Abstract

Photoacoustic computed tomography (PACT) holds great promise for biomedical imaging, but wide-spread implementation is impeded by the bulkiness of flash-lamp-pumped laser systems, which typically weigh between 50 - 200 kg, require continuous water cooling, and operate at a low repetition rate. Here, we demonstrate that compact lasers based on emerging diode technologies are well-suited for preclinical and clinical PACT. The diode-pumped laser used in this study had a miniature footprint (13 × 14 × 7 cm3), weighed only 1.6 kg, and outputted up to 80 mJ per pulse at 1064 nm. In vitro, the laser system readily provided over 4 cm PACT depth in chicken breast tissue. In vivo, in addition to high resolution, non-invasive brain imaging in living mice, the system can operate at 50 Hz, which enabled high-speed cross-sectional imaging of murine cardiac and respiratory function. The system also provided high quality, high-frame rate, and non-invasive three-dimensional mapping of arm, palm, and breast vasculature at multi centimeter depths in living human subjects, demonstrating the clinical viability of compact lasers for PACT.

© 2016 Optical Society of America

Full Article  |  PDF Article
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2016 (9)

D. Wang, Y. Wu, and J. Xia, “Review on photoacoustic imaging of the brain using nanoprobes,” Neurophotonics 3(1), 010901 (2016).
[Crossref] [PubMed]

K. Sivasubramanian and M. Pramanik, “High frame rate photoacoustic imaging at 7000 frames per second using clinical ultrasound system,” Biomed. Opt. Express 7(2), 312–323 (2016).
[Crossref] [PubMed]

Y. Zhou, D. Wang, Y. Zhang, U. Chitgupi, J. Geng, Y. Wang, Y. Zhang, T. R. Cook, J. Xia, and J. F. Lovell, “A Phosphorus Phthalocyanine Formulation with Intense Absorbance at 1000 nm for Deep Optical Imaging,” Theranostics 6(5), 688–697 (2016).
[Crossref] [PubMed]

H.-M. Schwab, M. F. Beckmann, and G. Schmitz, “Photoacoustic clutter reduction by inversion of a linear scatter model using plane wave ultrasound measurements,” Biomed. Opt. Express 7(4), 1468–1478 (2016).
[Crossref] [PubMed]

M. K. A. Singh, M. Jaeger, M. Frenz, and W. Steenbergen, “In vivo demonstration of reflection artifact reduction in photoacoustic imaging using synthetic aperture photoacoustic-guided focused ultrasound (PAFUSion),” Biomed. Opt. Express 7(8), 2955–2972 (2016).
[Crossref] [PubMed]

D. Wang, Y. Wang, Y. Zhou, J. F. Lovell, and J. Xia, “Coherent-weighted three-dimensional image reconstruction in linear-array-based photoacoustic tomography,” Biomed. Opt. Express 7(5), 1957–1965 (2016).
[Crossref] [PubMed]

Y. Wang, D. Wang, Y. Zhang, J. Geng, J. F. Lovell, and J. Xia, “Slit-enabled linear-array photoacoustic tomography with near isotropic spatial resolution in three dimensions,” Opt. Lett. 41(1), 127–130 (2016).
[Crossref] [PubMed]

A. Hussain, W. Petersen, J. Staley, E. Hondebrink, and W. Steenbergen, “Quantitative blood oxygen saturation imaging using combined photoacoustics and acousto-optics,” Opt. Lett. 41(8), 1720–1723 (2016).
[Crossref] [PubMed]

J. Yao, A. A. Kaberniuk, L. Li, D. M. Shcherbakova, R. Zhang, L. Wang, G. Li, V. V. Verkhusha, and L. V. Wang, “Multiscale photoacoustic tomography using reversibly switchable bacterial phytochrome as a near-infrared photochromic probe,” Nat. Methods 13(1), 67–73 (2016).
[PubMed]

2015 (7)

V. W. Wong, R. D. Katz, and J. P. Higgins, “Interpretation of upper extremity arteriography: vascular anatomy and pathology [corrected],” Hand Clin. 31(1), 121–134 (2015).
[Crossref] [PubMed]

C.-W. Wei, T.-M. Nguyen, J. Xia, B. Arnal, E. Y. Wong, I. M. Pelivanov, and M. O’Donnell, “Real-time integrated photoacoustic and ultrasound (PAUS) imaging system to guide interventional procedures: ex vivo study,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 62(2), 319–328 (2015).
[Crossref] [PubMed]

