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We have developed a three-dimensional Monte Carlo (MC) model of optical transport in skin and applied it to analysis of port wine stain treatment with sequential laser irradiation and intermittent cryogen spray cooling. Our MC model extends the approaches of the popular multi-layer model by Wang et al.1 to three dimensions, thus allowing treatment of skin inclusions with more complex geometries and arbitrary irradiation patterns. To overcome the obvious drawbacks of either "escape" or "mirror" boundary conditions at the lateral boundaries of the finely discretized volume of interest (VOI), photons exiting the VOI are propagated in laterally infinite tissue layers with appropriate optical properties, until they loose all their energy, escape into the air, or return to the VOI, but the energy deposition outside of the VOI is not computed and recorded. After discussing the selection of tissue parameters, we apply the model to analysis of blood photocoagulation and collateral thermal damage in treatment of port wine stain (PWS) lesions with sequential laser irradiation and intermittent cryogen spray cooling. © 2010 SPIE.

Our working hypothesis is that a dual-wavelength Nd:YAG laser, emitting simultaneously at 1064 and 532 nm, may induce stronger heating of PWS blood vessels relative to the epidermis than the customary KTP laser, due to conversion of hemoglobin to met-hemoglobin in the target blood vessels and the associated increase in NIR absorption. We apply pulsed photothermal radiometry to determine temperature depth profiles induced in PWS lesions by a dual-wavelength laser at sub-therapeutic radiant exposures. The results indicate no effect at 1 ms pulse duration and low radiant exposures (1-2 J/cm 2). Increased radiant exposure (3-4 J/cm2) and extended pulse duration (20-25 ms) result in increased energy deposition. In addition, two PWS lesions and one healthy skin site were irradiated at incrementally increasing radiant exposures, up to 9 J/cm2. Analysis of the laser-induced temperature profiles clearly revealed irreversible changes of tissue properties. Formation of met-hemoglobin and consequent increase of IR absorption was however not reliably detected. ©2007 SPIE-OSA.

We simulate temperature depth profiling in human skin using pulsed photothermal radiometry (PPTR). By taking into account blackbody emission characteristics, spectral variation of human skin IR absorption coefficient, detectivity of available radiation detectors, and shot noise, we compute realistic PPTR signals for a test temperature profile, representing a subsurface vascular lesion. Analysis of the reconstructed temperature profiles enables a performance comparison of quantum IR detectors utilizing different spectral acquisition bands. The results suggest that HgCdTe detector used in 6-10 μxm spectral band performs better than an InSb detector used at 4-5 μm. © EDP Sciences.

Selection of infrared (IR) detector is a key consideration in designing an experimental setup for temperature depth profiling using pulsed photothermal radiometry (PPTR). In addition to common detector characteristics, such as the spectral response, detector noise, and response speed, application-specific details must be taken into account to ensure optimal system performance. When comparing detectors with different spectral responses, blackbody emission characteristics must be considered in terms of influence on radiometric signal amplitude, as well as on background shot noise. In PPTR, optical penetration depth of the sample in the acquisition spectral band is also an important factor, affecting the stability of the temperature profile reconstruction. Moreover, due to spectral variation of IR absorption coefficient in watery tissues, the acquisition band must be appropriately narrowed to ensure the validity of the customary approximation of a constant absorption coefficient value in signal analysis. This reduces the signal-to-noise ratio, adversely affecting the stability and quality of the temperature profile reconstruction. We present a performance analysis of PPTR depth profiling in human skin using commercially available IR detectors (InSb, HgCdTe), operating in different spectral bands. A measurement simulation example, involving a simple, hyper-Gaussian temperature profile, and realistic noise levels, illustrates their expected performance.

Optical coherence tomography angiography (OCTA) is an emerging imaging modality that enables noninvasive visualization and analysis of tumor vasculature. OCTA has been particularly useful in clinical ocular oncology, while in this article, we evaluated OCTA in assessing microvascular changes in clinical nonocular oncology through a systematic review of the literature.

Hyperspectral imaging (HSI) is a promising imaging modality that uses visible light to obtain information about blood flow. It has the distinct advantage of being noncontact, nonionizing, and noninvasive without the need for a contrast agent. Among the many applications of HSI in the medical field are the detection of various types of tumors and the evaluation of their blood flow, as well as the healing processes of grafts and wounds. Since tumor perfusion is one of the critical factors in oncology, we assessed the value of HSI in quantifying perfusion changes during interventions in clinical oncology through a systematic review of the literature.

