Improving Diagnostic Yield of Capsule Endoscopy in Coeliac Disease: Can Flexible Spectral Imaging Colour Enhancement Play a Role?

INTRODUCTION: Flexible spectral imaging colour enhancement (FICE) is a form of virtual chromoendoscopy that is incorporated in the capsule reading software and that can be used by reviewers to enhance the delineation of lesions in the small bowel. This has been shown to be useful in the detection of pigmented (ulcers, angioectasias) lesions. However, its application to coeliac disease (CD) images from small bowel capsule endoscopies (SBCEs) has rarely been studied. METHODS: This was a European, multicentre study that included 5 expert capsule reviewers who were asked to evaluate a number of normal and abnormal de-identified images from SBCEs of patients with CD to determine whether the use of FICE and blue light can improve the detection of CD-related changes. RESULTS: Sensitivity and specificity of conventional white light in the delineation of CD-related changes were 100%. The next best image modification was FICE 1 with a sensitivity of 80% and a specificity of 100%. There was no difference between conventional white light, FICE and blue light for the identification of CD-related changes. There was a low agreement (Fleiss kappa 0.107; p = 0.147) between expert reviewers in selecting the best image modification that detected CD-related changes. CONCLUSIONS: FICE and blue light were not found to be superior to conventional white light in the delineation of macroscopic changes related to CD on SBCEs.

A Scheme for Ultrasensitive Detection of Molecules with Vibrational Spectroscopy in Combination with Signal Processing.

We show that combining vibrational spectroscopy with signal processing can result in a scheme for ultrasensitive detection of molecules. We consider the vibrational spectrum as a signal on the energy axis and apply a matched filter on that axis. On the example of a nerve agent molecule, we show that this allows detection of a molecule by its vibrational spectrum, even when the recorded spectrum is completely buried in noise when conventional spectroscopic detection is impossible. Detection is predicted to be possible with signal-to-noise ratios in the recorded spectra as low as 0.1. We have studied the importance of the spectral range used for detection as well as of the quality of the computed spectrum used to program the filter, specifically, the role of anharmonicity, of the exchange correlation functional, and of the basis set. The use of the full spectral range rather than of a narrow spectral window with key vibrations is shown to be advantageous, as well as accounting for anharmonicity.

Bioimpedance Spectroscopy Imprecisely Assesses Lean Body Mass in Pediatric Dialysis Patients.

OBJECTIVES: Alterations in body compositions are strongly associated with poor outcomes in end-stage renal disease patients. Hence, assessment of lean body mass is crucial for clinically monitoring these patients. The use of multifrequency bioimpedance spectroscopy measurements has also been advocated, but their usefulness in children is questioned. We investigated whether their application is appropriate for lean body mass measurement in pediatric patients receiving chronic dialysis. METHODS: Lean body mass estimates as assessed by multifrequency bioimpedance spectroscopy and by deuterium dilution were obtained for 15 patients (mean age 10.9 ±â€Š3.6 years). RESULTS: Lean body mass (mean ±â€Šstandard deviation) determined by bioimpedance was 24.2 ±â€Š10.7 and 24.4 ±â€Š10.3 kg by deuterium technique. Bland-Altman analysis showed a mean (±standard deviation) difference between the 2 methods of -0.25 ±â€Š2.30 kg with 95% limits of agreement of -4.80 to 4.25 kg. In a multiple linear regression model, the hydration status was associated with measurement bias after adjusting for age, sex, weight, and body surface area. CONCLUSIONS: Our results show a high level of agreement between measurements by bioimpedance and deuterium technique, but the limits of agreement were wide. These findings do not support the use of bioimpedance to individually assess lean body mass in pediatric dialysis patients with and without overhydration.

Background clean-up in Brillouin microspectroscopy of scattering medium.

Brillouin spectroscopy is an emerging tool for microscopic optical imaging as it allows for non-contact, non-invasive, direct assessment of the elastic properties of materials. However, strong elastic scattering and stray light from various sources often contaminate the Brillouin spectrum. A molecular absorption cell was introduced into the virtually imaged phased array (VIPA) based Brillouin spectroscopy setup to absorb the Rayleigh component, which resulted in a substantial improvement of the Brillouin spectrum quality.

Association of intraoperative tissue oxygenation with suspected risk factors for tissue hypoxia.

