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High resolution deep tissue photoacoustic imaging

3 Jun | By Biophotonics.World
Last two decades has witnessed an exponential rise in research related to photoacoustic (PA) imaging, due to the advantages this imaging modality offers. At Nanyang Technological University, Singapore, researchers have developed an acoustic resolution photoacoustic microscopy (ARPAM) system which uses 1064 nm laser pulses to excite the tissue. This system can perform in vivo imaging with a 130 µm lateral resolution, 57 µm axial resolution, at 11 mm imaging depth. PA imaging (PAI) is a non-invasive imaging technique having the advantages of optical contrast and ultrasound resolution. This method involves irradiation of the target sample/ tissue with laser pulses. Absorption of these pulses results in generation of pressure (acoustic) waves which can be detected using an ultrasound transducer (UST) to form the required image. The benefits of PAI has led to its vast use in various clinical and preclinical trials including imaging of breast, sentinel lymph node (SLN), vasculature etc. However, it still remains a challenge to maintain high resolution during deep tissue imaging. To that end, researchers from NTU developed a PAI system using laser pulses of wavelength 1064 nm for sample illumination, and a focused UST to record the generated PA signal. Laser pulses in the second window of near infrared (NIR-II) (i.e., 900-1200 nm wavelength) can go deeper in biological tissues, as compared to pulses in visible spectrum. “By using 1064 nm light for sample illumination, we achieved deep tissue imaging, and by employing a UST with central frequency of 30 MHz, we could attain good spatial resolution”, said Arunima Sharma, a researcher working with Dr. Manojit Pramanik, assistant professor at School of Chemical and Biomedical Engineering, NTU. The researchers initially characterized the developed system using commercially available 1951 USAF resolution test targets and carbon microspheres. These images confirmed the resolution of the system. Further, imaging a black tape inserted in chicken breast tissue ascertained the imaging depth of the system. Dr. Pramanik said, “Phantom experiments showed that our developed system could achieve a lateral resolution of 130 µm and an axial resolution of 57 µm at 11 mm depth in biological tissues. Once we had characterized the system, we realized its potential for various applications. In vivo experiments were performed to validate the system’s applications for preclinical imaging.” Feasibility of the system for in vivo imaging was shown by imaging SLN and urinary bladder in rats. Black ink was injected in the animal prior to imaging to get high optical contrast. SLN imaging is used for staging of breast cancer. In the acquired images, the flow of black ink in the lymph vessel was visible, confirming system’s ability to perform high resolution imaging of lymph vessel. Non-invasive identification of SLN and lymph vessel can aid in ease of cancer staging and even in needle guidance for aspiration biopsy. Following this, a urinary bladder filled with black ink was imaged to substantiate that the system can image deeply seated organs. Image of urinary bladder convinces the use of the developed system for photoacoustic cystography. “Images of lymph vessel, sentinel lymph node, and urinary bladder justify that the developed system can perform both high resolution as well as deep tissue imaging in animal models. These are just a couple of the many biological applications this system can offer,” commented Vijitha Periyasamy, a researcher in Dr. Pramanik’s group. One of the challenges of the system is development of FDA approved contrast agents which have strong absorbance at 1064 nm wavelength. There are many on-going research projects to solve this challenge. The authors are optimistic that the issue of contrast agent is not fundamental, and once sorted, the system will be extensively used for preclinical and clinical imaging. Original article V. Periyasamy, N. Das, A. Sharma, and M. Pramanik, “1064 nm acoustic resolution photoacoustic microscopy,” Journal of Biophotonics 12(5), e201800357 (2019). https://doi.org/10.1002/jbio.201800357

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