Proceedings Volume 7845

Optics in Health Care and Biomedical Optics IV

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Proceedings Volume 7845

Optics in Health Care and Biomedical Optics IV

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Volume Details

Date Published: 8 November 2010
Contents: 15 Sessions, 77 Papers, 0 Presentations
Conference: Photonics Asia 2010 2010
Volume Number: 7845

Table of Contents

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Table of Contents

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  • Front Matter: Volume 7845
  • Multimodal Biomedical Imaging
  • Optical Methods for Biomedical Applications
  • Advanced Optical Techniques for Diagnosis
  • Biomedical Imaging and Analysis
  • Diffuse Optical Imaging and Scattering Analysis
  • Spectroscopy and Tissue Diagnosis
  • Multiphoton Microscopy and Applications
  • Optical Interactions with Tissues and Cells
  • Nano-/Biophotonics
  • Photo-thermal Interaction and Calculations
  • Optical Techniques: Advances in Research
  • Mechanisms and Techniques in Photodynamic Therapy
  • Advanced Biomedical and Clinical Systems
  • Poster Session
Front Matter: Volume 7845
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Front Matter: Volume 7845
This PDF file contains the front matter associated with SPIE Proceedings volume 7845, including the Title Page, Copyright information, Table of Contents, Introduction, and the Conference Committee listing.
Multimodal Biomedical Imaging
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Quantitative phase microscopy of red blood cells with slightly-off-axis interference
Microscopic interferometry is a noncontact technique for quantitative phase imaging of live cells. The method combines the principles of single-shot slightly-off-axis interferometry and confocal microscopy and is characterized by real-time acquisition capabilities and optimized spatial resolution. However, slightly-off-axis interferometry requires less detector bandwidth than traditional off-axis interferometry and fewer phase-shifted steps than on-axis interferometry. Meanwhile, confocal microscopy allows microstructure magnification imaging. To validate the utility of this technique, experimental and theoretical comparisons are given. The potential of the technique for phase microcopy is demonstrated by experiments on red blood cells. This study will set the basis for interferometric phase measurements of dynamic processes with fine spatial details, especially for observing live biological cell dynamics.
Elimination of the twist distortion in IVUS and CAG image fusion based on the Frenet-Serret formulas
Hongxiao Li, Zhaoxia Zhang, Xiaodong Chen, et al.
Cardiovascular disease can be diagnosed at higher accuracy by the fusion of IVUS (Intravascular Ultrasound) and CAG (Coronary Angiography) data. In the IVUS images acquisition process, pull-back path of the ultrasonic probe will twist due to intravascular blood flow and friction with vascular wall, which causes image distortion in the fusion of such IVUS images. In this paper, a new method used for reducing the twist between adjacent frames of IVUS is presented. First, we establish a rough perspective projection imaging model from the crossing information of two almost perpendicular projective angiography images. Then we use a discrete approximation of the Frenet-Serret formulas to calculate IVUS frames' relative twist by sequential triangulation method and correct the twist. Finally, coronary lumen data extracted from the corrected IVUS images are added to 3D transducer paths which are reconstructed by the model mentioned above. Reconstruction of the coronary artery which contains the lumen information of IVUS removes blind spots in CAG and provides a full view of artery which is absent in IVUS images.
Optical Methods for Biomedical Applications
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Depletion kinetics of circulating prostate cancer cells studied by in vivo flow cytometer
Guangda Liu, Jin Guo, Yan Li, et al.
Prostate cancer is the most common malignancy in American men and the second leading cause of deaths from cancer, after lung cancer. The tumor usually grows slowly and remains confined to the gland for many years. During this time, the tumor produces little or no symptoms or outward signs. As the cancer advances, however, it can metastasize throughout other areas of the body, such as the bones, lungs, and liver. Surgical resection, hormonal therapy, chemotherapy and radiation therapy are the foundation of current prostate cancer therapies. Treatments for prostate cause both short- and long-term side effects that may be difficult to accept. Molecular mechanisms of prostate cancer metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of cancer cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern prostate cancer cell spread through the microenvironment in vivo in real-time confocal nearinfrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess prostate cancer cell spreading and the circulation kinetics of prostate cancer cells. A real- time quantitative monitoring of circulating prostate cancer cells by the in vivo flow cytometer will be useful to assess the effectiveness of the potential therapeutic interventions.
Evaluation of whole blood coagulation process by optical coherence tomography
Xiangqun Xu, Jia Lin
This study was to investigate the feasibility of using optical coherence tomography (OCT) to evaluate whole blood coagulation process. Attenuation coefficients and 1/e light penetration depth (D1/e) against time of human whole blood during in vitro clot formation under static were measured from the OCT profiles of reflectance vs depth. The results obtained clearly showed that the optical parameters are able to identify three stages during the in vitro blood clotting process. It is concluded that D1/e measured by OCT is a potential parameter to quantify and follow the liquid-gel transition of blood during clotting.
Dynamic temperature monitoring and control with fully distributed fiber Bragg grating sensor
Yuetong Ding, Na Chen, Zhenyi Chen, et al.
In this paper, fiber Bragg grating (FBG) is used as a fully distributed sensor to monitor tissue dynamic temperature changes during laser-induced interstitial thermotherapy (LITT). This work is mainly realized by the correlative single particle (CSP) algorithm, which is a rapid algorithm for spectrum reconstruction. Experimental LITT treatment was set up by using 532nm laser applicator on a piece of fresh liver tissue. In the experiments, the dynamic temperature profile was successfully demodulated with a refreshing speed of 11 seconds. With the aid of dynamic feedback, the thermotherapy boundary temperature was well controlled around 35°C during the treatment by adjusting the laser output power in real-time. Therefore, with this method, it is promising to precisely control the tissue temperature in vivo and improve the safety of the LITT remarkably.
Effects of the optical transfer function on velocity estimation with optical coherence tomography
Xianling Zhang, Wanrong Gao, Peng Li
Doppler optical coherence tomography (DOCT) is an extension of optical coherence tomography (OCT) for measuring blood flow dynamics simultaneously with the microscopic structures at high spatial and velocity resolution. In this paper, we analyze the effects of parameters of the DOCT system on the optical transfer function (OTF) which finally affects the accuracy of the velocity estimation. Experimental data are given to show the effects. The methods of overcoming the effects are also pointed out.
Advanced Optical Techniques for Diagnosis
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Single-detector polarization-sensitive OCT for biological tissue imaging
Yi Wang, Xiaodong Chen, Haifeng Li, et al.
In this paper, we built up a single-detector PS-OCT system using only one detector. It displays interference light oscillation caused by tissue birefringence as grey image, eliminating the time-comsuming calculation in conventional two-detector PS-OCT. The periodicity of grey scale indicates the birefringence distribution of tissue, which is far more straightforward than Muller matrix or Stokes vector in conventional two-detector PS-OCT. The the imaging theory and setup of single-detector PS-OCT is discussed in detail, and experiment with bovine cartilage proved its ability of detecting tissue birefringence.
Monitoring collagen remodeling on opto-thermal response of photoaged skin irradiated by Er:YAG laser with optical coherence tomography
The Optical Coherence Tomography technology was used to perform noninvasive cross-sectional imaging of internal structures in photoaged mouse skin irradiated by Er:YAG laser. The mice were irradiated chronically with a steady dose of ultraviolet irradiation. Various laser light doses were irradiated on the back skins of the photoaged mouse. An OCT was used to observe the process of the collagen remodeling in dermis. The relationship between optical characteristic parameter such as attenuation coefficient and light dose was discovered. The total attenuation coefficient increased when the light dose increased. Our findings showed that Er:YAG laser could be used for the symptoms of the photoaged skin with some degree of thermal damage in the dermis, and the OCT could image the progress of collagen remodeling in photoaged mouse dermis. The OCT may be a useful tool for the determination of optimal parameters for laser skin treatment.
Biomedical Imaging and Analysis
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Performance of hybrid system for fluorescence and micro-computed tomography in synchronous mode
Xin Liu, Yi Zhang, Fei Liu, et al.
Fluorescence diffuse optical tomography (FDOT) plays an important role in studying physiological and pathological processes of small animals in vivo. The low spatial resolution, however, limits the ability of FDOT in resolving the biodistributions of fluorescent markers. The anatomical information provided by X-ray computed tomography (CT) can be used to improve the image quality of FDOT. However, in most hybrid FDOT/CT systems, the projection data sets of optics and X-ray are acquired sequentially, which increases the acquisition time and bring in the unwanted soft tissue displacement. In this paper, we evaluate the performance of a synchronous FDOT/CT system, which allows for faster and concurrent imaging. Compared with previous FDOT/CT systems, the two subsystems (FDOT and CT) acquire projection images in synchronous mode, so the body position can keep consistent in the same projection data acquired by both subsystems. The experimental results of phantom and in vivo experiments suggest that the reconstruction quality of FDOT can be significantly improved when structural a priori information is utilized to constrain the reconstruction process. On the other hand, the synchronous FDOT/CT system decreases the imaging time.
Effect of electrode configurations on the focal spot of x-ray tube
Jinchuan Guo, Xikui Ren, Bin Zhou, et al.
