of spinal network with different parameters of epidural stimulation.

In this study functional ultrasound (fUS) imaging has been implemented to explore the local hemodynamics response induced by electrical epidural stimulation and to study real-time in vivo functional changes of the spinal cord, taking advantage of the superior spatiotemporal resolution provided by fUS. By quantifying the hemodynamics and electromyographic response features, we tested the hypothesis that the temporal hemodynamics response of the spinal cord to electrical epidural stimulation could reflect modulation of the spinal circuitry and accordingly respond to the changes in parameters of electrical stimulation. The results of this study for the first time demonstrate that the hemodynamics response to electrical stimulation could reflect a neural-vascular coupling of the spinal cord. Response in the dorsal areas to epidural stimulation was significantly higher and faster compared to the response in ventral spinal cord. Positive relation between the hemodynamics and the EMG responses was observed at the lower frequencies of epidural stimulation (20 and 40 Hz), which according to our previous findings can facilitate spinal circuitry after spinal cord injury, compared to higher frequencies (200 and 500 Hz). These findings suggest that different mechanisms could be involved in spinal cord hemodynamics changes during different parameters of electrical stimulation and for the first time provide the evidence that neural-vascular coupling of the spinal cord circuitry could be related to specific organization of spinal cord vasculature and hemodynamics.

Quantitative Inflammation Assessment for Crohn Disease Using Ultrasensitive Ultrasound Microvessel Imaging: A Pilot Study.

OBJECTIVES: Crohn disease (CD) is a chronic inflammation in the digestive tract that affects millions of Americans. Bowel vascularity has important diagnostic information because inflammation is associated with blood flow changes. We recently developed an ultrasensitive ultrasound microvessel imaging (UMI) technique with high vessel sensitivity. This study aimed to evaluate the feasibility of UMI to assist CD detection and staging. METHODS: Ultrasound microvessel imaging was performed on 76 bowel wall segments from 48 symptomatic patients with CD. Clinically indicated computed tomographic/magnetic resonance enterography was used as the reference standard. The vessel-length ratio (VLR, the number of vessel pixels in the bowel wall segment normalized to the segment length) was derived in both conventional color flow imaging (CFI) and UMI to quantitatively stage disease activity. Receiver operating characteristic curves were then analyzed between different disease groups. RESULTS: The VLR-CFI and VLR-UMI detected similar correlations between vascularization and disease activity: severe inflammation had a higher VLR than normal/mildly inflamed bowels (P < .05). No significant difference was found between quiescent and mild CD due to the small sample size. The VLR-CFI had more difficulties in distinguishing quiescent versus mild CD compared to the VLR-UMI. After combining the VLR-UMI with thickness, in the receiver operating characteristic curve analysis, the areas under the curves (AUCs) improved to AUC1 = 0.996 for active versus quiescent CD, AUC2 = 0.978 for quiescent versus mild CD, and AUC3 = 0.931 for mild versus severe CD, respectively, compared to those using thickness alone (AUC1 = 0.968; P = .04; AUC2 = 0.919; P = .16; AUC3 = 0.857; P = .01). CONCLUSIONS: Ultrasound microvessel imaging offers a safe and cost-effective tool for CD diagnosis and staging, which may potentially assist disease activity classification and therapy efficacy evaluation.

Three-Dimensional Shear Wave Elastography Using Acoustic Radiation Force and a 2-D Row-Column Addressing (RCA) Array.

Acoustic radiation force (ARF)-based shear wave elastography (SWE) is a clinically available ultrasound imaging mode that noninvasively and quantitatively measures tissue stiffness. Current implementations of ARF-SWE are largely limited to 2-D imaging, which does not provide a robust estimation of heterogeneous tissue mechanical properties. Existing 3-D ARF-SWE solutions that are clinically available are based on wobbler probes, which cannot provide true 3-D shear wave motion detection. Although 3-D ARF-SWE based on 2-D matrix arrays have been previously demonstrated, they do not provide a practical solution because of the need for a high channel-count ultrasound system (e.g., 1024-channel) to provide adequate volume rates and the delicate circuitries (e.g., multiplexers) that are vulnerable to the long-duration "push" pulses. To address these issues, here we propose a new 3-D ARF-SWE method based on the 2-D row-column addressing (RCA) array which has a much lower element count (e.g., 256), provides an ultrafast imaging volume rate (e.g., 2000 Hz), and can withstand the push pulses. In this study, we combined the comb-push shear elastography (CUSE) technique with 2-D RCA for enhanced SWE imaging field-of-view (FOV). In vitro phantom studies demonstrated that the proposed method had robust 3-D SWE performance in both homogenous and inclusion phantoms. An in vivo study on a breast cancer patient showed that the proposed method could reconstruct 3-D elasticity maps of the breast lesion, which was validated using a commercial ultrasound scanner. These results demonstrate strong potential for the proposed method to provide a viable and practical solution for clinical 3-D ARF-SWE.

