Microwave-induced thermoacoustic microscopy based on short-pulse microwave and high-frequency point-focused ultrasonic transducer.

BACKGROUND: As an emerging hybrid imaging modality, microwave-induced thermoacoustic imaging (MITAI) provides high contrast and deep tissue penetration, and has been extensively applied in cancer diagnosis, arthritis detection, and brain research. However, the previous studies had a limited spatial resolution of about 0.45-1.5 mm. PURPOSE: Here, we describe a microwave-induced thermoacoustic microscopy (MITAM) system to help overcome the resolution limitation of current MITAI to image more subtle tissue features. On this basis, this paper applies MITAM to the thin skin and to demonstrate the potential of MITAM in detecting scleroderma. METHODS: To achieve high resolution, short pulse width microwave (pulse width: 70 ns) and high-frequency ultrasonic point-focused transducer (center frequency: 25 MHz) were used to build the MITAM system. Two parallel copper wires with a diameter of 90 µm in the X/Y plane and Y/Z plane were imaged to estimate X/Y/Z resolution. Nine Balb/c mice were randomly divided into three groups and injected with different concentrations of bleomycin to induce scleroderma models. Their ex vivo skins were then imaged by our MITAM system. Visual observations were performed on the 3-dimensional skins MITAM images. And the mean value, Standard deviation, quartile distance, and signal-to-noise ratio were calculated to verify the results of the qualitative observations. Hematoxylin-Eosin (HE) and Masson staining were used to validate the findings of the MITAM. RESULTS: The thickness of each imaged skin was measured to be about 450 µm. As an organ composed of multiple layers of tissues, the skin needs to be imaged at high resolution for the detection of related diseases. The results obtained showed that the improved resolution (68 µm in the Z-axis and 135 µm in the X-axis/Y-axis) of MITAM over conventional MITAI allowed us to differentiate scleroderma skins from normal skins and to identify the severity of scleroderma skins, consistent with the pathological findings of these skins. CONCLUSIONS: The preliminary results obtained indicate that the MITAM can relieve the resolution limitation of traditional MITAI and has the potential to detection scleroderma. However, the transmission-type MITAM mentioned in this paper is difficult to image in vivo due to the narrow area between the antenna and the transducer. In the future, a reflective scanning MITAM will be constructed to detect scleroderma in vivo.

Noninvasive optoacoustic imaging of breast tumor microvasculature in response to radiotherapy.

Detailed insight into the radiation-induced changes in tumor microvasculature is crucial to maximize the efficacy of radiotherapy against breast cancer. Recent advances in imaging have enabled precise targeting of solid lesions. However, intratumoral heterogeneity makes treatment planning and monitoring more challenging. Conventional imaging cannot provide high-resolution observation and longitudinal monitoring of large-scale microvascular in response to radiotherapy directly in deep tissues. Herein, we report on an emerging non-invasive imaging assessment method of morphological and functional tumor microvasculature responses with high spatio-temporal resolution by means of optoacoustic imaging (OAI). In vivo imaging of 4T1 breast tumor response to a conventional fractionated radiotherapy at varying dose (14 × 2 Gy and 3 × 8 Gy) has been performed after 2 weeks following treatment. Remarkably, optoacoustic images can generate richful contrast for the tumor microvascular architecture. Besides, the functional status of tumor microvasculature and tumor oxygenation levels were further estimated using OAI. The results revealed the differential (size-dependent) nature of vascular responses to radiation treatments at varying doses. The vessels exhibited an decrease in their density accompanied by a decline in the number of vascular segments following irradiation, compared to the control group. The measurements further revealed an increase of tumor oxygenation levels for 14 × 2 Gy and 3 × 8 Gy irradiations. Our results suggest that OAI could be used to assess the response to radiotherapy based on changes in the functional and morphological status of tumor microvasculature, which are closely linked to the intratumor microenvironment. OAI assessment of the tumor microenvironment such as oxygenation status has the potential to be applied to precise radiotherapy strategy.

Evaluation of Tracheal Stenosis in Rabbits Using Multispectral Optoacoustic Tomography.

