Stanford Advisors


All Publications


  • 3D Multiparametric Photoacoustic Computed Tomography of Primary and Metastatic Tumors in Living Mice. ACS nano Kim, J., Lee, J., Choi, S., Lee, H., Yang, J., Jeon, H., Sung, M., Kim, W. J., Kim, C. 2024

    Abstract

    Photoacoustic computed tomography (PACT), an emerging imaging modality in preclinical cancer research, can provide multiparametric 3D information about structures, physiological functions, and pharmacokinetics. Here, we demonstrate the use of high-definition 3D multiparametric PACT imaging of both primary and metastatic tumors in living mice to noninvasively monitor angiogenesis, carcinogenesis, hypoxia, and pharmacokinetics. The high-definition PACT system with a 1024-element hemispherical ultrasound transducer array provides an isotropic spatial resolution of 380 mum, an effective volumetric field-of-view of 12.8 mm * 12.8 mm * 12.8 mm without scanning, and an acquisition time of <30 s for a whole mouse body. Initially, we monitor the structural progression of the tumor microenvironment (e.g., angiogenesis and vessel tortuosity) after tumor cell inoculation. Then, we analyze the change in oxygen saturation of the tumor during carcinogenesis, verifying induced hypoxia in the tumor's core region. Finally, the whole-body pharmacokinetics are photoacoustically imaged after intravenous injection of micelle-loaded IR780 dye, and the in vivo PACT results are validated in vivo and ex vivo by fluorescence imaging. By employing the premium PACT system and applying multiparametric analyses to subcutaneous primary tumors and metastatic liver tumors, we demonstrate that this PACT system can provide multiparametric analyses for comprehensive cancer research.

    View details for DOI 10.1021/acsnano.3c12551

    View details for PubMedID 38941553

  • X-ray free-electron laser induced acoustic microscopy (XFELAM). Photoacoustics Choi, S., Park, S., Kim, J., Kim, H., Cho, S., Kim, S., Park, J., Kim, C. 2024; 35: 100587

    Abstract

    The X-ray free-electron laser (XFEL) has remarkably advanced X-ray imaging technology and enabled important scientific achievements. The XFEL's extremely high power, short pulse width, low emittance, and high coherence make possible such diverse imaging techniques as absorption/emission spectroscopy, diffraction imaging, and scattering imaging. Here, we demonstrate a novel XFEL-based imaging modality that uses the X-ray induced acoustic (XA) effect, which we call X-ray free-electron laser induced acoustic microscopy (XFELAM). Initially, we verified the XA effect by detecting XA signals from various materials, then we validated the experimental results with simulation outcomes. Next, in resolution experiments, we successfully imaged a patterned tungsten target with drilled various-sized circles at a spatial resolution of 7.8 ± 5.1 µm, which is the first micron-scale resolution achieved by XA imaging. Our results suggest that the novel XFELAM can expand the usability of XFEL in various areas of fundamental scientific research.

    View details for DOI 10.1016/j.pacs.2024.100587

    View details for PubMedID 38312809

    View details for PubMedCentralID PMC10835452

  • Recent Advances in Contrast-Enhanced Photoacoustic Imaging: Overcoming the Physical and Practical Challenges. Chemical reviews Choi, W., Park, B., Choi, S., Oh, D., Kim, J., Kim, C. 2023; 123 (11): 7379-7419

    Abstract

    For decades now, photoacoustic imaging (PAI) has been investigated to realize its potential as a niche biomedical imaging modality. Despite its highly desirable optical contrast and ultrasonic spatiotemporal resolution, PAI is challenged by such physical limitations as a low signal-to-noise ratio (SNR), diminished image contrast due to strong optical attenuation, and a lower-bound on spatial resolution in deep tissue. In addition, contrast-enhanced PAI has faced practical limitations such as insufficient cell-specific targeting due to low delivery efficiency and difficulties in developing clinically translatable agents. Identifying these limitations is essential to the continuing expansion of the field, and substantial advances in developing contrast-enhancing agents, complemented by high-performance image acquisition systems, have synergistically dealt with the challenges of conventional PAI. This review covers the past four years of research on pushing the physical and practical challenges of PAI in terms of SNR/contrast, spatial resolution, targeted delivery, and clinical application. Promising strategies for dealing with each challenge are reviewed in detail, and future research directions for next generation contrast-enhanced PAI are discussed.

    View details for DOI 10.1021/acs.chemrev.2c00627

    View details for PubMedID 36642892

  • Theoretical and experimental comparison of the performance of gold, titanium, and platinum nanodiscs as contrast agents for photoacoustic imaging. RSC advances Wi, J. S., Kim, J., Kim, M. Y., Choi, S., Jung, H. J., Kim, C., Na, H. K. 2023; 13 (14): 9441-9447

    Abstract

    Exogenous contrast agents in photoacoustic imaging help improve spatial resolution and penetration depth and enable targeted molecular imaging. To screen efficient photoacoustic signaling materials as contrast agents, we propose a light absorption-weighted figure of merit (FOM) that can be calculated using material data from the literature and numerically simulated light absorption cross-sections. The calculated light absorption-weighted FOM shows that a Ti nanodisc has a photoacoustic conversion performance similar to that of an Au nanodisc and better than that of a Pt nanodisc. The photoacoustic imaging results of Ti, Au, and Pt nanodiscs, which are physically synthesized with identical shapes and dimensions, experimentally demonstrated that the Ti nanodisc could be a highly efficient contrast agent.