Tissue hypoxia may cause organ dysfunction, but not much is known about tissue oxygenation in the intraoperative setting. We studied microcirculatory tissue oxygen saturation (StO2) to determine representative values for anesthetized patients undergoing urological surgery and to test the hypothesis that StO2 is associated with known perioperative risk factors for morbidity and mortality, conventionally monitored variables, and hypotension requiring norepinephrine. Using near-infrared spectroscopy, we measured StO2 on the thenar eminence in 160 patients undergoing open urological surgery under general anesthesia (FiO2 0.35-0.4), and calculated its correlations with age, risk level for general perioperative complications and mortality (high if age ≥70 and procedure is radical cystectomy), mean arterial pressure (MAP), hemoglobin concentration (Hb), central venous oxygen saturation (ScvO2), and norepinephrine use. The time averaged StO2 was 86 ± 6 % (mean ± SD). In the multivariate analysis, Hb [standardized coefficient (SC) 0.21, p = 0.003], ScvO2 (SC 0.53, p < 0.001) and high risk level (SC 0.06, p = 0.03) were significant independent variables correlated with StO2. SStO2 was partly dependent on MAP only when this was below 65 mmHg (lowest MAP SC 0.20, p = 0.006, MAP area under the curve <65 mmHg SC 0.03, p = 0.02). Finally, StO2 was slightly lower in patients requiring norepinephrine (85 ± 6 vs. 89 ± 6 %, p = 0.001). Intraoperative StO2 in urological patients was comparable to that of healthy volunteers breathing room air as reported in the literature and correlated with known perioperative risk factors. Further research should investigate its association with outcome and the effect of interventions aimed at optimizing StO2.

Simultaneous measurement of quality factor and wavelength shift by phase shift microcavity ring down spectroscopy.

Optical resonant microcavities with ultra high quality factors are widely used for biosensing. Until now, the primary method of detection has been based upon tracking the resonant wavelength shift as a function of biodetection events. One of the sources of noise in all resonant-wavelength shift measurements is the noise due to intensity fluctuations of the laser source. An alternative approach is to track the change in the quality factor of the optical cavity by using phase shift cavity ring down spectroscopy, a technique which is insensitive to the intensity fluctuations of the laser source. Here, using biotinylated microtoroid resonant cavities, we show simultaneous measurement of the quality factor and the wavelength shift by using phase shift cavity ring down spectroscopy. These measurements were performed for disassociation phase of biotin-streptavidin reaction. We found that the disassociation curves are in good agreement with the previously published results. Hence, we demonstrate not only the application of phase shift cavity ring down spectroscopy to microcavities in the liquid phase but also simultaneous measurement of the quality factor and the wavelength shift for the microcavity biosensors in the application of kinetics measurements.

[Spectral analysis of the microvasculature of primary cutaneous melanoma]. / Introduction à l'analyse spectrale des réseaux microvasculaires du mélanome cutané primitif.

Cutaneous malignant melanoma represents one of the most dramatic skin cancers because its incidence is steadily growing in White populations. Of note, its metastatic risk and mortality dramatically increase when the primary neoplasm reaches about one millimeter thick. It is believed that angiogenesis and lymphangiogenesis associated with cutaneous melanoma potentially influence the neoplastic progression of the primary tumor and its metastases. In some instances, both the intratumoral and peritumoral microvasculature are correlated to booming of the tumoral growth fraction. In addition, the vascular network serves as a migration path for the intravascular and perivascular neoplastic spread. Hence, the quantification of the microvasculature might help establishing a prognostic factor of evolution. Among the available methods, spectral analysis of immunohistochemical sections highlighting vessels helps defining the microvasculature distribution. The benefit of using spectral analysis is discussed and the modalities of application of this analytical method are scrutinized.

Towards a field-compatible optical spectroscopic device for cervical cancer screening in resource-limited settings: effects of calibration and pressure.

Quantitative optical spectroscopy has the potential to provide an effective low cost, and portable solution for cervical pre-cancer screening in resource-limited communities. However, clinical studies to validate the use of this technology in resource-limited settings require low power consumption and good quality control that is minimally influenced by the operator or variable environmental conditions in the field. The goal of this study was to evaluate the effects of two sources of potential error: calibration and pressure on the extraction of absorption and scattering properties of normal cervical tissues in a resource-limited setting in Leogane, Haiti. Our results show that self-calibrated measurements improved scattering measurements through real-time correction of system drift, in addition to minimizing the time required for post-calibration. Variations in pressure (tested without the potential confounding effects of calibration error) caused local changes in vasculature and scatterer density that significantly impacted the tissue absorption and scattering properties Future spectroscopic systems intended for clinical use, particularly where operator training is not viable and environmental conditions unpredictable, should incorporate a real-time self-calibration channel and collect diffuse reflectance spectra at a consistent pressure to maximize data integrity.