P. K. Upputuri and M. Pramanik, “Performance characterization of low-cost, high-speed, portable pulsed laser diode photoacoustic tomography (PLD-PAT) system,” Biomed. Opt. Express 6(10), 4118–4129 (2015).
[Crossref] [PubMed]

B. Lashkari, S. S. Sean Choi, M. E. Khosroshahi, E. Dovlo, and A. Mandelis, “Simultaneous dual-wavelength photoacoustic radar imaging using waveform engineering with mismatched frequency modulated excitation,” Opt. Lett. 40(7), 1145–1148 (2015).
[Crossref] [PubMed]

A. Garcia-Uribe, T. N. Erpelding, A. Krumholz, H. Ke, K. Maslov, C. Appleton, J. A. Margenthaler, and L. V. Wang, “Dual-Modality Photoacoustic and Ultrasound Imaging System for Noninvasive Sentinel Lymph Node Detection in Patients with Breast Cancer,” Sci. Rep. 5, 15748 (2015).
[Crossref] [PubMed]

J. Yao, L. Wang, J.-M. Yang, K. I. Maslov, T. T. Wong, L. Li, C.-H. Huang, J. Zou, and L. V. Wang, “High-speed label-free functional photoacoustic microscopy of mouse brain in action,” Nat. Methods 12(5), 407–410 (2015).
[Crossref] [PubMed]

A. P. Jathoul, J. Laufer, O. Ogunlade, B. Treeby, B. Cox, E. Zhang, P. Johnson, A. R. Pizzey, B. Philip, T. Marafioti, M. F. Lythgoe, R. B. Pedley, M. A. Pule, and P. Beard, “Deep in vivo photoacoustic imaging of mammalian tissues using a tyrosinase-based genetic reporter,” Nat. Photonics 9, 239–246 (2015).

2014 (6)

L. V. Wang and L. Gao, “Photoacoustic microscopy and computed tomography: from bench to bedside,” Annu. Rev. Biomed. Eng. 16(1), 155–185 (2014).
[Crossref] [PubMed]

K. Daoudi, P. J. van den Berg, O. Rabot, A. Kohl, S. Tisserand, P. Brands, and W. Steenbergen, “Handheld probe integrating laser diode and ultrasound transducer array for ultrasound/photoacoustic dual modality imaging,” Opt. Express 22(21), 26365–26374 (2014).
[Crossref] [PubMed]

T. Furuyama, K. Satoh, T. Kushiya, and N. Kobayashi, “Design, synthesis, and properties of phthalocyanine complexes with main-group elements showing main absorption and fluorescence beyond 1000 nm,” J. Am. Chem. Soc. 136(2), 765–776 (2014).
[Crossref] [PubMed]

A. S. Hannah, D. VanderLaan, Y.-S. Chen, and S. Y. Emelianov, “Photoacoustic and ultrasound imaging using dual contrast perfluorocarbon nanodroplets triggered by laser pulses at 1064 nm,” Biomed. Opt. Express 5(9), 3042–3052 (2014).
[Crossref] [PubMed]

A. Dima, N. C. Burton, and V. Ntziachristos, “Multispectral optoacoustic tomography at 64, 128, and 256 channels,” J. Biomed. Opt. 19(3), 036021 (2014).
[Crossref] [PubMed]

Y. Zhang, M. Jeon, L. J. Rich, H. Hong, J. Geng, Y. Zhang, S. Shi, T. E. Barnhart, P. Alexandridis, J. D. Huizinga, M. Seshadri, W. Cai, C. Kim, and J. F. Lovell, “Non-invasive multimodal functional imaging of the intestine with frozen micellar naphthalocyanines,” Nat. Nanotechnol. 9(8), 631–638 (2014).
[Crossref] [PubMed]

2013 (4)

L. Wang, J. Xia, J. Yao, K. I. Maslov, and L. V. Wang, “Ultrasonically encoded photoacoustic flowgraphy in biological tissue,” Phys. Rev. Lett. 111(20), 204301 (2013).
[Crossref] [PubMed]

Z. Zha, Z. Deng, Y. Li, C. Li, J. Wang, S. Wang, E. Qu, and Z. Dai, “Biocompatible polypyrrole nanoparticles as a novel organic photoacoustic contrast agent for deep tissue imaging,” Nanoscale 5(10), 4462–4467 (2013).
[Crossref] [PubMed]

