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Applied Current Thermoacoustic Imaging (ACTAI) is a new imaging method which combines electromagnetic excitation with ultrasound imaging, and takes ultrasonic signal as medium and biological tissue conductivity as detection target. Taking the high contrast advantage of Electrical Impedance Tomography (EIT) and high resolution advantage of ultrasound imaging, ACTAI has broad application prospects in the field of biomedical imaging. Although ACTAI has high excitation efficiency and strong detectable Signal-to-Noise Ratio, yet while under low frequency electromagnetic excitation, it is still a big challenge to reconstruct a high-resolution image of target conductivity. This paper proposes a new method for reconstructing conductivity based on Generative Adversarial Network, and it consists of three main steps: firstly, use Wiener filtering deconvolution to restore the electrical signal output by the ultrasonic probe to a real acoustic signal. Then obtain the initial acoustic source image with filtered backprojection technology. Finally, match the conductivity image with the initial sound source image, which are used as training samples for generating the adversarial network to establish a deep learning model for conductivity reconstruction. After theoretical analysis and simulation research, it is found that by introducing machine learning, the new method can dig out the inverse problem solving model contained in the data, which further reconstruct a high-resolution conductivity image and has strong anti-interference characteristics. The new method provides a new way to solve the problem of conductivity reconstruction in Applied Current Thermoacoustic Imaging.

In recent years, there has been a progressive trend towards less invasive technologies for detecting metastatic cancer and guiding therapy with the goal of lower morbidity, better outcomes, and superior cosmetic appearance than traditional methods. This mini-review examines three emerging noninvasive hybrid technologies for detecting primary cancer, metastasis and guiding thermal therapy. Real-time thermoacoustic imaging and thermometry potentially provides valuable and critical feedback for guiding focused microwave ablation therapy. Label-free photoacoustic monitoring of cancer cells is a promising clinical diagnostic and theranostic tool for detecting metastatic disease and monitoring the response to therapy. Finally, immunologically targeted gold nanoparticles combined with photoacoustic imaging is able to detect lymph node micrometastasis in mouse models of breast cancer. These emerging techniques have the potential to improve the decision to biopsy, provide more accurate prognosis, and enhance the efficacy of therapy for early and late stage cancers.

Purpose Liver disease causes significant morbidity and mortality worldwide. Liver imaging plays an essential role in the noninvasive liver disease evaluation because of the limitation of liver biopsy. This paper aims to image in vivo liver with thermoacoustic imaging (TAI) and demonstrate this liver imaging technique with a cross-validation method. Methods The imaging system composed of a large aperture antenna and a flexible transducer array was used, and we performed the position calibration using the delay and sum algorithm. The localization wire was utilized in the cross-validation of in vivo liver TAI. Results We successfully validated in vivo liver TAI. In vivo images of different liver lobes without labels were observed. The imaging depth reached about 4 cm. Conclusions TAI has the potential to image the liver and provide useful dielectric properties of the liver tissue. This study realized the first in vivo liver TAI, suggesting its prospect in detecting liver disease noninvasively.

Purpose: To investigate the feasibility of microwave-induced thermoacoustic imaging (MTAI) in detecting small pancreatic tumors (< 10 mm in diameter) and to complement the limitation of current clinical imaging methods. Methods: A home-made MTAI system composed of a portable antenna and pulsed microwave generator was developed. The thermoacoustic nanoparticles were composed of the galectin-1 antibody for targeting pancreatic tumors and Fe3O4 nanoparticles as microwave absorbers (anti-Gal1-Fe3O4 nanoparticles). The microwave absorption properties of the nanoparticles were measured with a vector network analyzer and the resolving power of MTAI was investigated by imaging excised pancreatic tumors of different sizes (diameters of 1.0 mm, 3.1 mm, 5.0 mm, 7.2 mm). To simulate actual imaging scenarios, an in vivo heterozygosity model was constructed by covering the pancreatic tumors (~ 3 mm in diameter) in BALB/c nude mice with biologic tissue (~ 5 cm in depth). MTAI images of the heterozygosity model were acquired with/without the injection of the anti-Gal1-Fe3O4 nanoparticles and the thermoacoustic contrast from pancreatic tumors was evaluated with Student's paired t test. The data were analyzed with analysis of variance and nonparametric statistics. Results: Following intravenous infusion, anti-Gal1-Fe3O4 nanoparticles efficiently accumulated in the tumor. The MTAI contrast enhancement in pancreatic tumors with anti-Gal1-Fe3O4 nanoparticles was verified in vitro and in vivo. The pancreatic tumors were visible in nude mice examined with MTAI with a mean contrast enhancement ratio of 2.3 ± 0.15 (standard error of the mean) (P =. 001) at 6 h post-injection of the nanoparticles. MTAI identified tiny pancreatic tumors in deep tissues with high fidelity. Conclusion: MTAI offers deep imaging depth and high contrast when used with anti-Gal1-Fe3O4 nanoparticles. It can identify pancreatic tumors smaller than 5 mm, which is beyond the identification limit size (~10 mm) of other nondestructive clinical imaging methods. Thus, MTAI has great potential as an alternative imaging modality for early pancreatic cancer detection.