Ho proved in [A note on the total domination number, Util. Math. 77 (2008) 97–100] that the total domination number of the Cartesian product of any two graphs without isolated vertices is at least one half of the product of their total domination numbers. We extend a result of Lu and Hou from [Total domination in the Cartesian product of a graph and K2or Cn, Util. Math. 83 (2010) 313–322] by characterizing the pairs of graphs G and H for which γt(G□H)=12γt(G)γt(H)$\gamma _t \left( {G\square H} \right) = {1 \over 2}\gamma _t \left( G \right)\gamma _t \left( H \right)$ , whenever γt(H) = 2. In addition, we present an infinite family of graphs Gn with γt(Gn) = 2n, which asymptotically approximate equality in γt(Gn□Hn)≥12γt(Gn)2$\gamma _t \left( {G_n \square H_n } \right) \ge {1 \over 2}\gamma _t \left( {G_n } \right)^2 $.

Significance: Machine learning models for the direct extraction of tissue parameters from hyperspectral images have been extensively researched recently, as they represent a faster alternative to the well-known iterative methods such as inverse Monte Carlo and inverse adding-doubling (IAD)., Aim: We aim to develop a Bayesian neural network model for robust prediction of physiological parameters from hyperspectral images., Approach: We propose a two-component system for extracting physiological parameters from hyperspectral images. First, our system models the relationship between the measured spectra and the tissue parameters as a distribution rather than a point estimate and is thus able to generate multiple possible solutions. Second, the proposed tissue parameters are then refined using the neural network that approximates the biological tissue model., Results: The proposed model was tested on simulated and in vivo data. It outperformed current models with an overall mean absolute error of 0.0141 and can be used as a faster alternative to the IAD algorithm., Conclusions: Results suggest that Bayesian neural networks coupled with the approximation of a biological tissue model can be used to reliably and accurately extract tissue properties from hyperspectral images on the fly., (© 2025 The Authors.)

Significance: Developing stable, robust, and affordable tissue-mimicking phantoms is a prerequisite for any new clinical application within biomedical optics. To this end, a thorough understanding of the phantom structure and optical properties is paramount., Aim: We characterized the structural and optical properties of PlatSil SiliGlass phantoms using experimental and numerical approaches to examine the effects of phantom microstructure on their overall optical properties., Approach: We employed scanning electron microscope (SEM), hyperspectral imaging (HSI), and spectroscopy in combination with Mie theory modeling and inverse Monte Carlo to investigate the relationship between phantom constituent and overall phantom optical properties., Results: SEM revealed that microspheres had a broad range of sizes with average ( 13.47 ± 5.98 )    μ m and were also aggregated, which may affect overall optical properties and warrants careful preparation to minimize these effects. Spectroscopy was used to measure pigment and SiliGlass absorption coefficient in the VIS-NIR range. Size distribution was used to calculate scattering coefficients and observe the impact of phantom microstructure on scattering properties. The results were surmised in an inverse problem solution that enabled absolute determination of component volume fractions that agree with values obtained during preparation and explained experimentally observed spectral features. HSI microscopy revealed pronounced single-scattering effects that agree with single-scattering events., Conclusions: We show that knowledge of phantom microstructure enables absolute measurements of phantom constitution without prior calibration. Further, we show a connection across different length scales where knowledge of precise phantom component constitution can help understand macroscopically observable optical properties., (© 2024 The Authors.)

In 1965, Jack Edmonds characterized pairs of graphs G and G* with a bijection between their edge sets that form a pair of dual graphs realizing the vertices and countries of a map embedded in a surface. A necessary condition is that, if d = (d 1 , …, d n ) and t = (t 1 ,…, t m ) denote the degree sequences of two such graphs, then ∑ i = 1 n d i = ∑ j = 1 m t j = 2 l , where l is the number of edges in each of the two graphs and χ = n + m - l is the Euler characteristic of the surface. However, this condition is not sufficient, and it is an open question to characterize bi-vectors ( d, t ) that are geographic , that is, that can be realized as the degree sequences of pairs G and G* of surface-embedded graphs. The above question is a special case of the following one. A multigraph G is even if each vertex has even degree and 3-colored if G is equipped with a fixed proper coloring of its vertex set assigning each vertex a color in the set {1,2,3}. Let G be a 3-colored even multigraph embedded in a surface S so that every face is a triangle. Denote by d = (d 1 , …, d n ), t = (t 1 , …, t m ), and δ = (δ 1 , ..., …, δ k ) the sequences of half-degrees of vertices of G of colors 1, 2, and 3, respectively. Then, ∑ i = 1 n d i = ∑ j = 1 m t j = ∑ μ = 1 k t μ = l , where χ = n + k + m - l is the Euler characteristic of the surface S. A tri-vector (d, t, δ) satisfying the above conditions is called feasible . A feasible tri-vector is called geographic if it is realized by a 3-colored triangulation of a surface. Geographic tri-vectors extend the concept of geographic bi-vectors. We present a dataset of geographic bi-vectors and tri-vectors, along with realizations proving that they are geographic., (© 2024 The Author(s).)

