Hyperspectral imaging with machine learning for in vivo skin carcinoma margin assessment: a preliminary study.

Surgical excision is the most effective treatment of skin carcinomas (basal cell carcinoma or squamous cell carcinoma). Preoperative assessment of tumoral margins plays a decisive role for a successful result. The aim of this work was to evaluate the possibility that hyperspectral imaging could become a valuable tool in solving this problem. Hyperspectral images of 11 histologically diagnosed carcinomas (six basal cell carcinomas and five squamous cell carcinomas) were acquired prior clinical evaluation and surgical excision. The hyperspectral data were then analyzed using a newly developed method for delineating skin cancer tumor margins. This proposed method is based on a segmentation process of the hyperspectral images into regions with similar spectral and spatial features, followed by a machine learning-based data classification process resulting in the generation of classification maps illustrating tumor margins. The Spectral Angle Mapper classifier was used in the data classification process using approximately 37% of the segments as the training sample, the rest being used for testing. The receiver operating characteristic was used as the method for evaluating the performance of the proposed method and the area under the curve as a metric. The results revealed that the performance of the method was very good, with median AUC values of 0.8014 for SCCs, 0.8924 for BCCs, and 0.8930 for normal skin. With AUC values above 0.89 for all types of tissue, the method was considered to have performed very well. In conclusion, hyperspectral imaging can become an objective aid in the preoperative evaluation of carcinoma margins.

Comparative analysis of denoising techniques in burn depth discrimination from burn hyperspectral images.

This study analyzes and compares the performance of five denoising techniques (Lee filter, gamma filter, principal component analysis, maximum noise fraction, and wavelet transform) in order to identify the most appropriate one that lead to the most accurate classification of burned tissue in hyperspectral images. Fifteen hyperspectral images of burned patients were acquired and denoising techniques were applied to each image. Spectral angle mapper classifier was used for data classification and the confusion matrix was used for quantitative evaluation of the performances of the denoising methods. The results revealed that gamma filter performed better than other denoising techniques with values of overall accuracy and kappa coefficient of 91.18% and 0.8958 respectively. The lowest performance was detected for principal component analysis. In conclusion, the gamma filter could be considered an optimal choice for noise reduction in burn hyperspectral images and could be used for a more accurate diagnosis of burn depth.

Mapping the Distribution of Melanin Concentration in Different Fitzpatrick Skin Types Using Hyperspectral Imaging Technique.

Measuring skin melanin concentration in order to assess skin phototype according to Fitzpatrick's classification is a constant research goal. In this study, a new approach for assessing skin melanin concentration based on hyperspectral imaging combined with an appropriate analytical model that exploits specific spectral bands to generate maps of melanin content distribution on different Fitzpatrick skin phototypes is presented. Hyperspectral images from the proximal inner side of the forearms of 51 young volunteers covering the first four classes of Fitzpatrick's phototypes were acquired using a hyperspectral imaging system. The images were analyzed using a modified Beer-Lambert law that segregates the contribution of melanin from the other constituents to the skin absorption spectrum. The performance of the model was evaluated using the coefficient of determination (r-squared). The results revealed that the approach proposed in this study generated accurate melanin concentration distribution maps that allowed a correct classification of skin phototype. In conclusion, the proposed approach for assessing skin melanin concentration proved to be very reliable for classifying skin phototypes, and, as it provides maps that are easily read, it has the advantage of a possible extension of its applications to other research concerning skin pigmentation.

Burn characterization using object-oriented hyperspectral image classification.

This paper presents a new approach based on hyperspectral imaging combined with an object-oriented classification method that allows the generation of burn depth classification maps facilitating easier characterization of burns. Hyperspectral images of 14 patients diagnosed with burns on the upper and lower limbs were acquired using a pushbroom hyperspectral imaging system. The images were analyzed using an object-oriented classification approach that uses objects with specific spectral, textural and spatial attributes as the minimum unit for classifying information. The method performance was evaluated in terms of overall accuracy, sensitivity, precision and specificity computed from the confusion matrix. The results revealed that the approach proposed in this study performed well in differentiating burn classes with a high level of overall accuracy (95.99% ± 0.60%), precision (97.30% ± 2.46%), sensitivity (97.23% ± 3.02%) and specificity (98.02% ± 1.98%). In conclusion, the object-based approach for burns hyperspectral images classification can provide maps that can help surgeons identify with better precision different depths of burn wounds.

