Feasibility of detecting change in backscattered energy of acoustic harmonics in locally heated tissues.

Purpose: A real-time noninvasive thermometry technique is required to estimate the temperature distribution during hyperthermia to monitor and control the treatment. The main objective of this study is to demonstrate the possibility of detecting change in backscatter energy (CBE) of acoustic harmonics in tissue-mimicking gel phantoms and ex vivo bovine muscle tissues in which the temperature was locally increased within the hyperthermia regime. Materials and Methods: A peristaltic pump was used to circulate hot water through a needle inserted inside the samples to locally increase the temperature from 26 °C to 46 °C. The CBE of acoustic harmonics were used to identify the location of temperature changes in the samples. A conventional echo-shift technique was also implemented for comparison. Data collection was performed for two conditions to investigate the effect of motion on both techniques by: (1) inducing vibration in the sample through the peristatic pump and, (2) subsequently with no sample vibration while the pump was off. Results: Harmonics were able to determine the location of temperature rise in the presence and absence of vibration. In gel phantom, the mean contrast to noise ratio (CNR) in CBE maps reduced by a factor of 0.86 due to vibration whereas in gradient maps the CNR reduced by a factor of 8.3. Conclusions: The findings of this study suggest that the change in backscatter energy of acoustic harmonics can potentially be used to develop a noninvasive ultrasound-based thermometry technique with lower susceptibility to motion artifacts compared to the echo-shift method.

Skull's Photoacoustic Attenuation and Dispersion Modeling with Deterministic Ray-Tracing: Towards Real-Time Aberration Correction.

Although transcranial photoacoustic imaging has been previously investigated by several groups, there are many unknowns about the distorting effects of the skull due to the impedance mismatch between the skull and underlying layers. The current computational methods based on finite-element modeling are slow, especially in the cases where fine grids are defined for a large 3-D volume. We develop a very fast modeling/simulation framework based on deterministic ray-tracing. The framework considers a multilayer model of the medium, taking into account the frequency-dependent attenuation and dispersion effects that occur in wave reflection, refraction, and mode conversion at the skull surface. The speed of the proposed framework is evaluated. We validate the accuracy of the framework using numerical phantoms and compare its results to k-Wave simulation results. Analytical validation is also performed based on the longitudinal and shear wave transmission coefficients. We then simulated, using our method, the major skull-distorting effects including amplitude attenuation, time-domain signal broadening, and time shift, and confirmed the findings by comparing them to several ex vivo experimental results. It is expected that the proposed method speeds up modeling and quantification of skull tissue and allows the development of transcranial photoacoustic brain imaging.

High-Intensity Focused Ultrasound Thermal Lesion Detection Using Entropy Imaging of Ultrasound Radio Frequency Signal Time Series.

BACKGROUND: During the past few decades, high-intensity focused ultrasound (HIFU) modality has been gaining surging interest in various therapeutic applications such as non- or minimally-invasive cancer treatment. Among other attributes, robust and real-time HIFU treatment monitoring and lesion detection have become essential issues for successful clinical acceptance of the modality. More recently, ultrasound radio frequency (RF) time series imaging has been studied by a number of researchers. MATERIALS AND METHODS: The objective of this study is to investigate the applicability of entropy parameter of RF time series of ultrasound backscattered signals, a. k. a. Entropy imaging, toward HIFU thermal lesion detection. To this end, five fresh ex vivo porcine muscle tissue samples were exposed to HIFU exposures with total acoustic powers ranging from 30 to 110 Watts. The contrast-to-speckle ratio (CSR) values of the entropy images and their corresponding B-mode images of pre-, during- and post-HIFU exposure for each acoustic power were calculated. RESULTS: The novelty of this study is the use of Entropy parameter on ultrasound RF time series for the first time. Statistically significant differences were obtained between the CSR values for the B mode and entropy images at various acoustic powers. In case of 110 Watt, a CSR value 3.4 times higher than B-mode images was accomplished using the proposed method. Furthermore, the proposed method is compared with the scaling parameter of Nakagami imaging and same data which are used in this study. CONCLUSION: Entropy has the potential for using as an imaging parameter for differentiating lesions in HIFU surgery.

Temperature dependence of acoustic harmonics generated by nonlinear ultrasound wave propagation in water at various frequencies.