High-fidelity deep functional photoacoustic tomography enhanced by virtual point sources.

Photoacoustic tomography (PAT), a hybrid imaging modality that acoustically detects the optical absorption contrast, is a promising technology for imaging hemodynamic functions in deep tissues far beyond the traditional optical microscopy. However, the most clinically compatible PAT often suffers from the poor image fidelity, mostly due to the limited detection view of the linear ultrasound transducer array. PAT can be improved by employing highly-absorbing contrast agents such as droplets and nanoparticles, which, however, have low clinical translation potential due to safety concerns and regulatory hurdles imposed by these agents. In this work, we have developed a new methodology that can fundamentally improve PAT's image fidelity without hampering any of its functional capability or clinical translation potential. By using clinically-approved microbubbles as virtual point sources that strongly and isotropically scatter the local pressure waves generated by surrounding hemoglobin, we can overcome the limited-detection-view problem and achieve high-fidelity functional PAT in deep tissues, a technology referred to as virtual-point-source PAT (VPS-PAT). We have thoroughly investigated the working principle of VPS-PAT by numerical simulations and in vitro phantom experiments, clearly showing the signal origin of VPSs and the resultant superior image fidelity over traditional PAT. We have also demonstrated in vivo applications of VPT-PAT for functional small-animal studies with physiological challenges. We expect that VPS-PAT can find broad applications in biomedical research and accelerated translation to clinical impact.

High-Volume-Rate 3-D Ultrasound Imaging Using Fast-Tilting and Redirecting Reflectors.

Three-dimensional ultrasound imaging has many advantages over 2-D imaging such as more comprehensive tissue evaluation and less operator dependence. However, developing a low-cost and accessible 3-D ultrasound solution with high volume rate and imaging quality remains a challenging task. Recently, we proposed a 3-D ultrasound imaging technique: fast acoustic steering via tilting electromechanical reflectors (FASTER), which uses a fast-tilting acoustic reflector to steer ultrafast plane waves elevationally to achieve high-volume-rate 3-D imaging with conventional 1-D transducers. However, the initial FASTER implementation requires a water tank for acoustic wave conduction and cannot be conveniently used for regular handheld scanning. To address these limitations, here, we developed a novel ultrasound probe clip-on device that encloses a fast-tilting reflector, a redirecting reflector, and an acoustic wave conduction medium. The new FASTER 3-D imaging device can be easily attached to or removed from clinical ultrasound transducers, allowing rapid transformation from 2-D to 3-D imaging. In vitro B-mode studies demonstrated that the proposed method provided comparable imaging quality to conventional, mechanical-translation-based 3-D imaging while offering a much faster volume rate (e.g., 300 versus  âˆ¼  10 Hz). We also demonstrated 3-D power Doppler (PD) and 3-D super-resolution ultrasound localization microscopy (ULM) with the FASTER device. An in vivo imaging study showed that the FASTER device could clearly visualize the 3-D anatomy of the basilic vein. These results suggest that the newly developed redirecting reflector and the clip-on device could overcome key hurdles for future clinical translation of the FASTER 3-D imaging technology.

High Volume Rate 3-D Ultrasound Imaging Using Fast-Tilting and Redirecting Reflectors.