Thermoacoustic (TA) thermometry requires calibration to establish the relationship between the change in TA signal with the change in temperature. Previous studies have used a priori slopes values (i.e. TA signal vs temperature), typically determined experimentally from previously performed standard calibrations. However, standard calibration requires more than one test and is not robust to changing sample orientation or composition. The goal of this study is to compare a previously studied self-calibration method to the standard calibration method in estimating temperature using real-time 3D TA thermometry in bovine udder tissue kept in the same orientation for both methods. The self-calibration and standard methods estimated temperatures of the udder sample during localized heating with a normalized root mean square errors (NRMSE) of 7.1% and 8.4%, respectively. The predicted temperatures produced by the self-calibration method were less variable than the standard method. Overall, the qualitative and quantitative results comparing predicted change in temperature suggested that self-calibration is as accurate as standard calibration with less variability and less experimentation. These advantages point to self-calibration being a more preferred method to provide temperature predictions for feedback control in future breast cancer ablation therapy.

Abnormal hematocrit (Hct) is associated with an increased risk of pre-hypertension and all-cause death in general population, and people with a high Hct value are susceptible to arterial cardiovascular disease and venous thromboembolism. In this study, we report for the first time on the ability of thermoacoustic imaging (TAI) for in vivo evaluating Hct changes in human forearms. In vitro blood samples with different Hct values from healthy volunteers (n = 3) were prepared after centrifugation. TAI was performed using these samples in comparison with the direct measurements of conductivity. In vivo TAI was conducted in the forearm of healthy volunteers (n = 7) where Hct changes were produced through a vascular occlusion stimulation over a period of time. The results of in vitro blood samples obtained from the 3 healthy subjects show that the thermoacoustic (TA) signals changes due to the variation of blood conductivity are closely related to the changes in Hct. In addition, the in vivo TA signals obtained from the 7 healthy subjects consistently increase in the artery/muscle and decrease in the vein during venous or arterial occlusion because of the changed Hct value in their forearms. These findings suggest that TAI has the potential to become a new tool for monitoring Hct changes for a variety of pre-clinical and clinical applications.

Purpose To study the possibility of thermoacoustic imaging (TAI) toward hemorrhagic stroke detection. Methods A single-transducer circular-scanning TAI system was used for data collection. An agar powder-based, tissue-mimicking phantom enclosed by a human skull was applied to simulate the brain for thermoacoustic imaging of hemorrhagic stroke. Results Several phantom experiments mimicking hemorrhagic stroke detection were conducted, and the results showed that “hemorrhagic” targets as small as 0.9 mm in diameter could be detected. Conclusions This study suggests that TAI has the potential to be used for noninvasive hemorrhagic stroke detection and identification of hemorrhagic from ischemic stroke.

Purpose: Knee joint is one of the largest and most complex joints of the body. Knee joint diseases are common, and current clinical imaging technologies such as x-ray computed tomography, magnetic resonance imaging, and ultrasound imaging have limitations in the diagnosis of knee joint diseases. Emerging imaging technologies such as diffuse optical tomography and photoacoustic imaging (PAI) have been applied to the detection of osteoarthritis (OA). However, they are limited to small joints such as the finger and difficult to be used for large joints such as the knee. Thermoacoustic imaging (TAI), also an emerging modality, provides high contrast and deep tissue penetration. Here, the authors apply TAI to the knee joint and demonstrate the potential of TAI for imaging large joints. Methods: Adult New Zealand male rabbits (average weight = 2 kg) were chosen for this study. In a TAI experiment, a rabbit was placed in a holder to keep in a genuflex position after being injected with pentobarbital through its ear margin intravenous (30 mg/kg). The holder and the rabbit were then positioned under the horn antenna of the TAI system for signal acquisition and image reconstruction. After the experiment, the imaged knee joint was dissected and photographed. Identical procedures were performed for several rabbits (n = 4). Finally, detailed comparative analyses between TAI images and anatomical pictures of the knee joint were conducted. Results: There were high similarities between the reconstructed TAI images and anatomical pictures of the knee joint, in terms of the shape and size of various knee joint tissues. TAI could clearly image ligament, fat pad, and other joint tissues. The differences in appearance of TAI images due to motion effect of the knee joint were also discussed. Conclusions: TAI could reveal details of rabbit knee joint in high resolution. As the recovered TAI images represent the dielectric property distributions of joint tissues, TAI may offer a new tool for noninvasive detection of joint diseases such as OA.

The evolution of neurosurgery has been, and continues to be, closely associated with innovations in technology. Modern neurosurgery is wed to imaging technology and the future promises even more dependence on anatomic and, perhaps more importantly, functional imaging. The photoacoustic phenomenon was described nearly 140 yr ago; however, biomedical applications for this technology have only recently received significant attention. Light-based photoacoustic and microwave-based thermoacoustic technologies represent novel biomedical imaging modalities with broad application potential within and beyond neurosurgery. These technologies offer excellent imaging resolution while generally considered safer, more portable, versatile, and convenient than current imaging technologies. In this review, we summarize the current state of knowledge regarding photoacoustic and thermoacoustic imaging and their potential impact on the field of neurosurgery.

Non-invasive temperature monitoring of tissue at depth in real-time is critical to hyperthermia therapies such as high-intensity focused ultrasound. Knowledge of temperature allows for monitoring treatment as well as providing real-time feedback to adjust deposited power in order to maintain safe and effective temperatures. Microwave-induced thermoacoustic (TA) imaging, which combines the conductivity/dielectric contrast of microwave imaging with the resolution of ultrasound, shows potential for estimating temperature non-invasively in real-time by indirectly measuring the temperature dependent parameters from reconstructed images. In this work, we study the temperature dependent behavior of the generated pressure in the TA effect and experimentally demonstrate simultaneous imaging and temperature monitoring using TA imaging. The proof-of-concept experiments demonstrate millimeter spatial resolution while achieving degree-level accuracy.