Automatic detection of basal cell carcinoma by hyperspectral imaging.

The purpose of this study was to test the ability of hyperspectral imaging (HSI) combined with unsupervised anomaly detectors to automatically differentiate basal cell carcinoma (BCC) from normal skin. Hyperspectral images of the face of a female patient with a BCC of the lower lip were acquired using a visible/near-infrared HSI system and two anomaly detection algorithms (Reed-Xiaoli and Reed-Xiaoli/Uniform Target hybrid anomaly detectors) were used to detect pathological tissue from normal skin. The results revealed that the receiver operating characteristic curve of the Reed-Xiaoli/Uniform Target hybrid detector was higher than that of the Reed-Xiaoli detector in the range of false positive rates between 0 and 0.8. The area under curve values were good (0.7074 and 0.8607, respectively) with Reed-Xiaoli/Uniform Target hybrid detector performing better. In conclusion, HSI combined with either of two anomaly detectors can play a promising role in the automated screening of BCC.

New evidence from hyperspectral imaging analysis on the effect of photobiomodulation therapy on normal skin oxygenation.

The aim of this study was to assess the changes induced by photobiomodulation therapy in oxygenation of normal skin and underlying tissue using hyperspectral imaging combined with a chemometric regression approach. Eleven healthy adult volunteers were enrolled in this study. The dorsal side of the left hand of each subject was exposed to photobiomodulation therapy, while the correspondent side of the right hand was used as a control (placebo effect). Laser irradiation was performed with a laser diode system (635 nm, 15mW, 9 J/cm2) for 900 s. Changes in skin oxygenation were assessed before and after applying the photobiomodulation therapy and placebo using the hyperspectral imaging. Hyperspectral data analysis showed that variations of oxyhemoglobin and deoxyhemoglobin concentrations had no statistical significance in both groups. In conclusion, photobiomodulation therapy does not induce changes in oxyhemoglobin and deoxyhemoglobin concentrations in the normal skin measured from hyperspectral images, at least at λ = 635 nm and 900-s exposure time.

Object-oriented classification approach for bone metastasis mapping from whole-body bone scintigraphy.

PURPOSE: Whole-body bone scintigraphy is the most widely used method for detecting bone metastases in advanced cancer. However, its interpretation depends on the experience of the radiologist. Some automatic interpretation systems have been developed in order to improve diagnostic accuracy. These systems are pixel-based and do not use spatial or textural information of groups of pixels, which could be very important for classifying images with better accuracy. This paper presents a fast method of object-oriented classification that facilitates easier interpretation of bone scintigraphy images. METHODS: Nine whole-body images from patients suspected with bone metastases were analyzed in this preliminary study. First, an edge-based segmentation algorithm together with the full lambda-schedule algorithm were used to identify the object in the bone scintigraphy and the textural and spatial attributes of these objects were calculated. Then, a set of objects (224 objects, ~ 46% of the total objects) were selected as training data based on visual examination of the image, and were assigned to various levels of radionuclide accumulation before performing the data classification using both k-nearest-neighbor and support vector machine classifiers. The performance of the proposed method was evaluated using as metric the statistical parameters calculated from error matrix. RESULTS: The results revealed that the proposed object-oriented classification approach using either k-nearest-neighbor or support vector machine as classification methods performed well in detecting bone metastasis in terms of overall accuracy (86.62 ± 2.163% and 86.81 ± 2.137% respectively) and kappa coefficient (0.6395 ± 0.0143 and 0.6481 ± 0.0218 respectively). CONCLUSIONS: In conclusion, the described method provided encouraging results in mapping bone metastases in whole-body bone scintigraphy.

