Research

Fast Slide-Free Histology

The goal of breast-conserving surgery is to completely remove all of the cancer. Currently, no intraoperative tools can microscopically analyze the entire lumpectomy specimen, which results in 20 to 60% of patients undergoing second surgeries to achieve clearmargins. To address this critical need, we have laid the foundation for the development of a device that could allow accurate intraoperative margin assessment. We demonstrate that by taking advantage of the intrinsic optical contrast of breast tissue, photoacoustic microscopy (PAM) can achieve multilayered histology-like imaging of the tissue surface. The high correlation of the PAM images to the conventional histologic images allows rapid computations of diagnostic features such as nuclear size and packing density, potentially identifying small clusters of cancer cells. Because PAM does not require tissue processing or staining, it can be performed promptly and intraoperatively, enabling immediate directed re-excision and reducing the number of second surgeries.

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Reference: 

Terence T. W. Wong, Ruiying Zhang, Pengfei Hai, Chi Zhang, Miguel A. Pleitez, Rebecca L. Aft, Deborah V. Novack, and Lihong V. Wang, “Fast label-free multi-layered histology-like imaging of human breast cancer by photoacoustic microscopy,” Science Advances 3, e1602168 (2017) [Link]

*also selected as the cover rotator story in Science Advances

Whole-organ Imaging

Three-dimensional (3D) optical imaging of whole biological organs with microscopic resolution has remained a challenge. Most versions of such imaging techniques require special preparation of the tissue specimen. Here we demonstrate microtomy-assisted photoacoustic microscopy (mPAM) of mouse brains and other organs, which automatically acquires serial distortion-free and registration-free images with endogenous absorption contrasts. Without tissue staining or clearing, mPAM generates micrometer-resolution 3D images of paraffin- or agarose-embedded whole organs with high fidelity, achieved by label-free simultaneous sensing of DNA/RNA, hemoglobins, and lipids. mPAM provides histology-like imaging of cell nuclei, blood vessels, axons, and other anatomical structures, enabling the application of histopathological interpretation at the organelle level to analyze a whole organ. Its deep tissue imaging capability leads to less sectioning, resulting in negligible sectioning artifact. mPAM offers a new way to better understand complex biological organs.

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Reference:

Terence T. W. Wong, Ruiying Zhang, Chi Zhang, Hsun-Chia Hsu, Konstantin Maslov, Lidai Wang, Junhui Shi, Ruimin Chen, K. Kirk Shung, Qifa Zhou, and Lihong V. Wang, “Label-free automated three-dimensional imaging of whole organs by microtomy-assisted photoacoustic microscopy,” Nature Communications 8, 1386 (2017) [Link]

*also selected by Nature Communications to be indexed by Nature Index

Low-Cost Deep Tissue Imaging

While lasers have been commonly used as illumination sources in photoacoustic imaging, their high purchase and maintenance costs, as well as their bulkiness, have hindered the rapid clinical dissemination of photoacoustic imaging. With this in mind, we explore an alternative illumination source for photoacoustic tomography — a xenon flash lamp with high pulse energy and a micro-second pulse width. We demonstrate that, by using a single xenon flash lamp, we can image both a black latex cord placed in chicken breast tissue at a depth of up to 3.5 cm ex vivo, and an entire mouse body in vivo. Our findings indicate that the xenon flash lamp, producing optical illumination that is safe for humans, can be potentially applied to human tissue imaging.

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Reference:

Terence T. W. Wong, Yong Zhou, Alejandro Garcia-Uribe, Lei Li, Konstantin Maslov, Li Lin, Lihong V. Wang, "Use of a single xenon flash lamp for photoacoustic computed tomography of multiple-centimeter-thick biological tissue ex vivo and a whole mouse body in vivo," J. Biomed. Opt. 22(4), 041003 (2016) [Link]