Achieving Single Cell Acoustic Localisation with Deactivation Super Resolution.

Super-resolution optical microscopy enables optical imaging of cells, molecules and other biological structures beyond the diffraction limit. However, no similar method exists to super-resolve specific cells with ultrasound. Here we introduce Deactivation Super Resolution (DSR), an ultrasound imaging method that uses the acoustic deactivation of genetically encodable contrast agents to super-resolve individual cells with ultrasound as they navigate through structures that cannot be resolved by conventional imaging methods. DSR takes advantage of gas vesicles, which are air-filled sub-micron protein particles that can be expressed in genetically engineered cells to produce ultrasound contrast. Our experimental results show that DSR can distinguish sub-wavelength microstructures that standard B-mode ultrasound images fail to resolve by super- localizing individual mammalian cells. This study provides a proof of concept for the potential of DSR to serve as a super- resolution ultrasound technique for individual cell localization, opening new horizons in the field.

Enhanced Ultrasound Image Formation with Computationally Efficient Cross-Angular Delay Multiply and Sum Beamforming.

Ultrasound imaging is a valuable clinical tool. It is commonly achieved using the delay and sum beamformer algorithm, which takes the signals received by an array of sensors and generates an image estimating the spatial distribution of the signal sources. This algorithm, while computationally efficient, has limited resolution and suffers from high side lobes. Nonlinear processing has proven to be an effective way to enhance the image quality produced by beamforming in a computationally efficient manner. In this work, we describe a new beamforming algorithm called Cross-Angular Delay Multiply and Sum, which takes advantage of nonlinear compounding to enhance contrast and resolution. This is then implemented with a mathematical reformulation to produce images with tighter point spread functions and enhanced contrast at a low computational cost. We tested this new algorithm over a range of in vitro and in vivo scenarios for both conventional B-Mode and amplitude modulation imaging, and for two types of ultrasound contrast agents, demonstrating its potential for clinical settings.

Clinical efficacy and pharmacological mechanism analysis of Xubi Capsule in the treatment of patients with liver and kidney deficiency osteoarthritis.

To explore the clinical efficacy and pharmacological mechanism analysis of Xubi capsule in the treatment of patients with liver and kidney deficiency osteoarthritis (OA). In this single-center retrospective study, 120 patients with liver and kidney deficiency OA admitted to the Hangzhou Fuyang Hospital of Traditional Chinese Medicine from January 2020 to May 2022 were included, and patients were divided into the intervention group (n = 60) and the control group (n = 60) according to their treatment. The control group was treated with Ibuprofen, while the intervention group was treated with Xubi capsule combined with Ibuprofen. According to the network pharmacology method, the mechanism of the Xubi capsule in the treatment of patients with liver and kidney deficiency OA was analyzed. After the treatment, the total effective rate in the intervention group was 93.33%, which was significantly higher than that in the control group (P < .001). After treatment, compared with the control group, the degree of joint swelling and tenderness in the intervention group were lighter, the muscle strength was better, the level of erythrocyte sedimentation rate was lower, and the pain visual score was lower (P < .05), while the C-reactive protein level was significantly lower (P < .001). The effective chemical composition of Xubi capsules is 176, with quercetin and palmitoleic acid being the most associated with diseases. There are 209 intersection targets between drugs and diseases. A total of 119 gene ontology cellular components were significantly enriched. The combination of traditional Chinese medicine and Western medicine adopted in this study can effectively treat patients with liver and kidney deficiency OA and relieve the joint pain of patients. In a multicomponent and multitarget approach, the Xubi capsule breaks through the limitations of traditional nonsteroidal anti-inflammatory drugs and has good clinical application value.