Hyperspectral microscope imaging (HMI) is an emerging modality that integrates spatial information collected by standard laboratory microscopy and the spectral-based contrast obtained by hyperspectral imaging and may be instrumental in establishing novel quantitative diagnostic methodologies, particularly in histopathology. Further expansion of HMI capabilities hinges upon the modularity and versatility of systems and their proper standardization. In this report, we describe the design, calibration, characterization, and validation of the custom-made laboratory HMI system based on a Zeiss Axiotron fully motorized microscope and a custom-developed Czerny-Turner-type monochromator. For these important steps, we rely on a previously designed calibration protocol. Validation of the system demonstrates a performance comparable to classic spectrometry laboratory systems. We further demonstrate validation against a laboratory hyperspectral imaging system for macroscopic samples, enabling future comparison of spectral imaging results across length scales. An example of the utility of our custom-made HMI system on a standard hematoxylin and eosin-stained histology slide is also shown.

Optical techniques are often inadequate in estimating bruise age since they are not sensitive to the depth of chromophores at the location of the bruise. To address this shortcoming, we used pulsed photothermal radiometry (PPTR) for depth profiling of bruises with two wavelengths, 532 nm (KTP laser) and 1064 nm (Nd:YAG laser). Six volunteers with eight bruises of exactly known and documented times of injury were enrolled in the study. A homogeneous part of the bruise was irradiated first with a 5 ms pulse at 532 nm and then with a 5 ms pulse at 1064 nm. The resulting transient surface temperature change was collected with a fast IR camera. The initial temperature-depth profiles were reconstructed by solving the ill-posed inverse problem using a custom reconstruction algorithm. The PPTR signals and reconstructed initial temperature profiles showed that the 532 nm wavelength probed the shallow skin layers revealing moderate changes during bruise development, while the 1064 nm wavelength provided additional information for severe bruises, in which swelling was present. Our two-wavelength approach has the potential for an improved estimation of the bruise age, especially if combined with modeling of bruise dynamics., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Background and Objectives: In this study, we investigate the photothermal response of human hair using a pulsed laser source employed in the hair removal treatment. The purpose is to understand the dynamics behind the most common clinical practice to better define the salient features that may contribute to the efficiency of the process., Study Design/materials and Methods: Temperature changes of hair samples (dark brown color) from a human scalp (skin type Fitpatrick II) were measured by a thermal camera following irradiation with single and multiple neodymium: yttrium-aluminum-garnet (Nd:YAG) (1064 nm) and alexandrite (755 nm) laser pulses. Particularly, the hair was treated with an individual laser pulse of a sufficiently high fluence, or with a series of lower fluence laser pulses. We investigated the temperature increase in a broad range of fluence and number of pulses. From the data analysis we extrapolated important parameters such as thermal gain and threshold fluence that can be used for determining optimal parameters for the hair removal procedure. Our experimental investigations and hypothesis were supported by a numerical simulation of the light-matter interaction in a skin-hair model, and by optical transmittance measurements of the irradiated hair., Results: An enhancement of the temperature response of the irradiated hair, that deviates from the linear behavior, is observed when hair is subjected to an individual laser pulse of a sufficiently high fluence or to a series of lower fluence laser pulses. Here, we defined the nonlinear and rapid temperature built-up as an avalanche effect. We estimated the threshold fluence at which this process takes place to be at 10 and 2.5 J/cm 2 for 1064 and 755 nm laser wavelengths, respectively. The thermal gain expressed by the degree of the deviation from the linear behavior can be higher than 2 when low laser fluence and multiple laser pulses are applied (n = 50). The comparison of the calculated gain for the two different laser wavelengths and the number of pulses reveals a much higher efficiency when low fluence and multiple pulses are delivered. The avalanche effect manifests when the hair temperature exceeds 45°C. The enhanced temperature increase during the subsequent delivery of laser pulses could be ascribed to the temperature-induced changes in the hair's structural properties. Simulations of the hair temperature under Nd:YAG and alexandrite irradiation indicate that the avalanche phenomenon observed in the hair suspended in air may apply also to the hair located within the skin matrix. Namely, for the same fluence, similar temperature increase was obtained also for the hair located within the skin., Conclusion: The observed "avalanche" effect may contribute to the reported clinical efficacy of laser hair removal and may at least partially explain the observed efficacy of the brushing hair removal procedures where laser fluence is usually low. The repeated irradiation during the brushing procedure may lead to an avalanche-like gradual increase of the hair's thermal response resulting in sufficiently high final hair temperatures as required for effective hair reduction., (© 2022 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.)

