Jonathan Vappou

Pulse Wave Imaging for Noninvasive and Quantitative Measurement of Arterial Stiffness In Vivo

BACKGROUND Arterial stiffening is recognized to be associated with increased cardiovascular mortality and to be a major cause of several cardiovascular complications. Pulse wave velocity (PWV) has been widely accepted to be a reliable and robust measure of arterial stiffness. In this article, the novel ultrasound-based pulse wave imaging (PWI) method is hereby proposed for visualization of the pulse wave during its propagation and for calculation of the PWV. METHODS The PWV is estimated by measuring the spatiotemporal variation of the pulse wave-induced displacement of the arterial wall within the imaged segment. The method is compared to mechanical testing on aortic phantoms in order to evaluate its reliability and accuracy, and in vivo results are presented on normal abdominal aortas (N = 11). RESULTS Good agreement was found with mechanical testing on phantoms (r(2) = 0.92), showing the reliability of the method. In vivo average PWV and Youngs modulus were found to be equal to 4.4 +/- 0.6 m/s and 108 +/- 27 kPa, respectively. CONCLUSIONS Reliability and in vivo feasibility of the proposed PWI method were demonstrated in this study. Its simplicity of use and its capability of providing regional PWV render PWI a valuable tool for quantitative assessment of arterial stiffness. The utility of the method in a clinical setting has yet to be established and is part of an ongoing clinical study.

Arterial stiffness identification of the human carotid artery using the stress-strain relationship in vivo

Arterial stiffness is well accepted as a reliable indicator of arterial disease. Increase in carotid arterial stiffness has been associated with carotid arterial disease, e.g., atherosclerotic plaque, thrombosis, stenosis, etc. Several methods for carotid arterial stiffness assessment have been proposed. In this study, in vivo noninvasive assessment using applanation tonometry and an ultrasound-based motion estimation technique was applied in seven healthy volunteers (age 28±3.6years old) to determine pressure and wall displacement in the left common carotid artery (CCA), respectively. The carotid pressure was obtained using a calibration method by assuming that the mean and diastolic blood pressures remained constant throughout the arterial tree. The regional carotid arterial wall displacement was estimated using a 1D cross-correlation technique on the ultrasound radio frequency (RF) signals acquired at a frame rate of 505-1010Hz. Youngs moduli were estimated under two different assumptions: (i) a linear elastic two-parallel spring model and (ii) a two-dimensional, nonlinear, hyperelastic model. The circumferential stress (σ(θ)) and strain (ɛ(θ)) relationship was then established in humans in vivo. A slope change in the circumferential stress-strain curve was observed and defined as the transition point. The Youngs moduli of the elastic lamellae (E(1)), elastin-collagen fibers (E(2)) and collagen fibers (E(3)) and the incremental Youngs moduli before ( [Formula: see text] ) and after the transition point ( [Formula: see text] ) were determined from the first and second approach, respectively, to describe the contribution of the complex mechanical interaction of the different arterial wall constituents. The average moduli E(1), E(2) and E(3) from seven healthy volunteers were found to be equal to 0.15±0.04, 0.89±0.27 and 0.75±0.29MPa, respectively. The average moduli [Formula: see text] and [Formula: see text] of the intact wall (both the tunica adventitia and tunica media layers) were found to be equal to 0.16±0.04MPa and 0.90±0.25MPa, respectively. The average moduli [Formula: see text] and [Formula: see text] of the tunica adventitia were found to be equal to 0.18±0.05MPa and 0.84±0.22MPa, respectively. The average moduli [Formula: see text] and [Formula: see text] of the tunica media were found to be equal to 0.19±0.05MPa and 0.90±0.25MPa, respectively. The stiffness of the carotid artery increased with strain during the systolic phase. In conclusion, the feasibility of measuring the regional stress-strain relationship and stiffness of the normal human carotid artery was demonstrated noninvasively in vivo.

Magnetic resonance elastography compared with rotational rheometry for in vitro brain tissue viscoelasticity measurement

Magnetic resonance elastography (MRE) is an increasingly used method for non-invasive determination of tissue stiffness. MRE has shown its ability to measure in vivo elasticity or viscoelasticity depending on the chosen rheological model. However, few data exist on quantitative comparison of MRE with reference mechanical measurement techniques. MRE has only been validated on soft homogeneous gels under both Hookean elasticity and linear viscoelasticity assumptions, but comparison studies are lacking concerning viscoelastic properties of complex heterogeneous tissues. In this context, the present study aims at comparing an MRE-based method combined with a wave equation inversion algorithm to rotational rheometry. For this purpose, experiments are performed on in vitro porcine brain tissue. The dynamic behavior of shear storage (G- and loss (G′) moduli obtained by both rheometry and MRE at different frequency ranges is similar to that of linear viscoelastic properties of brain tissue found in other studies. This continuity between rheometry and MRE results consolidates the quantitative nature of values found by MRE in terms of viscoelastic parameters of soft heterogeneous tissues. Based on these results, the limits of MRE in terms of frequency range are also discussed.

