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      Estimating blood oxygenation from photoacoustic images: can a simple linear spectroscopic inversion ever work?

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          Abstract.

          Linear spectroscopic inversions, in which photoacoustic amplitudes are assumed to be directly proportional to absorption coefficients, are widely used in photoacoustic imaging to estimate blood oxygen saturation because of their simplicity. Unfortunately, they do not account for the spatially varying wavelength-dependence of the light fluence within the tissue, which introduces “spectral coloring,” a potentially significant source of error. However, accurately correcting for spectral coloring is challenging, so we investigated whether there are conditions, e.g., sets of wavelengths, where it is possible to ignore the spectral coloring and still obtain accurate oxygenation measurements using linear inversions. Accurate estimates of oxygenation can be obtained when the wavelengths are chosen to (i) minimize spectral coloring, (ii) avoid ill-conditioning, and (iii) maintain a sufficiently high signal-to-noise ratio (SNR) for the estimates to be meaningful. It is not obvious which wavelengths will satisfy these conditions, and they are very likely to vary for different imaging scenarios, making it difficult to find general rules. Through the use of numerical simulations, we isolated the effect of spectral coloring from sources of experimental error. It was shown that using wavelengths between 500 nm and 1000 nm yields inaccurate estimates of oxygenation and that careful selection of wavelengths in the 620- to 920-nm range can yield more accurate oxygenation values. However, this is only achievable with a good prior estimate of the true oxygenation. Even in this idealized case, it was shown that considerable care must be exercised over the choice of wavelengths when using linear spectroscopic inversions to obtain accurate estimates of blood oxygenation. This suggests that for a particular imaging scenario, obtaining accurate and reliable oxygenation estimates using linear spectroscopic inversions requires careful modeling or experimental studies of that scenario, taking account of the instrumentation, tissue anatomy, likely sO 2 range, and image formation process.

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          Most cited references38

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          Photoacoustic Microscopy.

          Photoacoustic microscopy (PAM) is a hybrid in vivo imaging technique that acoustically detects optical contrast via the photoacoustic effect. Unlike pure optical microscopic techniques, PAM takes advantage of the weak acoustic scattering in tissue and thus breaks through the optical diffusion limit (~1 mm in soft tissue). With its excellent scalability, PAM can provide high-resolution images at desired maximum imaging depths up to a few millimeters. Compared with backscattering-based confocal microscopy and optical coherence tomography, PAM provides absorption contrast instead of scattering contrast. Furthermore, PAM can image more molecules, endogenous or exogenous, at their absorbing wavelengths than fluorescence-based methods, such as wide-field, confocal, and multi-photon microscopy. Most importantly, PAM can simultaneously image anatomical, functional, molecular, flow dynamic and metabolic contrasts in vivo. Focusing on state-of-the-art developments in PAM, this Review discusses the key features of PAM implementations and their applications in biomedical studies.
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            Deep in vivo photoacoustic imaging of mammalian tissues using a tyrosinase-based genetic reporter

            Deep photoacoustic imaging of mammalian cells featuring genetically encoded contrast is reported.
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              Oxygenation of human tumors: evaluation of tissue oxygen distribution in breast cancers by computerized O2 tension measurements.

              Direct oxygen partial pressure (pO2) readings in breast cancers, in fibrocystic disease, and in the normal breast have been obtained using a novel technique which allows for the systematic evaluation of the oxygenation status as a function of pathological staging and histological grading. Measurements were performed in awake pre- and postmenopausal patients with well-defined arterial blood gas status. The measuring procedure encompasses a computerized electrode movement in the tissue which avoids significant compression artifacts and allows routine measurement in human tumors before, during, and after treatment. Using this reliable technique, pO2 measurements in the normal breast and in fibrocystic disease resulted in oxygenation patterns which were characteristic for normal, adequately supplied tissues. The median pO2 values were 65 and 67 mm Hg, respectively, with no pO2 readings below 12.5 mm Hg in the normal breast, and less than or equal to 5 mm Hg in fibrocystic disease, respectively. In contrast, in breast cancers the median pO2 value was 30 mm Hg (pooled data for pathological stages T1-T4). To date, 6 of 15 breast cancers exhibited pO2 values between zero and 2.5 mm Hg, i.e., tissue areas with less than half-maximum radiosensitivity. The oxygenation pattern in breast cancers and the occurrence of hypoxia and/or anoxia did not correlate with either the pathological stages and histological grades or with a series of clinically relevant parameters. No significant differences were found between pre- and postmenopausal tumors and between lobular and ductal carcinomas. Tumor-to-tumor variability in the oxygenation pattern was more pronounced than intra-tumor heterogeneity. pO2 variations within a tumor cannot be predicted, e.g., as a function of the measuring site (tumor center versus periphery).
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                Author and article information

                Contributors
                Journal
                J Biomed Opt
                J Biomed Opt
                JBOPFO
                JBO
                Journal of Biomedical Optics
                Society of Photo-Optical Instrumentation Engineers
                1083-3668
                1560-2281
                17 December 2019
                December 2019
                17 December 2019
                : 24
                : 12
                : 121914
                Affiliations
                [1]University College London , Department of Medical Physics and Biomedical Engineering, London, United Kingdom
                Author notes
                [* ]Address all correspondence to Benjamin T. Cox, E-mail: b.cox@ 123456ucl.ac.uk
                Author information
                https://orcid.org/0000-0001-7296-4093
                Article
                JBO-190237SSR 190237SSR
                10.1117/1.JBO.24.12.121914
                7005536
                31849203
                7cf3f489-1967-48a4-97ac-4673fd97d4ff
                © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.
                History
                : 4 July 2019
                : 21 November 2019
                Page count
                Figures: 7, Tables: 0, References: 52, Pages: 13
                Funding
                Funded by: EPSRC Centre for Doctoral Training in Medical Imaging
                Award ID: EP/L016478/1
                Funded by: European Union’s Horizon 2020
                Award ID: 732411
                Funded by: European Research Council
                Award ID: 741149
                Categories
                Special Section Celebrating the Exponential Growth of Biomedical Optoacoustic/Photoacoustic Imaging
                Paper
                Custom metadata
                Hochuli et al.: Estimating blood oxygenation from photoacoustic images…

                Biomedical engineering
                blood oxygen saturation,multiwavelength photoacoustic tomography,light fluence

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