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      A transparent broadband ultrasonic detector based on an optical micro-ring resonator for photoacoustic microscopy.

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          Abstract

          Photoacoustic microscopy (PAM) does not rely on contrast agent to image the optical absorption contrast in biological tissue. It is uniquely suited for measuring several tissue physiological parameters, such as hemoglobin oxygen saturation, that would otherwise remain challenging. Researchers are designing new clinical diagnostic tools and multimodal microscopic systems around PAM to fully unleash its potential. However, the sizeable and opaque piezoelectric ultrasonic detectors commonly used in PAM impose a serious constraint. Our solution is a coverslip-style optically transparent ultrasound detector based on a polymeric optical micro-ring resonator (MRR) with a total thickness of 250 μm. It enables highly-sensitive ultrasound detection over a wide receiving angle with a bandwidth of 140 MHz, which corresponds to a photoacoustic saturation limit of 287 cm(-1), at an estimated noise-equivalent pressure (NEP) of 6.8 Pa. We also established a theoretical framework for designing and optimizing the MRR for PAM.

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          Most cited references33

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          Optical coherence tomography.

          A technique called optical coherence tomography (OCT) has been developed for noninvasive cross-sectional imaging in biological systems. OCT uses low-coherence interferometry to produce a two-dimensional image of optical scattering from internal tissue microstructures in a way that is analogous to ultrasonic pulse-echo imaging. OCT has longitudinal and lateral spatial resolutions of a few micrometers and can detect reflected signals as small as approximately 10(-10) of the incident optical power. Tomographic imaging is demonstrated in vitro in the peripapillary area of the retina and in the coronary artery, two clinically relevant examples that are representative of transparent and turbid media, respectively.
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            Two-photon excitation fluorescence microscopy.

            Two-photon fluorescence microscopy is one of the most important recent inventions in biological imaging. This technology enables noninvasive study of biological specimens in three dimensions with submicrometer resolution. Two-photon excitation of fluorophores results from the simultaneous absorption of two photons. This excitation process has a number of unique advantages, such as reduced specimen photodamage and enhanced penetration depth. It also produces higher-contrast images and is a novel method to trigger localized photochemical reactions. Two-photon microscopy continues to find an increasing number of applications in biology and medicine.
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              Label-free oxygen-metabolic photoacoustic microscopy in vivo.

              Almost all diseases, especially cancer and diabetes, manifest abnormal oxygen metabolism. Accurately measuring the metabolic rate of oxygen (MRO(2)) can be helpful for fundamental pathophysiological studies, and even early diagnosis and treatment of disease. Current techniques either lack high resolution or rely on exogenous contrast. Here, we propose label-free metabolic photoacoustic microscopy (mPAM) with small vessel resolution to noninvasively quantify MRO(2) in vivo in absolute units. mPAM is the unique modality for simultaneously imaging all five anatomical, chemical, and fluid-dynamic parameters required for such quantification: tissue volume, vessel cross-section, concentration of hemoglobin, oxygen saturation of hemoglobin, and blood flow speed. Hyperthermia, cryotherapy, melanoma, and glioblastoma were longitudinally imaged in vivo. Counterintuitively, increased MRO(2) does not necessarily cause hypoxia or increase oxygen extraction. In fact, early-stage cancer was found to be hyperoxic despite hypermetabolism.
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                Author and article information

                Journal
                Sci Rep
                Scientific reports
                Springer Science and Business Media LLC
                2045-2322
                2045-2322
                Mar 28 2014
                : 4
                Affiliations
                [1 ] 1] Department of Biomedical Engineering, Northwestern University, Evanston IL 60208 [2].
                [2 ] 1] Department of Biomedical Engineering, Northwestern University, Evanston IL 60208 [2] Department of Mechanical Engineering, Northwestern University, Evanston IL 60208 [3].
                [3 ] Department of Mechanical Engineering, Northwestern University, Evanston IL 60208.
                [4 ] 1] Department of Biomedical Engineering, Northwestern University, Evanston IL 60208 [2] Department of Ophthalmology, Northwestern University, Chicago IL 60611.
                Article
                srep04496
                10.1038/srep04496
                3968454
                24675547
                3ca80fb3-adf5-449e-a6c8-83f2ec04234f
                History

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