A. Buehler, M. Kacprowicz, A. Taruttis, and V. Ntziachristos, “Real-time handheld multispectral optoacoustic imaging,” Opt. Lett. 38(9), 1404–1406 (2013).
[Crossref] [PubMed]

R. A. Kruger, C. M. Kuzmiak, R. B. Lam, D. R. Reinecke, S. P. Del Rio, and D. Steed, “Dedicated 3D photoacoustic breast imaging,” Med. Phys. 40(11), 113301 (2013).
[Crossref] [PubMed]

2012 (5)

J. Xia, M. R. Chatni, K. Maslov, Z. Guo, K. Wang, M. Anastasio, and L. V. Wang, “Whole-body ring-shaped confocal photoacoustic computed tomography of small animals in vivo,” J. Biomed. Opt. 17(5), 050506 (2012).
[Crossref] [PubMed]

L. V. Wang and S. Hu, “Photoacoustic tomography: in vivo imaging from organelles to organs,” Science 335(6075), 1458–1462 (2012).
[Crossref] [PubMed]

G. Ku, M. Zhou, S. Song, Q. Huang, J. Hazle, and C. Li, “Copper Sulfide Nanoparticles as a New Class of Photoacoustic Contrast Agent for Deep Tissue Imaging at 1064 nm,” ACS Nano 6(8), 7489–7496 (2012).
[Crossref] [PubMed]

H. Ke, T. N. Erpelding, L. Jankovic, C. Liu, and L. V. Wang, “Performance characterization of an integrated ultrasound, photoacoustic, and thermoacoustic imaging system,” J. Biomed. Opt. 17(5), 056010 (2012).
[Crossref] [PubMed]

B. Cox, J. G. Laufer, S. R. Arridge, and P. C. Beard, “Quantitative spectroscopic photoacoustic imaging: a review,” J. Biomed. Opt. 17(6), 061202 (2012).
[Crossref] [PubMed]

2011 (2)

A. Danielli, C. P. Favazza, K. Maslov, and L. V. Wang, “Single-wavelength functional photoacoustic microscopy in biological tissue,” Opt. Lett. 36(5), 769–771 (2011).
[Crossref] [PubMed]

J. L. Sandell and T. C. Zhu, “A review of in-vivo optical properties of human tissues and its impact on PDT,” J. Biophotonics 4(11-12), 773–787 (2011).
[Crossref] [PubMed]

2010 (3)

B. E. Treeby and B. T. Cox, “k-Wave: MATLAB toolbox for the simulation and reconstruction of photoacoustic wave fields,” J. Biomed. Opt. 15(2), 021314 (2010).
[Crossref] [PubMed]

K. Homan, S. Kim, Y.-S. Chen, B. Wang, S. Mallidi, and S. Emelianov, “Prospects of molecular photoacoustic imaging at 1064 nm wavelength,” Opt. Lett. 35(15), 2663–2665 (2010).
[Crossref] [PubMed]

Y. Jin, C. Jia, S.-W. Huang, M. O’Donnell, and X. Gao, “Multifunctional nanoparticles as coupled contrast agents,” Nat. Commun. 1(4), 41 (2010).
[Crossref] [PubMed]

2009 (1)

2008 (1)

K. Maslov and L. V. Wang, “Photoacoustic imaging of biological tissue with intensity-modulated continuous-wave laser,” J. Biomed. Opt. 13, 024006 (2008).

2006 (3)

T. J. Allen and P. C. Beard, “Pulsed near-infrared laser diode excitation system for biomedical photoacoustic imaging,” Opt. Lett. 31(23), 3462–3464 (2006).
[Crossref] [PubMed]

R. G. Kolkman, W. Steenbergen, and T. G. van Leeuwen, “In vivo photoacoustic imaging of blood vessels with a pulsed laser diode,” Lasers Med. Sci. 21(3), 134–139 (2006).
[Crossref] [PubMed]

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging,” Nat. Biotechnol. 24(7), 848–851 (2006).
[Crossref] [PubMed]

2005 (3)

M. Xu and L. V. Wang, “Universal back-projection algorithm for photoacoustic computed tomography,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 71(1), 016706 (2005).
[Crossref] [PubMed]

B. P. Schneider and K. D. Miller, “Angiogenesis of breast cancer,” J. Clin. Oncol. 23(8), 1782–1790 (2005).
[Crossref] [PubMed]

G. Ku and L. V. Wang, “Deeply penetrating photoacoustic tomography in biological tissues enhanced with an optical contrast agent,” Opt. Lett. 30(5), 507–509 (2005).
[Crossref] [PubMed]

2004 (1)

T. Murray and O. Balogun, “High-sensitivity laser-based acoustic microscopy using a modulated excitation source,” Appl. Phys. Lett. 85(14), 2974–2976 (2004).
[Crossref]

2003 (1)

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, “Noninvasive laser-induced photoacoustic tomography for structural and functional in vivo imaging of the brain,” Nat. Biotechnol. 21(7), 803–806 (2003).
[Crossref] [PubMed]

1998 (1)

Aguirre, A.

