Method to estimate the deviation from ideal uniaxial compression during freehand elastography.

Quasi-static ultrasound elastography was introduced in the early 1990s to provide a way to visualize the mechanical properties of target tissue. Most commonly, only the axial strain is imaged and referred to as an Axial Strain Elastogram (ASE) or elastogram for simplicity. It has been shown that one can image the axial-shear strain distributions as well in addition to ASE. The image of the axial-shear strain is referred to as an axial-shear strain elastogram (ASSE). It has also been shown that the presence or absence of non-zero axial-shear strain values inside the inclusion (referred to as fill-in) along with contrasting margin at its boundary may serve as a potential feature from ASSE that can aid in non-invasive breast lesion classification. However, during freehand elastography, deviations from uniaxial compression often occur typically appearing in several of the frames of a cine-loop obtained during compression. It was shown recently that accounting for such deviations would be important for reliable interpretation of the "fill-in" observed in ASSE. In this article, we describe a method to estimate the angle of iso-displacement contour at a given depth and use this as a measure to quantify the deviation from the desired uniaxial compression during freehand elastography. We validate the estimated angle obtained from the axial-displacement map against the designed values in simulation and tissue-mimicking phantom experiments. The potential of the angle estimate to detect unreliable ASSE frames among the freehand-acquired data cine-loop is demonstrated using example cases of in vivo breast lesion data. Based on the results, we conclude that the angle of the iso-displacement contour from the axial-displacement map can be used as a metric to qualify an ASSE frame as reliable to interpret or not. Importantly, this metric can be obtained in real time and thus can provide operator feedback to guide and improve in vivo freehand elastography data acquisition quality.

An analysis of the segmentation threshold used in axial-shear strain elastography.

Axial-shear strain elastography was introduced recently to image the tumor-host tissue boundary bonding characteristics. The image depicting the axial-shear strain distribution in a tissue under axial compression was termed as an axial-shear strain elastogram (ASSE). It has been demonstrated through simulation, tissue-mimicking phantom experiments, and retrospective analysis of in vivo breast lesion data that metrics quantifying the pattern of axial-shear strain distribution on ASSE can be used as features for identifying the lesion boundary condition as loosely-bonded or firmly-bonded. Consequently, features from ASSE have been shown to have potential in non-invasive breast lesion classification into benign versus malignant. Although there appears to be a broad concurrence in the results reported by different groups, important details pertaining to the appropriate segmentation threshold needed for - (1) displaying the ASSE as a color-overlay on top of corresponding Axial Strain Elastogram (ASE) and/or sonogram for feature visualization and (2) ASSE feature extraction are not yet fully addressed. In this study, we utilize ASSE from tissue mimicking phantom (with loosely-bonded and firmly-bonded inclusions) experiments and freehand - acquired in vivo breast lesion data (7 benign and 9 malignant) to analyze the effect of segmentation threshold on ASSE feature value, specifically, the "fill-in" feature that was introduced recently. We varied the segmentation threshold from 20% to 70% (of the maximum ASSE value) for each frame of the acquisition cine-loop of every data and computed the number of ASSE pixels within the lesion that was greater than or equal to this threshold value. If at least 40% of the pixels within the lesion area crossed this segmentation threshold, the ASSE frame was considered to demonstrate a "fill-in" that would indicate a loosely-bonded lesion boundary condition (suggestive of a benign lesion). Otherwise, the ASSE frame was considered not to demonstrate a "fill-in" indicating a firmly-bonded lesion boundary condition (suggestive of a malignant lesion). The results demonstrate that in the case of in vivo breast lesion data the appropriate range for the segmentation threshold value seems to be 40-60%. It was noted that for a segmentation threshold within this range (for example, at 50%) all of the analyzed breast lesion cases can be correctly classified into benign and malignant, based on the percentage number of frames within the acquisition cine-loop that demonstrate a "fill-in".

Dynamic frame pairing in real-time freehand elastography.

