Showing papers in "Biomedical spectroscopy and imaging in 2011"
TL;DR: The study reveals that the multispectral camera provides accurate reconstruction of hyperspectral cube which can be used for analysis of skin reflectance spectrum.
Abstract: This paper presents the validation of a new multispectral camera specifically developed for dermatological application based on healthy participants from five different Skin PhotoTypes (SPT) The multispectral system provides images of the skin reflectance at different spectral bands, coupled with a neural network-based algorithm that reconstructs a hyperspectral cube of cutaneous data from a multispectral image The flexibility of neural network based algorithm allows reconstruction at different wave ranges The hyperspectral cube provides both high spectral and spatial information The study population involves 150 healthy participants The participants are classified based on their skin phototype according to the Fitzpatrick Scale and population covers five of the six types The acquisition of a participant is performed at three body locations: two skin areas exposed to the sun (hand, face) and one area non exposed to the sun (lower back) and each is reconstructed at 3 different wave ranges The validation is performed by comparing data acquired from a commercial spectrophotometer with the reconstructed spectrum obtained from averaging the hyperspectral cube The comparison is calculated between 430 to 740 nm due to the limit of the spectrophotometer used The results reveal that the multispectral camera is able to reconstruct hyperspectral cube with a goodness of fit coefficient superior to 0,997 for the average of all SPT for each location The study reveals that the multispectral camera provides accurate reconstruction of hyperspectral cube which can be used for analysis of skin reflectance spectrum
20 citations
TL;DR: Saliva SERS of 21 lung cancer patients and 22 normal people were measured and differentiated in this article, where principal component analysis (PCA) and linear discriminant analysis (LDA) were used to deduce and discriminate the two groups of data, resulted in accuracy, sensitivity, and specificity being 84, 94, and 81%, respectively.
Abstract: Surface enhanced Raman spectroscopy (SERS) has shown the advantage of detecting low concentration biofluids presently. Saliva SERS of 21 lung cancer patients and 22 normal people were measured and differentiated in this paper. Intensities of most peaks of lung cancer patients are weaker than that of normal people, some are stronger but with a small change rate. Those peaks were assigned to proteins and nucleic acids which indicate a corresponding decrease of substance in saliva. Principal component analysis (PCA) and linear discriminant analysis (LDA) were used to deduce and discriminate the two groups of data, resulted in accuracy, sensitivity, and specificity being 84%, 94%, and 81%, respectively. In conclusion, SERS of saliva has the ability of predicting lung cancer.
18 citations
TL;DR: The results show that hyper-spectral video endoscopy exhibits a large potential to become an important imaging technology for medical imaging devices that provide additional diagnostic information about the tissue under investigation.
Abstract: This paper presents a hyper-spectral video endoscopy system which utilizes a combination of auto-fluorescence imaging and white-light reflectance spectroscopy for intra-surgery tissue classification. The results of the first clinical study consisting of 59 cases of otolaryngoscopic examinations and thorax surgeries are discussed in this paper. The main focus of this application is the detection of tumor tissue, although hyper-spectral video endoscopy is not limited to cancer detection. The results show that hyper-spectral video endoscopy exhibits a large potential to become an important imaging technology for medical imaging devices that provide additional diagnostic information about the tissue under investigation.
18 citations
TL;DR: An experimental RGB imaging system based on commercial color camera was constructed, and its potential for mapping of hemoglobin distribution in skin was studied, proposing a novel approach for studies of skin capillary refill by RGB analysis.
Abstract: An experimental RGB imaging system based on commercial color camera was constructed, and its potential for mapping of hemoglobin distribution in skin was studied. Two types of LEDs (RGB and white “warm” LEDs) were compared as illuminators for acquiring images of vascular and pigmented skin malformations. A novel approach for studies of skin capillary refill by RGB analysis has been proposed and discussed.
14 citations
TL;DR: This paper presents the calibration and test results obtained by mean of a hyperspectral reflectance and flexible video endoscope setup, intended to be gastrointestinal cancer detection, and fabricated hard tissue phantoms which mimic different types of tissue in terms of its reflection properties for evaluation.