The grating-based x-ray phase-contrast imaging have more advantages over the conventional x-ray imaging techniques based on the attenuation of x-rays in soft tissues in the medical diagnosis. However, until now the phase contrast imaging technique have not been put into practical uses, one of the reasons is that there is no compact x-ray source suitable for phase signal detection. The x-ray tube that can be used as the source of phase contrast imaging system is becoming the focus of research, the key issues of which could be the shape and the uniformity of focal spot. This paper provided and studied one kind of x-ray tube based on the electron impinging target. According to the system design of the phase contrast imaging, an x-ray tube with square focal spot of 0.8 mm side length was needed. An electrode structure which could form a planar electric field distribution was so designed that the emitted electrons from filament could move to target along straight paths. For comparison, an axis-symmetry field x-ray tube was designed too. The electron trajectories were simulated following the computation of the electric potential distributions in the two cases of electrode structure, respectively. The simulation results show that the x-ray tube of planar field structure may lend more regular square shape to focus spot than the axis-symmetry field structures.
Characterization of photoacoustic signal using wavelet analysis
In this paper, we present the continuous wavelet analysis for extract the information of photoacoutical signal sampled with a focoused transducer. The results demonstrate that wavelet transform of photoacoustic signals with 1 time averaging could reconstruct the localization and the size of absorbers, and it greatly reduced the data acquisition time. In addition, the results indicate that the localization and the size of absorbers could be recovered as the value of signal-to-noise ratio (SNR) is in the range from 0.3 to1.
Multispectral colour analysis for quantitative evaluation of pseudoisochromatic color deficiency tests
Multispectral color analysis was used for spectral scanning of Ishihara and Rabkin color deficiency test book images. It was done using tunable liquid-crystal LC filters built in the Nuance II analyzer. Multispectral analysis keeps both, information on spatial content of tests and on spectral content. Images were taken in the range of 420-720nm with a 10nm step. We calculated retina neural activity charts taking into account cone sensitivity functions, and processed charts in order to find the visibility of latent symbols in color deficiency plates using cross-correlation technique. In such way the quantitative measure is found for each of diagnostics plate for three different color deficiency carrier types - protanopes, deutanopes and tritanopes. Multispectral color analysis allows to determine the CIE xyz color coordinates of pseudoisochromatic plate design elements and to perform statistical analysis of these data to compare the color quality of available color deficiency test books.
Diffuse Optical Imaging and Scattering Analysis
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Quantitative analysis of dehydration in porcine skin caused by optical clearing agents
Tingting Yu, Xiang Wen, Shu Duan, et al.
Dehydration is supposed to be one of mechanisms of optical clearing, but current studies merely gave some qualitative descriptions. Here an analysis method was established to evaluate the water content of skin with PLS method based on the measurements of near-infrared reflectance spectroscopy and weight of porcine skin. Furthermore, a commercial spectrometer with integrating sphere was used to measure the reflectance and transmittance after treatment with different agents. Then the established method was used to evaluate the water content, while the Inverse Adding-Double algorithm was used to calculate the reduced scattering coefficients. The results show that both the water contents and reduced scattering coefficients decrease during the optical clearing process, and there is direct relationship between the optical clearing efficacy and dehydration. With the treating time last, the relative change in reduced scattering coefficient is larger than that in dehydration of skin, and the difference between the changes depends on the agents. Therefore, we conclude that dehydration is the main mechanism of skin optical clearing during the 60 min treatment of the agents, but for some OCAs, i.e., PEG400, glycerol, or D-sorbitol, there might be some other mechanisms contributing to the optical clearing efficacy.
Study on the backscattering Mueller matrix of the sphere-cylinder scattering model of anisotropic tissues
Most biological tissues are anisotropic turbid media containing fibrous structures, such as collagen fibers, axons, or myofibrils. Tests using both unpolarized and polarized lights indicate that the anisotropic tissues can be approximated to a scattering medium containing cylindrical and spherical scatterers. Mueller matrix, as a representative measurement to examine polarization properties, can be used to analyze some important information of turbid media. In this paper, we measure the two dimensional backscattering Mueller matrix of a microsphere-silk phantom composed of a slab of well aligned silk fibers submerged in microsphere solution. We also use a polarization sensitive Monte Carlo simulation program to analyze the Mueller matrix of sphere-cylinder scattering media, such as the microsphere-silk sample. We present systematic analysis about the relationship between the characteristic features in all the Mueller matrix elements and the important parameters of the sphere-cylinder scattering medium approximating biological tissues, such as the sphere-cylinder ratio, direction of the cylinders, diameters of both types of scatterers, etc. These experimental and simulation results confirm the practicability of backscattered Mueller matrix characterizing such anisotropic scattering media like biological tissues.
The influence of molecules adsorbed on surface enhanced Raman scattering
Xingfang Zhang, Yuanyun Zhang, Jie Cao, et al.
The relationship between the SERS signal intensity properties and the soaking times in a given concentration of 4-aminothiophenol (4-ATP) solution is experimentally investigated. The results show that the relationship depends on the specific position of the SERS excitation wavelength within the LSPR spectrum of the SERS substrates. In the case of LSPR peak wavelength of the SERS substrate located at the right side of ideal excitation wavelength arrangement, the SERS intensity no longer increases monotonically with the soaking time, which is different from the previous result reported.
Spectroscopy and Tissue Diagnosis
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Feasibility study for rapid determination of alanine aminotransferase concentration in whole blood by using visible and near infrared spectroscopy
Furong Huang, Zhe Chen, Jianhui Yu, et al.
Visible and Near infrared spectroscopy was applied for the fast determination of alanine aminotransferase with whole blood. First, spectra of different thickness (0.5mm, 1mm, 2mm, 4mm ) were investigated to explore Optimal Optical Path for determination. The results show that the whole blood sample with 0.5mm thickness is more suitable for spectral analysis. And then Near infrared spectroscopy of 176 samples were collected. Multiplicative scatter correction and second-order differential method have been used to spectral pretreatment. Stepwise multiple linear regression method and partial least squares regression method have been employed to establish quantitative detection model to predict content of alanine aminotransferase in whole blood. The alanine aminotransferase measured presents best result in calibration and prediction by Near-Infrared Spectroscopy with partial least squares regression calibration model, and the calibration correlation coefficient, the standard error of calibration and the standard error of prediction are 0.98, 2.42 and 7.22 respectively.
Discriminant analysis for classification of colonic tissue autofluorescence spectra
Lina Liu, Bingyang Liu, Weihua Li, et al.
This study evaluates the potential of a discriminant analysis to classify colonic mucosa from autofluorescence spectral characteristics. With 337 nm excitation, the autofluorescence spectra of colonic tissues were measured using a FLS920 spectrofluorimeter. Principal component analysis (PCA) combined with Fisher's discriminant analysis was performed for tissue classification. As a result, the sensitivity and specificity of the discriminant analysis is 92.3% and 90.5%, respectively. The results suggest the relative concentrations of collagen and nicotinamide adenine dinucleotide (NADH) are the potential diagnostic biomarkers for colonic tissue classification using autofluorescence spectroscopy, and the discriminant analysis based on PCA is useful to differentiate adenocarcinoma from normal tissue.
Raman micro-spectroscopy for classification of nasopharyngeal tissue in vitro
Yongzeng Li, Ying Su, Wei Huang, et al.
Nasopharyngeal carcinoma is one of the most serious diseases which is mostly found in Asia, especially in South China. Early detection and diagnosis is crucial to effective treatment and can greatly improve survival rate. Recent developments in tissue spectroscopy may significantly expand our ability to diagnose this tumor rapidly and accurately. In this work, Raman spectra of nasopharyngeal tissue in vitro were acquired and analyzed with principal component analysis. Consistent spectral differences appear to exist between normal and cancerous tissue, mainly in five bands located at 853cm-1, 937cm-1, 1094cm-1, 1260-1340cm-1, 1530-1580 cm-1, respectively. Statistical analysis was performed using PCA which can easily divide the samples to two groups with a high sensitivity and specificity. The results presented here demonstrate Raman spectroscopy has the potential ability to detect and diagnose cancerous tissue nondestructively and rapidly which may be a very helpful diagnosis tool in the future.
Multiphoton Microscopy and Applications
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The analysis of aging skin based on multiphoton microscopy
Aging is a very important issue not only in dermatology, but also in cosmetic science. Cutaneous aging involves both chronological and photoaging aging process. The chronological aging is induced with the passage of time. And the photoaging skin is the extrinsic aging caused by sun exposure. The aim of this study is to use multiphoton microscopy (MPM) in vivo to assess intrinsic-age-related and photo-age-related difference. The changes of dermal collagen are measured in quantitively. The algorithm that we used automatically produced the transversal dermal map from MPM. Others, the texture of dermis are analyzed by Fourier transform and Gray Level Co-occurrence Matrix. And the object extraction in textured images is proposed based on the method in object edge extraction, and the aim of it is to detect the object hidden in the skin texture in difference aging skin. The result demonstrates that the approach is effective in detecting the object in epidermis and dermis textured image in different aging skin. It could help to further understand the aging mechanism.
Cell flow analysis with a two-photon fluorescence fiber probe
We report the use of a sensitive double-clad fiber (DCF) probe for in situ cell flow velocity measurements and cell analysis by means of two-photon excited fluorescence correlation spectroscopy (FCS). We have demonstrated the feasibility to use this fiber probe for in vivo two-photon flow cytometry previously. However, because of the viscosity of blood and the non-uniform flow nature in vivo, it is problematic to use the detected cell numbers to estimate the sampled blood volume. To precisely calibrate the sampled blood volume, it is necessary to conduct real time flow velocity measurement. We propose to use FCS technique to measure the flow velocity. The ability to measure the flow velocities of labeled cells in whole blood has been demonstrated. Our two-photon fluorescence fiber probe has the ability to monitor multiple fluorescent biomarkers simultaneously. We demonstrate that we can distinguish differently labeled cells by their distinct features on the correlation curves. The ability to conduct in situ cell flow analysis using the fiber probe may be useful in disease diagnosis or further comprehension of the circulation system.
