Kidney cortex shear wave motion simulations based on segmented biopsy histology.

BACKGROUND AND OBJECTIVE: Biopsy stands as the gold standard for kidney transplant assessment, yet its invasive nature restricts frequent use. Shear wave elastography (SWE) is emerging as a promising alternative for kidney transplant monitoring. A parametric study involving 12 biopsy data sets categorized by standard biopsy scores (3 with normal histology, 3 with interstitial inflammation (i), 3 with interstitial fibrosis (ci), and 3 with tubular atrophy (ct)), was conducted to evaluate the interdependence between microstructural variations triggered by chronic allograft rejection and corresponding alterations in SWE measurements. METHODS: Heterogeneous shear wave motion simulations from segmented kidney cortex sections were performed employing the staggered-grid finite difference (SGFD) method. The SGFD method allows the mechanical properties to be defined on a pixel-basis for shear wave motion simulation. Segmentation techniques enabled the isolation of four histological constituents: glomeruli, tubules, interstitium, and fluid. Baseline ex vivo Kelvin-Voigt mechanical properties for each constituent were drawn from established literature. The parametric evaluation was then performed by altering the baseline values individually. Shear wave velocity dispersion curves were measured with the generalized Stockwell transform in conjunction with slant frequency-wavenumber analysis (GST-SFK) algorithm. By fitting the curve within the 100-400 Hz range to the Kelvin-Voigt model, the rheological parameters, shear elasticity (µ1) and viscosity (µ2), were estimated. A time-to-peak algorithm was used to estimate the group velocity. The resultant in silico models emulated the heterogeneity of kidney cortex within the shear wave speed (SWS) reconstructions. RESULTS: The presence of inflammation showed considerable spatial composition disparities compared to normal cases, featuring a 23 % increase in interstitial area and a 19 % increase in glomerular area. Concomitantly, there was a reduction of 12 % and 47 % in tubular and fluid areas, respectively. Consequently, mechanical changes induced by inflammation predominate in terms of rheological differentiation, evidenced by increased elasticity and viscosity. Mild tubular atrophy showed significant elevation in group velocity and µ1. Conversely, mild and moderate fibrosis exhibited negligible alterations across all parameters, compatible with relatively limited morphological impact. CONCLUSIONS: This proposed model holds promise in enabling patient-specific simulations of the kidney cortex, thus facilitating exploration into how pathologies altering cortical morphology correlates to modifications in SWE-derived rheological measurements. We demonstrated that inflammation caused substantial changes in measured mechanical properties.

Lung ultrasound in young children with neurological impairment: A proposed integrative clinical tool for deaeration-detection related to feeding.

Infants and children with neurological impairment, such as cerebral palsy (CP), often experience abnormal ingestion functions, including oropharyngeal dysphagia and gastroesophageal reflux disease, which led to aspiration-related respiratory complications, morbidity, hospitalization, or death. There is a lack of evidence-based, repeatable, infant-friendly instrumental procedures to assess aspiration-risk in infants with CP or other neurological disorders, with also a lack of clinical assessment measures to support the use of more invasive diagnostic techniques. To this purpose, in the current study we explore the feasibility of lung ultrasound (LUS), to assess lung deaeration possibly related to aspiration during meal, in a cohort of 35 subjects affected by CP or other encephalopathies, and 10 controls in the same age-range. We coupled LUS procedure with meal caregiver administration for each child. Our results support the feasibility of this innovative approach in the clinical setting. Exploratory findings revealed a number of lung abnormalities likely related to abnormal ingestion function in subjects. Subgroup analyses revealed possible differences in LUS abnormalities between CP and other encephalopathies, possibly related to different mechanism of disease or dysfunction. Also, some evidences arose about the possible relationship between such LUS abnormalities and feeding and swallowing abilities in CP or other encephalopathies. LUS showed preliminarily feasibility and effectiveness in detecting meal-related LUS abnormalities in a dynamic manner in the clinical setting. This approach demonstrated usefulness as a potential tool for improving assessment and management in complex care of infants and young children with severe neurological disorders.

A Novel Small Molecule Neurotrophin-3 Analogue Promotes Inner Ear Neurite Outgrowth and Synaptogenesis In vitro.