Objective: Photoacoustic tomography (PAT) and multispectral optoacoustic tomography (MSOT) are evolving technologies that are capable of delivering real-time, high-resolution images of tissues. The purpose of this study was to evaluate the feasibility of using PAT and MSOT for detecting histology in a rabbit tracheal stenosis model. Method: A total of 12 rabbits (9 stenosis and three control) were randomly divided into four groups (A, B, C and D). Each group consisted of three rabbits, which were staged at the first, fourth, and eighth weeks of stenosis progression, respectively. PAT/MSOT images and corresponding histology from these experimental animals were compared, for analyzing the morphologic features and quantitative tracheal measurements in different tracheal stenosis stage. Result: Both the PAT images and corresponding histology indicated the most severe degree of stenosis in group C. MSOT images indicated notable differences in tracheal contents of group B and D. Conclusion: This study suggests that PAT/MSOT are potentially valuable non-invasive modality which are capable of evaluating tracheal structure and function in vivo.

First assessment of thermoacoustic tomography for in vivo detection of rheumatoid arthritis in the finger joints detection of rheumatoid arthritis in the finger joints.

BACKGROUND: The diagnosis of rheumatoid arthritis (RA) is complicated because of the complexity of symptoms and joint structures. Current clinical imaging techniques for the diagnosis of RA have strengths and weaknesses. Emerging imaging techniques need to be developed for the diagnosis or auxiliary diagnosis of RA. PURPOSE: This study aimed to demonstrate the potential of thermoacoustic tomography (TAT) for in vivo detection of RA in the finger joints. METHODS: Finger joints were imaged by a TAT system using three different microwave illumination methods including pyramidal horn antenna, and parallel in-phase and anti-phase microwave illuminations. Both diseased and healthy joints were imaged and compared when the three microwave illumination methods were used. Magnetic resonance imaging (MRI) of all the joints was performed to validate the TAT findings. In addition, two diseased joints were imaged at two time points by the pyramidal horn antenna-based TAT to track/monitor the progression of RA during a time period of 16 months. Three-dimensional (3-D) TAT images of the joints were also obtained. RESULTS: The TAT images of the diseased joints displayed abnormalities in bone and soft tissues compared to the healthy ones. The TAT images by pyramidal horn antenna and in-phase microwave illumination showed high similarity in image appearance, while the anti-phase-based TAT images provided different information about the disease. We found that the TAT findings matched well with the MRI images. The 3-D TAT images effectively displayed the stereoscopic effect of joint lesions. Finally, it was evident that TAT could detect the development of the lesions in 16 months. CONCLUSION: TAT can noninvasively visualize bone lesions and soft tissue abnormalities in the joints with RA. This first in vivo assessment of TAT provides a foundation for its clinical application to the diagnosis and monitoring of RA in the finger joints.

Technical Note: Compact thermoacoustic imaging system based on a low-cost and miniaturized microwave generator for in vivo biomedical imaging.

PURPOSE: Most of existing thermoacoustic imaging (TAI) studies generally utilized a linear modulator-based high peak power magnetron generator (MG) for efficient TA signal excitation. However, a linear modulator-based MG is bulky and expensive. Here we present a low-cost and compact thermoacoustic imaging (TAI) system based on a miniaturized MG. METHODS: The MG is based on solid-state modulator and operates at 3.05 ± 0.025 GHz, with a peak power of up to 60 kW and adjustable pulse duration from 70 to 600 ns. The dimensions and weight of this MG are 350 × 210 × 70 mm3 (Width × Length × Height) and 7.5 kg, respectively. RESULTS: The spatial resolution of the miniaturized MG-based TAI system is determined to be from 0.3 to 1.4 mm using controlled phantom experiments. The system is further evaluated using in vivo experiments where the finger joints and vasculature in the forearm and opisthenar of human participants are successfully imaged. CONCLUSIONS: This study suggests that the miniaturized MG based TAI systems can be used for in vivo joint and vascular imaging with multiscale resolutions (0.3-1.4 mm).

Integrated thermoacoustic and ultrasound imaging based on the combination of a hollow concave transducer array and a linear transducer array.