Collagen alteration as quantitative optical biomarker of epithelial tumor progression
Collagen plays an important role during epithelial tumor progression. Visualizing collagen alteration may become an intrinsic indicator for evaluating epithelial tumor progression. In this work, we demonstrate that collagen alteration can be used as quantitative optical biomarker of epithelial tumor progression by use of second harmonic generation microscopy.
Optical Interactions with Tissues and Cells
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A role for Nrf2 in UVA-mediated heme oxygenase induction and protection from membrane damage in human skin fibroblasts
Haibin Li, Linhao Li, Linhong Deng, et al.
Our previous study has shown that Ultraviolet-A (UVA) irradiation induces heme oxygenase 1 (HO-1) expression in cultured human primary skin fibroblasts FEK4. In the present study, we demonstrate a coordinated induction of HO-1 and NF-E2-related factor 2 (Nrf2) following UVA irradiation or hemin treatment. The induction of HO-1 by either UVA irradiation or hemin treatment was largely abolished by down-regulation of Nrf2 with its targeted short interfering RNA (siNrf2). The study further reveals that knockdown of Nrf2 protein increased UVA-induced cell death measured by MTS assay. These findings together indicate that Nrf2-mediated induction of HO-1 expression may provide a cytoprotection for human skin cells from oxidative damage.
Photonic homeostatics
Timon Cheng-Yi Liu, Fan-Hui Li
Photonic homeostatics is a discipline to study the establishment, maintenance, decay, upgrading and representation of function-specific homoestasis (FSH) by using photonics. FSH is a negative-feedback response of a biosystem to maintain the function-specific fluctuations inside the biosystem so that the function is perfectly performed. A stress may increase sirtuin 1 (SIRT1) activities above FSH-specific SIRT1 activity to induce a function far from its FSH. On the one hand, low level laser irradiation or monochromatic light (LLL) can not modulate a function in its FSH or a stress in its stress-specific homeostasis (StSH), but modulate a function far from its FSH or a stress far from its StSH. On the other hand, the biophotons from a biosystem with its function in its FSH should be less than the one from the biosystem with its function far from its FSH. The non-resonant interaction of low intensity laser irradiation or monochromatic light (LIL) and a kind of membrane protein can be amplified by all the membrane proteins if the function is far from its FSH. This amplification might hold for biophoton emission of the membrane protein so that the photonic spectroscopy can be used to represent the function far from its FSH, which is called photonomics.
Light induced heme oxygenase 1 is suppressed by Bach1 in human skin keratinocytes
Ruoqi Xu, Wanqian Liu, Jin Zhang, et al.
Ultraviolet A (UVA) radiation is an oxidizing agent that strongly induces the heme oxygenase 1(HO-1) expression in cultured human skin fibroblasts, but weakly induces it in skin keratinocytes. Here, we report that low basal levels of HO- 1 and much higher basal levels of HO-2 protein were observed in keratinocytes compared with fibroblasts. Silencing of Bach1 strongly increased HO-1 levels in HaCaT transformed keratinocytes and these HO-1 levels were not further increased by either UVA irradiation or silencing of HO-2. This is consistent with the conclusion that high constitutive levels of HO-2 expression in keratinocytes are responsible for the resistance of these cells to HO-1 induction by UVA radiation and that Bach1 plays a predominant role in influencing the lack of HO-1 expression in keratinocytes. Bach1 inhibition reduced the 500 kJ/m2 UVA-induced cell damage by LDH membrane integrity and MTS viability assays. These results suggest that Bach1 inhibition protect against high dose of UVA irradiation induced damage in keratinocytes.
The effect of 630-nm light stimulation on the sEMG signal of forearm muscle
Dan D. Yang, W. Sheng Hou, Xiao Y. Wu, et al.
This study aimed to explore if the red light irradiation can affect the electrophysiology performance of flexor digitorum superficialis (FDS) and fatigue recovery. Four healthy volunteers were randomly divided into two groups. In the designed force-tracking tasks, all subjects performed the four fingertip isometric force production except thumb with a load of 30% of the maximum voluntary contraction (MVC) force until exhaustion. Subsequently, for the red light group, red light irradiation (640 nm wavelength, 0.23J/cm2, 20 min) was used on the right forearm; for the control group, the subjects relaxed without red light irradiation. Then subjects were required to perform fatigue trail again, and sEMG signal was collected simultaneously from FDS during finger force production. Average rectified value (ARV) and median frequency (MF) of sEMG were calculated. Compared to the control group, the red light irradiation induced more smoother value of ARV between 30% and 40%, and the value of MF was obviously large and smooth. The above electrophysiological markers indicated that recovery from muscle fatigue may be positively affected by the red light irradiation, suggesting that sEMG would become a power tool for exploring the effect of red light irradiation on local muscle fatigue.
Brain lesion induced by 1319nm laser radiation
The laser-tissue interaction has not been well defined at the 1319 nm wavelength for brain exposure. The goal of this research effort was to identify the behavioral and histological changes of brain lesion induced by 1319 nm laser. The experiment was performed on China Kunming mice. Unilateral brain lesions were created with a continuous-wave Nd:YAG laser (1319nm). The brain lesions were identified through behavioral observation and histological haematoxylin and eosin (H&E) staining method. The behavior change was observed for a radiant exposure range of 97~773 J/cm2. The histology of the recovery process was identified for radiant exposure of 580 J/cm2. Subjects were sacrificed 1 hour, 1 week, 2 weeks, 3 months, 7 months and 13 months after laser irradiation. Results showed that after laser exposure, behavioral deficits, including kyphosis, tail entasia, or whole body paralysis could be noted right after the animals recovered from anesthesia while gradually disappeared within several days and never recurred again. Histologically, the laser lesion showed a typical architecture dependent on the interval following laser treatment. The central zone of coagulation necrosis is not apparent right after exposure but becomes obvious within several days. The nerotic tissue though may persist for a long time, will finally be completely resorbed. No carbonization granules formed under our exposure condition.
Nano-/Biophotonics
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Fluoroimmunoassay for antigen based on fluorescence quenching between quantum dots and gold nanoparticles
Peng Huang, Kan Wang, Omar Pandoli, et al.
A unique, sensitive, and highly specific fluoroimmunoassay system for antigen detection using gold and quantum dot nanoparticles has been developed. The assay is based on the fluorescence quenching of quantum dots caused by gold nanoparticles coated with antibody. To demonstrate its analytical capabilities, the CdTe quantum dots were coated with anti-HBsAg monoclonal antibodies (QDs-MAb1) and gold nanoparticles coated with another anti-HBsAg monoclonal antibodies (GNPs-MAb2) which specifically bound with HBsAg could sandwich the HBsAg captured by the immunoreactions. The sandwich-type immunocomplex was formed and the fluorescence intensity of quantum dots was measured. The results showed that the fluorescence intensity of quantum dots at 570 nm was negative linear proportional to the HBsAg concentration logarithm, and the limit of detection of the HBsAg was 0.928 ng/mL. This new system can be extended to detect target molecules with matched antibodies and has broad potential applications in immunoassay and disease diagnosis.
The effects of Ce3+ and Ce4+ on the stability of fibroblast growth factor-2
Liwei Sun, Hao Feng, Rui Jiang, et al.
The interaction between tri or tetravalent cerium ions and basic fibroblast growth factor (FGF-2) at 0.1-6: 1 molar ratio under physiological condition was studied by fluorescence and CD spectrum. The different spectra alterations of FGF-2 induced by Ce3+ and Ce4+ showed that Ce3+ and Ce4+ caused different conformational changes of FGF-2 respectively, though both of them destabilized the protein. The instability of FGF-2 in the presence of Ce3+ is involved in the oxidation of its free cystein of protein, but that this treatment nearly does not affect the biological activity. As to Ce4+, it not only induced the conformational changes of protein but also inhibits its activity in a dose-dependent manner, which could be relative to the electrostatic repulsion between Ce4+ and its basic amino acid residues (pI=9.6) or the specific binding of Ce4+ to deprotonated amino acid residues. The interesting results would be helpful to investigate the problem of the stability of proteins.
Photo-thermal Interaction and Calculations
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Effects of MTZs parameters during non-ablative fractional photothermolysis treatments: a numerical study
Jing-bo Ma, Ji-zhuang Zhang
The novel method of non-ablative FP is acknowledged as an effective technique by offering significant clinical improvement while minimal risk of complications. A new time-dependent mathematical model was built up to investigate the photo-thermal interactions during FP treatments. With this model, effects of treatment-affecting parameters, such as diameter, density and energy of the micro laser beam as well as skin cooling, were numerically investigated. Different photo-thermal behaviors with various treatment parameters were particularly discussed, based on which, a novel concept of programmable treatment procedure (PTP) was proposed. With this technique, desired therapeutic outcomes may be obtained from personalized treatments.
A numerical investigation of photo-thermal interactions during laser sebaceous gland treatment
Ji-zhuang Zhang, Jing-bo Ma
Aberrations of sebaceous follicles usually cause great mental suffering and unconfidence to the patients. A new time-dependent mathematical model was built up to investigate the photo-thermal interactions during laser sebaceous gland treatment. With this model, effects of treatment-affecting parameters, such as diameter and depth of the sebaceous gland, laser energy density, pulse repetition, and especially cooling methods, were numerically investigated. The simulated results showed that skin cooling is essentially necessary for achieving ideal therapeutical outcomes in laser sebaceous gland treatment, and CSC is the most effective cooling method. A simple but valid method to improve the therapeutical outcomes of laser sebaceous gland treatment, named as adaptive temperature control (ATC), was proposed. The results and conclusions are useful for optimizing laser sebaceous gland treatments and for designing new treatment procedures.