Ultrasound-based thermometry requires a temperature-sensitive acoustic parameter that can be used to estimate the temperature by tracking changes in that parameter during heating. The objective of this study is to investigate the temperature dependence of acoustic harmonics generated by nonlinear ultrasound wave propagation in water at various pulse transmit frequencies from 1 to 20 MHz. Simulations were conducted using an expanded form of the Khokhlov-Zabolotskaya-Kuznetsov nonlinear acoustic wave propagation model in which temperature dependence of the medium parameters was included. Measurements were performed using single-element transducers at two different transmit frequencies of 3.3 and 13 MHz which are within the range of frequencies simulated. The acoustic pressure signals were measured by a calibrated needle hydrophone along the axes of the transducers. The water temperature was uniformly increased from 26 °C to 46 °C in increments of 5 °C. The results show that the temperature dependence of the harmonic generation is different at various frequencies which is due to the interplay between the mechanisms of absorption, nonlinearity, and focusing gain. At the transmit frequencies of 1 and 3.3 MHz, the harmonic amplitudes decrease with increasing the temperature, while the opposite temperature dependence is observed at 13 and 20 MHz.

Temperature dependence of acoustic harmonics generated by nonlinear ultrasound beam propagation in ex vivo tissue and tissue-mimicking phantoms.

PURPOSE: Hyperthermia is a cancer treatment technique that could be delivered as a stand-alone modality or in conjunction with chemotherapy or radiation therapy. Noninvasive and real-time temperature monitoring of the heated tissue improves the efficacy and safety of the treatment. A temperature-sensitive acoustic parameter is required for ultrasound-based thermometry. In this paper the amplitude and the energy of the acoustic harmonics of the ultrasound backscattered signal are proposed as suitable parameters for noninvasive ultrasound thermometry. MATERIALS AND METHODS: A commercial high frequency ultrasound imaging system was used to generate and detect acoustic harmonics in tissue-mimicking gel phantoms and ex vivo bovine muscle tissues. The pressure amplitude and the energy content of the backscattered fundamental frequency (p1 and E1), the second (p2 and E2) and the third (p3 and E3) harmonics were detected in pulse-echo mode. Temperature was increased from 26° to 46 °C uniformly through both samples. The amplitude and the energy content of the harmonics and their ratio were measured and analysed as a function of temperature. RESULTS: The average p1, p2 and p3 increased by 69%, 100% and 283%, respectively as the temperature was elevated from 26° to 46 °C in tissue samples. In the same experiment the average E1, E2 and E3 increased by 163%, 281% and 2257%, respectively. A similar trend was observed in tissue-mimicking gel phantoms. CONCLUSIONS: The findings suggest that the harmonics generated due to nonlinear ultrasound beam propagation are highly sensitive to temperature and could potentially be used for noninvasive ultrasound tissue thermometry.

Unmitigated numerical solution to the diffraction term in the parabolic nonlinear ultrasound wave equation.

Various numerical algorithms have been developed to solve the Khokhlov-Kuznetsov-Zabolotskaya (KZK) parabolic nonlinear wave equation. In this work, a generalized time-domain numerical algorithm is proposed to solve the diffraction term of the KZK equation. This algorithm solves the transverse Laplacian operator of the KZK equation in three-dimensional (3D) Cartesian coordinates using a finite-difference method based on the five-point implicit backward finite difference and the five-point Crank-Nicolson finite difference discretization techniques. This leads to a more uniform discretization of the Laplacian operator which in turn results in fewer calculation gridding nodes without compromising accuracy in the diffraction term. In addition, a new empirical algorithm based on the LU decomposition technique is proposed to solve the system of linear equations obtained from this discretization. The proposed empirical algorithm improves the calculation speed and memory usage, while the order of computational complexity remains linear in calculation of the diffraction term in the KZK equation. For evaluating the accuracy of the proposed algorithm, two previously published algorithms are used as comparison references: the conventional 2D Texas code and its generalization for 3D geometries. The results show that the accuracy/efficiency performance of the proposed algorithm is comparable with the established time-domain methods.

Thermometry using entropy imaging of ultrasound radio frequency signal time series.