XueBiJing injection improves the symptoms of sepsis-induced acute lung injury by mitigating oxidative stress and ferroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: XBJ injection is approved by the China Food and Drug Administration for the adjunctive treatment of sepsis, and it is derived from the traditional Chinese medicine (TCM) prescription XuefuZhuyu Decoction. It consists of five Chinese herbal extracts: Carthamus tinctorius, Paeonia lactiflora, Salvia miltiorrhiza, Conioselinum anthriscoides 'Chuanxiong' and Angelica sinensis. AIM OF THE STUDY: The purpose of this study was to explore the relationship between ferroptosis and acute septic lung injury, and to evaluate the improvement effect of XBJ injection on acute lung injury in sepsis. MATERIALS AND METHODS: Acute lung injury was induced in rats by cecum ligation and puncture, and these rats were treated with XBJ injection. Oxidative stress and inflammation levels were assessed in serum and lung tissue, and tissue samples were collected for histological and protein analyses. To illustrate the mechanism of the improvement effect of XBJ on acute lung injury in sepsis, serum lipidomics was carried out to investigate whether XBJ prevents oxidative stress-induced lipid metabolism disorders. Furthermore, protein expression of ferroptosis-related genes was also examined. RESULTS: XBJ was shown to be effective in alleviating sepsis-induced ALI. XBJ also improves sepsis-induced acute lung injury by reducing lipid peroxidation and inflammation and modulating ferroptosis pathways. Specifically, compared with the sham group, XBJ downregulated the levels of Fe2+, MDA and GSSG, and reversed the decrease in the levels of GSH and GSH/GSSH in lung tissue. Metabolic pathways such as glycerophospholipid metabolism, phospholipid metabolism, and lipid metabolism associated with ferroptosis were obtained by lipidomic analysis of differential lipid metabolite enrichment, suggesting that ferroptosis occurs in septic rats, and that XBJ inhibits ferroptosis and thereby improves sepsis-induced ALI. Furthermore, XBJ optimises iron metabolism and lipid oxide metabolism by regulating the expression of a series of proteins that are closely related to ferroptosis, such as GPX4, ACSL4, x-CT, and FTH1. CONCLUSIONS: Our findings, initially, indicated that XBJ ameliorates sepsis-induced ALI by reducing oxidative stress and ferroptosis, revealing a previously unrecognised mechanism by which XBJ ameliorates sepsis-induced ALI.

Cost-effectiveness of sotorasib as a second-line treatment for non-small cell lung cancer with KRASG12C mutation in China and the United States.

Purpose: To evaluate the cost-effectiveness of sotorasib versus docetaxel in non-small cell lung cancer (NSCLC) patients with KRASG12C mutation from the China and United States'social perspective. Materials and Methods: A Markov model that included three states (progression-free survival, post-progression survival, and death) was developed. Incremental cost-effectiveness ratio (ICER), quality-adjusted life-year (QALY), and incremental QALY were calculated for the two treatment strategies. One-way sensitivity analysis was used to investigate the factors that had a greater impact on the model results, and tornado diagrams were used to present the results. Probabilistic sensitivity analysis was performed with 1,000 Monte Carlo simulations. Assume distributions based on parameter types and randomly sample all parameter distributions each time., The results were presented as cost-effectiveness acceptable curves. Results: This economic evaluation of data from the CodeBreak 200 randomized clinical trial. In China, sotorasib generated 0.44 QAYL with a total cost of $84372.59. Compared with docetaxel, the ICER value of sotorasib was $102701.84/QALY, which was higher than willingness to pay (WTP), so sotorasib had no economic advantage. In the US, sotorasib obtained 0.35 QALY more than docetaxel, ICER was $15,976.50/QALY, which was more than 1 WTP but less than 3 WTP, indicating that the increased cost of sotorasib was acceptable. One-way sensitivity analysis showed that the probability of sotorasib having economic benefits gradually increased when the cost of follow-up examination was reduced in China. And there was no influence on the conclusions within the range of changes in China. When the willingness to pay (WTP) exceeds $102,500, the probability of sotorasib having cost effect increases from 0% to 49%. Conclusion: Sotorasib had a cost effect from the perspective in the United States. However, sotorasib had no cost effect from the perspective in China, and only when the WTP exceeds $102,500, the probability of sotorasib having cost effect increases from 0% to 49%.