3-D ultrasound imaging has many advantages over 2-D imaging such as more comprehensive tissue evaluation and less operator dependence. Although many 3-D ultrasound imaging techniques have been developed in the last several decades, a low-cost and accessible solution with high imaging volume rate and imaging quality remains elusive. Recently we proposed a new, high volume rate 3-D ultrasound imaging technique: Fast Acoustic Steering via Tilting Electromechanical Reflectors (FASTER), which uses a water-immersible and fast-tilting acoustic reflector to steer ultrafast plane waves in the elevational direction to achieve high volume rate 3-D ultrasound imaging with conventional 1-D array transducers. However, the initial implementation of FASTER imaging only involves a single fast-tilting acoustic reflector, which is inconvenient to use because the probe cannot be held in the regular upright position. Also, conventional FASTER imaging can only be performed inside a water tank because of the necessity of using water for acoustic conduction. To address these limitations of conventional FASTER, here we developed a novel ultrasound probe clip-on device that encloses a fast-tilting reflector, a redirecting reflector, and an acoustic wave conduction medium. The new FASTER 3-D imaging device can be easily attached to or removed from clinical ultrasound transducers, allowing rapid transformation from 2-D to 3-D ultrasound imaging. In vitro B-mode imaging studies demonstrated that the proposed method provided comparable imaging quality (e.g., spatial resolution and contrast-to-noise ratio) to conventional, mechanical-translation-based 3-D imaging while providing a much faster 3-D volume rate (e.g., 300 Hz vs ∻10 Hz). In addition to B-mode imaging, we also demonstrated 3-D power Doppler imaging and 3-D super-resolution ultrasound localization microscopy with the newly developed FASTER device. An in vivo imaging study showed that the FASTER device could clearly visualize the 3-D anatomy of the basilic vein of a healthy volunteer, and customized beamforming was implemented to accommodate the speed of sound difference between the acoustic medium and the imaging object (e.g., soft tissue). These results suggest that the newly developed redirecting reflector and the clip-on device could overcome key hurdles for future clinical translation of the FASTER 3-D imaging technology.

Ultrasound-targeted microbubble destruction mediates PDE5i/NO integration for cavernosum remodeling and penile rehabilitation.

Erectile dysfunction (ED) caused by cavernous nerve injury (CNI) is refractory to heal mainly ascribed to the adverse remodeling of the penis induced by ineffectual microvascular perfusion, fibrosis, and neurotrophins scarcity in cavernosum. Phosphodiesterase type V inhibitors (PDE5i) have been regarded as an alternative candidate drug for avoiding penile neuropathy. However, the therapeutic efficacy is severely limited due to poor accumulation under systemic medication and endogenous nitric oxide (NO) deficiency in cavernosum. Herein, an innovative liposomal microbubble (MB) loaded with both Sildenafil (one of PDE5i) and NO was designed. Ultrasound-targeted MB destruction (UTMD)-mediated efficient release and integration erectogenic agents into corpus cavernosum with high biosafety. On a bilateral CNI rat model, the multifunctional MB-cooperated UTMD improved microvascular perfusion in penis, simultaneously, alleviated hypoxia and oxidative stress, indicating successful activation of NO-cyclic guanosine monophosphate pathway. Also, evaluation of the endothelial/muscular composition, intracavernosal pressure, and neural integrity in the penis proved that coordinated intervention reversed the abnormal structural remodeling and promoted the recovery of functional erection. Our work demonstrates that MB loading Sildenafil and NO combined with UTMD hold great promise to "awaken" the efficacy of PDE5i in neurogenic ED, which provided a superior option for ensuring penile rehabilitation.

Three-Dimensional Shear Wave Elastography Using a 2D Row Column Addressing (RCA) Array.

Objective. To develop a 3D shear wave elastography (SWE) technique using a 2D row column addressing (RCA) array, with either external vibration or acoustic radiation force (ARF) as the shear wave source. Impact Statement. The proposed method paves the way for clinical translation of 3D SWE based on the 2D RCA, providing a low-cost and high volume rate solution that is compatible with existing clinical systems. Introduction. SWE is an established ultrasound imaging modality that provides a direct and quantitative assessment of tissue stiffness, which is significant for a wide range of clinical applications including cancer and liver fibrosis. SWE requires high frame rate imaging for robust shear wave tracking. Due to the technical challenges associated with high volume rate imaging in 3D, current SWE techniques are typically confined to 2D. Advancing SWE from 2D to 3D is significant because of the heterogeneous nature of tissue, which demands 3D imaging for accurate and comprehensive evaluation. Methods. A 3D SWE method using a RCA array was developed with a volume rate up to 2000 Hz. The performance of the proposed method was systematically evaluated on tissue-mimicking elasticity phantoms and in an in vivo case study. Results. 3D shear wave motion induced by either external vibration or ARF was successfully detected with the proposed method. Robust 3D shear wave speed maps were reconstructed for phantoms and in vivo. Conclusion. The high volume rate 3D imaging provided by the 2D RCA array provides a robust and practical solution for 3D SWE with a clear pathway for future clinical translation.

In vivo assessment of hypertensive nephrosclerosis using ultrasound localization microscopy.