Understanding the tissue changes and molecular mechanisms of preclinical models is essential for creating an optimal experimental design for credible translation into clinics. In our study, a chlorhexidine (CHX)-induced mouse model of peritoneal fibrosis was used to analyze histological and molecular/cellular alterations induced by 1 and 3 weeks of intraperitoneal CHX application. CHX treatment for 1 week already caused injury, degradation, and loss of mesothelial cells, resulting in local inflammation, with the most severe structural changes occurring in the peritoneum around the ventral parts of the abdominal wall. The local inflammatory response in the abdominal wall showed no prominent differences between 1 and 3 weeks. We observed an increase in polymorphonuclear cells in the blood but no evidence of systemic inflammation as measured by serum levels of serum amyloid A and interleukin-6. CHX-induced fibrosis in the abdominal wall was more pronounced after 3 weeks, but the gene expression of fibrotic markers did not change over time. Complement system molecules were strongly expressed in the abdominal wall of CHX-treated mice. To conclude, both histological and molecular changes were already present in week 1, allowing examination at the onset of fibrosis. This is crucial information for refining further experiments and limiting the amount of unnecessary animal suffering.

Anatomically accurate models of a human finger can be useful in simulating various disorders. In order to have potential clinical value, such models need to include a large number of tissue types, identified by an experienced professional, and should be versatile enough to be readily tailored to specific pathologies. Magnetic resonance images were acquired at ultrahigh magnetic field (7 T) with a radio-frequency coil specially designed for finger imaging. Segmentation was carried out under the supervision of an experienced radiologist to accurately capture various tissue types (TTs). The final segmented model of the human index finger had a spatial resolution of 0.2 mm and included 6,809,600 voxels. In total, 15 TTs were identified: subcutis, Pacinian corpuscle, nerve, vein, artery, tendon, collateral ligament, volar plate, pulley A4, bone, cartilage, synovial cavity, joint capsule, epidermis and dermis. The model was applied to the conditions of arthritic joint, ruptured tendon and variations in the geometry of a finger. High-resolution magnetic resonance images along with careful segmentation proved useful in the construction of an anatomically accurate model of the human index finger. An example illustrating the utility of the model in biomedical applications is shown. As the model includes a number of tissue types, it may present a solid foundation for future simulations of various musculoskeletal disease processes in human joints.

Hyperspectral imaging (HSI) is a promising optical modality that is already being used in numerous applications. Further expansion of the capabilities of HSI depends on the modularity and versatility of the systems, which would, inter alia , incorporate profilometry, fluorescence imaging, and Raman spectroscopy while following a rigorous calibration and verification protocols, thus offering new insights into the studied samples as well as verifiable, quantitative measurement results applicable to the development of quantitative metrics. Considering these objectives, we developed a custom-made laboratory HSI system geared toward biomedical applications. In this report, we describe the design, along with calibration, characterization, and verification protocols needed to establish such systems, with the overall goal of standardization. As an additional novelty, our HSI system uses a custom-built broadband LED-based light source for reflectance imaging, which is particularly important for biomedical applications due to the elimination of sample heating. Three examples illustrating the utility and advantages of the integrated system in biomedical applications are shown. Our attempt presents both the development of a custom-based laboratory HSI system with novel LED light source as well as a framework which may improve technological standards in HSI system design.

