Lingyan Shi | University of California, San Diego (original) (raw)

Papers by Lingyan Shi

Highlights d Tauopathy neurons accumulate LDs d Tauopathy neurons release excess unsaturated lipi... more Highlights d Tauopathy neurons accumulate LDs d Tauopathy neurons release excess unsaturated lipids, taken up by microglia d LD-accumulating microglia are pro-inflammatory and impaired in phagocytosis d Neuronal AMPK inhibits LD accumulation in neurons and microglia

Lipids play crucial roles in many biological processes. Mapping spatial distributions and examini... more Lipids play crucial roles in many biological processes. Mapping spatial distributions and examining the metabolic dynamics of different lipid subtypes in cells and tissues are critical to better understanding their roles in aging and diseases. Commonly used imaging methods (such as mass spectrometry-based, fluorescence labeling, conventional optical imaging) can disrupt the native environment of cells/tissues, have limited spatial or spectral resolution, or cannot distinguish different lipid subtypes. Here we present a hyperspectral imaging platform that integrates a Penalized Reference Matching algorithm with Stimulated Raman Scattering (PRM-SRS) microscopy. Using this platform, we visualize and identify high density lipoprotein particles in human kidney, a high cholesterol to phosphatidylethanolamine ratio inside granule cells of mouse hippocampus, and subcellular distributions of sphingosine and cardiolipin in human brain. Our PRM-SRS displays unique advantages of enhanced chemical specificity, subcellular resolution, and fast data processing in distinguishing lipid subtypes in different organs and species.

Raman microscopy is a vibrational imaging technology that can detect molecular chemical bond vibr... more Raman microscopy is a vibrational imaging technology that can detect molecular chemical bond vibrational signals. Since this signal is originated from almost every vibrational mode of molecules with different vibrational energy levels, it provides spatiotemporal distribution of various molecules in living organisms without the need for any labeling. The limitations of low signal strength in Raman microscopy have been effectively addressed by incorporating a stimulated emission process, leading to the development of stimulated Raman scattering (SRS) microscopy. Furthermore, the issue of low spatial resolution has been resolved through the application of computational techniques, specifically image deconvolution. In this article, we present a comprehensive guide to super-resolution SRS microscopy using an Adam-based pointillism deconvolution (A-PoD) algorithm, complemented by a user-friendly graphical user interface (GUI). We delve into the crucial parameters and conditions necessary for achieving super-resolved images through SRS imaging. Additionally, we provide a step-by-step walkthrough of the preprocessing steps and the use of GUI-supported A-PoD. This complete package offers a user-friendly platform for super-resolution SRS microscopy, enhancing the versatility and applicability of this advanced microscopy technique to reveal nanoscopic multimolecular nature.

Triple negative breast cancer (TNBC) is a highly aggressive form of cancer. Detecting TNBC early ... more Triple negative breast cancer (TNBC) is a highly aggressive form of cancer. Detecting TNBC early is crucial for improving disease prognosis and optimizing treatment. Unfortunately, conventional imaging techniques fall short in providing a comprehensive differentiation of TNBC subtypes due to their limited sensitivity and inability to capture subcellular details. In this study, we present a multimodal imaging platform that integrates heavy water (D 2 O)-probed stimulated Raman scattering (DO-SRS), two-photon fluorescence (TPF), and second harmonic generation (SHG) imaging. This platform allows us to directly visualize and quantify the metabolic activities of TNBC subtypes at a subcellular level. By utilizing DO-SRS imaging, we were able to identify distinct levels of de novo lipogenesis, protein synthesis, cytochrome c metabolic heterogeneity, and lipid unsaturation rates in various TNBC subtype tissues. Simultaneously, TPF imaging provided spatial distribution mapping of NAD[P]H and flavin signals in TNBC tissues, revealing a high redox ratio and significant lipid turnover rate in TNBC BL2 (HCC1806) samples. Furthermore, SHG imaging enabled us to observe diverse orientations of collagen fibers in TNBC tissues, with higher anisotropy at the tissue boundary compared to the center. Our multimodal imaging platform offers a highly sensitive and subcellular approach to characterizing not only TNBC, but also other tissue subtypes and cancers.