Background: Tissue mechanical parameters such as elasticity are of great significance for the assessment of biological histopathological and physiological characteristics. Here, we propose a new approach called thermoacoustic elastography (TAE) for imaging tissue elastic modulus. Methods: Central to TAE is an image reconstruction algorithm that allows the recovery of both microwave energy loss and elastic modulus distributions. The algorithm is first evaluated using simulated data under various practical scenarios, including a varied range of microwave energy loss and elastic modulus between the heterogeneity and background region, different noise levels, and multiple targets. The feasibility of the proposed TAE was then validated by imaging the elastic modulus distribution of agar phantoms with various elastic modulus and microwave energy loss. Results: The results from both the simulated and phantom experiments show that the recovered elastic modulus by TAE agree well with the exact values, having an average error of less than 12.74%. Conclusions: The findings from this study suggest that TAE provides a new addition to the family of elasticity imaging and may have broad application prospects, such as cirrhosis and atherosclerosis detection.

Towards clinical application for breast cancer detection, phantom experiments were conducted to optimize our thermoacoustic imaging (TAI) system. We compared the imaging performance of the conventional horn antenna (HA)-based and a new handheld dipole antenna (HDA)-based TAI systems. We determined that the HAD-based TAI outperformed the HA-based TAI. We then conducted experiments to determine the best angle of the HAD relative to a breast-shaped phantom, and found that the best image quality was obtained when the angle was 90 degrees.

Thermoacoustic imaging (TAI) is used to in vivo image rabbit knee joints and human index fingers. The results show that TAI is able to reveal various joint tissues and bones based on the tissue dielectric property distributions. This provides a foundation for TAI’s clinical applications for detection of joint and bone diseases.

Background and objective Microwave-induced thermoacoustic imaging (MITAI) represents an innovative imaging approach for detection of breast cancer at initial phases by integrating the benefits provided by procedures of microwave and ultrasound imaging. The present investigation examines an innovative three-dimensional numerical modeling of MITAI as a problem with multi-physics nature. Methods Simulations are performed by the use of COMSOL software. An anatomically realistic breast phantom representing various parts of a real breast, such as three different types of tissue, fibro-connective/glandular, transitional; and fatty, is taken into consideration along with a tumor. This breast phantom with a tumor is irradiated by a 2.45 GHz pulsed rectangular waveguide. The temperature increase and its consequent pressure caused by electromagnetic absorption are analyzed. Results More temperature increase occurs in the tumor area than in the other parts of the breast, the fact which results in further increase in the pressure in the tumor area than other parts. This makes the tumor distinguishable. The ability of the MITAI process regarding the tumor size, shape (both geometrical shape and spatial orientation), location, the irradiation power level, and the pulse width is also investigated. It is demonstrated that tumor size does not have a significant impact on the efficiency of detection. In fact, very small tumors in the early stages of cancer development (with a radius of 0.25 cm) are also detectable by employing the MITAI technique. The geometrical shape of the tumor does not considerably affect the detecting performance just by itself. The spatial orientation of the tumor actually has a great impact on it. The location of the tumor is an essential factor involved in detection efficiency of MITAI. Tumors located in the fatty tissues would be much easier to be detected than those in the glandular tissues. Moreover, results denote that with augmentation of the irradiation power level or increasing the pulse width, stronger acoustic waves would be produced to make tumor detection easier. Conclusion These modeling and techniques may be applied aiming for determination of the amount of the generated pressure differences and acoustic pressure magnitude, and can be utilized as an effective prognosticator in practical tests.

Microwave imaging (MWI) and microwave thermoacoustic imaging (MTAI) show great potential for early- stage breast tumor detection. MWI suffers from low spatial resolution for accurate diagnosis, while MTAI is unable to provide quantitative dielectric information and its image quality degrades due to acoustic heterogeneity of breast tissue. To compensate for these drawbacks, we propose a microwave-based dual imaging modality, by combining the conventional MWI and MTAI, for breast tumor detection. First, a low-resolution MWI image will be utilized to provide a rough estimate of the high-dielectric region in breast. Then, the high-dielectric region will be incorporated in MTAI reconstruction to mitigate the acoustic heterogeneity effect. Finally, medical images with ultrasonic resolution and quantitative dielectric information of breast tissue can be ob- tained. We verified this idea by imaging anatomically realistic numerical breast phantoms. Simulation results demonstrate the feasibility of the proposed dual imaging modality by significantly improving the image fidelity and providing quantitative dielectric information.

This work proposes the design of a monitoring system based on thermoacoustic imaging for breast cancer hyperthermia. The monitoring technique is improved compared to previously reported works. Detailed design procedure of three parts of the system is introduced. Practical experimental system based on this work can be built to validate the thermo acoustic monitoring technique.

We present preliminary data for a novel platform that integrates focused microwave therapy (FMT) with thermoacoustic imaging (TAI) for mapping temperature, quantifying the heat zone, and guiding the delivery of focused heat. The longterm objectives of this study are to 1) Design and build an image-guided FMT system that is noninvasive, safe and effective for treating small or large locally aggressive solid breast tumors as a possible replacement or complement to invasive surgery; 2) Benchmark performance and optimize TAI-guided FMT platform using in numerical breast phantom and excised tissue. We present the overall system concept, numerical simulations and initial bench-top results related to the proposed platform.