Low intensity focused ultrasound (LIFU) is a novel approach that could activate drug release and considerably improve the delivery of anticancer drug. LIFU treatment has some features like is able to penetrate deep into the tissue and being non-invasive, as a consequence LIFU displays great capability for controlling the drug release and improving the chemotherapy treatment efficiency. The goal of this study is to research the feasibility of the entropy parameter of RF time series of ultrasound backscattered signals for measuring the changes in temperature induced by a LIFU device. Entropy Imaging is a technique for reconstructing ultrasound images based on the average uncertainty of time-series in a signal. Furthermore, the Shannon Entropy can quantify the uncertainty of a random process and is usually used as a measure for the information content of probability distributions. In this study, we use the Entropy Imaging method for measuring the LIFU-induced temperature changes in the deep region of ex vivo porcine tissue samples. The results obtained show that the changes of entropy parameter of RF time series signal are proportional to temperature changes recorded by a calibrated thermocouple in the temperature range of 37-47°C. In conclusion, in this study we show that Shannon entropy of RF time series signal possesses promising features like succinctly capturing the available information in a system by considering the uncertainty in a given data that can be used, as a new method, to measure temperature changes non-invasively and quantitatively in the deep region of tissue.

Noninvasive calibrated tissue temperature estimation using backscattered energy of acoustic harmonics.

PURPOSE: A real-time and non-invasive thermometry technique is essential in thermal therapies to monitor and control the treatment. Ultrasound is an attractive thermometry modality due to its relatively high sensitivity to change in temperature and fast data acquisition and processing capabilities. A temperature-sensitive acoustic parameter is required for ultrasound thermometry in order to track the changes in that parameter during the treatment. Currently, the main ultrasound thermometry methods are based on variation in the attenuation coefficient, the change in backscattered energy of the signal (CBE), the backscattered radio-frequency (RF) echo-shift due to change in the speed of sound and thermal expansion of the medium, and change in the amplitudes of the acoustic harmonics. In this work, an ultrasound thermometry method based on second harmonic CBE (CBEh2) and combined fundamental and second harmonic CBE (CBEcomb) is used to produce 2D temperature maps, detect localized heated region generated by low intensity focused ultrasound (LIFU), and control temperature in the heated region. MATERIALS AND METHODS: Ex vivo pork muscle tissue samples were exposed to localized LIFU heating source and 2D temperature maps were produced from the RF data acquired by a 4.2 MHz linear array probe using a Verasonics Vantage™ ultrasound scanner (Verasonics Inc., Redmond, WA) after the exposure. Calibrated needle thermocouples were also placed in the ex vivo tissue sample close to the LIFU focal zone for temperature calibration purposes. The estimated temperature maps were the established echo-shift technique. A tissue motion compensation algorithm was also used to reduce the susceptibility to motion artifacts. RESULTS: 2D temperature maps were generated using CBE of acoustic harmonic and echo-shift techniques. The results show a direct correlation between the CBE of acoustic harmonics and focal tissue temperature for a range of temperatures from 37 °C (baseline) to 47 °C. CONCLUSIONS: The findings of this study show that the CBE of acoustic harmonics technique can be used to noninvasively estimate temperature change in tissue in the hyperthermia temperature range.

Real-Time Control of Nanoparticle-Mediated Thermal Therapy Using Photoacoustic Imaging.

OBJECTIVE: This work aims to determine whether photoacoustic (PA) thermometry from a commercially available PA imaging system can be used to control the temperature in nanoparticle-mediated thermal therapies. METHODS: The PA imaging system was interfaced to obtain PA images while scanning ex-vivo tissue. These images were then used to obtain temperature maps in real-time during heating. Validation and calibration of the PA thermometry were done using a fluoroptic thermometer. This thermometer was also used to develop and tune a software-based proportional integral derivative (PID) controller. Finally, a PA-based PID closed-loop controller was used to control gold nanorod (GNR) mediated laser therapy. RESULTS: The use of GNRs substantially enhanced laser heating; the temperature rise increased 7-fold by injecting a GNR solution with a concentration of 0.029 mg/mL. The control experiments showed that the desired temperature could be achieved and maintained at a targeted location in the ex-vivo tissue. The steady-state mean absolute deviations (MAD) from the targeted temperature during control were between 0.16 [Formula: see text] and 0.5 [Formula: see text], depending on the experiment. CONCLUSION: It was possible to control hyperthermia treatments using a software-based PID controller and a commercial PA imaging system. SIGNIFICANCE: The monitoring and control of the temperature in thermal-based therapies are important for assuring a prescribed temperature to the target tissue while minimizing the temperature of the surrounding healthy tissue. This easily implemented non-invasive control system will facilitate the realization of a broad range of hyperthermia treatments.