Correlation-induced spectral changes in tissues.

We report experimental evidence of correlation-induced spectral changes in biological tissues. The overall spectral shift in our transmission measurements is to the red and the mean wavelength of the original spectrum is up 10% larger. These results indicate that the spectral changes due to elastic scattering are significant and likely to hinder all spectroscopic measurements based on the inelastic (i.e., emission and absorption) interaction between light and tissues. Thus, simultaneous morphology and spectral measurements are required for accurate measurements spectroscopic information.

Nonlinear phase dispersion spectroscopy.

Nonlinear phase dispersion spectroscopy is introduced as a means to retrieve wideband, high spectral resolution profiles of the wavelength-dependent real part of the refractive index. The method is based on detecting dispersion effects imparted to a light field with low coherence transmitted through a thin sample and detected interferometrically in the spectral domain. The same sampled signal is also processed to yield quantitative phase maps and spectral information regarding the total attenuation coefficient using spectral-domain phase microscopy and spectroscopic optical coherence tomography (SOCT), respectively. Proof-of-concept experiments using fluorescent and nonfluorescent polystyrene beads and another using a red blood cell demonstrate the ability of the method to quantify various absorptive/dispersive features. The increased sensitivity of this method, novel to our knowledge, is compared to intensity-based spectroscopy (e.g., SOCT), and potential applications are discussed.

Fruit and Vegetable Intake Assessed by Repeat 24 h Recalls, but Not by A Dietary Screener, Is Associated with Skin Carotenoid Measurements in Children.

Accurate measurement of fruit and vegetable (FV) intake is important for nutrition surveillance and evaluation of dietary interventions. We compared two tools for reporting FV intake to objective measurement of skin carotenoids among children. FV cups/day was assessed by repeated 24 h dietary recalls (24H FV) and the National Cancer Institute's All-Day Fruit and Vegetable Screener (NCI FV). Skin carotenoids were measured by repeated resonance Raman spectroscopy (RRS) of the palm. FV cups were regressed on RRS scores in unadjusted, field-based, and research-setting models with covariates feasible in each scenario. Data were baseline values from children aged 2-12 years in low-income households enrolled in a healthy eating randomized trial in four U.S. states (n = 177). Twenty-four-hour FV cups were associated with skin carotenoids in all models (p < 0.001) but NCI FV cups were not. Predicted RRS scores for discrete 24H FV cups provide a guide to interpretation of RRS in children (2 cups FV intake ~36,000 RRS units), with the research-setting scenario generally providing the narrowest prediction range (+/-1924). When self-reported data are required, 24 h recalls are more accurate than NCI FV screener data; and, when limited time, resources, or literacy must be considered, RRS scores can be quickly obtained and easily interpreted.

Role of spectral counting in quantitative proteomics.

Spectral count, defined as the total number of spectra identified for a protein, has gained acceptance as a practical, label-free, semiquantitative measure of protein abundance in proteomic studies. In this review, we discuss issues affecting the performance of spectral counting relative to other label-free methods, as well as its limitations. Possible consequences of modifications, which are commonly applied to raw spectral counts to improve abundance estimations, are considered. The use of spectral counting for different types of quantitation studies is explored and critiqued. Different statistical methods and underlying frameworks that have been applied to spectral count analysis are described and compared, and problem areas that undermine confident statistical analysis are considered. Finally, the issue of accurate estimation of false-discovery rates is addressed and identified as a major current challenge in quantitative proteomics.

Part II: defining and quantifying individual and co-cultured intracellular proteomes of two thermophilic microorganisms by GeLC-MS2 and spectral counting.