Sensorineural hearing loss is irreversible and is associated with the loss of spiral ganglion neurons (SGNs) and sensory hair cells within the inner ear. Improving spiral ganglion neuron (SGN) survival, neurite outgrowth, and synaptogenesis could lead to significant gains for hearing-impaired patients. There has therefore been intense interest in the use of neurotrophic factors in the inner ear to promote both survival of SGNs and re-wiring of sensory hair cells by surviving SGNs. Neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) represent the primary neurotrophins in the inner ear during development and throughout adulthood, and have demonstrated potential for SGN survival and neurite outgrowth. We have pioneered a hybrid molecule approach to maximize SGN stimulation in vivo, in which small molecule analogues of neurotrophins are linked to bisphosphonates, which in turn bind to cochlear bone. We have previously shown that a small molecule BDNF analogue coupled to risedronate binds to bone matrix and promotes SGN neurite outgrowth and synaptogenesis in vitro. Because NT-3 has been shown in a variety of contexts to have a greater regenerative capacity in the cochlea than BDNF, we sought to develop a similar approach for NT-3. 1Aa is a small molecule analogue of NT-3 that has been shown to activate cells through TrkC, the NT-3 receptor, although its activity on SGNs has not previously been described. Herein we describe the design and synthesis of 1Aa and a covalent conjugate of 1Aa with risedronate, Ris-1Aa. We demonstrate that both 1Aa and Ris-1Aa stimulate neurite outgrowth in SGN cultures at a significantly higher level compared to controls. Ris-1Aa maintained its neurotrophic activity when bound to hydroxyapatite, the primary mineral component of bone. Both 1Aa and Ris-1Aa promote significant synaptic regeneration in cochlear explant cultures, and both 1Aa and Ris-1Aa appear to act at least partly through TrkC. Our results provide the first evidence that a small molecule analogue of NT-3 can stimulate SGNs and promote regeneration of synapses between SGNs and inner hair cells. Our findings support the promise of hydroxyapatite-targeting bisphosphonate conjugation as a novel strategy to deliver neurotrophic agents to SGNs encased within cochlear bone.

Evaluation of meso-substituted cationic corroles as potential antibacterial agents.

Cationic derivatives of 5,10,15-tris[4-(pyridin-4-ylsulphanyl)-2,3,5,6-tetrafluorophenyl]-corrolategallium(III)pyridine and 5,10,15-tris[4-(pyridin-2-ylsulfanyl)-2,3,5,6-tetrafluorophenyl]-correlategallium(III)pyridine were synthesized and their photosensitizing properties against the naturally bioluminescent Gram-negative bacterium Allivibrio fischeri were evaluated. The cationic corrole derivatives exhibited antibacterial activity at micromolar concentrations against this Gram-negative bacterium strain.

Remarkably Stereospecific Utilization of ATP α,ß-Halomethylene Analogues by Protein Kinases.

ATP analogues containing a CXY group in place of the α,ß-bridging oxygen atom are powerful chemical probes for studying ATP-dependent enzymes. A limitation of such probes has been that conventional synthetic methods generate a mixture of diastereomers when the bridging carbon substitution is nonequivalent (X ≠ Y). We report here a novel method based on derivatization of a bisphosphonate precursor with a d-phenylglycine chiral auxiliary that enables preparation of the individual diastereomers of α,ß-CHF-ATP and α,ß-CHCl-ATP, which differ only in the configuration at the CHX carbon. When tested on a dozen divergent protein kinases, these individual diastereomers exhibit remarkable diastereospecificity (up to over 1000-fold) in utilization by the enzymes. This high selectivity can be exploited in an enzymatic approach to obtain the otherwise inaccessible diastereomers of α,ß-CHBr-ATP. The crystal structure of a tyrosine kinase Src bound to α,ß-CHX-ADP establishes the absolute configuration of the CHX carbon and helps clarify the origin of the remarkable diastereospecificity observed. We further synthesized the individual diastereomers of α,ß-CHF-γ-thiol-ATP and demonstrated their utility in labeling a wide spectrum of kinase substrates. The novel ATP substrate analogues afforded by these two complementary strategies should have broad application in the study of the structure and function of ATP-dependent enzymes.

Automated Compression Device for Viscoelasticity Imaging.

