Wibool Piyawattanametha

National Electronics and Computer Technology Center, Bang Kadi, Pathum Thani, Thailand

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Publications (68)99.47 Total impact

  • SPIE Photonics West; 10/2013
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    ABSTRACT: A new chapter in the history of medical diagnosis happened when the first X-ray technology was invented in the late 1800s. Since then, many non-invasive and minimally invasive imaging techniques have been invented for clinical diagnosis to research in cellular biology, drug discovery, and disease monitoring. These imaging modalities have leveraged the benefits of significant advances in computer, electronics, and information technology and, more recently, targeted molecular imaging. The development of targeted contrast agents such as fluorescent and nanoparticle probes has made it possible to selectively view specific biological events and processes in both in vivo and ex vivo systems with great sensitivity and selectivity. Thus, these contrast agents or targeted molecular probes have become a mainstay in modern medicinal and biological research. Many promising results have showed potentials to translate to clinical applications. In this review, we describe a discussion of employing imaging probes and optical microendoscopic imaging techniques for cancer diagnosis to enable favorable treatment outcome.
    Advanced drug delivery reviews 10/2013; · 11.96 Impact Factor
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    ABSTRACT: A MEMS based handheld multi-spectral confocal microscope has been developed as a noninvasive imaging instrument for cervical cancer screening. Tissue imaging depth of up to 400 μm was demonstrated. The maximum speed of image collection is up to 10 Hz with field of view (FOV) around 200×158 pixel2 size. Our handheld prototype is able to visualize cancer cells with cellular resolution (transverse resolution = 5 μm and axial resolution = 6 μm). Biological imaging demonstration was carried out on cell culture and tissues of human cervix.
    Solid-State Sensors, Actuators and Microsystems (TRANSDUCERS & EUROSENSORS XXVII), 2013 Transducers & Eurosensors XXVII: The 17th International Conference on; 01/2013
  • W. Piyawattanametha
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    ABSTRACT: Progress toward early diagnosis of cancer would have important clinical benefits in reducing cancer mortality; thus, there is an important need to image cellular features of cancer in vivo and in real-time. In this paper, we describe a review of microelectromechanical systems (MEMS) scanner based endoscopic optical coherence tomography (OCT), two-photon (2P), and confocal imaging. These modalities can provide submicron- and micro-scale resolution to reveal both cells and molecular features of early cancer diagnosis.
    Optical MEMS and Nanophotonics (OMN), 2013 International Conference on; 01/2013
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    ABSTRACT: In this paper, two different designs of two-dimensional MEMs scanner were tested to find their characteristic responses in dynamic mode by applying a fixed voltage at different electrical biasing waveforms: sinusoidal, triangle, square and saw-tooth waveforms. The collected data from the experiment has proven that the significance of MEMS scanner design and driving input signals.
    IEEE International Conference on Electron Devices and Solid State Circuit (EDSSC); 12/2012
  • Numfon Khemthongcharoen, Athisake Ruangpracha, Wibool Piyawattanametha
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    ABSTRACT: This work demonstrates the application of phage display technology for molecular diagnosis utility. We propose a novel phage-displayed peptide which specifically bind to p16INK4a, a cervical cancer biomarker. Whole phage particles were developed as a molecular tracer for ex vivo cells imaging technique. Increase in specific phages binding to p16INK4a overexpressed cells is improved when the cells were initially permeabilized in order to make phage penetrable pores on the target cell membranes. We also proved that fluorescence signal could be obviously enhanced due to tremendous interaction sites for fluorescence dye labeling available on capsid proteins around phage particles. Evaluation of p16INK4a binding phages to discriminate between p16INK4a overexpressed cervical cancer cells versus normal fibroblast cells demonstrated higher fluorescence intensity of 2.5 fold over native phages.
    IEEE 6th International Conference on Nano/Molecular Medicine and Engineering (NANOMED), 2012; 11/2012
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    ABSTRACT: We present a 9.6-mm fiber-coupled probe for femtosecond laser microsurgery and nonlinear imaging. Towards enabling clinical use, we successfully reduced the volume of our earlier 18-mm surgery probe by 5 times, while improving optical performance.
