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High intensity focused ultrasound (HIFU) is a form of thermal ablation technique, which can treat a variety of medical afflictions. One promising therapeutic use is the permanent destruction of nerves non-invasively in patients with severe spasticity or certain types of pain (e.g., phantom limb pain). To this end, HIFU requires ultrasound guidance, which allows the non-invasive, target-specific deposition of thermal energy to the targeted nerve, thereby blocking axonal conduction. In this paper, a composite system comprising both ultrasound-imaging and HIFU therapy was developed and used to induce localized non-invasive nerve blockage in an in vivo large animal study. Five pigs were used with the femoral nerve as the target. Calibrated needle thermocouples inserted at the target site were employed to monitor the target tissue temperature. The degree of nerve blockage was assessed by measuring compound action potential (CAP) signal with a clinical nerve electrophysiology system before and after HIFU exposures. An average CAP signal amplitude reduction of 49% of baseline with a standard deviation of 9% was observed after 20–30 min post exposure. These results demonstrate the feasibility of the proposed ultrasound-guided HIFU modality as a potential non-invasive nerve ablation method., The complete portable HIFU/Imaging system is shown on the left. A close up of the applicator is shown on the right. The imaging probe in the middle of the HIFU transducer. The clear acrylic cylinder is the water jacket which can be sealed with a latex membrane.

Ultrasound waves have been widely used in diagnostic and therapeutic medical applications. Accurate and effective simulation of ultrasound beam propagation and its interaction with tissue has been proved to be important. The nonlinear nature of the ultrasound beam propagation, especially in the therapeutic regime, plays an important role in the mechanisms of interaction with tissue. There are three main approaches in current computational fluid dynamics (CFD) methods to model and simulate nonlinear ultrasound beams: macroscopic, mesoscopic and microscopic approaches. In this work, a mesoscopic CFD method based on the Lattice-Boltzmann model (LBM) was investigated. In the developed method, the Boltzmann equation is evolved to simulate the flow of a Newtonian fluid with the collision model instead of solving the Navier-Stokes, continuity and state equations which are used in conventional CFD methods. The LBM has some prominent advantages over conventional CFD methods, including: (1) its parallel computational nature; (2) taking microscopic boundaries into account; and (3) capability of simulating in porous and inhomogeneous media. In our proposed method, the propagating medium is discretized with a square grid in 2 dimensions with 9 velocity vectors for each node. Using the developed model, the nonlinear distortion and shock front development of a finiteamplitude diffractive ultrasonic beam in a dissipative fluid medium was computed and validated against the published data. The results confirm that the LBM is an accurate and effective approach to model and simulate nonlinearity in finite-amplitude ultrasound beams with Mach numbers of up to 0.01 which, among others, falls within the range of therapeutic ultrasound regime such as high intensity focused ultrasound (HIFU) beams. A comparison between the HIFU nonlinear beam simulations using the proposed model and pseudospectral methods in a 2D geometry is presented

