Contrast-enhanced ultrasound of abdominal organs in cats

The primary aim of this thesis was the evaluation of the perfusion of normal organs in cats using contrast-enhanced ultrasound (CEUS), to serve as a reference for later clinical studies. Little is known of the use of CEUS in cats, especially regarding its safety and the effects of anesthesia on the procedure, thus, secondary aims here were to validate the quantitative analyzing method, to investigate the biological effects of CEUS on feline kidneys, and to assess the effect of anesthesia on splenic perfusion in cats undergoing CEUS. -- The studies were conducted on healthy, young, purpose-bred cats. CEUS of the liver, left kidney, spleen, pancreas, small intestine, and mesenteric lymph nodes was performed to characterize the normal perfusion of these organs on ten anesthetized, male cats. To validate the quantification method, the effects of placement and size of the region of interest (ROI) on perfusion parameters were investigated using CEUS: Three separate sets of ROIs were placed in the kidney cortex, varying in location, size, or depth. The biological effects of CEUS on feline kidneys were estimated by measuring urinary enzymatic activities, analyzing urinary specific gravity, pH, protein, creatinine, albumin, and sediment, and measuring plasma urea and creatinine concentrations before and after CEUS. Finally, the impact of anesthesia on contrast enhancement of the spleen was investigated by imaging cats with CEUS first awake and later under anesthesia on separate days. -- Typical perfusion patterns were found for each of the studied organs. The liver had a gradual and more heterogeneous perfusion pattern due to its dual blood flow and close proximity to the diaphragm. An obvious and statistically significant difference emerged in the perfusion between the kidney cortex and medulla. Enhancement in the spleen was very heterogeneous at the beginning of imaging, indicating focal dissimilarities in perfusion. No significant differences emerged in the perfusion parameters between the pancreas, small intestine, and mesenteric lymph nodes. -- The ROI placement and size were found to have an influence on the quantitative measurements of CEUS. Increasing the depth or the size of the ROI decreased the peak intensity value significantly, suggesting that where and how the ROI is placed does matter in quantitative analyses. --- A significant increase occurred in the urinary N-acetyl-β-D-glucosaminidase (NAG) to creatinine ratio after CEUS. No changes were noted in the serum biochemistry profile after CEUS, with the exception of a small decrease in blood urea concentration. The magnitude of the rise in the NAG/creatinine ratio was, however, less than the circadian variation reported earlier in healthy cats. Thus, the changes observed in the laboratory values after CEUS of the left kidney did not indicate any detrimental effects in kidneys. Heterogeneity of the spleen was observed to be less and time of first contrast appearance earlier in nonanesthetized cats than in anesthetized ones, suggesting that anesthesia increases heterogeneity of the feline spleen in CEUS. ---- In conclusion, the results suggest that CEUS can be used also in feline veterinary patients as an additional diagnostics aid. The perfusion patterns found in the imaged organs were typical and similar to those seen earlier in other species, with the exception of the heterogeneous perfusion pattern in the cat spleen. Differences in the perfusion between organs corresponded with physiology. Based on the results, estimation of focal perfusion defects of the spleen in cats should be performed with caution and after the disappearance of the initial heterogeneity, especially in anesthetized or sedated cats. Finally, these results indicate that CEUS can be used safely to analyze kidney perfusion also in cats. Future clinical studies are needed to evaluate the full potential of CEUS in feline medicine as a tool for diagnosing lesions in various organ systems.

Elastic property estimation using Ultrasound Assisted Optical Elastography through Remote Palpation - A simulation study - art. no. 61640Q

We propose an effective elastography technique in which an acoustic radiation force is used for remote palpation to generate localized tissue displacements, which are directly correlated to localized variations of tissue stiffness and are measured using a light probe in the same direction of ultrasound propagation. The experimental geometry has provision to input light beam along the ultrasound propagation direction, and hence it can be prealigned to ensure proper interception of the focal region by the light beam. Tissue-mimicking phantoms with homogeneous and isotropic mechanical properties of normal and malignant breast tissue are considered for the study. Each phantom is insonified by a focusing ultrasound transducer (1 MHz). The focal volume of the transducer and the ultrasound radiation force in the region are estimated through solving acoustic wave propagation through medium assuming average acoustic properties. The forward elastography problem is solved for the region of insonification assuming the Lame's parameters and Poisson's ratio, under Dirichlet boundary conditions which gives a distribution of displacement vectors. The direction of displacement, though presented spatial variation, is predominantly towards the ultrasound propagation direction. Using Monte Carlo (MC) simulation we have traced the photons through the phantom and collected the photons arriving at the detector on the boundary of the object in the direction of ultrasound. The intensity correlations are then computed from detected photons. The intensity correlation function computed through MC simulation showed a modulation whose strength is found to be proportional to the amplitude of displacement and inversely related to the storage (elastic) modulus. It is observed that when the storage modulus in the focal region is increased the computed displacement magnitude, as indicated by the depth of modulation in the intensity autocorrelation, decreased and the trend is approximately exponential.