Noninvasive measurement of tissue viscoelastic properties is gaining more attention for screening and diagnostic purposes. Recently, measuring dynamic response of tissue under a constant force has been studied for estimation of tissue viscoelastic properties in terms of retardation times. The essential part of such a test is an instrument that is capable of creating a controlled axial force and is suitable for clinical applications. Such a device should be lightweight, portable, and easy to use for patient studies to capture tissue dynamics under external stress. In this paper, we present the design of an automated compression device for studying the creep response of materials with tissue-like behaviors. The device can be used to apply a ramp-and-hold force excitation for a predetermined duration of time and it houses an ultrasound probe for monitoring the creep response of the underlying tissue. To validate the performance of the device, several creep tests were performed on tissue-mimicking phantoms, and the results were compared against those from a commercial mechanical testing instrument. Using a second-order Kelvin-Voigt model and surface measurement of the forces and displacements, retardation times T1 and T2 were estimated from each test. These tests showed strong agreement between our automated compression device and the commercial mechanical testing system, with an average relative error of 2.9% and 12.4%, for T1 and T2, respectively. Also, we present the application of compression device to measure local retardation times for four different phantoms with different size and stiffness.

Area-based study identifies risk factors associated with missed antenatal corticosteroid prophylaxis in women delivering preterm infants.

AIM: All women delivering a preterm infant should receive antenatal corticosteroid prophylaxis, but many miss this opportunity. We determined the risk factors associated with missed prophylaxis in a geographically defined area of Italy. METHODS: We prospectively studied all mothers who delivered babies between 24 and 31 completed weeks of gestation, from 2009 to 2013, in all maternity units in Tuscany. RESULTS: Of 1232 mothers, 186 (15.1%) did not receive prophylaxis. The risk was higher in migrant mothers, with an adjusted risk ratio (RR) of 1.28 and 95% confidence interval (95% CI) of 1.04-1.56, and in mothers hospitalised for less than 24 hours (RR 4.09, 95% CI: 2.90-5.78). Preterm prelabour rupture of membranes (RR 0.63, 95% CI: 0.41-0.96) and maternal antepartum transfer (RR 0.24, 95% CI: 0.18-0.32) were protective. Hospital level at birth and gestational age did not influence the prophylaxis rate. The population-attributable fractions were 50.4% for late hospital admissions and 10.2% for migrant status. CONCLUSION: In a highly organised network of hospitals, neither level of care nor gestational age influenced prophylaxis. Timely arrival of women in hospital, better recognition of the imminence of delivery and tighter steroids administration guidelines are the most relevant targets to further increase prophylaxis.

Ultrasonic method to characterize shear wave propagation in micellar fluids.

Viscoelastic micellar fluid characteristics have been measured with mechanically generated shear waves and showed good agreement to shear oscillatory methods. In this paper, shear waves in wormlike micellar fluids using ultrasound were successfully generated and detected. Micellar fluids of different concentrations (100, 200, 300, and 400 mM) were studied with ultrasound-based and conventional rheology methods. The measured micellar fluid complex modulus from oscillatory shear tests between 0.001 and 15.91 Hz was characterized with an extended Maxwell fluid model. The elastic and viscous parameters found using rheological testing were used to estimate shear wave phase velocity over a frequency range from 100 to 500 Hz, and compared to shear wave velocity measured with ultrasound-based methods with a mean absolute error 0.02 m/s. The shear wave frequency content was studied and an increase in shear wave center frequency was found as a function of micellar fluid concentration. Moreover, the bias found in the shear wave group velocity with respect to rheological measurement is attributed to the micellar fluid viscous component. Finally, the shear wave phase velocity evaluated at the center frequency agreed well with the rheological measurements.

Shear Wave Elastography Quantifies Stiffness in Ex Vivo Porcine Artery with Stiffened Arterial Region.

Five small porcine aortas were used as a human carotid artery model, and their stiffness was estimated using shear wave elastography (SWE) in the arterial wall and a stiffened artery region mimicking a stiff plaque. To optimize the SWE settings, shear wave bandwidth was measured with respect to acoustic radiation force push length and number of compounded angles used for motion detection with plane wave imaging. The mean arterial wall and simulated plaque shear moduli varied from 41 ± 5 to 97 ± 10 kPa and from 86 ± 13 to 174 ± 35 kPa, respectively, over the pressure range 20-120 mmHg. The results revealed that a minimum bandwidth of approximately 1500 Hz is necessary for consistent shear modulus estimates, and a high pulse repetition frequency using no image compounding is more important than a lower pulse repetition frequency with better image quality when estimating arterial wall and plaque stiffness using SWE.