Imaging of blood vessel structure in combination with functional information about blood oxygenation can be important in characterizing many different health conditions in which the growth of new vessels contributes to the overall condition. In this paper, we present a method for extracting comprehensive maps of the vasculature from hyperspectral images that include tissue and vascular oxygenation. We also show results from a preclinical study of peritonitis in mice. First, we analyze hyperspectral images using Beer-Lambert exponential attenuation law to obtain maps of hemoglobin species throughout the sample. We then use an automatic segmentation algorithm to extract blood vessels from the hemoglobin map and combine them into a vascular structure-oxygenation map. We apply this methodology to a series of hyperspectral images of the abdominal wall of mice with and without induced peritonitis. Peritonitis is an inflammation of peritoneum that leads, if untreated, to complications such as peritoneal sclerosis and even death. Characteristic inflammatory response can also be accompanied by changes in vasculature, such as neoangiogenesis. We demonstrate a potential application of the proposed segmentation and processing method by introducing an abnormal tissue fraction metric that quantifies the amount of tissue that deviates from the average values of healthy controls. It is shown that the proposed metric successfully discriminates between healthy control subjects and model subjects with induced peritonitis and has a high statistical significance., Competing Interests: The authors declare that there are no conflicts of interest related to this article., (© 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Analysing diffuse reflectance spectra to extract properties of biological tissue requires modelling of light transport within the tissue, considering its absorption, scattering, and geometrical properties. Due to the layered skin structure, skin tissue models are often divided into multiple layers with their associated optical properties. Typically, in the analysis, some model parameters defining these properties are fixed to values reported in the literature to speed up the fitting process and improve its performance. In the absence of consensus, various studies use different approaches in fixing the model parameters. This study aims to assess the effect of fixing various model parameters in the skin spectra fitting process on the accuracy and robustness of a GPU-accelerated two-layer inverse adding-doubling (IAD) algorithm. Specifically, the performance of the IAD method is determined for noiseless simulated skin spectra, simulated spectra with different levels of noise applied, and in-vivo measured reflectance spectra from hyperspectral images of human hands recorded before, during, and after the arterial occlusion. Our results suggest that fixing multiple parameters to a priori known values generally improves the robustness and accuracy of the IAD algorithm for simulated spectra. However, for in-vivo measured spectra, these values are unknown in advance and fixing optical parameters to incorrect values significantly deteriorates the overall performance. Therefore, we propose a method to improve the fitting performance by pre-estimating model parameters. Our findings could be considered in all future research involving the analysis of diffuse reflectance spectra to extract optical properties of skin tissue., Competing Interests: The authors declare that there are no conflicts of interest related to this article., (© 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Significance: Hyperspectral imaging (HSI) has emerged as a promising optical technique. Besides optical properties of a sample, other sample physical properties also affect the recorded images. They are significantly affected by the sample curvature and sample surface to camera distance. A correction method to reduce the artifacts is necessary to reliably extract sample properties., Aim: Our aim is to correct hyperspectral images using the three-dimensional (3D) surface data and assess how the correction affects the extracted sample properties., Approach: We propose the combination of HSI and 3D profilometry to correct the images using the Lambert cosine law. The feasibility of the correction method is presented first on hemispherical tissue phantoms and next on human hands before, during, and after the vascular occlusion test (VOT)., Results: Seven different phantoms with known optical properties were created and imaged with a hyperspectral system. The correction method worked up to 60 deg inclination angle, whereas for uncorrected images the maximum angles were 20 deg. Imaging hands before, during, and after VOT shows good agreement between the expected and extracted skin physiological parameters., Conclusions: The correction method was successfully applied on the images of tissue phantoms of known optical properties and geometry and VOT. The proposed method could be applied to any reflectance optical imaging technique and should be used whenever the sample parameters need to be extracted from a curved surface sample.

We have augmented a recently introduced method for noninvasive analysis of skin structure and composition and applied it to monitoring of dynamical processes in traumatic bruises. The approach combines diffuse reflectance spectroscopy in visible spectral range and pulsed photothermal radiometry. Data from both techniques are analyzed simultaneously using a numerical model of light and heat transport in a four-layer model of human skin. Compared to the earlier presented approach, the newly introduced elements include two additional chromophores ( β -carotene and bilirubin), individually adjusted thickness of the papillary dermal layer, and analysis of the bruised site using baseline values assessed from intact skin in its vicinity. Analyses of traumatic bruises in three volunteers over a period of 16 days clearly indicate a gradual, yet substantial increase of the dermal blood content and reduction of its oxygenation level in the first days after injury. This is followed by the emergence of bilirubin and relaxation of all model parameters towards the values characteristic for healthy skin approximately two weeks after the injury. The assessed parameter values and time dependences are consistent with existing literature. Thus, the presented methodology offers a viable approach for objective characterization of the bruise healing process.