In vivo characterization of the aortic wall stress-strain relationship.

Arterial stiffness has been shown to be a good indicator of arterial wall disease. However, a single parameter is insufficient to describe the complex stress-strain relationship of a multi-component, non-linear tissue such as the aorta. We therefore propose a new approach to measure the stress-strain relationship locally in vivo noninvasively, and present a clinically relevant parameter describing the mechanical interaction between aortic wall constituents. The slope change of the circumferential stress-strain curve was hypothesized to be related to the contribution of elastin and collagen, and was defined as the transition strain (epsilon(theta)(T)). A two-parallel spring model was employed and three Youngs moduli were accordingly evaluated, i.e., corresponding to the: elastic lamellae (E(1)), elastin-collagen fibers (E(2)) and collagen fibers (E(3)). Our study was performed on normal and Angiotensin II (AngII)-treated mouse abdominal aortas using the aortic pressure after catheterization and the local aortic wall diameters change from a cross-correlation technique on the radio frequency (RF) ultrasound signal at 30 MHz and frame rate of 8 kHz. Using our technique, the transition strain and three Youngs moduli in both normal and pathological aortas were mapped in 2D. The slope change of the circumferential stress-strain curve was first observed in vivo under physiologic conditions. The transition strain was found at a lower strain level in the AngII-treated case, i.e., 0.029+/-0.006 for the normal and 0.012+/-0.004 for the AngII-treated aortas. E(1), E(2) and E(3) were equal to 69.7+/-18.6, 214.5+/-65.8 and 144.8+/-55.2 kPa for the normal aortas, and 222.1+/-114.8, 775.0+/-586.4 and 552.9+/-519.1 kPa for the AngII-treated aortas, respectively. This is because of the alteration of structures and content of the wall constituents, the degradation of elastic lamella and collagen formation due to AngII treatment. While such values illustrate the alteration of structure and content of the wall constituents related to AngII treatment, limitations regarding physical assumptions (isotropic, linear elastic) should be kept in mind. The transition strain, however, was shown to be a pressure independent parameter that can be clinically relevant and noninvasively measured using ultrasound-based motion estimation techniques. In conclusion, our novel methodology can assess the stress-strain relationship of the aortic wall locally in vivo and quantify important parameters for the detection and characterization of vascular disease.

Towards child versus adult brain mechanical properties.

The characterization of brain tissue mechanical properties is of crucial importance in the development of realistic numerical models of the human head. While the mechanical behavior of the adult brain has been extensively investigated in several studies, there is a considerable paucity of data concerning the influence of age on mechanical properties of the brain. Therefore, the implementation of child and infant head models often involves restrictive assumptions like properties scaling from adult or animal data. The present study presents a step towards the investigation of the effects of age on viscoelastic properties of human brain tissue from a first set of dynamic oscillatory shear experiments. Tests were also performed on three different locations of brain (corona radiata, thalamus and brainstem) in order to investigate regional differences. Despite the limited number of child brain samples a significant increase in both storage and loss moduli occurring between the age of 5 months and the age of 22 months was found, confirmed by statistical Students t-tests (p=0.104,0.038 and 0.054 for respectively corona radiata, thalamus and brain stem samples locations respectively). The adult brain appears to be 3-4 times stiffer than the young child one. Moreover, the brainstem was found to be approximately 2-3 times stiffer than both gray and white matter from corona radiata and thalamus. As a tentative conclusion, this study provides the first rheological data on the human brain at different ages and brain regions. This data could be implemented in numerical models of the human head, especially in models concerning pediatric population.

Physiologic Cardiovascular Strain and Intrinsic Wave Imaging

Cardiovascular disease remains the primary killer worldwide. The heart, essentially an electrically driven mechanical pump, alters its mechanical and electrical properties to compensate for loss of normal mechanical and electrical function. The same adjustment also is performed in the vessels, which constantly adapt their properties to accommodate mechanical and geometrical changes related to aging or disease. Real-time, quantitative assessment of cardiac contractility, conduction, and vascular function before the specialist can visually detect it could be feasible. This new physiologic data could open up interactive therapy regimens that are currently not considered. The eventual goal of this technology is to provide a specific method for estimating the position and severity of contraction defects in cardiac infarcts or angina. This would improve care and outcomes as well as detect stiffness changes and overcome the current global measurement limitations in the progression of vascular disease, at little more cost or risk than that of a clinical ultrasound.