Improvement of Shear Wave Motion Detection Using Harmonic Imaging in Healthy Human Liver.

Quantification of liver elasticity is a major application of shear wave elasticity imaging (SWEI) to non-invasive assessment of liver fibrosis stages. SWEI measurements can be highly affected by ultrasound image quality. Ultrasound harmonic imaging has exhibited a significant improvement in ultrasound image quality as well as for SWEI measurements. This was previously illustrated in cardiac SWEI. The purpose of this study was to evaluate liver shear wave particle displacement detection and shear wave velocity (SWV) measurements with fundamental and filter-based harmonic ultrasound imaging. In a cohort of 17 patients with no history of liver disease, a 2.9-fold increase in maximum shear wave displacement, a 0.11 m/s decrease in the overall interquartile range and median SWV and a 17.6% increase in the success rate of SWV measurements were obtained when filter-based harmonic imaging was used instead of fundamental imaging.

Fetal programming and systemic sclerosis.

OBJECTIVE: This study investigated whether birthweight is linked to an increased risk of the development of systemic sclerosis. STUDY DESIGN: This was a multicenter case-control study with perinatal data that were obtained from 332 cases with systemic sclerosis and 243 control subjects. Birthweight was treated as a dichotomous variable (<2500 g vs ≥2500 g); low birthweight was defined as a weight <2500 g; small for gestational age was defined as birthweight <10th percentile for gestational age adjusted for sex. The relationship between systemic sclerosis and both low birthweight and small for gestational age was expressed with the crude (univariate analysis) and adjusted (multivariate analysis) odds ratio (OR). RESULTS: Significantly increased ORs were observed in the univariate analysis for low birthweight (OR, 2.59; 95% confidence interval [CI], 1.39-5.05) and small for gestational age (OR, 2.60; 95% CI, 1.34-5.32) subjects. Similarly increased risks were confirmed for both conditions in the multivariate analysis (OR, 3.93; 95% CI, 1.92-8.07; and OR, 2.58; 95% CI, 1.28-5.19), respectively. CONCLUSION: Low birthweight and small for gestational age at birth are risk factors for the adult onset of systemic sclerosis.

Characterization of transverse isotropy in compressed tissue-mimicking phantoms.

Tissues such as skeletal muscle and kidneys have well-defined structure that affects the measurements of mechanical properties. As an approach to characterize the material properties of these tissues, different groups have assumed that they are transversely isotropic (TI) and measure the shear wave velocity as it varies with angle with respect to the structural architecture of the organ. To refine measurements in these organs, it is desirable to have tissue-mimicking phantoms that exhibit similar anisotropic characteristics. Some approaches involve embedding fibers into a material matrix. However, if a homogeneous solid is under compression due to a static stress, an acoustoelastic effect can manifest that makes the measured wave velocities change with the compression stress. We propose to exploit this characteristic to demonstrate that stressed tissue mimicking phantoms can be characterized as a TI material. We tested six phantoms made with different concentrations of gelatin and agar. Stress was applied by the weight of a water container centered on top of a plate on top of the phantom. A linear array transducer and a V-1 Verasonics system were used to induce and measure shear waves in the phantoms. The shear wave motion was measured using a compound plane wave imaging technique. Autocorrelation was applied to the received in-phase/quadrature data. The shear wave velocity, c, was estimated using a Radon transform method. The transducer was mounted on a rotating stage so measurements were made every 10° over a range of 0° to 360°, where the stress is applied along 0° to 180° direction. The shear moduli were estimated. A TI model was fit to the data and the fractional anisotropy was evaluated. This approach can be used to explore many configurations of transverse isotropy with the same phantom, simply by applying stress to the tissue-mimicking phantom.

Shear wave vibrometry evaluation in transverse isotropic tissue mimicking phantoms and skeletal muscle.