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    ABSTRACT: Near-infrared confocal microendoscopy is a promising technique for deep in vivo imaging of tissues and can generate high-resolution cross-sectional images at the micron-scale. We demonstrate the use of a dual-axis confocal (DAC) near-infrared fluorescence microendoscope with a 5.5-mm outer diameter for obtaining clinical images of human colorectal mucosa. High-speed two-dimensional en face scanning was achieved through a microelectromechanical systems (MEMS) scanner while a micromotor was used for adjusting the axial focus. In vivo images of human patients are collected at 5 frames/sec with a field of view of 362×212 μm(2) and a maximum imaging depth of 140 μm. During routine endoscopy, indocyanine green (ICG) was topically applied a nonspecific optical contrasting agent to regions of the human colon. The DAC microendoscope was then used to obtain microanatomic images of the mucosa by detecting near-infrared fluorescence from ICG. These results suggest that DAC microendoscopy may have utility for visualizing the anatomical and, perhaps, functional changes associated with colorectal pathology for the early detection of colorectal cancer.
    Journal of Biomedical Optics 02/2012; 17(2):021102. · 2.88 Impact Factor
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    ABSTRACT: Our work demonstrated a MEMS based handheld dual-axis confocal microscope for cervical cancer screening. Imaging demonstration is performed with plants and animal tissue biopsies. The data is collected and displayed in real time with 2-5 Hz.
    Electrical Engineering/Electronics, Computer, Telecommunications and Information Technology (ECTI-CON), 2012 9th International Conference on; 01/2012
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    ABSTRACT: We demonstrated a handheld multispectral fluorescence confocal microscope for cervical cancer diagnostic using dual-axis confocal microscope architecture and a microelectromechanical systems scanner. The real time images are acquired with frame rate up to 15 Hz.
    Optical MEMS and Nanophotonics (OMN), 2012 International Conference on; 01/2012
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    ABSTRACT: We describe a 2-D MEMS scanner for a handheld multispectral confocal microscope for early detection of cervical cancer. The MEMS scanner has an inner gimbal design with torsional springs separated from the reflectors to reduce light loss while maintaining chip size to 3.25 × 3.25 mm2. The devices are large-scale batch fabricated using a double layer SOI process. The scanner has electrostatic optical deflection angles of 3.25° for the inner axis at 75 V and ±1.6° for the outer axis at 60 V. The device has resonance frequencies of 2.84 kHz and 452 Hz for the inner and outer axis torsional modes respectively.
    Optical MEMS and Nanophotonics (OMN), 2012 International Conference on; 01/2012
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    Wibool Piyawattanametha, Zhen Qiu
    12/2011; , ISBN: 978-953-51-0306-6
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    ABSTRACT: The problem of limited field of view when visualizing biomedical specimens with high-magnification microscopes can be solved by using image mosaicing or image stitching technique to merge multiple microscopic images acquired from the specimens to create a seamless stitched image. The image mosaicing technique is commonly used in automatically map construction as a path planning system for vision-based robot navigation. By using this technique as the application of digital pathology, it is helpful for pathologists to view different parts of the specimens at high resolution on computer display. In this paper, we present an automatic image mosaicing algorithm which is implemented by using motion estimation technique in image registration step i.e. estimating the two-dimensional translation between each pair of image sequence by using optical flow and phase correlation methods. The aligned images are then fused together using multi-resolution image blending. These algorithms were accomplished to demonstrate the synthetic image sequences in microscopic resolution.