Nature Light-Science & Applications, 2024

Cancer is a major public health problem and the second leading cause of death worldwide, with 10 ... more Cancer is a major public health problem and the second
leading cause of death worldwide, with 10 million deaths
in 20201. Early detection of cancer or precancerous
change allows for early intervention and can improve
survival rates. However, early detection of many cancers,
such as esophageal and ovarian cancers, is still poor,
which are often diagnosed at advanced stages. This is
more likely due to multiple remaining challenges, such as
finding and validating biomarkers for multicancer types,
and technologies applied for cancer detection.

Stimulated Raman scattering (SRS) microscopy is a nonlinear optical imaging method. It has emerge... more Stimulated Raman scattering (SRS) microscopy is a nonlinear optical imaging method. It has emerged as a powerful technology for quantitative imaging of nanoparticles (NPs) in diverse material systems. (1) This Viewpoint presents an overview of recent advancements of SRS microscopy in this field, highlighting its principles and advantages.

Nature Light Science & Applications

A new approach for early detection of multiple cancers is presented by integrating SERS spectrosc... more A new approach for early detection of multiple cancers is presented by integrating SERS spectroscopy of serum molecular fingerprints and machine learning. Cancer is a major public health problem and the second leading cause of death worldwide, with 10 million deaths in 2020 1. Early detection of cancer or precancerous change allows for early intervention and can improve survival rates. However, early detection of many cancers, such as esophageal and ovarian cancers, is still poor,

Journal of Innovative Optical Health Sciences

Although birefringence was discovered just three years after white light was separated into diffe... more Although birefringence was discovered just three years after white light was separated into different colors, polarimetry has lagged behind spectroscopy in characterizing diverse materials, likely due to our naked eyes' limited sensitivity to polarizations. Recent advancements in light sources, polarization optics, detectors, displays, data processing, and feature extraction techniques are rapidly propelling polarimetry as a convenient and potent tool for probing the distinct properties of complex and turbid materials. It is well known now that polarization properties of a material encode rich information on its distinct features, including not only the bulk optical properties related with dispersions and absorptions, but also distribution and microstructural properties of the scattering particles in turbid media such as the size, shape, orientation and alignment, surface morphology and internal structure, etc. All these features can be used for differentiating different materials, sensing ambient environment around scatterers, or monitoring dynamic processes in complex systems.

GEN Biotechnology

Studies have shown that brain lipid metabolism is associated with biological aging and influenced... more Studies have shown that brain lipid metabolism is associated with biological aging and influenced by dietary and genetic manipulations; however, the underlying mechanisms are elusive. High-resolution imaging techniques propose a novel and potent approach to understanding lipid metabolic dynamics in situ. Applying deuterium water (D 2 O) probing with stimulated Raman scattering (DO-SRS) microscopy, we revealed that lipid metabolic activity in Drosophila brain decreased with aging in a sex-dependent manner. Female flies showed an earlier occurrence of lipid turnover decrease than males. Dietary restriction (DR) and downregulation of insulin/IGF-1 signaling (IIS) pathway, two scenarios for lifespan extension, led to significant enhancements of brain lipid turnover in old flies. Combining SRS imaging with deuterated bioorthogonal probes (deuterated glucose and deuterated acetate), we discovered that, under DR treatment and downregulation of IIS pathway, brain metabolism shifted to use acetate as a major carbon source for lipid synthesis. For the first time, our study directly visualizes and quantifies spatiotemporal alterations of lipid turnover in Drosophila brain at the single organelle (lipid droplet) level. Our study not only demonstrates a new approach for studying brain lipid metabolic activity in situ but also illuminates the interconnection of aging, dietary, and genetic manipulations on brain lipid metabolic regulation.