A novel real-time monitoring method is presented based on thermoacoustic imaging for applications in breast cancer hyperthermia. In the proposed technique, thermoacoustic imaging combined with compressive sensing is implemented to improve monitoring efficiency. Numerical modeling work is done using a breast phantom, which has realistic dielectric properties and internal structures, to validate feasibility of the presented technique. Results of the modeling work clearly show the effectiveness of the monitoring method. This technique can also find applications in other types of hyperthermia.

Intraoperative imaging (IOI) is performed to guide delineation and localization of regions of surgical interest. While oncological surgical planning predominantly utilizes x-ray computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US), intraoperative guidance mainly remains on surgeon interpretation and pathology for confirmation. Over the past decades however, intraoperative guidance has evolved significantly with the emergence of several novel imaging technologies, including fluorescence-, Raman, photoacoustic-, and radio-guided approaches. These modalities have demonstrated the potential to further optimize precision in surgical resection and improve clinical outcomes for patients. Not only can these technologies enhance our understanding of the disease, they can also yield large imaging datasets intraoperatively that can be analyzed by deep learning approaches for more rapid and accurate pathological diagnosis. Unfortunately, many of these novel technologies are still under preclinical or early clinical evaluation. Organizations like the Intra-Operative Imaging Study Group of the European Society for Molecular Imaging (ESMI) support interdisciplinary interactions with the aim to improve technical capabilities in the field, an approach that can succeed only if scientists, engineers, and physicians work closely together with industry and regulatory bodies to resolve roadblocks to clinical translation. In this review, we provide an overview of a variety of novel IOI technologies, discuss their challenges, and present future perspectives on the enormous potential of IOI for oncological surgical navigation.

In this chapter, a brief introduction of the conventional single-wave imaging and emerging multi-wave imaging modalities is provided to show the state-of-art in Sect. 1.1. Single-wave imaging modalities include optical imaging, microwave imaging and magnetic imaging spreading the whole EM spectrum, as well as ultrasound imaging, elastography, etc. Emerging multi-wave imaging modalities include laser-induced photoacoustic imaging, microwave-induced thermoacoustic imaging, magnetically mediated thermoacoustic imaging, etc. Then the research motivation and major contribution of this thesis is introduced in Sect. 1.2.

This article reports a real-time thermoacoustic imaging system for breast cancer screening. The experimental results show that it realizes the fast three-dimensional thermoacoustic imaging, therefore it has the potential to become a routine breast screening method.

We present a pilot study for the first time that microwave-induced thermoacoustic tomography (TAT) has the potential to detect osteoarthritis (OA) in the finger jointsin vitro. In this study, we use rabbit hind feet to imitate humans finger joints, one rabbits hind feet was examined carefully by a TAT scanner, and the two-dimensional (2D) thermoacoustic images were reconstructed by the delay-and-sum algorithm. The difference of absorption coefficient of bone and articular cartilage has been displayed clearly in the reconstruction images.

Here, we demonstrate that thermoacoustic imaging (TAI) is able to image human blood vessels in vivo without the use of any contrast agent. By optimizing the polarization direction of the antenna used, the microwave energy deposition in blood vessels is significantly enhanced, allowing the in vivo acquisition of thermoacoustic vascular images. Specifically, the fore arms of two adult male volunteers were imaged, and the blood vessels 5.5 mm below the skin in the forearm were recovered by TAI in both cross- and sagittal sections. Ultrasound imaging was used to cross-validate the images of blood vessels thermoacoustically imaged. The results obtained suggest that TAI may have the potential to become a new tool for examining vascular diseases.Here, we demonstrate that thermoacoustic imaging (TAI) is able to image human blood vessels in vivo without the use of any contrast agent. By optimizing the polarization direction of the antenna used, the microwave energy deposition in blood vessels is significantly enhanced, allowing the in vivo acquisition of thermoacoustic vascular images. Specifically, the fore arms of two adult male volunteers were imaged, and the blood vessels 5.5 mm below the skin in the forearm were recovered by TAI in both cross- and sagittal sections. Ultrasound imaging was used to cross-validate the images of blood vessels thermoacoustically imaged. The results obtained suggest that TAI may have the potential to become a new tool for examining vascular diseases.

Microwave-based thermoacoustic tomography (TAT), based on the measurement of ultrasonic waves induced by microwave pulses, can reveal tissue dielectric properties that may be closely related to the physiological and pathological status of the tissues. Using microwaves as the excitation source improved imaging depth because of their deep penetration into biological tissues. We demonstrate, for the first time, in vivo microwave-based thermoacoustic imaging in rats. The transducer is rotated around the rat in a full circle, providing a full two-dimensional view. Instead of a flat ultrasonic transducer, we used a virtual line detector based on a cylindrically focused transducer. A 3 GHz microwave source with 0.6 µs pulse width and an electromagnetically shielded transducer with 2.25 MHz central frequency provided clear cross-sectional images of the rat’s body. The high imaging contrast, based on the tissue’s rate of absorption, and the ultrasonically defined spatial resolution combine to reveal the spine, kidney, muscle, and other deeply seated anatomical features in the rat’s abdominal cavity. This non-invasive and non-ionizing imaging modality achieved an imaging depth beyond 6 cm in the rat’s tissue. Cancer diagnosis based on information about tissue properties from microwave band TAT can potentially be more accurate than has previously been achievable.

