Photoacoustic (PA) imaging is a biomedical imaging method that can provide both structural and functional information of living tissues beyond the optical diffusion limit by combining the concepts of conventional optical and ultrasound imaging methods. Although endogenous chromophores can be utilized to acquire PA images of biological tissues, exogenous contrast agents that absorb near-infrared (NIR) lights have been extensively explored to improve the contrast and penetration depth of PA images. Here, we demonstrate Bi2Se3 nanoplates, that strongly absorbs NIR lights, as a contrast agent for PA imaging. In particularly, the Bi2Se3 nanoplates produce relatively strong PA signals with an optical wavelength of 1064 nm, which has several advantages for deep tissue imaging including: (1) relatively low absorption by other intrinsic chromophores, (2) cost-effective light source using Nd:YAG laser, and (3) higher available energy than other NIR lights according to American National Standards Institute (ANSI) safety limit. We have investigated deep tissue imaging capability of the Bi2Se3 nanoplates by acquiring in vitro PA images of microtubes under chicken breast tissues. We have also acquired in vivo PA images of bladders, gastrointestinal tracts, and sentinel lymph nodes in mice after injection of the Bi2Se3 nanoplates to verify their applicability to a variety of biomedical research. The results show the promising potential of the Bi2Se3 nanoplates as a PA contrast agent for deep tissue imaging with an optical wavelength of 1064 nm.
Non-invasive treatment of tumor is beneficial for the favorable prognosis of the patients. High Intensity Focused Ultrasound (HIFU) is an emerging non-invasive treatment tool that ablates tumor lesions by increasing local temperature without damaging surrounding tissues. In HIFU therapy, accurate focusing of the HIFU energy into the target lesion and real-time assessment of thermal distribution are critical for successful and safe treatment. Photoacoustic (PA) imaging is a novel biomedical imaging technique that can visualize functional information of biological tissues based on optical absorption and thermoelastic expansion. One unique feature of PA imaging is that the amplitude of the PA signal reflects the local temperature. Here, we demonstrate a real-time temperature monitoring system that can evaluate thermal distribution during HIFU therapy. We have integrated a HIFU treatment system, a clinical ultrasound (US) machine, and a tunable laser system and have acquired real-time PA/US images of in vitro phantoms and in vivo animals during HIFU therapy without interference from the therapeutic US waves. We have also evaluated the temperature monitoring capability of the system by comparing the amplitude of PA signals with the measured temperature in melanoma tumor bearing mice. Although much more updates are required for clinical applications, the results show the promising potential of the system to ensure accurate and safe HIFU therapy by monitoring the thermal distribution of the treatment area.
Visualization methods are very important in biomedical imaging. As a technology that understands life, biomedical imaging has the unique advantage of providing the most intuitive information in the image. This advantage of biomedical imaging can be greatly improved by choosing a special visualization method. This is more complicated in volumetric data. Volume data has the advantage of containing 3D spatial information. Unfortunately, the data itself cannot directly represent the potential value. Because images are always displayed in 2D space, visualization is the key and creates the real value of volume data. However, image processing of 3D data requires complicated algorithms for visualization and high computational burden. Therefore, specialized algorithms and computing optimization are important issues in volume data. Photoacoustic-imaging is a unique imaging modality that can visualize the optical properties of deep tissue. Because the color of the organism is mainly determined by its light absorbing component, photoacoustic data can provide color information of tissue, which is closer to real tissue color. In this research, we developed realistic tissue visualization using acoustic-resolution photoacoustic volume data. To achieve realistic visualization, we designed specialized color transfer function, which depends on the depth of the tissue from the skin. We used direct ray casting method and processed color during computing shader parameter. In the rendering results, we succeeded in obtaining similar texture results from photoacoustic data. The surface reflected rays were visualized in white, and the reflected color from the deep tissue was visualized red like skin tissue. We also implemented the CUDA algorithm in an OpenGL environment for real-time interactive imaging.