Abstract: Cancer is the second most cause of death in the world after cardiovascular related disease. This paper presents the calibration and test results obtained by mean of a hyperspectral reflectance and flexible video endoscope setup. Its application field is intended to be gastrointestinal cancer detection. We fabricated hard tissue phantoms which mimic different types of tissue in terms of its reflection properties for evaluation. The reflectance properties of the phantoms are set by varying the concentration of ink or titanium oxide. The goal is to achieve a similar reflectance properties as in actual respective tissues in vivo. A modified endoscope was used to discriminate the normal and tumor tissue phantoms with reflectance measurements. This hyperspectral endoscope setup consists of a light source, a camera and a camera controller that are compatible for use with conventional video endoscopes and video monitors. This setup allows the operator to switch between conventional white light imaging mode (WLI) and hyperspectral imaging mode (HSI). A significant imaging contrast between normal and tumor tissue phantoms has been provided.
14 citations
TL;DR: In this article, a tissue oxygen and temperature monitor based on white-light reflectance spectroscopy is presented, which takes into account the tissue scattering and melanin absorption for the calculation of tissue haemoglobin concentration and oxygen saturation.
Abstract: We report the design of a tissue oxygen and temperature monitor. The non-inv asive, fibre based device monitors tissue haemoglobin (Hb) and oxygen saturation (SO 2 ) and is based on white-light reflectance spectroscopy.Visible light with wavelengths in the 500 650nm range is utilized . The spectroscopic algorithm takes into account the tissue scattering and melanin absorption for the calculation of tissue haemoglobin concentration and oxygen saturation. The monitor can probe superfi cial layers of tissue with a high spatial resolution (mm 3 ) and a high temporal resolution (40 Hz). It provides an accurate measurement with the accuracy of SO 2 at 2 % and high reliability with less than 2 % variation of continuous SO 2 measurement over 12 hours. It can also form a modular system when used in conjunction with a laser Doppler monitor, enabling simultaneous measure ments of Hb, SO 2 and blood flow. W e found experimentally that the influence of the source-detector separation on the haemoglobin parameters is small. his finding is discussed by Monte Carlo Tsimulations for the depth sensitivity profile. T he influence of probe pressure and the skin pigmentation on the measurement parameters are assessed before in vivo experiment al data is presented . T he co mbination with laser D oppler flowmetry demonstrates t he importance of a measurement of both the haemoglobin and the blood flow parameters for a full description of blood tissue perfusion. This is discussed in experimental data on human skin during cuff occlusion and after hyperemisation by a pharmacological cream. Strongcorrelation is observed between tissue oxygen (Hb and SO
13 citations
TL;DR: Analysis of data obtained in the spectral range 450-950 nm using multispectral camera have led to a novel image processing algorithm capable to distinguish melanoma from pigmented nevi and different areas of activity of melanoma.
Abstract: A clinical trial on multi-spectral imaging of malignant and non-malignant skin pathologies comprising 22 melanomas and 59 pigmented nevi was performed in Latvian Oncology Center. Analysis of data obtained in the spectral range 450–950 nm using multispectral camera have led to a novel image processing algorithm capable to distinguish melanoma from pigmented nevi and different areas of activity of melanoma. The proposed methodology and potential clinical applications are discussed.
13 citations
TL;DR: In this article, the diffusely reflected light from 41 tissue models with discrete blood vessels with diameters ranging from 6.25 to 100 μm were simulated using the Monte Carlo technique, and a reverse engineering approach was then utilized to find the model that had an optimal spectral fit to each of the simulated models.
Abstract: Light absorption in tissue is generally decreased when chromophores are spatially concentrated rather than being homogeneously distributed. In tissue, this applies to hemoglobin located in blood vessels (vessel packaging). In this paper, the diffusely reflected light from 41 tissue models with discrete blood vessels with diameters ranging from 6.25 to 100 μm were simulated using the Monte Carlo technique. A reverse engineering approach was then utilized to find the model that had an optimal spectral fit to each of the simulated models. The average vessel diameter was one fitting parameter in the adaptive model. The estimated vessel diameter from the optimal fit model was compared to the known diameter from the simulated models. Two different methods to calculate the vessel packaging effect were used, one existing based on a simple analytic expression and a new method based on path length distributions. Both methods had similar performance. For the new method, the absolute RMS deviation of the estimated vessel diameter was 5.5 μm for vessel diameters ≤ 25 μm, and the relative RMS deviation was 21 % for vessel diameters > 25 μm.