High-resolution non-confocal non-line-of-sight imaging based on spherical-slice transform from spatial and temporal frequency to space and time.

Current non-confocal non-line-of-sight (NLOS) imaging faces the problems of low resolution and limited scene adaptability. We propose a non-confocal NLOS imaging method based on spherical-slice transform from spatial and temporal frequency to space and time. Simulation and experimental results show that the proposed method has high-resolution reconstruction without artifact interference, shape distortion, and position offset. Furthermore, it has strong scene adaptability. After GPU acceleration, the reconstruction time of the proposed method can be reduced to several hundred milliseconds for the PF32 photon array camera with 32 × 32 detection units. In the future, the proposed method has great potential for application in real-time NLOS imaging systems.

Transcutaneous Imaging of Rabbit Kidney Using 3-D Acoustic Wave Sparsely Activated Localization Microscopy with a Row-Column-Addressed Array.

OBJECTIVE: Super-resolution ultrasound (SRUS) imaging through localizing and tracking microbubbles, also known as ultrasound localization microscopy (ULM), can produce sub-diffraction resolution images of micro-vessels. We have recently demonstrated 3-D selective SRUS with a matrix array and phase change contrast agents (PCCAs). However, this method is limited to a small field of view (FOV) and by the complex hardware required. METHOD: This study proposed 3-D acoustic wave sparsely activated localization microscopy (AWSALM) using PCCAs and a 128+128 row-column-addressed (RCA) array, which offers ultrafast acquisition with over 6 times larger FOV and 4 times reduction in hardware complexity than a 1024-element matrix array. We first validated this method on an in-vitro microflow phantom and subsequently demonstrated non-invasively on a rabbit kidney in-vivo. RESULTS: Our results show that 3-D AWSALM images of the phantom covering a 25×25×40 mm 3 volume can be generated under 5 seconds with an 8 times resolution improvement over the system point spread function. The full volume of the rabbit kidney can be covered to generate 3-D microvascular structure, flow speed and direction super-resolution maps under 15 seconds, combining the large FOV of RCA with the high resolution of SRUS. Additionally, 3-D AWSALM is selective and can visualize the microvasculature within the activation volume and downstream vessels in isolation. Sub-sets of the kidney microvasculature can be imaged through selective activation of PCCAs. CONCLUSION: Our study demonstrates large FOV 3-D AWSALM using an RCA probe. SIGNIFICANCE: 3-D AWSALM offers an unique in-vivo imaging tool for fast, selective and large FOV vascular flow mapping.

Application of quantum dots in brain diseases and their neurotoxic mechanism.

The early-stage diagnosis and therapy of brain diseases pose a persistent challenge in the field of biomedicine. Quantum dots (QDs), nano-luminescent materials known for their small size and fluorescence imaging capabilities, present promising capabilities for diagnosing, monitoring, and treating brain diseases. Although some investigations about QDs have been conducted in clinical trials, the concerns about the toxicity of QDs have continued. In addition, the lack of effective toxicity evaluation methods and systems and the difference between in vivo and in vitro toxicity evaluation hinder QDs application. The primary objective of this paper is to introduce the neurotoxic effects and mechanisms attributable to QDs. First, we elucidate the utilization of QDs in brain disorders. Second, we sketch out three pathways through which QDs traverse into brain tissue. Ultimately, expound upon the adverse consequences of QDs on the brain and the mechanism of neurotoxicity in depth. Finally, we provide a comprehensive summary and outlook on the potential development of quantum dots in neurotoxicity and the difficulties to be overcome.

A convenient calf proportion index calculator for survival prediction in overweight and obese patients with cancer.

