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PROCEEDINGS OF SPIE

SPIEDigitalLibrary.org/conference-proceedings-of-spie

Tomographic imaging with an

LED-based photoacoustic-ultrasound

system

Kalloor Joseph, Francis, Kuniyil Ajith Singh, Mithun,

Steenbergen, Wiendelt

Francis Kalloor Joseph, Mithun Kuniyil Ajith Singh, Wiendelt Steenbergen,

"Tomographic imaging with an LED-based photoacoustic-ultrasound system,"

Proc. SPIE 11240, Photons Plus Ultrasound: Imaging and Sensing 2020,

112401U (17 February 2020); doi: 10.1117/12.2545974

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Tomographic imaging with an LED-based

photoacoustic-ultrasound system

Kalloor Joseph Francis

a

, Mithun Kuniyil Ajith Singh

b

, and Wiendelt Steenbergen

a a

Biomedical Photonic Imaging group, Technical Medical Center, University of Twente, The

Netherlands

b

Research and Business Development Division, Cyberdyne INC, Cambridge Innovation Center,

Rotterdam, The Netherlands

ABSTRACT

Combined Photoacoustic (PA) and Ultrasound (US) imaging systems are finding more preclinical and clinical applications. However, majority of the commercial systems use expensive pulsed lasers. In most small animal studies and clinical applications like arthritis screening of finger joints, there is a need for tomographic imaging. In this work, we present PA and US tomographic imaging using a commercial imaging system with LED arrays as illumination source. We employ multiangle spatial compounding of PA and US images using a probe with a linear array transducer and four LED arrays, to form dual-mode tomographic images. Using phantom experiments, the proposed approach is validated and thoroughly tested. Further, the potential of the system is demonstrated by imaging knee joint and abdominal region of a mouse. This proposed approach has several advantages. First, the resolution and signal to noise ratio (SNR) are improved with the compounding of images from multiple angles. The resolution improvement owes to better axial resolution compared to lateral and high SNR with averaging. Secondly, the limited view artifacts and loss of information from the use of a linear array US probe is tackled. The US tomographic images of the mouse-knee RA model show structural details of the joint and blood vessels were visible in the tomographic PA images. The whole animal images enabled improved functional and structural information. An affordable PA/US tomographic imaging system with potential in clinical arthritis-screening and small animal imaging is presented.

Keywords: Photoacoustic, ultrasound, tomography, finger joint, small animal

1. INTRODUCTION

In photoacoustic (PA) imaging, pulsed illumination on optical absorbers results in thermoelastic expansion giving out pressure waves.1 These pressure waves can be detected for imaging.2 Transducers which are used to detect PA signals can also be used for ultrasound (US) imaging.3 Combined PA and US imaging has potential in biomedical applications as both structional and functional information of the tissue can be obtained.4 PA

has shown promise in many biomedical applications including cancer imaging, brain function imaging, surgical guidance, treatment monitoring and many more.5–8 One of the simplest ways to combine the US and PA imaging

is to use a conventional US imaging system and plug-in a light source for PA illumination.9 This approach can

also enable wide acceptance of PA imaging where the US is already in use. In combined PA and US imaging using conventional US systems, linear transducer arrays are preferred for faster reconstruction and system integration.10

One of the disadvantages of using linear transducer-based imaging is the directional nature of the transducer, resulting in a limited-view of the target and artifacts.11 Custom made transducers with curved detection surface

can solve this limited view problem. However, the system will become more expensive with additional hardware and software. An alternative approach is to have tomographic imaging in applications where a large view angle of the target tissue is possible. Commercially available tomographic imaging systems use pulsed laser and are both expensive and bulky.12 Hence, there is a requirement for an inexpensive tomographic imaging system which

can combine both US and PA imaging.

Further author information:

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Recent developments in LED-based PA imaging have shown great potential to be a cost-effective and portable system for clinical applications.13 Using a commercially available LED-based system with a linear transducer array for tomographic imaging can be advantageous for many clinical and pre-clinical applications. LED-based tomographic imaging with single element transducer scanning around the sample was previously reported.14,15

Tomographic imaging using a linear transducer array was reported by multiple groups in the past16–18

In this work, we have combined tomographic imaging using a linear transducer array and LED-based PA imaging using a commercially available system. We demonstrate resolution improvement using the proposed approach. We report two applications using the system namely, (i) finger joint imaging and (ii) small animal imaging. An ex vivo mouse knee was imaged to test the system and further imaged an in vivo human finger joint. Additionally, we present our preliminary results in small animal abdominal imaging.

2. MATERIALS AND METHODS

Figure 1. Tomographic ultrasound and photoacoustic imaging system for (a) finger joint imaging and (b) small animal imaging. (c) Portable LED-based photoacoustic imaging system. (d) Linear transducer array and (e) LED array used in this configuration.