12 citations
TL;DR: A newly developed portable multi-spectral photoplethysmography device has been used for studies of 11 healthy subjects and the proposed methodology and potential clinical applications are discussed.
Abstract: A photoplethysmography (PPG) signal can provide very useful information about a subject's hemodynamic status in a hospital or home environment. A newly developed portable multi-spectral photoplethysmography device has been used for studies of 11 healthy subjects. Multi-spectral photoplethysmography (MS-PPG) biosensor intended for analysis of peripheral blood volume pulsations at different vascular depths has been designed and experimentally tested. Multi-spectral monitoring was performed by means of a three–wavelengths (405 nm, 660 nm and 780 nm) laser diode and a single photodiode with multi-channel signal output processing. The proposed methodology and potential clinical applications are discussed.
12 citations
TL;DR: In order to create an experimental model closer to the real conditions encountered by the cell in vivo, 3-D collagen gels have been evaluated as a substrate for the spectroscopic study of live cells and it is demonstrated that neither the medium used for cell culture nor the collagen gelt themselves contribute to the spectra collected.
Abstract: Due to its high lateral resolution, Raman microspectrsocopy is rapidly becoming an accepted technique for the subcellular imaging of single cells. Although the potential of the technique has frequently been demonstrated, many improvements have still to be realised to enhance the relevancy of the data collected. Although often employed, chemical fixation of cells can cause modifications to the molecular composition and therefore influence the observations made. However, the weak contribution of water to Raman spectra offers the potential to study live cells cultured in vitro using an immersion lens, giving the possibility to record highly specific spectra from cells in their original state. Unfortunately, in common 2-D culture models, the contribution of the substrates to the spectra recorded requires significant data pre-processing causing difficulties in developing automated methods for the correction of the spectra. Moreover, the 2-D in vitro cell model is not ideal and dissimilarities between different optical substrates within in vitro cell cultures results in morphological and functional changes to the cells. The interaction between the cells and their microenvironment is crucial to their behavior but also their response to different external agents such as radiation or anticancer drugs. In order to create an experimental model closer to the real conditions encountered by the cell in vivo, 3-D collagen gels have been evaluated as a substrate for the spectroscopic study of live cells. It is demonstrated that neither the medium used for cell culture nor the collagen gels themselves contribute to the spectra collected. Thus the background contributions are reduced to that of the water. Spectral measurements can be made in full cell culture medium, allowing prolonged measurement times. Optimizations made in the use of collagen gels for live cells analysis by Raman spectroscopy are encouraging and studying live cells within a collagenous microenvironment seems perfectly accessible.
11 citations
TL;DR: The most sensitive parameter was the lifetime T2 in the short-wavelength channel, which corresponds to the neuronal retina, and changes in lifetime point to a loss of free NADH and an increased contribution of protein-bound NADH in the pre-stage of diabetic retinopathy.
Abstract: Measurements of time-resolved autofluorescence (FLIM) at the human ocular fundus of diabetic patients permit the detection of early pathologic alterations before signs of diabetic retinopathy are visible. The measurements were performed by the Jena Fluorescence Lifetime Laser Scanner Ophthalmoscope applying time-correlated single photon counting (TCSPC) in two spectral channels (K1: 490–560 nm, K2:560–700ps). The fluorescence was excited by 70 ps pulses (FWHM) at 448 nm. The decay of fluorescence intensity was triple-exponentially approximated. The frequency of amplitudes, lifetimes, and relative contributions was compared in fields of the same size and position in healthy subjects and in diabetic patients. The most sensitive parameter was the lifetime T2 in the short-wavelength channel, which corresponds to the neuronal retina. The changes in lifetime point to a loss of free NADH and an increased contribution of protein-bound NADH in the pre-stage of diabetic retinopathy.
TL;DR: The recent progress towards designing a fiber-based Raman probe, which - in perspective - might be incorporated into the working channel of a surgical endoscope, is presented, anticipated to contribute to the clinical routine.
