Transcranial ultrasound simulation with uncertainty estimation

Transcranial ultrasound simulations are increasingly used to predict in situ exposure parameters for ultrasound therapies in the brain. However, there can be considerable uncertainty in estimating the acoustic medium properties of the skull and brain from computed tomography (CT) images. This paper shows how the resulting uncertainty in the simulated acoustic field can be predicted in a computationally efficient way using linear uncertainty propagation. Results for a representative transcranial simulation using a focused bowl transducer at 500 kHz show good agreement with unbiased uncertainty estimates obtained using Monte Carlo

j-Wave: An open-source differentiable wave simulator

We present an open-source differentiable acoustic simulator, j-Wave, which can solve time-varying and time-harmonic acoustic problems. It supports automatic differentiation, which is a program transformation technique that has many applications, especially in machine learning and scientific computing. j-Wave is composed of modular components that can be easily customized and reused. At the same time, it is compatible with some of the most popular machine learning libraries, such as JAX and TensorFlow. The accuracy of the simulation results for known configurations is evaluated against the widely used k-Wave toolbox and a cohort of acoustic simulation software. j-Wave is available from https://github.com/ucl-bug/jwave

Novel Biological Therapies for Severe Asthma Endotypes

Severe asthma comprises several heterogeneous phenotypes, underpinned by complex pathomechanisms known as endotypes. The latter are driven by intercellular networks mediated by molecular components which can be targeted by specific monoclonal antibodies. With regard to the biological treatments of either allergic or non-allergic eosinophilic type 2 asthma, currently available antibodies are directed against immunoglobulins E (IgE), interleukin-5 (IL-5) and its receptor, the receptors of interleukins-4 (IL-4) and 13 (IL-13), as well as thymic stromal lymphopoietin (TSLP) and other alarmins. Among these therapeutic strategies, the best choice should be made according to the phenotypic/endotypic features of each patient with severe asthma, who can thus respond with significant clinical and functional improvements. Conversely, very poor options so far characterize the experimental pipelines referring to the perspective biological management of non-type 2 severe asthma, which thereby needs to be the focus of future thorough research

Classical and learned MR to pseudo-CT mappings for accurate transcranial ultrasound simulation

Model-based treatment planning for transcranial ultrasound therapy typically involves mapping the acoustic properties of the skull from an x-ray computed tomography (CT) image of the head. Here, three methods for generating pseudo-CT images from magnetic resonance (MR) images were compared as an alternative to CT. A convolutional neural network (U-Net) was trained on paired MR-CT images to generate pseudo-CT images from either T1-weighted or zero-echo time (ZTE) MR images (denoted tCT and zCT, respectively). A direct mapping from ZTE to pseudo-CT was also implemented (denoted cCT). When comparing the pseudo-CT and ground truth CT images for the test set, the mean absolute error was 133, 83, and 145 Hounsfield units (HU) across the whole head, and 398, 222, and 336 HU within the skull for the tCT, zCT, and cCT images, respectively. Ultrasound simulations were also performed using the generated pseudo-CT images and compared to simulations based on CT. An annular array transducer was used targeting the visual or motor cortex. The mean differences in the simulated focal pressure, focal position, and focal volume were 9.9%, 1.5 mm, and 15.1% for simulations based on the tCT images, 5.7%, 0.6 mm, and 5.7% for the zCT, and 6.7%, 0.9 mm, and 12.1% for the cCT. The improved results for images mapped from ZTE highlight the advantage of using imaging sequences which improve contrast of the skull bone. Overall, these results demonstrate that acoustic simulations based on MR images can give comparable accuracy to those based on CT

Multi-Frame Rate Plane Wave Contrast-Enhance Ultrasound Imaging for Tumour Vasculature Imaging and Perfusion Quantification