OBJECTIVE: This study aimed to define the calf proportion index (CPI) and investigate its association with malnutrition and survival in overweight and obese patients with cancer. METHODS: This multicenter observational cohort study included 3499 patients diagnosed with cancer, including 3145 overweight and 354 obese individuals. The CPI was defined as the ratio of the cross-sectional area of the calf circumference (CC) to the body surface area (BSA). A CPI calculator that automatically calculated the CPI and survival probability based on the patient's sex, height, weight, and CC was developed. RESULTS: During a median follow-up of 44.1 months, 935 deaths were recorded. Receiver operating characteristic curves revealed that the CPI was better than CC and BSA as a predictor of survival, with AUCs for the 3-year mortality rate were 0.574, 0.553 and 0.529, respectively. In overweight and obese patients with cancer, the optimal CPI cut-off value was 0.65 % for men and 0.57 % for women. The Kaplan-Meier curve revealed that patients with a low CPI had lower survival. After adjusting confounding factors, a low CPI was an independent risk factor for overweight (hazard ratio [HR]: 1.29, 95 % confidence interval [CI]: 1.11-1.51, P < 0.001) and obesity (HR: 1.92, 95 % CI: 1.20-3.09, P = 0.007) in patients with cancer. The CPI exhibited significant prognostic value in patients with lung and digestive system cancers. The risk of malnutrition was significantly higher in patients with a low CPI (HR: 1.25, 95 % CI: 1.04-1.50, P = 0.019). CONCLUSIONS: The CPI is a useful prognostic indicator in overweight and obese patients with cancer, especially in obese patients.

The survival and cost-effectiveness analysis of adjunctive Chinese medicine therapy for patients with non-small cell lung cancer: a nationwide cohort study in Taiwan.

Introduction: Cancer, particularly lung cancer, is a significant global healthcare challenge. Non-Small Cell Lung Cancer (NSCLC) constitutes 85% of cases. Patients often seek alternative therapies like Chinese medicine alongside Western treatments. This study investigates the survival outcomes and cost-effectiveness of adjunctive Chinese medicine therapy for NSCLC patients in Taiwan. Methods: We utilized the National Health Insurance Research Database in a retrospective cohort study from 2000 to 2018, focusing on NSCLC patients diagnosed between 2007 and 2013. After propensity score matching 1:5 ratio, then compared patients with and without adjunctive Chinese medicine therapy. Survival outcomes, cost-effectiveness, and sensitivity analyses were conducted. Results: The study involved 43,122 NSCLC patients with 5.76% receiving adjunctive Chinese medicine. There is no significant associated between the risk of death and adjuvant Chinese medicine therapy until 181-365 days of adjuvant treatment could reduce the risk of death (HR = 0.88, 95% CI: 0.80-0.98). Cost-effectiveness analysis showed an incremental cost-effectiveness ratio of 880,908 NT$/year. Conclusion: Adjunctive Chinese medicine therapy, particularly when administered for 181-365 days, significantly reduced the mortality risk among stage IV NSCLC patients. The cost-effectiveness aligns with willingness-to-pay thresholds, indicating economic benefit.

Metformin-Induced Invertase Unfolding: Enzyme Kinetics and Activity Regulation.

The effects of metformin on invertase activity and its inhibition on sucrose digestion were studied. The rapid unfolding kinetics of invertases, followed a two-state model with an inactive intermediate formation. The dynamic interaction between metformin and invertase caused the secondary structure of the enzyme to become less ß-sheet, more α-helix, and random coiling oriented, which weakened the binding force between enzyme and its substrate. Metformin acted as a chaotrope and disrupted the hydrogen bonds of water, which facilitated the unfolding of invertase. However, some sugar alcohols, which promoted the H-bond formation of water, could repair the secondary structure of metformin-denatured invertase and therefore regulate the enzyme activity. This research enriches our understanding of the mechanism of enzyme unfolding induced by guanidine compounds. Moreover, because metformin and sugar substitutes are of concern to diabetes, this research also provides useful information for understanding the activity of the digestive enzyme that coexists with metformin and sugar alcohols.

BpAFP, a Broussonetia papyrifera latex chitinase, exhibits a dual role in resisting to both Verticillium wilt disease and lepidopterous pests, Plutella xylostella and Prodenia litura.