    View details for DOI 10.1039/d3ra00795b

    View details for PubMedID 36968039

    View details for PubMedCentralID PMC10034477

  • Deep Learning Enhances Multiparametric Dynamic Volumetric Photoacoustic Computed Tomography In Vivo (DL-PACT). Advanced science (Weinheim, Baden-Wurttemberg, Germany) Choi, S., Yang, J., Lee, S. Y., Kim, J., Lee, J., Kim, W. J., Lee, S., Kim, C. 2022; 10 (1): e2202089

    Abstract

    Photoacoustic computed tomography (PACT) has become a premier preclinical and clinical imaging modality. Although PACT's image quality can be dramatically improved with a large number of ultrasound (US) transducer elements and associated multiplexed data acquisition systems, the associated high system cost and/or slow temporal resolution are significant problems. Here, a deep learning-based approach is demonstrated that qualitatively and quantitively diminishes the limited-view artifacts that reduce image quality and improves the slow temporal resolution. This deep learning-enhanced multiparametric dynamic volumetric PACT approach, called DL-PACT, requires only a clustered subset of many US transducer elements on the conventional multiparametric PACT. Using DL-PACT, high-quality static structural and dynamic contrast-enhanced whole-body images as well as dynamic functional brain images of live animals and humans are successfully acquired, all in a relatively fast and cost-effective manner. It is believed that the strategy can significantly advance the use of PACT technology for preclinical and clinical applications such as neurology, cardiology, pharmacology, endocrinology, and oncology.

    View details for DOI 10.1002/advs.202202089

    View details for PubMedID 36354200

    View details for PubMedCentralID PMC9811490

  • Practical review on photoacoustic computed tomography using curved ultrasound array transducer. Biomedical engineering letters Yang, J., Choi, S., Kim, C. 2022; 12 (1): 19-35

    Abstract

    Photoacoustic computed tomography (PACT) has become a promising imaging modality from laboratory to clinical research. Of many components of PACT system, the ultrasound (US) array transducer is an essential device to simultaneously receive photoacoustic (PA) signals from several directions in a parallel manner. Many research groups and companies have developed various types of US array transducers while accounting the properties of the PA waves to achieve better image quality, deeper imaging depth, faster imaging speed, and a wider field of view. In this review, we present the implementation and application of the state-of-the-art PACT systems using several types of curved US arrays: arc-shaped, ring-shaped, and hemispherical array transducers. Furthermore, we discuss the current limitations of PACT and also potential future directions for enhancing them.

    View details for DOI 10.1007/s13534-021-00214-8

    View details for PubMedID 35186358

    View details for PubMedCentralID PMC8825902

  • In situ x-ray-induced acoustic computed tomography with a contrast agent: a proof of concept. Optics letters Choi, S., Park, S., Pyo, A., Kim, D. Y., Min, J. J., Lee, C., Kim, C. 2022; 47 (1): 90-93

    Abstract

    X-ray-induced acoustic computed tomography (XACT) has shown great potential as a hybrid imaging modality for real-time non-invasive x-ray dosimetry and low-dose three-dimensional (3D) imaging. While promising, one drawback of the XACT system is the underlying low signal-to-noise ratio (SNR), limiting its in vivo clinical use. In this Letter, we propose the first use of a conventional x-ray computed tomography contrast agent, Gastrografin, for improving the SNR of in situ XACT imaging. We obtained 3D volumetric XACT images of a mouse's stomach with orally injected Gastrografin establishing the proposal's feasibility. Thus, we believe, in the future, our proposed technique will allow in vivo imaging and expand or complement conventional x-ray modalities, such as radiotherapy and accelerators.

    View details for DOI 10.1364/OL.447618

    View details for PubMedID 34951888

  • Synchrotron X-ray induced acoustic imaging. Scientific reports Choi, S., Park, E. Y., Park, S., Kim, J. H., Kim, C. 2021; 11 (1): 4047

    Abstract

    X-ray induced acoustic imaging (XAI) is an emerging biomedical imaging technique that can visualize X-ray absorption contrast at ultrasound resolution with less ionizing radiation exposure than conventional X-ray computed tomography. So far, medical linear accelerators or industrial portable X-ray tubes have been explored as X-ray excitation sources for XAI. Here, we demonstrate the first feasible synchrotron XAI (sXAI). The synchrotron generates X-rays, with a dominant energy of 4 to 30 keV, a pulse-width of 30 ps, a pulse-repetition period of 2 ns, and a bunch-repetition period of 940 ns. The X-ray induced acoustic (XA) signals are processed in the Fourier domain by matching the signal frequency with the bunch-repetition frequency. We successfully obtained two-dimensional XA images of various lead targets. This novel sXAI tool could complement conventional synchrotron applications.

