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Bioengineering

Photoacoustic Cystography

Published: June 11th, 2013

DOI:

10.3791/50340

1Department of Biomedical Engineering, University at Buffalo, The State University of New York, 2Department of Creative IT Engineering, Pohang University of Science and Technology (POSTECH) , 3School of Electrical Engineering and Computer Science, Kyungpook National University

Photoacoustic cystography (PAC) has a great potential to map urinary bladders, a radiation sensitive internal organ in pediatric patients, without using any ionizing radiation or toxic contrast agent. Here we demonstrate the use of PAC for mapping urinary bladders with an injection of optical-opaque tracers in rats in vivo.

Conventional pediatric cystography, which is based on diagnostic X-ray using a radio-opaque dye, suffers from the use of harmful ionizing radiation. The risk of bladder cancers in children due to radiation exposure is more significant than many other cancers. Here we demonstrate the feasibility of nonionizing and noninvasive photoacoustic (PA) imaging of urinary bladders, referred to as photoacoustic cystography (PAC), using near-infrared (NIR) optical absorbents (i.e. methylene blue, plasmonic gold nanostructures, or single walled carbon nanotubes) as an optical-turbid tracer. We have successfully imaged a rat bladder filled with the optical absorbing agents using a dark-field confocal PAC system. After transurethral injection of the contrast agents, the rat's bladders were photoacoustically visualized by achieving significant PA signal enhancement. The accumulation was validated by spectroscopic PA imaging. Further, by using only a laser pulse energy of less than 1 mJ/cm2 (1/20 of the safety limit), our current imaging system could map the methylene-blue-filled-rat-bladder at the depth of beyond 1 cm in biological tissues in vivo. Both in vivo and ex vivo PA imaging results validate that the contrast agents were naturally excreted via urination. Thus, there is no concern regarding long-term toxic agent accumulation, which will facilitate clinical translation.

X-ray cystography1 is an imaging process to identify bladder-related diseases such as bladder cancer, vesicoureteral reflux, blockage of ureters, neurogenic bladder, etc.2-5 Typically, urines are voided and a radio-opaque agent is injected through a catheter. Then, fluoroscopic X-ray images are acquired to delineate urinary bladders. However, the key safety issue is that harmful ionizing radiation is used in this procedure. The percentage of cumulative cancer risk to age 75 years owing to diagnostic X-rays ranges from 0.6 to 1.8%.6 In addition, the carcinogenic threat is significant in pediatric patients. A UK study showed tha....

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1. Deep Reflection Mode Photoacoustic Cystography (PAC) System

  1. System configuration17, 18
    1. A Q-switched Nd:YAG laser (SLII-10; Continuum; 532 nm) pumps a wavelength-tunable laser (Surelite OPO PLUS; Continuum; wavelength tuning range: 680 to 2,500 nm).
    2. The pulse duration of each laser shot is ~5 nsec, and the laser repetition rate is 10 Hz.
    3. The wavelength depends on the optical absorption peak of the used contrast agent. If methylene blue serves as the contrast agen.......

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Figure 1 shows the In vivo nonionizing and noninvasive PAC using optically turbid methylene blue (MB). The control PA image was obtained at 667 nm, at the peak optical absorption for MB (Figure 1A). Although the blood vessels in the FOV are clearly visualized, the bladder is invisible because it is optically transparent at this wavelength. As shown in Figure 1B, the bladder is clearly revealed in the PA image acquired at 0.2 hr post-injection of MB. To confirm t.......

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In conclusion, we have shown the possibility of nonionizing PAC using nontoxic optical absorbers in a rat model in vivo. We have successfully imaged a rat bladder filled with optical absorbents using our nonionizing and noninvasive PAC system. Two critical safety issues have been resolved in our approach: (1) the use of nonionizing radiation for cystographic applications and (2) no accumulation of contrast agents in the body.

Our clinical interest includes monitoring vesicoureteral re.......

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This work was supported in part by a grant from the pilot studies program of the University at Buffalo Clinical and Translational Research Center and the Buffalo Translational Consortium, a grant from Roswell Park Alliance Foundation, startup funds from the University at Buffalo, IT Consilience Creative Program of MKE, and NIPA (C1515-1121-0003) and NRF grant of MEST (2012-0009249).

....

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Name Company Catalog Number Comments
Name of Reagent/Material Company Catalog Number Comments
Q-switched Nd:YAG laser Continuum SLII-10 pump laser
OPO laser Continuum Surelite OPO PLUS tunable laser
Prisms Thorlabs PS908 light deliver
Ultrasound transducer Olympus NDT V308 5 MHz
Ultraoundpulser/receiver Olympus NDT 5072PR amplifier
Oscilloscope Tektronix TDS5054 data acquisition
Scanning stage Danaher Dover XY6060 raster scanning
Methylene blue Sigma-Aldrich M9140-25G contrast agent
Rats Harlan Spague-Dawley animal subject
Isoflourane vaporizer Euthanex EZ-155 anesthesia
Ultrasound gel Sonotech Clear Image singles acoustic coupling

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