In this work, we revise the preparation procedure and conduct an in depth characterization of optical properties for the recently proposed silicone-based tissue-mimicking optical phantoms in the spectral range from 475 to 925 nm. The optical properties are characterized in terms of refractive index and its temperature dependence, absorption and reduced scattering coefficients and scattering phase function related quantifiers. The scattering phase function and related quantifiers of the optical phantoms are first assessed within the framework of the Mie theory by using the measured refractive index of SiliGlass and size distribution of the hollow silica spherical particles that serve as scatterers. A set of purely absorbing optical phantoms in cuvettes is used to evaluate the linearity of the absorption coefficient with respect to the concentration of black pigment that serves as the absorber. Finally, the optical properties in terms of the absorption and reduced scattering coefficients and the subdiffusive scattering phase function quantifier γ are estimated for a subset of phantoms from spatially resolved reflectance using deep learning aided inverse models. To this end, an optical fiber probe with six linearly arranged optical fibers is used to collect the backscattered light at small and large distances from the source fiber. The underlying light propagation modeling is based on the stochastic Monte Carlo method that accounts for all the details of the optical fiber probe., Competing Interests: The authors declare that there are no conflicts of interest., (© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

Optical imaging systems use a light source that illuminates a sample and a photodetector that detects light reflected from or transmitted through the sample. The sample surface curvature, surface-to-camera distance, and illumination-source-to-surface distance significantly affect the measured signal, resulting in image artifacts. To correct the images, a three-dimensional (3D) profilometry system was used to obtain 3D surface information. The 3D information enables image correction using Lambert cosine law and height correction. In this study, the feasibility of the correction method for push-broom hyperspectral imaging of three different objects is presented. Results show a significant reduction of image artifacts, making further image analysis more accurate and robust. The presented 3D profilometry method is applicable to all push-broom imaging systems and the described correction procedure can be applied to all spectral or monochromatic imaging systems.

Motivation: Discovering the evolution of a tumor may help identify driver mutations and provide a more comprehensive view on the history of the tumor. Recent studies have tackled this problem using multiple samples sequenced from a tumor, and due to clinical implications, this has attracted great interest. However, such samples usually mix several distinct tumor subclones, which confounds the discovery of the tumor phylogeny., Results: We study a natural problem formulation requiring to decompose the tumor samples into several subclones with the objective of forming a minimum perfect phylogeny. We propose an Integer Linear Programming formulation for it, and implement it into a method called MIPUP. We tested the ability of MIPUP and of four popular tools LICHeE, AncesTree, CITUP, Treeomics to reconstruct the tumor phylogeny. On simulated data, MIPUP shows up to a 34% improvement under the ancestor-descendant relations metric. On four real datasets, MIPUP's reconstructions proved to be generally more faithful than those of LICHeE., Availability and Implementation: MIPUP is available at https://github.com/zhero9/MIPUP as open source., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2018. Published by Oxford University Press.)

We generalize the notion of λ-superstrings, presented in a previous paper, to the notion of weighted λ-superstrings. This generalization entails an important improvement in the applications to vaccine designs, as it allows epitopes to be weighted by their immunogenicities. Motivated by these potential applications of constructing short weighted λ-superstrings to vaccine design, we approach this problem in two ways. First, we formalize the problem as a combinatorial optimization problem (in fact, as two polynomially equivalent problems) and develop an integer programming (IP) formulation for solving it optimally. Second, we describe a model that also takes into account good pairwise alignments of the obtained superstring with the input strings, and present a genetic algorithm that solves the problem approximately. We apply both algorithms to a set of 169 strings corresponding to the Nef protein taken from patiens infected with HIV-1. In the IP-based algorithm, we take the epitopes and the estimation of the immunogenicities from databases of experimental epitopes. In the genetic algorithm we take as candidate epitopes all 9-mers present in the 169 strings and estimate their immunogenicities using a public bioinformatics tool. Finally, we used several bioinformatic tools to evaluate the properties of the candidates generated by our method, which indicated that we can score high immunogenic λ-superstrings that at the same time present similar conformations to the Nef virus proteins., Competing Interests: The authors have declared that no competing interests exist.

