Hybrid imaging system for developing novel neural contrast agents

Neural contrast agents have a vast array of applications from molecular imaging to mapping membrane potential. We describe a hybrid neural recording system capable of ultrasonic, photoacoustic and optical imaging designed to develop and test the next-generation of neural contrast agents. Photoacoustic imaging (PA), in particular, provides optical contrast with good penetration and high spatial resolution, making it an attractive tool for noninvasive neural imaging. To demonstrate the system, we chose a commercial dye (NK2761) commonly used for optical imaging of neural tissue to enhance PA images of live lobster nerve cord. The abdominal segment was excised, stained and placed in a custom neural chamber. Photoacoustic and ultrasound images were collected using a clinical ultrasound scanner and a 10-MHz linear probe. A wavelength-tunable pulsed laser source (5 nsec, ̃15 mJ) operating at 20 Hz produced PA waves. Longitudinal scans of the nerve cord were collected and displayed every 7 seconds. Without a contrast agent, the peak PA signal was 5 dB over noise. An additional 29 dB was achieved after the nerve was submerged in dye for 20 minutes. The contrast enhancement was consistent with the measured optical absorbance of the stained nerve. Photoacoustic images approached 200-μm spatial resolution. The hybrid system provided several hours of imaging, electrical stimulation and recording, serving as a robust testbed for developing novel contrast for neural applications.