Harmonic Motion Imaging for Tumor Imaging and Treatment Monitoring

Palpation is an established screening procedure for the detection of several superficial cancers including breast, thyroid, prostate, and liver tumors through both self and clinical examinations. This is because solid masses typically have distinct stiffnesses compared to the surrounding normal tissue. In this paper, the application of Harmonic Motion Imaging (HMI) for tumor detection based on its stiffness as well as its relevance in thermal treatment is reviewed. HMI uses a focused ultrasound (FUS) beam to generate an oscillatory acoustic radiation force for an internal, non-contact palpation to internally estimate relative tissue hardness. HMI studies have dealt with the measurement of the tissue dynamic motion in response to an oscillatory acoustic force at the same frequency, and have been shown feasible in simulations, phantoms, ex vivo human and bovine tissues as well as animals in vivo. Using an FUS beam, HMI can also be used in an ideal integration setting with thermal ablation using high-intensity focused ultrasound (HIFU), which also leads to an alteration in the tumor stiffness. In this paper, a short review of HMI is provided that encompasses the findings in all the aforementioned areas. The findings presented herein demonstrate that the HMI displacement can accurately depict the underlying tissue stiffness, and the HMI image of the relative stiffness could accurately detect and characterize the tumor or thermal lesion based on its distinct properties. HMI may thus constitute a non-ionizing, cost-efficient and reliable complementary method for noninvasive tumor detection, localization, diagnosis and treatment monitoring.

Non-invasive measurement of local pulse pressure by pulse wave-based ultrasound manometry (PWUM)

Central blood pressure (CBP) has been established as a relevant indicator of cardiovascular disease. Despite its significance, CBP remains particularly challenging to measure in standard clinical practice. The objective of this study is to introduce pulse wave-based ultrasound manometry (PWUM) as a simple-to-use, non-invasive ultrasound-based method for quantitative measurement of the central pulse pressure. Arterial wall displacements are estimated using radiofrequency ultrasound signals acquired at high frame rates and the pulse pressure waveform is estimated using both the distension waveform and the local pulse wave velocity. The method was tested on the abdominal aorta of 11 healthy subjects (age 35.7 ± 16 y.o.). PWUM pulse pressure measurements were compared to those obtained by radial applanation tonometry using a commercial system. The average intra-subject variability of the pulse pressure amplitude was found to be equal to 4.2 mmHg, demonstrating good reproducibility of the method. Excellent correlation was found between the waveforms obtained by PWUM and those obtained by tonometry in all subjects (0.94 < r < 0.98). A significant bias of 4.7 mmHg was found between PWUM and tonometry. PWUM is a highly translational method that can be easily integrated in clinical ultrasound imaging systems. It provides an estimate of the pulse pressure waveform at the imaged location, and may offer therefore the possibility to estimate the pulse pressure at different arterial sites. Future developments include the validation of the method against invasive estimates on patients, as well as its application to other large arteries.

Comparison of four different techniques to evaluate the elastic properties of phantom in elastography: is there a gold standard?

Elastographic techniques used in addition to imaging techniques (ultrasound, resonance magnetic or optical) provide new clinical information on the pathological state of soft tissues. However, system-dependent variation in elastographic measurements may limit the clinical utility of these measurements by introducing uncertainty into the measurement. This work is aimed at showing differences in the evaluation of the elastic properties of phantoms performed by four different techniques: quasi-static compression, dynamic mechanical analysis, vibration-controlled transient elastography and hyper-frequency viscoelastic spectroscopy. Four Zerdine® gel materials were tested and formulated to yield a Youngs modulus over the range of normal and cirrhotic liver stiffnesses. The Youngs modulus and the shear wave speed obtained with each technique were compared. Results suggest a bias in elastic property measurement which varies with systems and highlight the difficulty in finding a reference method to determine and assess the elastic properties of tissue-mimicking materials. Additional studies are needed to determine the source of this variation, and control for them so that accurate, reproducible reference standards can be made for the absolute measurement of soft tissue elasticity.

Dynamic viscoelastic shear properties of soft matter by magnetic resonance elastography using a low-field dedicated system

A magnetic resonance elastography (MRE) based method that consists in measuring dynamic viscoelastic parameters of soft matter by analysis of propagating shear waves at different frequencies is proposed. Dynamic shear tests were performed on soft gels with a dedicated magnetic resonance imaging system at low field (0.1T) and were compared with results obtained with a mechanical rotational rheometer. Storage and loss moduli were plotted against frequency with both methods and good agreement was found between their results in the shared frequency range. Therefore, it is shown that the described method could be a reliable and accessible tool for three-dimensional dynamic mechanical analysis on soft matter able to overcome dynamic range, sample dimensions and directional limitations of mechanical rheometers. Advantages and limits of the method are discussed.