Lianyu Guo

Multispectral scanning during endoscopy guides biopsy of dysplasia in Barrett's esophagus

Esophageal cancer is increasing in frequency in the United States faster than any other cancer. Barretts esophagus, an otherwise benign complication of esophageal reflux, affects approximately three million Americans and precedes almost all cases of esophageal cancer. If detected as high-grade dysplasia (HGD), most esophageal cancers can be prevented. Standard-of-care screening for dysplasia uses visual endoscopy and a prescribed pattern of biopsy. This procedure, in which a tiny fraction of the affected tissue is selected for pathological examination, has a low probability of detection because dysplasia is highly focal and visually indistinguishable. We developed a system called endoscopic polarized scanning spectroscopy (EPSS), which performs rapid optical scanning and multispectral imaging of the entire esophageal surface and provides diagnoses in near real time. By detecting and mapping suspicious sites, guided biopsy of invisible, precancerous dysplasia becomes practicable. Here we report the development of EPSS and its application in several clinical cases, one of which merits special consideration.

Photon diffusion near the point-of-entry in anisotropically scattering turbid media

From astronomy to cell biology, the manner in which light propagates in turbid media has been of central importance for many decades. However, light propagation near the point-of-entry in turbid media has never been analytically described, until now. Here we report a straightforward and accurate method that overcomes this longstanding, unsolved problem in radiative transport. Our theory properly treats anisotropic photon scattering events and takes the specific form of the phase function into account. As a result, our method correctly predicts the spatially dependent diffuse reflectance of light near the point-of-entry for any arbitrary phase function. We demonstrate that the theory is in excellent agreement with both experimental results and Monte Carlo simulations for several commonly used phase functions.

Gold nanorod light scattering labels for biomedical imaging

Gold nanorods can be used as extremely bright labels for differential light scattering measurements using two closely spaced wavelengths, thereby detecting human disease through several centimeters of tissue in vivo. They have excellent biocompatibility, are non-toxic, and are not susceptible to photobleaching. They have narrow, easily tunable plasmon spectral lines and thus can image multiple molecular targets simultaneously. Because of their small size, gold nanorods can be transported to various tissues inside the human body via the vasculature and microvasculature, and since they are smaller than vascular pore sizes, they can easily cross vascular space and enter individual cells.

Spectral Imaging With Scattered Light: From Early Cancer Detection to Cell Biology

This paper reports the evolution of scanning spectral imaging techniques using scattered light for minimally invasive detection of early cancerous changes in tissue and cell biology applications. Optical spectroscopic techniques have shown promising results in the diagnosis of disease on a cellular scale. They do not require tissue removal, can be performed in vivo, and allow for real-time diagnoses. Fluorescence and Raman spectroscopy are most effective in revealing molecular properties of tissue. Light scattering spectroscopy (LSS) relates the spectroscopic properties of light elastically scattered by small particles, such as epithelial cell nuclei and organelles, to their size, shape, and refractive index. It is capable of characterizing the structural properties of tissue on cellular and subcellular scales. However, in order to be useful in the detection of early cancerous changes that are otherwise not visible to the naked eye, it must rapidly survey a comparatively large area while simultaneously detecting these cellular changes. Both goals are achieved by combining LSS with spatial scanning imaging. Two examples are described in this paper. The first reviews a clinical system for screening patients with Barretts esophagus. The second presents a novel advancement in confocal light absorption and scattering spectroscopic microscopy.

Single Cell Spectroscopy for Isolating Fetal Cells from Maternal Blood

Non-invasive genetic screening by using fetal nucleated cells that are isolated from maternal blood remains a medically-relevant challenge. We present a combined approach which utilizes spectroscopy for identifying fetal cells as the final step.

Spectroscopic and Fluorescence Microscopy for Isolating Fetal Nucleated Red Blood Cells from Maternal Blood

We present a combined approach for isolating fetal nucleated red blood cells from the maternal blood supply for the purpose of genetic screening. The final step, spectroscopic microscopy, identifies fetal cells with native contrast.

Label-Free Spectroscopic Identification of Fetal Nucleated Red Blood Cells from Maternal Blood

We present a spectroscopic microscopy system for measuring transmission and reflectance from erythrocytes. Spectroscopic markers are used to distinguish between fetal and adult cells for the application of genetic screening from maternal blood.

Phase Function Corrected Diffusion Approximation for Light Transport in Turbid Media

Many optical imaging and spectroscopy applications require understanding how light propagates in turbid media near point-of-entry. We report an analytic solution to this problem that demonstrates excellent agreement with simulations and experiments.

Optical Spectroscopic Properties of Brown Fat Reveal Pathophysiological Conditions

A double-integrating-sphere system measures the absorption and scattering coefficients of brown and white fat. The optical spectroscopic properties of the fat tissue are sensitive to the pathophysiological conditions of mice.

Differential spectral imaging with gold nanorod light scattering labels

Gold nanorods have the potential to be employed as extremely bright molecular marker labels. However, samples containing a large number of gold nanorods usually exhibit relatively wide spectral lines. This linewidth limits the use of the nanorods since it would be rather difficult to image several types of nanorod markers simultaneously. We measured native scattering spectra of single gold nanorods with the CLASS microscope and found that single gold nanorods have a narrow spectrum as predicted by the theory. That suggests that nanorod-based molecular markers with controlled narrow aspect ratios should provide spectral lines sufficiently narrow for effective biomedical imaging.