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Ultrasound vascular imaging (UVI) is a valuable tool for monitoring the physiological states and evaluating the pathological diseases. Advancing from conventional two-dimensional (2D) to three-dimensional (3D) UVI would enhance the vasculature visualization, thereby improving its reliability. Row-column array (RCA) has emerged as a promising approach for cost-effective ultrafast 3D imaging with a low channel count. However, ultrafast RCA imaging is often hampered by high-level sidelobe artifacts and low signal-to-noise ratio (SNR), which makes RCA-based UVI challenging. In this study, we propose a spatial-temporal similarity weighting (St-SW) method to overcome these challenges by exploiting the incoherence of sidelobe artifacts and noise between datasets acquired using orthogonal transmissions. Simulation, in vitro blood flow phantom, and in vivo experiments were conducted to compare the proposed method with existing orthogonal plane wave imaging (OPW), row-column-specific frame-multiply-and-sum beamforming (RC-FMAS), and XDoppler techniques. Qualitative and quantitative results demonstrate the superior performance of the proposed method. In simulations, the proposed method reduced the sidelobe level by 31.3 dB, 20.8 dB, and 14.0 dB, compared to OPW, XDoppler, and RC-FMAS, respectively. In the blood flow phantom experiment, the proposed method significantly improved the contrast-to-noise ratio (CNR) of the tube by 26.8 dB, 25.5 dB, and 19.7 dB, compared to OPW, XDoppler, and RC-FMAS methods, respectively. In the human submandibular gland experiment, it not only reconstructed a more complete vasculature but also improved the CNR by more than 15 dB, compared to OPW, XDoppler, and RC-FMAS methods. In summary, the proposed method effectively suppresses the side-lobe artifacts and noise in images collected using an RCA under low SNR conditions, leading to improved visualization of 3D vasculatures.
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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.
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Técnicas de Imagem por Elasticidade , Humanos , Técnicas de Imagem por Elasticidade/métodos , Ultrassonografia , Movimento (Física) , Imagens de Fantasmas , AcústicaRESUMO
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.
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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 â¼ 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.
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Imageamento Tridimensional , Ultrassonografia Doppler , Ultrassonografia/métodos , Ultrassonografia Doppler/métodos , Acústica , Transdutores , Imagens de FantasmasRESUMO
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 âË»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.
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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.
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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.
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Fígado , Microvasos , Ratos , Animais , Microcirculação , Ratos Sprague-Dawley , Fígado/patologia , Microvasos/diagnóstico por imagem , Microvasos/patologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologiaRESUMO
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.
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Fígado Gorduroso , Hepatopatia Gordurosa não Alcoólica , Fígado Gorduroso/diagnóstico por imagem , Humanos , Fígado/diagnóstico por imagem , Imagens de Fantasmas , Projetos Piloto , Ultrassonografia/métodosRESUMO
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.
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Processamento de Imagem Assistida por Computador , Microvasos , Imagens de Fantasmas , Reprodutibilidade dos Testes , Razão Sinal-Ruído , UltrassonografiaRESUMO
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.
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Fígado , Imageamento por Ressonância Magnética , Humanos , Fígado/diagnóstico por imagem , Imagens de Fantasmas , Análise de Componente Principal , Ultrassonografia/métodosRESUMO
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.
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Hipertensão , Nefroesclerose , Insuficiência Renal Crônica , Animais , Hipertensão Renal , Microscopia , Nefrite , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
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.
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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.
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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.
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Microscopia , Vasos Retinianos , Animais , Velocidade do Fluxo Sanguíneo , Hemodinâmica , Microbolhas , Coelhos , Fluxo Sanguíneo Regional/fisiologia , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência ÓpticaRESUMO
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.
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Técnicas de Imagem por Elasticidade , Síndromes da Dor Miofascial , Técnicas de Imagem por Elasticidade/métodos , Humanos , Músculo Esquelético , Síndromes da Dor Miofascial/diagnóstico por imagem , Projetos Piloto , Pontos-Gatilho/diagnóstico por imagem , UltrassonografiaRESUMO
Background: Placement of the clinical vagus nerve stimulating cuff is a standard surgical procedure based on anatomical landmarks, with limited patient specificity in terms of fascicular organization or vagal anatomy. As such, the therapeutic effects are generally limited by unwanted side effects of neck muscle contractions, demonstrated by previous studies to result from stimulation of (1) motor fibers near the cuff in the superior laryngeal and (2) motor fibers within the cuff projecting to the recurrent laryngeal. Objective: Conventional non-invasive ultrasound, where the transducer is placed on the surface of the skin, has been previously used to visualize the vagus with respect to other landmarks such as the carotid and internal jugular vein. However, it lacks sufficient resolution to provide details about the vagus fascicular organization, or detail about smaller neural structures such as the recurrent and superior laryngeal branch responsible for therapy limiting side effects. Here, we characterize the use of ultrasound with the transducer placed in the surgical pocket to improve resolution without adding significant additional risk to the surgical procedure in the pig model. Methods: Ultrasound images were obtained from a point of known functional organization at the nodose ganglia to the point of placement of stimulating electrodes within the surgical window. Naïve volunteers with minimal training were then asked to use these ultrasound videos to trace afferent groupings of fascicles from the nodose to their location within the surgical window where a stimulating cuff would normally be placed. Volunteers were asked to select a location for epineural electrode placement away from the fascicles containing efferent motor nerves responsible for therapy limiting side effects. 2-D and 3-D reconstructions of the ultrasound were directly compared to post-mortem histology in the same animals. Results: High-resolution ultrasound from the surgical pocket enabled 2-D and 3-D reconstruction of the cervical vagus and surrounding structures that accurately depicted the functional vagotopy of the pig vagus nerve as confirmed via histology. Although resolution was not sufficient to match specific fascicles between ultrasound and histology 1 to 1, it was sufficient to trace fascicle groupings from a point of known functional organization at the nodose ganglia to their locations within the surgical window at stimulating electrode placement. Naïve volunteers were able place an electrode proximal to the sensory afferent grouping of fascicles and away from the motor nerve efferent grouping of fascicles in each subject (n = 3). Conclusion: The surgical pocket itself provides a unique opportunity to obtain higher resolution ultrasound images of neural targets responsible for intended therapeutic effect and limiting off-target effects. We demonstrate the increase in resolution is sufficient to aid patient-specific electrode placement to optimize outcomes. This simple technique could be easily adopted for multiple neuromodulation targets to better understand how patient specific anatomy impacts functional outcomes.