Assessment of ultrasound modulation of near infrared light on the quantification of scattering coefficient

Purpose: To assess the effect of ultrasound modulation of near infrared (NIR) light on the quantification of scattering coefficient in tissue-mimicking biological phantoms.Methods: A unique method to estimate the phase of the modulated NIR light making use of only time averaged intensity measurements using a charge coupled device camera is used in this investigation. These experimental measurements from tissue-mimicking biological phantoms are used to estimate the differential pathlength, in turn leading to estimation of optical scattering coefficient. A Monte-Carlo model base numerical estimation of phase in lieu of ultrasound modulation is performed to verify the experimental results. Results: The results indicate that the ultrasound modulation of NIR light enhances the effective scattering coefficient. The observed effective scattering coefficient enhancement in tissue-mimicking viscoelastic phantoms increases with increasing ultrasound drive voltage. The same trend is noticed as the ultrasound modulation frequency approaches the natural vibration frequency of the phantom material. The contrast enhancement is less for the stiffer (larger storage modulus) tissue, mimicking tumor necrotic core, compared to the normal tissue. Conclusions: The ultrasound modulation of the insonified region leads to an increase in the effective number of scattering events experienced by NIR light, increasing the measured phase, causing the enhancement in the effective scattering coefficient. The ultrasound modulation of NIR light could provide better estimation of scattering coefficient. The observed local enhancement of the effective scattering coefficient, in the ultrasound focal region, is validated using both experimental measurements and Monte-Carlo simulations. (C) 2010 American Association of Physicists in Medicine. [DOI: 10.1118/1.3456441]

A novel two sources ultrasound modulated optical tomographic system for screening breast cancer through elasticity characterization

The study of non-invasive characterization of elastic properties of soft biological tissues has been a focus of active researches since recent years. Light is highly scattered by biological tissues and hence, sophisticated reconstruction algorithms are required to achieve good imaging depth and a reasonable resolution. Ultrasound (US), on the otherhand, is less scattered by soft tissues and it has been in use for imaging in biomedical ultrasound systems. Combination of the contrast sensitivity of light and good localization of ultrasound provides a challenging technique for characterization of thicker tissues deep inside the body non-invasively. The elasticity of the tissues is characterized by studying the response of tissues to mechanical excitation induced by an acoustic radiation force (remotely) using an optical laser. The US modulated optical signals which traverse the tissue are detected by using a CCD camera as detector array and the pixel map formed on the CCD is used to characterize the embedded inhomogeneities. The use of CCD camera improves the signal-noise-ratio (SNR) by averaging the signals from all of the CCD pixels.

Detection and Evaluation of Impact damage in CFRP Laminates Using Ultrasound C-Scan and IR Thermography

Advanced composite structural components made up of Carbon Fibre Reinforced Polymers (CFRP) used in aerospace structures such as in Fuselage, Leading & Trailing edges of wing and tail, Flaps, Elevator, Rudder and entire wing structures encounter most critical type of damage induced by low velocity impact (<10 m/s) loads. Tool dropped during maintenance & service,and hailstone impacts on runways are common and unavoidable low-velocity impacts. These lowvelocity impacts induce defects such as delaminations, matrix cracking and debonding in the layered material, which are sub-surface in nature and are barely visible on the surface known as Barely Visible Impact Damage (BVID). These damages may grow under service load, leading to catastrophic failure of the structure. Hence detection, evaluation and characterization of these types of damage is of major concern in aerospace industries as the life of the component depends on the size and shape of the damage.In this paper, details of experimental investigations carried out and results obtained from a low-velocity impact of 30 Joules corresponding to the hailstone impact on the wing surface,simulated on the 6 mm CFRP laminates using instrumented drop-weight impact testing machine are presented. The Ultrasound C-scan and Infrared thermography imaging techniques were utilized extensively to detect, evaluate and characterize impact damage across the thickness of the laminates.