Quasi-static ultrasound (US) elastography is now a well-established technique that involves acquiring US (RF/envelope) signals from an imaging plane before and after a small quasi-static compression to form axial strain elastograms (ASE). The image quality of the ASEs is a function of the applied axial strain. This relationship was extensively investigated and formalized in terms of strain filter in the literature. Most of the work in elastography formed elastograms by choosing pre- and post-compression frames separated by a desired compression strain. Although this approach is feasible in simulations and in vitro/in vivo experiments that involve controlled compression, it has been a challenge to do this during freehand compression in real time. In this work, we describe a one-prediction-one- correction method that dynamically selects pre- and post- compression frames to form an elastogram, based on the applied axial strain level. We validate the method using controlled compression experiments on phantoms and compare the performance of the dynamic frame pairing method against successive-frame pairing method in terms of the contrast-to-noise ratio (CNRe). Further, we demonstrate the advantages of the new method with the help of freehand acquired data from phantom experiments and in vivo breast data. The results demonstrate that the frame-pairing identified by the dynamic method matched the frame pairing that was designed to yield an applied axial strain of ~1%. The CNRe obtained by the traditional approach varied from as low as ~5 to as high as ~25, depending on the choice of skip number and compression rate. However, the dynamic frame pairing method provided elastograms with a CNRe that was consistently around ~20, irrespective of the compression rate. The results from analysis of 22 in vivo breast data demonstrated that the dynamic pairing method generated elastograms such that the frame-average axial strain (FAAS) of each frame in the cine-loop is consistently ~1% (0.011 ± 0.001).

Real-time monitoring of high-intensity focused ultrasound treatment using axial strain and axial-shear strain elastograms.

Axial strain elastograms (ASEs) have been found to help visualize sonographically invisible thermal lesions. However, in most studies involving high-intensity focused ultrasound (HIFU)-induced thermal lesions, elastography imaging was performed separately later, after the lesion was formed. In this article, the feasibility of monitoring, in real time, tissue elasticity variation during HIFU treatment and immediately thereafter is explored using quasi-static elastography. Further, in addition to ASEs, we also explore the use of simultaneously acquired axial-shear strain elastograms (ASSEs) for HIFU lesion visualization. Experiments were performed on commercial porcine liver samples in vitro. The HIFU experiments were conducted at two applied acoustic power settings, 35 and 20 W. The experimental setup allowed us to interrupt the HIFU pulse momentarily several different times during treatment to perform elastographic compression and data acquisition. At the end of the experiments, the samples were cut along the imaging plane and photographed to compare size and location of the formed lesion with those visualized on ASEs and ASSEs. Single-lesion and multiple-lesion experiments were performed to assess the contribution of ASEs and ASSEs to lesion visualization and treatment monitoring tasks. At both power settings, ASEs and ASSEs provided accurate location information during HIFU treatment. At the low-power setting case, ASEs and ASSEs provide accurate lesion size in real-time monitoring. Lesion appearance in ASEs and ASSEs was affected by the cavitation bubbles produced at the high-power setting. The results further indicate that the cavitation bubbles influence lesion appearance more in ASEs than in ASSEs. Both ASEs and ASSEs provided accurate size information after a waiting period that allowed the cavitation bubbles to disappear. The results indicate that ASSEs not only improve lesion visualization and size measurement of a single lesion, but, under certain conditions, also help to identify untreated gaps between adjacent lesions with high contrast.

SonoKnife for ablation of neck tissue: in vivo verification of a computer layered medium model.

PURPOSE: This study aimed to determine which treatment parameters of the SonoKnife device can be used to safely and effectively perform non-invasive thermal ablation of subcutaneous tissue. METHODS: A three-dimensional computational layered medium model was constructed to simulate thermal ablation treatment of the SonoKnife device. The acoustic and thermal fields were calculated with the Fast Object-Oriented C++ Ultrasound-Simulator software and a finite difference code, respectively. Subcutaneous tissue was represented as layers of skin, fat and muscle. The simulations were conducted for ultrasound frequencies of 1 or 3.5 MHz. The thermal dose model was used to predict the size and location of the ablated regions. The computer simulations were verified by using the SonoKnife to perform subcutaneous ablations in the neck area of healthy pigs, in vivo. Triphenyltetrazolium chloride viability stain was used to differentiate viable tissue from ablated regions ex vivo. RESULTS: The simulations for the layered medium model suggest that operating the SonoKnife at frequency of 1 MHz is more effective and safer than 3.5 MHz providing skin cooling is applied prior to ablation. These predictions were in agreement with the results observed in the animal studies. The required sonication time for ablation increased from 50 to 300 s by using 1 MHz. CONCLUSION: Our modelling and animal studies suggest that 1 MHz with pretreatment skin cooling are the optimal settings to operate the SonoKnife to safely and effectively perform subcutaneous thermal ablation of porcine skin. More work is needed to optimise skin cooling and define the optimal sonication time.

Cancer treatment using an optically inert Rose Bengal derivative combined with pulsed focused ultrasound.