Purpose: Microwave-induced thermoacoustic tomography (TAT) is a noninvasive modality based on the differences in microwave absorption of various biological tissues. In this paper, the feasibility of the early breast tumor detection by TAT system has been discussed and validated experimentally. Methods: A fast TAT system, which based on three 128-elements transducers, a 384-64ch switch and a parallel data acquisition system (DAS), was developed to reconstruct the three-dimensional (3D) image of a breast model with similar microwaveabsorption coefficient to breast tissue. A novel method to explore the ability of TAT system to distinguish absorption coefficient was introduced and the minimum absorption coefficient difference that can be distinguished clearly by our TAT system is 12 m−1. Results: The potential applications of the TAT system were clearly demonstrated by successfully mapping breast model with mimicked tumors and microcalcification. An imaging experiment of human breast tumor embedding in the breast model was performed and the tumor was visualized by the 3D thermoacoustic volume. Conclusions: The thermoacousticimages match well with the samples and achieve penetration depth of 6 cm. The experimental results indicate that TAT has a great potential to be used for detecting early-stage breast cancers with high contrast and high resolution.

Multimodal imaging based on complementary detection principles has great potential for improving the accuracy of tumor diagnosis. Fe3O4 core/Au shell nanoparticles (Fe3O4@Au NPs) can be used as an effective multimodal contrast agent due to combining the advantageous and highly complementary features of the Fe3O4 core and gold shell. In the present work, we have developed a novel Fe3O4@Au NP based probe for targeting and multimodal imaging of cancer cells. The prepared Fe3O4@Au NPs have been characterized by transmission electron microscopy (TEM), visible spectra and SERS. The potential use of the prepared Fe3O4@Au NPs as a multimodal contrast probe for magnetic resonance imaging (MRI), microwave-induced thermoacoustic imaging and photoacoustic imaging was then evaluated. Importantly, when conjugated with a cancer cell targeted molecular and fluorescent dye, the Fe3O4@Au NPs could be internalized by the corresponding cancer cells selectively and sensitively, and fluorescence imaging was realized at the same time. The bio-modified Fe3O4@Au NPs incorporating multiple functionalities into one single nano-structured system can be effectively used for targeting and multimodal imaging of cancer cells simultaneously.

Microwave-induced thermoacoustic (TA) imaging is efficient in detecting anomalous absorption areas, especially breast tumors. The operation of previous imaging systems has generally suffered from complexity, and early-stage tumors could be missed because of signal loss. In this paper, we report a variable-curvature and multi-dimensional screening method realized by combining a redesigned adaptive algorithm and an integrated TA breast screening system (ITBCS) comprising a flexible detector and a traction device designed for multi-axis rotation. In contrast to conventional TA imaging systems, the proposed system improves the ability to identify early-stage breast tumors, with a simplified system and operational process. Variable curvature is achieved by the flexible characteristics of the detector, which achieves good shape adaptation between the tissue and the detector. Moreover, multi-dimensional scanning is achieved by the multi-axis traction device and meets the requirements for angle transformation and dynamic imaging. The experimental results indicate that ITBCS exhibits a good performance in detecting breast tumors. Faster screening makes inspection more efficient, thereby improving clinical applicability and providing a convenient facility for large-scale physical examination.

Intravascular photoacoustic (IVPA) imaging is based on the detection of laser-induced acoustic waves generated within the arterial tissue under pulsed laser irradiation. In general, laser radiant energy levels are kept low (20 mJ/cm(2)) during photoacoustic imaging to conform to general standards for safe use of lasers on biological tissues. However, safety standards in intravascular photoacoustic imaging are not yet fully established. Consequently, monitoring spatio-temporal temperature changes associated with laser-tissue interaction is important to address thermal safety of IVPA imaging. In this study we utilize the IVUS-based strain measurements to estimate the laser-induced temperature increase. Temporal changes in temperature were estimated in a phantom modeling a vessel with an inclusion. A cross-correlation-based time delay estimator was used to assess temperature-induced strains produced by different laser radiant energies. The IVUS-based remote measurements revealed temperature increases of 0.7+/-0.3 degrees C, 2.9+/-0.2 degrees C and 5.0+/-0.2 degrees C, for the laser radiant energies of 30 mJ/cm(2), 60 mJ/cm(2) and 85 mJ/cm(2), respectively. The technique was then used in imaging of ex vivo samples of a normal rabbit aorta. For arterial tissues, a temperature elevation of 1.1 degrees C was observed for a laser fluence of 60 mJ/cm(2) and lesser than 1 degrees C for lower energy levels normally associated with IVPA imaging. Therefore, the developed ultrasound technique can be used to monitor temperature during IVPA imaging. Furthermore, the analysis based on the Arrhenius thermal damage model indicates no thermal injury in the arterial tissue, suggesting the safety of IVPA imaging.

Photoacoustic imaging (also called optoacoustic or thermoacoustic imaging) can image vascularity clearly with simultaneous high contrast and high spatial resolution, and has the potential to be an application for tumor diagnosis and treatment monitoring. In a unique photoacoustic system, a single pulse laser beam was used as the light source for both cancer treatment and for concurrently generating ultrasound signals for photoacoustic imaging. The photoacoustic system was used to detect early tumor on the rat back, and the vascular structure around the tumor could be imaged clearly with optimal contrast. This system was also used to monitoring damage of the vascular structures before, during and after photodynamic therapy of tumor. This work demonstrates that photoacoustic imaging can potentially be used to guide photodynamic therapy and other phototherapies using vascular changes during treatment. Prospective application of photoacoustic imaging is to characterize and monitor the accumulation of gold nanoshells in vivo to guide nanoshell-based thermal tumor therapy.