Ultrasound-modulated optical tomography: recovery of amplitude of vibration in the insonified region from boundary measurement of light correlation

We address a certain inverse problem in ultrasound-modulated optical tomography: the recovery of the amplitude of vibration of scatterers [p(r)] in the ultrasound focal volume in a diffusive object from boundary measurement of the modulation depth (M) of the amplitude autocorrelation of light [phi(r, tau)] traversing through it. Since M is dependent on the stiffness of the material, this is the precursor to elasticity imaging. The propagation of phi(r, tau) is described by a diffusion equation from which we have derived a nonlinear perturbation equation connecting p(r) and refractive index modulation [Delta n(r)] in the region of interest to M measured on the boundary. The nonlinear perturbation equation and its approximate linear counterpart are solved for the recovery of p(r). The numerical results reveal regions of different stiffness, proving that the present method recovers p(r) with reasonable quantitative accuracy and spatial resolution. (C) 2011 Optical Society of America

Ultrasound modulated optical tomography: Young's modulus of the insonified region from measurement of natural frequency of vibration

We demonstrate a method to recover the Young's modulus (E) of a tissue-mimicking phantom from measurements of ultrasound modulated optical tomography (UMOT). The object is insonified by a dualbeam, confocal ultrasound transducer (US) oscillating at frequencies f(0) and f(0) + Delta f and the variation of modulation depth (M) in the autocorrelation of light traversed through the focal region of the US transducer against Delta f is measured. From the dominant peaks observed in the above variation, the natural frequencies of the insonified region associated with the vibration along the US transducer axis are deduced. A consequence of the above resonance is that the speckle fluctuation at the resonance frequency has a higher signal-to-noise to ratio (SNR). From these natural frequencies and the associated eigenspectrum of the oscillating object, Young's modulus (E) of the material in the focal region is recovered. The working of this method is confirmed by recovering E in the case of three tissue-mimicking phantoms of different elastic modulus values. (C) 2011 Optical Society of America

Ultrasound Assisted Optical Tomography: Estimation of phase Shift experienced by photon on transit through US insonified region for detection of breast tumor

A Monte Carlo model of ultrasound modulation of multiply scattered coherent light in a highly scattering media has been carried out for estimating the phase shift experienced by a photon beam on its transit through US insonified region. The phase shift is related to the tissue stiffness, thereby opening an avenue for possible breast tumor detection. When the scattering centers in the tissue medium is exposed to a deterministic forcing with the help of a focused ultrasound (US) beam, due to the fact that US-induced oscillation is almost along particular direction, the direction defined by the transducer axis, the scattering events increase, thereby increasing the phase shift experienced by light that traverses through the medium. The phase shift is found to increase with increase in anisotropy g of the medium. However, as the size of the focused region which is the region of interest (ROI) increases, a large number of scattering events take place within the ROI, the ensemble average of the phase shift (Delta phi) becomes very close to zero. The phase of the individual photon is randomly distributed over 2 pi when the scattered photon path crosses a large number of ultrasound wavelengths in the focused region. This is true at high ultrasound frequency (1 MHz) when mean free path length of photon l(s) is comparable to wavelength of US beam. However, at much lower US frequencies (100 Hz), the wavelength of sound is orders of magnitude larger than l(s), and with a high value of g (g 0.9), there is a distinct measurable phase difference for the photon that traverses through the insonified region. Experiments are carried out for validation of simulation results.

Ultrasound modulation of coherent light in a multiple-scattering medium: experimental verification of nonzero average phase carried by light

We demonstrate the phase fluctuation introduced by oscillation of scattering centers in the focal volume of an ultrasound transducer in an optical tomography experiment has a nonzero mean. The conditions to be met for the above are: (i) the frequency of the ultrasound should be in the vicinity of the most dominant natural frequency of vibration of the ultrasound focal volume, (ii) the corresponding acoustic wavelength should be much larger than l(n)*, a modified transport mean-free-path applicable for phase decorrelation and (iii) the focal volume of the ultrasound transducer should not be larger than 4 - 5 times (l(n)*)(3). We demonstrate through simulations that as the ratio of the ultrasound focal volume to (l(n)*)(3) increases, the average of the phase fluctuation decreases and becomes zero when the focal volume becomes greater than around 4(l(n)*)(3); and through simulations and experiments that as the acoustic frequency increases from 100 Hz to 1 MHz, the average phase decreases to zero. Through experiments done in chicken breast we show that the average phase increases from around 110 degrees to 130 degrees when the background medium is changed from water to glycerol, indicating that the average of the phase fluctuation can be used to sense changes in refractive index deep within tissue.