Aging is associated with progressive declines in physiological integrity and functions alongside ... more Aging is associated with progressive declines in physiological integrity and functions alongside increases in vulnerability to develop a number of diseases. The brain regulates sensory and motor functions as well as endocrine functions, and age-associated changes in brain are likely prerequisite for the organismal aging. Lipid metabolism has been associated with brain aging, which could be easily intervened by diets and lifestyles. However, the underlying mechanism through which brain lipid metabolism is regulated by diet during aging is elusive. Using stimulated Raman scattering (SRS) imaging combined with deuterium water (D2O) labeling, we visualized that lipid metabolic activities were changed by diet manipulation in aging Drosophila brain. Furthermore, we illuminated that insulin/IGF-1 signaling (IIS) pathway mediates the transformation of brain lipid metabolic changes in both an aging- and a diet-dependent manner. The lipid droplets (LDs) in the brain gradually became inert in ...

Ultrafast Nonlinear Imaging and Spectroscopy X

Quantification of molecular colocalization is an essential issue in understanding many biological... more Quantification of molecular colocalization is an essential issue in understanding many biological processes in living organisms. To measure the spatial distribution of multiple biomolecules, an ideal way is to image them one by one in the exact same region of interest and the same focus plane. To achieve this goal, we integrated multiple optical imaging modalities including stimulated Raman scattering (SRS), multiphoton fluorescence (MPF), and second harmonic generation (SHG) all together into one multimodal microscopy. We further combined deuterium oxide probing with stimulated Raman scattering (DO-SRS) for visualizing newly synthesized protein and lipid molecules, in addition to macromolecules (protein and lipid, NADH and Flavin, collagen) imaged with label free SRS, MPF, and SHG. We quantitatively measured the metabolic dynamics in cells and animals under various conditions, including HeLa cells grew in different serine concentrations, Drosophila ovaries in young and old individuals, and two different types of breast cancer tissues from xenograft mouse models. The results show the capabilities and advantages of this multimodal imaging system in accessing the spatial distributions of multiple molecules quantitatively.

Lipids play crucial roles in many biological processes under physiological and pathological condi... more Lipids play crucial roles in many biological processes under physiological and pathological conditions. Mapping spatial distribution and examining metabolic dynamics of different lipids in cells and tissues in situ are critical for understanding aging and diseases. Commonly used imaging methods, including mass spectrometry-based technologies or labeled imaging techniques, tend to disrupt the native environment of cells/tissues and have limited spatial or spectral resolution, while traditional optical imaging techniques still lack the capacity to distinguish chemical differences between lipid subtypes. To overcome these limitations, we developed a new hyperspectral imaging platform that integrates a Penalized Reference Matching algorithm with Stimulated Raman Scattering (PRM-SRS) microscopy. With this new approach, we directly visualized and identified multiple lipid species in cells and tissues in situ with high chemical specificity and subcellular resolution. High density lipoprote...

Frontiers in Oncology

Triple negative breast cancer (TNBC) is a particularly aggressive cancer subtype that is difficul... more Triple negative breast cancer (TNBC) is a particularly aggressive cancer subtype that is difficult to diagnose due to its discriminating epidemiology and obscure metabolome. For the first time, 3D spatial and chemometric analyses uncover the unique lipid metabolome of TNBC under the tandem modulation of two key metabolites – insulin and methionine - using non-invasive optical techniques. By conjugating heavy water (D2O) probed Raman scattering with label-free two-photon fluorescence (TPF) microscopy, we observed altered de novo lipogenesis, 3D lipid droplet morphology, and lipid peroxidation under various methionine and insulin concentrations. Quantitative interrogation of both spatial and chemometric lipid metabolism under tandem metabolite modulation confirms significant interaction of insulin and methionine, which may prove to be critical therapeutic targets, and proposes a powerful optical imaging platform with subcellular resolution for metabolic and cancer research.

Proceedings of the National Academy of Sciences

Significance This article demonstrates a high-throughput technique to map cell images to cell pos... more Significance This article demonstrates a high-throughput technique to map cell images to cell positions. The technology uses a three-dimensional (3D) imaging flow cytometer to record multiparameter 3D cell images at a throughput of 1,000 cells/s and a cell placement robot to place the exiting cells from the imaging system on a filter plate in a first-in–first-out manner so the cells on the plate have the same order as the cells that are imaged. Innovative algorithms were developed to match the cell sequences from the imaging and placement modules to detect and eliminate errors to ensure high accuracy. The technology forms an unprecedented bridge between single-cell molecular analysis and single-cell image analysis to connect phenotype and genotype analysis with single-cell resolution.