The development of microwave breast cancer detection and treatment techniques has been driven by reports of substantial contrast in the dielectric properties of malignant and normal breast tissues. However, definitive knowledge of the dielectric properties of normal and diseased breast tissues at microwave frequencies has been limited by gaps and discrepancies across previously published studies. To address these issues, we conducted a large-scale study to experimentally determine the ultrawideband microwave dielectric properties of a variety of normal, malignant and benign breast tissues, measured from 0.5 to 20 GHz using a precision open-ended coaxial probe. Previously, we reported the dielectric properties of normal breast tissue samples obtained from reduction surgeries. Here, we report the dielectric properties of normal (adipose, glandular and fibroconnective), malignant (invasive and non-invasive ductal and lobular carcinomas) and benign (fibroadenomas and cysts) breast tissue samples obtained from cancer surgeries. We fit a one-pole Cole-Cole model to the complex permittivity data set of each characterized sample. Our analyses show that the contrast in the microwave-frequency dielectric properties between malignant and normal adipose-dominated tissues in the breast is considerable, as large as 10:1, while the contrast in the microwave-frequency dielectric properties between malignant and normal glandular/fibroconnective tissues in the breast is no more than about 10%.

Microwave-induced thermoacoustic (TA) imaging combines the dielectric/conductivity contrast in the microwave range with the high resolution of ultrasound imaging. Lack of ionizing radiation exposure in TA imaging makes this technique suitable for frequent screening applications, as with breast cancer screening. In this paper we demonstrate breast tumor classification based on TA imaging. The sensitivity of the signal-based classification algorithm to errors in the estimation of tumor locations is investigated. To reduce this sensitivity, we propose to use the interferogram of received pressure waves as the feature basis used for classification, and demonstrate the robustness based on a finite-difference time-domain (FDTD) simulation framework.

As a hybrid mechanism integrating the advantages of microwave imaging and ultrasound imaging, such as non-ionizing radiation, high dielectric contrast and excellent spatial resolution, microwave-induced thermoacoustic imaging (TAI) holds promise for breast cancer detection (R. A. Kruger et al, Radiology, 216, 279–283, 2000).

Low frequency alternating magnetic field (AMF) had been advocated for thermoacoustic imaging to exploit their inherent deeper penetrations. AMF induced thermoacoustic imaging of magnetic nanoparticles is particularly appealing since the system setup is inherently compatible with nanoparticle hyperthermia therapy. More importantly, owing to the capacity of thermoacoustics for accurate temperature measurement, the integration of AMF induced thermoacoustic imaging into nanoparticle hyperthermia therapy will potentially enable a theranostic platform with imaging guidance and temperature monitoring capabilities. We present herein the AMF induced thermoacoustic process of magnetic nanoparticles experimentally and then investigate furthermore its utilization in temperature monitoring for the nanoparticle hyperthermia. To demonstrate the concept of an integrated theranostic system with minimal overhead, a single coil is used for both the hyperthermia heating and thermoacoustic imaging by interleaving the two processes in time domain. In thermoacoustic imaging mode, the power is set at the amplifier's maximum value whereas to avoid excess heating of the coil in hyperthermia-mode, the power is switched to a lower value and the coil is further cooled by static water. Phantom imaging results of the magnetic nanoparticles and the self temperature monitoring with sub-degree accuracy during hyperthermia process are demonstrated. These proof-of-concept experiments showcase the potential to integrate thermoacoustic imaging with nanoparticle hyperthermia system. © (2015) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only. Published version

Microwave-induced thermoacoustic imaging (TAI) can map the microwave absorption distribution of targets, which depends on the electrical and magnetic properties. Although carbon nanotubes (CNTs) with good electrical properties have been used as TAI contrast agents, the negligible magnetic absorption hinders its application for sensitive detection. In order to exploit CNTs with electrical and magnetic absorption properties as agent of TAI, the ferromagnetic material-filled multi-walled CNTs (MMWCNTs) are investigated. In this study, the folic acid conjugated plain multiwalled CNTs (MWCNTs) and MMWCNTs were injected through the tail-vein of mice separately, and TAI and magnetic resonance imaging (MRI) were performed. The results show the MMWCNTs can clearly image the size and edge of the tumor with the TAI contrast enhancement of 67% and T2 signal intensity decrease of four fifths compared to MWCNTs. This study demonstrated the hybrid particles have the potential to be a high-sensitive contrast agent for accurate tumor detection. From the Clinical Editor: Novel imaging modalities are emerging. Microwave-induced thermoacoustic imaging (TAI) relies on the absorption distribution of microwave of targets. In this article the authors investigate the use of ferromagnetic material-filled multi-walled CNTs as contrast agents for both TAI and MRI in an in-vivo model for tumors. The positive findings would imply that the application of dual-modality probe could provide more accurate imaging for the clinical setting.

