Tissue Doppler imaging of carotid plaque wall motion: a pilot study

BACKGROUND: Studies suggest the physical and mechanical properties of vessel walls and plaque may be of clinical value in the diagnosis and treatment of cardiovascular atherosclerotic disease. The purpose of this pilot study was to investigate the potential clinical application of ultrasound Tissue Doppler Imaging (TDI) of Arterial Wall Motion (AWM) and to quantify simple wall motion indices in normal and diseased carotid arteries. METHODS: 224 normal and diseased carotid arteries (0–100% stenoses) were imaged in 126 patients (age 25–88 years, mean 68 ± 11). Longitudinal sections of the carotid bifurcation were imaged using a Philips HDI5000 scanner and L12-5 probe under optimized TDI settings. Temporal and spatial AWMs were analyzed to evaluate the vessel wall displacements and spatial gradients at peak systole averaged over 5 cardiac cycles. RESULTS: AWM data were successfully extracted in 91% of cases. Within the carotid bifurcation/plaque region, the maximum wall dilation at peak systole ranged from -100 to 750 microns, mean 335 ± 138 microns. Maximum wall dilation spatial gradients ranged 0–0.49, mean 0.14 ± 0.08. The AWM parameters showed a wide variation and had poor correlation with stenoses severity. Case studies illustrated a variety of pertinent qualitative and quantitative wall motion features related to the biophysics of arterial disease. CONCLUSION: Our clinical experience, using a challenging but realistic imaging protocol, suggests the use of simple quantitative AWM measures may have limitations due to high variability. Despite this, pertinent features of AWM in normal and diseased arteries demonstrate the potential clinical benefit of the biomechanical information provided by TDI

Mycobacterium tuberculosis releases an antacid that remodels phagosomes

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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.Peer reviewe

Assessing the performance of vessel wall tracking algorithms: the importance of the test phantom

There is widespread clinical interest in assessing the mechanical properties of tissues and vessel walls. This study investigated the importance of the test phantom in providing a realistic assessment of clinical wall tracking performance for a variety of ultrasound modalities. B-mode, colour Doppler and Tissue Doppler Imaging (TDI) cineloop images were acquired using a Philips HDI5000 scanner and L12-5 probe. In-vivo longitudinal sections of 30 common carotid arteries and in-vitro images of pulsatile flow of a blood mimicking fluid through walled and wall-less tissue and vessel mimicking flow phantoms were analysed. Vessel wall tracking performance was assessed for our new probabilistic B-mode algorithm (PROBAL), and 3 different techniques implemented by Philips Medical Systems, based on B-mode edge detection (LDOT), colour Doppler (CVIQ) and TDI (TDIAWM). Precision (standard deviation/mean) of the peak systole dilations for respective PROBAL, LDOT, CVIQ and TDIAWM techniques were: 15.4 ± 8.4%, 23 ± 12.7%, 10 ± 10% and 10.3 ± 8.1% for the common carotid arteries; 6.4%, 22%, 11.6% and 34.5% for the wall-less flow phantom, 5.3%, 9.8%, 23.4% and 2.7% for the C-flex walled phantom and 3.9%, 2.6%, 1% and 3.2% for the latex walled phantom. The test phantom design and construction had a significant effect on the measurement of wall tracking performance

Validation of a new blood-mimicking fluid for use in Doppler flow test objects

A blood-mimicking fluid (BMF) suitable for use in Doppler flow test objects is described and characterised, The BMF consists of 5 mu m diameter nylon scattering particles suspended in a fluid base of water, glycerol, dextran and surfactant, The acoustical properties of various BMF preparations were measured under uniform flow to study the effects of particle size, particle concentration, surfactant concentration, flow rate and stability, The physical properties, (density, viscosity and particle size), and acoustical properties (velocity, backscatter and attenuation) of the BR-IF are within draft International Electrotechnical Commission requirements. (C) 1998 World Federation for Ultrasound in Medicine & Biology