Miguel Bernal

Material property estimation for tubes and arteries using ultrasound radiation force and analysis of propagating modes

Arterial elasticity has been proposed as an independent predictor of cardiovascular diseases and mortality. Identification of the different propagating modes in thin shells can be used to characterize the elastic properties. Ultrasound radiation force was used to generate local mechanical waves in the wall of a urethane tube or an excised pig carotid artery. The waves were tracked using pulse-echo ultrasound. A modal analysis using two-dimensional discrete fast Fourier transform was performed on the time-space signal. This allowed the visualization of different modes of propagation and characterization of dispersion curves for both structures. The urethane tube/artery was mounted in a metallic frame, embedded in tissue-mimicking gelatin, cannulated, and pressurized over a range of 10-100 mmHg. The k-space and the dispersion curves of the urethane tube showed one mode of propagation, with no effect of transmural pressure. Fitting of a Lamb wave model estimated Youngs modulus in the urethane tube around 560 kPa. Youngs modulus of the artery ranged from 72 to 134 kPa at 10 and 100 mmHg, respectively. The changes observed in the artery dispersion curves suggest that this methodology of exciting mechanical waves and characterizing the modes of propagation has potential for studying arterial elasticity.

RSNA/QIBA: Shear wave speed as a biomarker for liver fibrosis staging

An interlaboratory study of shear wave speed (SWS) estimation was performed. Commercial shear wave elastography systems from Fibroscan, Philips, Siemens and Supersonic Imagine, as well as several custom laboratory systems, were involved. Fifteen sites were included in the study. CIRS manufactured and donated 11 pairs of custom phantoms designed for the purposes of this investigation. Dynamic mechanical tests of equivalent phantom materials were also performed. The results of this study demonstrate that there is very good agreement among SWS estimation systems, but there are several sources of bias and variance that can be addressed to improve consistency of measurement results.

Anisotropic polyvinyl alcohol hydrogel phantom for shear wave elastography in fibrous biological soft tissue: a multimodality characterization.

Shear wave elastography can provide quantitative evaluation of soft tissues viscoelastic properties based on the measurement of shear wave speed in the medium. Muscular and cerebral tissues are composed of fibers which induce a strong anisotropic effect on the mechanical behavior. Currently, these tissues cannot be accurately represented by existing elastography phantoms and there is an urgent need of developing new anisotropic tissue mimicking phantoms. In the present study we propose an original multimodality imaging characterization of a transverse isotropic (TI) polyvinyl alcohol (PVA) cryogel. The mechanical anisotropy is induced in the PVA hydrogel by stretching the physical crosslinks of the polymeric chains while undergoing freezing cycling [1]. Multiple properties of these phantoms were investigated using a variety of techniques at different scale. The mechanical (dynamic and static) properties were studied using Supersonic Shear wave Imaging (SSI) technique [2] and Full-Field Optical Coherence Tomography (FF-OCT) strain imaging. The optical and ultrasonic spatial coherence properties were measure by FF-OCT volumetric imaging [3] and Backscatter Tensor Imaging (BTI) [4], respectively. The results suggest that this type of phantom (TI) could be used in the development of techniques and equipment to study anisotropy, such as the design of new ultrasound probes for cardiac and musculoskeletal application.

Phase aberration correction using ultrasound radiation force and vibrometry optimization

We describe a phase aberration correction method that uses dynamic ultrasound radiation force to harmonically vibrate an object using amplitude modulated continuous wave ultrasound. The phase of each element of an annular array transducer is adjusted to maximize the radiation force and obtain optimal focus of the ultrasound beam. The maximization of the radiation force is performed by monitoring the velocity of scatterers in the focus region. We present theory that shows focal optimization with radiation force has a well-behaved cost function. Experimental validation is shown by correction of manual defocusing of an annular array as well as correcting for a lens-shaped aberrator placed near the transducer. A Doppler laser vibrometer and a pulse-echo Doppler ultrasound method were used to monitor the velocity of a sphere used as a target for the transducer. By maximizing the radiation force-induced vibration of scatterers in the focal region, the resolution of the ultrasound beam can be recovered after aberration defocusing.