Purpose: The aims of this study are: (a) to investigate the capability of photoacoustic (PA) method in detecting high-intensity focused ultrasound (HIFU) treatments in muscle tissuesin vitro; and (b) to determine the optical properties of HIFU-treated and native tissues in order to assist in the interpretation of the observed contrast in PA detection of HIFU treatments. Methods: A single-element, spherically concaved HIFU transducer with a centre frequency of 1 MHz was utilized to create thermal lesions in chicken breast tissuesin vitro. To investigate the detectability of HIFU treatments photoacoustically, PA detection was performed at 720 and 845 nm on seven HIFU-treated tissue samples. Within each tissue sample, PA signals were acquired from 22 locations equally divided between two regions of interest within two volumes in tissue – a HIFU-treated volume and an untreated volume. Optical spectroscopy was then carried out on 10 HIFU-treated chicken breast specimens in the wavelength range of 500–900 nm, in 1-nm increments, using a spectrophotometer with an integrating sphere attachment. The authors’ optical spectroscopy raw data (total transmittance and diffuse reflectance) were used to obtain the optical absorption and reduced scattering coefficients of HIFU-induced thermal lesions and native tissues by employing the inverse adding-doubling method. The aforementioned interaction coefficients were subsequently used to calculate the effective attenuation coefficient and light penetration depth of HIFU-treated and native tissues in the wavelength range of 500–900 nm. Results: HIFU-treated tissues produced greater PA signals than native tissues at 720 and 845 nm. At 720 nm, the averaged ratio of the peak-to-peak PA signal amplitude of HIFU-treated tissue to that of native tissue was 3.68 ± 0.25 (mean ± standard error of the mean). At 845 nm, the averaged ratio of the peak-to-peak PA signal amplitude of HIFU-treated tissue to that of native tissue was 3.75 ± 0.26 (mean ± standard error of the mean). The authors’ spectroscopic investigation has shown that HIFU-treated tissues have a greater optical absorption and reduced scattering coefficients than native tissues in the wavelength range of 500–900 nm. In fact, at 720 and 845 nm, the ratio of the optical absorption coefficient of HIFU-treated tissues to that of native tissues was 1.13 and 1.17, respectively; on the other hand, the ratio of the reduced scattering coefficient of HIFU-treated tissues to that of native tissues was 13.22 and 14.67 at 720 and 845 nm, respectively. Consequently, HIFU-treated tissues have a higher effective attenuation coefficient and a lower light penetration depth than native tissues in the wavelength range 500–900 nm. Conclusions: Using a PA approach, HIFU-treated tissues interrogated at 720 and 845 nm optical wavelengths can be differentiated from untreated tissues. Based on the authors’ spectroscopic investigation, the authors conclude that the observed PA contrast between HIFU-induced thermal lesions and untreated tissue is due, in part, to the increase in the optical absorption coefficient, the reduced scattering coefficient and, therefore, the deposited laser energy fluence in HIFU-treated tissues.

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%.

This work investigated the transient characteristics of tissue attenuation coefficient before, during and after HIFU treatment at different total acoustic powers (TAP) in ex vivo porcine muscle tissues. Dynamic changes of attenuation coefficient parameters were correlated with conventional B-mode ultrasound images over the whole HIFU treatment process. Two-dimensional pulse-echo radiofrequency (RF) data were acquired to estimate the changes of least squares attenuation coefficient slope (Δβ) and attenuation coefficient intercept (Δα0) averaged in the region of interest, and to construct Δβ, Δα0, and B-mode images simultaneously. During HIFU treatment, bubble activities were visible as strong hyperechoic regions in the B-mode images, causing fluctuations in Δβ and Δα0 estimations during treatment. Δβ and Δα0 increased with the appearance of bubble clouds in the B-mode images to values in the range of 1.5-2.5 [dB/(MHz.cm)] and 4-5 [dB/cm], respectively. After the treatment, Δβ and Δα0 gradually decreased, accompanied by fadeout of hyperechoic spot in the B-mode images, until they were stable at ranges of 0.75-1 [dB/(MHz.cm)] and 1-1.5 [dB/cm], respectively. In conclusion, Δβ and Δα0 images outperformed B-mode images in detecting HIFU thermal lesions by having significantly higher contrast to speckle ratios at all investigated TAP values.

Background This study investigated the dynamic changes of tissue attenuation coefficients before, during, and after high-intensity focused ultrasound (HIFU) treatment at different total acoustic powers (TAP) in ex vivo porcine muscle tissue. It further assessed the reliability of employing changes in tissue attenuation coefficient parameters as potential indicators of tissue thermal damage. Methods Two-dimensional pulse-echo radio frequency (RF) data were acquired before, during, and after HIFU exposure to estimate changes in least squares attenuation coefficient slope (Δβ) and attenuation coefficient intercept (Δα0). Using the acquired RF data, Δβ and Δα0 images, along with conventional B-mode ultrasound images, were constructed. The dynamic changes of Δβ and Δα0, averaged in the region of interest, were correlated with B-mode images obtained during the HIFU treatment process. Results At a HIFU exposure duration of 40 s and various HIFU intensities (737–1,068 W/cm2), Δβ and Δα0 increased rapidly to values in the ranges 1.5–2.5 dB/(MHz.cm) and 4–5 dB/cm, respectively. This rapid increase was accompanied with the appearance of bubble clouds in the B-mode images. Bubble activities appeared as strong hyperechoic regions in the B-mode images and caused fluctuations in the estimated Δβ and Δα0 values. After the treatment, Δβ and Δα0 values gradually decreased, accompanied by fade-out of hyperechoic spots in the B-mode images. At 10 min after the treatment, they reached values in ranges 0.75–1 dB/(MHz.cm) and 1–1.5 dB/cm, respectively, and remained stable within those ranges. At a long HIFU exposure duration of around 10 min and low HIFU intensity (117 W/cm2), Δβ and Δα0 gradually increased to values of 2.2 dB/(MHz.cm) and 2.2 dB/cm, respectively. This increase was not accompanied with the appearance of bubble clouds in the B-mode images. After HIFU treatment, Δβ and Δα0 gradually decreased to values of 1.8 dB/(MHz.cm) and 1.5 dB/cm, respectively, and remained stable at those values. Conclusions Δβ and Δα0 estimations were both potentially reliable indicators of tissue thermal damage. In addition, Δβ and Δα0 images both had significantly higher contrast-to-speckle ratios compared to the conventional B-mode images and outperformed the B-mode images in detecting HIFU thermal lesions at all investigated TAPs and exposure durations.