Monte Carlo simulation of non-invasive glucose measurement based on FMCW LIDAR
Bing Xiong, Wenxiong Wei, Nan Liu, et al.
Continuous non-invasive glucose monitoring is a powerful tool for the treatment and management of diabetes. A glucose measurement method, with the potential advantage of miniaturizability with no moving parts, based on the frequency modulated continuous wave (FMCW) LIDAR technology is proposed and investigated. The system mainly consists of an integrated near-infrared tunable semiconductor laser and a detector, using heterodyne technology to convert the signal from time-domain to frequency-domain. To investigate the feasibility of the method, Monte Carlo simulations have been performed on tissue phantoms with optical parameters similar to those of human interstitial fluid. The simulation showed that the sensitivity of the FMCW LIDAR system to glucose concentration can reach 0.2mM. Our analysis suggests that the FMCW LIDAR technique has good potential for noninvasive blood glucose monitoring.
Optical Techniques: Advances in Research
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A simple method to fulfill particle trapping by optical tweezers array
Xiaoming Hu, Jingfang Li, Yanhuang Zhou, et al.
We adopt double-plate sheering interferometers to perform an optical tweezers array system. In the optical tweezers array system, the reflecting mirror is replaced by an optical scanner to be a beam translator. The optical scanner is driven by an input signal to control the interference strips movement. However, if the interference strips move periodically, the trapped particles would move along with the strips with the same regulation. So, the particles could not be separated from the other particles. We use an external modulating device to be a shutter to control the laser beam. Then the trapped particles would continue moving because of inertia during the laser beam is blocked, and be trapped again after the shutter opens. If the moving speed of liquid is limited properly, the particles can be separated continuingly and collected. At the end of this article, we illustrate the result of conducting the novel method and characteristics of the system.
Fast confocal endomicroscopy based on multi-fiber parallel scanning
Confocal endomicroscopy has been developed very quickly for its high resolution and high sensitivity. It could be used for early diagnoses of disease, such as cancer. In existing confocal endomicroscopy, fiber bundle or single fiber was used for transferring exciting laser and excited fluorescence signal. Neither of these technologies had high resolution nor high imaging speed. In this paper, a fast confocal endomicroscopy(FCM) is presented. In the FCM, a multi-fiber array with 9 fibers is used for light signal transferring, including exciting laser and excited fluorescence. In the distal end of the endomicroscopy, the fibers are arranged in two dimension and form a 3X3 area array. The fibers are not arrayed closely, but with space. Under driving of a MEMS scanner, the fibers move and scan tissue in parallel. Each fiber takes charge of 1/9 of the whole diagnoses field. Then the whole field is scanned and image is acquired. In the other end, the fibers are arranged in linear array. Exciting laser is coupled into the linear fiber array and transferred to the distal end of the area fiber array. Fluorophore molecules in tissue are excited and emit fluorescence. The fluorescence is collected into the 3X3 area fiber array and transferred to the linear array end. An imaging objective lens couples the fluorescence from the fiber end to a CCD, which converts the light intensity into electrical signal. Image of tissue is reconstructed from the electrical signal. By parallel scanning, the imaging speed of confocal endomicroscope is improved by several times, which is associated with the number of fibers in the array.
Noninvasive evaluation system of fractured bone based on speckle interferometry
Shinya Yamanada, Shigeru Murata, Yohsuke Tanaka
This paper presents a noninvasive evaluation system of fractured bone based on speckle interferometry using a modified evaluation index for higher performance, and the experiments are carried out to examine the feasibility in evaluating bone fracture healing and the influence of some system parameters on the performance. From experimental results, it is shown that the presence of fractured part of bone and the state of bone fracture healing are successfully estimated by observing fine speckle fringes on the object surface. The proposed evaluation index also can successfully express the difference between the cases with cut and without it. Since most system parameters are found not to affect the performance of the present technique, the present technique is expected to be applied to various patients that have considerable individual variability.
Mechanisms and Techniques in Photodynamic Therapy
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Kinetic analysis of singlet oxygen generation in a living cell using Singlet Oxygen Sensor Green
Yi Shen, Huiyun Lin, Zufang Huang, et al.
Singlet oxygen (1O2) can be generated in a living cell upon focused laser irradiation of an intracellular photosensitizer. In this study, 1O2 generation from the plasma membrane-targeted protoporphyrin IX (PpIX) in human nasopharyngeal carcinoma CNE2 cells was monitored indirectly by using the fluorescence probe Singlet Oxygen Sensor Green agent (SOSG). The confocal images indicate that the fluorescence of SOSG in the vicinity of the cells that incubated with PpIX was dramatically enhanced with the increased irradiation time, while there is no significant enhancement for the control cells. Moreover, the fluorescence of SOSG is dramatically enhanced with the increase of the intracellular PpIX in CNE2 cells for the same photoirradiation time. These observations imply that the 1O2 generated from the plasma membrane-targeted PpIX in the CNE2 cells can be escaped into the extracellular medium and to react with the SOSG to produce SOSG-EP, and the fluorescence enhancement of SOSG around the cells mainly depends on the intracellular PpIX. Our findings may be useful for further monitored the 1O2 that can be escaping from the living cells.
Photodynamic therapy for port wine stains assisted by a novel robotic system
Naiyan Huang, Jianguo Zhu, Ying Wang, et al.
Port wine stains (PWS) is a vascular malformation consisting of dilated capillaries in the superficial dermis. Photodynamic therapy (PDT) is an effective approach in the treatment of PWS. However, the procedure of treatment is a low efficient and hard work, as the doctor need to hold laser fiber to irradiate for 20 min to 50 min per lesion. So an assisted novel robotic system was developed to instead part of doctor's work. The robotic system consisted of 7 degrees of freedom, in which there were 5 passive joints and 2 active joints. Binocular surveillance system was used as guidance for the robot. Clinical trial compared 20 patients (38 lesions) treated by the robotic system with another 20 patients (38 lesions) treated by a doctor. The patients in both groups were injected intravenously with photosensitizer (PSD-007, 4-5mg/kg) and irradiated with 532 nm laser (100mW/cm2, 120-300J/cm2) immediately. Both groups had same good therapeutic results. The robotic system is helpful in the PWS-PDT and hopefully would become a part of PWS therapy machine in the future.
Effect of concentration on photobleaching of hematoporphrin monomethyl ether (HMME) in solutions
Y. Wang, Y. Gu
To analyze the effect of concentration on the photobleaching of HMME, the loss of HMME absorption in simplex solution (PBS) and complex solution (albumin buffer) was monitored using steady-state absorption spectra during 532nm laser irradiation. Three concentrations (4, 10, 80μmol/L) were set for each type solution. Photobleaching curves at each concentration were drawn according to the concentration and time during irradiation. Photobleaching rate coefficients (k) at each concentration were calculated with a mathematical model for singlet oxygen-mediated photobleaching reaction. Then the photobleaching of HMME under different concentrations were compared using the photobleaching rate coefficients (k) and the slope of photobleaching curves. Finally, the effect of concentration on HMME photobleaching was analyzed combining the existence state of HMME at each concentration. The results showed that in both PBS and albumin buffer, the photobleaching rate coefficient of HMME was the largest at 4μmol/L, smaller at 10μmol/L, and the smallest at 80μmol/L. In conclusion, there is a concentration-dependent relationship in the photobleaching rate of HMME, photobleaching will be inhibited when the concentration of HMME increased above certain level at which HMME aggregates formed.
Determination of singlet oxygen quantum yield of HiPorfin using Singlet Oxygen Sensor Green
Huiyun Lin, Yi Shen, Defu Chen, et al.
Singlet oxygen (1O2) is widely considered to be the predominant cytotoxic agent for photodynamic therapy (PDT), and the 1O2 quantum yield is a key characteristic for the newly developed photosensitizers. In this study, 1O2 generation from the HiPorfin is monitored indirectly by using the fluorescence probe Singlet Oxygen Sensor Green (SOSG). The good linear relationship between the concentration of HiPorfin and the initial reaction rate of SOSG is observed, and the 1O2 quantum yield of HiPorfin is determined to be 0.124 ± 0.001, as compared to the standard reference of Rose Bengal. The results suggest that SOSG can be useful for 1O2 quantum yield determination for the potential photosensitizers in PDT.
Advanced Biomedical and Clinical Systems
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Confocal fluorescence microendoscopy using a digital micro-mirror device
Zhifeng Feng, Liqiang Wang, Huilong Duan
A design of confocal fluorescence microendoscopy utilizing a digital micro-mirror device (DMD) is described. Laser beams of the microendoscope are coupled into the body through a telescopic optics system, rather than through fibers or fiber bundles which are widely used in existing microendoscopes. Each micro-mirror of the DMD is used as a confocal pinhole. The DMD not only couples the laser beams into the body by a random time-varying speckle pattern and performs the scanning mechanism of the body tissue with different positions, but also couples the fluorescent signal emitted from the markers out to the CCD camera. Because of the CCD's integration feature and DMD's rapid parallel scanning feature, a complete predetermined depth tomography image accumulated by different scanning patterns of DMD can be acquired through only one CCD exposure procedure. The objective lens to realize high resolution and high sensitivity fluorescence imaging is the other function of the telescopic optics, with a numerical aperture of 0.35. The resolution of confocal microendoscope is superior to 228 lp/mm determined by 1951USAF resolution test target. Images of a tendon specimen are also shown to demonstrate practical application of the design. The confocal microendoscope using a DMD permits the acquisition of high-resolution real-time confocal images of epithelial tissue in vivo organ and realizes the aim of non-invasive diagnosis and treatment.