PURPOSE: As a typical chronic kidney disease (CKD), hypertensive nephrosclerosis (HN) is a common syndrome of hypertension, characterized by chronic kidney microvascular damage. Early diagnosis of microvascular damage using conventional ultrasound imaging encounters challenges in sensitivity and specificity owing to the inherent diffraction limit. Ultrasound localization microscopy (ULM) has been developed to obtain microvasculature and microvascular hemodynamics within the kidney, and would be a promising tool for the early diagnosis of CKD. METHODS: In this study, the advantage of quantitative indexes obtained by using ULM (mean arterial blood flow speeds of different segments of interlobular arteries) over indexes obtained using conventional clinical serum (ß2-microglobulin, serum urea nitrogen, and creatinine) and urine (24-h urine volume and urine protein) tests and ultrasound Doppler imaging (peak systolic velocity [PSV], end-diastolic velocity [EDV], and resistance index [RI]) and contrast-enhanced ultrasound imaging (CEUS; rise time [RT], peak intensity [IMAX], mean transit time [mTT], and area under the time-intensity curve [AUC]) for early diagnosis of HN were investigated. Examinations were carried out on six spontaneously hypertensive rats (SHR) and five normal Wistar-Kyoto (WKY) rats at the age of 10 weeks. RESULTS: The experimental results show that the indicators derived from conventional clinical inspections (serum and urine tests) and ultrasound imaging (PSV, EDV, RI, RT, IMAX, mTT, and AUC) do not show significant difference between hypertensive and healthy rats (p > 0.05), while the TTP of the SHR group (28.52 ± 5.52 s) derived from CEUS is significantly higher than that of the WKY group (18.68 ± 7.32 s; p < 0.05). The mean blood flow speed in interlobular artery of SHR (12.47 ± 1.06 mm/s) derived from ULM is significantly higher than that of WKY rats (10.13 ± 1.17 mm/s; p < 0.01). CONCLUSION: The advantages of ULM over conventional clinical inspections and ultrasound imaging methods for early diagnosis of HN were validated. The quantitative results show that ULM can effectively diagnose HN at the early stage by detecting the blood flow speed changes of interlobular arteries. ULM may promise a reliable technique for early diagnosis of HN in the future.

Reverberation clutter signal suppression in ultrasound attenuation estimation using wavelet-based robust principal component analysis.

Objective. Ultrasound attenuation coefficient estimation (ACE) has diagnostic potential for clinical applications such as quantifying fat content in the liver. Previously, we have proposed a system-independent ACE technique based on spectral normalization of different frequencies, called the reference frequency method (RFM). This technique does not require a well-calibrated reference phantom for normalization. However, this method may be vulnerable to severe reverberation clutter introduced by the body wall. The clutter superimposed on liver echoes may bias the estimation.Approach. We proposed to use robust principal component analysis, combined with wavelet-based sparsity promotion, to suppress the severe reverberation clutters. The capability to mitigate the reverberation clutters was validated through phantom andin vivostudies.Main Results. In the phantom studies with added reverberation clutters, higher normalized cross-correlation and smaller mean absolute errors were attained as compared to RFM results without the proposed method, demonstrating the capability to reconstruct tissue signals from reverberations. In a pilot patient study, the correlation between ACE and proton density fat fraction (PDFF), a measurement of liver fat by MRI as a reference standard, was investigated. The proposed method showed an improvement of the correlation (coefficient of determination,R = 0.82) as compared with the counterpart without the proposed method (R = 0.69).Significance: The proposed method showed the feasibility of suppressing the reverberation clutters, providing an important basis for the development of a robust ACE with large reverberation clutters.

Super-Resolution Ultrasound Localization Microscopy for Visualization of the Ocular Blood Flow.

OBJECTIVE: The ocular vascular system plays an important role in preserving the visual function. Alterations in either anatomy or hemodynamics of the eye may have adverse effects on vision. Thus, an imaging approach that can monitor alterations of ocular blood flow of the deep eye vasculature ranging from capillary-level vessels to large supporting vessels would be advantageous for detection of early stage retinal and optic nerve diseases. METHODS: We propose a super-resolution ultrasound localization microscopy (ULM) technique that can assess both the microvessel and flow velocity of the deep eye with high resolution. Ultrafast plane wave imaging was acquired using an L22-14v linear array on a high frequency Verasonics Vantage system. A robust microbubble localization and tracking technique was applied to reconstruct ULM images. The experiment was first performed on pre-designed flow phantoms in vitro and then tested on a New Zealand white rabbit eye in vivo calibrated to various intraocular pressures (IOP) - 10 mmHg, 30 mmHg and 50 mmHg. RESULTS: We demonstrated that retinal/choroidal vessels, central retinal artery, posterior ciliary artery, and vortex vein were all visible at high resolution. In addition, reduction of vascular density and flow velocity were observed with elevated IOPs. CONCLUSION: These results indicate that super-resolution ULM is able to image the deep ocular tissue while maintaining high resolution that is comparable with optical coherence tomography angiography. SIGNIFICANCE: Capability to detect subtle changes of blood flow may be clinically important in detecting and monitoring eye diseases such as glaucoma.