Computer-aided detection of bone metastasis in bone scintigraphy images using parallelepiped classification method.

OBJECTIVE: Accurate diagnosis of metastatic tissue on bone scintigraphy images is of paramount importance in making treatment decisions. Although several automated systems have developed, more and better interpretation methods are still being sought. In the present study, a new modality for bone metastasis detection from bone scintigraphy images using parallelepiped classification (PC) as method for mapping the radionuclide distribution is presented. METHODS: Bone scintigraphy images from 12 patients with bone metastases were analyzed using the parallelepiped classifier that generated color maps of scintigraphic images. Seven classes of radionuclide accumulation have been identified and fed into machine learning software. The accuracy of the proposed method was evaluated by statistical measurements in a confusion matrix. Overall accuracy, producer's and user's accuracies and κ coefficient were computed from each confusion matrix associated with the individual case. RESULTS: The results revealed that the method is sufficiently precise to differentiate the metastatic bone from normal tissue (overall classification accuracy = 87.58 ± 2.25% and κ coefficient = 0.8367 ± 0.0252). The maps are easier to read (due to better contrast) and can detect even slightest differences in accumulation levels among pixels. CONCLUSIONS: In conclusion, these preliminary data suggest that bone scintigraphy combined with PC method could play an important role in the detection of bone metastasis, allowing for an easier but correct interpretation of the images, with effects on the diagnosis accuracy and decision making on the treatment to be applied.

Fractionated Irradiation in Photobiomodulation Therapy of Ankle Sprain.

OBJECTIVE: The aim of this study was to test whether fractionated irradiation in photobiomodulation therapy enhances short-term recovery in patients with moderate severity ankle sprain. DESIGN: Nineteen patients were randomly assigned to one of two groups: one group receiving photobiomodulation therapy combined with the standard rest, icing, compression, and elevation treatment, or a group receiving only standard treatment. Group 1 patients were irradiated using a laser system (635 nm, 15 mW) according to a double-fractionated irradiation scheme consisting of two sessions (4.5 and 9 J/cm) separated by a 30-min time interval. Short-term outcomes (reflectance, pain, and clinical outcomes) were assessed at baseline, 10 days, and 6 wks after treatment. RESULTS: Reflectance data analysis showed significant changes in group 1 (P = 0.027). There was also an ankle function score improvement more in group 1 than in group 2, with a significant short-term effect (P = 0.011) but without significant long-term effects (P = 0.178). Compared with group 2, group 1 had an immediate effect on pain reduction, but no long-term effect (P = 0.074). CONCLUSIONS: Combined with standard treatment, fractionated irradiation photobiomodulation therapy has been shown to have favorable short-term effects on the recovery of patients with ankle sprains, but its long-term effects should be improved.

Hyperspectral index-based metric for burn depth assessment.

Burn depth objective classification is of paramount importance for decision making and treatment. Despite the wide variety of burn depth assessment methods tested so far, none of them have gained wide clinical application. Here, we introduce a new approach for burn depth assessment based on hyperspectral imaging combined with a spectral index-based technique that exploits specific spectral bands to map skin areas with different burn degrees. The spectral index amplifies the contrast between normal skin and areas with different degrees of burn, taking advantage of the differences in spectral amplitudes that occur as a result of the morphological and physiological changes occurring in burned skin. We demonstrate that by using the new measurable spectral index, it is possible to generate accurate burn classification maps showing spatial distribution of burn types in the affected body areas, facilitating the decision-making process and prognosis evaluation. The results highlight the potential of the new hyperspectral metric in the field of burn depth classification and its applicability in hospital settings seems promising.

Simulated altitude exposure assessment by hyperspectral imaging.

