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ABSTRACT: Currently, hematoxylin-eosin (H-E) stained histopathology is the golden standard for diagnosing lung cancer. This time-consuming procedure needs tissue biopsy, sample fixation, slicing, and labeling. Therefore, the availability of a noninvasive optical diagnosis that can obtain real-time analysis comparable to golden standard H-E stained histopathology will be of extraordinary benefit to the medical community. In this study, we investigated whether multiphoton imaging can make real-time optical diagnosis for normal and cancerous lung tissue, compared with H-E stained histopathology. In the normal lung tissue, we found that multiphoton imaging could display normal lung parenchyma composed of alveolar spaces separated by thin septa. In the cancerous lung tissue, multiphoton imaging clearly illustrated that cancer cells displayed marked cellular and nuclear pleomorphism. These cancer cells were characterized by irregular size and shape, enlarged nuclei, and increased nuclear-cytoplasmic ratio. All of these histopathological features of tissue architecture and cell morphology identified by multiphoton images were readily correlated with H-E staining images. All together, multiphoton imaging can make real-time optical diagnosis for lung cancer. This study provides the groundwork for further using multiphoton imaging to perform real-time noninvasive "optical biopsy" for lung cancer in the near future. SCANNING 9999:XX-XX, 2013. © 2013 Wiley Periodicals, Inc.
Scanning 02/2013; · 1.07 Impact Factor
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ABSTRACT: Esophageal cancer is one of the most common cancer and leading cause of cancer death worldwide. Multiphoton microscopy (MPM) has become a novel optical tool of choice for imaging tissue architecture and cellular morphology based on two-photon excited fluorescence and second harmonic generation. In this study, we used MPM to image microstructure of human normal esophagus, carcinoma in situ, and early invasive carcinoma in order to investigate the morphological change of tissue structure during the early phase of tumor progression. The diagnostic features such as the appearance of cancerous cells, the absence of the basement membrane were extracted to distinguish between normal and cancerous esophagus tissue. The infiltration depth during tumor progression was determined by the appearance of cancerous cells. The significant change of layer structure between cancerous tissue and normal esophagus was described. We also quantitatively described the differences of morphology between normal and cancerous cells. These results correlated well with the corresponding histological findings. With the advancement of clinically miniaturized MPM and the multi-photon probe, combining MPM with standard endoscopy will therefore allow us to make a real-time in vivo diagnosis of early esophageal cancer at the cellular level. SCANNING 9999:1-4, 2013. © Wiley Periodicals, Inc.
Scanning 02/2013; · 1.07 Impact Factor
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ABSTRACT: Collagen change is a major feature in the photoaged human skin. Here, we present the use of intrinsic second harmonic generation (SHG) signal as a novel means to quantify collagen change with photoaging. We obtain the SHG images of the superficial dermis from ex vivo the cheek skin and the abdomen skin of eight patients aged 55-60 years. The results show that SHG signal can quantitatively reveal collagen change between normal and photoaged human skin in three dimensions. By comparing normal with photoaged dermis, there are significant differences in the collagen content and fine structure, providing substantial potential to be applied in vivo for the clinical diagnosis of human skin photoaging. SCANNING 00: 1-4, 2012. © 2012 Wiley Periodicals, Inc.
Scanning 11/2012; · 1.07 Impact Factor
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ABSTRACT: Papulonodular mucinosis (PM) is a cutaneous clue to the presence and activity of silent lupus erythematosus (LE), but the exact pathogenesis is still under secret. Moreover, the currently available treatments for PM are not satisfactory. To demonstrate the possibility of multiphoton microscopy (MPM) to trace the pathological state of PM and evaluate the treatment efficacy, epidermal and dermal alteration in skin lesion with PM before and after treatment was examined using MPM. Microstructure of epidermis as well as content and distribution of collagen and elastin in dermis were quantified to characterize the pathological states of PM. The results showed significant morphological difference between skin lesion before and after treatment, indicating the possibility of MPM to assess the therapeutic efficacy. With the advancement on MPM miniaturization and enhancement of contrast and depth of imaging, the MPM technique can be applied in in vivo tracking PM formation and progression, and leading the better understanding the PM pathogenesis and mechanism of response to any treatment, helping to establish novel effective therapies for PM. SCANNING 00: 1-6, 2012. © 2012 Wiley Periodicals, Inc.