    View details for DOI 10.1038/s41598-021-83604-3

    View details for PubMedID 33603050

    View details for PubMedCentralID PMC7893053

  • Versatile Single-Element Ultrasound Imaging Platform using a Water-Proofed MEMS Scanner for Animals and Humans. Scientific reports Choi, S., Kim, J. Y., Lim, H. G., Baik, J. W., Kim, H. H., Kim, C. 2020; 10 (1): 6544

    Abstract

    Single-element transducer based ultrasound (US) imaging offers a compact and affordable solution for high-frequency preclinical and clinical imaging because of its low cost, low complexity, and high spatial resolution compared to array-based US imaging. To achieve B-mode imaging, conventional approaches adapt mechanical linear or sector scanning methods. However, due to its low scanning speed, mechanical linear scanning cannot achieve acceptable temporal resolution for real-time imaging, and the sector scanning method requires specialized low-load transducers that are small and lightweight. Here, we present a novel single-element US imaging system based on an acoustic mirror scanning method. Instead of physically moving the US transducer, the acoustic path is quickly steered by a water-proofed microelectromechanical (MEMS) scanner, achieving real-time imaging. Taking advantage of the low-cost and compact MEMS scanner, we implemented both a tabletop system for in vivo small animal imaging and a handheld system for in vivo human imaging. Notably, in combination with mechanical raster scanning, we could acquire the volumetric US images in live animals. This versatile US imaging system can be potentially used for various preclinical and clinical applications, including echocardiography, ophthalmic imaging, and ultrasound-guided catheterization.

    View details for DOI 10.1038/s41598-020-63529-z

    View details for PubMedID 32300153

    View details for PubMedCentralID PMC7162865

  • Super Wide-Field Photoacoustic Microscopy of Animals and Humans In Vivo. IEEE transactions on medical imaging Baik, J. W., Kim, J. Y., Cho, S., Choi, S., Kim, J., Kim, C. 2020; 39 (4): 975-984

    Abstract

    Acoustic-resolution photoacoustic micro-scopy (AR-PAM) is an emerging biomedical imaging modality that combines superior optical sensitivity and fine ultrasonic resolution in an optical quasi-diffusive regime (~1-3 mm in tissues). AR-PAM has been explored for anatomical, functional, and molecular information in biological tissues. Heretofore, AR-PAM systems have suffered from a limited field-of-view (FOV) and/or slow imaging speed, which have precluded them from routine preclinical and clinical applications. Here, we demonstrate an advanced AR-PAM system that overcomes both limitations of previous AR-PAM systems. The new AR-PAM system demonstrates a super wide-field scanning that utilized a 1-axis water-proofing microelectromechanical systems (MEMS) scanner integrated with two linear stepper motor stages. We achieved an extended FOV of 36 ×80 mm2 by mosaicking multiple volumetric images of 36 ×2.5 mm2 with a total acquisition time of 224 seconds. For one volumetric data (i.e., 36 ×2.5 mm2), the B-scan imaging speed over the short axis (i.e., 2.5 mm) was 83 Hz in humans. The 3D volumetric image was also provided by using MEMS mirror scanning along the X-axis and stepper-motor scanning along the Y-axis. The super-wide FOV mosaic image was realized by registering and merging all individual volumetric images. Finally, we obtained multi-plane whole-body in-vivo PA images of small animals, illustrating distinct multi-layered structures including microvascular networks and internal organs. Importantly, we also visualized microvascular networks in human fingers, palm, and forearm successfully. This advanced MEMS-AR-PAM system could potentially enable hitherto not possible wide preclinical and clinical applications.

    View details for DOI 10.1109/TMI.2019.2938518

    View details for PubMedID 31484110

  • GPU-accelerated 3D volumetric X-ray-induced acoustic computed tomography. Biomedical optics express Lee, D., Park, E. Y., Choi, S., Kim, H., Min, J. J., Lee, C., Kim, C. 2020; 11 (2): 752-761

    Abstract

    X-ray acoustic imaging is a hybrid biomedical imaging technique that can acoustically monitor X-ray absorption distribution in biological tissues through the X-ray induced acoustic effect. In this study, we developed a 3D volumetric X-ray-induced acoustic computed tomography (XACT) system with a portable pulsed X-ray source and an arc-shaped ultrasound array transducer. 3D volumetric XACT images are reconstructed via the back-projection algorithm, accelerated by a custom-developed graphics processing unit (GPU) software. Compared with a CPU-based software, the GPU software reconstructs an image over 40 times faster. We have successfully acquired 3D volumetric XACT images of various lead targets, and this work shows that the 3D volumetric XACT system can monitor a high-resolution X-ray dose distribution and image X-ray absorbing structures inside biological tissues.

    View details for DOI 10.1364/BOE.381963

    View details for PubMedID 32133222

    View details for PubMedCentralID PMC7041460