Cui Lab
Our ongoing projects include a coherent optical adaptive technique-based two-photon microscopy, acoustic wave guided optical phase conjugation, and ultra-high speed two-photon microscopy for pushing the speed of deep tissue fluorescence imaging to the theoretical limit. Moreover, several other new techniques are being designed, including multiplex stimulated emission microscopy, multichannel excitation two-photon microscopy, and novel one-photon microscopy for deep tissue fluorescence imaging. The ultimate goal is to advance the frontier of optical molecular imaging and sensing to provide unprecedented detection depth, quality, sensitivity, and speed for a broad range of applications in biology and medicine
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.
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Meng Cui Lab Head
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Reto Fiolka Postdoctoral Associate
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Ke Si Postdoctoral Associate
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Kerry Sobieski
Janelia Publications
We show through experiments and simulations that parallel phase modulation, a technique developed in the field of adaptive optics, can be employed to quickly determine the spectral phase profile of ultrafast laser pulses and to perform phase compensation as well as pulse shaping. Different from many existing ultrafast pulse measurement methods, the technique reported here requires no spectrum measurements of nonlinear signals. Instead, the power of nonlinear signals is used directly to quickly measure the spectral phase, a convenient feature for applications such as two-photon fluorescence microscopy. The method is found to work with both smooth and even completely random distortions. The experimental results are verified with MIIPS measurements.
A large number of degrees of freedom are required to produce a high quality focus through random scattering media. Previous demonstrations based on spatial phase modulations suffer from either a slow speed or a small number of degrees of freedom. In this work, a high speed wavefront determination technique based on spatial frequency domain wavefront modulations is proposed and experimentally demonstrated, which is capable of providing both a high operation speed and a large number of degrees of freedom. The technique was employed to focus light through a strongly scattering medium and the entire wavefront was determined in 400 milliseconds, ~three orders of magnitude faster than the previous report.
A parallel wavefront optimization method is demonstrated experimentally to focus light through random scattering media. The simultaneous modulation of multiple phase elements, each at a unique frequency, enables a parallel determination of the optimal wavefront. Compared to a pixel-by-pixel measurement, the reported parallel method uses the target signal in a highly efficient way. With 441 phase elements, a high-quality focus was formed through a glass diffuser with a peak-to-background ratio of ∼270. The accuracy and repeatability of the system were tested through experiments.
Janelia Positions
Postdoc and research scientist positions are available for highly motivated and skilled experimentalists. Research background in optical science and engineering (such as optical microscopy, spectroscopy, AMO physics, nonlinear optics, holography, adaptive optics, laser optics, and ultrafast optics) is preferred. The ultimate goal of our lab is to develop new technologies that may impact the way biomedical research is performed. Strong interest towards this line of research is a plus. For application, please send email to Dr. Meng Cui.
To apply, please send your CV and include three references. In the subject line, include the word "Postdoc". If you have specific salary requirements, please include them in your e-mail; all information is confidential. HHMI is an equal opportunity employer.