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Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo

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Abstract

At present, clinicians routinely apply ultrasound endoscopy in a variety of interventional procedures that provide treatment solutions for diseased organs. Ultrasound endoscopy not only produces high-resolution images, but also is safe for clinical use and broadly applicable. However, for soft tissue imaging, its mechanical wave–based image contrast fundamentally limits its ability to provide physiologically specific functional information. By contrast, photoacoustic endoscopy possesses a unique combination of functional optical contrast and high spatial resolution at clinically relevant depths, ideal for imaging soft tissues. With these attributes, photoacoustic endoscopy can overcome the current limitations of ultrasound endoscopy. Moreover, the benefits of photoacoustic imaging do not come at the expense of existing ultrasound functions; photoacoustic endoscopy systems are inherently compatible with ultrasound imaging, thereby enabling multimodality imaging with complementary contrast. Here we present simultaneous photoacoustic and ultrasonic dual-mode endoscopy and show its ability to image internal organs in vivo, thus illustrating its potential clinical application.

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Figure 1: Illustration of simultaneous, multiwavelength photoacoustic (PA) and ultrasonic (US) endoscopy.
Figure 2: Simultaneous, co-registered, PAE-EUS pseudocolor images from a rabbit esophagus in vivo.
Figure 3: RMAP images over a full 360° angular FOV (views from the inside of the esophagus).
Figure 4: Simultaneous, co-registered, PAE-EUS colonoscopic pseudocolor images of a rat colon acquired in vivo.
Figure 5: Lymphovascular system imaging in vivo near a rat colon.

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Acknowledgements

We thank J. Ballard for his attentive reading of the manuscript. We also thank J. Kalishman, P. Jiménez-Bluhm, and L. Andrews-Kaminsky for helping with animal preparation, surgery, and image interpretation. We thank B. Matthews, V. Tsytsarev, G. Lanza, R. Senior, and J. Atkinson for helpful discussion on the experimental results. This work was sponsored in part by US National Institutes of Health grants R01 CA157277, R01 EB000712, R01 EB008085, R01 CA134539, P41-EB2182, and U54 CA136398 (Network for Translational Research). J.-M.Y. was supported in part by a Korea Research Foundation Grant funded by the Korean government (KRF-2007-357-C00039).

Author information

Authors and Affiliations

Authors

Contributions

J.-M.Y. built the system, did the experiments, and wrote the manuscript. C.F. developed the data acquisition program, carried out the experiments, and co-wrote the manuscript. R.C., Q.Z., and K.K.S. designed and fabricated the ultrasonic transducers. J.Y. contributed to the data processing algorithms and also assisted with data processing and experiments. X.C. helped with the experiments. K.M. contributed to the system development. L.V.W. directed the project, conceived the endoscope design, discussed the experiments and revised the manuscript.

Corresponding authors

Correspondence to Qifa Zhou or Lihong V Wang.

Ethics declarations

Competing interests

L.V.W. has a financial interest in Microphotoacoustics, Inc. and Endra, Inc., which, however, did not support this work.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–12 and Supplementary Discussion (PDF 940 kb)

Supplementary Video 1

A video of the integrated PA-US dual-mode endoscopic probe demonstrates radial scanning with the probe's rotating mirror, which is shown directing a 562 nm laser beam. (MOV 1245 kb)

Supplementary Video 2

An in vivo, simultaneously acquired PA-US endoscopic movie of a rabbit esophagus. The movie presents only a portion of the entire three dimensional scan. The displayed section shows the lower esophagus and consists of 1,400 slices (~7 cm) taken from a total of 2,800 slices (~14 cm) presented in Figure 2. The bottom of each panel corresponds to the ventral side of the animal. The movie is six times faster than the actual B-scan acquisition rate of ~4 Hz. Respiratory motion generated the dominant image fluctuation seen in the video. (MOV 8168 kb)

Supplementary Video 3

Combined, co-registered PA-US three-dimensional images of the organs and structures surrounding the esophagus. The movie corresponds to the three-dimensionally rendered image, Figure 2c, composed of the entire 2,800-slice cylindrical PA and US data sets acquired over a 14 cm range with an 18 mm diameter covering a 270° angular range from the ventral side of the animal. Partial slices are shown in Supplementary Video 2. The red and green colors correspond to PA and US signals, respectively, and the left-hand side of the image corresponds to the lower esophagus. To more clearly display the structures surrounding the esophagus, we excluded PA signals generated from the esophagus. (MOV 1756 kb)

Supplementary Video 4

Combined, co-registered PA-US three-dimensional images of the organs and structures surrounding the esophagus over the entire 360°. This movie was produced by combining the ventral (Fig. 2) and dorsal (Supplementary Fig. 5) PA-US volumetric data sets covering 14 cm in length and 18 mm in diameter. The red and green colors correspond to PA and US signals, respectively, and the left-hand side of the image corresponds to the lower esophagus. To more clearly display the structures surrounding the esophagus, we excluded PA signals generated from the esophagus. (MOV 1758 kb)

Supplementary Video 5

Combined, co-registered PA-US three-dimensional images of a rat colon and its surrounding structures. The movie corresponds to the three-dimensionally rendered image, Figure 4a, composed of the entire 1,100-slice cylindrical PA and US data sets, covering 5.5 cm in length and 12 mm in diameter. The red and green colors correspond to PA and US signals, respectively, and the right-hand side of the image corresponds to the posterior end of the animal (i.e., the anus). (MOV 1760 kb)

Supplementary Video 6

An in vivo, co-registered lymphovascular PA-US colonoscopy movie acquired from a rat. The movie shows 1,800 B-scan slices covering ~7.2 cm in length and spanning 12 mm in diameter. In the left panel, the red and blue colors represent blood and lymphatic (Evans blue) systems, respectively. The movie is six times faster than the actual B-scan acquisition rate of ~4 Hz. Non-periodic peristaltic motion of the colon occurs intermittently throughout the video. (MOV 10542 kb)

Supplementary Video 7

Combined, co-registered PA-US three-dimensional images showing the lymphovascular system near a rat colon. The movie corresponds to the three-dimensionally rendered image, Figure 5e, composed of the entire 1,800-slice cylindrical PA and US data sets acquired over a 7.2 cm range with an 12 mm diameter covering a 270° angular range from the dorsal side of the colon. The red and green colors correspond to PA and US signals showing the vasculature and tissue's density distribution, respectively, and the blue colors show the Evans blue concentration (i.e., lymphatic system). The right-hand side of the image corresponds to the posterior end of the animal (i.e., the anus). (MOV 1763 kb)

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Yang, JM., Favazza, C., Chen, R. et al. Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo. Nat Med 18, 1297–1302 (2012). https://doi.org/10.1038/nm.2823

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