Testing the human body's reaction to hypoxia (including the one generated by high altitude) is important in aeronautic medicine. This paper presents a method of monitoring blood oxygenation during experimental hypoxia using hyperspectral imaging (HSI) and a spectral unmixing model based on a modified Beer­Lambert law. A total of 20 healthy volunteers (males) aged 25 to 60 years were included in this study. A line-scan HSI system was used to acquire images of the faces of the subjects. The method generated oxyhemoglobin and deoxyhemoglobin distribution maps from the foreheads of the subjects at 5 and 10 min of hypoxia and after recovery in a high oxygen breathing mixture. The method also generated oxygen saturation maps that were validated using pulse oximetry. An interesting pattern of desaturation on the forehead was discovered during the study, showing one of the advantages of using HSI for skin oxygenation monitoring in hypoxic conditions. This could bring new insight into the physiological response to high altitude and may become a step forward in air crew testing.

An Analysis of Human Dorsal Hand Skin Texture Using Hyperspectral Imaging Technique for Assessing the Skin Aging Process.

Skin texture has become an important issue in recent research with applications in the cosmetic industry and medicine. In this paper, we analyzed the dependence of skin texture features on wavelength as well as on different parameters (age and gender) of human participants using grey-level co-occurrence matrix and hyperspectral imaging technique for a more accurate quantitative assessment of the aging process. A total of 42 healthy participants (men and women; age range, 20-70 years) was enrolled in this study. A region of interest was selected from the hyperspectral images. The results were analyzed in terms of texture using the gray-level co-occurrence matrix which generated four features (homogeneity, contrast, entropy, and correlation). The results showed that most of these features displayed variations with wavelength (the exception was entropy), with higher variations in women. Only correlation in both sexes and contrast in men proved to vary statistically significant with age, making them the targeted variables in future attempts to characterize aging skin using the complex method of hyperspectral imaging. In conclusion, by using hyperspectral imaging some measure of the degree of damage or the aging process of the hand skin can be obtained, mainly in terms of correlation values. At the present time, reasonable explanations that can link the process of skin aging and the above mentioned features could not be found, but deeper investigations are on the way.

Algorithm for mapping cutaneous tissue oxygen concentration using hyperspectral imaging.

The measurement of tissue oxygenation plays an important role in the diagnosis and therapeutic assessment of a large variety of diseases. Many different methods have been developed and are currently applied in clinical practice for the measurement of tissue oxygenation. Unfortunately, each of these methods has its own limitations. In this paper we proposed the use of hyperspectral imaging as new method for the assessment of the tissue oxygenation level. To extract this information from hyperspectral images a new algorithm for mapping cutaneous tissue oxygen concentration was developed. This algorithm takes into account and solves some problems related to setting and calculation of some parameters derived from hyperspectral images. The algorithm was tested with good results on synthetic images and then validated on the fingers of a hand with different blood irrigation states. The results obtained have proved the ability of hyperspectral imaging together with the developed algorithm to map the oxy- and deoxyhemoglobin distribution on the analyzed fingers. These are only preliminary results and other studies should be done before this approach to be used in the clinical setting for the diagnosis and monitoring of various diseases.

Hyperspectral imaging-based wound analysis using mixture-tuned matched filtering classification method.

Hyperspectral imaging is a technology that is beginning to occupy an important place in medical research with good prospects in future clinical applications. We evaluated the role of hyperspectral imaging in association with a mixture-tuned matched filtering method in the characterization of open wounds. The methodology and the processing steps of the hyperspectral image that have been performed in order to obtain the most useful information about the wound are described in detail. Correlations between the hyperspectral image and clinical examination are described, leading to a pattern that permits relative evaluation of the square area of the wound and its different components in comparison with the surrounding normal skin. Our results showed that the described method can identify different types of tissues that are present in the wounded area and can objectively measure their respective abundance, which proves its value in wound characterization. In conclusion, the method that was described in this preliminary case presentation shows promising results, but needs further evaluation in order to become a reliable and useful tool.

Characterization of burns using hyperspectral imaging technique - a preliminary study.

