PHOTOACOUSTIC MICROSCOPY SYSTEM COMPANY PROFILE MicroPhotoAcoustics, Inc. (MPA)—a spin-off from Advanced Optowave Coporation—was founded in 2010 with the inventors of three-dimensional photoacoustic microscopy. Multiple patents have been licensed from Dr. Lihong Wang’s lab, Optical Imaging Laboratory at Washington University in St. Louis. MPA provides commerical photoacoustic microscopy (PAM) systems at both optical resolution (OR-PAM) and acoustic resolution (AR-PAM) worldwide. TECHNOLOGY OVERVIEW Photoacoustic microscopy is the fastest growing biomedical imaging technology, which affords high-resolution sensing of rich optical contrast in vivo at super-depths—depths beyond the optical transport mean free path (~1 mm in the skin). Although commercially available high-resolution three-dimensional optical imaging modalities—including confocal microscopy, two-photon microscopy and optical coherence tomography—have fundamentally impacted biomedicine, none can reach super-depths in tissue. In PAM, short-pulsed laser light is absorbed by biological tissue and converted to transient heating, which is subsequently converted into an ultrasonic wave due to thermoelastic expansion. Detection of the ultrasonic wave yields a tomographic image. Taking advantage of low ultrasonic scattering, PAM equivalently improves tissue optical transparency by a factor of 1000 and consequently enables super-depth penetration at high resolution. As a unique feature, PAM is exquisitely sensitive to optical absorption, most sensitive among all imaging modalities. PAM enables in vivo imaging of the smallest blood vessels (i.e., capillaries) and single cells with intrinsic tissue contrast (i.e., no exogenous contrast agent injected into the tissue). Both functional and molecular imaging based on optical contrast have been achieved by PAM. Copyright ©2011 MicroPhotoAcoustics, Inc. 1 Comparison of Optical Microscopy Technologies Imaging Capability Confocal Microscopy Two-photon Microscopy Optical Coherence Tomography Photoacoustic Microscopy 1 mm 1 mm by OR-PAM 3 mm by AR-PAM (50 MHz) Fluorescence, Fluorescence scattering Scattering, polarization Absorption Resolution ~Depth/200 ~Depth/100 ~Depth/100 ~Depth/100 Multiscale imaging N N N Y Sensitivity to absorption Low (6%) None Low (0.4%) High (100%) Doppler sensing N N Y Y Speckle artifact N N Y N Oxygen saturation of hemoglobin N N N (poor sensitivity) Y Intrinsic-contrast melanin imaging N N N Y Molecular imaging Y Y N (poor sensitivity) Y Reporter gene imaging Y Y N Y Imaging of metabolic rate of oxygen N N N Y Depth 0.2 mm Contrast Copyright ©2011 MicroPhotoAcoustics, Inc. 0.5 mm 2 SYSTEM LAYOUT Copyright ©2011 MicroPhotoAcoustics, Inc. 3 APPLICATIONS 1) High resolution μm lateralresolution) brain 500 µm Copyright ©2011 MicroPhotoAcoustics, Inc. 4 2) Capillary and single red blood cell 500 µm Capillary bed 50 µm RBC Copyright ©2011 MicroPhotoAcoustics, Inc. 5 3) Oxygenation saturation. Structural and functional microvascular imaging of a nude mouse ear in vivo by OR-PAM. pper nm; right: vessel-by-vessel oxygenation saturation (sO2) mapping based on dual-wavelength measurements. The arteries and veins can be identified based on the sO2 map. A1, a representative arteriole; V1, a representative venule; lower: whole ear sO2 map. 1 sO2 100 µm 0.4 1 sO2 500 µm Copyright ©2011 MicroPhotoAcoustics, Inc. 0 6 4) Contrast agents. Intravital PAM of amyloid plaques with Congo Red Dye. Fluorescence TPM 100 µm OR-PAM 100 µm Copyright ©2011 MicroPhotoAcoustics, Inc. 7 5) Label-free PAM of ocular microvasculature in vivo. 200 µm (µm) Copyright ©2011 MicroPhotoAcoustics, Inc. 8 6) Tumor angiogenesis monitoring.Longitudinalmonitoring mediated neovascularization ina mouse . Non-transgenic mouse Transgenic HIF mouse d0 d3 Stage 1: Development d1 d14 d60 Stage 2: Maintenance d30 500 µm Copyright ©2011 MicroPhotoAcoustics, Inc. 9 7) Human finger cuticle. 500 µm 200 µm Low sO2 Copyright ©2011 MicroPhotoAcoustics, Inc. High sO2 10 Transverse blood flow. Simultaneous photoacoustic imaging of oxygen saturation and blood flow. (a) MAP of structural image. (b) MAP of oxygen saturation image measured by two wavelengths 560 nm and 570 nm. (c) Blood flow image measured by the Doppler bandwidth broadening. The flow direction was determined by a bidirectional motor scanning. (d) The vascular traces with the oxygen saturation, averaged along the segments of the vessels. (e) The vascular traces with the blood flow velocity, in millimeters per second, averaged along the segments of the vessels. (f) The transverse velocity profile of the blood flow indicated by the dashed line in (c). Scale bar = 250 μm. Optical absorption (d) Min (a) Max 8) 1.0 Oxygen saturation (b) (e) 0.9 0.8 0.7 0.6 (f) 0 -2 -4 Copyright ©2011 MicroPhotoAcoustics, Inc. 6 velocity (mm/s) 2. Flow velocity (mm/s) (c) 4 4 2 0 -2 -4 -6 0200400600800 1000 Position (µm) 11 9) Monitoring of melanoma th .(a)PAM in the ear acquired before injection of melanoma cells. (b) PAM image where in vivo red blood cells (RBCs) can be identified (the close-up image indicates the biconcave structure of RBCs). (c) PAM image of blood vessels and melanoma taken four days after injecting melanoma cells. The melanoma image is extracted by taking the difference of the two PAM images [(a) and (c)] and is plotted in gray: MT, melanoma tumor. (d) Optical microscopy image (0.057 NA) of the same area in (a) and (c). a) b) 200 µm 20 µm 5 µm RBC c) d) MT Vasculature m a x m i n Melanoma Copyright ©2011 MicroPhotoAcoustics, Inc. 12 10) Image of 25 µm PAM image of section without staining. Section thickness: 6 µm. 25 µm Optical micrograph (20X, 0.45 N.A.) of the section stained by hematoxylin and eosin. Copyright ©2011 MicroPhotoAcoustics, Inc. 13 TECHNICAL SPECIFICATIONS In vivo imaging at tissue depths up to 1.2 mm OR-PAM Systems Lateral resolution down to 5 µm Axial resolution down to 15 µm Integrated, KHz tunable laser In vivo imaging at tissue depths up to 3 mm AR-PAM Systems Axial resolution down to 15 µm Lateral resolution down to 45 µm Integrated, KHz tunable laser Copyright ©2011 MicroPhotoAcoustics, Inc. 14 MicroPhotoAcoustics Inc 113 Comac Street Ronkonkoma, NY 11779, USA Tel :1-631-974-6268, Fax:1-631-389-2554 Web: www.biompa.com MicroPhotoAcoustics Inc. follows a policy of continuous product improvement. Specifications are subject to change without notice. MicroPhotoAcoustics Inc offers a limited warranty for its products. For full details on warranty coverage, or for further product information, please contact MicroPhotoAcoustics Inc. Copyright ©2011 MicroPhotoAcoustics, Inc. 15
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