Frontiers in Molecular Biosciences, 2021

Oxidative imbalance plays an essential role in the progression of many diseases that include canc... more Oxidative imbalance plays an essential role in the progression of many diseases that include cancer and neurodegenerative diseases. Aromatic amino acids (AAA) such as phenylalanine and tryptophan have the capability of escalating oxidative stress because of their involvement in the production of Reactive Oxygen Species (ROS). Here, we use D2O (heavy water) probed stimulated Raman scattering microscopy (DO-SRS) and two Photon Excitation Fluorescence (2PEF) microscopy as a multimodal imaging approach to visualize metabolic changes in HeLa cells under excess AAA such as phenylalanine or trytophan in culture media. The cellular spatial distribution of de novo lipogenesis, new protein synthesis, NADH, Flavin, unsaturated lipids, and saturated lipids were all imaged and quantified in this experiment. Our studies reveal ∼10% increase in de novo lipogenesis and the ratio of NADH to flavin, and ∼50% increase of the ratio of unsaturated lipids to saturated lipid in cells treated with excess p...

Frontiers in Aging, 2022

Emerging studies have shown that lipids and proteins play versatile roles in various aspects of a... more Emerging studies have shown that lipids and proteins play versatile roles in various aspects of aging. High-resolution in situ optical imaging provides a powerful approach to study the metabolic dynamics of lipids and proteins during aging. Here, we integrated D2O probing and stimulated Raman scattering (DO-SRS) microscopy to directly visualize metabolic changes in aging Drosophila ovary. The subcellular spatial distribution of de novo protein synthesis and lipogenesis in ovary was quantitatively imaged and examined. Our Raman spectra showed that early stages follicles were protein-enriched whereas mature eggs were lipid-enriched. DO-SRS imaging showed a higher protein synthesis in the earlier developing stages and an increased lipid turned over at the late stage. Aged (35 days) flies exhibited a dramatic decrease in metabolic turnover activities of both proteins and lipids, particularly, in the germ stem cell niche of germarium. We found an accumulation of unsaturated lipids in the...

Aging Cell, 2022

Lipid metabolism plays crucial roles during aging processes, but how it is regulated by diets and... more Lipid metabolism plays crucial roles during aging processes, but how it is regulated by diets and how it interplays with aging still remain unclear. We proposed a new optical imaging platform by integrating heavy water (D2O) probing with stimulated Raman scattering (DO‐SRS) microscopy, for the first time, to directly visualize and quantify lipid metabolism regulated by different diets and insulin signaling pathway in Drosophila fat body during aging. We found that calorie restriction, low protein diet, and (moderately) high protein and high sucrose diets enhanced lipid turnover in flies at all ages, while (moderately) high fructose and glucose diets only promoted lipid turnover in aged flies. The measured lipid turnover enhancements under diverse diets were due to different mechanisms. High protein diet shortened the lifespan while all other diets extended the lifespan. Downregulating the insulin signaling pathway enhanced lipid turnover, which is likely related to lifespan increase, while upregulating insulin signaling pathway decreased lipid turnover that would shorten the lifespan. Our study offers the first approach to directly visualize spatiotemporal alterations of lipid turnover in aging Drosophila in situ, for a better understanding of the interconnections between lipid metabolism, diets, and aging.