Pulsed high intensity focused ultrasound (HIFU) has been combined with a photo-insensitive Rose Bengal derivative (RB2) to provide a synergistic cytotoxicity requiring the presence of both ultrasonic cavitation and drug. In vitro tests have shown that a short treatment (less than 30 s) of pulsed HIFU with peak negative pressure >7 MPa (~27 W acoustic power at 1.4 MHz) destroys >95% of breast cancer cells MDA-MB-231 in suspension with >10 µM of the compound. Neither the pulsed HIFU nor the RB2 compound was found to have any significant impact on the viability of the cells when used alone. Introducing an antioxidant (N-acetylcysteine) reduced the effectiveness of the treatment. In vivo tests using these same cells growing as a xenograft in nu/nu mice were also done. An ultrasound contrast agent (Optison) and lower frequency (1.0 MHz) was used to help initiate cavitation at the tumor site. We were able to demonstrate tumor regression with cavitation alone, however, addition of RB2 compound injected i.v. yielded a substantial synergistic improvement.

SonoKnife: feasibility of a line-focused ultrasound device for thermal ablation therapy.

PURPOSE: To evaluate the feasibility of line-focused ultrasound for thermal ablation of superficially located tumors. METHODS: A SonoKnife is a cylindrical-section ultrasound transducer designed to radiate from its concave surface. This geometry generates a line-focus or acoustic edge. The motivation for this approach was the noninvasive thermal ablation of advanced head and neck tumors and positive neck nodes in reasonable treatment times. Line-focusing may offer advantages over the common point-focusing of spherically curved radiators such as faster coverage of a target volume by scanning of the acoustic edge. In this paper, The authors report studies using numerical models and phantom and ex vivo experiments using a SonoKnife prototype. RESULTS: Acoustic edges were generated by cylindrical-section single-element ultrasound transducers numerically, and by the prototype experimentally. Numerically, simulations were performed to characterize the acoustic edge for basic design parameters: transducer dimensions, line-focus depth, frequency, and coupling thickness. The dimensions of the acoustic edge as a function of these parameters were determined. In addition, a step-scanning simulation produced a large thermal lesion in a reasonable treatment time. Experimentally, pressure distributions measured in degassed water agreed well with acoustic simulations, and sonication experiments in gel phantoms and ex vivo porcine liver samples produced lesions similar to those predicted with acoustic and thermal models. CONCLUSIONS: Results support the feasibility of noninvasive thermal ablation with a SonoKnife.

Partially polymerized liposomes: stable against leakage yet capable of instantaneous release for remote controlled drug delivery.

A critical issue for current liposomal carriers in clinical applications is their leakage of the encapsulated drugs that are cytotoxic to non-target tissues. We have developed partially polymerized liposomes composed of polydiacetylene lipids and saturated lipids. Cross-linking of the diacetylene lipids prevents the drug leakage even at 40 °C for days. These inactivated drug carriers are non-cytotoxic. Significantly, more than 70% of the encapsulated drug can be instantaneously released by a laser that matches the plasmon resonance of the tethered gold nanoparticles on the liposomes, and the therapeutic effect was observed in cancer cells. The remote activation feature of this novel drug delivery system allows for precise temporal and spatial control of drug release.

Comparison study of three different image reconstruction algorithms for MAT-MI.

In this paper, we report a theoretical study on magnetoacoustic tomography with magnetic induction (MAT-MI). According to the description of signal generation mechanism using Green's function, the acoustic dipole model was proposed to describe acoustic source excited by the Lorentz force. Using Green's function, three kinds of reconstruction algorithms based on different models of acoustic source (potential energy, vectored acoustic pressure, and divergence of Lorenz force) are deduced and compared, and corresponding numerical simulations were conducted to compare these three kinds of reconstruction algorithms. The computer simulation results indicate that the potential energy method and vectored pressure method can directly reconstruct the Lorentz force distribution and give a more accurate reconstruction of electrical conductivity.

Reconstruction of vectorial acoustic sources in time-domain tomography.

A new theory is proposed for the reconstruction of curl-free vector field, whose divergence serves as acoustic source. The theory is applied to reconstruct vector acoustic sources from the scalar acoustic signals measured on a surface enclosing the source area. It is shown that, under certain conditions, the scalar acoustic measurements can be vectorized according to the known measurement geometry and subsequently be used to reconstruct the original vector field. Theoretically, this method extends the application domain of the existing acoustic reciprocity principle from a scalar field to a vector field, indicating that the stimulating vectorial source and the transmitted acoustic pressure vector (acoustic pressure vectorized according to certain measurement geometry) are interchangeable. Computer simulation studies were conducted to evaluate the proposed theory, and the numerical results suggest that reconstruction of a vector field using the proposed theory is not sensitive to variation in the detecting distance. The present theory may be applied to magnetoacoustic tomography with magnetic induction (MAT-MI) for reconstructing current distribution from acoustic measurements. A simulation on MAT-MI shows that, compared to existing methods, the present method can give an accurate estimation on the source current distribution and a better conductivity reconstruction.

