"Our study is the first to show that ICG-doped SWNTs can be used to image sentinel lymph nodes (SLNs) and the bladder in live animals," Chulhong Kim from the State University of New York at Buffalo told medicalphysicsweb. "Typically, radioactive or opaque tracers are used to visualize these structures using ionizing (X-ray-based) imaging modalities. Photoacoustic imaging uses non-ionizing radiation, and has the potential to be portable."

Nanotube-enhanced imaging

Photoacoustic imaging is rapidly emerging as a viable alternative in many situations. Although the fundamentals of the technique and its capabilities are now well documented, contrast agents still play a vital role, particularly in the case of organs that are optically and radiologically transparent, such as lymphatics and the bladder.

The Buffalo team, working with collaborators at Pukyong National University and Kyungpook National University both in Korea, developed its own photoacoustic imaging system and synthesized SWNTs with indocyanine green (ICG) dye molecules attached to their surface. In a phantom study, the researchers found that ICG-doped SWNTs absorbed four times more light than SWNTs alone, implying that the doped SWNTs would serve as an excellent photoacoustic contrast agent.

"ICG can easily be conjugated with SWNTs and has a strong optical absorption across the near-infrared spectrum between 600 and 900 nm," said Kim. "Our photoacoustic system uses a laser with a wavelength of 820 nm, which is close to the absorption peak of ICG-doped SWNTs."

Small-animal studies

The team then went on to test its system on six rats: three in which a SLN was imaged and three where the bladder was studied. In all cases, the first step was to acquire a control image prior to the ICG-doped SWNTs being administered.

In the SLN study, the vasculatures in the axilla were visible in the control image but the SLN was not, due to its lack of intrinsic optical absorption. After an intradermal injection of ICG-doped SWNTs, the team reported that the SLN was clearly visible with a stronger contrast than the surrounding blood vessels. Similarly, in the bladder study, the bladder could not be seen on the control image, but was clearly visible after the ICG-doped SWNTs had been introduced through a catheter.

"It takes about 10 to 20 minutes for the ICG-doped SWNTs to accumulate in the lymph nodes but accumulation in the bladder is immediate," commented Kim. "With our system, it takes around 25 minutes to acquire one 3D photoacoustic image with a field-of-view of 25 x 25 x 10 cm in the x, y and z axes. However, photoacoustic imaging can be easily adapted with conventional ultrasound imaging, which is real time."

Looking to the future

Following the success of this proof-of-principle study, Kim and his colleagues say that they would now like to perform in vivo molecular photoacoustic imaging using target-sensitive ICG-doped SWNTs to visualize metastatic lymph nodes. They would also like to delineate bladders in larger animals using a hand-held photoacoustic probe to show the technique's potential for clinical translation.

"We feel that mapping bladders using this method could easily be translated to clinical practice," said Kim. "However, for lymph node mapping, we need further studies to investigate the toxicity of carbon nanotubes in vivo."

Related articles in PMB
In vivo non-ionizing photoacoustic mapping of sentinel lymph nodes and bladders with ICG-enhanced carbon nanotubes
Jasung Koo et al Phys. Med. Biol. 57 7853
In vivo carbon nanotube-enhanced non-invasive photoacoustic mapping of the sentinel lymph node
Manojit Pramanik et al Phys. Med. Biol. 54 3291