654 IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. 57, NO. 3, MARCH 2010 Real-time Chirp-Coded Imaging With a Programmable Ultrasound Biomicroscope Matt´ eo R. Bosisio, Jean-Michel Hasquenoph, Laurent Sandrin, Member, IEEE, Pascal Laugier, S. Lori Bridal ∗ , Senior Member, IEEE, and Sylvain Yon, Member, IEEE Abstract—Ultrasound biomicroscopy (UBM) of mice can pro- vide a testing ground for new imaging strategies. The UBM system presented in this paper facilitates the development of imaging and measurement methods with programmable design, arbitrary wave- form coding, broad bandwidth (2–80 MHz), digital filtering, pro- grammable processing, RF data acquisition, multithread/multicore real-time display, and rapid mechanical scanning (≤170 frames/s). To demonstrate the capacities of the UBM system, chirp (1.28, 2.56, and 5.12 μs durations) sequences with matched filter analysis are implemented in real time. Chirp and conventional impulse imag- ing (31 and 46 MHz center frequencies) of a wire phantom at fast sectorial scanning (0.7 ◦ ms −1 , 20 frames/s one-way image rate) are compared. Axial and lateral resolutions at the focus with chirps approach impulse imaging resolutions. Chirps yield 10–15 dB gain in SNR and a 2–3 mm gain in imaging depth. Real-time impulse and chirp-coded imaging (at 10–5 frames/s) are demonstrated in the mouse, in vivo. The system’s open structure favors test and implementation of new sequences. Index Terms—Biomedical acoustic imaging, chirp modulation, finite-impulse response (FIR) digital filters, matched filters, signal analysis. I. INTRODUCTION U SE of small animals for the study of human disease and drug development has rapidly increased during the last decades [1], [2]. Noninvasive imaging plays an important role in the longitudinal characterization of phenotypes and pathology. Research in this domain has been fuelled by the need to adapt imaging techniques to small animals [3]–[8]. Manuscript received February 3, 2009; revised June 18, 2009 and July 27, 2009. First published September 29, 2009; current version published February 17, 2010. This work was supported by the Programme Interdisciplinaire Im- agerie du Petit Animal (Centre National de la Recherche Scientifique, CNRS— Institut National de la Sant´ e et de la Recherche M´ edicale—Commissariat a l’Energie Atomique, and by the Fondation pour la Recherche et la Technologie, French Research Ministry. The work of M. R. Bosisio was supported by the Association Nationale de la Recherche et de la Technologie. Asterisk indicates corresponding author. M. R. Bosisio was with the Laboratoire d’Imagerie Param´ etrique UMR 7623, Universit´ e Pierre et Marie Curie UPMC Paris 6 and CNRS, Paris F-75005, France, and with the Department of Research and Development, Echosens S.A., Paris F-75013, France (e-mail: matteo.bosisio@gmail.com). J.-M. Hasquenoph and L. Sandrin are with the Department of Re- search and Development, Echosens S.A., Paris F-75013, France (e-mail: hasquenoph8@aol.com; laurent.sandrin@echosens.com). P. Laugier is with the Laboratoire d’Imagerie Param´ etrique UMR 7623, UPMC Paris 6 and CNRS, Paris F-75005, France (e-mail: laugier@lip.bhdc. jussieu.fr). ∗ S. L. Bridal is with the Laboratoire d’Imagerie Param´ etrique UMR 7623, UPMC Paris 6 and CNRS, Paris F-75005, France (e-mail: lori.bridal@upmc.fr). S. Yon was with the Department of Research and Development, Echosens S.A., Paris F-75013, France. He is now with Theraclion, Paris 75014, France (e-mail: sylvainyon@gmail.com). Color versions of one or more of the figures in this paper are available online at http://ieeexplore.ieee.org. Digital Object Identifier 10.1109/TBME.2009.2033036 Ultrasound biomicroscopy (UBM) is an established and rapidly growing high-resolution (>30 MHz) imaging technique that provides anatomical and functional information on living small animals [6], [9]–[16]. The most widely used, commer- cially available UBM system is a single-channel UBM scanner with mechanically scanned single-element transducers between 20 and 80 MHz center frequency (Vevo 770, Visualsonics, Inc., Toronto, ON, Canada). It can provide up to 240 frames/s (at 1-mm image width), high resolution (up to 30 μm), 3-D or 2-D B-mode imaging, image-guided needle placement, and linear contrast-enhanced ultrasound for the assessment of tissue per- fusion [6]. Recently, Visualsonics has added a system with a 64-channel HF linear array (from 9 to 70 MHz) that can provide imaging at up to 1000 frames/s, wider fields of view, and color and power Doppler modes. Although UBM has demonstrated rapid growth and a large variety of useful applications in recent years, important work remains to design and implement new real-time imaging strate- gies, more efficient digital signal processing (DSP), digital com- puting, and image analysis for HF ultrasound. New imaging strategies such as nonlinear contrast, 3-D, Doppler color flow, ul- trahigh frame-rate retrospective imaging synchronized on ECG, and high frame rate with directional Doppler have been recently demonstrated with a single-channel UBM [13], [15]–[18]. It has also been shown that linear frequency-modulated (LFM) sig- nals, or chirp excitation with mismatched filters (MFs) present high SNR improvement (12–18 dB) compared to conventional impulse imaging while maintaining temporal sidelobes below 60–100 dB [19]–[21]. Mamou and Ketterling [22] and Mamou et al. [23] demonstrated that image quality could be improved with 17-MHz chirp excitation using a nonreal-time annular array. The development and testing of such new ultrasound-based imaging strategies is often limited to adaptation of commercially available equipment and/or off-the-shelf electronics resulting in costly solutions that lack flexibility and portability. A truly open and fully digital UBM system dedicated to research is not readily available in the market. Historically, work toward this goal has principally been limited due to challenges in transducer technol- ogy and A/D electronics. The first UBM real-time scanner [24] presented a logarithmic amplifier detector that demodulated the backscattered RF data directly to envelope-compressed signals (A-scan lines). This baseband envelope technique was the state- of-the-art for clinical multichannel, real-time ultrasound sys- tems until the end of the 1980s (and remains so for continu- ous Doppler modalities). It allowed digitization of the HF sig- nals in quadrature by two A/D converters at significantly lower 0018-9294/$26.00 © 2009 IEEE