A multi-frame rate plane wave imaging strategy is developed to simultaneously image tumor vasculature and quantify tumor perfusion. Customised imaging sequences interleaving a short but high frame rate (HFR) plane wave imaging sequence with a long but low frame rate imaging (LFR) sequence were implemented using a programmable ultrasound research platform. The results from a spatio-temporal coherence processing technique of ours demonstrated a significant improvement in the SNR and vasculature contrast when compared with the existing ultrafast Power Doppler (PD) using the same data. Initial perfusion quantification using LFR imaging was also demonstrated. Mean time intensity curve and some parametric measures were generated. Combining both structural and functional perfusion imaging using the multiframe rate sequences, a better evaluation of the tumour angiogenesis can be assessed

Peripheral depletion of NK cells and imbalance of the Treg/Th17 axis in idiopathic pulmonary fibrosis patients

The immune response plays an unsettled role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), the contribution of inflammation being controversial as well. Emerging novel T cell sub-populations including regulatory T lymphocytes (Treg) and interleukin (IL)-17 secreting T helper cells (Th17) may exert antithetical actions in this scenario. Phenotype and frequency of circulating immune cell subsets were assessed by multi-parametric flow cytometry in 29 clinically stable IPF patients and 17 healthy controls. The interplay between Treg lymphocytes expressing transforming growth factor (TGF)-β and Th17 cells was also investigated. Proportion and absolute number of natural killer (NK) cells were significantly reduced in IPF patients in comparison with controls (p90%) expressed TGF-β upon stimulation. Interestingly, the frequency of Th17 cells was significantly compromised in IPF patients (p=0.000) leading to an increased TGF-β/IL-17 ratio (4.2±2.3 vs 0.5±0.3 in controls, p=0.000). Depletion of NK and Th17 cells along with a not compromised Treg compartment delineate the existence of an "immune profile" that argue against the recent hypothesis of IPF as an autoimmune disease. Our findings along with the imbalance of the Treg/Th17 axis more closely suggest these immune perturbations to be similar to those observed in cancer. Clinical relevance, limitations and perspectives for future research are discussed. © 2014 Elsevier Ltd

Idiopathic pulmonary fibrosis telemedicine management during COVID-19 outbreak

The present report investigates the impact of a Telemedicine Service (TMS) on the management of Idiopathic Pulmonary Fibrosis (IPF) during coronavirus disease of 2019 (COVID-19) outbreak in Italy. The TMS comprised 3 phone numbers, active 12 h per day, and an email address, monitored every 4 h by trained physicians; chat-and videoconference-services were also offered. At the end of the study period, our staff contacted all patients, to get information about the final outcome (i.e. composite hospitalisations/all causes of death). Outcomes were compared with a cohort of patients who attended our unit in the same period of the previous year (when no TMS was available). 189 patients participated in the present study. From 11th March to 4th May 2020, 61% of patients made at least one TMS access, mostly by emails (53%), followed by phone calls (33%). With regard to the primary outcome, TMS patients experienced a significant lower rate of events of the 182 patients of the no-TMS cohort (p < 0.001). Specifically, a significant difference was observed for IPF hospitalisation (p < 0.001) whereas no differences were observed with regard to deaths (p = 0.64). TMS permits patients to be followed up even during COVID-19 lockdown, with an encouraging impact on outcomes

Effects of motion on high frame rate contrast enhanced echocardiography and its correction

Contrast echocardiography (CE) ultrasound with microbubble contrast agents have significantly advanced our capability in assessing cardiac function, including myocardium perfusion imaging and quantification. However in conventional CE techniques with line by line scanning, the frame rate is limited to tens of frames per second and image quality is low. Recent research works in high frame-rate (HFR) ultrasound have shown significant improvement of the frame rate in non-contrast cardiac imaging. But with a higher frame rate, the coherent compounding of HFR CE images shows some artifacts due to the motion of the microbubbles. In this work we demonstrate the impact of this motion on compounded HFR CE in simulation and then apply a motion correction algorithm on in-vivo data acquired from the left ventricle (LV) chamber of a sheep. It shows that even if with the fast flow found inside the LV, the contrast is improved at least 100%