Advanced Chemical Microscopy for Life Science and Translational Medicine 2022, 2022

Understanding metabolism is of great significance to decipher various physiological and pathogeni... more Understanding metabolism is of great significance to decipher various physiological and pathogenic processes. While great progress has been made to profile gene expression, how to capture organ-, tissue-, and cell-type-specific metabolic profile (i.e., metabolic tissue atlas) in complex mammalian systems is lagging behind, largely owing to the lack of metabolic imaging tools with high resolution and high throughput. Here, the authors applied mid-infrared imaging coupled with heavy water (D 2 O) metabolic labeling to a scope of mouse organs and tissues. The premise is that, as D 2 O participates in the biosynthesis of various macromolecules, the resulting broad C-D vibrational spectrum should interrogate a wide range of metabolic pathways. Applying multivariate analysis to the C-D spectrum, the authors successfully identified both inter-organ and intra-tissue metabolic signatures of mice. A large-scale metabolic atlas map between different organs from the same mice is thus generated. Moreover, leveraging the power of unsupervised clustering methods, spatially-resolved metabolic signatures of brain tissues are discovered, revealing tissue and cell-type specific metabolic profile in situ. As a demonstration of this technique, the authors captured metabolic changes during brain development and characterized intratumoral metabolic heterogeneity of glioblastoma. Altogether, the integrated platform paves a way to map the metabolic tissue atlas for complex mammalian systems.

Nature Light-Science & Applications, 2024

Nature Light Science & Applications

Journal of Innovative Optical Health Sciences

GEN Biotechnology

Ultrafast Nonlinear Imaging and Spectroscopy X

Frontiers in Oncology

Proceedings of the National Academy of Sciences

Frontiers in Molecular Biosciences, 2021

Frontiers in Aging, 2022

Aging Cell, 2022

Advanced Chemical Microscopy for Life Science and Translational Medicine 2022, 2022

Brain Sciences

Defining the relationship between vascular development and the expression of hypoxia-inducible fa... more Defining the relationship between vascular development and the expression of hypoxia-inducible factors (Hifs) and vascular endothelial growth factor (Vegf) in the auditory brainstem is important to understand how tissue hypoxia caused by oxygen shortage contributes to sensory deficits in neonates. In this study, we used histology, molecular labeling, confocal microscopy and 3D image processing methods to test the hypothesis that significant maturation of the vascular bed in the medial nucleus of the trapezoid body (MNTB) occurs during the postnatal period that precedes hearing onset. Isolectin-B4 histochemistry experiments suggested that the MNTB vasculature becomes more elaborate between P5 and P10. When combined with a cell proliferation marker and immunohistochemistry, we found that vascular growth coincides with a switch in the localization of proliferating cells to perivascular locations, and an increase in the density of microglia within the MNTB. Furthermore, microglia were i...

Frontiers in Optics / Laser Science

A new theoretical model is presented on the underlying mechanism for odd higher harmonics generat... more A new theoretical model is presented on the underlying mechanism for odd higher harmonics generation (HHG) produced by ultrafast laser pulses from the nonlinear optical-electronic response n2 for SPM effects in rare gas molecules.

Multiphoton Microscopy in the Biomedical Sciences XX

2018 Conference on Lasers and Electro-Optics (CLEO), 2018

Brain samples from Alzheimer's patients and aged-matched controls were studied using label-fr... more Brain samples from Alzheimer's patients and aged-matched controls were studied using label-free fluorescence. Increased tryptophan metabolite to tryptophan ratios were seen in the hippocampus and Brodmann's area 9 in Alzheimer's patients as compared to normal.

Frontiers in Optics + Laser Science APS/DLS, 2019

Majorana like photons are introduced from class of classically entangled Cylindrical Vector Vorte... more Majorana like photons are introduced from class of classically entangled Cylindrical Vector Vortex Beams. An enhanced transmission is observed in mouse brain from Majorana vector photons with orbital angular momentum due to their non-separability.

Frontiers in Optics, 2018

Light transmission of Laguerre-Gaussian (LG) vortex beams in different local regions in mouse bra... more Light transmission of Laguerre-Gaussian (LG) vortex beams in different local regions in mouse brain tissue is investigated. Transmittance is measured in ballistic region with various polarizations states and orbital angular momentums (OAM).