Abstract: A basic problem intrinsic to many clinical diagnostic procedures as well as minimally invasive surgeries is the online in-vivo classification of tissue Associated with this problem is the task to determine the boundaries between tissue sections of various degrees of disease progression, which cannot be identified easily This problem is partly founded in the imaging modalities conventionally used, ie, white-light endoscopy or fluorescence-based endoscopic imaging These techniques allow for extracting of only a limited parameter set for judging the physiological or pathological state of tissue Furthermore, fluorescence-based endoscopy relies on the administration of external labels, which principally disturbs the native tissue These problems can be circumvented using Raman microspectroscopy as a diagnostic tool Raman microscopy allows to record vibrational spectra at each sampling point Therefore the molecular fingerprint of the sample can be deciphered with spatial resolution [1] [2] [3] [4] It has been shown that Raman spectroscopy in combination with advanced statistical methods can be used to identify and grade tissue samples However, the conventional approach of judging excised tissue sections by Raman microscopy does not present an approach which can be readily used in the clinics Here we present our recent progress towards designing a fiber-based Raman probe, which - in perspective - might be incorporated into the working channel of a surgical endoscope Thereby, it is anticipated to contribute to the clinical routine We will review the general design principle of such a device and the specific design strategy for our Raman probe in concert with comparative measurements employing a set of home-built and commercially-available devices
TL;DR: The diffusion capabilities of free fluorophores inside the heterogeneous three dimensional structure of Staphylococcus aureus biofilm were studied and the study was extended to BODIPY-vancomycin in order to better understand the mechanisms involved in the high tolerance of the bacteria embedded in a biofilm to the antibiotic.
Abstract: The diffusion capabilities of free fluorophores inside the heterogeneous three dimensional structure of Staphylococcus aureus biofilm were studied by an original image-based Fluorescence Recovery After Photobleaching method. The study was extended to BODIPY-vancomycin in order to better understand the mechanisms involved in the high tolerance of the bacteria embedded in a biofilm to the antibiotic.
TL;DR: In this paper, the authors report advances in the fabrication and anticipated performance of a polymer biosensor photonic chip developed in the European Union project P3SENS (FP7-ICT4-248304).
Abstract: In this work, we report advances in the fabrication and anticipated performance of a polymer biosensor photonic chip developed in the European Union project P3SENS (FP7-ICT4-248304). Due to the low cost requirements of point-of-care applications, the photonic chip is fabricated from nanocomposite polymeric materials, using highly scalable nano-imprint-lithography (NIL). A suitable microfluidic structure transporting the analyte solutions to the sensor area is also fabricated in polymer and adequately bonded to the photonic chip. We first discuss the design and the simulated performance of a high-Q resonant cavity photonic crystal sensor made of a high refractive index polyimide core waveguide on a low index polymer cladding. We then report the advances in doped and undoped polymer thin film processing and characterization for fabricating the photonic sensor chip. Finally the development of the microfluidic chip is presented in details, including the characterisation of the fluidic behaviour, the technological and material aspects of the 3D polymer structuring and the stable adhesion strategies for bonding the fluidic and the photonic chips, with regards to the constraints imposed by the bioreceptors supposedly already present on the sensors.
TL;DR: In this paper, the authors developed new methods for cell identification, micromanipulation and sorting based on spectroscopic methods and microfluidic systems, which achieved a prediction accuracy of 92.2% on the single cell level.
Abstract: Circulating epithelial tumor cells are of increasing importance for tumor diagnosis and therapy monitoring of cancer patients. The definite identification of the rare tumor cells within numerous blood cells is challenging. Therefore, within the research initiative “Jenaer Zell-Identifizierungs-Gruppe” (JenZIG) we develop new methods for cell identification, micromanipulation and sorting based on spectroscopic methods and microfluidic systems. In this contribution we show, that classification models based on Raman spectroscopic analysis allow a precise discrimination of tumor cells from non-tumor cells with high prediction accuracies, up to more than 99% for dried cells. That holds true for unknown cell mixtures (tumor cells and leukocytes/erythrocytes) under dried conditions as well as in solution using the Raman laser as an optical tweezers to keep the cells in focus. We extended our studies by using a capillary system consisting of a quartz capillary, fiber optics and an adjustable fitting to trap cells. This system allows a prediction accuracy of 92.2% on the single cell level, and is a prerequisite for the development of a cell sorting and identification device based on a microfluidic chip. Initial experiments show that tumor cell lines can be differentiated from healthy leukocyte cells with an accuracy of more than 98%.