Paper mulberry (Broussonetia papyrifera) is a fast-growing tree known for its tolerance to diverse biotic and abiotic stresses. To explore genes combating Verticillium wilt, a devasting and formidable disease damage to cotton and many economically significant crops, we purified an antifungal protein, named BpAFP, from the latex of paper mulberry. Based on peptide fingerprint, we cloned the full cDNA sequence of BpAFP and revealed that BpAFP belongs to Class I chitinases, sharing 74 % identity with B. papyrifera leaf chitinase, PMAPII. We further introduced BpAFP into Arabidopsis, tobacco, and cotton. Transgenic plants exhibited significant resistance to Verticillium wilt. Importantly, BpAFP also demonstrated insecticidal activity against herbivorous pests, Plutella xylostella, and Prodenia litura, when feeding the larvae with transgenic leaves. Our finding unveils a dual role of BpAFP in conferring resistance to both plant diseases and lepidopterous pests.

Differences in regional distribution and inequality in health workforce allocation in hospitals and primary health centers in China: A longitudinal study.

BACKGROUND: In 2009, China launched a new round of healthcare reform to provide households with secure, efficient, convenient, equitable and affordable healthcare services. Healthcare reform is underpinned by three critical pillars: the health workforce, funding, and infrastructure, with reform of the health workforce being particularly significant. OBJECTIVE: This study analyses the disparities in regional distribution and the inequity of healthcare workforce allocation across hospitals and primary health centers in China over twelve years. DESIGN: Retrospective longitudinal data from the National Health Statistics Yearbook 2011-2022 and National Statistical Yearbook in China from 2011 to 2022 were collected for analysis. PARTICIPANTS: The focus was on hospitals and primary health centers, explicitly examining their health technician and nursing workforce. METHODS: The research utilized four key indicators of the healthcare workforce to evaluate the distribution of health resources between hospitals and primary health centers. Furthermore, the Gini coefficient and Theil index were employed to assess the inequality in allocating the health workforce. RESULTS: Between 2010 and 2021, there was a nationwide increase in the ratio of health workers per 1000 population in hospitals and primary health centers. It is noted that rural districts had higher ratios than urban districts in terms of the number of health technicians and nurses per 1000 population, whether in hospitals or primary health centers; western districts had higher ratios than eastern and central districts did. In the same year, at different levels of medical institutions, the Theil indices of health technicians and nurses in hospitals were lower than those in primary health centers in terms of both demographic and geographical dimensions. Regarding the allocation of the health workforce by population, the Gini coefficient remained below 0.3, while for geographical allocation, it exceeded 0.4. CONCLUSIONS: This study analyzed the temporal trends and inequality of health-resource allocation at the hospital and primary health center levels in China, noting trends of improvements in the quantity and inequality in health workforce allocation from 2010 to 2021, suggesting the success of the government's efforts to advance healthcare reform since 2009. The allocation of health workforce based on population exhibits greater fairness compared to geographical distribution.

Ultrafast 3-D Transcutaneous Super Resolution Ultrasound Using Row-Column Array Specific Coherence-Based Beamforming and Rolling Acoustic Sub-aperture Processing: In Vitro, in Rabbit and in Human Study.

OBJECTIVE: This study aimed to realise 3-D super-resolution ultrasound imaging transcutaneously with a row-column array which has far fewer independent electronic channels and a wider field of view than typical fully addressed 2-D matrix arrays. The in vivo image quality of the row-column array is generally poor, particularly when imaging non-invasively. This study aimed to develop a suite of image formation and post-processing methods to improve image quality and demonstrate the feasibility of ultrasound localisation microscopy using a row-column array, transcutaneously on a rabbit model and in a human. METHODS: To achieve this, a processing pipeline was developed which included a new type of rolling window image reconstruction, which integrated a row-column array specific coherence-based beamforming technique with acoustic sub-aperture processing. This and other processing steps reduced the 'secondary' lobe artefacts, and noise and increased the effective frame rate, thereby enabling ultrasound localisation images to be produced. RESULTS: Using an in vitro cross tube, it was found that the procedure reduced the percentage of 'false' locations from ∼26% to ∼15% compared to orthogonal plane wave compounding. Additionally, it was found that the noise could be reduced by ∼7 dB and the effective frame rate was increased to over 4000 fps. In vivo, ultrasound localisation microscopy was used to produce images non-invasively of a rabbit kidney and a human thyroid. CONCLUSION: It has been demonstrated that the proposed methods using a row-column array can produce large field of view super-resolution microvascular images in vivo and in a human non-invasively.