This paper presents the design and construction of a pair of figure-of-eight coils, coupled by magnetic resonance coupling (MRC), which could generate (150 V/m per Ampere) electric field at the focal points for electromagnetic therapy related applications. The E field generated at the targeted site would be significantly enhanced under the same amount of current flowing through the MRC figure-of-eight coils compared to normal coils, due to the superposition of E field contributed by the coils. Furthermore, the MRC figure-of-eight coil is designed and the results are verified in theory, simulation, and experiments. In the ex vivo tissue measurement, 35% current and 82% ohmic power improvements were observed. Since it can enhance the current and ohmic power, the MRC figure-of-eight coils are promising solutions for electromagnetic therapy applications. The potential applications of the coils include noninvasive radio frequency (RF) stimulation, thermoacoustic imaging, electromagnetic field therapies, and RF ablation, etc.

Applying the thermoacoustic (TA) effect to diagnostic imaging was first proposed in the 1980s. The object under test is irradiated by high-power pulses of electromagnetic energy, which heat tissue and cause thermal expansion. Outgoing TA pressure pulses are detected by ultrasound transducers and reconstructed to provide images of the object. The TA contrast mechanism is strongly dependent upon the frequency of the irradiating electromagnetic pulse. When very high frequency (VHF) electromagnetic irradiation is utilized, TA signal production is driven by ionic content. Prostatic fluids contain high levels of ionic metabolites, including citrate, zinc, calcium, and magnesium. Healthy prostate glands produce more ionic metabolites than diseased glands. VHF pulses are therefore expected to generate stronger TA signal in healthy prostate glands than in diseased glands. A benchtop system for performing ex vivo TA computed tomography with VHF energy is described and images are presented. The system utilizes irradiation pulses of 700 ns duration exceeding 20 kW power. Reconstructions frequently visualize anatomic landmarks such as the urethra and verumontanum. TA reconstructions from three freshly excised human prostate glands with little, moderate, and severe cancerous involvement are compared with histology. TA signal strength is negatively correlated with percent cancerous involvement in this small sample size. For the 45 regions of interest analyzed, a reconstruction value of 0.4 mV provides 100% sensitivity but only 29% specificity. This sample size is far too small to draw sweeping conclusions, but the results warrant a larger volume study including comparison of TA images to the gold standard, histology.

Microwave-induced thermoacoustic imaging (TAI) is a noninvasive modality based on the differences in microwave absorption of various biological tissues. TAI has been extensively researched in recent years, and several studies have revealed that TAI possesses advantages such as high resolution, high contrast, high imaging depth and fast imaging speed. In this paper, we reviewed the development of the TAI technique, its excitation source, data acquisition system and biomedical applications. It is believed that TAI has great potential applications in biomedical research and clinical study.

Photoacoustic imaging (PAI) and thermoacoustic imaging (TAI) are two emerging biomedical imaging techniques that both utilize ultrasonic signals as an information carrier. Unique advantages of PAI and TAI are their abilities to provide high resolution functional information such as hemoglobin and blood oxygenation and tissue dielectric properties relevant to physiology and pathology. These two methods, however, may have a limited detection depth and lack of endogenous contrast. An exogenous contrast agent is often needed to effectively resolve these problems. Such agents are able to greatly enhance the imaging contrast and potentially break through the imaging depth limit. Furthermore, a receptor-targeted contrast agent could trace the molecular and cellular biological processes in tissues. Thus, photoacoustic and thermoacoustic molecular imaging can be outstanding tools for early diagnosis, precise lesion localization, and molecular typing of various diseases. The agents also could be used for therapy in conjugation with drugs or in photothermal therapy, where it functions as an enhancer for the integration of diagnosis and therapy. In this article, we present a detailed review about various exogenous contrast agents for photoacoustic and thermoacoustic molecular imaging. In addition, challenges and future directions of photoacoustic and thermoacoustic molecular imaging in the field of translational medicine are also discussed.

Microwave-induced thermoacoustic imaging (TAI) has been actively researched in the past decade and shown to be a promising non-ionizing technology for breast cancer detection [1, 2]. TAI develops an image indicative of the internal structures of a biological sample by exploiting emanated acoustic waves from absorbed microwave energy in the sample due to the thermoacoustic effect [3]. As a hybrid modality, TAI integrates several attractive merits, including large contrast, high spatial resolution and low cost of implementation.

Ex vivo imaging of fresh prostate specimens was performed to test the hypothesis that the thermoacoustic (TA) contrast mechanism generated with very high frequency electromagnetic (EM) irradiation is sensitive to prostate cancer. Ex vivo imaging was performed immediately after radical prostatectomy, performed as part of normal care. Irradiation pulsewidth was 700 ns and duty cycle was extremely low. Typical specific absorption rate (SAR) throughout the prostate was 70-90 kW/kg during pulsing, but time-averaged SAR was below 2 W/kg. TA pressure pulses generated by rapid heating due to EM energy deposition were detected using single element transducers. 15g/L glycine powder mixed into DI water served as acoustic couplant, which was chilled to prevent autolysis. Spatial encoding was performed by scanning in tomographic “step-and-shoot” mode, with 3 mm translation between slices and 1.8-degree rotation between tomographic views. Histology slides for 3 cases scanned with 2.25 MHz transducers were marked for comparison to TA reconstructions. These three cases showed little, moderate, and severe involvement in the histology levels surrounding the verumontanum. TA signal strength decreased with percent cancerous involvement. When VHF is used for tissue heating, the TA contrast mechanism is driven by ionic content and we observed suppressed TA signal from diseased prostate tissue in the peripheral zone. For the 45 regions of interest analyzed, a reconstruction value of 0.4 mV provides 100% sensitivity but only 29% specificity.