    IEEE International Conference on Robotics and Biomimetics (ROBIO), 2011; 12/2011
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    ABSTRACT: We present the optical design of a 9.6-mm diameter fiber-coupled probe for combined femtosecond laser microsurgery and nonlinear optical imaging. Towards enabling clinical use, we successfully reduced the dimensions of our earlier 18-mm microsurgery probe by half, while improving optical performance. We use analytical and computational models to optimize the miniaturized lens system for off-axis scanning aberrations. The optimization reveals that the optical system can be aberration-corrected using simple aspheric relay lenses to achieve diffraction-limited imaging resolution over a large field of view. Before moving forward with custom lenses, we have constructed the 9.6-mm probe using off-the-shelf spherical relay lenses and a 0.55 NA aspheric objective lens. In addition to reducing the diameter by nearly 50% and the total volume by 5 times, we also demonstrate improved lateral and axial resolutions of 1.27 µm and 13.5 µm, respectively, compared to 1.64 µm and 16.4 µm in our previous work. Using this probe, we can successfully image various tissue samples, such as rat tail tendon that required 2-3 × lower laser power than the current state-of-the-art. With further development, image-guided, femtosecond laser microsurgical probes such as this one can enable physicians to achieve the highest level of surgical precision anywhere inside the body.
    Optics Express 05/2011; 19(11):10536-52. · 3.55 Impact Factor
  • W. Piyawattanametha, M.J. Schnitzer
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    ABSTRACT: We present a portable microendoscope based on a microelectromechanical systems (MEMS) scanner, compound gradient refractive index micro-lenses and a photonics bandgap fiber (PBF). It overcomes the size (2.0 × 1.9 × 1.1 cm<sup>3</sup>) and weight (less than 3 grams) limitations of conventional two-photon fluorescence microscopy toward freely moving subjects. The microendoscope utilizes a photonic bandgap fiber for laser excitation and large core fiber for fluorescence collection. We demonstrated cortical blood flow imaging in live mice with transverse (Δx) and axial resolutions (Δz) of 1.6 μm and 13.5 μm, respectively.
    Nano/Micro Engineered and Molecular Systems (NEMS), 2011 IEEE International Conference on; 03/2011
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    ABSTRACT: We demonstrate an optical configuration of MEMS based a single-axis confocal microscope imaging setup with 12.7 millimeters diameter commercial lenses. The configuration deploys lens models of optical design software, ZEMAX, to predict optical performance of the actual imaging setup. With this optical design, the maximum field of view is 150 μm × 30 μm with 11.96 μm transverse resolutions and 1.98 mm axial resolution.
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    ABSTRACT: Advancing molecular therapies for the treatment of skin diseases will require the development of new tools that can reveal spatiotemporal changes in the microanatomy of the skin and associate these changes with the presence of the therapeutic agent. For this purpose, we evaluated a handheld dual-axis confocal (DAC) microscope that is capable of in vivo fluorescence imaging of skin, using both mouse models and human skin. Individual keratinocytes in the epidermis were observed in three-dimensional image stacks after topical administration of near-infrared (NIR) dyes as contrast agents. This suggested that the DAC microscope may have utility in assessing the clinical effects of a small interfering RNA (siRNA)-based therapeutic (TD101) that targets the causative mutation in pachyonychia congenita (PC) patients. The data indicated that (1) formulated indocyanine green (ICG) readily penetrated hyperkeratotic PC skin and normal callused regions compared with nonaffected areas, and (2) TD101-treated PC skin revealed changes in tissue morphology, consistent with reversion to nonaffected skin compared with vehicle-treated skin. In addition, siRNA was conjugated to NIR dye and shown to penetrate through the stratum corneum barrier when topically applied to mouse skin. These results suggest that in vivo confocal microscopy may provide an informative clinical end point to evaluate the efficacy of experimental molecular therapeutics.
    Journal of Investigative Dermatology 12/2010; 131(5):1061-6. · 6.19 Impact Factor
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    ABSTRACT: Recent advances in optical imaging have led to the development of miniature microscopes that can be brought to the patient for visualizing tissue structures in vivo. These devices have the potential to revolutionize health care by replacing tissue biopsy with in vivo pathology. One of the primary limitations of these microscopes, however, is that the constrained field of view can make image interpretation and navigation difficult. In this paper, we show that image mosaicing can be a powerful tool for widening the field of view and creating image maps of microanatomical structures. First, we present an efficient algorithm for pairwise image mosaicing that can be implemented in real time. Then, we address two of the main challenges associated with image mosaicing in medical applications: cumulative image registration errors and scene deformation. To deal with cumulative errors, we present a global alignment algorithm that draws upon techniques commonly used in probabilistic robotics. To accommodate scene deformation, we present a local alignment algorithm that incorporates deformable surface models into the mosaicing framework. These algorithms are demonstrated on image sequences acquired in vivo with various imaging devices including a hand-held dual-axes confocal microscope, a miniature two-photon microscope, and a commercially available confocal microendoscope.