Alexandridis, P.

Y. Zhang, M. Jeon, L. J. Rich, H. Hong, J. Geng, Y. Zhang, S. Shi, T. E. Barnhart, P. Alexandridis, J. D. Huizinga, M. Seshadri, W. Cai, C. Kim, and J. F. Lovell, “Non-invasive multimodal functional imaging of the intestine with frozen micellar naphthalocyanines,” Nat. Nanotechnol. 9(8), 631–638 (2014).
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Supplementary Material (6)

NameDescription
» Visualization 1: MOV (777 KB)      Visualization 1
» Visualization 2: MOV (1508 KB)      Visualization 2
» Visualization 3: MOV (1524 KB)      Visualization 3
» Visualization 4: MOV (879 KB)      Visualization 4
» Visualization 5: MOV (815 KB)      Visualization 5
» Visualization 6: MOV (891 KB)      Visualization 6

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Figures (5)

Fig. 1
Fig. 1

Compact laser and photoacoustic setups used in phantom, animal and human imaging studies. (a). Photographs of the diode-pumped Nd:YAG laser. (b) Maximum pulse energy at different pulse repetition frequencies. (c) The original laser beam profile and the homogenized laser beam profile. (d) Schematic drawing of the setup used for tube phantom experiment, DAQ: data acquisition. (e) Schematic drawing of the setup used for mouse brain imaging. (f) Schematic drawing of the setup used for trunk imaging. (g) Top view of the three-quarter ring transducer array, FOV: field of view. (h) Schematic drawing of the set up used for human imaging.

Fig. 2
Fig. 2

Chicken breast tissue experiment. (a) Photograph of the tube phantom experiment. (b) Overlaid averaged photoacoustic (color scale) and ultrasound (gray scale) images of the contrast-containing tube at 4.1 cm depth. (c) SNR of photoacoustic signals of the tube at different depths.

Fig. 3
Fig. 3

Mouse anatomical and functional imaging. (a) PA image of cerebral vasculature of a mouse brain. CoS, confluence of sinuses; ICV, inferior cerebral vein; SSS, superior sagittal sinus; TS, transverse sinus. (b) PA cross sectional image of the heart region (Visualization 1). ST, sternum; HT, heart; LL, left lung; RR, right lung. (c) PA cross sectional image of the liver region (Visualization 2). LLV, left lobe of liver; PV, portal vein; RLV, right lobe of liver; IVC, inferior vena cava. (d) PA cross sectional image of the kidney region (Visualization 3). RK, right kidney; LK, left kidney; BM, backbone muscles. (e) M-mode photoacoustic image of cardiac and respiratory motion. (f) Movement of ribcage. (g) Movement of heart wall. Frames at the peaks labeled with red arrows were averaged to improve SNR of Fig. 3(b). Mice: female Swiss Webster, 21 g.

Fig. 4
Fig. 4

In vivo arm and palm imaging of healthy human volunteers. (a) Photograph of human arm (red box indicates the imaged region). Subject: male, 25 years old. (b) Depth-encoded maximum amplitude projection (MAP) photoacoustic image of the human arm (Visualization 4). x, y and z correspond to axial, lateral and elevation directions of the transducer array, respectively. MAP was performed along the axial direction. (c) Photograph of human palm (red box indicates the imaging region). Subject: male, 23 years old. (d) Depth-encoded MAP photoacoustic image of human palm (Visualization 5), MAP was performed along the axial direction of transducer array

Fig. 5
Fig. 5

Breast imaging setup and result. (a) Schematic drawing of the breast imaging setup. (b) Depth-encoded MAP photoacoustic image of breast vasculature in a healthy human volunteer (Visualization 6). Subject: female, 23 years old. x, y and z correspond to axial, lateral and elevation directions the transducer, respectively. MAP was performed along the axial direction of transducer array.

Tables (1)

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Table 1 Comparison of compact laser and the Nd:YAG laser

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