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Figure 2. (a) Photoacoustic point spread function (PSF) obtained from a single angular view. (b) PSF from tomographic imaging. (c) 1D analysis of PSF along the lateral and axial direction through the center

study. A 128 element linear transducer array with 7 MHz center frequency and 80% bandwidth was used. Four LED array units having 576 elements (36 × 4 in each array) at 850 nm wavelength were used for illumination. Each LED array had pulse energy of 200 µJ and a pulse duration of 70 ns.

For the illumination, we have developed a configuration using four LED array units, as shown in Fig.1. Two LED units along the long axis of the transducer array and the other two along the short axis of the transducer within the imaging plane. An angle of 30.8◦ was used for the LED units placed along the long axis of the transducer so that the light intersects at the focus of the transducer in a non-scattering medium. The other two LEDs placed in the imaging plane were placed at an angle of 105◦with the transducer’s surface. Additionally a tilt of 5◦ was also introduced with respect to the imaging plane. This tilt is to minimize the reflected acoustic waves reaching the transducer surface causing reflection artifact.

For ultrasound detection, the linear transducer array was rotated around the target using a motor. The motor can scan the entire 360◦with an accuracy of 0.1with a rotating speed of 8.8 deg/sec. The opening angle of a single element in the transducer used in this work is 26.8± 0.2◦. In a theoretical calculation, it was found that a minimum of 14 angular views is required to have a full-view tomographic imaging.19 We have considered

18 angular views covering 360◦ for tissue imaging, considering an oversampling for practical applications. The US and PA images obtained from multiple angles were reconstructed to form B-scan images. The B-scan images from multiple angles were then rotated to the respective angles and interpolated to a larger grid. The rotated and interpolated images were then combined using spatial compounding.18

In the first experiment, a black suture wire (Vetsuture, France) of 30µm diameter was imaged for resolution analysis. The resolution of the system with a single view and in the tomographic mode were compared. In the second experiment, an ex vivo mouse knee was imaged to test the capability of the system for joint imaging. This was followed by an in vivo finger joint imaging of a healthy volunteer. In the final experiment, the abdominal region of a white mouse was imaged. The mouse was reused from another study after sacrificing.

3. RESULTS AND DISCUSSION

The spatial resolution analysis is shown in Figure 2. Figure. 2 a shows point spread function (PSF) of the system from a single of the target using the linear transducer array. The axial Full-Width Half Max (FWHM) was measured to be 0.22 mm and lateral FWHM was 0.47 mm. PSF from tomographic reconstruction using spatial compounding of 18 angular views is shown in Fig. 2b. The tomographic imaging provided a symmetric PSF. Both axial and lateral resolutions were measured to be 0.31 mm. It can be observed that lateral PSF improved with spatial compounding with the degradation of axial PSF. The signal to noise ratio was also found to improve with spatial compounding due to averaging from multiple views.

Imaging using a mouse knee with the tomographic imaging system is shown in Fig. 3. The photograph of the mouse knee in Fig. 3a shows the joint with multiple blood vessels around it. In the US image3b, both the bones are visible with the tissue around it. With 850 nm LEDs, the absorption of blood was targeted in the PA

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Figure 3. (a)Photograph of the mouse knee joint. (b) Photoacoustic tomographic image of the joint. (c) Ultrasound tomographic image of the joint

Figure 4. (a) Cross-section of the proximal interphalangeal joint. (b) Photoacoustic tomographic image of the joint. (c) Ultrasound tomographic image of the joint.

imaging. Figure. 3c shows PA image overlaid on the US image showing the blood vessels around the joint. As the plane passing through the center of the sample was selected for imaging, the larger blood vessel visible on the surface of the sample in the photograph is not completely captured.

A cross-section of the interphalangeal joint of a human finger is shown in Fig. 4a. Major structures are the bone at the joint, the tissue around it, blood vessels and the skin covering the finger. In the PA image in Fig. 4b high signal can be observed from both the skin and the blood vessels. There are also reflection artifacts which can be seen towards the center of the PA imaging due to the acoustic reflection from the bone. In the US image

4c the bone and the tissue around can be seen.

The results from a preliminary small animal imaging study using the system are shown in Fig. 5. The US tomographic image in Fig. 5a shows the backbone of the mouse, left and right kidneys and the stomach. Figure.

5b shows PA image overlaid on the US image showing several blood vessels around the organs.

These results show the potential of the tomographic imaging system in finger joint imaging for diseases such as rheumatoid arthritis. This can also be potentially used for small animal imaging for preclinical studies. Currently, the system takes 43 seconds to form a tomographic image. Future work will direct towards making the imaging fast and in vivo imaging.

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Figure 5. (a) Photoacoustic and (b) combined photoacoustic and ultrasound tomographic image of abdomen of a mouse.

4. CONCLUSION

In this work, we have demonstrated a cost-effective way to perform tomographic ultrasound and photoacoustic imaging using a commercial LED-based system. The results show the potential of this method in in vivo finger joint imaging and small animal cadaver imaging. This LED-based tomographic imaging system is eye-safe, relatively faster than laser-based systems and can be used for point-of-care applications.

