Fast label-free multilayered histology-like imaging of human breast cancer by photoacoustic microscopy

Wong, Terence T. W.; Zhang, Ruiying; Hai, Pengfei; Zhang, Chi; Pleitez, Miguel A.; Aft, Rebecca; Novack, Deborah V.; Wang, Lihong V.

doi:10.1126/sciadv.1602168

Cited by 213 publications

(183 citation statements)

References 39 publications

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“…31,32 We demonstrated that UV-PAM was able to provide analysis of the same quality as postoperative histological analysis and that it required less time. 33 This demonstration suggested that UV-PAM could potentially provide accurate intraoperative SMA, reducing the rate of re-excision in cancer surgeries. Further technical advances in UV-PAM can help this technology achieve its full potential.…”

Section: Introductionmentioning

confidence: 93%

“…The current UV-PAM system acquires photoacoustic (PA) signals on a point-by-point basis with raster scanning, so its imaging speed is limited by the repetition rate of the laser, a critical bottleneck to practical clinical applications such as intraoperative SMA. 33 In this study, we developed a multifocal UV-PAM (MF-UV-PAM) system to mitigate this limitation. By exciting the biological specimens with multiple optical spots, and subsequently reconstructing the induced PA signals at these points, imaging can be accelerated by increasing the number of excitation foci.…”

Section: Introductionmentioning

confidence: 99%

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High-throughput ultraviolet photoacoustic microscopy with multifocal excitation

et al. 2018

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Abstract. Ultraviolet photoacoustic microscopy (UV-PAM) is a promising intraoperative tool for surgical margin assessment (SMA), one that can provide label-free histology-like images with high resolution. In this study, using a microlens array and a one-dimensional (1-D) array ultrasonic transducer, we developed a high-throughput multifocal UV-PAM (MF-UV-PAM). Our new system achieved a 1.6 AE 0.2 μm lateral resolution and produced images 40 times faster than the previously developed point-by-point scanning UV-PAM. MF-UV-PAM provided a readily comprehensible photoacoustic image of a mouse brain slice with specific absorption contrast in ∼16 min, highlighting cell nuclei. Individual cell nuclei could be clearly resolved, showing its practical potential for intraoperative SMA.

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Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

High-throughput ultraviolet photoacoustic microscopy with multifocal excitation

et al. 2018

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“…Furthermore, PAM's label-free nature enables it to image differently embedded organs for different applications, e.g., paraffin and agarose are the most common embedding materials used in conventional histology and neuroscience, respectively. Here, we demonstrate the first label-free mPAM, using UV light for histology-like imaging without staining 5 , in whole organs (e.g., mouse brains), most of them formalin-fixed and paraffin-or agarose-embedded for minimal morphological deformation. Furthermore, mPAM with dual wavelength illuminations is also employed to image a mouse brain slice, demonstrating the potential for label-free imaging of multiple biomolecules.…”

Section: Introductionmentioning

confidence: 99%

Whole-organ atlas imaged by label-free high-resolution photoacoustic microscopy assisted by a microtome

Wong

Zhang

Hsu

et al. 2018

Photons Plus Ultrasound: Imaging and Sensing 2018

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In biomedical imaging, all optical techniques face a fundamental trade-off between spatial resolution and tissue penetration. Therefore, obtaining an organelle-level resolution image of a whole organ has remained a challenging and yet appealing scientific pursuit. Over the past decade, optical microscopy assisted by mechanical sectioning or chemical clearing of tissue has been demonstrated as a powerful technique to overcome this dilemma, one of particular use in imaging the neural network. However, this type of techniques needs lengthy special preparation of the tissue specimen, which hinders broad application in life sciences. Here, we propose a new label-free three-dimensional imaging technique, named microtomy-assisted photoacoustic microscopy (mPAM), for potentially imaging all biomolecules with 100% endogenous natural staining in whole organs with high fidelity. We demonstrate the first label-free mPAM, using UV light for label-free histology-like imaging, in whole organs (e.g., mouse brains), most of them formalin-fixed and paraffin-or agarose-embedded for minimal morphological deformation. Furthermore, mPAM with dual wavelength illuminations is also employed to image a mouse brain slice, demonstrating the potential for imaging of multiple biomolecules without staining. With visible light illumination, mPAM also shows its deep tissue imaging capability, which enables less slicing and hence reduces sectioning artifacts. mPAM could potentially provide a new insight for understanding complex biological organs.

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“…PAT has been demonstrated capable of providing structural, functional, and metabolic information [12][13][14][15][16] . PAT has also successfully measured the elastic properties of biological tissue, including strain 5 , the viscosity-elasticity ratio 17 , and vascular compliance 18 .…”

Section: Introductionmentioning

confidence: 99%

Quantitative photoacoustic elastography of Young’s modulus in humans

Hai

Zhou

Gong

et al. 2017

Photons Plus Ultrasound: Imaging and Sensing 2017

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Elastography can noninvasively map the elasticity distribution of biological tissue, which is often altered in pathological states. In this work, we report quantitative photoacoustic elastography (QPAE), capable of measuring Young's modulus of human tissue in vivo. By combining photoacoustic elastography with a stress sensor having known stress-strain behavior, QPAE can simultaneously measure strain and stress, from which Young's modulus is calculated. We first applied QPAE to quantify the Young's modulus of tissue-mimicking agar phantoms with different concentrations. The measured values fitted well with both the empirical expectations based on the agar concentrations and those measured in independent standard compression tests. We then demonstrated the feasibility of QPAE by measuring the Young's modulus of human skeletal muscle in vivo. The data showed a linear relationship between muscle stiffness and loading. The results proved that QPAE can noninvasively quantify the absolute elasticity of biological tissue, thus enabling longitudinal imaging of tissue elasticity. QPAE can be exploited for both preclinical biomechanics studies and clinical applications.

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Fast label-free multilayered histology-like imaging of human breast cancer by photoacoustic microscopy

Abstract: A photoacoustic microscope system provides label-free multilayered histology-like imaging of unprocessed human breast specimens.

Cited by 213 publications

References 39 publications

High-throughput ultraviolet photoacoustic microscopy with multifocal excitation

High-throughput ultraviolet photoacoustic microscopy with multifocal excitation

Whole-organ atlas imaged by label-free high-resolution photoacoustic microscopy assisted by a microtome

Quantitative photoacoustic elastography of Young’s modulus in humans

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