Automatic force-controlled 3D photoacoustic system for human peripheral vascular imaging.

Photoacoustic (PA) imaging provides unique advantages in peripheral vascular imaging due to its high sensitivity to hemoglobin. Nevertheless, limitations associated with handheld or mechanical scanning by stepping motor techniques have precluded photoacoustic vascular imaging from advancing to clinical applications. As clinical applications require flexibility, affordability, and portability of imaging equipment, current photoacoustic imaging systems developed for clinical applications usually use dry coupling. However, it inevitably induces uncontrolled contact force between the probe and the skin. Through 2D and 3D experiments, this study proved that contact forces during the scanning could significantly affect the vascular shape, size, and contrast in PA images, due to the morphology and perfusion alterations of the peripheral blood vessels. However, there is no available PA system that can control forces accurately. This study presented an automatic force-controlled 3D PA imaging system based on a six-degree-of-freedom collaborative robot and a six-dimensional force sensor. It is the first PA system that achieves real-time automatic force monitoring and control. This paper's results, for the first time, demonstrated the ability of an automatic force-controlled system to acquire reliable 3D PA images of peripheral blood vessels. This study provides a powerful tool that will advance PA peripheral vascular imaging to clinical applications in the future.

Monitoring neonatal brain hemorrhage progression by photoacoustic tomography.

Neonatal brain hemorrhage (NBH) is the most common neurological disorder in neonates and its clinical interventions are very limited. Understanding the pathology of NBH by non-invasive in-vivo characterization of standardized animal models is essential for developing potential treatments. Currently, there is no suitable tool to provide non-invasive, non-ionizing dynamic imaging of neonatal mouse models with high resolution, high contrast, and deep imaging depth. In this study, we implemented a fast 3D photoacoustic tomography (PAT) system suitable for imaging neonatal mouse brains with good image quality and demonstrated its feasibility in non-invasive monitoring of the dynamic process of NBH in the whole neonatal mouse brain. The results present a high resolution and sensitivity for NBH detection. Both morphological and hemodynamic changes of the hematoma were accurately obtained. Our results demonstrated the potential of PAT as a powerful tool for the preclinical study of neonatal brain hemorrhage.

Acoustic Beam Mapping for Guiding HIFU Therapy In Vivo Using Sub-Therapeutic Sound Pulse and Passive Beamforming.

OBJECTIVE: Although HIFU has been successfully applied in various clinical applications in the past two decades for the ablation of many types of tumors, one bottleneck in its wider applications is the lack of a reliable and affordable strategy to guide the therapy. This study aims at estimating the therapeutic beam path at the pre-treatment stage to guide the therapeutic procedure. METHODS: An incident beam mapping technique using passive beamforming was proposed based on a clinical HIFU system and an ultrasound imaging research system. An optimization model was created to map the cross-like beam pattern by maximizing the total energy within the mapped area. This beam mapping technique was validated by comparing the estimated focal region with the HIFU-induced actual focal region (damaged region) through simulation, in-vitro, ex-vivo and in-vivo experiments. RESULTS: The results of this study showed that the proposed technique was, to a large extent, tolerant of sound speed inhomogeneities, being able to estimate the focal location with errors of 0.15 mm and 0.93 mm under in-vitro and ex-vivo situations respectively, and slightly over 1 mm under the in-vivo situation. It should be noted that the corresponding errors were 6.8 mm, 3.2 mm, and 9.9 mm respectively when the conventional geometrical method was used. CONCLUSION: This beam mapping technique can be very helpful in guiding the HIFU therapy and can be easily applied in clinical environments with an ultrasound-guided HIFU system. SIGNIFICANCE: The technique is safe and can potentially be adapted to other ultrasound-related beam manipulating applications.

In-vivo hemodynamic imaging of acute prenatal ethanol exposure in fetal brain by photoacoustic tomography.

Prenatal ethanol exposure (PEE) can lead to structural and functional abnormalities in fetal brain. Although neural developmental deficits due to PEE have been recognized, the immediate effects of PEE on fetal brain vasculature and hemodynamics remain poorly understood. One of the major obstacles that preclude the rapid advancement of studies on fetal vascular dynamics is the limitation of the imaging techniques. Thus, a technique for noninvasive in-vivo imaging of fetal vasculature and hemodynamics is desirable. In this study, we explored the dynamic changes of the vessel dimeter, density and oxygen saturation in fetal brain after acute maternal ethanol exposure in the second-trimester equivalent murine model using a real-time photoacoustic tomography system we developed for imaging embryo of small animals. The results indicate a significant decrease in fetal brain vessel diameter, perfusion and oxygen saturation. This work demonstrated that PAT can provide high-resolution noninvasive imaging ability to monitor fetal vascular dynamics.

Fan-shaped scanning approach for miniaturized photoacoustic tomography.

We describe a novel scanning approach for miniaturized photoacoustic tomography (PAT), based on fan-shaped scanning of a single transducer at one or two discrete positions. This approach is tested and evaluated using several phantom and animal experiments. The results obtained show that this new scanning approach provides high image quality in the configuration of miniaturized handheld or endoscopic PAT with improved effective field of view and penetration depth.

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.

Miniature fluorescence molecular tomography (FMT) endoscope based on a MEMS scanning mirror and an optical fiberscope.

We present a novel FMT endoscope by using a MEMS scanning mirror and an optical fiberscope. The diameter of this highly miniaturized FMT device is only 5 mm. To our knowledge, this is the smallest FMT device we found so far. Several phantom experiments based on indocyanine green (ICG) were conducted to demonstrate the imaging ability of this device. Two tumor-bearing mice were systematically injected with tumor-targeted NIR fluorescent probes (ATF-PEG-IO-830) and were then imaged to further demonstrate the ability of this FMT endoscope for imaging small animals.

GPU-based acceleration and mesh optimization of finite-element-method-based quantitative photoacoustic tomography: a step towards clinical applications.

Finite element method (FEM)-based time-domain quantitative photoacoustic tomography (TD-qPAT) is a powerful approach, as it provides highly accurate quantitative imaging capability by recovering absolute tissue absorption coefficients for functional imaging. However, this approach is extremely computationally demanding, and requires days for the reconstruction of one set of images, making it impractical to be used in clinical applications, where a large amount of data needs to be processed in a limited time scale. To address this challenge, here we present a graphic processing unit (GPU)-based parallelization method to accelerate the image reconstruction using FEM-based TD-qPAT. In addition, to further optimize FEM-based TD-qPAT reconstruction, an adaptive meshing technique, along with mesh density optimization, is adopted. Phantom experimental data are used in our study to evaluate the GPU-based TD-qPAT algorithm, as well as the adaptive meshing technique. The results show that our new approach can considerably reduce the computation time by at least 136-fold over the current central processing unit (CPU)-based algorithm. The quality of image reconstruction is also improved significantly when adaptive meshing and mesh density optimization are applied.