Ultrasound radiation force-based methods can quantitatively evaluate tissue viscoelastic material properties. One of the limitations of the current methods is neglecting the inherent anisotropy nature of certain tissues. To explore the phenomenon of anisotropy in a laboratory setting, we created two phantom designs incorporating fibrous and fishing line material with preferential orientations. Four phantoms were made in a cube-shaped mold; both designs were arranged in multiple layers and embedded in porcine gelatin using two different concentrations (8%, 14%). An excised sample of pork tenderloin was also studied. Measurements were made in the phantoms and the pork muscle at different angles by rotating the phantom with respect to the transducer, where 0° and 180° were defined along the fibers, and 90° and 270° across the fibers. Shear waves were generated and measured by a Verasonics ultrasound system equipped with a linear array transducer. For the fibrous phantom, the mean and standard deviations of the shear wave speeds along (0°) and across the fibers (90°) with 8% gelatin were 3.60  ±  0.03 and 3.18  ±  0.12 m s(-1) and with 14% gelatin were 4.10  ±  0.11 and 3.90  ±  0.02 m s(-1). For the fishing line material phantom, the mean and standard deviations of the shear wave speeds along (0°) and across the fibers (90°) with 8% gelatin were 2.86  ±  0.20 and 2.44  ±  0.24 m s(-1) and with 14% gelatin were 3.40  ±  0.09 and 2.84  ±  0.14 m s(-1). For the pork muscle, the mean and standard deviations of the shear wave speeds along the fibers (0°) at two different locations were 3.83  ±  0.16 and 3.86  ±  0.12 m s(-1) and across the fibers (90°) were 2.73  ±  0.18 and 2.70  ±  0.16 m s(-1), respectively. The fibrous and fishing line gelatin-based phantoms exhibited anisotropy that resembles that observed in the pork muscle.

THE EFFECTS OF TIME AND MOISTURE ON ELASTICITY IMAGING PHANTOM PHYSICAL AND MECHANICAL PROPERTIES: A PILOT STUDY / EFECTOS DE TIEMPO Y HUMEDAD EN LAS PROPIEDADES MECÁNICAS Y FÍSICAS DE UN FANTOMA DE IMÁGENES DE ELASTICIDAD: ESTUDIO PILOTO / EFEITOS DO TEMPO E UMIDADE NAS PROPRIEDADES MECÂNICAS E FÍSICAS DE UMA FANTOMA DE IMAGENES DE ELASTICIDADE: UM ESTUDO PILOTO

Elasticity imaging phantoms are used to mimic human tissue as a means of testing and validating non-invasive techniques for measuring mechanical properties of human tissues. Limited studies of phantom stability have shown that phantom stiffness change over time when exposed to air. The goals of this study were to investigate how the physical and mechanical properties of elasticity imaging phantoms change with time and moisture state. Two moisture states were tested; a dry state where the phantom was exposed to open air and a wet state where the phantom was submerged in water for 480 minutes. Polyvinyl alcohol (PVA) phantoms (cylindrical shape) were used. The properties of the phantom were found using flat indentation tests and a test battery that included a precondition test, a 0.05 mm/s triangle test, a 5 mm/s triangle test and a ten-second ramp-and-hold relaxation test. This battery was done at multiple time points: 0, 15, 30, 45, 60, 120, 180, 240, 360 and 480 minutes. At each time point, the modulus, stiffness and relaxation at 10 seconds were calculated. In addition, the mass and volume of the phantoms were measured at each time point. The physical and mechanical properties of the phantoms were found to be statistically dependent on moisture state and time (p<0.05). The stiffness and moduli of the dry samples increased with time while the mass and volume decreased with time. Additionally, a strong correlation was found between the change in mass and change in modulus/stiffness for the dry phantoms. For the wet samples, the modulus and stiffness decreased with time while the mass and volume increase with time. The properties of the phantom begin to change within 15 minutes, the percentage change of the mechanical and physical properties remained, on average, under 10% during the first hour and increased up to 50% during 8 hours. These property changes of phantoms should be considered when using phantoms to test or validate non-invasive techniques.