The short wavelength infrared (SWIR) region (1000-2500 nm) has three near-infrared (NIR) windows ... more The short wavelength infrared (SWIR) region (1000-2500 nm) has three near-infrared (NIR) windows (1100-1350 nm, 1600-1870 and 2100-2350 nm). These windows have received increased attention in imaging and spectroscopy. We investigated the total attenuation lengths (lt) (based on absorption and scattering properties of light) through human normal and malignant prostate and breast tissues. It was found, using window III (at a wavelength of 1700 nm), that lt from prostate normal and cancerous tissues were 589 and 216 microns, whereas lt from breast normal and cancerous tissues were 271 and 106 microns. This non-invasive SWIR technique can show how prostate and breast cancer are different from normal prostate and breast. This could be important for patients who have hundreds of potential tumors, in which numerous biopsies are not possible. Important examples include patients with multiple skin, lung or bowel lesions. For example, patients with Von Recklinghausen’s Disease (neurofibromato...

Applied Optics

Key optical properties of calcite were measured to unravel the difference between stimulated Rama... more Key optical properties of calcite were measured to unravel the difference between stimulated Raman scattering (SRS) and self-phase modulation (SPM) for the supercontinuum (SC) for ordinary (O) wave and extraordinary (E) wave. These properties are group velocity dispersion, walk-off, spontaneous Raman spectra and cross section, optical 1086cm-1 phonon linewidth, nonlinear susceptibility (χ3), steady-state and transient SRS, and SC caused from SPM. These are investigated for O-waves and E-waves from a 2.7 cm thick calcite crystal. Using 390 fs pulses (∼0.8µJ pulse energy) at 517 nm, the O-wave produced a stronger sharp SRS peak at 1086cm-1 and a weaker SC spectrum in the visible range than the E-wave. The salient difference found between the O- and E-waves for SRS and SPM in calcite is attributed to the larger Raman cross section and the size of nonlinear susceptibility (χ3) for O-waves as compared to E-waves.

Optics Communications

Abstract Majorana-like photons are introduced in this paper, which are attributed to the polariza... more Abstract Majorana-like photons are introduced in this paper, which are attributed to the polarization and wavefront of special function class of optical vector vortex beams. A Majorana photon is a photon that is identical to its anti-photon. It has within itself both chirality, right and left-handed twist in polarization and wavefront. A theory is presented which reveals that certain types of cylindrical vector vortex photons that are spin–orbit coupled beams – radial, and azimuthal Laguerre-Gaussian, hybrid π -vector beams, and Airy beams – are Majorana-like based on their SAM (polarization) and OAM (wavefront) modes Majorana-like vector photons may play an important role in free-space fiber communication, propagation, quantum computing, optical computing, and imaging in turbid and bio-media as non-separable entangled polarized photons— a quantum mechanical entity.

Journal of Biomedical Optics

Glioma is one of the most refractory types of brain tumor. Accurate tumor boundary identification... more Glioma is one of the most refractory types of brain tumor. Accurate tumor boundary identification and complete resection of the tumor are essential for glioma removal during brain surgery. We present a method based on visible resonance Raman (VRR) spectroscopy to identify glioma margins and grades. A set of diagnostic spectral biomarkers features are presented based on tissue composition changes revealed by VRR. The Raman spectra include molecular vibrational fingerprints of carotenoids, tryptophan, amide I/II/III, proteins, and lipids. These basic in situ spectral biomarkers are used to identify the tissue from the interface between brain cancer and normal tissue and to evaluate glioma grades. The VRR spectra are also analyzed using principal component analysis for dimension reduction and feature detection and support vector machine for classification. The cross-validated sensitivity, specificity, and accuracy are found to be 100%, 96.3%, and 99.6% to distinguish glioma tissues from normal brain tissues, respectively. The area under the receiver operating characteristic curve for the classification is about 1.0. The accuracies to distinguish normal, low grade (grades I and II), and high grade (grades III and IV) gliomas are found to be 96.3%, 53.7%, and 84.1% for the three groups, respectively, along with a total accuracy of 75.1%. A set of criteria for differentiating normal human brain tissues from normal control tissues is proposed and used to identify brain cancer margins, yielding a diagnostic sensitivity of 100% and specificity of 71%. Our study demonstrates the potential of VRR as a label-free optical molecular histopathology method used for in situ boundary line judgment for brain surgery in the margins.