ROS-mediated NRF2/p-ERK1/2 signaling-involved mitophagy contributes to macrophages activation induced by CdTe quantum dots.

Cadmium telluride (CdTe) quantum dots (QDs) have garnered significant attention for tumor imaging due to their exceptional properties. However, there remains a need for further investigation into their potential toxicity mechanisms and corresponding enhancements. Herein, CdTe QDs were observed to accumulate in mouse liver, leading to a remarkable overproduction of IL-1ß and IL-6. Additionally, there was evidence of macrophage infiltration and activation following exposure to 12.5 µmol/kg body weight of QDs. To elucidate the underlying mechanism of macrophage activation, CdTe QDs functionalized with 3-mercaptopropionic acid (MPA) were utilized. In vitro experiments revealed that 1.0 µM MPA-CdTe QDs activated PINK1-dependent mitophagy in RAW264.7 macrophages. Critically, the autophagic flux remained unimpeded, as demonstrated by the absence of p62 accumulation, LC3 turnover assay results, and successful fusion of autophagosomes with lysosomes. Mechanically, QDs increased reactive oxygen species (ROS) and mitoROS by damaging both mitochondria and lysosomes. ROS, in turn, inhibited NRF2, resulting in the phosphorylation of ERK1/2 and subsequent activation of mitophagy. Notably, 1.0 µM QDs disrupted lysosomes but autophagic flux was not impaired. Eventually, the involvement of the ROS-NRF2-ERK1/2 pathway-mediated mitophagy in the increase of IL-1ß and IL-6 in macrophages was confirmed using Trolox, MitoTEMPO, ML385, specific siRNAs, and lentivirus-based interventions. This study innovatively revealed the pro-inflammatory rather than anti-inflammatory role of mitophagy in nanotoxicology, shedding new light on the mechanisms of mitochondrial disorders induced by QDs and identifying several molecular targets to comprehend the toxicological mechanisms of CdTe QDs.

Transthoracic ultrasound localization microscopy of myocardial vasculature in patients.

Myocardial microvasculature and haemodynamics are indicative of potential microvascular diseases for patients with symptoms of coronary heart disease in the absence of obstructive coronary arteries. However, imaging microvascular structure and flow within the myocardium is challenging owing to the small size of the vessels and the constant movement of the patient's heart. Here we show the feasibility of transthoracic ultrasound localization microscopy for imaging myocardial microvasculature and haemodynamics in explanted pig hearts and in patients in vivo. Through a customized data-acquisition and processing pipeline with a cardiac phased-array probe, we leveraged motion correction and tracking to reconstruct the dynamics of microcirculation. For four patients, two of whom had impaired myocardial function, we obtained super-resolution images of myocardial vascular structure and flow using data acquired within a breath hold. Myocardial ultrasound localization microscopy may facilitate the understanding of myocardial microcirculation and the management of patients with cardiac microvascular diseases.

Universal scaling law for chiral antiferromagnetism.

The chiral antiferromagnetic (AFM) materials, which have been widely investigated due to their rich physics, such as non-zero Berry phase and topology, provide a platform for the development of antiferromagnetic spintronics. Here, we find two distinctive anomalous Hall effect (AHE) contributions in the chiral AFM Mn3Pt, originating from a time-reversal symmetry breaking induced intrinsic mechanism and a skew scattering induced topological AHE due to an out-of-plane spin canting with respect to the Kagome plane. We propose a universal AHE scaling law to explain the AHE resistivity ( ρ A H ) in this chiral magnet, with both a scalar spin chirality (SSC)-induced skew scattering topological AHE term, a s k and non-collinear spin-texture induced intrinsic anomalous Hall term, b i n . We found that a s k and b i n can be effectively modulated by the interfacial electron scattering, exhibiting a linear relation with the inverse film thickness. Moreover, the scaling law can explain the anomalous Hall effect in various chiral magnets and has far-reaching implications for chiral-based spintronics devices.