Identifying and delineating invisible anatomical and pathological details during surgery guides surgical procedures in real time. Various intraoperative imaging modalities have been increasingly employed to minimize such surgical risks as anatomical changes, damage to normal tissues, and human error. However, current methods provide only structural information, which cannot identify critical structures such as blood vessels. The logical next step is an intraoperative imaging modality that can provide functional information. Here, we have successfully developed a photoacoustic (PA) image-guided navigation system for surgery by integrating a position tracking system and a real-time clinical photoacoustic/ultrasound (PA/US) imaging system. PA/US images were acquired in real time and overlaid on pre-acquired cross-sectional magnetic resonance (MR) images. In the overlaid images, PA images represent the optical absorption characteristics of the surgical field, while US and MR images represent the morphological structure of surrounding tissues. To test the feasibility of the system, we prepared a tissue mimicking phantom which contained two samples, methylene blue as a contrast agent and water as a control. We acquired real-time overlaid PA/US/MR images of the phantom, which were well-matched with the optical and morphological properties of the samples. The developed system is the first approach to a novel intraoperative imaging technology based on PA imaging, and we believe that the system can be utilized in various surgical environments in the near future, improving the efficacy of surgical guidance.
Thyroid cancer is one of the most prevalent cancers. About 3-8% of the people in the United States have thyroid nodules, and 5-15% of these nodules are malignant. Fine-needle aspiration biopsy (FNAB) is a standard procedure to diagnose malignity of nodules. However, about 10-20% of FNABs produce indeterminable results, which leads to repeat biopsies and unnecessary surgical operations. We have explored photoacoustic (PA) imaging as a new method to identify cancerous nodules. In a pilot study to test its feasibility, we recruited patients with thyroid nodules (currently 36 cases with 21 malignant and 15 benign nodules), acquired in vivo PA and ultrasound (US) images of the nodules in real time using a recently-developed clinical PA/US imaging system, and analyzed the acquired data offline. The preliminary results show that malignant and benign nodules could be differentiated by utilizing their PA amplitudes at different excitation wavelengths. This is the first in vivo PA analysis of thyroid nodules. Although a larger-scale study is needed for statistical significance, the preliminary results show the good potential of PA imaging as a non-invasive tool for triaging thyroid cancer.
We have successfully developed a clinical real-time photoacoustic/ultrasound (PA/US) imaging system. The PA/US imaging system was adapted with a FDA approved commercial US imaging system and a portable pulsed laser system. All image processing and display tasks were performed in real-time by using a graphical processing unit of the US imaging system. We have tested performances of the system by measuring maximum penetration depth, noise equivalent sensitivity, and axial resolution of contrast agent deposited microtubes under chicken breast tissues. By adapting various US transducers (i.e., linear, convex, phased, and endocavity), adaptable capability of the system was verified. In addition, volumetric PA/US imaging was performed by applying a linear scanning along an elevational direction. We have successfully acquired volumetric PA/US images of human forearms in vivo. We believe that the developed clinical real-time PA/US imaging system can be utilized in various preclinical and clinical studies in the near future.
We have demonstrated a novel microbubbles methylene blue solution, called to “MB2” solution for a dual modality contrast. We have photoacoustically and ultrasonically imaged and quantified aqueous solutions of MB2 by varying the concentration of either microbubbles or methylene blue to investigate the dual modal imaging capability. Interestingly, as the microbubbles concentration increased with the constant methylene blue concentration, photoacoustic (PA) signal was greatly attenuated in the MB2 solution. Conversely, when methylene blue concentration increased with the fixed microbubbles concentration, no interference was observed in ultrasound (US) signals. To further confirm our findings, we switched the PA and ultrasound (US) signals using conventional ultrasound. We compared the PA and US signals of the MB2 solution before and after sonication. The PA amplitude increased 2.5 times. Conversely, the US signals were initially strong, but decreased 2.5 times following sonication. Moreover, we used a clinically modified PA/US imaging system to disrupt the microbubbles in MB2 and recover the PA signals.
Ultrasound and photoacoustic imaging are highly complementary modalities since both use ultrasonic detection for operation. Increasingly, photoacoustic and ultrasound have been integrated in terms of hardware instrumentation. To generate a broadly accessible dual-modality contrast agent, we generated microbubbles (a standard ultrasound contrast agent) in a solution of methylene blue (a standard photoacoustic dye). This MB 2 solution was formed effectively and was optimized as a dual-modality contrast solution. As microbubble concentration increased (with methylene blue concentration constant), photoacoustic signal was attenuated in the MB 2 solution. When methylene blue concentration increased (with microbubble concentration held constant), no ultrasonic interference was observed. Using an MB 2 solution that strongly attenuated all photoacoustic signal, high powered ultrasound could be used to burst the microbubbles and dramatically enhance photoacoustic contrast (>800 -fold increase), providing a new method for spatiotemporal control of photoacoustic signal generation.