Fantomas de imágenes de elasticidad se utilizan para imitar el tejido humano como un medio de ensayo y validación de técnicas no invasivas para medir las propiedades mecánicas de los tejidos humanos. La estabilidad de los fantomas se ha estudiado anteriormente y se ha encontrado que su elasticidad cambia con respecto al tiempo cuando están expuestas al aire. Los objetivos de este estudio fueron investigar cómo las propiedades físicas y mecánicas de los fantomas de imágenes de elasticidad cambian con el tiempo y el estado de humedad. Dos estados de humedad fueron examinados; un estado seco, donde el fantoma se expone al aire libre y un estado húmedo, donde el fantoma se sumergió en el agua. Se utiliza alcohol polivinílico (PVA) para crear los fantomas (forma cilíndrica). Las propiedades del fantoma se encontraron utilizando pruebas de indentación planas y una batería de pruebas que incluyeron una prueba de condición, a 0.05 mm/s prueba triangular, una prueba triangular 5 mm/s, y ensayo de relajación de rampa-retención de diez segundos. Esta batería se realiza en múltiples puntos de tiempo: 0, 15, 30, 45, 60, 120, 180, 240, 360 y 480 minutos. En cada punto de tiempo, se calcularon el módulo, la rigidez y la relajación en 10 segundos. Además, la masa y el volumen de los fantomas se midieron en cada punto de tiempo. Se encontró que las propiedades físicas y mecánicas de los fantomas son dependientes estadísticamente del estado de humedad y el tiempo (p <0,05). La rigidez y módulos de las muestras secas se incrementaron con el tiempo mientras que la masa y el volumen disminuyó con el tiempo. Adicionalmente, una fuerte correlación fue encontrada entre los cambios de masa respecto al cambio de módulo para las muestras secas. Para las muestras húmedas, el módulo y la rigidez disminuyeron con el tiempo, mientras que aumentó la masa y el volumen con el tiempo. Las propiedades de los fantomas comienzan a cambiar dentro de los 15 minutos, pero el porcentaje de cambio de las propiedades mecánicas y físicas se mantuvo, en promedio, menos del 10% durante la primera hora y aumentó hasta el 50% en las 8 horas. Estos cambios en las propiedades de los fantomas deben ser considerados cuando se utilizan para probar o validar las técnicas no invasivas.

Fantomas de imagenes de elasticidade foram utilizadas para imitar o tecido humano como um meio de testes e validação de técnicas não invasivas para medir as propriedades mecânicas dos tecidos humanos. A estabilidade dos fantomas foi estudada previamente e descobriram que a elasticidade se altera com o tempo quando é exposta ao ar. Os objetivos deste estudo foram investigar como as propriedades físicas e mecânicas dos fantomas de imagem de elasticidade mudam ao longo do tempo e o estado de umidade. Dois estados de umidade foram examinados; um estado de seca, em que o fantoma está exposta ao ar livre e um estado úmido, onde o fantoma foi imersa em água. é usado Álcool polivinílico (PVA) para criar o fantoma (forma cilíndrica). As propriedades do fantoma foram encontrados por meio de testes de indentação planas e uma bateria de testes, incluindo um teste de condição, a 0,05 mm / s teste triangular, um teste triangular de 5 mm / s, e teste de relaxamento rampa de Retenção de dez segundos. Esta bateria é realizada em vários pontos de tempo: 0, 15, 30, 45, 60, 120, 180, 240, 360 e 480 minutos. Em cada ponto de tempo, foram calculados o módulo de elasticidade, rigidez e relaxamento em 10 segundos,. Além disso, a massa e volume dos fantomas foram medidos em cada ponto de tempo. Verificou-se que as propriedades físicas e mecânicas dos fantomas são dependentes estatisticamente do estado de umidade e tempo (p <0,05). A rigidez e módulos das amostras secas aumentou com o tempo, enquanto a massa e volume diminuiu com o tempo. Além disso, foi encontrada uma forte correlação entre as alterações na massa com respeito à alteração do módulo para amostras secas. Para as amostras molhadas, o módulo de elasticidade e rigidez diminuiu ao longo do tempo, enquanto o aumento da massa e do volume ao longo do tempo. As propriedades dos fantomas começam a mudar dentro dos 15 minutos, mas a percentagem de variação das propriedades mecânicas e físicas permaneceram, em média, menos de 10% durante a primeira hora, e aumentou até 50% em 8 horas. Essas alterações nas propriedades dos fantomas deve ser considerado quando é usado para testar ou validar as técnicas não invasivas.