Scanning 06/2012; · 1.07 Impact Factor
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ABSTRACT: The layer structures of the esophageal and oral tissues were investigated by using spectral imaging technology based on two-photon
excited fluorescence (TPEF) and second-harmonic generation (SHG). Because spectral imaging technology allows a simultaneous
record of both the spectra and image, it is capable of identifying the layered structures of the epithelial tissues, including
the keratinizing layer, epithelial cell layer and stromal layer in the molecular level, which are strongly correlated to tissue
pathology. All this work indicates that this technique has the potential to provide more accurate and comprehensive information
for the early pathological diagnosis of tissues with the stratified squamous epithelia.
Frontiers of Optoelectronics in China 04/2012; 1(1):33-38.
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ABSTRACT: Liver or lung biopsy for suspicious lesions has several disadvantages such as bleeding, bile leak or pneumothorax, needle track seeding, and time-consuming histopathological procedure. The ability to directly observe cellular and subcellular details and then perform "optical biopsy" is a major goal in the development of new interventional techniques. Multiphoton microscopy (MPM) enables real-time noninvasive visualization of tissue architecture and cell morphology in live tissue. We performed a study to evaluate whether MPMcan make real-time optical diagnosis for liver cancer and lung metastasis using an orthotopic rat model with Morris hepatoma. We found that real-time high-resolution MPMimaging could clearly show tissue architecture and cell morphology. In the normal liver tissue, MPMimaging clearly revealed the blood-filled sinusoids and cords of hepatocytes. In the cancerous tissue, MPMimaging clearly illustrated that cancer cells displayed marked cellular and nuclear pleomorphism. MPMimages were comparable to golden standard hematoxylin-eosin staining images. Moreover, MPMimaging had deep penetration with the capability of optical sectioning. In short, MPMcan make real-time optical diagnosis for liver cancer and lung metastasis. This study provides the groundwork for further using multiphoton endoscopy to perform real-time noninvasive "optical biopsy" for liver cancer and lung metastasis in the near future.
Scanning 02/2012; 34(4):271-7. · 1.07 Impact Factor
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Jun Yan, Shuangmu Zhuo,
Gang Chen,
Xiufeng Wu,
Dong Zhou,
Shusen Xie,
Jiahao Jiang,
Mingang Ying,
Fan Jia,
Jianxin Chen,
Jian Zhou
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ABSTRACT: Recently, the miniaturized multiphoton microscopy (MPM) and multiphoton probe allow the clinical use of multiphoton endoscopy for diagnosing cancer via "optical biopsy". The purpose of this study was to establish MPM optical diagnostic features for liver cancer and evaluate the sensitivity, specificity, and accuracy of MPM optical diagnosis. Firstly, we performed a pilot study to establish the MPM diagnostic features by investigating 60 surgical specimens, and found that high-resolution MPM images clearly demonstrated apparent differences between benign and malignant liver lesions in terms of their tissue architecture and cell morphology. Cancer cells, characterized by irregular size and shape, enlarged nuclei, and increased nuclear-cytoplasmic ratio, were identified by MPM images, which were comparable to hematoxylin-eosin staining images. Secondly, we performed a blinded study to evaluate the sensitivity, specificity, and accuracy of MPM optical diagnosis by investigating another 164 specimens, and found that the sensitivity, specificity, and accuracy of MPM diagnosis was 96.32%, 96.43%, and 96.34%, respectively. In conclusion, it is feasible to use MPM to diagnose liver cancer and differentiate benign and malignant liver lesions. This preclinical study provides the groundwork for further using multiphoton endoscopy to perform real-time noninvasive "optical biopsy" for liver lesions in the near future.