Laser-induced hard tissue ablation by assisted with a liquid film on target tissue surface
Xianzeng Zhang, Haibin Zhao, Zhenlin Zhan, et al.
The objective of this study was to investigate the influence of an applied water film on bone hard tissue ablation by pulse CO2 laser. Fresh bovine shank bone in vitro used in the experiment were put on a PC-controlled motorized linear drive stage and moved repeatedly through focused beam of laser without and with a water film of 0.4 mm and 1 mm on target tissue. The wavelength of pulse CO2 laser was 10.64 μm, pulse repetition rate was 60 Hz, the energy density was 18-84 J/cm2 and the beam diameter of about 400 μm. The moving speed of stage was 12 mm/s, scanning times was 5. The surface morphology and microstructure of ablation grooves were examined by stereomicroscope and scanning electron microscope (SEM) respectively. The geometry of the groove was measured with optical coherence tomography (OCT), and the thermal injury was examined by histology. It shows that water film on the target tissue surface plays an important role during the ablation process. A proper thickness of water film applied to target tissue surface could improve the regular of cut shape, smooth the cut surface, produce the same or even larger ablation rate and efficiency, and reduce the thermal injury around the groove by compared with dry ablation condition. Moreover, the addition of water could alter the microstructure of bone sample.
Poster Session
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Research on laser induced pain effect
P. Chen, J. R. Wang, Y. C. Li, et al.
To study 1.06μm laser causing pain in human skin. The skin of human dorsum hand was irradiated by a Nd: YAG laser. The energy of each pulse and whether the subjects felt a painful sensation after each stimulus were recorded. The pain threshold was defined as the laser dose at which the subjects reported a painful sensation to 50% of stimulus deliveries. The pain thresholds were determined under 3 different beam diameter and pulse duration conditions. The influence of skin temperature on the pain caused by laser stimulus was also explored. As the temperature of skin was about 30°C, the pain thresholds were 394mJ/mm2, 36.4mJ/mm2 and 8.92mJ/mm2 respectively under the stimulating condition of 1.20mm beam diameter and 85μs pulse duration, 1.20mm beam diameter and 20ns pulse duration and 2.56mm beam diameter and 20ns pulse duration. Under the first condition, when skin temperature was 25°C and radiant exposure was 383mJ/mm2, the probability of laser stimulus causing pain was 16.7%; when skin temperature was 39°C and radiant exposure was 361mJ/mm2, the probability was 56.7%. The threshold of 1.06μm laser stimulus causing pain decreases with decreasing pulse duration, increasing beam diameter and skin temperature.
Uniform mesoporous dye-doped silica nanoparticles as a multifunctional drug carrier for in vivo early tumor diagnosis
Jie Cao, Junfei Xia, Dawei Deng, et al.
In this report, we synthesized multifunctional dye-doped mesoporous silica nanoparticles(MSNs) by encapsulating near-infrared dyes into the nanoparticles. In order to enhance the targeting property, the surface was modified with amino group for further conjugation of targeted ligands. In addition, we explored the influence of the synthetic temperature on the particle morphology. The optical properties, morphology and structure of the as-prepared dye-doped silica nanoparticles were characterized. Results indicated the dye-doped silica nanoparticles can be used as a good probe for early tumor diagnosis and have the potential to serve as a targeted carrier for antitumor drugs.
The influence of laser pulse on time resolved reflectance and transmittance in slab media
C. Zhao, M. Zhao
In this paper, the mathematical equation of the flatheaded Gauss laser pulse is given. Based on the Diffusion equation, by using the Gauss laser pulses in different pulse width and shapes for the incident light sources, we get the simulations of the time-resolved reflectance, transmittance and their pulse shapes in the boundary condition of homogeneous slab. The simulation results show that the ultra short Gauss laser pulse is widened by the diffusive scattering, in addition, the various medium parameters have different influence on the reflected and transmitted intensity of the laser pulse. In the boundary condition of homogeneous slab media, the interactions between the absorption coefficient, the scattering coefficient, the anisotropy coefficient, the pulse width and the pulse shape of the incident laser pulse all have been investigated. This study is useful for the optical noninvasive measurement of the optical properties of tissue.
Optical trapping gold nanoparticles by a pulse laser
XiaoYu Liu, Feng Wang
Gold nanoparticles are widely employed in nanomaterials, nanobiotechnology and health care, but generally they are considered difficult to trap stably. Compared with the continuous laser which is popular to the optical trapping, pulse laser has a relatively larger power in its work pulse, which is useful for trap particles. So this paper comprehensively analyzes the forces (the radiation forces, the gravitation, and the Brownian motion) on the gold nanoparticles in the optical tweezers formed by a pulse laser, through building up a mathematical model. Finally gets the dependence relation between the characteristics of the pulse laser and that of the gold nanoparticles.
Fluorescence lifetime imaging using multi-dimension time-correlated single photon counting method
Cuixia Sheng, Heijing Tang
The key technology of fluorescence lifetime imaging is introduced in this article. Time-correlated single photon counting (TCSPC) in Time-domain method is adopted to record fluorescence lifetime . The principle of TCSPC and the Multi-wavelength imaging method are introduced in the paper. The counting efficiency and the amount of information in the data can be increased by recording the fluorescence in several wavelength channels simultaneously. Multi-wavelength imaging was also successfully used to separate different chromophores in stead-state images.
An analytic scheme for time-domain diffuse fluorescence tomography in circular geometry: methodology and validation
Jiao Li, Feng Gao, Xin Wang, et al.
Near-infrared fluorescence diffuse optical tomography has proven to be an efficient tool for visualizing the bio-distributions of fluorescent markers in tissue. We present a two-dimensional image reconstruction method for time-domain fluorescence diffuse optical tomography on a turbid medium of circular domain. The methodology is based on a linear generalized pulse spectrum technique that employs the analytical solution to the Laplace-transformed time-domain photon-diffusion equation to construct a Born normalized inverse model. A pair of real domain transform-factors is introduced to simultaneously reconstruct the fluorescent yield and lifetime images and the resultant linear inversions are solved using an algebraic reconstruction technique. The algorithm is validated using simulated data, and the spatial resolution, noise-robustness and so on are assessed. The experimental validation is performed using a multi-channel time-correlated single-photon-counting system and a cylinder phantom that embeds a fluorescent target made from 1%-Intralipid solution and Cy5.5 agent. The results show that the approach retrieves the position and shape of the target with a reasonable accuracy.
Development of a novel spectrometer for tongue coating analyzer based on volume holography transmissive grating
Zhong Ren, Guodong Liu, Longmin Dai, et al.
Tongue diagnosis (TD) is an important diagnostic methods in the traditional Chinese medicine (TCM). According to the viewpoint of TCM, the changes of the tongue coating (TC) can reflect the pathological state of the patient. And the nature or severity of diseasec can be determined by observing the TC. Over the years, TD is mostly depended on the subjective experience of the Chinese physician. And the diagnostic results will be impacted by.some factors, e.g. the different light sources or environmental brightness. Recently years, the method of digital image processing has been used into the TD. But its application is limited by the complicated algorithm, time-consuming and big error, etc. Therefore, a novel tongue coating analyzer(TCA) is designed in this paper. Meanwhile, a novel spectrometer for TCA based on the volume holography transmissive (VHT) grating is developed. In this spectrometer, since the VHT grating doesn't produce the stray-light due to the absence of the grooves of classical surface-embossed gratings, the VHT grating is used as the diffraction grating instead of the classical plane or concave grating. Experimental results show that the performances of the spectrometer for TCA have been improved by using the VHT grating, optimizing the light-path structure and software algorithm, etc. Compared with the others, this spectrometer for TCA has many advantages, such as, less diffraction, wider spectrum range, higher efficiency and resolution, etc. The spectrum range of the spectrometer for TCA can reach 300-1000nm, its resolution can reach 1nm and the optical density is larger than 3.
Improvement of the frequency-domain inverse Monte Carlo simulation
Huijuan Zhao, Xiaoqing Zhou, Shuying Zhang, et al.
This article aims at the optical property (absorption coefficient and scatter coefficient) reconstruction from the frequency-domain (FD) near-infrared diffuse measurement on small tissues, such as a cervix, for which inverse Monte Carlo (MC) simulation is the suitable choice. To achieve the fast and accurate reconstruction based on the inverse Monte Carlo simulation, following techniques were adopted. First, in the forward calculation, a database, which include the frequency-domain information calculated from MC simulation for a series of optical parameters of tissue, were established with fast methods. Then, in the reconstruction procedure, Levenberg-Marquardt (L-M) optimization was adopted and Multiple Polynomial Regression (MPR) method was used to rapidly get the FD information at any optical properties by best fitting the curved surface formed by the above database. At Last, in the reconstruction, to eliminate the influence of the initial guess of optical properties on the reconstruction accuracy, cluster analysis method was introduced into L-M reconstruction algorithm to determine the region of the initial guess. The reconstruction algorithm was demonstrated with simulation data. The results showed that it takes less than 0.5s to reconstruction one set of optical properties. The average relative error from the reconstruction algorithm joined with cluster analysis is 10% lower than that without cluster analysis.