Probing the intracellular proteome of Thermotoga maritima and Caldicellulosiruptor saccharolyticus in pure and co-culture affords a global investigation into the machinery and mechanisms enduring inside the bacterial thermophilic cell at the time of harvest. The second of a two part study, employing GeLC-MS(2) a variety of proteins were confidently identified with <1% false discovery rate, and spectral counts for label-free relative quantification afforded indication of the dynamic proteome as a function of environmental stimuli. Almost 25% of the T. maritima proteome and 10% of the C. saccharolyticus proteome were identified. Through comparison of growth temperatures for T. maritima, a protein associated with chemotaxis was uniquely present in the sample cultivated at the non-optimal growth temperature. It is suspected that movement was induced due to the non-optimal condition as the organism may need to migrate in the culture to locate more nutrients. The inventory of C. saccharolyticus proteins identified in these studies and attributed to spectral counting, demonstrated that two CRISPR-associated proteins had increased expression in the pure culture versus the co-culture. Further focusing on this relationship, a C. saccharolyticus phage-shock protein was identified in the co-culture expanding a scenario that the co-culture had decreased antiviral resistance and accordingly an infection-related protein was present. Alterations in growth conditions of these bacterial thermophilic microorganisms offer a glimpse into the intricacy of microbial behavior and interaction.

Using fit functions in computational dielectric spectroscopy.

This work deals with the development of an appropriate set of fit functions for describing dielectric spectra based on simulated raw data. All these fit functions are of exponential character with properly chosen cofunctions. The type of the cofunctions is different for translation, rotation and their coupling. As an alternative to multiexponential fits we also discuss Kohlrausch-Williams-Watts functions. Since the corresponding Fourier-Laplace series for these stretched exponentials has severe convergence problems, we represent their Fourier-Laplace spectrum as a Havriliak-Negami expression with properly chosen parameters. A general relation between the parameter of the Kohlrausch-Williams-Watts and the Havriliak-Negami parameters is given. The set of fit functions is applied to the concrete simulation of the hydrated ionic liquid 1-ethyl-3-methyl-imidazolium triflate with H(2)O. The systematic variation of the water mole fraction permits to study the gradual transition from a neutral molecular liquid to molecular ionic liquids.

Temporal effects on spectroscopic line shapes, resolution, and sensitivity of the broad-band sum frequency generation.

Sum frequency generation (SFG) is a surface-selective spectroscopy that provides a wealth of molecular-level information on the structure and dynamics at surfaces and interfaces. This paper addresses the general issue of spectral resolution and sensitivity of the broad-band (BB) SFG that involves a spectrally narrow nonresonant (usually visible) and a BB resonant (usually infrared) laser pulses. We examine how the spectral width and temporal shape of the two pulses, and the time delay between them, relate to the spectroscopic line shape and signal level in the BB-SFG measurement. By combining experimental and model calculations, we show that the best spectral resolution and highest signal level are simultaneously achieved when the nonresonant narrow-band upconversion pulse arrives with a nonzero time delay after the resonant BB pulse. The nonzero time delay partially avoids the linear trade-off of improving spectral resolution at the expense of decreasing signal intensity, which is common in BB-SFG schemes utilizing spectral filtering to produce narrow-band visible pulses.

Development of image mappers for hyperspectral biomedical imaging applications.

A new design and fabrication method is presented for creating large-format (>100 mirror facets) image mappers for a snapshot hyperspectral biomedical imaging system called an image mapping spectrometer (IMS). To verify this approach a 250 facet image mapper with 25 multiple-tilt angles is designed for a compact IMS that groups the 25 subpupils in a 5 x 5 matrix residing within a single collecting objective's pupil. The image mapper is fabricated by precision diamond raster fly cutting using surface-shaped tools. The individual mirror facets have minimal edge eating, tilt errors of <1 mrad, and an average roughness of 5.4 nm.

Fast spark discharge-laser-induced breakdown spectroscopy method for rice botanic origin determination.

A simple, fast, and efficient spark discharge-laser-induced breakdown spectroscopy (SD-LIBS) method was developed for determining rice botanic origin using predictive modeling based on support vector machine (SVM). Seventy-two samples from four rice varieties (Guri, Irga 424, Puitá, and Taim) were analyzed by SD-LIBS. Spectral lines of C, Ca, Fe, Mg, N and Na were selected as input variables for prediction model fitting. The SVM algorithm parameters were optimized using a central composite design (CCD) to find the better classification performance. The optimum model for discriminating rice samples according to their botanical variety was obtained using C = 5.25 and γ = 0.119. This model achieved 96.4% of correct predictions in test samples and showed sensitivities and specificities per class within the range of 92-100%. The developed method is robust and eco-friendly for rice botanic identification since its prediction results are consistent and reproducible and its application does not generate chemical waste.

Determinants and Suitability of Carotenoid Reflection Score as a Measure of Carotenoid Status.