TL;DR: The method for detection of neuraminidase activity using fluorescent microscopy was proposed, it provided a high signal level and information on cellular localization of the studied enzyme, and the increase of sialid enzyme activity on apoptotic cells was demonstrated in comparison to viable and primary necrotic cells.
Abstract: Here we describe a novel approach to sialidase activity estimation. Sialidases (EC 3.2.1.18, exo-α-sialidases), also known as neuraminidases, are the group of enzymes, which hydrolyze the glycoside bound between terminal sialic acid and subsequent carbohydrate residue in glycoproteins and glycolipids. Sialic acids are the group of monosaccharides with acidic properties, since they are acetylated or glycolylated derivates of neuraminic acid. Flu and some other viruses use neuraminidase activity to infect host cells. The level of sialylation was shown to be tightly connected with tumor cell invasiveness and metastatic potential, sialylation level also determines the clearance of aged or virus-infected cells. Thus, detection of sialidase activity is of primary importance for clinical diagnostics as well as life science research.The authors developed the assay for both visualization and estimation of sialidase activity in living cells. Previously known methods for sialidase activity detection required destruction of cellular material, or were low-sensitive, or provided no information on the activity localization in certain intracellular compartment. To overcome these problems, a fluorogenic neuraminidase substrate, 4-MUNA was utilized, and the method for detection of neuraminidase activity using fluorescent microscopy was proposed, it provided a high signal level and information on cellular localization of the studied enzyme. By using this approach the increase of sialidase activity on apoptotic cells was demonstrated in comparison to viable and primary necrotic cells.
TL;DR: The conclusion is that the selected features can maintain the information of original spectra well and Raman spectroscopy of serum has the potential for the diagnosis of colorectal cancer.
Abstract: Raman spectroscopy of tissues has been widely studied for the diagnosis of various cancers, but biofluids were seldom used as the analyte because of the low concentration. Herein, serum of 30 normal people, 46 colon cancer, and 44 rectum cancer patients were measured Raman spectra and analyzed. The information of Raman peaks (intensity and width) and that of the fluorescence background (baseline function coefficients) were selected as parameters for statistical analysis. Principal component regression (PCR) and partial least square regression (PLSR) were used on the selected parameters separately to see the performance of the parameters. PCR performed better than PLSR in our spectral data. Then linear discriminant analysis (LDA) was used on the principal components (PCs) of the two regression method on the selected parameters, and a diagnostic accuracy of 88% and 83% were obtained. The conclusion is that the selected features can maintain the information of original spectra well and Raman spectroscopy of serum has the potential for the diagnosis of colorectal cancer.
TL;DR: A comparative analysis between the cellular lifetimes from different diagnoses demonstrates significant diagnostic potential, and multispectral fluorescence lifetime imaging as a non-invasive technique for the diagnosis of skin lesions is described.
Abstract: Multispectral fluorescence lifetime imaging (FLIM) using two photon microscopy as a non-invasive technique for the diagnosis of skin lesions is described. Skin contains fluorophores including elastin, keratin, collagen, FAD and NADH. This endogenous contrast allows tissue to be imaged without the addition of exogenous agents and allows the in vivo state of cells and tissues to be studied. A modified DermaInspect® multiphoton tomography system was used to excite autofluorescence at 760 nm in vivo and on freshly excised ex vivo tissue. This instrument simultaneously acquires fluorescence lifetime images in four spectral channels between 360-655 nm using time-correlated single photon counting and can also provide hyperspectral images. The multispectral fluorescence lifetime images were spatially segmented and binned to determine lifetimes for each cell by fitting to a double exponential lifetime model. A comparative analysis between the cellular lifetimes from different diagnoses demonstrates significant diagnostic potential.
TL;DR: The autofluorescence photobleaching intensity dynamics of in vivo skin and skin pathologies under continuous 532 nm laser irradiation have been studied and results illustrate potentiality of the technology.
Abstract: The autofluorescence photobleaching intensity dynamics of in vivo skin and skin pathologies under continuous 532 nm laser irradiation have been studied. Overall the 141 human skin malformations were investigated by laser induced skin autofluorescence photobleaching analysis. Details of equipment are described along with some measurement results illustrating potentiality of the technology.