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.

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 $^\circ {\kern-0.70007pt}\text{C}$ and 0.5 $^\circ {\kern-0.70007pt}\text{C}$ , 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.

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.

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 (

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.

Frequency compounding is an ultrasound imaging technique used to improve signal-to-noise ratio (SNR). In this work, a nonlinear frequency compounding (NLFC) method was introduced, and its application in noninvasive tissue thermometry investigated. The NLFC method was used to produce two-dimensional maps of the temperature sensitive change in backscattered energy of acoustic harmonics (hCBE), during heating of ex vivo porcine tissue with a low intensity focused ultrasound transducer. A hCBE-to-temperature calibration was performed, and temperature maps produced and compared with a theoretical COMSOL based model. Last, a comparative study of the NLFC and previously used nonlinear single frequency (NLSF) methods was completed to quantify the improvement in SNR of the produced hCBE maps. When using the NLFC method, a SNR of 6.06 ± 1.28 was found. SNR values of 3.70 ± 0.53 and 4.38 ± 0.84 were found while using central frequencies of 4.31 and 5.43 MHz, respectively, with the NLSF method. This translates to an improvement of (64.13 ± 4.16)% over the 4.31 MHz NLSF, and (38.72 ± 2.97)% over the 5.43 MHz NLSF methods overall. It was concluded that the NLFC method can produce hCBE and temperature maps with superior image SNR over the NLSF method.

A real-time and non-invasive thermometry method is crucial for thermal therapies to monitor and control the treatment. Ultrasound can be used as an attractive thermometry modality for its relatively high sensitivity to change in temperature and fast data collection and processing abilities. In this work, an ultrasound thermometry method based on the change in backscattered energy (CBE) is used to control the tissue temperature using a closed-loop controller in real-time. A clinical high-frequency ultrasound scanner was used to acquire RF echo data from ex vivo porcine tissue samples while the tissue was being exposed to an interstitial laser heating source. The control system was used to rapidly increase the temperature from 37°C (baseline temperature) to 43 °C (target temperature) and maintain the target temperature for about 6 minutes. The results show that the ultrasound thermometry based on CBE generated by a high-frequency ultrasound scanner can be used to generate 2D temperature maps of a localized heating region in the hyperthermia temperature range (∼43°C). The estimated temperature varied by an average of ±0.8 °C compared to a calibrated fiber-optic measurement. Thus, a non-invasive ultrasound thermometry method based on the CBE technique can be used for real-time monitoring and control of hyperthermia treatments, using the interstitial laser heating source with acceptable accuracy.

Synthetic aperture focusing techniques (SAFT) make the lateral spatial resolution of the conventional ultrasound imaging from a single-element focused transducer more uniform. In this work, two new frequency-domain SAFT (FD-SAFT) algorithms are proposed, which are based on 2D matched filtering techniques. The first algorithm is the FD-SAFT virtual disk source (FD-VDS) that treats the focus of a focused transducer as a finite sized virtual source and the diffraction effect in the far-field is accounted for in the image reconstruction. The second algorithm is the FD-SAFT deconvolution (FD-DC) that uses the simulated point spread function of the imaging system as a matched filter kernel in the image reconstruction. These algorithms were implemented for pulsed and linear frequency modulated chirp excitations. The performance of these algorithms was studied using a series of simulations and experiments, and it was compared with the conventional B-mode and time-domain virtual point source SAFT (TD-VPS) 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 tissue image quality. The results showed that the FD-VDS had the highest spatial resolution and FD-DC had the second highest spatial resolution. In addition, FD-DC had generally the highest SNR. The computation run time of the proposed methods was significantly lower than the TD-VPS. Furthermore, chirp excitation improves the SNR of all methods by about 8 dB without significantly affecting the spatial resolution and sidelobe level. Thus, the FD-VDS and FD-DC methods offer efficient solutions to make the spatial resolution of conventional B-mode imaging more uniform.