Microwave-induced thermoacoustic imaging (TAI) is a promising hybrid modality for breast cancer detection. Reliable diagnosis of breast carcinoma by TAI depends on the contrast in the microwave dielectric properties between the abnormal and surrounding normal tissues. However, the insufficient (merely 10%) endogenous dielectric contrast between the malignant and healthy glandular tissues, from which breast tumors usually originate, greatly challenges the feasibility of TAI in clinical applications, especially for discriminating early-stage breast malignancies.

Thermoacoustic imaging (TAI) is a promising hybrid modality for breast cancer detection utilizing the advantages of microwave and ultrasound. This paper presents a summary of our research work on TAI and spectroscopy for breast cancer detection.

Ex vivo thermoacoustic (TA) imaging of large porcine specimens demonstrates the feasibility of performing whole organ TA imaging. A smaller system optimized for ex vivo prostate cancer imaging has been developed and is currently in use to determine whether the TA contrast mechanism can visualize prostate cancer.

The authors performed thermoacoustic computed tomography (CT) with 434-MHz radio waves in five patients with documented breast cancer. Three of the patients underwent imaging before chemotherapy was initiated and two at the conclusion of their primary chemotherapy. In the former three patients, thermoacoustic CT demonstrated contrast enhancement in the region of the tumor. In the latter two patients, no contrast enhancement was seen, and pathologic examination after surgical resection of the area of original tumor confirmed complete remission of disease.

We have constructed a thermoacoustic computed tomography scanner for imaging soft tissue in the human body. Thermoacoustic signals are induced in soft tissue by irradiation with 434 MHz rf energy. The thermoacoustic signals are detected by an array of transducers mounted on a hemispherical bowl. A three-dimensional, filtered backprojection algorithm is used to reconstruct rf absorption patterns within soft tissue. We have demonstrated soft tissue differentiation sufficient to delineate the normal internal structures of an excised lamb kidney using safe levels of rf radiation.

Current imaging modalities face challenges in clinical applications due to limitations in resolution or contrast. Microwave-induced thermoacoustic imaging may provide a complementary modality for medical imaging, particularly for detecting foreign objects due to their different absorption of electromagnetic radiation at specific frequencies. A thermoacoustic tomography system with a multielement linear transducer array was developed and used to detect foreign objects in tissue. Radiography and thermoacoustic images of objects with different electromagnetic properties, including glass, sand, and iron, were compared. The authors' results demonstrate that thermoacoustic imaging has the potential to become a fast method for surgical localization of occult foreign objects.

Thermoacoustic (TA) imaging provides a novel contrast mechanism that may enable visualization of cancerous lesions which are not robustly detected by current imaging modalities. Prostate cancer (PCa) is the most notorious example. Imaging entire prostate glands requires 6 cm depth penetration. We therefore excite TA signal using submicrosecond VHF pulses (100 MHz). We will present reconstructions of fresh prostates imaged in a well-controlled benchtop TA imaging system. Chilled glycine solution is used as acoustic couplant. The urethra is routinely visualized as signal dropout; surgical staples formed from 100-micron wide wire bent to 3 mm length generate strong positive signal.

Here, we report a new method using combined magnetic resonance (MR)–Photoacoustic (PA)–Thermoacoustic (TA) imaging techniques, and demonstrate its unique ability for in vivo cancer detection using tumor-bearing mice. Circular scanning TA and PA imaging systems were used to recover the dielectric and optical property distributions of three colon carcinoma bearing mice While a 7.0-T magnetic resonance imaging (MRI) unit with a mouse body volume coil was utilized for high resolution structural imaging of the same mice. Three plastic tubes filled with soybean sauce were used as fiducial markers for the co-registration of MR, PA and TA images. The resulting fused images provided both enhanced tumor margin and contrast relative to the surrounding normal tissues. In particular, some finger-like protrusions extending into the surrounding tissues were revealed in the MR/TA infused images. These results show that the tissue functional optical and dielectric properties provided by PA and TA images along with the anatomical structure by MRI in one picture make accurate tumor identification easier. This combined MR–PA–TA-imaging strategy has the potential to offer a clinically useful triple-modality tool for accurate cancer detection and for intraoperative surgical navigation.

Photoacoustic and thermoacoustic phantom images obtained with a multi-channel breast scanner designed for breast cancer screening are presented here. A tunable laser system (OPOTEK Vibrant 355 I, Calsbad,CA) with a pulse duration of 5 ns was used for photoacoustic irradiation, and a 3.0 GHz microwave source with a pulse width of 0.3-1 μs was used for thermoacoustic tomography. Multiple (>=16) 2.25 MHz single-element unfocused ultrasonic transducers at different depths were scanned simultaneously for a full 360° to obtain a full data set for three-dimensional (3D) tomography. Negative acoustic lenses were attached to these unfocused transducers to increase their acceptance angles. An ultrasound receiving system with 64 parallel receiving channels (Verasonics Inc. Redmond, WA) was used for data acquisition. A filtered backprojection algorithm was used to reconstruct two-dimensional (2D) and 3D images. Different phantoms were imaged to evaluate the performance of the scanner. A lateral resolution of less than 1 mm and an elevational resolution of less than 5 mm were achieved. The phantom studies demonstrate that this scanner can potentially provide high-resolution, dual-modality, three-dimensional images and can potentially be used for human breast cancer screening.