In this proof-of-concept study we combine two optical techniques to enable assessment of structure and composition of human skin in vivo: Pulsed photothermal radiometry (PPTR), which involves measurements of transient dynamics in mid-infrared emission from sample surface after exposure to a light pulse, and diffuse reflectance spectroscopy (DRS) in visible part of the spectrum. The analysis involves simultaneous fitting of measured PPTR signals and DRS with corresponding predictions of a Monte Carlo model of light-tissue interaction. By using a four-layer optical model of skin we obtain a good match between the experimental and model data when scattering properties of the epidermis and dermis are also optimized on an individual basis. The assessed parameter values correlate well with literature data and demonstrate the expected trends in controlled tests involving temporary obstruction of peripheral blood circulation using a pressure cuff, and acute as well as seasonal sun tanning., Competing Interests: The authors declare that there are no conflicts of interests related to this article.

We present two new problems of combinatorial optimization and discuss their applications to the computational design of vaccines. In the shortest λ-superstring problem, given a family S1,...,S(k) of strings over a finite alphabet, a set Τ of "target" strings over that alphabet, and an integer λ, the task is to find a string of minimum length containing, for each i, at least λ target strings as substrings of S(i). In the shortest λ-cover superstring problem, given a collection X1,...,X(n) of finite sets of strings over a finite alphabet and an integer λ, the task is to find a string of minimum length containing, for each i, at least λ elements of X(i) as substrings. The two problems are polynomially equivalent, and the shortest λ-cover superstring problem is a common generalization of two well known combinatorial optimization problems, the shortest common superstring problem and the set cover problem. We present two approaches to obtain exact or approximate solutions to the shortest λ-superstring and λ-cover superstring problems: one based on integer programming, and a hill-climbing algorithm. An application is given to the computational design of vaccines and the algorithms are applied to experimental data taken from patients infected by H5N1 and HIV-1.

In three-dimensional (3-D) modeling of light transport in heterogeneous biological structures using the Monte Carlo (MC) approach, space is commonly discretized into optically homogeneous voxels by a rectangular spatial grid. Any round or oblique boundaries between neighboring tissues thus become serrated, which raises legitimate concerns about the realism of modeling results with regard to reflection and refraction of light on such boundaries. We analyze the related effects by systematic comparison with an augmented 3-D MC code, in which analytically defined tissue boundaries are treated in a rigorous manner. At specific locations within our test geometries, energy deposition predicted by the two models can vary by 10%. Even highly relevant integral quantities, such as linear density of the energy absorbed by modeled blood vessels, differ by up to 30%. Most notably, the values predicted by the customary model vary strongly and quite erratically with the spatial discretization step and upon minor repositioning of the computational grid. Meanwhile, the augmented model shows no such unphysical behavior. Artifacts of the former approach do not converge toward zero with ever finer spatial discretization, confirming that it suffers from inherent deficiencies due to inaccurate treatment of reflection and refraction at round tissue boundaries.

Pulsed photothermal radiometry (PPTR) allows noninvasive determination of laser-induced temperature depth profiles in optically scattering layered structures. The obtained profiles provide information on spatial distribution of selected chromophores such as melanin and hemoglobin in human skin. We apply the described approach to study time evolution of incidental bruises (hematomas) in human subjects. By combining numerical simulations of laser energy deposition in bruised skin with objective fitting of the predicted and measured PPTR signals, we can quantitatively characterize the key processes involved in bruise evolution (i.e., hemoglobin mass diffusion and biochemical decomposition). Simultaneous analysis of PPTR signals obtained at various times post injury provides an insight into the variations of these parameters during the bruise healing process. The presented methodology and results advance our understanding of the bruise evolution and represent an important step toward development of an objective technique for age determination of traumatic bruises in forensic medicine.

Hyperspectral images of tissue contain extensive and complex information relevant for clinical applications. In this work, wavelet decomposition is explored for feature extraction from such data. Wavelet methods are simple and computationally effective, and can be implemented in real-time. The aim of this study was to correlate results from wavelet decomposition in the spectral domain with physical parameters (tissue oxygenation, blood and melanin content). Wavelet decomposition was tested on Monte Carlo simulations, measurements of a tissue phantom and hyperspectral data from a human volunteer during an occlusion experiment. Reflectance spectra were decomposed, and the coefficients were correlated to tissue parameters. This approach was used to identify wavelet components that can be utilized to map levels of blood, melanin and oxygen saturation. The results show a significant correlation (p <0.02) between the chosen tissue parameters and the selected wavelet components. The tissue parameters could be mapped using a subset of the calculated components due to redundancy in spectral information. Vessel structures are well visualized. Wavelet analysis appears as a promising tool for extraction of spectral features in skin. Future studies will aim at developing quantitative mapping of optical properties based on wavelet decomposition.