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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.
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Fígado , Fígado/diagnóstico por imagem , Imagens de Fantasmas , Razão Sinal-Ruído , UltrassonografiaRESUMO
Ultrasound localization microscopy (ULM) has been proposed to image microvasculature beyond the ultrasound diffraction limit. Although ULM can attain microvascular images with a sub-diffraction resolution, long data acquisition time and processing time are the critical limitations. Deep learning-based ULM (deep-ULM) has been proposed to mitigate these limitations. However, microbubble (MB) localization used in deep-ULMs is currently based on spatial information without the use of temporal information. The highly spatiotemporally coherent MB signals provide a strong feature that can be used to differentiate MB signals from background artifacts. In this study, a deep neural network was employed and trained with spatiotemporal ultrasound datasets to better identify the MB signals by leveraging both the spatial and temporal information of the MB signals. Training, validation and testing datasets were acquired from MB suspension to mimic the realistic intensity-varying and moving MB signals. The performance of the proposed network was first demonstrated in the chicken embryo chorioallantoic membrane dataset with an optical microscopic image as the reference standard. Substantial improvement in spatial resolution was shown for the reconstructed super-resolved images compared with power Doppler images. The full-width-half-maximum (FWHM) of a microvessel was improved from 133µm to 35µm, which is smaller than the ultrasound wavelength (73µm). The proposed method was further tested in anin vivohuman liver data. Results showed the reconstructed super-resolved images could resolve a microvessel of nearly 170µm (FWHM). Adjacent microvessels with a distance of 670µm, which cannot be resolved with power Doppler imaging, can be well-separated with the proposed method. Improved contrast ratios using the proposed method were shown compared with that of the conventional deep-ULM method. Additionally, the processing time to reconstruct a high-resolution ultrasound frame with an image size of 1024 × 512 pixels was around 16 ms, comparable to state-of-the-art deep-ULMs.
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Microvasos , Animais , Embrião de Galinha , Galinhas , Processamento de Imagem Assistida por Computador , Microbolhas , Microscopia , Microvasos/diagnóstico por imagem , Redes Neurais de Computação , UltrassonografiaRESUMO
Non-invasive detection of microvascular alterations in deep tissuesin vivoprovides critical information for clinical diagnosis and evaluation of a broad-spectrum of pathologies. Recently, the emergence of super-resolution ultrasound localization microscopy (ULM) offers new possibilities for clinical imaging of microvasculature at capillary level. Currently, the clinical utility of ULM on clinical ultrasound scanners is hindered by the technical limitations, such as long data acquisition time, high microbubble (MB) concentration, and compromised tracking performance associated with low imaging frame-rate. Here we present a robust in-human ULM on a high frame-rate (HFR) clinical ultrasound scanner to achieve super-resolution microvessel imaging using a short acquisition time (<10 s). Ultrasound MB data were acquired from different human tissues, including a healthy liver and a diseased liver with acute-on-chronic liver failure, a kidney, a pancreatic tumor, and a breast mass using an HFR clinical scanner. By leveraging the HFR and advanced processing techniques including sub-pixel motion registration, MB signal separation, and Kalman filter-based tracking, MBs can be robustly localized and tracked for ULM under the circumstances of relatively high MB concentration associated with standard clinical MB administration and limited data acquisition time in humans. Subtle morphological and hemodynamic information in microvasculature were shown based on data acquired with single breath-hold and free-hand scanning. Compared with contrast-enhanced power Doppler generated based on the same MB dataset, ULM showed a 5.7-fold resolution improvement in a vessel based on a linear transducer, and provided a wide-range blood flow speed measurement that is Doppler angle-independent. Microvasculatures with complex hemodynamics can be well-differentiated at super-resolution in both normal and pathological tissues. This preliminary study implemented the ultrafast in-human ULM in various human tissues based on a clinical scanner that supports HFR imaging, indicating the potentials of the technique for various clinical applications. However, rigorous validation of the technique in imaging human microvasculature (especially for those tiny vessel structure), preferably with a gold standard, is still required.
Assuntos
Microbolhas , Microscopia , Ultrassonografia , Estudos de Viabilidade , Humanos , Microvasos/diagnóstico por imagemRESUMO
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.