Ambulatory arterial stiffness index is not correlated with the pressor response to laboratory stressors in normotensive humans

Background Ambulatory arterial stiffness index (AASI) is a novel estimate of arterial stiffness, which independently predicts cardiovascular mortality, even in normotensive individuals. Additionally, other markers derived from ambulatory blood pressure (BP) monitoring, including variability, pulse pressure, nocturnal dipping, and morning BP surge, have all been shown to be predictive of end-organ damage and cardiovascular disease. Exaggerated cardiovascular reactivity to sympathoexcitatory stimuli may also predict future incidence of hypertension. The purpose of this investigation was to test the hypothesis that AASI and other derivations of ambulatory BP, including pulse pressure, 24-h blood pressure variability, dipping, and morning surge, would be correlated with the pressor response to common physiological stress maneuvers. Method We measured continuous heart rate and arterial BP during head-up tilt, mental stress, cold pressor test, and isometric handgrip to fatigue in 67 healthy, normotensive, nonobese individuals (43 women, 24 men, mean age ± SD: 28 ± 6 years). Then, 24-h ambulatory BP was obtained, and AASI was defined as 1 minus the slope of diastolic on systolic BP in individual 24-h ambulatory BP recordings. Results Although all measures were widely variable among patients, there was no relationship between AASI, pulse pressure, blood pressure variability, dipping, and morning surge with the pressor responses. Conclusion We conclude that in the absence of aging, cardiovascular, or autonomic disease, the novel stiffness index (AASI) or other ambulatory BP indices are either poorly correlated with or mechanistically unrelated to the complex pressor response to common provocations of sympathoexcitation.

Shear Wave Elastography Quantification of Blood Elasticity During Clotting

Deep venous thrombosis (DVT) affects millions of people worldwide. A fatal complication occurs when the thrombi detach and create a pulmonary embolism. The diagnosis and treatment of DVT depends on clots age. The elasticity of thrombi is closely related to its age. Blood was collected from pigs and anticoagulated using ethylenediaminetetraacetic acid (EDTA). Coagulation was initiated using calcium ions. Supersonic shear wave imaging was used to generate shear waves using 100 μs tone bursts of 8 MHz. Tracking of the shear waves was done by ultrafast imaging. Postprocessing of the data was done using Matlab(®). Two-dimensional (2-D) maps of elasticity were obtained by calculating the speed of shear wave propagation. Elasticity varied with time from around 50 Pa at coagulation to 1600 Pa at 120 min after which the elasticity showed a natural decreased (17%) because of thrombolytic action of plasmin. Ejection of the serum from the clot showed a significant decrease in the elasticity of the clot next to the liquid pool (65% decrease), corresponding to the detachment of the clot from the beaker wall. The use of a thrombolytic agent (Urokinase) on the coagulated blood decreased the shear elasticity close to the point of injection, which varied with time and distance. Supersonic imaging proved to be useful mapping the 2-D clots elasticity. It allowed the visualization of the heterogeneity of mechanical properties of thrombi and has potential use in predicting thrombi breakage as well as in monitoring thrombolytic therapy.

Transcriptomic regulations in oligodendroglial and microglial cells related to brain damage following fetal growth restriction

Fetal growth restriction (FGR) is a major complication of human pregnancy, frequently resulting from placental vascular diseases and prenatal malnutrition, and is associated with adverse neurocognitive outcomes throughout life. However, the mechanisms linking poor fetal growth and neurocognitive impairment are unclear. Here, we aimed to correlate changes in gene expression induced by FGR in rats and abnormal cerebral white matter maturation, brain microstructure, and cortical connectivity in vivo. We investigated a model of FGR induced by low‐protein‐diet malnutrition between embryonic day 0 and birth using an interdisciplinary approach combining advanced brain imaging, in vivo connectivity, microarray analysis of sorted oligodendroglial and microglial cells and histology. We show that myelination and brain function are both significantly altered in our model of FGR. These alterations, detected first in the white matter on magnetic resonance imaging significantly reduced cortical connectivity as assessed by ultrafast ultrasound imaging. Fetal growth retardation was found associated with white matter dysmaturation as shown by the immunohistochemical profiles and microarrays analyses. Strikingly, transcriptomic and gene network analyses reveal not only a myelination deficit in growth‐restricted pups, but also the extensive deregulation of genes controlling neuroinflammation and the cell cycle in both oligodendrocytes and microglia. Our findings shed new light on the cellular and gene regulatory mechanisms mediating brain structural and functional defects in malnutrition‐induced FGR, and suggest, for the first time, a neuroinflammatory basis for the poor neurocognitive outcome observed in growth‐restricted human infants. GLIA 2016;64:2306–2320

