Contrast enhanced ultrasound is a radiation-free imaging modality which uses encapsulated gas microbubbles for improved visualization of the vascular bed deep within the tissue. It has recently been used to enable imaging with unprecedented subwavelength spatial resolution by relying on super-resolution techniques. A typical preprocessing step in super-resolution ultrasound is to separate the microbubble signal from the cluttering tissue signal. This step has a crucial impact on the final image quality. Here, we propose a new approach to clutter removal based on robust principle component analysis (PCA) and deep learning. We begin by modeling the acquired contrast enhanced ultrasound signal as a combination of a low rank and sparse components. This model is used in robust PCA and was previously suggested in the context of ultrasound Doppler processing and dynamic magnetic resonance imaging. We then illustrate that an iterative algorithm based on this model exhibits improved separation of microbubble signal from the tissue signal over commonly practiced methods. Next, we apply the concept of deep unfolding to suggest a deep network architecture tailored to our clutter filtering problem which exhibits improved convergence speed and accuracy with respect to its iterative counterpart. We compare the performance of the suggested deep network on both simulations and in-vivo rat brain scans, with a commonly practiced deep-network architecture and the fast iterative shrinkage algorithm, and show that our architecture exhibits better image quality and contrast.
Maintenance of normal myocardial function depends intimately on synchronous tissue contraction driven by electrical activation and on adequate nutrient perfusion in support thereof. Bioreactors have been used to mimic aspects of these factors in vitro to engineer cardiac tissue, but due to design limitations, previous bioreactor systems have yet to simultaneously support nutrient perfusion, electrical stimulation, and unconstrained (i.e., not isometric) tissue contraction. To the best of our knowledge, the bioreactor system described herein is the first to integrate in concert these three key factors. We present the design of our bioreactor and characterize its capability in integrated experimental and mathematical modeling studies. We then culture cardiac cells obtained from neonatal rats in porous, channeled elastomer scaffolds with the simultaneous application of perfusion and electrical stimulation, with controls excluding either one or both of these two conditions. After eight days of culture, constructs grown with the simultaneous perfusion and electrical stimulation exhibited substantially improved functional properties, as evidenced by a significant increase in contraction amplitude (0.23±0.10% vs. 0.14±0.05, 0.13±0.08, or 0.09±0.02% in control constructs grown without stimulation, without perfusion, or either stimulation or perfusion, respectively). Consistently, these constructs had significantly improved DNA contents, cell distribution throughout the scaffold thickness, cardiac protein expression, cell morphology and overall tissue organization than either control group. Thus, the simultaneous application of medium perfusion and electrical conditioning enabled by the use of the novel bioreactor system may accelerate the generation of fully functional, clinically sized cardiac tissue constructs.
The high intensity focused ultrasound (HIFU) and thermosensitive cerasomes (HTSCs) were successfully assembled by employing cerasome-forming lipid (CFL) in combination with the component lipids of conventional low temperature sensitive liposomes (LTSLs) including 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG-2000) and 1-stearoyl-2-hydroxy-sn-glycero-3-phosphocholine (MSPC). The HTSCs showed spherical shape with a mean diameter around 200 nm, exhibiting good biocompatibility. Both hydrophilic and lipophilic drugs can be efficiently encapsulated into HTSCs. In addition, the release rate of HTSCs could be conveniently adjusted by varying the molar ratios of CFL to DPPC. The drug loaded HTSCs showed much longer blood circulation time (half-life >8.50 ± 1.49 h) than conventional LTSLs (0.92 ± 0.17 h). An in vitro study demonstrated that the drug loaded HTSCs are highly stable at 37 °C and show a burst release at 42 °C, providing a capability to act synergistically against tumors. We found that the HTSCs with a proportion of 43.25% of CFL could release more than 90% hydrophilic drugs in 1 min at an elevated temperature of 42 °C generated by HIFU exposure. After intravenous injection of doxorubicin (DOX) loaded HTSCs at 5 mg DOX/kg, followed by double HIFU sonication, the tumor growth of the adenocarcinoma (MDA-MB-231) bearing mice could be significantly inhibited. Therefore, the drug loaded HTSCs combined with HIFU hold great potential for efficient local chemotherapy of cancer due to the ability to deliver high concentration of chemotherapy drugs directly to the tumor, achieve maximum therapeutic efficacy and minimal side effects, and avoid the damage to the healthy tissues caused by systemic administration of drugs.