Comparison between radiation forces on gold nanoparticles and on polystyrene nanobeads
XiaoYu Liu, Feng Wang
Gold nanoparticles have found broad applications in nanomaterials and nanobiotechnology and health care. They are considered to be superior handles or probes relative to polystyrene beads for their own specific physical characteristics. But unfortunately they are considered difficult to trap stably by optical tweezers still owing to their specific physical characteristics. In this paper, numerical studies are carried out to show that how the radiation forces on the gold particles dependant on the parameters of the lasers and of the particles. The results show that a stable trap for gold particles needs a more strictly choice of lasers than polystyrene nanobeads for given particle size and other conditions.
Signal and noise analysis of optical coherence tomography in highly scattering material at 1550nm
Lin Lin, Yingjun Gao, Mei Zhang
The signal and noise properties of standard time domain optical coherence tomography system are analyzed in near-infrared region based on extended Huygens-Fresnel principle. The signal-to-noise ratio and maximum probing depth are estimated for scattering media with discontinuity plane inside. In numerical simulation, the relationship between coherent signal and scattering coefficients, and depth dependence SNR are calculated. The difference between specular and diffuse reflection is given out and analyzed. Numerical result is verified by well established experiment with different concentration mixture solution of IntralipidTM, from 1% to 15%. The OCT system consists of fiber Michelson interferometer and 1550 nm ASE optical source with coherent length of 14μm. Both numerical and experimental results show that multiple scattering events are the main reason for decreasing of signal-to-noise ratio. According to the research, wavelength at 1550 nm is also suitable for imaging of biomedical tissue because of lower scattering coefficients. More than 2 mm penetration depth is obtained in experiment for 10% IntralipidTM which has scattering coefficient similar to skin tissue.
Imaging model of optical sectioning of thick specimen
Chen Hua, Hongxia Xie
Based on the cartesian coordinate system, a coaxial couple cartesian coordinate system is designed whose z-axis is coaxial but z-axis coordinate is independent, and its xy plane is different but coordinate is the same. The object space and the image space are set in the two sub-cartesian coordinates respectively. In the coaxial couple cartesian coordinate system, according to the principle of optical imaging, a form of the optical microscope's imaging model of optical sectioning biological thick specimen is derived. The model form show that if a biological thick specimen is expressed as a pile of slices with tiny interval, and a slice among the slices is put in microscope's focal plane, then the thick specimen's image in image plane is the superposition of the focal plane image and all of the defocus images. In the model form, thick specimen's image is simply sorted into focal plane image and defocus image to make it easy to look insight, so the model clearly reflects the imaging relationship between the slice of thick specimen, and it is conducive to the analysis of the microscope's imaging characteristics for thick specimen. And the stack of optical section according to the model is equivalent to the mathematical model of three-dimensional imaging of thick specimen.
A method for determining optical properties of human tissues by measuring diffuse reflectance with CCD
P. Sun, Run Q. Yang, Feng H. Xie, et al.
It is important to measure optical properties noninvasively, quickly and accurately in vivo for disease diagnostics and medical therapeutics. In this study, we measured the absorption coefficient and the reduced scattering coefficient of human tissues by measuring diffuse reflectance with CCD, examined the techniques involved, such as quantization of diffusion approximation theory, effective reverse fitting algorithm, and the data selection and processing method, and finally concluded about the accuracy of this method. The experimental results indicate that the error is less than or equal to 8% using the diffusion theory, under the condition that the reduced scattering coefficient is one order of magnitude greater than the absorption coefficient. The stability and precision of optical property measurements are significantly improved by using the multi-step iterative fitting method and using the ring areas to determine the diffuse reflectance center. The efficiency of reverse algorithm is greatly enhanced by selecting a one-dimensional array on the straight line crossing both the entry point and the diffusion center for fitting. The error of measured absorption coefficient and scattering coefficient of the Intralipid solution and human forearm tissues are less than 5% with our method. These results can provide important technical information for application of the diffusion theory.
Surfaced-enhanced Raman spectroscopy of nasopharyngeal carcinoma cell using gol nanoparticles
Rong Chen, Hao Huang, Li-qing Sun, et al.
The surface-enhanced Raman scattering (SERS) spectroscopy and normal Raman spectroscopy of single living human nasopharyngeal carcinoma cells(CNE-1) were tested and analyzed by gold nanoparticles incubation into cells. The characteristic Raman bands in the SERS spectra of living cells were tentatively assigned. Six obvious Raman bands (718, 1001, 1123, 1336, 1446, 1660 cm-1) were observed in the normal Raman spectroscopy of living CNE-1 cells. Colloidal gold nanoparticles that were introduced inside cells resulted in strongly enhanced Raman signals of the native chemical constituents of the cells, and over twenty SERS Raman bands were observed in the SERS spectroscopy of living CNE-1 cells. Four vibrations of the DNA backbone (1026, 1097, 1336 and 1585 cm-1) confirmed that some gold nanoparticles were able to enter the nucleus. The results showed that, based on colloidal gold, the SERS spectroscopy might provide a sensitive and structurally selective detecting method for native chemicals inside a cell, such as DNA and phenylalanine.
New optical method for noninvasive blood glucose measurement by optical ultrasonic modulation
Lili Zhu, Jieqing Lin, Wenming Xie, et al.
A new optical technique for continuous, noninvasive monitoring of blood glucose levels based on ultrasonic modulation of scattering light is proposed. The ultrasound-modulated scattered light has an accurate separation of scattering and absorption changes in tissue. And the optical scattering and absorbing coefficient of tissue depend on the concentration of glucose in the extracellular fluid. As the glucose induced to scattering and absorption changes, the ultrasoundmodulated light also changes. In this paper, a correlation is observed between ultrasound-modulated light intensity as well as its modulation depth and blood glucose concentration in phantom experiments. In addition, some researches about ultrasound-modulated signal affected by the temperature of glucose aqueous solution are done. Preliminary experiments find that this method is a promising noninvasive blood glucose measurement.
Marginal characteristics of skin scarred dermis quantitatively extracted from multiphoton microscopic imaging
Xiaoqin Zhu, Shuangmu Zhuo, Liqin Zheng, et al.
Multiphoton microscopy based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) was applied to examine the marginal regions at dermis of normal, atrophic and keloid scars. High-contrast, high-resolution image showed an obvious boundary at scar margin and different morphological patterns of collagen or elastin on the two sides. Since the degree of the morphological alteration between the two sides of boundary at scar margin was varied among different types of scars, alteration degree of SHG-to-TPEF index was defined as a quantitative indicator for discrimination. It will help to determine the most appropriate clinical treatment strategy for different types of scars and potentially monitor therapy in vivo.
A processing technology of two-photon microscopic image of nasopharyngeal cancer cells
Hongxin Lin, Tingyin Wang, Rong Chen, et al.
Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in china, with a deep and hidden localization. Recently, methods for early diagnosis of NPC has become one of the most important research topics in medical field. Early monitoring of morphological change of NPC cells during the carcinogenesis is of great importance, and early information extracted from the NPC cells during the initial stage of NPC is critical for diagnosis and treatment. In this paper, image processing methods for two-photon microscopic image of NPC cells was investigated with the purpose of providing useful information for early diagnosis and treatment of NPC. There is abundant information in a two-photon microscopic image of NPC cells, which can be analyzed and processed by means of computer and image pattern processing algorithm. In this paper, firstly, a mathematical method of transform of Bottom-hat based on Matlab platform was employed to enhance the image of NPC cells, making the image easier to distinguish; Then, several classical edge detection algorithms were compared and discussed, for example, Roberts operator, Prewitt operator, and Canny operator etc. According to the inherent characteristics of two-photon microscopic image of NPC cells, corrosion algorithm was used to define the edge of NPC cells. Furthermore, the article gets the iterative threshold segmentation after noise denoising, on the other hand, improved discriminant analysis was adopted for threshold segmentation of NPC cells, better results were obtained.
Radiation force on a chiral sphere by a Gaussian beam
Qing-chao Shang, Zhen-sen Wu, Zheng-jun Li, et al.
Based on the generalized Lorenz-Mie theory (GLMT), the incident Gaussian beam and scattered fields of the chiral sphere are expressed in terms of the spherical vector wave functions. An expression of the radiation force on the chiral sphere in a Gaussian beam is derived from the theory of electromagnetic momentum. The influence of the chiral parameter, the beam waist radius and the radius of the chiral sphere on radiation force is discussed numerically.
A novel nasopharyngeal cancer detection based on plasma SERS combined with PCA-LDA statistical analysis
Shangyuan Feng, Juqiang Lin, Jianji Pan, et al.
In order to develop a novel and simple blood test for non-invasive nasopharyngeal cancer detection, a surface-enhanced Raman spectroscopy (SERS) method was presented for blood plasma biochemical analysis. High quality SERS spectrum from human plasma-Ag NP mixture can be obtained using a confocal Raman system. SERS measurements were performed on normal and cancer groups of plasma samples. The measured SERS spectra revealed some specific biomolecular differences in nasopharyngeal cancer plasma. Principal component analysis of the measured SERS spectra separated the spectral features of the two groups into two distinct clusters with little overlaps. Linear discriminate analysis based on the PCA generated features differentiated the nasopharyngeal cancer SERS spectra from normal SERS spectra with high sensitivity (97.7%) and specificity (100%). The results from this exploratory study illustrated great promising for developing SERS human plasma analysis into a clinical tool for non-invasive detection of nasopharyngeal cancers.