Journal of biomedical optics, Apr 1, 2017

There are three short wavelength infrared (SWIR) optical windows outside the conventionally used ... more There are three short wavelength infrared (SWIR) optical windows outside the conventionally used first near-infrared (NIR) window (650 to 950 nm). They occur in the 1000- to 2500-nm range and may be considered second, third, and fourth NIR windows. The second (1100 to 1350 nm) and third windows (1600 to 1870 nm) are now being explored through label-free linear and multiphoton imaging. The fourth window (2100 to 2350 nm) has been mostly ignored because of water absorption and the absence of sensitive detectors and ultrafast lasers. With the advent of new technology, use of window IV is now possible. Absorption and scattering properties of light through breast and prostate cancer, bone, lipids, and intralipid solutions at these windows were investigated. We found that breast and prostate cancer and bone have longer total attenuation lengths at NIR windows III and IV, whereas fatty tissues and intralipid have longest lengths at windows II and III. Since collagen is the major chromophor...

Complex Light and Optical Forces X, 2016

Light transmission of Laguerre Gaussian (LG) vortex beams with different orbital angular momentum... more Light transmission of Laguerre Gaussian (LG) vortex beams with different orbital angular momentum (OAM) values (L) in scattering beads and mouse brain tissue media were experimentally investigated for the first time in comparison with Gaussian (G) beams. The LG beams with different OAM were generated using a spatial light modulator (SLM) in reflection mode. The scattering beads media consist of various sizes and concentrations of latex beads in water solutions. The transmissions of LG and G beams through scattering beads and brain tissue media were measured with different ratios of sample thicknesses (z) to scattering mean free path (ls) of the turbid media, z/ls. The results indicate that within the ballistic region where z/ls is small, the LG and G beams show no significant difference, while in the diffusive region where z/ls is higher, the vortex beams show higher transmission than G beams. In the diffusive region, the LG beams with higher L values show higher transmission than the beams with lower L values due to the eigen channels in the media. The transition points from the ballistic to diffusive regions for different scattering beads and brain tissue media were studied.

Complex Light and Optical Forces XI, 2017

Transmittance of Laguerre-Gaussian (LG) vortex beams in mouse brain tissue is measured with diffe... more Transmittance of Laguerre-Gaussian (LG) vortex beams in mouse brain tissue is measured with different orbital angular momentums (OAM). The transition point from ballistic to diffusive region for the mouse brain tissue is determined at about 480 μm. The observed transmittances of the LG beams show independence on OAM modes in both ballistic and diffusive regions, which may be attributed to the interference effects from brain tissue.

Frontiers in Optics 2016, 2016

Multiphoton Microscopy in the Biomedical Sciences XVI, 2016

The blood–brain barrier (BBB) is a unique structure between the cerebral blood circulation and th... more The blood–brain barrier (BBB) is a unique structure between the cerebral blood circulation and the delicate neural environment that is important in regulating the movement of molecules and ions involved in brain development and function. However, little is known about the physiological permeability of molecules and ions across the BBB during brain development. In this study we applied an innovative approach to examine the development of BBB properties quantitatively. Two-photon microscopy was employed to measure BBB permeability in real time in vivo. Vascular growth and specific interactions between astrocyte end feet and microvessels were studied by using a combination of IB4 histochemistry, immunohistochemistry, confocal microscopy and 3D analysis.

Biomedical Optics 2016, 2016

This study applies optical window (III, 1,600-1,870 nm) for deep brain imaging. In vivo experimen... more This study applies optical window (III, 1,600-1,870 nm) for deep brain imaging. In vivo experiment was conducted on mice with skull thinning and skull intact by using a homemade 1620nm multiphoton microscopy.

Diagnostic Endoscopy, edited by Haishan Zeng, is a new book recently published by CRC Press. This... more Diagnostic Endoscopy, edited by Haishan Zeng, is a new book recently published by CRC Press. This book is clearly organized and incorporates both well-established and new theories and principles of endoscopy that are
used in laboratory and clinical practice. It will help enlighten the medical community to unlock the value of applying
spectroscopy to medicine, and to educate undergraduate and graduate students in the field of biomedical optics.