Surgical burn treatment depends on accurate estimation of burn depth. Many methods have been used to asses burns, but none has gained wide acceptance. Hyperspectral imaging technique has recently entered the medical research field with encouraging results. In this paper we present a preliminary study (case presentation) that aims to point out the value of this optical method in burn wound characterization and to set up future lines of investigation. A hyperspectral image of a leg and foot with partial thickness burns was obtained in the fifth postburn day. The image was analyzed using linear spectral unmixing model as a tool for mapping the investigated areas. The article gives details on the mathematical bases of the interpretation model and correlations with clinical examination pointing out the advantages of hyperspectral imaging technique. While the results were encouraging, further more extended and better founded studies are being prepared before recognizing hyperspectral imaging technique as an applicable method of burn wound assessment.

Increased number of fractionated irradiation sessions does not improve the cellular response to methyl aminolevulinate-mediated photodynamic therapy.

BACKGROUND: In the search to improve the efficacy of photodynamic therapy different approaches have been investigated until now. One of these approaches is the use of double fractionated irradiation schemes. This study aims to investigate the effect of increasing the numbers of fractionated irradiation sessions in methyl aminolevulinate-mediated photodynamic therapy on dysplastic oral keratinocytes by monitoring the changes in optical properties of cell culture. METHODS: Forty cell cultures were divided into four experimental groups (single, double and triple fractionated irradiation scheme and control). Cells were incubated with 1mM methyl aminolevulinate and after 2h they were exposed to laser radiation (λ=635 nm, P=15 mW). The exposure time was 900 s for the single irradiation scheme, 300 s + 600 s for the double fractionated irradiation scheme with dark interval between sessions of 30 min and 300 s + 300 s + 300 s for the triple fractionated irradiation scheme with two dark intervals between sessions of 30 min. Two optical parameters (refractive index and extinction coefficient) were calculated from diffuse reflectance spectra of cell cultures using the Kramers-Kronig relations. RESULTS: The results demonstrate that the use of double fractionated irradiation scheme led to changes in optical parameters of cell cultures more important than the use of the single and triple fractionated irradiation schemes in photodynamic therapy. CONCLUSIONS: In conclusion, increasing too much the number of irradiation sessions cannot lead to an improved photodynamic effect.

Optical techniques for the noninvasive diagnosis of skin cancer.

PURPOSE: The aim of this paper is to provide an overview of the most investigated optical diagnostic techniques: optical coherence tomography, fluorescence spectrometry, reflectance spectrometry, Raman spectroscopy, and confocal microscopy. METHODS: A search of three databases was conducted using specific keywords and explicit inclusion and exclusion criteria for the analysis of the performances of these techniques in the pre- and postoperative diagnosis of skin cancers. RESULTS: Optical coherence tomography has shown promising results in the assessment of deep margins of skin tumors and inflammatory skin diseases, but differentiating premalignant from malignant lesions proved to be less effective. Fluorescence spectroscopy proved to be effective in revealing the biochemical composition of tissue; early detection of malignant melanoma was reliable only with stepwise two-photon excitation of melanin, while tumoral margin assessment and differential diagnosis between malignant and non-malignant lesions showed some conflicting results. Characterization of the structural properties of tissue can be made using diffuse reflectance spectrometry, and the values of the specificity and sensitivity of this method are ranging between 72-92 % and 64-92 %, respectively. Raman spectroscopy proved to have better results both in carcinoma and melanoma diagnosis with sensitivities and specificities above 90 % and high above 50 %, respectively. Confocal microscopy is the closest technique to pathological examination and has gained the most clinical acceptance, despite the need for a standardization of the interpretation algorithm. CONCLUSIONS: In conclusion, these optical techniques proved to be effective in the diagnosis of skin cancer, but further studies are needed in finding the appropriate method or combination of methods that can have wide clinical applications.

Optical method for monitoring of photodynamic inactivation of bacteria.