The targeted behavior of folate-decorated N-succinyl-N′-octyl chitosan evaluated by NIR system in mouse model
Hongyan Zhu, Dawei Deng, Haiyan Chen, et al.
The development of more selective delivery systems for cancer diagnosis and chemotherapy is one of the most important goals of current anticancer research. The purpose of this study is to construct and evaluate the folate-decorated, self-assembled nanoparticles as candidates to deliver near infrared fluorescent dyes into tumors and to investigate the mechanisms underlying the tumor targeting with folate-decorated, self-assembled nanoparticles. Folate-decorated N-succinyl-N'-octyl chitosan (folate-SOC) were synthesized. The chemical modification chitosan could self-assemble into stable micelles in aqueous medium. Micelle size determined by size analysis was around 140 nm in a phosphate-buffered saline (PBS, PH 7.4). Folate-SOC could maintain their structure for up to 15 days in PBS. Near infrared dye ICG-Der-01 as a mode drug was loaded in the micelles, and the entrapment efficiency (EE) and drug loading (DL) were investigated. The targeted behavior of folate-SOC was evaluated by near-infrared fluorescence imaging in vivo on different groups of denuded mice, with A549 or Bel-7402 tumors. The optical imaging results indicated that folated-decorated SOC showed an excellent tumor specificity in Bel-7402 tumor-bearing mice, and weak tumor specificity in A549 tumor bearing mice. We believe that this work can provide insight for the engineering of nanoparticles and be extended to cancer therapy and diagnosis so as to deliver multiple therapeutic agents and imaging probes at high local concentrations.
Monitoring the process of tissue healing of rat skin in vivo after laser irradiation based on optical coherence tomography
It is imperative to evaluate the tissue wound healing response after laser irradiation so as to develop effective devices for this clinical indication, and evaluate the thermal damage degree to take appropriate treatment. In our research, we prepare 6 white rat (approximately 2 months old, weight :28±2g). Each rat was injected intraperitoneally a single dose of 2% pentobarbital sodium. After the rat was anesthetized, the two side of the rats' back were denuded and antisepsised a standardized. An Er:YAG laser (2940nm, 2.5J/cm2, single spot, 4 times) was irradiated on rat skin in vivo, and the skin which before irradiated and the process of renovating scathe that irradiated after Er:YAG laser were observed by an Optical coherence tomography (OCT). The tissue recovery is about a twelve -day period. The results indicate that the scattering coefficient of post- tissue has changed distinctly. The and flexibility fiber is the chief component of rat dermis and the collagen is the main scattering material. The normal tissue has a large scattering coefficient, after laser irradiated, the collagen became concreting and putrescence and caused the structure change. It became more uniform density distribution, which results in a reduced scattering coefficient. In a word, OCT can noninvasively monitor changes in collagen structure and the recover process in thermal damage through monitor the tissue scattering coefficient.
Monitoring changes of optical attenuation coefficients of acupuncture points during laser acupuncture by optical coherence tomography
The physical properties of acupuncture point were important to discover the mechanism of acupuncture meridian. In this paper, we used an optical coherence tomography to monitor in vivo the changes of optical attenuation coefficients of Hegu acupuncture point and non-acupuncture point during laser irradiation on Yangxi acupuncture point. The optical attenuation coefficients of Hegu acupuncture point and non-acupuncture point were obtained by fitting the raw data according to the Beer-Lambert's law. The experimental results showed that the optical attenuation coefficient of Hegu acupuncture point decreased during the laser acupuncture, in contrast to a barely changed result in that of non-acupuncture point. The significant change of optical attenuation coefficient of Hegu acupuncture point indicated that there was a correlation between Hegu and Yangxi acupuncture points to some extent.
Autofluorescence characteristics of human leukemia cells and mononuclear cells
Lifu Xiao, Xiaoying Liao, Lisheng Lin, et al.
Autofluorescence spectroscopy is a powerful method to identify the endogenous fluorophores in normal and cancerous cells. The purpose of this study is to characterize the autofluorescence spectra of human normal and leukemia cells. Autofluorescence measurements of each cell line are performed over a wide range of cell concentrations. All of the leukemia cells indicate a statistically significant increase in the tryptophan fluorescence relative to that of the normal cells, while no statistically significant differences are observed in the reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD) fluorescence between the normal and leukemia cells. The results suggest that the differences in autofluorescence spectra for leukemia cells and mononuclear cells may be attributed in part to differences in endogenous fluorophores of different cells.
Shear bond strength of a self-etch adhesive to Er:YAG laser-prepared dentin
Zhenlin Zhan, Weiliang Wu, Xianzeng Zhang, et al.
The purpose of this study was to determine the shear bond strength of a self-etch adhesive to Er:YAG laser-prepared dentin and evaluate the resin-dentin interface. Extracted sound human molars were sectioned and wet-ground to expose flat dentin surfaces. These surfaces were subsequently irradiated by an Er:YAG laser with a wavelength of 2.94 μm and pulse repetition rate of 20 Hz. Energy density was set at 20 J/cm2 and spot size was 2 mm. The conventional bur was used as a control group. After surface treatments, a self-etch adhesive was bonded to the irradiated dentin surface and then a resin composite was applied to the dentin surface. Specimens were subjected to shear bond strength test after 24 h of storage in water. The bonding interface was examined by laser confocal scanning microscope (LCSM) after specimens were serially sectioned into multiple slices. The results revealed that Er:YAG laser irradiation did not present advantages compared to the conventional bur.
Wavelength-swept laser around 1300nm based on polygon filter in Littrow telescope-less configuration
Minghui Chen, Zhihua Ding, Ling Wang, et al.
A high-speed linear wavelength-swept laser source working at center wavelength of 1309 nm is demonstrated. Wavelength tuning is performed using a compact polygon filter in Littrow telescope-less configuration. The repetition frequency of the wavelength-swept laser source is up to 50 kHz with the polygon scanned at a speed of 694 rotations per second. The turning range is 130 nm and full width at half maximum (FWHM) is 61 nm. The average output power can reach to 7 mW. The developed swept laser source can be implemented in optical frequency domain imaging, optical reflectometry, and other test or measurement applications.
Comparison of two linear differential polarization imaging methods in tissue characterization
Dongzhi Li, Ran Liao, Nan Zeng, et al.
Linear differential polarization imaging can improve image quality and characterize the polarization properties of biological tissues. Degree of polarization imaging (DOPI) yields images based on photons backscattered from the superficial layers, but shows different measurement results for different incident polarization or sample orientations. The rotating linear polarization imaging (RLPI) method can characterize the anisotropic properties of tissues, by recording the linear differential polarization as a function of multi-incident and multi-detection polarization angles and gives a set of new parameters insensitive to incident polarization angles. The physical meanings, dependence on the incident polarization angles and the imaging depth of the parameters of the rotating linear polarization imaging will be compared with those of degree of polarization imaging, which indicate the application potential of the two linear differential polarization imaging methods in tissue imaging and medical diagnosis.
Large format x-ray image detector of high resolution and sensitivity
Jinchuan Guo, Bin Zhou, Xin Liu, et al.
X-ray phase contrast imaging technique that can be used as a practical diagnostic tool for medical purposes requires the image detector of higher resolution and sensitivity, and of larger format as well. The above mentioned parameters cannot be come to their best on one detector at present, so there is some kind of compromise among these parameters, for example, improving one parameter may be at the cost of impairing another one. This paper designed an x-ray image detector composed of a structured scintillation screen, optic taper and CCD camera etc. Photo-assisted electrochemical etching method was used to make an array of deep holes in the crystal silicon. The scintillator (CsI:Tl) was molten into the deep holes after the silicon wafer had been heat-oxidized. When the screen was coupled with CCD camera by optic taper, the detector fabrication was finished. We use the detector and an x-ray tube of 1mm focal spot to image a test pattern, the spatial resolution better than 20lp/mm was obtained under the x-ray tube voltage of 45kVp and current of 2mA. The total image pixel of this detector is 2048 x 2048, with the 13.5 micrometer pixel size of the camera. The ratio of the input face size of optic taper to output size was 2:1. High sensitivity was implemented by the course of x-rays in the scintillator, the longer the course, the more the x-ray was absorbed, and the higher the sensitivity. In our detector scintillation screen, the depth of the holes was great than 150 micrometers, with the 1.5 micrometers side length of the square section of a hole.
A sphere-cylinder scattering model for skeletal muscle
Tianliang Yun, Nan Zeng, Honghui He, et al.
We acquired polarized reflectance images and Mueller matrix of fresh bovine skeletal muscle. Using polarization-dependent Monte Carlo simulations based on a sphere-cylinder scattering model, we are able to reproduce the characteristic features in the experiment results. We also simulate the changes of reflectance profile during stretching and rigor process, which are regarded as the changes of cylinders' diameter and the cylinder-sphere ratio in our model. The good agreement between simulations and experiments indicates that the unique pattern of polarized reflectance of skeletal muscles can also be due to scattering of well aligned fibrous myofibrils rather than coherent diffraction on the sarcomeres. It provides another angle to understand the interaction between photons and skeletal muscle and a proper model which characterizes the microstructure of the skeletal muscle. In addition, we give a parameter K calculated from the M12 element of Mueller matrix. The K-value is sensitive to different parameters in sphere-cylinder scattering model, therefore it is expected to use for monitoring the states of the skeletal muscle.