    IEEE transactions on bio-medical engineering 10/2010; 58(1):159-71. · 2.15 Impact Factor
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    Wibool Piyawattanametha, Thomas D Wang
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    ABSTRACT: We demonstrate a miniature, near-infrared microscope (λ = 785 nm) that uses a novel dual axes confocal architecture. Scalability is achieved with post-objective scanning, and a MEMS mirror provides real time (>4 Hz) in vivo imaging. This instrument can achieve sub-cellular resolution with deep tissue penetration and large field of view. An endoscope-compatible version can image digestive tract epithelium to guide tissue biopsy and monitor therapy.
    IEEE Journal of Selected Topics in Quantum Electronics 07/2010; 16(4):804-814. · 4.08 Impact Factor
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    Wibool Piyawattanametha, Thomas D. Wang
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    ABSTRACT: In this chapter, we present the theory, design and implementation of a novel dual axes confocal microscope in both tabletop and miniature form factors. Separate illumination and collection of light using the region of overlap between the two beams (focal volume) provide a number of advantages for purposes of miniaturization and in vivo imaging. The instruments were developed with 785 nm illumination to take advantage of the “optical window” in tissue where the high dynamic range and deep tissue penetration of this novel architecture can be demonstrated. This instrument is able to achieve sub-cellular resolution (~5 µm), sufficient for in vivo histopathological evaluation. Performance of the dual axes confocal microscope is demonstrated by collecting both en face images in real time and 3D volumetric images with post-processing at a maximum interrogating depth of 300 µm for both ex vivo and in vivo samples. Furthermore, we used this instrument as a test bed to further scale down the dimensions of this architecture to a 5.5 mm diameter package for endoscope compatibility. The size of the instrument has been reduced with a more compact aligning mechanism. We have demonstrated a tissue penetration depth with the dual axes confocal microscope that is unmatched by any other endoscope-compatible instrument. From our in vivo experiments, fluorescence images can be collected up to a depth of 300 μm, limited by the maximum travel of the piezoelectric actuator. Greater depths have been achieved with our tabletop instruments (>500 μm). These results demonstrate the large working distance and high dynamic range of the dual axes confocal architecture to enable deep subsurface tissue imaging. Further improvements in performance can be achieved by increasing light throughput. The relatively low output power of 2 mW can be significantly increased with use of either silver or gold coatings as the reflective surfaces of the MEMS scanner and parabolic mirror, rather than aluminum. In addition, a higher power fiber-coupled laser source can be used. Future development of dual axes confocal architecture will focus on achieving the theoretical levels of performance in a miniature instrument package. In addition, repeatability and reliability will be addressed. We will take advantage of the high dynamic range of the system by developing new z-axis actuators that rapidly scan the focal volume perpendicular to the tissue surface to achieve deep penetration in vertical cross-sections. This orientation provides a powerful view for studying the epithelium and presents a comprehensive picture of the biological differentiation patterns in this thin layer of metabolically active tissue. The epithelium forms the inner lining of all hollow organs, and is accessible by medical endoscopes. In addition, we will extend this approach to multispectral imaging capabilities by developing achromatic optics using the same basic optical
    04/2010; , ISBN: 978-953-307-086-5

Publication Stats

661 Citations
99.47 Total Impact Points


  • 2013
    • National Electronics and Computer Technology Center
      Bang Kadi, Pathum Thani, Thailand
  • 2006–2012
    • Stanford University
      • • Department of Pediatrics
      • • Department of Electrical Engineering
      Stanford, CA, United States
  • 2008–2011
    • University of Texas at Austin
      • Department of Mechanical Engineering
      Texas City, TX, United States
  • 2010
    • Stanford Medicine
      Stanford, California, United States
  • 2000–2006
    • University of California, Los Angeles
      • Department of Electrical Engineering
      Los Angeles, CA, United States