Skull acoustic aberration correction in photoacoustic microscopy using a vector space similarity model: a proof-of-concept simulation study.

Skull bone represents a highly acoustical impedance mismatch and a dispersive barrier for the propagation of acoustic waves. Skull distorts the amplitude and phase information of the received waves at different frequencies in a transcranial brain imaging. We study a novel algorithm based on vector space similarity model for the compensation of the skull-induced distortions in transcranial photoacoustic microscopy. The results of the algorithm tested on a simplified numerical skull phantom, demonstrate a fully recovered vasculature with the recovery rate of 91.9%.

Effect of Human Umbilical Cord Perivascular Cell-Conditioned Media in an Adult Zebrafish Model of Traumatic Brain Injury.

The pathophysiological events of secondary brain injury contribute to poor outcome after traumatic brain injury (TBI). The neuroprotective effects of mesenchymal cells have been extensively studied and evidence suggests that their effects are mostly mediated through paracrine effects. Human umbilical cord perivascular cells (HUCPVCs) are mesenchymal stem cells with potential therapeutic value in TBI. In this study, we assessed the effect of HUCPVC-conditioned media (CM) in an established adult zebrafish model of TBI induced by pulsed high-intensity focused ultrasound (pHIFU). This model demonstrates similarities to mammalian outcome after TBI. Administration of HUCPVC-CM 1 h postinjury (hpi) resulted in improved outcome after pHIFU-induced TBI. Western blot and immunohistochemistry results demonstrated that the HUCPVC-CM reduced (p < 0.05) reactive astrogliosis at 24 hpi. Moreover, at 24 hpi, the HUCPVC-CM treatment resulted in reduced apoptosis in HUCPVC-CM-treated zebrafish. Behavioral analysis demonstrated improvement in locomotor activity (p < 0.05) and anxiety (p < 0.05) at 6 and 24 hpi following HUCPVC-CM treatment. Overall, HUCPVC-CM treatment improved acute outcome measures in pHIFU-injured zebrafish. Collectively, the data demonstrate a cell-free treatment approach for traumatic brain injuries.

Remote ischemic conditioning improves outcome independent of anesthetic effects following shockwave-induced traumatic brain injury.

Traumatic brain injury due to primary blast exposure is a major cause of ongoing neurological and psychological impairment in soldiers and civilians. Animal and human evidence suggests that low-level blast exposure is capable of inducing white matter injury and behavioural deficits. There are currently no effective therapies to treat the underlying suspected pathophysiology of low-level primary blast or concussion. Remote ischemic conditioning (RIC) has been shown to have cardiac, renal and neuro-protective effects in response to brief cycles of ischemia. Here we examined the effects of RIC in two models of blast injury. We used a model of low-level primary blast in rats to evaluate the effects of RIC neurofilament expression. We subsequently used a model of traumatic brain injury in adult zebrafish using pulsed high intensity focused ultrasound (pHIFU) to evaluate the effects of RIC on behavioural outcome and apoptosis in a post-traumatic setting. In blast exposed rats, RIC pretreatment modulated NF200 expression suggesting an innate biological buffering effect. In zebrafish, behavioural deficits and apoptosis due to pHIFU-induced brain injury were reduced following administration of serum derived from RIC rats. The results in the zebrafish model demonstrate the humoral effects of RIC independent of anesthetic effects that were observed in the rat model of injury. Our results indicate that RIC is effective in improving outcome following modeled brain trauma in pre- and post-injury paradigms. The results suggest a potential role for innate biological systems in the protection against pathophysiological processes associated with impairment following shockwave induced trauma.

High-Intensity Focused Ultrasound Lesion Detection Using Adaptive Compressive Sensing Based on Empirical Mode Decomposition.

