"Our multimodal system is the first to use optical means to gather both the photoacoustic ultrasound waves and the OCT signal," Wolfgang Drexler, head of the Center for Medical Physics and Biomedical Engineering at Medical University Vienna, told medicalphysicsweb. "An all-optical approach makes it easy to fuse PAT and OCT and allows us to exploit the advantages of these two complimentary techniques."

Best of both

Although the individual advantages of PAT and OCT are well documented, a hybrid instrument has proved problematic to produce because of the differing detection requirements of photoacoustic (PA) and OCT signals. The key enabling component in the team's combined PAT/OCT scanner is a transparent optically addressed ultrasound sensor based on a Fabry Perot (FP) polymer film interferometer, which was developed by Paul Beard and his team at University College London, UK.

As Drexler and Beard describe in their paper, the transparent nature of the ultrasound sensor overcomes many of the design challenges that have hindered the development of hybrid instruments. For example, both the OCT probe and PA excitation beams can now pass directly through the sensor, which in turn provides the convenience of a backward mode imaging configuration. It also means that the PA detection point and OCT probe beam can be co-located so the images are inherently co-registered.

In addition to the ultrasound sensor that detects the PA signals, the other principal components of the instrument are a laser system to excite the PA signal, a 1050 nm spectral-domain OCT system, and an optical scan engine that spatially maps the PA and OCT signals.

The system works by first placing the ultrasound sensor on the surface of interest, using a drop of water to provide the necessary optical coupling. Nanosecond pulses from the laser system then excite the PA signal, which is read out by raster scanning a 1550 nm focused laser beam across the surface of the ultrasound sensor. To obtain the OCT image, a 1050 nm probe beam is combined with the 1550 nm ultrasound interrogation beam. Both beams follow identical paths through the scanner and are scanned over the same lateral region.

Evaluating performance

The team carried out experiments on a tissue-mimicking phantom, the skin of a nude mouse and the palm of a human volunteer to assess the performance of its combined PAT/OCT scanner. Work on the phantom tested the accuracy of the registration between the PAT and OCT images, which turned out to be less than the dimensions of a single voxel (25 x 25 x 6 µm).

In vivo OCT and PAT images of the mouse skin. The animation shows volume rendered representations of fused OCT-PAT image data at different viewing angles with the OCT image successively resected. Animation courtesy of Wolfgang Drexler, from Biomed. Opt. Express 2 2202.

Next, PAT and OCT data were acquired and fused together to create images of the skin on the flank of an anaesthetized hairless mouse. Acquisition times were 7 min for the PAT data and 24 s for OCT. While the PAT images showed the distribution of blood vessels, OCT images detailed the various layers of the skin, such as the epidermis, dermis and hypodermis. Similarly, combined image slices from the palm of a human volunteer showed the thickness of the various layers of the skin and the distribution of blood vessels.

The authors report axial and lateral resolutions of 8 and 18 µm, respectively, in their OCT images and 20 and between 50 and 100 µm in their PAT images. They add that the system can image to a depth of almost 5 mm.

"Going forward, we are focusing on decreasing PAT acquisition times and combining functional OCT with PAT," commented Drexler. "Our long-term goal is enabling multimodal PAT/OCT-based molecular imaging (with endogenous or exogenous) contrast agents for preclinical and clinical trials."