To integrate the high resolution of ultrasound imaging (UI) and the high tissue specificity of thermoacoustic imaging (TAI) and to achieve an easy and precise co-registration of the two different imaging modalities, we present and demonstrate a hybrid thermoacoustic and ultrasound (TA/US) imaging system based on the combination of a novel hollow concave array and a commercial linear array. This TA/US imaging system can provide enhanced imaging of both tissues' mechanical and dielectric properties. We verified the effective imaging performance of the hybrid TA/US system using tissue phantom experiments.In vivoTA/US imaging of the wrist and foot in healthy volunteers was also demonstrated using the hybrid system. This hollow concave array provided enhanced imaging performance for TAI because of its wide angular coverage with an optimal center frequency, showing a large effective imaging field of view (FOV) and improved images with high contrast and superior quality. Compared with stand-alone UI or TAI, the hybrid TA/US imaging presented more complete tissue anatomical structures, like skin, muscles, tendons, blood vessels, and bones for possible human disease diagnosis, although the US image quality using the hybrid system was slightly lower because the distance between the tissue and commercial ultrasound array was not ideal. This study suggests that the hybrid TA/US imaging approach has the potential to become a clinical tool for diagnosis of diseases in the wrist and foot.

Photoacoustic imaging of hemodynamic changes in forearm skeletal muscle during cuff occlusion.

Characterizations of circulatory and metabolic function in skeletal muscle are of great importance in clinical settings. Here in this study, we investigate the utility of photoacoustic tomography (PAT) to monitor the hemodynamic changes in forearm skeletal muscle during cuff occlusion. We show high quality photoacoustic (PA) images of human forearm in comparison with ultrasound images. Besides, we track the hemodynamic changes in the forearm during cuff occlusion cross-validated with near-infrared spectroscopy. Our study suggests that PAT, as a new tool, could be applied to common diseases affecting skeletal muscle in the future.

Thermoacoustic tomography of germinal matrix hemorrhage in neonatal mouse cerebrum.

BACKGROUND: Microwave-induced thermoacoustic tomography (TAT) has potential for detecting germinal matrix hemorrhage (GMH). However, it has not been demonstrated in vivo. OBJECTIVE: To demonstrate the feasibility of TAT for in vivo detecting GMH by using neonatal mouse. METHODS: A cylindrical-scanning TAT system was developed with optimized microwave irradiation and ultrasound detection for neonatal mouse imaging. Neonatal mice were used to develop GMH model by injection of autologous blood into the periventricular region. After TAT experiments, the animals were sacrificed, frozen and excised to validate the TAT findings. The detailed comparative analyses of the TAT images and corresponding photographs of the excised brain tissues were conducted. RESULTS: Satisfactory matches are identified between the TAT images and corresponding histological sections, in terms of the shape and size of the brain tissues. Some organs and tissues were also identified. Particularly, comparing to the corresponding histological sections, using TAT enables to more accurately detect the hematoma region at different depths in the neonatal mouse brain. CONCLUSIONS: This study demonstrates for the first time that TAT can detect GMH in neonatal mouse cerebrum in vivo. This represents the first important step towards the in vivo diagnosis and grading of hemorrhage in the infant human brain.

Technical Note: Anti-phase microwave illumination-based thermoacoustic tomography of in vivo human finger joints.

PURPOSE: Thermoacoustic tomography (TAT) has been studied to image joints. While several joint tissues could be thermoacoustically imaged, tendons and bone could not be recovered completely or clearly. The purpose of this study was to overcome this limitation. METHODS: We developed a novel TAT system based on anti-phase microwave illumination method to image the proximal interphalangeal joint and middle phalanx of a right middle finger from a healthy volunteer. The performance of this new system for imaging joints and tendons was compared with that by in-phase microwave illumination and a conventional pyramidal horn antenna. RESULTS: Anti-phase microwave illumination can produce relatively homogeneous electric (E)-Field distributions inside the joint tissues. The homogeneous E-Field distributions can enhance the detectability of flexor tendon and extensor tendon. Anti-phase microwave illumination could image the flexor tendon, and extensor tendon and bone, which were not clearly imaged by the in-phase microwave illumination or by the horn antenna. The images generated by the in-phase microwave illumination and pyramidal horn antenna were almost identical in terms of the tissue types they imaged. CONCLUSIONS: Anti-phase illumination can overcome the limitation associated with the conventional TAT by adding the ability of completely delineating tendons and bone in the joints. This study paves the way for us to continue the study and to validate its utility in detection of joint diseases.

Thermoacoustic imaging of rabbit knee joints.

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.