Journal of Biomedical Optics 02/2012; 17(2):026004. · 3.16 Impact Factor
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ABSTRACT: Since changes in the basement membranes are the critical indicators for differentiating normal, precancerous, and cancerous colonic tissues, direct visualization of these warning signs is essential for the early diagnosis and treatment of colonic cancer. Here, we present that second harmonic generation (SHG) microscopy can probe the changes of basement membranes in different colonic cancer stages. Our results also show the capability of using the quantitative analyses of images for quantifying these changes in different cancer stages. These results suggest that SHG microscopy has the potential in label-freely imaging the changes of basement membranes for effectively distinguishing between normal, precancerous, and cancerous colonic tissues. To our knowledge, this is the first demonstration of the dynamics of basement membrane changes in different colonic cancer stages using entirely intrinsic source of contrast.
PLoS ONE 01/2012; 7(6):e38655. · 4.09 Impact Factor
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ABSTRACT: Most colorectal cancers arise from dysplastic lesions, such as adenomatous polyps, and these lesions are difficult to be detected by the current endoscopic screening approaches. Here, we present the use of an intrinsic second-harmonic generation (SHG) signal as a novel means to differentiate between normal and dysplastic human colonic tissues. We find that the SHG signal can quantitatively identify collagen change associated with colonic dysplasia that is indiscernible by conventional pathologic techniques. By comparing normal with dysplastic mucosa, there were significant differences in collagen density and collagen fiber direction, providing substantial potential to become quantitative intrinsic biomarkers for in vivo clinical diagnosis of colonic dysplasia.
Journal of Biomedical Optics 12/2011; 16(12):120501. · 3.16 Impact Factor
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ABSTRACT: Mouse is an important animal model to investigate skin physiological and pathological states. In this article, multiphoton microscopic imaging of in vivo hair mouse skin based on two-photon excited fluorescence and second harmonic generation was examined. Our results show that multiphoton microscopy can clearly display microstructure of stratum corneum, stratum spinosum, and dermis of in vivo mouse skin. The main components of epidermis and dermis such as corneocytes, spinosum cell, collagen fibers, and hair follicles can be distinctly identified in MPM images. Using the optional HRZ 200 fine focusing stage, thickness of different layers can be easily assessed. The results demonstrate that MPM can be regarded as an efficient method for in vivo investigation of skin physiological and pathological states by using hair mouse animal model.
Scanning 09/2011; 34(3):170-3. · 1.07 Impact Factor
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ABSTRACT: In contrast to colonoscopy biopsy, which contains several disadvantages such as bleeding, sampling error, crush artifact, and time-consuming pathological procedure, multiphoton microscopy (MPM) enables direct noninvasive visualization of tissue architecture and cell morphology in live tissues without the administration of exogenous contrast agents. We performed a proof-of-principle study to evaluate the feasibility of using MPM to make real-time noninvasive optical diagnosis of colorectal cancer by investigating 30 fresh, unfixed, and unstained full-thickness colorectal specimens. We found that MPM images demonstrated irregular tubular structures, reduced stroma, and cellular and nuclear pleomorphism in the cancerous tissues. Cancer cells, characterized by irregular size and shape, enlarged nuclei, and increased nuclear-cytoplasmic ratio, were clearly observed in MPM images, which were comparable to golden standard hematoxylin-eosin staining images. Our findings showed that MPM had the potential to make real-time noninvasive optical diagnosis of colorectal cancer. With miniaturization and integration of colonoscopy, MPM has a promising future in real-time noninvasive "optical biopsy" for colorectal cancer.
Scanning 09/2011; 34(3):181-5. · 1.07 Impact Factor
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ABSTRACT: Changes of dermal collagen are characteristic for chronic lymphedema. To evaluate these changes, a real-time imaging based on two-photon excited fluorescence and second-harmonic generation was developed for investigating collagen of lymphedematous mouse and rat tail skin in vivo. Our findings showed that the technique could image the morphological changes and distribution of collagen in lymphedematous mouse and rat tail skin in vivo. More importantly, it may allow visualization of dynamic collagen alteration during the progression of lymphedema. Our findings demonstrated that multiphoton microscopy may have potential in a clinical setting as an in vivo diagnostic and monitoring system for therapy in lymphology.