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.

In the present work we have designed a novel gold nanoparticle (GNP) based nanodrug delivery system, which has been loaded with a naturally occurring anticancer molecule, curcumin. GNPs were selected as drug carrier due to their unique properties including high surface area, small size, inertness, low toxicity and high stability. The drug delivery system was synthesized by a green, one pot method which involved simple mixing of reactants, with no heating or toxic chemicals. Additionally, GNPs also display intrinsic anti-cancer attributes on their own, which is expected to further amplify the anticancer effect of the system. Curcumin release was activated by a handheld low intensity pulsed ultrasound (LIPUS) device. It is hypothesized that the moderate rise in tissue temperature (up to 43°C) together with mechanical effects of LIPUS beam induces effective release of curcumin from the surface of GNP. The developed nanodrug delivery system was characterized by UV-vis spectroscopy, fluorescence and hyperspectral imaging.

In order for a prescribed thermal dose to be delivered accurately during thermotherapy, the availability of a reliable and robust thermometry technique is of the utmost importance. To this end, an ultrasound based nonlinear single frequency method (NLSF) was originally proposed by our group, based on the temperature sensitive change in acoustic harmonics backscattered energy. The NLSF, however, suffers from limitations in that it produced high standard deviation and low signal-to-noise ratio (SNR) when performing temperature calibrations was applied to tissue thermometry. In this work a novel nonlinear frequency compounding (NLFC) method is introduced, which utilizes the advantages of frequency compounding to improve SNR. All NLFC input parameters were optimized to maximize SNR of both B-mode and backscattered energy images in a tissue mimicking phantom. The NLFC method was then used to produce 2D temperature maps for heating and cooling of ex vivo porcine tissue samples with a focused ultrasound transducer. The new NLFC method was able to produce superior temperature maps over the previously developed NLSF with percent improvements of up to 64.1%.

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.

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.

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.

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 modeconversionattheskullsurface. Thespeedoftheproposedframeworkisevaluated. Wevalidate 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.

Despite the promising results of the recent novel transcranial photoacoustic (PA) brain imaging technology, it has been demonstrated that the presence of the skull severely affects the performance of this imaging modality. We theoretically investigate the effects of acoustic heterogeneity induced by skull on the PA signals generated from single particles, with firstly developing a mathematical model for this phenomenon and then explore experimental validation of the results. The model takes into account the frequency dependent attenuation and dispersion effects occur with wave reflection, refraction and mode conversion at the skull surfaces. Numerical simulations based on the developed model are performed for calculating the propagation of photoacoustic waves through the skull. The results show a strong agreement between simulation and ex-vivo study. The findings are as follow: The thickness of the skull is the most PA signal deteriorating factor that affects both its amplitude (attenuation) and phase (distortion). Also we demonstrated that, when the depth of target region is low and it is comparable to the skull thickness, however, the skull-induced distortion becomes increasingly severe and the reconstructed image would be strongly distorted without correcting these effects. It is anticipated that an accurate quantification and modeling of the skull transmission effects would ultimately allow for aberration correction in transcranial PA brain imaging.

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.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.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.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.

The thermal mechanism of acoustic modulation of the reversible electrical activities of peripheral nerves is investigated using the soliton model, and a numerical solution is presented for its non-homogenous version. Our results indicate that heating a small segment of the nerve will increase the action potential conduction velocity and decrease its amplitude. Moreover, cooling the nerve will have the reverse effects, and cooling to temperatures below the nerve melting point can reflect back a significant portion of the action potentials. These results are consistent with the theory of the soliton model, as well as with the experimental findings. Although there exists a discrepancy between the results of the soliton model and experimental pulse amplitude data, from the free energy point of view, the experiments are compatible with Heimburg and Jackson theory. We conclude that the presented model accompanied by the free energy view is capable of simulating the effects of thermal energy on nerve function. One potential application of the developed theoretical model will be investigation of the reversible and irreversible effects of thermal energy induced by various energy modalities, including therapeutic ultrasound, on nerve function.

