Prototype study on a miniaturized dual-modality imaging system for photoacoustic microscopy and confocal fluorescence microscopy

It is beneficial to study tumor angiogenesis and microenvironments by imaging the microvasculature and cells at the same time. Photoacoustic microscopy (PAM) is capable of sensitive three-dimensional mapping of microvasculature, while fluorescence microscopy may be applied to assessment of tissue pathology. In this work, a fiber-optic based PAM and confocal fluorescence microscopy (CFM) dual-modality imaging system was designed and built, serving as a prototype of a miniaturized dual-modality imaging probe for endoscopic applications. As for the design, we employed miniature components, including a microelectromechanical systems (MEMS) scanner, a miniature objective lens, and a small size optical microring resonator as an acoustic detector. The system resolutions were calibrated as 8.8 μm in the lateral directions for both PAM and CFM, and 19 μm and 53 μm in the axial direction for PAM and CFM, respectively. Images of the animal bladders ex vivo were demonstrated to show the ability of the system in imaging not only microvasculature but also cellular structure.

[1]  Tao Ling,et al.  Miniaturized all-optical photoacoustic microscopy based on microelectromechanical systems mirror scanning. , 2012, Optics letters.

[2]  Tao Ling,et al.  High-sensitivity and wide-directivity ultrasound detection using high Q polymer microring resonators. , 2011, Applied physics letters.

[3]  Qifa Zhou,et al.  Photoacoustic ophthalmoscopy for in vivo retinal imaging , 2010, Optics express.

[4]  Yu Wang,et al.  Integrated Photoacoustic and Fluorescence Confocal Microscopy , 2010, IEEE Transactions on Biomedical Engineering.

[5]  Pai-Chi Li,et al.  All-optical scanhead for ultrasound and photoacoustic dual-modality imaging. , 2012, Optics express.

[6]  Joseph C Liao,et al.  Optical biopsy of human bladder neoplasia with in vivo confocal laser endomicroscopy. , 2009, The Journal of urology.

[7]  A. Borowsky,et al.  Laser scanning-based tissue autofluorescence/fluorescence imaging (LS-TAFI), a new technique for analysis of microanatomy in whole-mount tissues. , 2012, The American journal of pathology.

[8]  Andrew H. Beck,et al.  Dynamic real-time microscopy of the urinary tract using confocal laser endomicroscopy. , 2011, Urology.

[9]  Lihong V. Wang,et al.  Photoacoustic imaging and characterization of the microvasculature. , 2010, Journal of biomedical optics.

[10]  Scott B. Raymond,et al.  Smart optical probes for near-infrared fluorescence imaging of Alzheimer’s disease pathology , 2008, European Journal of Nuclear Medicine and Molecular Imaging.

[11]  Lihong V. Wang,et al.  In vivo integrated photoacoustic and confocal microscopy of hemoglobin oxygen saturation and oxygen partial pressure. , 2011, Optics letters.

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

[13]  Da Xing,et al.  Preclinical photoacoustic imaging endoscope based on acousto-optic coaxial system using ring transducer array. , 2010, Optics letters.

[14]  R. Webb,et al.  Video-rate confocal scanning laser microscope for imaging human tissues in vivo. , 1999, Applied optics.

[15]  S. Emelianov,et al.  Photoacoustic imaging in cancer detection, diagnosis, and treatment guidance. , 2011, Trends in biotechnology.

[16]  Thomas D. Wang,et al.  Miniature near-infrared dual-axes confocal microscope utilizing a two-dimensional microelectromechanical systems scanner. , 2007, Optics letters.

[17]  Qifa Zhou,et al.  Reflection-mode submicron-resolution in vivo photoacoustic microscopy. , 2012, Journal of biomedical optics.

[18]  P. Low,et al.  Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results , 2011, Nature Medicine.

[19]  Olav Solgaard,et al.  Fast-scanning two-photon fluorescence imaging based on a microelectromechanical systems two- dimensional scanning mirror. , 2006, Optics letters.

[20]  Jürgen Lademann,et al.  Clinical applicability of in vivo fluorescence confocal microscopy for noninvasive diagnosis and therapeutic monitoring of nonmelanoma skin cancer. , 2008, Journal of biomedical optics.

[21]  Tristan Barrett,et al.  Selective molecular imaging of viable cancer cells with pH-activatable fluorescence probes , 2009, Nature Medicine.

[22]  Jan Scrimgeour,et al.  Fiber-based confocal microscope for cryogenic spectroscopy. , 2008, The Review of scientific instruments.

[23]  P Schneede,et al.  Endoscopic detection of transitional cell carcinoma with 5-aminolevulinic acid: results of 1012 fluorescence endoscopies. , 2001, Urology.

[24]  Sheng-Wen Huang,et al.  High-frequency ultrasound sensors using polymer microring resonators , 2007, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[25]  Kung-Bin Sung,et al.  Fiber optic confocal reflectance microscopy: a new real-time technique to view nuclear morphology in cervical squamous epithelium in vivo. , 2003, Optics express.