Scanning 07/2011; 33(6):463-7. · 1.07 Impact Factor
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ABSTRACT: Early detection of fibroadenoma (FA) is critical for preventing subsequent breast cancer. In this work, we show that label-free second harmonic generation (SHG) imaging is feasible and effective in quantitatively differentiating the fibroadenomal tissue from normal breast tissue. With the advent of the clinical portability of miniature SHG microscopy, we believe that the technique has great potential in offering a noninvasive in vivo imaging tool for early detection of FA and monitoring the treatment responses of FA in clinics.
Scanning 05/2011; 33(4):208-10. · 1.07 Impact Factor
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ABSTRACT: Multiphoton microscopy was used to study the extracellular matrix of keloid at the molecular level without tissue fixation and staining. Direct imaging of collagen and elastin was achieved by second harmonic generation and two-photon excited fluorescence, respectively. The morphology and quantity of collagen and elastin in keloid were characterized and quantitatively analyzed in comparison to normal skin. The study demonstrated that in keloid, collagen content increased in both the upper dermis and the deep dermis, while elastin mostly showed up in the deep dermis and its quantity is higher compared to normal skin. This suggests the possibility that abnormal fibroblasts synthesized an excessive amount of collagen and elastin at the beginning of keloid formation, corresponding to the observed deep dermis, while after a certain time point, the abnormal fibroblast produced mostly collagen, corresponding to the observed upper dermis. The morphology of collagen and elastin in keloid was disrupted and presented different variations. In the deep dermis, elastic fibers showed node structure, while collagen showed obviously regular gaps between adjacent bundles. In the upper dermis, collagen bundles aligned in a preferred direction, while elastin showed as sparse irregular granules. This new molecular information provided fresh insight about the development process of keloid.
Journal of Biomedical Optics 05/2011; 16(5):051305. · 3.16 Impact Factor
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ABSTRACT: Multiphoton microscopy (MPM) was applied to examine the marginal region at dermis of keloid compared with atrophic scar. High-resolution large-area image showed an obvious boundary at the scar margin and different morphological patterns of elastin and collagen on the two sides, further visualized by the focused three-dimensional images. Content alteration of elastin or collagen between the two sides of boundary was quantified to show significant difference between keloid and atrophic scar. Owing to the raised property of keloid with overproduced collagen on the scar side, the content alteration was positive for elastin and negative for collagen. On the contrary, the content alteration was negative for elastin and positive for collagen in the atrophic scar case due to the atrophic collagen on the scar side. It indicated that examination of the scar margin by MPM may lead a new way to discriminate different types of scars and better understand the scarring mechanisms.
Scanning 04/2011; 33(4):195-200. · 1.07 Impact Factor
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ABSTRACT: Establishing diagnostic features is essential and significant for developing multiphoton endoscopy to make an early diagnosis of gastric cancer at the cellular level. Until now, these diagnostic features have not been clearly described and understood.
Study of diagnostic features based on multiphoton microscopy (MPM).
Establishing diagnostic features to identify the mucosa and submucosa of human normal and cancerous gastric tissues by investigating their multiphoton microscopic images.
Fujian Normal University and Fujian Provincial Tumor Hospital.
Ten pairs of normal and cancerous specimens were obtained from 10 patients (ages 51-68 years) undergoing radical gastrectomy.
MPM was performed on specimens.
Establishment of diagnostic features.
MPM has the ability to exhibit not only the mucosal and submucosal microstructures of normal and cancerous gastric tissues but also the distribution and content of abnormal cells in these 2 layers. More importantly, it can provide the diagnostic features to qualitatively and quantitatively differentiate between normal and cancerous gastric tissues.
The selection bias and preparation of specimen.
