Calibration-free absolute quantification of particle concentration by statistical analyses of photoacoustic signals in vivo
Currently, laser fluence calibration is typically required for quantitative measurement of particle concentration in photoacoustic imaging. Here, we present a calibration-free method to quantify the absolute particle concentration by statistically analyzing photoacoustic signals. The proposed method is based on the fact that Brownian motion induces particle count fluctuation in the detection volume. If the count of particles in the detection volume is assumed to follow the Poisson distribution, its expected value can be calculated by the photoacoustic signal mean and variance. We first derived a theoretical model for photoacoustic signals. Then, we applied our method to quantitative measurement of different concentrations of various particles, including red blood cells. Finally, we performed in vivo experiments to demonstrate the potential of our method in biological applications. The experimental results agreed well with the predictions from the theoretical model suggesting that our method can be used for noninvasive measurement of absolute particle concentrations in deep tissue without fluence calibration.
Additional Information© 2014 Society of Photo-Optical Instrumentation Engineers (SPIE). Paper 130767R received Oct. 24, 2013; revised manuscript received Jan. 27, 2014; accepted for publication Jan. 28, 2014; published online Mar. 3, 2014. The authors would like to thank James Ballard and Seema Dahlheimer for this paper editing. We also appreciate technical assistance and useful discussions with Jinyang Liang, Chi Zhang, Chenghung Yeh, Lidai Wang, Arie Krumholz and Da-Kang Yao. This work was sponsored in part by National Institutes of Health Grants Nos. DP1 EB016986 (NIH Director's Pioneer Award), R01 CA186567 (NIH Director's Transformative Research Award), R01 EB016963, R01 CA134539, R01 CA157277, and R01 CA159959. L.W. has a financial interest in Microphotoacoustics, Inc. and Endra, Inc., which, however, did not support this work. K.M. has a financial interest in Microphotoacoustics, Inc., which, however, did not support this work.
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