A widely used approach to solving the inverse problem in electrocardiography involves computing potentials on the epicardium from measured electrocardiograms (ECGs) on the torso surface. The main challenge of solving this electrocardiographic imaging (ECGI) problem lies in its intrinsic ill-posedness. While many regularization techniques have been developed to control wild oscillations of the solution, the choice of proper regularization methods for obtaining clinically acceptable solutions is still a subject of ongoing research. However there has been little rigorous comparison across methods proposed by different groups. This study systematically compared various regularization techniques for solving the ECGI problem under a unified simulation framework, consisting of both 1) progressively more complex idealized source models (from single dipole to triplet of dipoles), and 2) an electrolytic human torso tank containing a live canine heart, with the cardiac source being modeled by potentials measured on a cylindrical cage placed around the heart. We tested 13 different regularization techniques to solve the inverse problem of recovering epicardial potentials, and found that non-quadratic methods (total variation algorithms) and first-order and second-order Tikhonov regularizations outperformed other methodologies and resulted in similar average reconstruction errors., (© 2013.)

Background and Objectives: Nd:YAP laser emitting at 1,342 nm appears promising for nonablative skin rejuvenation treatment, based on favorable absorption properties of water and melanin in this part of the spectrum. A quantitative determination of energy deposition characteristics of Nd:YAP in normal human skin should enable design of a safe and effective treatment protocol for future human studies., Study Design: Energy deposition profile of a prototype Nd:YAP laser was determined using pulsed photothermal radiometry. This technique involves time-resolved measurement of mid-infrared emission from a sample after pulsed laser irradiation. The laser-induced temperature depth profile is reconstructed from the radiometric transients using a custom optimization algorithm, developed and tested earlier in our group. Measurements were performed on the extremities of four healthy volunteers at low radiant exposure (2.8 J/cm(2) ). For the purpose of comparison, energy deposition characteristics of commercial Nd:YAG and KTP lasers (at 1,064 and 532 nm, respectively), were also determined at the same test sites., Results: On average, the Nd:YAP laser deposits 50% of the absorbed energy within the top 0.36 mm of skin and 90% within 0.86 mm, which is significantly shallower than the Nd:YAG laser. The ratio between the dermal versus epidermal heating is more favorable and shows a smaller inter- and intra-patient variance as compared to both Nd:YAG and KTP laser., Conclusions: Energy deposition characteristics of the 1,342 nm Nd:YAP laser are very suitable for controlled heating of the upper dermis, as required for nonablative skin rejuvenation. The risks of overheating the epidermis or subcutis should be significantly reduced in comparison with the 1,064 nm Nd:YAG laser., (Copyright © 2012 Wiley Periodicals, Inc.)

Background and Objective: Despite application of cryogen spray (CS) precooling, customary treatment of port wine stain (PWS) birthmarks with a single laser pulse does not result in complete lesion blanching for a majority of patients. One obvious reason is nonselective absorption by epidermal melanin, which limits the maximal safe radiant exposure. Another possible reason for treatment failure is screening of laser light within large PWS vessels, which prevents uniform heating of the entire vessel lumen. Our aim is to identify the parameters of sequential CS cooling and laser irradiation that will allow optimal photocoagulation of various PWS blood vessels with minimal risk of epidermal thermal damage., Study Design and Methods: Light and heat transport in laser treatment of PWS are simulated using a custom 3D Monte Carlo model and 2D finite element method, respectively. Protein denaturation in blood and skin are calculated using the Arrhenius kinetic model with tissue-specific coefficients. Simulated PWS vessels with diameters of 30-150 µm are located at depths of 200-600 µm, and shading by nearby vessels is accounted for according to PWS histology data from the literature. For moderately pigmented and dark skin phototypes, PWS blood vessel coagulation and epidermal thermal damage are assessed for various parameters of sequential CS cooling and 532-nm laser irradiation, i.e. the number of pulses in a sequence (1-5), repetition rate (7-30 Hz), and radiant exposure., Results: Simulations of PWS treatment in darker skin phototypes indicate specific cooling/irradiation sequences that provide significantly higher efficacy and safety as compared to the customary single-pulse approach across a wide range of PWS blood vessel diameters and depths. The optimal sequences involve three to five laser pulses at repetition rates of 10-15 Hz., Conclusions: Application of the identified cooling/irradiation sequences may offer improved therapeutic outcome for patients with resistant PWS, especially in darker skin phototypes., (Copyright © 2011 Wiley-Liss, Inc.)