TL;DR: In this paper, a rapid label-free approach for molecular histopathology is presented and reviewed using nonlinear interferometric vibrational imaging (NIVI), a coherent anti-Stokes Raman scattering (CARS)-based technique that uses interferometry and signal processing approaches to acquire Raman-like profiles with suppression of the nonresonant background.
Abstract: A rapid label-free approach for molecular histopathology is presented and reviewed. Broadband vibrational spectra are generated by nonlinear interferometric vibrational imaging (NIVI), a coherent anti-Stokes Raman scattering (CARS)-based technique that uses interferometry and signal processing approaches to acquire Raman-like profiles with suppression of the non-resonant background. This allows for the generation of images that provide contrast based on quantitative chemical composition with high spatial and spectral resolution. Algorithms are demonstrated for reducing the diagnostic spectral information into color-coded composite images for the rapid identification of chemical constituents in skin, as well as differentiating normal from abnormal tissue in a pre-clinical tumor model for human breast cancer. This technology and methodology could result in an alternative method to the traditional histological staining and subjective interpretation procedure currently used in the diagnosis of disease, and has the potential for future in vivo molecular histopathology.
TL;DR: In this paper, Fourier transform infrared (FTIR) images recorded with a FPA detector have been demonstrated to identify the primary tumours of brain metastases, but the strong absorption of water makes it difficult to transfer the results to non-dried tissues.
Abstract: Vibrational spectroscopic imaging methods are novel tools to visualise chemical component in tissue without staining. Fourier transform infrared (FTIR) imaging is more frequently applied than Raman imaging so far. FTIR images recorded with a FPA detector have been demonstrated to identify the primary tumours of brain metastases. However, the strong absorption of water makes it difficult to transfer the results to non-dried tissues. Raman spectroscopy with near infrared excitation can be used instead and allows collecting the chemical fingerprint of native specimens. Therefore, Raman spectroscopy is a promising tool for tumour diagnosis in neurosurgery. Scope of the study is to compare FTIR and Raman images to visualize the tumour border and identify spectral features for classification. Brain metastases were obtained from patients undergoing surgery at the university hospital. Brain tissue sections were shock frozen, cryosectioned, dried and the same areas were imaged with both spectroscopic method. To visualise the chemical components, multivariate statistical algorithms were applied for data analysis. Furthermore classification models were trained using supervised algorithms to predict the primary tumor of brain metastases. Principal component regression (PCR) was used for prediction based on FTIR images. Support vector machines (SVM) were used for prediction based on Raman images. The principles are shown for two specimens. In the future, the study will be extended to larger data sets.
TL;DR: The potential of IR, Raman and CARS microscopy to characterize the constitution of atherosclerotic plaques as well as the structure of the surrounding tissue is compared and spectral decomposition algorithms such as vertex component analysis (VCA) were introduced.
Abstract: Atherosclerotic plaques are mainly composed of proteoglycans, triglycerides, cholesterol, cholesterolester and crystalline calcium. From histopathological characterizations it is known that the composition of these atherosclerotic plaques can vary to a great extent, due to different risk factors as smoking, hyperlipedemia, or genetic background ect. The individual plaque components can be spectroscopically easily identified. Furthermore, spectroscopic imaging technologies offer the possibility to study the plaque compositions in a more quantitative manner than traditional staining techniques. Here, we compare the potential of IR, Raman and CARS microscopy to characterize the constitution of atherosclerotic plaques as well as the structure of the surrounding tissue. For data analysis and image reconstruction spectral decomposition algorithms such as vertex component analysis (VCA) were introduced. The results are in good agreement with the histopathology. Aim of the study is to correlate the compositional characteristics of atherosclerotic plaques with individual disease patterns.
TL;DR: The results are used to guide developments in photoacoustic mammography in order to pave the way towards an optimal technique for early diagnosis of breast cancer.