These findings provide the groundwork for further establishing diagnostic criteria.
Gastrointestinal endoscopy 04/2011; 73(4):802-7. · 6.71 Impact Factor
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ABSTRACT: Multiphoton microscopic imaging of collagen plays an important role in noninvasive diagnoses of human tissue. In this study, two-photon fluorescence and second-harmonic generation (SHG) imaging of collagen in human skin dermis and submucosa of colon and stomach tissues were investigated based on multiphoton microscopy (MPM). Our results show that multiphoton microscopic image of collagen bundles exhibits apparently different pattern in human tissues. The collagen bundles can simultaneously reveal its SHG and two-photon excited fluorescence images in the submucosa of colon and stomach, whereas it solely emit SHG signal in skin dermis. The intensity spectral information from tissues further demonstrated the above results. This indicates that collagen bundles have completely different space arrangement in these tissues. Our experimental results bring more detailed information of collagen for the application of MPM in human noninvasive imaging.
Scanning 02/2011; 33(1):53-6. · 1.07 Impact Factor
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ABSTRACT: Real-time histology or virtual biopsy for the diagnosis of colonic cancer is of great medical significance. In this work, we show that label-free multiphoton imaging is feasible and effective in monitoring colonic cancer progression by providing cellular and subcellular details in fresh, unfixed, unstained colonic specimens. Our results also demonstrate the capability of using tissue quantitative analysis of the redox ratio for quantifying colonic cancer progression. These results suggest that multiphoton microscopy has potential to become an in situ histological tool, which is free from the labeling requirement of conventional methods, for the early diagnosis and detection of malignant lesions in the colon.
Biomedical Optics Express 01/2011; 2(3):615-9. · 2.33 Impact Factor
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ABSTRACT: Using a combination of autofluorescence from cells and second-harmonic generation (SHG) signal from collagen, multiphoton microscopy (MPM) imaging can provide detailed real-time information on tissue architecture and cellular morphology in live tissue without administration of exogenous contrast agents. The purpose of this study is to evaluate the feasibility of using MPM to histologically diagnose gastric cancer by using fresh, unfixed, unstained gastric specimens, compared with gold-standard hematoxylin-eosin (H-E)-stained histopathology.
A pilot study was performed between June 2009 and December 2009. Ten cases with gastric carcinoma confirmed by preoperative endoscopic biopsy underwent radical gastrectomy. The fresh specimen was opened, and a piece of cancer tissue and a piece of normal tissue each with a size of 1-1.5 cm across and 0.2 cm in thickness were taken and snap-frozen. A 5-μm slide was sectioned for MPM examination, and the remainder of the tissue went through routine histopathological procedure. MPM images and H-E-stained images were compared by the same attending pathologist.
MPM images were acquired by two channels: broadband autofluorescence from cells, and SHG from tissue collagen. Peak multiphoton autofluorescence intensity was detected in mucosa excited at 800 nm. Cancer cells, characterized by irregular size and shape, enlarged nuclei, and increased nuclear-to-cytoplasmic ratio, were identified by MPM images, which were confirmed by H-E-stained images. Regular architectures of gastric pits and gastric glands in the normal tissue of the same specimens were clearly revealed by MPM images, which were comparable to H-E-stained images.
It is feasible to use MPM to diagnose gastric cancer by "optical biopsy." With miniaturization and integration of endoscopy, MPM has the potential to provide real-time histological diagnosis without invasive biopsy for gastric cancer in the future.
Surgical Endoscopy 11/2010; 25(5):1425-30. · 4.01 Impact Factor
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ABSTRACT: This work reports on the measurement of optical properties from nine normal and cancerous human esophageal stroma pairs using reflectance-based confocal microscopy. It was found that the scattering coefficient of cancerous stroma is significantly lower than that of normal stroma. The results suggest that the decreased scattering in cancerous stroma may provide a possible indicator for differentiating normal and cancerous stroma.
Lasers in Medical Science 11/2010; 25(6):911-3. · 2.00 Impact Factor
