Contactless Ultrasonic Cavitation for the Prevention of Shunt Obstruction in Hydrocephalus: A Proof-of-Concept Study.

Obstructive failure of implanted shunts is the most common complication in the treatment of hydrocephalus. Biological material and debris accumulate in the inner walls of the valve and catheters block the normal flow of the drained cerebrospinal fluid causing severe symptoms with high morbidity and mortality. Unfortunately, at present, there is no effective preventive protocol or cleaning procedure available. To assess whether externally applied, focused ultrasound beams can be used to resuspend deposits accumulated in brain shunts safely. A computational model of an implanted brain shunt was implemented to test the initial design parameters of a system comprising several ultrasound transducers. Under laboratory conditions, configurations with 3 and 4 transducers were arranged in a triangle and square pattern with their radiation axis directed towards a target model of the device, 2 catheters and a brain shunt filled with water and deposited graphite powder. The ultrasound beams were then concentrated on the device across a head model. The computational model revealed that by using only 3 transducers, the acoustic field intensity on the valve was approximately twice that on the brain surface suggesting that acoustic cavitation could be selectively achieved. Resuspension of graphite deposits inside the catheters and the valve were then physically demonstrated and video-recorded with no temperature increase. The technology presented here has the potential to be used routinely as a noninvasive, preventive cleaning procedure to reduce the likelihood of obstruction-related events in patients with hydrocephalus treated with an implanted shunt

Hyperspectral image processing for the identification and quantification of lentiviral particles in fluid samples

Optical spectroscopic techniques have been commonly used to detect the presence of biofilm-forming pathogens (bacteria and fungi) in the agro-food industry. Recently, near-infrared (NIR) spectroscopy revealed that it is also possible to detect the presence of viruses in animal and vegetal tissues. Here we report a platform based on visible and NIR (VNIR) hyperspectral imaging for non-contact, reagent free detection and quantification of laboratory-engineered viral particles in fluid samples (liquid droplets and dry residue) using both partial least square-discriminant analysis and artificial feed-forward neural networks. The detection was successfully achieved in preparations of phosphate buffered solution and artificial saliva, with an equivalent pixel volume of 4 nL and lowest concentration of 800 TU·μ L−1. This method constitutes an innovative approach that could be potentially used at point of care for rapid mass screening of viral infectious diseases and monitoring of the SARS-CoV-2 pandemic.This research was funded by grants number COV20-00080 and COV20-00173 of the 2020 Emergency Call for Research Projects about the SARS-CoV-2 virus and the COVID-19 disease of the Institute of Health ‘Carlos III’, Spanish Ministry of Science and Innovation, and by grant number EQC2019-006240-P of the 2019 Call for Acquisition of Scientifc Equipment, FEDER Program, Spanish Ministry of Science and Innovation. This work has been supported by the European Commission through the JRC HUMAINT project. ABR was supported by grant number RTI2018-094465-J funded by the Spanish National Agency of Research

Optical imaging spectroscopy for rapid, primary screening of SARS-CoV-2: a proof of concept

Effective testing is essential to control the coronavirus disease 2019 (COVID-19) transmission. Here we report a-proof-of-concept study on hyperspectral image analysis in the visible and near-infrared range for primary screening at the point-of-care of SARS-CoV-2. We apply spectral feature descriptors, partial least square-discriminant analysis, and artificial intelligence to extract information from optical diffuse reflectance measurements from 5 µL fluid samples at pixel, droplet, and patient levels. We discern preparations of engineered lentiviral particles pseudotyped with the spike protein of the SARS-CoV-2 from those with the G protein of the vesicular stomatitis virus in saline solution and artificial saliva. We report a quantitative analysis of 72 samples of nasopharyngeal exudate in a range of SARS-CoV-2 viral loads, and a descriptive study of another 32 fresh human saliva samples. Sensitivity for classification of exudates was 100% with peak specificity of 87.5% for discernment from PCR-negative but symptomatic cases. Proposed technology is reagent-free, fast, and scalable, and could substantially reduce the number of molecular tests currently required for COVID-19 mass screening strategies even in resource-limited settings.This research was funded by Grants Number COV20-00080 and COV20-00173 of the 2020 Emergency Call for Research Projects about the SARS-CoV-2 virus and the COVID-19 disease of the Institute of Health ‘Carlos III’, Spanish Ministry of Science and Innovation, and by Grant Number EQC2019-006240-P funded by MICIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”. ABR was supported by Grant Number RTI2018-094465-J-I00 funded by MICIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”. This work has been supported by the European Commission through the Joint Research Center (JRC) HUMAINT project

Optical imaging spectroscopy for rapid, primary screening of SARS-CoV-2: a proof of concept

Effective testing is essential to control the coronavirus disease 2019 (COVID-19) transmission. Here we report a-proof-of-concept study on hyperspectral image analysis in the visible and near-infrared range for primary screening at the point-of-care of SARS-CoV-2. We apply spectral feature descriptors, partial least square-discriminant analysis, and artificial intelligence to extract information from optical diffuse reflectance measurements from 5 µL fluid samples at pixel, droplet, and patient levels. We discern preparations of engineered lentiviral particles pseudotyped with the spike protein of the SARS-CoV-2 from those with the G protein of the vesicular stomatitis virus in saline solution and artificial saliva. We report a quantitative analysis of 72 samples of nasopharyngeal exudate in a range of SARS-CoV-2 viral loads, and a descriptive study of another 32 fresh human saliva samples. Sensitivity for classification of exudates was 100% with peak specificity of 87.5% for discernment from PCR-negative but symptomatic cases. Proposed technology is reagent-free, fast, and scalable, and could substantially reduce the number of molecular tests currently required for COVID-19 mass screening strategies even in resource-limited settings

Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS): Assessment & Validation of Imaging Modality Performance across the NAFLD Spectrum in a Prospectively Recruited Cohort Study (The LITMUS Imaging Study): Study Protocol

Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome with global prevalence reaching epidemic levels. Despite the high disease burden in the population only a small proportion of those with NAFLD will develop progressive liver disease, for which there is currently no approved pharmacotherapy. Identifying those who are at risk of progressive NAFLD currently requires a liver biopsy which is problematic. Firstly, liver biopsy is invasive and therefore not appropriate for use in a condition like NAFLD that affects a large proportion of the population. Secondly, biopsy is limited by sampling and observer dependent variability which can lead to misclassification of disease severity. Non-invasive biomarkers are therefore needed to replace liver biopsy in the assessment of NAFLD. Our study addresses this unmet need.The LITMUS Imaging Study is a prospectively recruited multi-centre cohort study evaluating magnetic resonance imaging and elastography, and ultrasound elastography against liver histology as the reference standard. Imaging biomarkers and biopsy are acquired within a 100-day window. The study employs standardised processes for imaging data collection and analysis as well as a real time central monitoring and quality control process for all the data submitted for analysis. It is anticipated that the high-quality data generated from this study will underpin changes in clinical practice for the benefit of people with NAFLD.Study Registration: clinicaltrials.gov: NCT0547972