Modelling the impulse diffraction field of shear waves in transverse isotropic viscoelastic medium

The generation of shear waves from an ultrasound focused beam has been developed as a major concept for remote palpation using shear wave elastography (SWE). For muscular diagnostic applications, characteristics of the shear wave profile will strongly depend on characteristics of the transducer as well as the orientation of muscular fibers and the tissue viscoelastic properties. The numerical simulation of shear waves generated from a specific probe in an anisotropic viscoelastic medium is a key issue for further developments of SWE in fibrous soft tissues. In this study we propose a complete numerical tool allowing 3D simulation of a shear wave front in anisotropic viscoelastic media. From the description of an ultrasonic transducer, the shear wave source is simulated by using Fields II software and shear wave propagation described by using the Greens formalism. Finally, the comparison between simulations and experiments are successively performed for both shear wave velocity and dispersion profile in a transverse isotropic hydrogel phantom, in vivo forearm muscle and in vivo biceps brachii.

Functional ultrasound imaging of brain activity in human newborns

Functional ultrasound imaging with high spatiotemporal resolution monitors brain function in babies. (f)USIng technologies to image the newborn brain Electroencephalography (EEG) and functional neuroimaging enable us to better understand brain functions and to detect abnormalities. However, it is challenging to use these technologies at the bedside because of their size, lack of portability, and cost. Demene et al. have developed a portable customized and noninvasive system, called fUSI (functional ultrasound imaging), that is capable of continuous video-EEG recording and fast ultrasound imaging of the brain microvasculature in newborn babies. They applied fUSI to monitor brain activity and neurovascular changes in two neonates with abnormal cortical development, demonstrating the value of fUSI for the bedside monitoring of cerebral activity in neonates. Functional neuroimaging modalities are crucial for understanding brain function, but their clinical use is challenging. Recently, the use of ultrasonic plane waves transmitted at ultrafast frame rates was shown to allow for the spatiotemporal identification of brain activation through neurovascular coupling in rodents. Using a customized flexible and noninvasive headmount, we demonstrate in human neonates that real-time functional ultrasound imaging (fUSI) is feasible by combining simultaneous continuous video–electroencephalography (EEG) recording and ultrafast Doppler (UfD) imaging of the brain microvasculature. fUSI detected very small cerebral blood volume variations in the brains of neonates that closely correlated with two different sleep states defined by EEG recordings. fUSI was also used to assess brain activity in two neonates with congenital abnormal cortical development enabling elucidation of the dynamics of neonatal seizures with high spatiotemporal resolution (200 μm for UfD and 1 ms for EEG). fUSI was then applied to track how waves of vascular changes were propagated during interictal periods and to determine the ictal foci of the seizures. Imaging the human brain with fUSI enables high-resolution identification of brain activation through neurovascular coupling and may provide new insights into seizure analysis and the monitoring of brain function.

Measurement of biaxial mechanical properties of soft tubes and arteries using piezoelectric elements and sonometry.

Arterial elasticity has gained importance in recent decades because it has been shown to be an independent predictor of cardiovascular diseases. Several in vivo and ex vivo techniques have been developed to characterize the elastic properties of vessels. In vivo techniques tend to ignore the anisotropy of the mechanical properties in the vessel wall, and therefore fail to characterize elasticity in different directions. Ex vivo techniques have been focused on studying the mechanical properties in different axes. In this paper, we present a technique that uses piezoelectric elements to measure the elasticity of soft tubes and excised arteries in two directions while maintaining the natural structure of these vessels. This technique uses sonometry data from piezoelectric elements to measure the strain in the longitudinal and circumferential directions while the tubes/arteries are being pressurized. We conducted experiments on urethane tubes to evaluate the technique and compared the experimental results with mechanical testing done on the materials used for making the tubes. We then performed sonometry experiments on excised pig carotid arteries assuming that they are transversely isotropic materials. To evaluate the sensitivity of this technique to changes in the material properties, we changed the temperature of the saline bath in which the arteries were immersed. The calculated Youngs modulus from sonometry experiments for the urethane tubes and the mechanical testing values showed good agreement, deviating no more than 13.1%. The elasticity values from the excised arteries and the behavior with the temperature changed agreed with previous work done in similar arteries. Therefore, we propose this technique for nondestructive testing of the biaxial properties of soft material tubes and excised arteries in their natural physiological shape.