Reliability and in vivo feasibility of the proposed PWI method were demonstrated in this study. Its simplicity of use and its capability of providing regional PWV render PWI a valuable tool for quantitative assessment of arterial stiffness. The utility of the method in a clinical setting has yet to be established and is part of an ongoing clinical study.
It is critical for the recovery of manufacturing industry against COVID-19 by analyzing its impact from supply chain perspective and exploring corresponding countermeasures. Firstly, this paper studies the initial impact caused by worldwide spread of the coronavirus, such as production disruption of raw material and spare parts, unsatisfied market demand due to setbacks in logistics, increasing bankruptcy risk for small and mediumsized enterprises (SMEs), and demand fluctuation enlargement. Secondly, the aftershock of COVID-19 is analyzed. With the trend of regionalization and digitalization, two-step countermeasures are proposed to help the recovery of manufacturing industry within the pandemic and better prepare for the post-COVID-19 world from supply chain perspective.
Arterial stiffness is well accepted as a reliable indicator of arterial disease. Increase in carotid arterial stiffness has been associated with carotid arterial disease, e.g., atherosclerotic plaque, thrombosis, stenosis, etc. Several methods for carotid arterial stiffness assessments have been proposed. In this study, in-vivo noninvasive assessment using applanation tonometry and an ultrasound-based motion estimation technique was applied in seven healthy volunteers (age 28 ± 3.6 years old) to determine pressure and wall displacement in the left common carotid artery (CCA), respectively. The carotid pressure was obtained using a calibration method by assuming that the mean and diastolic blood pressures remained constant throughout the arterial tree. The regional carotid arterial wall displacement was estimated using a 1D cross-correlation technique on the ultrasound radio frequency (RF) signals acquired at a frame rate of 505–1010 Hz. Young’s moduli were estimated under two different assumptions: (i) a linear elastic two-parallel spring model and (ii) a two-dimensional, nonlinear, hyperelastic model. The circumferential stress (σθ) and strain (εθ) relationship was then established in humans in vivo. A slope change in the circumferential stress-strain curve was observed and defined as a transition point. The Young’s moduli of the elastic lamellae (E1), elastin-collagen fibers (E2) and collagen fibers (E3) and the incremental Young’s moduli before (E0≤εθ<ε0T) and after the transition point (EεθT≤εθ) were determined from the first and second approach, respectively, to describe the contribution of the complex mechanical interaction of the different arterial wall constituents. The average E1, E2 and E3 from seven healthy volunteers were found to be equal to 0.15 ± 0.04, 0.89 ± 0.27 and 0.75 ± 0.29 MPa, respectively. The average E0≤εθ<εθTInt and EεθT≤εθInt of the intact wall (both the tunica adventitia and tunica media layers) were found to be equal to 0.16 ± 0.04 MPa and 0.90 ± 0.25 MPa, respectively. The average E0≤εθ<εθTAd and EεθT≤εθAd of the tunica adventitia were found to be equal to 0.18 ± 0.05 MPa and 0.84 ± 0.22 MPa, respectively. The average EεθT≤εθMe and EεθT≤εθMe of the tunica media were found to be equal to 0.19 ± 0.05 MPa and 0.90 ± 0.25 MPa, respectively. The stiffness of the carotid artery increased with strain during the systolic phase of cardiac cycle. In conclusion, the feasibility of measuring the regional stress-strain relationship and stiffness of the normal human carotid artery noninvasively was demonstrated in human in vivo.
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