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.