Detecting heart failure from B-mode ultrasound characterization of arterial pulse waves.

This study investigated the sensitivity and specificity of identifying heart failure with reduced ejection fraction (HFrEF) from measurements of the intensity and timing of arterial pulse waves. Previously validated methods combining ultrafast B-mode ultrasound, plane-wave transmission, singular value decomposition (SVD), and speckle tracking were used to characterize the compression and decompression ("S" and "D") waves occurring in early and late systole, respectively, in the carotid arteries of outpatients with left ventricular ejection fraction (LVEF) < 40%, determined by echocardiography, and signs and symptoms of heart failure, or with LVEF ≥ 50% and no signs or symptoms of heart failure. On average, the HFrEF group had significantly reduced S-wave intensity and energy, a greater interval between the R wave of the ECG and the S wave, a reduced interval between the S and D waves, and an increase in the S-wave shift (SWS), a novel metric that characterizes the shift in timing of the S wave away from the R wave of the ECG and toward the D wave (all P < 0.01). Receiver operating characteristics (ROCs) were used to quantify for the first time how well wave metrics classified individual participants. S-wave intensity and energy gave areas under the ROC of 0.76-0.83, the ECG-S-wave interval gave 0.85-0.88, and the S-wave shift gave 0.88-0.92. Hence the methods, which are simple to use and do not require complex interpretation, provide sensitive and specific identification of HFrEF. If similar results were obtained in primary care, they could form the basis of techniques for heart failure screening.NEW & NOTEWORTHY We show that heart failure with reduced ejection fraction can be detected with excellent sensitivity and specificity in individual patients by using B-mode ultrasound to detect altered pulse wave intensity and timing in the carotid artery.

Understanding the effects of microbubble concentration on localization accuracy in super-resolution ultrasound imaging.

Super-resolution ultrasound (SRUS) through localising and tracking of microbubbles (MBs) can achieve sub-wavelength resolution for imaging microvascular structure and flow dynamics in deep tissuein vivo. The technique assumes that signals from individual MBs can be isolated and localised accurately, but this assumption starts to break down when the MB concentration increases and the signals from neighbouring MBs start to interfere. The aim of this study is to gain understanding of the effect of MB-MB distance on ultrasound images and their localisation. Ultrasound images of two MBs approaching each other were synthesised by simulating both ultrasound field propagation and nonlinear MB dynamics. Besides the distance between MBs, a range of other influencing factors including MB size, ultrasound frequency, transmit pulse sequence, pulse amplitude and localisation methods were studied. The results show that as two MBs approach each other, the interference fringes can lead to significant and oscillating localisation errors, which are affected by both the MB and imaging parameters. When modelling a clinical linear array probe operating at 6 MHz, localisation errors between 20 and 30µm (∼1/10 wavelength) can be generated when MBs are ∼500µm (2 wavelengths or ∼1.7 times the point spread function (PSF)) away from each other. When modelling a cardiac probe operating at 1.5 MHz, the localisation errors were as high as 200µm (∼1/5 wavelength) even when the MBs were more than 10 wavelengths apart (2.9 times the PSF). For both frequencies, at smaller separation distances, the two MBs were misinterpreted as one MB located in between the two true positions. Cross-correlation or Gaussian fitting methods were found to generate slightly smaller localisation errors than centroiding. In conclusion, caution should be taken when generating and interpreting SRUS images obtained using high agent concentration with MBs separated by less than 1.7 to 3 times the PSF, as significant localisation errors can be generated due to interference between neighbouring MBs.