Linear polarization detection of polarization-sensitive optical coherence tomography in the early detection of the application of dental caries
Lei Li, Nan Zeng, Lifeng Yang
Polarization-Sensitive Optical Coherence Tomography (PS-OCT) is an important functional OCT. By extracting the polarization properties from PS-OCT signals we can obtain more information about the structural and optical features of tissues or materials. Dental caries is one of the most prevalent chronic diseases of people worldwide. The primary caries detection and the structure transformation of the enamel and dentin between sound and broken teeth are given serious attention by dentists. In this paper, using our Fourier-domain polarization-sensitive optical coherence tomography (FD-PS-OCT) setup by three incident linear polarization states and two detection states, we can get the 9 Mueller matrix elements from M11to M33 of the decay areas of the artificial caries measured. We also applied our polarized sensitive Monte Carlo program in the simulation of the PS-OCT detection process. We used a sphere-cylinder scattering model as an approximation of anisotropic tissues to describe the optical properties of tooth. By comparing the Mueller matrix elements of both experimental and simulation results, especially the diagonal elements (M11, M22 and M33), we reach the point that the main structural change of the caries that affects its scattering features is the expanded diameter of the enamel rods and dentinal tubules caused by the acid corrosion due to caries lesion.
Measurements of retinal temperature increase during photodynamic therapy for choroidal neovascularization
Hongxia Chen, Zaifu Yang, Ying Gu, et al.
To study the risk of retinal thermal injury from 532 nm laser during photodynamic therapy (PDT) for choroidal neovascularization (CNV) by measuring the retinal temperature increase of rabbit eyes. A microthermocouple technique was developed to measure retinal temperature increase during PDT in pigmented and non-pigmented rabbit eyes. The 532 nm laser exposures were performed with 100-s duration, 2-mm spot size, and retinal irradiance ranging from 400 to 1600 mW/cm2. A K-type microthermocouple was inserted through the sclerotomy and advanced until the tip reached the retina at the posterior pole. The thermocouple was connected a computer that recorded and analyzed retinal temperature data. The results showed that the retinal temperature increase during laser exposure was proportional to retinal irradiance with a particular spot diameter, exposure duration, wavelength, and fundus pigmentation. And the measured retinal temperature increases in pigmented rabbits were a little higher than those in albino rabbits under the same radiant condition. Retinal threshold irradiance required for visible lesions at laser wavelength of 532 nm with 2.0-mm spot size and 100-s duration was 1657 mW/cm2 in albino and 1003 mW/cm2 in pigmented rabbits, respectively, corresponding to retinal temperature increase of about 8 °C and 6 °C. The measured temperatures in albino and pigmented rabbit eyes were both lower than the model predictions, especially in pigmented rabbits. Therefore, further parameter modifying should be performed to obtain accuracy prediction of retinal temperature.
Sensitivities of the spatial-resolved diffuse reflectance to scattering parameters
Xiao-juan Zhang, Wei Yang, Ying Liu
The sensitivity expressions of spatial-resolved diffuse reflectance to first-order, second-order and third-order scattering parameter are derived in the P3 approximation of transport theory. The influence of first-order scattering parameter on the P3 approximation and diffusion approximation reflectance are compared, it is demonstrated that the sensitivity is distinct with that of the diffusion approximation in the region of about two transport mean free paths. The numerical analysis of second-order and third-order scattering parameter sensitivity expressions are also done. It is found that the sensitivities change with source-detector separations and reach a maximum in the region of between one transport mean free path and two transport mean free paths, and are positive in the region of beyond one transport mean free path. The influence of third-order optical parameter on the diffusing reflectance can be ignored by compared with the influence of second-order optical parameter.
Minimal invasive treatment using 6.02 micrometer DFG laser for carious dentin
Kunio Awazu, Katsunori Ishii, Masayuki Saiki, et al.
Conventional laser light sources for the treatment of a hard tissue in dental are good for removal of caries. However these lasers cannot achieve to give a selective treatment effect for caries without a side effect for normal tissue. The objective of this study is to develop the minimal invasive treatment technique of carious dentin by selective absorption effect using the laser with a wavelength of 6.02 μm which corresponds to an absorption peak of organic matters called amide 1 band. Mid-infrared nanosecond pulsed laser by difference-frequency generation was used for the experiment of selective treatment. A tunable wavelength range, pulse width and repetition rate is from 5.5 to 10 μm, 5 ns and 10 Hz, respectively. The laser with a wavelength of 6.02 μm and predetermined energy parameters was irradiated to a carious dentin model. After laser irradiation, the surface and cross-sectional surface of samples were observed. Average power density about 15 W/cm2 realized to excavate a demineralized region selectively. In the same energy condition, serious side effect was not observed on the surface of normal dentin. A wavelength of 6.02 μm realizes a selective excavation of carious dentin. Using 6.02 μm is a novel and promising technique toward to next-generation dental treatment procedure for realizing minimal intervention.
Finger temperature controller for non-invasive blood glucose measurement
Xiqin Zhang, Choon Meng Ting, Joon Hock Yeo
Blood glucose level is an important parameter for doctors to diagnose and treat diabetes. The Near-Infra-Red (NIR) spectroscopy method is the most promising approach and this involves measurement on the body skin. However it is noted that the skin temperature does fluctuate with the environmental and physiological conditions and we found that temperature has important influences on the glucose measurement. In-vitro and in-vivo investigations on the temperature influence on blood glucose measurement have been carried out. The in-vitro results show that water temperature has significant influence on water absorption. Since 90% of blood components are water, skin temperature of measurement site has significant influence on blood glucose measurement. Also the skin temperature is related to the blood volume, blood volume inside capillary vessels changes with skin temperature. In this paper the relationship of skin temperature and signal from the skin and inside tissue was studied at different finger temperatures. Our OGTT (oral glucose tolerance test) trials results show the laser signals follow the skin temperature trend and the correlation of signal and skin temperature is much stronger than the correlation of signal and glucose concentration. A finger heater device is designed to heat and maintain the skin temperature of measurement site. The heater is controlled by an electronic circuit according to the skin temperature sensed by a thermocouple that is put close to the measurement site. In vivo trials were carried out and the results show that the skin temperature significantly influences the signal fluctuations caused by pulsate blood and the average signal value.
Electro-acupuncture at different acupoints modulating the relative specific brain functional network
Jiliang Fang, Xiaoling Wang, Yin Wang, et al.
Objective: The specific brain effects of acupoint are important scientific concern in acupuncture. However, previous acupuncture fMRI studies focused on acupoints in muscle layer on the limb. Therefore, researches on acupoints within connective tissue at trunk are warranted. Material and Methods: Brain effects of acupuncture on abdomen at acupoints Guanyuan (CV4) and Zhongwan (CV12) were tested using fMRI on 21 healthy volunteers. The data acquisition was performed at resting state, during needle retention, electroacupuncture (EA) and post-EA resting state. Needling sensations were rated after every electroacupuncture (EA) procedure. The needling sensations and the brain functional activity and connectivity were compared between CV4 and CV12 using SPSS, SPM2 and the local and remote connectivity maps. Results and conclusion: EA at CV4 and CV12 induced apparent deactivation effects in the limbic-paralimbic-neocortical network. The default mode of the brain was modified by needle retention and EA, respectively. The functional brain network was significantly changed post EA. However, the minor differences existed between these two acupoints. The results demonstrated similarity between functional brain network mode of acupuncture modulation and functional circuits of emotional and cognitive regulation. Acupuncture may produce analgesia, anti-anxiety and anti-depression via the limbic-paralimbic-neocortical network (LPNN).
Study on pathological area of knee by infrared imaging
Shu-wang Chen, Cong-cong Wang
The application of infrared imaging in biomedical fields has been very broad, but the research results of the lesion of knee by using of infrared imaging have seldom been reported at present. On the basis of infrared images research, we present the exploring image analysis and relate the programming optimum entropy algorithm about infrared imaging analysis. The paper demonstrates the comparative study on the infrared images contrast between the pathological knee and the reference normal group through the optimum entropy algorithm. The rule of variation between the normal image and pathological changes of level about knee lesion in patients is gained. The research results provide a kind of methods for the clinical diagnosis of the pathological knee and also discuss the value of application about the optimum entropy algorithm in infrared imaging analysis. Contrasting the MRI or CT, the infrared imaging is cheap and harmless. So the method can be used in health care and prophylactic detection.
Optimization of fiber optic probe distance for biomedical spectroscopy
Bowen Wang, Yan Tang, Xiaolei Zhang, et al.
We present a theoretical model to maximize the illumination and collection efficiency in designing fiber optic probes for biomedical spectroscopy measurement. This model is in general applicable to probes with single or multiple fibers. We investigated a number of probe configurations and find that contact measurement is very inefficient for multi-fiber probes. Contact measurement is a good choice for single-fiber probes, but for multi-fiber probes, there is an optimal probe distance. By carefully choosing the probe and sample distance, the signal can be enhanced by 5-10 fold. Experiments demonstrate the distance dependence of collection efficiency in multi-fiber probes.
Diagnosis gynecological tumors based on urine first derivative spectra
Shumei Gao, Lu Jun, Guoqing Chen
We investigate the use of first derivative intrinsic fluorescence spectroscopy as an adjunctive tool for early diagnosis or screening on gynecological tumors. The first derivative intrinsic fluorescence spectra from limosis morning urine of gynecologic cancerous patient and the healthy group are measured. And Combining the first order derivative spectra method and clinic diagnosis standard to cluster analysis the information, we obtained that the diagnostic sensitivity and specificity are 81% and 75% based on the judgment of setting γ=300, respectively. It may be applied to early diagnose gynecological tumors using intrinsic urine fluorescence spectra.