Confocal dual-frequency enhances the damaging effect of high-intensity focused ultrasound in tissue-mimicking phantom.

The volume of the lesions created by conventional single-frequency high-intensity focused ultrasound (HIFU) is small, which leads to long treatment duration in patients who are undergoing tumor ablation. In this study, the lesions induced by confocal dual-frequency HIFU in an optically transparent tissue-mimicking phantom were investigated and compared with the lesions created by conventional single-frequency HIFU. The results show that using different exposure times resulted in lesions of different sizes in both dual-frequency and single-frequency HIFU modes at the same spatially averaged intensity level (ISAL = 4900 W cm(-2)), but the lesion dimensions made in dual-frequency mode were significantly larger than those made in single-frequency mode. Difference frequency acoustic fields that exist in the confocal region of dual-frequency HIFU may be the reason for the enlargement of the lesions' dimensions. The dual-frequency HIFU mode may represent a new technique to improve the ablation efficiency of HIFU. The total time for the ablation of a tumor can be reduced, thus requiring less therapy time and reducing possible patient complications.

Acoustic vector tomography and its application to magnetoacoustic tomography with magnetic induction (MAT-MI).

A new tomographic algorithm for reconstructing a curl-free vector field, whose divergence serves as acoustic source is proposed. It is shown that under certain conditions, the scalar acoustic measurements obtained from a surface enclosing the source area can be vectorized according to the known measurement geometry and then be used to reconstruct the vector field. The proposed method is validated by numerical experiments. This method can be easily applied to magnetoacoustic tomography with magnetic induction (MAT-MI). A simulation study of applying this method to MAT-MI shows that compared to existing methods, the proposed method can give an accurate estimation of the induced current distribution and a better reconstruction of electrical conductivity within an object.

Magnetoacoustic tomographic imaging of electrical impedance with magnetic induction.

Magnetoacoustic tomography with magnetic induction (MAT-MI) is a recently introduced method for imaging tissue electrical impedance properties by integrating magnetic induction and ultrasound measurements. In the present study, we have developed a focused cylindrical scanning mode MAT-MI system and the corresponding reconstruction algorithms. Using this system, we demonstrated 3-dimensional MAT-MI imaging in a physical phantom, with cylindrical scanning combined with ultrasound focusing, and the ability of MAT-MI in imaging electrical conductivity properties of biological tissue.

Acoustic power measurement of high intensity focused ultrasound in medicine based on radiation force.

How to measure the acoustic power of HIFU is one of the most important tasks in its medical application. In the paper a whole series of formula for calculating the radiation force related to the acoustic power radiated by a single element focusing transducer and by the focusing transducer array were given. Various system of radiation force balance (RFB) to measure the acoustic power of HIFU in medicine were designed and applied in China. In high power experiments, the dependence of radiation force acting the absorbing target on the target position at the beam axis of focusing transducer was fined. There is a peak value of "radiation force" acting the absorbing target in the focal region when the acoustic power through the focal plane exceeds some threshold. In order to avoid this big measurement error caused by the 'peak effect' in focal region, the distance between the absorbing target of RFB and the focusing transducer or transducer array was defined to be equal to or less than 0.7 times of the focal length in the National Standard of China for the measurements of acoustic power and field characteristics of HIFU. More than six different therapeutic equipments of HIFU have been examined by RFB for measuring the acoustic power since 1998. These results show that RFB with the absorbing target is valid in the acoustic power range up to 500W with good linearity for the drive voltage squared of focusing transducer or array. The uncertainty of measurement is within +/-15%.

Calibration of a focusing transducer and miniature hydrophone as well as acoustic power measurement based on free-field reciprocity in a spherically focused wave field.

The free-field transmitting voltage response at the pressure focus of a spherically focusing transducer was defined and calibrated based on the reciprocity theorem of a free-field spherically focused acoustic wave. The acoustic power, the radiation conductance, and the pressure at the pressure focus were derived and measured accordingly from the transmitting current response on the imaginary mirror symmetric spherical surface of the radiating surface. A miniature hydrophone was calibrated by the self-reciprocity of the spherically focusing source. Comparison results show that the measured acoustic power deviation between the reciprocity method and the radiation force balance method are within +/- 5% for two air-backed focusing transducers at 1.53 MHz and 5.27 MHz, respectively, and the maximum deviation of a hydrophone calibration between the new method and the free-field plane wave reciprocity method is within 1.4 dB in the frequency range from 1 MHz to 2 MHz in experiments.