5. ACKNOWLEDGMENTS

We acknowledge initial funding from NC3Rs as part of CRACK IT challenge, grant number CRACKITRT-P1-3.

REFERENCES

[1] Xu, M. and Wang, L. V., “Photoacoustic imaging in biomedicine,” Review of scientific instruments 77(4), 041101 (2006).

[2] Francis, K. J., Chinni, B., Channappayya, S. S., Pachamuthu, R., Dogra, V. S., and Rao, N., “Characteri-zation of lens based photoacoustic imaging system,” Photoacoustics 8, 37–47 (2017).

[3] Rao, N., Kalloor, F., Chinni, B., Han, Z., and Dogra, V., “Innovative approach for including dual mode ultrasound and volumetric imaging capability within a medical photoacoustic imaging camera system,” in [Optical Tomography and Spectroscopy ], OW4D–2, Optical Society of America (2018).

[4] Das, D. and Pramanik, M., “Combined ultrasound and photoacoustic imaging of blood clot during microbubble-assisted sonothrombolysis,” Journal of biomedical optics 24(12), 121902 (2019).

[5] Attia, A. B. E., Balasundaram, G., Moothanchery, M., Dinish, U., Bi, R., Ntziachristos, V., and Olivo, M., “A review of clinical photoacoustic imaging: Current and future trends,” Photoacoustics , 100144 (2019). [6] Zhao, T., Desjardins, A. E., Ourselin, S., Vercauteren, T., and Xia, W., “Minimally invasive photoacoustic

imaging: Current status and future perspectives,” Photoacoustics , 100146 (2019).

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

[8] Francis, K. J. and Manohar, S., “Photoacoustic imaging in percutaneous radiofrequency ablation: device guidance and ablation visualization,” Physics in Medicine & Biology 64(18), 184001 (2019).

[9] Francis, K. J., Rascevska, E., and Manohar, S., “Photoacoustic imaging assisted radiofrequency ablation: Illumination strategies and prospects,” in [TENCON 2019-2019 IEEE Region 10 Conference (TENCON) ], 118–122, IEEE (2019).

[10] Oeri, M., Bost, W., Tretbar, S., and Fournelle, M., “Calibrated linear array-driven photoacoustic/ultrasound tomography,” Ultrasound in medicine & biology 42(11), 2697–2707 (2016).

[11] Mercep, E., Jeng, G., Morscher, S., Li, P.-C., and Razansky, D., “Hybrid optoacoustic tomography and pulse-echo ultrasonography using concave arrays,” IEEE transactions on ultrasonics, ferroelectrics, and frequency control 62(9), 1651–1661 (2015).

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[12] Fatima, A., Kratkiewicz, K., Manwar, R., Zafar, M., Zhang, R., Huang, B., Dadashzadesh, N., Xia, J., and Avanaki, M., “Review of cost reduction methods in photoacoustic computed tomography,” Photoacoustics , 100137 (2019).

[13] Xia, W., Kuniyil Ajith Singh, M., Maneas, E., Sato, N., Shigeta, Y., Agano, T., Ourselin, S., J West, S., and E Desjardins, A., “Handheld real-time led-based photoacoustic and ultrasound imaging system for accurate visualization of clinical metal needles and superficial vasculature to guide minimally invasive procedures,” Sensors 18(5), 1394 (2018).

[14] Allen, T. J. and Beard, P. C., “High power visible light emitting diodes as pulsed excitation sources for biomedical photoacoustics,” Biomedical optics express 7(4), 1260–1270 (2016).

[15] Leskinen, J., Pulkkinen, A., Tick, J., and Tarvainen, T., “Photoacoustic tomography setup using led illumi-nation,” in [Opto-Acoustic Methods and Applications in Biophotonics IV ], 11077, 110770Q, International Society for Optics and Photonics (2019).

[16] Oraevsky, A. A., Andreev, V. A., Karabutov, A. A., and Esenaliev, R. O., “Two-dimensional optoacous-tic tomography: transducer array and image reconstruction algorithm,” in [Laser-Tissue Interaction X: Photochemical, Photothermal, and Photomechanical ], 3601, 256–267, International Society for Optics and Photonics (1999).

[17] Gateau, J., Caballero, M. ´A. A., Dima, A., and Ntziachristos, V., “Three-dimensional optoacoustic tomog-raphy using a conventional ultrasound linear detector array: Whole-body tomographic system for small animals,” Medical physics 40(1), 013302 (2013).

[18] Francis, K. J., Chinni, B., Channappayya, S. S., Pachamuthu, R., Dogra, V. S., and Rao, N., “Multiview spatial compounding using lens-based photoacoustic imaging system,” Photoacoustics 13, 85–94 (2019). [19] Xu, Y., Wang, L. V., Ambartsoumian, G., and Kuchment, P., “Reconstructions in limited-view

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