BACKGROUND: The main goal of ultrasound therapy is to have clinical effects in the tissue without damage to the intervening and surrounding tissues. Treatments have been developed for both in vitro and in clinical applications. HIFU therapy is one of these. Non-invasive surgeries, such as HIFU, have been developed to treat tumors or to stop bleeding. In this approach, an adequate imaging method for monitoring and controlling the treatment is required. METHODS: In this paper, an adaptive compressive sensing representation of ultrasound RF echo signals is presented based on empirical mode decomposition (EMD). According to the different numbers of intrinsic mode functions (IMFs) produced by the EMD, the ultrasound signals is adaptively compressive sampled in the source and then adaptively reconstructed in the receiver domains. In this paper, a new application of compressive sensing based on EMD (CS-EMD) in the monitoring of high-intensity focused ultrasound (HIFU) treatment is presented. Non-invasive surgeries such as HIFU have been developed for various therapeutic applications. In this technique, a suitable imaging method is necessary for monitoring of the treatment to achieve adequate treatment safety and efficacy. So far, several methods have been proposed, such as ultrasound radiofrequency (RF) signal processing techniques, and imaging methods such as X-ray, MRI, and ultrasound to monitor HIFU lesions. RESULTS: In this paper, a CS-EMD method is used to detect the HIFU thermal lesion dimensions using different types of wavelet transform. The results of the processing on the real data demonstrate the potential for this technique in image-guided HIFU therapy. CONCLUSIONS: In this study, a new application of compressive sensing in the field of monitoring of the HIFU treatment is presented. To the best of our knowledge, so far no studies on compressive sensing have been carried out in the monitoring of the HIFU. Based on the results obtained, it was showed that the number of measurements and Intrinsic Mode Functions have the function of noise reduction. In addition, results were shown that the successful reconstruction of the compressive sensing signals can be gained using a threshold based algorithm. To this end, in this paper it was shown that by selecting an suitable number of measurements, the sparse transform, and a thresholding algorithm, we can achieve a more accurate detection of the HIFU thermal lesion size.

Efficient Frequency-Domain Synthetic Aperture Focusing Techniques for Imaging With a High-Frequency Single-Element Focused Transducer.

Synthetic aperture focusing techniques (SAFT) make the spatial resolution of the conventional ultrasound imaging from a single-element focused transducer more uniform in the lateral direction. In this work, two new frequency-domain (FD-SAFT) algorithms are proposed, which are based on the synthetic aperture radar's wavenumber algorithm, and 2-D matched filtering technique for the image reconstruction. The first algorithm is the FD-SAFT virtual source (FD-SAFT-VS) that treats the focus of a focused transducer as a virtual source having a finite size and the diffraction effect in the far-field is taken into consideration in the image reconstruction. The second algorithm is the FD-SAFT deconvolution (FD-SAFT-DE) that uses the simulated point spread function of the imaging system as a matched filter kernel in the image reconstruction. The performance of the proposed algorithms was studied using a series of simulations and experiments, and it was compared with the conventional B-mode and time-domain SAFT (TD-SAFT) imaging techniques. The image quality was analyzed in terms of spatial resolution, sidelobe level, signal-to-noise ratio (SNR), contrast resolution, contrast-to-speckle ratio, and ex vivo image quality. The results showed that the FD-SAFT-VS had the smallest spatial resolution and FD-SAFT-DE had the second smallest spatial resolution. In addition, FD-SAFT-DE had generally the largest SNR. The computation run time of FD-SAFT-VS and FD-SAFT-DE, depending on the image size, was lower by 4 to 174 times and 4 to 189 times, respectively, compared to the TD-SAFT-virtual point source.

Assessment of the effect of strontium, lead, and aluminum in bone on dual-energy x-ray absorptiometry and quantitative ultrasound measurements: A phantom study.