Photodynamic inactivation is a new promising approach to treat bacterial infections. Usually, the evaluation of the efficacy of this method is done through time-consuming and labor-intensive microbiological test methods. This paper describes the development and implementation of an optical method to evaluate the photodynamic inactivation of bacteria based on non-invasive diffuse reflectance measurements. Five Staphylococcus aureus cultures and 15 mice have been used in this study. A skin lesion was created on the back of all animals, and it was contaminated with S. aureus (5.16 ± 0.013 log CFU/ml). Toluidine Blue O (c = 8.67 × 10 (- 3) M) has been used as a photosensitiser agent. The bacterial cultures and animals were exposed to laser radiation (λ = 635 nm, P = 15 mW, DE = 8.654 J/cm(2)) for 20 min. The photodynamic inactivation of bacteria was monitored by acquiring the wounds' reflection spectra at different time points and by microbiological exams on the bioptical material. The good correlation between the diffuse reflectance and colony-forming units demonstrates the value of this optical method based on diffuse reflectance measurements as a rapid technique to monitor photodynamic bacterial inactivation.

In vivo study of age-related changes in the optical properties of the skin.

The optical properties of the skin (absorption coefficient, scattering coefficient, refractive index) may serve to characterize the skin and are important for correct light dosimetry in many optical diagnostic procedures and laser treatments especially photodynamic therapy and laser therapy. We determined in vivo the optical properties of tissues near the wrist, elbow and knee in subjects of different ages using diffuse reflectance spectroscopy, having in view the establishment of laser system types for the laser treatment of posttraumatic lesions in subjects of different ages. Diffuse reflection of light from biological tissue is due to the variation in refractive index of tissular and cellular components and the surrounding medium and depends on the wavelength of the incident optical radiation. The diffuse reflectance spectrum of the tissues tested showed two maxima localized at lamda(M1) is approximately 610 nm and lambda(M2) is approximately 675 nm. Laser systems which emit radiation at these wavelengths are not efficient for the treatment of joints, regardless of the subject's age. The deep tissues have a strong absorption in the range 630-700 nm, which indicates that for treating posttraumatic lesions we can use laser systems such as the He-Ne laser, the GaAlAs laser, and the InGaAlAs laser. Using Kramers-Kronig analysis of the diffuse reflectance spectra, the optical parameters n(omega) and k(omega) were determined. The age-dependent changes in these optical parameters of tissue must be taken into consideration and the use of laser treatments or optical diagnosis methods must be based on a knowledge of these properties and of the optical radiation parameters.

In vivo comparison of simple and double-fractionated low-level laser irradiation schemes on the healing of rat skin lesions.

OBJECTIVE: To compare the efficacy of a simple irradiation scheme with that of a double-fractionated irradiation scheme on the healing of rat skin lesions using in vivo monitoring of tissue diffuse reflectance. BACKGROUND DATA: Low-level laser therapy (LLLT) is used in medicine for treating a wide range of pathological conditions. The practical benefits of laser treatment of acute and chronic conditions were obtained, using a single session of irradiation per day. MATERIALS AND METHODS: Thirty Wistar rats were divided into three experimental groups (controls, simple laser irradiation scheme, and double-fractionated laser irradiation scheme). A skin lesion was created on the calf of the right hind leg of all rats. The laser irradiation parameters were lambda = 635 nm and power = 15 mW. The exposure time was 600 s for the simple laser irradiation scheme and 300 s x 2 for the double-fractionated laser irradiation scheme on 3 consecutive days. The optical properties of tissue were studied by processing and analyzing the diffuse reflectance spectra of injured skin, acquired before and after each laser irradiation. RESULTS: The results demonstrate that, using a simple laser irradiation scheme (single daily irradiation session: t exp 1 =600 s, power = 15 mW, lambda = 635 nm), healing of the skin lesion began after 3 consecutive treatment days. The application of the double-fractionated laser irradiation scheme (2 daily irradiation sessions: t exp 2 = t exp 1/2 = 300 s, power = 15 mW and lambda = 635 nm) led to a reduction in treatment time to 2 days. CONCLUSION: In conclusion, a double-fractionated irradiation scheme is more efficient than simple irradiation scheme for LLLT in rat skin lesions.