Optical-Resolution Photoacoustic Microscopy Using Transparent Ultrasound Transducer

The opacity of conventional ultrasound transducers can impede the miniaturization and workflow of current photoacoustic systems. In particular, optical-resolution photoacoustic microscopy (OR-PAM) requires the coaxial alignment of optical illumination and acoustic-detection paths through complex beam combiners and a thick coupling medium. To overcome these hurdles, we developed a novel OR-PAM method on the basis of our recently reported transparent lithium niobate (LiNbO3) ultrasound transducer (Dangi et al., Optics Letters, 2019), which was centered at 13 MHz ultrasound frequency with 60% photoacoustic bandwidth. To test the feasibility of wearable OR-PAM, optical-only raster scanning of focused light through a transducer was performed while the transducer was fixed above the imaging subject. Imaging experiments on resolution targets and carbon fibers demonstrated a lateral resolution of 8.5 µm. Further, we demonstrated vasculature mapping using chicken embryos and melanoma depth profiling using tissue phantoms. In conclusion, the proposed OR-PAM system using a low-cost transparent LiNbO3 window transducer has a promising future in wearable and high-throughput imaging applications, e.g., integration with conventional optical microscopy to enable a multimodal microscopy platform capable of ultrasound stimulation.

[1]  Yannis M Paulus,et al.  High-resolution, in vivo multimodal photoacoustic microscopy, optical coherence tomography, and fluorescence microscopy imaging of rabbit retinal neovascularization , 2018, Light, science & applications.

[2]  Wei Liu,et al.  High-speed widefield photoacoustic microscopy of small-animal hemodynamics. , 2018, Biomedical optics express.

[3]  Qifa Zhou,et al.  Label-free automated three-dimensional imaging of whole organs by microtomy-assisted photoacoustic microscopy , 2017, Nature Communications.

[4]  Ex Ovo Model for Directly Visualizing Chick Embryo Development , 2012 .

[5]  Rui Cao,et al.  Functional and oxygen-metabolic photoacoustic microscopy of the awake mouse brain , 2017, NeuroImage.

[6]  Lei Xi,et al.  Ultracompact high-resolution photoacoustic microscopy. , 2018, Optics letters.

[7]  Vasilis Ntziachristos,et al.  Dual‐wavelength hybrid optoacoustic‐ultrasound biomicroscopy for functional imaging of large‐scale cerebral vascular networks , 2018, Journal of biophotonics.

[8]  Bernhard R. Tittmann,et al.  High temperature ultrasonic transducer up to 1000 °C using lithium niobate single crystal , 2010 .

[9]  Hao F. Zhang,et al.  Disposable ultrasound-sensing chronic cranial window by soft nanoimprinting lithography , 2019, Nature Communications.

[10]  Lihong V. Wang,et al.  Single-cell label-free photoacoustic flowoxigraphy in vivo , 2013, Proceedings of the National Academy of Sciences.

[11]  Rudra Pratap,et al.  Ring PMUT array based miniaturized photoacoustic endoscopy device , 2019, BiOS.

[12]  Afshin Kashani Ilkhechi,et al.  Transparent capacitive micromachined ultrasonic transducers (CMUTs) for photoacoustic applications. , 2019, Optics express.

[13]  Sanjiv S. Gambhir,et al.  Simultaneous transrectal ultrasound and photoacoustic human prostate imaging , 2019, Science Translational Medicine.

[14]  Ömer Oralkan,et al.  Backward-Mode Photoacoustic Imaging Using Illumination Through a CMUT With Improved Transparency , 2018, IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control.

[15]  Qing-Ming Wang,et al.  The effective electromechanical coupling coefficient of piezoelectric thin-film resonators , 2005 .

[16]  Lihong V. Wang,et al.  Optical-resolution photoacoustic microscopy for in vivo imaging of single capillaries. , 2008, Optics letters.

[17]  Mehdi Kiani,et al.  A Comprehensive Study of Ultrasound Transducer Characteristics in Microscopic Ultrasound Neuromodulation , 2019, IEEE Transactions on Biomedical Circuits and Systems.

[18]  Jin Young Kim,et al.  High-speed and high-SNR photoacoustic microscopy based on a galvanometer mirror in non-conducting liquid , 2016, Scientific Reports.

[19]  Mohammad Ali Ansari,et al.  MECHANISMS OF LASER-TISSUE INTERACTION: I. OPTICAL PROPERTIES OF TISSUE , 2011 .

[20]  Wei Liu,et al.  Quad-mode functional and molecular photoacoustic microscopy , 2018, Scientific Reports.

[21]  Cheng Sun,et al.  Optical Detection of Ultrasound in Photoacoustic Imaging , 2017, IEEE Transactions on Biomedical Engineering.

[22]  K. Kirk Shung,et al.  Ultrasonic transducers and arrays , 1996 .

[23]  Visweshwar Srinivasan,et al.  Towards a Low-Cost and Portable Photoacoustic Microscope for Point-of-Care and Wearable Applications , 2020, IEEE Sensors Journal.

[24]  S. Tillery,et al.  Transcranial Pulsed Ultrasound Stimulates Intact Brain Circuits , 2010, Neuron.

[25]  Sri-Rajasekhar Kothapalli,et al.  Lithium niobate-based transparent ultrasound transducers for photoacoustic imaging. , 2019, Optics letters.

[26]  Jianguo Ma,et al.  Ultrahigh Frequency (100 MHz–300 MHz) Ultrasonic Transducers for Optical Resolution Medical Imagining , 2016, Scientific Reports.

[27]  John T. Wei,et al.  Interstitial assessment of aggressive prostate cancer by physio‐chemical photoacoustics: An ex vivo study with intact human prostates , 2018, Medical physics.

[28]  Junjie Yao,et al.  In vivo photoacoustic microscopy with 7.6-µm axial resolution using a commercial 125-MHz ultrasonic transducer , 2012, Journal of biomedical optics.

[29]  Peter A Lewin,et al.  Piezoelectric Materials for Imaging , 2007, Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine.

[30]  Lihong V. Wang,et al.  High-speed label-free functional photoacoustic microscopy of mouse brain in action , 2015, Nature Methods.

[31]  Adrien E Desjardins,et al.  All-optical forward-viewing photoacoustic probe for high-resolution 3D endoscopy , 2018, Light: Science & Applications.

[32]  Jan Laufer,et al.  In vivo preclinical photoacoustic imaging of tumor vasculature development and therapy. , 2012, Journal of biomedical optics.

[33]  Qifa Zhou,et al.  Alumina/epoxy nanocomposite matching layers for high-frequency ultrasound transducer application , 2009, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[34]  N Cascinelli,et al.  Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[35]  Eben L. Rosenthal,et al.  Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging , 2018, Annals of Surgical Oncology.

[36]  K. Kirk Shung,et al.  High frequency ultrasound: A new frontier for ultrasound , 2009, 2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[37]  Benjamin A. Rockwell,et al.  A procedure for multiple-pulse maximum permissible exposure determination under the Z136.1-2000 American National Standard for Safe Use of Lasers , 2001 .