Carotenoids, orange-coloured pigments found in vegetables, fruit, eggs and dairy foods, act as antioxidants and vitamin A precursors in the human body. Skin carotenoid concentration is a biomarker of vegetable and fruit intake. The aim was to identify determinants of skin carotenoid concentration by measuring "Veggie Meter™" carotenoid reflection spectroscopy scores (CRS) from the fingertip of adults with a range of ages, ethnicity and body size. Frequencies of daily intake of vegetables and fruit and weekly intake of pumpkin and carrot, dark green leafy vegetables (DGLV), eggs (yolk), and dairy were determined from a self-completed food-frequency-questionnaire. A total of 571 (324 Women, 247 Men) adults, aged 16 to 85 years, completed measurements. The CRS ranged from 83 to 769, with a median of 327. Women and men did not score differently. For all participants there were negative correlations of CRS with weight (r = -0.312) and BMI (r = -0.338) and positive correlations with weekly intakes of DGLV (r = 0.242) and carrots and pumpkin (r = 0.202). Based on a review of health outcomes associated with plasma carotenoids, 82% of the participants in the current study are at moderate risk, or more, of negative health outcomes. Determinants of carotenoid status were body size, intake of DGLV, carrots and pumpkin, and ethnicity.

High frequency oscillations (80-500 Hz) in the preictal period in patients with focal seizures.

PURPOSE: Intracranial depth macroelectrode recordings from patients with focal seizures demonstrate interictal and ictal high frequency oscillations (HFOs, 80-500 Hz). These HFOs are more frequent in the seizure-onset zone (SOZ) and reported to be linked to seizure genesis. We evaluated whether HFO activity changes in a systematic way during the preictal period. METHODS: Fifteen minutes of preictal intracranial electroencephalography (EEG) recordings were evaluated in seven consecutive patients with well-defined SOZ. EEG was filtered at 500 Hz and sampled at 2,000 Hz. Ripples (80-250 Hz) and fast ripples (250-500 Hz) were visually marked, and spectral analysis was performed in seizure-onset as well as nonseizure-onset channels. Linear regressions fitted to the power trends corresponding to intervals of 1, 5, and 15 min before the seizure onset was calculated. RESULTS: Total rates of HFOs were significantly higher in the SOZ than outside. Preictal increases and decreases in HFO rates and band power could be detected in all patients, and they were not limited to the SOZs. These measures were very variable, and no systematic trends were observed when comparing patients or seizures in the same patient. DISCUSSION: High frequencies in the range of 80-500 Hz are present during the preictal period and are more prominent in the SOZ. They do not change in a systematic way before seizure onset for the horizons we tested. The 80-500 Hz band may be used for the localization of seizure-onset areas but may be more difficult to use for seizure prediction purposes.

EEG spectral changes underlying BOLD responses contralateral to spikes in patients with focal epilepsy.

PURPOSE: Simultaneous electroencephalogram and functional magnetic resonance imaging (EEG-fMRI) in patients with focal epilepsy and unilateral spikes often shows positive blood oxygenation level-dependent (BOLD) responses (activations), not only ipsilateral but also contralateral to the spikes. We aimed to investigate whether minimal EEG changes could underlie these contralateral BOLD responses by using EEG spectral analysis. METHODS: We studied 19 patients with focal epilepsy and unilateral spikes. According to the pattern of BOLD activation, patients were divided into Group 1 (ipsi- and contralateral to the spikes) or Group 2 (only ipsilateral). EEG from outside the scanner was used to mark spikes similar to those recorded in the scanner. Epochs of 640 ms before and after the peak of the spikes were chosen as baseline and spike epochs. Spectral analysis was performed in referential montage (FCz reference), and differences between baselines and spikes were analyzed by paired t-test. RESULTS: Significant EEG changes in electrodes contralateral to the spikes were seen in 9 of 10 patients in Group 1 and in only 2 of 10 patients in Group 2 (one patient had two types of spikes that were analyzed separately). Spectral changes were seen in delta and/or theta bands in all patients except one (in Group 1) who had changes in all bands. DISCUSSION: Significant contralateral EEG changes occurred in 90% of contralateral BOLD activations and in only 20% of patients without contralateral BOLD responses. The reason why these changes predominate in lower frequencies rather than in higher frequencies is unclear. These spectral changes in areas corresponding to contralateral activations might reflect poorly synchronized but possibly intense neuronal activity.