Quantitative estimation of mechanical and optical properties from ultrasound assisted optical tomography data

We demonstrate quantitative optical property and elastic property imaging from ultrasound assisted optical tomography data. The measurements, which are modulation depth M and phase phi of the speckle pattern, are shown to be sensitively dependent on these properties of the object in the insonified focal region of the ultrasound (US) transducer. We demonstrate that Young's modulus (E) can be recovered from the resonance observed in M versus omega (the US frequency) plots and optical absorption (mu(a)) and scattering (mu(s)) coefficients from the measured differential phase changes. All experimental observations are verified also using Monte Carlo simulations. (c) 2012 Society of Photo-Optical Instrumentation Engineers (SPIE). DOI: 10.1117/1.JBO.17.10.101507]

Diffusing-wave spectroscopy in an inhomogeneous object: Local viscoelastic spectra from ultrasound-assisted measurement of correlation decay arising from the ultrasound focal volume

We demonstrate diffusing-wave spectroscopy (DWS) in a localized region of a viscoelastically inhomogeneous object by measurement of the intensity autocorrelation g(2)(tau)] that captures only the decay introduced by the temperature-induced Brownian motion in the region. The region is roughly specified by the focal volume of an ultrasound transducer which introduces region specific mechanical vibration owing to insonification. Essential characteristics of the localized non-Markovian dynamics are contained in the decay of the modulation depth M(tau)], introduced by the ultrasound forcing in the focal volume selected, on g(2)(tau). The modulation depth M(tau(i)) at any delay time tau(i) can be measured by short-time Fourier transform of g(2)(tau) and measurement of the magnitude of the spectrum at the ultrasound drive frequency. By following the established theoretical framework of DWS, we are able to connect the decay in M(tau) to the mean-squared displacement (MSD) of scattering centers and the MSD to G*(omega), the complex viscoelastic spectrum. A two-region composite polyvinyl alcohol phantom with different viscoelastic properties is selected for demonstrating local DWS-based recovery of G*(omega) corresponding to these regions from the measured region specific M(tau(i))vs tau(i). The ultrasound-assisted measurement of MSD is verified by simulating, using a generalized Langevin equation (GLE), the dynamics of the particles in the region selected as well as by the usual DWS experiment without the ultrasound. It is shown that whereas the MSD obtained by solving the GLE without the ultrasound forcing agreed with its experimental counterpart covering small and large values of tau, the match was good only in the initial transients in regard to experimental measurements with ultrasound.

Intense Acoustic Burst Ultrasound Modulated Optical Tomography for Elasticity Mapping of Soft Biological Tissue Mimicking Phantom: A Laser Speckle Contrast Analysis Study

This report addresses the assessment of variation in elastic property of soft biological tissues non-invasively using laser speckle contrast measurement. The experimental as well as the numerical (Monte-Carlo simulation) studies are carried out. In this an intense acoustic burst of ultrasound (an acoustic pulse with high power within standard safety limits), instead of continuous wave, is employed to induce large modulation of the tissue materials in the ultrasound insonified region of interest (ROI) and it results to enhance the strength of the ultrasound modulated optical signal in ultrasound modulated optical tomography (UMOT) system. The intensity fluctuation of speckle patterns formed by interference of light scattered (while traversing through tissue medium) is characterized by the motion of scattering sites. The displacement of scattering particles is inversely related to the elastic property of the tissue. We study the feasibility of laser speckle contrast analysis (LSCA) technique to reconstruct a map of the elastic property of a soft tissue-mimicking phantom. We employ source synchronized parallel speckle detection scheme to (experimentally) measure the speckle contrast from the light traversing through ultrasound (US) insonified tissue-mimicking phantom. The measured relative image contrast (the ratio of the difference of the maximum and the minimum values to the maximum value) for intense acoustic burst is 86.44 % in comparison to 67.28 % for continuous wave excitation of ultrasound. We also present 1-D and 2-D image of speckle contrast which is the representative of elastic property distribution.

Ultrasound-modulated optical tomography: direct recovery of elasticity distribution from experimentally measured intensity autocorrelation

Based on an ultrasound-modulated optical tomography experiment, a direct, quantitative recovery of Young's modulus (E) is achieved from the modulation depth (M) in the intensity autocorrelation. The number of detector locations is limited to two in orthogonal directions, reducing the complexity of the data gathering step whilst ensuring against an impoverishment of the measurement, by employing ultrasound frequency as a parameter to vary during data collection. The M and E are related via two partial differential equations. The first one connects M to the amplitude of vibration of the scattering centers in the focal volume and the other, this amplitude to E. A (composite) sensitivity matrix is arrived at mapping the variation of M with that of E and used in a (barely regularized) Gauss-Newton algorithm to iteratively recover E. The reconstruction results showing the variation of E are presented. (C) 2015 Optical Society of America