The biophotonics laboratory develops novel and robust optical techniques for optical molecular imaging and sensing.
The advance of optical technologies has revolutionized a broad range of biomedical research fields. During the past two decades, novel optical imaging techniques have been developed to provide unprecedented resolution, sensitivity, and speed. However, the optical penetration depth in tissues remains very limited.
Elastic scattering is the dominant process during optical wave propagation in tissues. If there is a way to suppress elastic scattering, the penetration depth of optical imaging could be improved by about two orders of magnitudes, which could open up many possibilities for both scientific research and medical applications.
The two most widely used accurate deep tissue optical imaging techniques are Optical Coherence Tomography (OCT) and two-photon fluorescence microscopy. OCT detects the ballistic light reflection and can provide ~1 mm penetration depth. Two-photon microscopy employs ballistic light for illumination and collects both scattered and ballistic fluorescence signals. Unlike OCT, two-photon microscopy provides molecular contrast (fluorescence) and the penetration depth is ~0.5 mm. Using longer excitation wavelength (1,200-1,300 nm), two-photon microscopy can achieve improved penetration depth (~1mm). At greater penetration depth, the ballistic component could be easily overwhelmed by the out-of-focus scattered components. In addition, the accumulated aberration becomes significant. Adaptive optics has been employed to compensate for the aberration in optical microscopy. To date, the successful demonstrations have shown that it is possible to improve the image quality (resolution, signal strength). However, the improvement in optical penetration depth is moderate. To further increase the penetration depth, novel methods that employ not only the ballistic light but also the scattered light for imaging should be explored. One of our primary research goals is to develop new technologies to control and use the scattered light for deep tissue molecular imaging.
Another important line of research is the development of hybrid imaging methods that combine light with sound. One method is to use light absorption to generate sound, a method called photoacoustic tomography. The other method is to use sound to modulate light, known as ultrasound modulated optical tomography. These hybrid methods, which combine the optical imaging contrast (absorption) with the penetration depth of the ultrasound, are very promising for clinical applications. However, the sensitivity and the spatial resolution are far from start-of-the-art optical microscopy. Our laboratory is developing a new type of hybrid imaging method that may potentially provide higher sensitivity and spatial resolution.
For practical biomedical applications, imaging speed is very important. High-speed imaging can allow scientists to capture very fast biological events. One of our research goals is to develop a robust and flexible ultra-high speed deep tissue imaging technology that can provide imaging speed at the theoretical limit (fluorescence decay rate) in deep tissues. Unlike previous attempts, our method can conveniently work with commercially available laser sources and the total data rate can be easily varied to match the decay rate of the fluorophore.
The Laser was first demonstrated at the Hughes Research Laboratory in 1960. Now, half a century has passed and the development of laser technologies continues to change both scientific research and our daily life. The capabilities of laser science for revealing the properties of materials and for performing measurement at unprecedented sensitivity and resolution are truly amazing. In addition to optical imaging, our laboratory is exploring new technologies of using laser to perform sensitive measurements.