Improved Ultrasound Attenuation Estimation with Non-uniform Structure Detection and Removal.

Accurate detection of liver steatosis is important for liver disease management. Ultrasound attenuation coefficient estimation (ACE) has great potential in quantifying liver fat content. The ACE methods commonly assume uniform tissue characteristics. However, in vivo tissues typically contain non-uniform structures, which may bias the attenuation estimation and lead to large standard deviations. Here we propose a series of non-uniform structure detection and removal (NSDR) methods to reduce the impact from non-uniform structures during ACE analysis. The effectiveness of NSDR was validated through phantom and in vivo studies. In a pilot clinical study, ACE with NSDR provided more robust in vivo performance as compared with ACE without NSDR, indicating its potential for in vivo applications.

Adaptive and Robust Vessel Quantification in Contrast-Free Ultrafast Ultrasound Microvessel Imaging.

The morphological features of vasculature in diseased tissue differ significantly from those in normal tissue. Therefore, vasculature quantification is crucial for disease diagnosis and staging. Ultrasound microvessel imaging (UMI) with ultrafast ultrasound acquisitions has been determined to have potential in clinical applications given its superior sensitivity in blood flow detection. However, the presence of spatial-dependent noise caused by a low imaging signal-to-noise ratio and incoherent clutter artifacts caused by moving hyperechoic scatterers degrades the performance of UMI and the reliability of vascular quantification. To tackle these issues, we proposed an improved UMI technique along with an adaptive vessel segmentation workflow for robust vessel identification and vascular feature quantification. A previously proposed sub-aperture cross-correlation technique and a normalized cross-correlation technique were applied to equalize the spatially dependent noise level and suppress the incoherent clutter artifact. A square operator and non-local means filter were then used to better separate the blood flow signal from residual background noise. On the de-noised ultrasound microvessel image, an automatic and adaptive vessel segmentation method was developed based on the different spatial patterns of blood flow signal and background noise. The proposed workflow was applied to a CIRS phantom, to a Doppler flow phantom and to an inflammatory bowel, kidney and liver, to validate its feasibility. Results revealed that automatic adaptive, and robust vessel identification performance can be achieved using the proposed method without the subjectivity caused by radiologists/operators.

Morphological Reconstruction Improves Microvessel Mapping in Super-Resolution Ultrasound.

Generation of super-resolution (SR) ultrasound (US) images, created from the successive localization of individual microbubbles in the circulation, has enabled the visualization of microvascular structure and flow at a level of detail that was not possible previously. Despite rapid progress, tradeoffs between spatial and temporal resolution may challenge the translation of this promising technology to the clinic. To temper these tradeoffs, we propose a method based on morphological image reconstruction. This method can extract from ultrafast contrast-enhanced US (CEUS) images hundreds of microbubble peaks per image (312-by-180 pixels) with intensity values varying by an order of magnitude. Specifically, it offers a fourfold increase in the number of peaks detected per frame, requires on the order of 100 ms for processing, and is robust to additive electronic noise (down to 3.6-dB CNR in CEUS images). By integrating this method to an SR framework, we demonstrate a sixfold improvement in spatial resolution, when compared with CEUS, in imaging chicken embryo microvessels. This method that is computationally efficient and, thus, scalable to large data sets may augment the abilities of SR-US in imaging microvascular structure and function.

Liraglutide reduces attenuation coefficient as a measure of hepatic steatosis during 16 weeks' treatment in nondiabetic obese patients: A pilot trial.