IN VIVO SWINE KIDNEY VISCOELASTICITY DURING ACUTE GRADUAL DECREASE IN RENAL BLOOD FLOW: PILOT STUDY / VISCOELASTICIDAD RENAL DURANTE LA DISMINUCIÓN GRADUAL DE FLUJO SANGUÍNEO EN UN MODELO PORCINO IN VIVO: ESTUDIO PILOTO

Elasticity imaging methods have been used to study kidney mechanical properties and have demonstrated that the kidney elastic modulus increases with disease state. However, studies in swine suggest that kidney elastic modulus is also affected by hemodynamic variables. A newly emerging method called Shearwave Dispersion Ultrasound Vibrometry (SDUV) offers a tool to determine renal elasticity and viscosity in vivo. The purpose of this study was directed toward evaluating the feasibility of SDUV for in vivo measurements of healthy swine kidney during acute gradual decease of renal blood flow. In this study in vivo SDUV measurements were made on a group of 5 normal swine kidneys at baseline renal blood flow (RBF) and 25, 50, 75 and 100% decrease in RBF. The shear elastic modulus at full baseline was 7.04 ± 0.92 kPa and 3.48 ± 0.20 kPa at 100% decrease in RBF. The viscosity did not change between baseline (2.23 ± 0.33 Pa•s) and 100% decrease in RBF (2.03 ± 0.32 Pa•s). The data from this study indicates that other variables such as local blood flow, pressure and volume as well as method accuracy need to be measured to illustrate the relationship between shear elasticity and viscosity associated with acute kidney processes.

Métodos de imágenes de elasticidad se han utilizado para estudiar las propiedades mecánicas renales y han demostrado que el módulo elástico de los riñones del aumenta con el estado de enfermedades renales. Sin embargo, estudios en cerdos sugieren que el riñón módulo elástico también se ve afectada por las variables hemodinámicas. Un método emergente llamado Shearwave Dispersion Ultrasound Vibrometry (SDUV) ofrece una herramienta para determinar la elasticidad y la viscosidad renal. El propósito de este estudio se dirige a la evaluación de la viabilidad de SDUV para mediciones las propiedades viscoelasticas del riñón saludable durante variación aguda del flujo sanguíneo renal. En este estudio el método SDUV se realizó en un grupo de 5 riñones porcinos normales al inicio del flujo sanguíneo renal (RBF) basal y 25, 50, 75 y 100% de disminución en el RBF. El módulo elástico basal fue de 7,04 ± 0,92 kPa y 3,48 ± 0,20 kPa a 100% de disminución del RBF. La viscosidad no cambió entre el momento basal (2,23 ± 0,33 Pa • s) y el 100% de disminución del RBF (2,03 ± 0,32 Pa • s). Los datos de este estudio indican que variables tales como el flujo local de sangre, la presión y el volumen así como el método exactitud deben ser medidos para ilustrar la relación entre la elasticidad y la viscosidad asociada con los procesos renales agudos.

In vivo swine kidney viscoelasticity during acute gradual decrease in renal blood flow: pilot study.

Elasticity imaging methods have been used to study kidney mechanical properties and have demonstrated that the kidney elastic modulus increases with disease state. However, studies in swine suggests that kidney elastic modulus is also affected by hemodynamic variables. A newly emerging method called Shearwave Dispersion Ultrasound Vibrometry (SDUV) offers a tool to determine renal elasticity and viscosity in vivo. The purpose of this study is directed toward evaluating the feasibility of SDUV for in vivo measurements of healthy swine kidney during acute gradual decease of renal blood flow. In this study in vivo SDUV measurements were made on a group of 5 normal swine kidneys at baseline renal blood flow (RBF) and 25, 50, 75 and 100% decrease in RBF. The shear elastic modulus at full baseline was 7.04 ± 0.92 kPa and 3.48 ± 0.20 kPa at 100% decrease in RBF. The viscosity did not change between baseline (2.23 ± 0.33 Pa·s) and 100% decrease in RBF (2.03 ± 0.32 Pa·s). The data from this study indicates that other variables such as local blood flow, pressure and volume as well as method accuracy need to be measured to illustrate the relationship between shear elasticity and viscosity associated with acute kidney processes.

Loss tangent and complex modulus estimated by acoustic radiation force creep and shear wave dispersion.