Time-delay estimation determines the relative displacement between two ultrasound echo signals. In this paper, we propose a new time-delay estimation algorithm which uses only the sign function to obtain the corresponding timedelay estimate. The performance of the proposed algorithm was compared with two established algorithms, i.e., normalized cross-correlation (NCC) and sum of squared differences (SSD), using metrics such as statistical analysis and computational time. All simulated ultrasound echo signals were generated using ultrasound simulation software. The results indicated that overall, the proposed algorithm had similar accuracy and precision compared with the NCC and SSD algorithms; however, the computational time of the proposed algorithm was about 70% less than NCC and SSD, which showed a significant improvement.

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.

This paper presents a method for modeling and simulation of shear wave generation from a nonlinear Acoustic Radiation Force Impulse (ARFI) that is considered as a distributed force applied at the focal region of a HIFU transducer radiating in nonlinear regime. The shear wave propagation is simulated by solving the Navier’s equation from the distributed nonlinear ARFI as the source of the shear wave. Then, the Wigner-Ville Distribution (WVD) as a time-frequency analysis method is used to detect the shear wave at different local points in the region of interest. The WVD results in an estimation of the shear wave time of arrival, its mean frequency and local attenuation which can be utilized to estimate medium’s shear modulus and shear viscosity using the Voigt model.

Bone quantity, as determined by the current gold standard, dual energy X-ray absorptiometry (DXA), through measured areal bone mineral density (aBMD), is subject to positive biases if bone strontium levels are high. This is of particular concern for populations administered strontium-based compounds for the treatment of osteoporosis. This study investigated the dependence of bone mineral density (BMD) determinations, and associated ultrasound-determined indices, obtained by quantitative ultrasound (QUS), on bone strontium content using a new generation of trabecular bone-mimicking phantoms.A new generation of bone-mimicking phantoms, consisting of hydroxyapatite (HA) and gelatin, was developed. Castor oil layers were included in these phantoms to create a multilayer bone-mimicking phantom. These phantoms were prepared using a bone mineral fraction consisting of varying strontium concentrations in the range of 0-2.5% mol/mol as strontium-substituted HA. The effect of varying bone strontium content on determined quality indices was evaluated based on determined speed of sound (SOS), broadband ultrasound attenuation (BUA) and determined quantitative ultrasound index (QUI) for phantoms with varying BMD values and varying strontium concentration using two QUS systems: a clinical Sahara® system and an in-house research system with two identical transducers with center frequency of 1 MHz. The two QUS systems were also compared through a Bland-Altman analysis.Both the clinical system and the research QUS systems showed a strong dependency between BMD and BUA, indicating a potential for QUS to be used as a means of estimating BMD (p = 0.001). SOS was found to have no correlation to BMD (p = 0.546). There was no correlation observed between BUA and increasing bone strontium concentrations for the research (p = 0.749) and clinical (p = 0.609) QUS systems. Similarly, no dependency was observed between the SOS and bone strontium levels up to 2.5 mol/mol [Sr/(Sr+Ca)]% for the research (p = 0.862) and clinical (p = 0.481) QUS systems. No effect on the QUI values was observed with changing strontium levels with either research (p = 0.939) or clinical QUS systems (p = 0.931). A Bland-Altman analysis showed that there was a clear offset in determined QUI values for both systems but they are in agreement with one another.Bone quality can be assessed through the use of QUS while increasing bone strontium concentration was found to have no effect on QUS-determined quality indices. This study concludes that QUS can potentially be used for the determination of bone quality without introducing biases due to bone strontium levels as is known to be the case with DXA determined aBMD.

This paper proposes a new numerical framework to simulate ultrasound wave propagation in 3D viscoelastic heterogeneous media based on the elastodynamic wave equation including a 3D second-order time-domain perfectly matched layer formulation. A finite difference discretization of this formulation is presented, along with a stability analysis. The resulting model is capable of simulating 3D shear and longitudinal acoustic waves for arbitrary source geometries and excitations, together with arbitrary initial and boundary conditions. A simulation example is provided to show the application of our proposed method for tissue elastography imaging. Specifically, the propagation of shear waves from a localized lesion to the surrounding normal tissue is examined.

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.

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 were 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. This article is protected by copyright. All rights reserved.

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.