BACKGROUND AND AIM: Liraglutide, a long-acting GLP-1 analog, is approved for the treatment of obesity with improvements in fasting blood glucose, hemoglobin A1c, and cardiovascular health. Our aim was to measure the impact of liraglutide dose for obesity on hepatic steatosis measured by ultrasound. METHODS: A single-center, randomized, double-blind, placebo-controlled pilot trial was undertaken in nondiabetic obese, otherwise healthy patients aged 18-65 years. Participants were randomly assigned to receive subcutaneous liraglutide (3.0 mg) or placebo over 16 weeks with dose escalation following US Food and Drug Administration guidelines. Both groups received standardized nutritional and behavioral counseling during the 16 weeks. Hepatic fat content was measured by ultrasound at baseline, 8 weeks, and 16 weeks as an attenuation coefficient (ACE). Effects of treatment were assessed using t-test for the entire groups and for patient subgroup with baseline ACE >0.66 (indicating significant steatosis). RESULTS: Among 30 patients (93% female) enrolled, 16 were randomized to placebo and 14 to liraglutide. Baseline body mass indices (BMIs) and average age were similar in the two groups. After 16 weeks, the liraglutide group had a significant improvement in steatosis ACE scores (-0.068 ± 0.02 vs -0.0077 ± 0.02 placebo, P = 0.05). Change in steatosis was positively correlated with change in BMI (R2 = 0.402, P = 0.0007). Within the liraglutide group, patients with baseline ACE >0.66 had improvement in ACE (-0.134 ± 0.03) compared to those without significant steatosis (-0.041 ± 0.02, P = 0.05). CONCLUSIONS: In this pilot trial, liraglutide, 3.0 mg over 16 weeks, reduced hepatic steatosis; a reduction in hepatic steatosis is correlated with BMI reduction, and effects are particularly evident in those with a significant degree of steatosis by ultrasound imaging.

Noise Suppression for Ultrasound Attenuation Coefficient Estimation Based on Spectrum Normalization.

Ultrasound attenuation coefficient estimation (ACE) has great diagnostic potential for fatty liver detection and assessment. In a previous study, we proposed a reference phantom-free ACE method, called reference frequency method (RFM), which does not require a calibrated phantom for normalization. The power of each frequency component can be normalized by the power of an adjacent frequency component in the spectrum to cancel system-dependent effects such as focusing and time gain compensation (TGC). RFM demonstrated accurate ACE in both phantom and in in-vivo liver studies. However, our study also showed that the robustness and penetration of RFM were affected by noise in the ACE signals. Here we propose a noise suppression (NS) and a signal-to-noise ratio (SNR) quality control method to reduce the influence of noise on ACE-RFM performance. The proposed methods were tested in harmonic ACE because harmonic imaging is a more frequently used mode than fundamental imaging for abdominal applications. After applying the NS and SNR control methods, the noise-induced bias for attenuation estimation in harmonic ACE was effectively reduced, leading to significantly improved effective penetration depth. The proposed methods directly measure the noise spectrum of the ultrasound system, which can also be adapted to other spectrum-based ACE methods, such as the reference phantom method and the spectra shift method.

Simultaneous Noise Suppression and Incoherent Artifact Reduction in Ultrafast Ultrasound Vascular Imaging.

Ultrasound vascular imaging based on ultrafast plane wave imaging and singular value decomposition (SVD) clutter filtering has demonstrated superior sensitivity in blood flow detection. However, ultrafast ultrasound vascular imaging is susceptible to electronic noise due to the weak penetration of unfocused waves, leading to a lower signal-to-noise ratio (SNR) at larger depths. In addition, incoherent clutter artifacts originating from strong and moving tissue scatterers that cannot be completely removed create a strong mask on top of the blood signal that obscures the vessels. Herein, a method that can simultaneously suppress the background noise and incoherent artifacts is proposed. The method divides the tilted plane or diverging waves into two subgroups. Coherent spatial compounding is performed within each subgroup, resulting in two compounded data sets. An SVD-based clutter filter is applied to each data set, followed by a correlation between the two data sets to produce a vascular image. Uncorrelated noise and incoherent artifacts can be effectively suppressed with the correlation process, while the coherent blood signal can be preserved. The method was evaluated in wire-target simulations and phantom, in which around 7-10-dB SNR improvement was shown. Consistent results were found in a flow channel phantom with improved SNR by the proposed method (39.9 ± 0.2 dB) against conventional power Doppler (29.1 ± 0.6 dB). Last, we demonstrated the effectiveness of the method combined with block-wise SVD clutter filtering in a human liver, breast tumor, and inflammatory bowel disease data sets. The improved blood flow visualization may facilitate more reliable small vessel imaging for a wide range of clinical applications, such as cancer and inflammatory diseases.