Elasticity imaging methods have been used to study tissue mechanical properties and have demonstrated that tissue elasticity changes with disease state. In current shear wave elasticity imaging methods typically only shear wave speed is measured and rheological models, e.g. Kelvin-Voigt, Maxwell and Standard Linear Solid, are used to solve for tissue mechanical properties such as the shear viscoelastic complex modulus. This paper presents a method to quantify viscoelastic material properties in a model-independent way by estimating the complex shear elastic modulus over a wide frequency range using time-dependent creep response induced by acoustic radiation force. This radiation force induced creep method uses a conversion formula that is the analytic solution of a constitutive equation. The proposed method in combination with shearwave dispersion ultrasound vibrometry is used to measure the complex modulus so that knowledge of the applied radiation force magnitude is not necessary. The conversion formula is shown to be sensitive to sampling frequency and the first reliable measure in time according to numerical simulations using the Kelvin-Voigt model creep strain and compliance. Representative model-free shear complex moduli from homogeneous tissue mimicking phantoms and one excised swine kidney were obtained. This work proposes a novel model-free ultrasound-based elasticity method that does not require a rheological model with associated fitting requirements.

Shear elastic modulus estimation from indentation and SDUV on gelatin phantoms.

Tissue mechanical properties such as elasticity are linked to tissue pathology state. Several groups have proposed shear wave propagation speed to quantify tissue mechanical properties. It is well known that biological tissues are viscoelastic materials; therefore, velocity dispersion resulting from material viscoelasticity is expected. A method called shearwave dispersion ultrasound vibrometry (SDUV) can be used to quantify tissue viscoelasticity by measuring dispersion of shear wave propagation speed. However, there is not a gold standard method for validation. In this study, we present an independent validation method of shear elastic modulus estimation by SDUV in three gelatin phantoms of differing stiffness. In addition, the indentation measurements are compared to estimates of elasticity derived from shear wave group velocities. The shear elastic moduli from indentation were 1.16, 3.40, and 5.6 kPa for a 7%, 10%, and 15% gelatin phantom, respectively. SDUV measurements were 1.61, 3.57, and 5.37 kPa for the gelatin phantoms, respectively. Shear elastic moduli derived from shear wave group velocities were 1.78, 5.2, and 7.18 kPa for the gelatin phantoms, respectively. The shear elastic modulus estimated from the SDUV, matched the elastic modulus measured by indentation. On the other hand, shear elastic modulus estimated by group velocity did not agree with indentation test estimations. These results suggest that shear elastic modulus estimation by group velocity will be bias when the medium being investigated is dispersive. Therefore, a rheological model should be used in order to estimate mechanical properties of viscoelastic materials.

Shearwave dispersion ultrasound vibrometry (SDUV) on swine kidney.

Shearwave dispersion ultrasound vibrometry (SDUV) is used to quantify both tissue shear elasticity and shear viscosity by evaluating dispersion of shear wave propagation speed over a certain bandwidth (50 to 500 Hz). The motivation for developing elasticity imaging techniques is the desire to diagnose disease processes. However, it is important to study the mechanical properties of healthy tissues; such data can enhance clinical knowledge and improve understanding of the mechanical properties of tissue. The purpose of this study is to evaluate the feasibility of using SDUV for in vitro measurements of renal cortex shear elasticity and shear viscosity in healthy swine kidneys. Eight excised kidneys from female pigs were used in these in vitro experiments and a battery of tests was performed to gain insight into the material proper ties of the renal cortex. In these 8 kidneys, the overall renal cortex elasticity and viscosity were 1.81 ± 0.17 kPa and 1.48 ± 0.49 Pa-s, respectively. In an analysis of the material properties over time after excision, there was not a statistically significant difference in shear elasticity over a 24-h period, but a statistically significant difference in shear viscosity was found. Homogeneity of the renal cortex was examined and it was found that shear elasticity and shear viscosity were statistically different within a kidney, suggesting global tissue inhomogeneity. In creases of more than 30% in shear elasticity and shear viscosity were observed after immersion in 10% formaldehyde. Finally, it was found that the renal cortex is rather anisotropic. Two values for shear elasticity and shear viscosity were measured depending on shear wave propagation direction. These various tests elucidated different aspects of the material properties and the structure of the ex vivo renal cortex.