PURPOSE: Dual-energy X-ray absorptiometry (DXA) is the gold standard technique to measure areal bone mineral density (aBMD) for the diagnosis of osteoporosis. Because DXA relies on the attenuation of photon to estimate aBMD, deposition of bone-seeking metallic elements such as strontium, lead, and aluminum that differ in atomic numbers from calcium can cause inaccurate estimation of aBMD. Quantitative ultrasound (QUS) is another technique available to assess bone health by measuring broadband ultrasound attenuation (BUA), speed of sound (SOS), and an empirically derived quantity called stiffness index (SI). Because the acoustic properties are not prone to significant change due to changes in microscopic atomic composition of bone, it is hypothesized that QUS is unaffected by the presence of bone-seeking elements in the bone. The objective of this study was to investigate the effect of strontium, lead, and aluminum on DXA-derived aBMD and QUS parameters using bone-mimicking phantoms compatible with both techniques. METHODS: Bone-mimicking phantoms were produced by homogeneously mixing finely powdered hydroxyapatite compounds that contain varying concentrations of strontium, lead, or aluminum with porcine gelatin solution. Seven strontium-substituted phantoms were produced with varying molar ratio of Sr/(Sr + Ca) ranging from 0% to 2%. Four lead-doped phantoms and four aluminum-doped phantoms were constructed with the respective analyte concentrations ranging from 50 to 200 ppm. An additional 0 ppm phantom was produced to be used as a baseline for the lead and aluminum phantom measurements. All phantoms had uniform volumetric bone mineral density (vBMD) of 200 mg/cm3 , and were assessed using a Hologic Horizon® DXA device and a Hologic Sahara® QUS device. Furthermore, theoretical aBMD bias for mol/mol% substitution of calcium with the three bone-seeking elements was calculated. RESULTS: Strong positive linear relationship was found between aBMD measured by DXA and strontium concentration (P < 0.001, r = 0.995). From the measurement of lead and aluminum phantoms using DXA, no statistically significant relationship was observed between aBMD and the analyte concentrations. For the QUS system, with an exception of BUA and lead concentration that exhibited statistically significant relationship (P < 0.038, r = 0.899), no statistically significant change was observed in all QUS parameters with respect to the clinically relevant concentration of all three elements. The calculated theoretical aBMD bias induced by 1 mol/mol% substitution of calcium with strontium, lead, and aluminum were 10.8%, 4.6%, and -0.7%, respectively. CONCLUSION: aBMD measured by DXA was prone to overestimation in the presence of strontium, but acoustic parameters measured by QUS are independent of strontium concentration. The deviation in aBMD induced by the clinically relevant concentrations of lead and aluminum under 200 ppm could not be detected using the Hologic Horizon® DXA device. Furthermore, the SI measured by the QUS system was not affected by lead or aluminum concentrations used in this study.

Toward high-intensity focused ultrasound lesion quantification using compressive sensing theory.

Compressive sensing theory has in recent years been increasingly used in various pattern recognition applications. Compressive sensing theory makes it possible, under certain assumptions, to recover a signal or an image sampled below the Nyquist sampling limit. In this work, a new application of compressive sensing based on the threshold algorithm, in the area of controlling and monitoring of high-intensity focused ultrasound therapy, was investigated. In this work, a new method of high-intensity focused ultrasound lesion detection is presented based on a modified compressive sensing method in combination with the threshold algorithm and the wavelet transforms. In this study, analysis of the suggested method is performed using two sets of data: simulated and experimental ultrasound radio frequency data. The results of processing the data show that the proposed algorithm results in enhancement of the high-intensity focused ultrasound lesion contrast in comparison with the ultrasound B-mode and standard compressive sensing imaging methods. The results of the study show that the modified compressive sensing method could effectively detect thermal lesions in vitro. Comparing the estimated size of the thermal lesion (8.3 mm × 8.4 mm) using the proposed algorithm with the actual size of that from physical examination (10.1 mm × 9 mm) shows that we could detect high-intensity focused ultrasound thermal lesions with the difference of 0.8 mm × 0.5 mm.

A Novel Model of Traumatic Brain Injury in Adult Zebrafish Demonstrates Response to Injury and Treatment Comparable with Mammalian Models.

Traumatic brain injury (TBI) is a leading cause of death and morbidity in industrialized countries with considerable associated health care costs. The cost and time associated with pre-clinical development of TBI therapeutics is lengthy and expensive with a poor track record of successful translation to the clinic. The zebrafish is an emerging model organism in research with unique technical and genomic strengths in the study of disease and development. Its high degree of genetic homology and cell signaling pathways relative to mammalian species and amenability to high and medium throughput assays has potential to accelerate the rate of therapeutic drug identification. Accordingly, we developed a novel closed-head model of TBI in adult zebrafish using a targeted, pulsed, high-intensity focused ultrasound (pHIFU) to induce mechanical injury of the brain. Western blot results indicated altered microtubule and neurofilament expression as well as increased expression of cleaved caspase-3 and beta APP (ß-APP; p < 0.05). We used automated behavioral tracking software to evaluate locomotor deficits 24 and 48 h post-injury. Significant behavioral impairment included decreased swim distance and velocity (p < 0.05), as well as heightened anxiety and altered group social dynamics. Responses to injury were pHIFU dose-dependent and modifiable with MK-801, MDL-28170, or temperature modulation. Together, results indicate that the zebrafish exhibits responses to injury and intervention similar to mammalian TBI pathophysiology and suggest the potential for use to rapidly evaluate therapeutic compounds with high efficiency.