Abstract: Worldwide, yearly about 450,000 women die from the consequences of breast cancer. Current imaging modalities are not optimal in discriminating benign from malignant tissue. Visualizing the malignancy-associated increased hemoglobin concentration might significantly improve early diagnosis of breast cancer. Since photoacoustic imaging can visualize hemoglobin in tissue with optical contrast and ultrasound-like resolution, it is potentially an ideal method for early breast cancer imaging. The Twente Photoacoustic Mammoscope (PAM) has been developed specifically for breast imaging. Recently, a large clinical study has been started in the Medisch Spectrum Twente in Oldenzaal using PAM. In PAM, the breast is slightly compressed between a window for laser light illumination and a flat array ultrasound detector. The measurements are performed using a Q-switched Nd:YAG laser, pulsed at 1064 nm and a 1 MHz unfocused ultrasound detector array. Three-dimensional data are reconstructed using a delay and sum reconstruction algorithm. Those reconstructed images are compared with conventional imaging and histopathology. In the first phase of the study 12 patients with a malignant lesion and 2 patients with a benign cyst have been measured. The results are used to guide developments in photoacoustic mammography in order to pave the way towards an optimal technique for early diagnosis of breast cancer
TL;DR: In this paper, a specialized transient digitizer system was developed for spectroscopic collection of fluorescence wavelength-time matrices (WTMs) from biological tissues, which is compact, utilizes fiber optic probes for clinical compatibility, and offers rapid collection of high signal-to-noise ratio (>100) time and wavelength resolved fluorescence.
Abstract: A specialized transient digitizer system was developed for spectroscopic collection of fluorescence wavelength-time matrices (WTMs) from biological tissues. The system is compact, utilizes fiber optic probes for clinical compatibility, and offers rapid collection of high signal-to-noise ratio (>100) time- and wavelength- resolved fluorescence. The system is compatible with excitation sources operating in excess of 25 kHz. Wavelength-resolved measurement range is 300?800 nm with ≥ 0.01 nm steps. Time-resolved measurement depth is 128 ns with fixed 0.2 ns steps. The information-rich WTM data provides comprehensive fluorescence sensing capabilities, as demonstrated on tissue simulating phantoms. Extracting wavelength-resolved fluorophore lifetimes illustrates the potential of using the technology to resolve exogenous or endogenous fluorophore contributions in tissue samples in a clinical setting for tissue diagnostics and monitoring.
TL;DR: It can be seen that modern analyzing method is a useful tool for the analysis of serum spectra for diagnosing diseases.
Abstract: In this paper, Raman spectra of human serum were measured using Raman spectroscopy, then the spectra was analyzed component analysis (PCA). Then linear discriminant analysis (LDA) was utilized to differentiate the loading score of different diseases as the diagnosing algorithm. Artificial neural network (ANN) was used for cross-validation. The diagnosis sensitivity and specificity by PCA-LDA are 88% and 79%, while that of the PCA-ANN are 89≊ and 95%. It can be seen that modern analyzing method is a useful tool for the analysis of serum spectra for diagnosing diseases.
TL;DR: In this article, it was shown that spectrally and spatially resolved reflectance in combination with a determination of absorption and reduced scattering coefficients from a look-up table provides a means for quantification of chromophores, although the accuracy largely depends on the tissue model.
Abstract: Chromophore concentrations from skin contain information about the blood parameters, for example total hemoglobin content or antioxidant status of the skin. Deviations from the normal values of the concentrations may indicate pathologies. As the chromophore concentrations are determined from skin absorption coefficients, the optical absorption spectra of the isolated skin chromophores have to be known in advance, enabling least squares fitting of the basis spectra to the skin absorption coefficient. It could be shown that spectrally and spatially resolved reflectance in combination with a determination of absorption and reduced scattering coefficients from a look-up table provides a means for quantification of chromophores, although the accuracy largely depends on the tissue model. Good qualitative results can also be obtained with the homogenous tissue model used here. For example, it could be shown that the hemoglobin basis spectra determined from human whole blood and the pure water absorption fit very well to the skin absorption coefficients, but the ex vivo carotene spectra does not. Therefore it was examined how the carotene spectra change from ex vivo to in vivo. Interindividual and interpositional variation of the optical parameters could also be evaluated using this method as well as the dependence of determined optical parameters on the source-detector separation.
TL;DR: In order to confirm the possibility of the method to evaluate changes in the optical properties of cerebral cortex, in vivo experiments for exposed rat brain during CSD evoked by the pinprick stimulation were performed.