Performance study of a new time-delay estimation algorithm in ultrasonic echo signals and ultrasound elastography.

Time-delay estimation has countless applications in ultrasound medical imaging. Previously, we proposed a new time-delay estimation algorithm, which was based on the summation of the sign function to compute the time-delay estimate (Shaswary et al., 2015). We reported that the proposed algorithm performs similar to normalized cross-correlation (NCC) and sum squared differences (SSD) algorithms, even though it was significantly more computationally efficient. In this paper, we study the performance of the proposed algorithm using statistical analysis and image quality analysis in ultrasound elastography imaging. Field II simulation software was used for generation of ultrasound radio frequency (RF) echo signals for statistical analysis, and a clinical ultrasound scanner (Sonix® RP scanner, Ultrasonix Medical Corp., Richmond, BC, Canada) was used to scan a commercial ultrasound elastography tissue-mimicking phantom for image quality analysis. The statistical analysis results confirmed that, in overall, the proposed algorithm has similar performance compared to NCC and SSD algorithms. The image quality analysis results indicated that the proposed algorithm produces strain images with marginally higher signal-to-noise and contrast-to-noise ratios compared to NCC and SSD algorithms.

Radio Frequency Ultrasound Time Series Signal Analysis to Evaluate High-intensity Focused Ultrasound Lesion Formation Status in Tissue.

High-intensity focused ultrasound (HIFU) is a novel treatment modality used by scientists and clinicians in the recent decades. This modality has had a great and significant success as a noninvasive surgery technique applicable in tissue ablation therapy and cancer treatment. In this study, radio frequency (RF) ultrasound signals were acquired and registered in three stages of before, during, and after HIFU exposures. Different features of RF time series signals including the sum of amplitude spectrum in the four quarters of the frequency range, the slope, and intercept of the best-fit line to the entire power spectrum and the Shannon entropy were utilized to distinguish between the HIFU-induced thermal lesion and the normal tissue. We also examined the RF data, frame by frame to identify exposure effects on the formation and characteristics of a HIFU thermal lesion at different time steps throughout the treatment. The results obtained showed that the spectrum frequency quarters and the slope and intercept of the best fit line to the entire power spectrum both increased two times during the HIFU exposures. The Shannon entropy, however, decreased after the exposures. In conclusion, different characteristics of RF time series signal possess promising features that can be used to characterize ablated and nonablated tissues and to distinguish them from each other in a quasi-quantitative fashion.

Shear wave elastography using Wigner-Ville distribution: a simulated multilayer media study.

Shear Wave Elastography (SWE) is a quantitative ultrasound-based imaging modality for distinguishing normal and abnormal tissue types by estimating the local viscoelastic properties of the tissue. These properties have been estimated in many studies by propagating ultrasound shear wave within the tissue and estimating parameters such as speed of wave. Vast majority of the proposed techniques are based on the cross-correlation of consecutive ultrasound images. In this study, we propose a new method of wave detection based on time-frequency (TF) analysis of the ultrasound signal. The proposed method is a modified version of the Wigner-Ville Distribution (WVD) technique. The TF components of the wave are detected in a propagating ultrasound wave within a simulated multilayer tissue and the local properties are estimated based on the detected waves. Image processing techniques such as Alternative Sequential Filters (ASF) and Circular Hough Transform (CHT) have been utilized to improve the estimation of TF components. This method has been applied to a simulated data from Wave3000™ software (CyberLogic Inc., New York, NY). This data simulates the propagation of an acoustic radiation force impulse within a two-layer tissue with slightly different viscoelastic properties between the layers. By analyzing the local TF components of the wave, we estimate the longitudinal and shear elasticities and viscosities of the media. This work shows that our proposed method is capable of distinguishing between different layers of a tissue.