Abstract: We present a new method determining the absorption coefficients and the reduced scattering coefficients of in vivo rat cerebral cortex using single reflectance fiber probe with two source-collector geometries. Experiments with optical phantoms were conducted to evaluate the performance of the proposed fiber probe system. In order to confirm the possibility of the method to evaluate changes in the optical properties of cerebral cortex, we performed in vivo experiments for exposed rat brain during CSD evoked by the pinprick stimulation.
TL;DR: The results show that the performance on highly-noisy data, obtained using inexpensive equipment, is still high even when the classification is applied on a distinct hold-out set of test data, an important consideration when developing clinically viable diagnostic applications.
Abstract: Support Vector Machines have been used successfully for the classification of data in a wide range of applications. A key factor affecting the accuracy of the classification is the choice of kernel. In this paper we propose the use of Support Vector Machines with a correlation kernel. The correlation kernel is an appropriate choice when performing classification of Raman spectra because it reduces the need for pre-processing. Pre-processing can greatly affect the accuracy of the results because it introduces user bias and over-fitting effects. The correlation kernel is “self-normalizing” and produces superior classification performance with minimal pre-processing. Our results show that the performance on highly-noisy data, obtained using inexpensive equipment, is still high even when the classification is applied on a distinct hold-out set of test data. This is an important consideration when developing clinically viable diagnostic applications.
TL;DR: Novel nanosensitizer based optical biopsy imaging technique has the potential to provide an alternative to tissue biopsy and will enable clinicians to make real-time diagnosis, determine surgical margins during operative procedures and perform targeted treatment of cancers.
Abstract: We report novel bioconjugated nanosensitizers as optical and therapeutic probes for the detection, monitoring and treatment of cancer. These nanosensitisers, consisting of hypericin loaded bioconjugated gold nanoparticles, can act as tumor cell specific therapeutic photosensitizers for photodynamic therapy coupled with additional photothermal effects rendered by plasmonic heating effects of gold nanoparticles. In addition to the therapeutic effects, the nanosensitizer can be developed as optical probes for state-of-the-art multi-modality in-vivo optical imaging technology such as in-vivo 3D confocal fluorescence endomicroscopic imaging, optical coherence tomography (OCT) with improved optical contrast using nano-gold and Surface Enhanced Raman Scattering (SERS) based imaging and bio-sensing. These techniques can be used in tandem or independently as in-vivo optical biopsy techniques to specifically detect and monitor specific cancer cells in-vivo. Such novel nanosensitizer based optical biopsy imaging technique has the potential to provide an alternative to tissue biopsy and will enable clinicians to make real-time diagnosis, determine surgical margins during operative procedures and perform targeted treatment of cancers.
TL;DR: Ordinary least squares analysis shows promise for extraction of useful biochemical information and could aid the histopathologist and ultimately lead to automated histopathological processing.
Abstract: Histopathology provides the gold standard assessment of colonoscopic biopsies. Infrared spectroscopy can potentially map biochemical changes across a tissue section identifying disease. The purpose of this study was to determine if infrared spectroscopy could classify different colorectal pathologies and to investigate biochemical composition. Colonoscopic tissue biopsies were snap frozen at colonoscopy. 10 micron thick sections were mounted on CaF2 slides. 3-D spectral datasets (2 spatial dimensions and one spectral) were measured from thawed specimens using a Perkin Elmer infrared imaging system in transmission mode. Contiguous tissue sections stained with H&E were reviewed by a specialist gastrointestinal pathologist for comparison. Tissue spectra from epithelial tissues were classified using principal components fed linear discriminant analysis with leave one out cross validation. Reference spectra from purchased biochemicals (Sigma-Aldrich) were measured. Ordinary least squares analysis estimated the relative biochemical signal contribution from epithelial regions. Spectra from tissue epithelia measured from normal tissue, hyperplastic polyps, adenomatous polyps, cancer and ulcerative colitis samples were classified with accuracies in excess of 90%. Ordinary least squares analysis demonstrated a higher DNA to cytoplasm ratio in cancer compared to normal tissue. FTIR spectra from epithelia can be used to classify colorectal pathologies with high accuracy. Ordinary least squares analysis shows promise for extraction of useful biochemical information. These techniques could aid the histopathologist and ultimately lead to automated histopathological processing.