Miguel G. Ramírez-Elías

Use of Raman spectroscopy for the early detection of filaggrin-related atopic dermatitis

Background: Filaggrin (FLG) gene mutations, which result in complete or incomplete loss of proFLG/FLG peptides, have been reported as an important predisposing factor for atopic dermatitis (AD) and secondary atopic phenotypes such as atopic asthma.

Noise and Artifact Characterization of in Vivo Raman Spectroscopy Skin Measurements

In this work principal component analysis (PCA), a multivariate pattern recognition technique, is used to characterize the noise contribution of the experimental apparatus and two commonly used methods for fluorescence removal used in biomedical Raman spectroscopy measurements. These two methods are a fifth degree polynomial fitting and an iterative variation of it commonly known as the Vancouver method. The results show that the noise in Raman spectroscopy measurements is related to the spectral resolution of the measurement equipment, the intrinsic variability of the biological measurements, and the fluorescence removal algorithm used.

Noninvasive detection of filaggrin gene mutations using Raman spectroscopy

Knowledge of the existence of filaggrin (FLG) gene mutations might be helpful for a subclassification of patients with atopic dermatitis (AD) which can be used to introduce individualized treatments. In this work the filaggrin content in the skin is assessed using Raman spectroscopy and the results are compared to FLG genotyping of Mexican-mestizo patients. Results showed that the 2282del4 and R501X mutations present in the European population but absent in people of Asian or African descent are also present in the Mexican-mestizo population. The results also showed that patients with filaggrin gene mutations presented lower filaggrin concentrations measured using the vector correlation of their skin Raman spectra and a fixed spectrum of pure human recombinant filaggrin, these results indicate that Raman spectroscopy may be used as a noninvasive tool to detect FLG gene mutations.

Noninvasive estimation of chronological and photoinduced skin damage using Raman spectroscopy and principal component analysis.

Skin aging can be attributed to endogenous and exogenous factors which modify the hydration and protein structure of the skin which can be measured using Raman spectroscopy.

Raman spectroscopy analysis of the skin of patients with melasma before standard treatment with topical corticosteroids, retinoic acid, and hydroquinone mixture

Melasma is an abnormal acquired hyperpigmentation of the face of unknown origin, it is considered a single disease and very little has been found regarding its pathogenesis. It is usually assumed that melasma is due to excessive melanin production, but previous work using Raman spectroscopy showed degraded molecules of melanin in some melasma subjects, which may help to explain the success or failure of the standard therapy.

Fluorescence background removal method for biological Raman spectroscopy based on empirical mode decomposition

Raman spectroscopy of biological tissue presents fluorescence background, an undesirable effect that generates false Raman intensities. This paper proposes the application of the Empirical Mode Decomposition (EMD) method to baseline correction. EMD is a suitable approach since it is an adaptive signal processing method for nonlinear and non-stationary signal analysis that does not require parameters selection such as polynomial methods. EMD performance was assessed through synthetic Raman spectra with different signal to noise ratio (SNR). The correlation coefficient between synthetic Raman spectra and the recovered one after EMD denoising was higher than 0.92. Additionally, twenty Raman spectra from skin were used to evaluate EMD performance and the results were compared with Vancouver Raman algorithm (VRA). The comparison resulted in a mean square error (MSE) of 0.001554. High correlation coefficient using synthetic spectra and low MSE in the comparison between EMD and VRA suggest that EMD could be an effective method to remove fluorescence background in biological Raman spectra.

Detection of hydroquinone by Raman spectroscopy in patients with melasma before and after treatment

Melasma is an acquired, facial hyperpigmentation without a specific origin. It is regularly associated with multiple etiologic factors such as pregnancy, genetic, racial, and from estrogen administration. Among the methods to treat skin hyperpigmentation a series of skin bleaching agents have been used. At present, the most commonly used agent is known as hydroquinone. Nowadays, it is known that hydroquinone can cause cancer in animals with unknown relevance to humans.

Noninvasive detection of collagen regeneration after an isotretinoin treatment and ablative laser surgery in patients with acne scars by Raman spectroscopy

Background: To the date, oral isotretinoin is the most effective treatment for acne scars, and by combining their use with an ablative surgery results in improving the effects of the skin restoration. However, it is highly recommended by dermatologists, to wait for a period of 6 months between the isotretinoin treatment and the laser surgery, and that relative high period of time can lead to negative effects like anxiety or psychological distress in the patients. Our objective is to demonstrate that combining an ablative laser surgery and an isotretinoin treatment at therapeutic doses improves the acne wound healing in a considerably short period of time in comparison with previous studies. Additionally, it is of our interest to evaluate the wound healing due the collagen regeneration by the use of Raman spectroscopy, recently used as a non-invasive medical tool for skin diseases. Method: The study was performed in 9 patients who underwent on an oral isotretinoin treatment due to the presence of acne scars on the face. All patients received one single treatment with a CO2 Ablative Fractional Laser (AFL) on four zones of the face within a range of four weeks after isotretinoin treatment. Additionally, an untreated measurement in the elbow side of the arm acted as a control. Both treatments, the isotretinoin and the ablative surgery, were performed by the same dermatologist. The patients were evaluated by means of Raman spectroscopy before and after the treatment and for the data processing, two different statistical approaches were applied to the Raman spectra with the objective to assess the presence of a specific collagen type. Results: The patients showed normal wound healing post AFL treatments and it was shown that with a therapeutic dose of oral isotretinoin and with one single laser surgery in a relative short period of time, a collagen regeneration was observed. Conclusion: When combined AFL surgery and isotretinoin treatment at therapeutic doses, a regeneration of a type of collagen is observed, which is quantified non-invasively by Raman spectroscopy.

Evaluation of liver fibrosis using Raman spectroscopy and infrared thermography: A pilot study

Liver fibrosis is a pathological process that can escalate to cirrhosis and then liver failure, a major public health concern that affect hundreds of millions of people in both developed and developing countries. Detection of liver fibrosis during its earlier stages is a matter of great importance which may allow prevention of development of cirrhosis in patients with chronic liver disease. In this work, Raman spectroscopy and thermography were evaluated to detect early pathological signs of liver fibrosis in rats in which liver fibrosis was induced using carbon tetrachloride. Results show that Raman spectra of healthy and fibrotic livers significantly differ among each other and can be classified by principal component analysis and discriminant analysis. The PCA-LDA method has a sensitivity of 100%, specificity 85% and diagnostic accuracy of 93.5%. Thermography also revealed characteristic temperature patterns for fibrotic livers compared to healthy livers. Current data suggest that Raman spectroscopy and thermography could be used to detect fibrosis in ex vivo liver samples.

Denoising of Raman spectroscopy for biological samples based on Empirical Mode Decomposition

Raman spectroscopy of biological samples presents undesirable noise and fluorescence generated by the biomolecular excitation. The reduction of these types of noise is a fundamental task to obtain the valuable information of the sample under analysis. This paper proposes the application of the empirical mode decomposition (EMD) for noise elimination. EMD is a parameter-free and adaptive signal processing method useful for the analysis of nonstationary signals. EMD performance was compared with the commonly used Vancouver algorithm (VRA) through artificial data (Teflon), synthetic (Vitamin E and paracetamol) and biological (Mouse brain and human nails) Raman spectra. The correlation coefficient (ρ) was used as performance measure. Results on synthetic data showed a better performance of EMD (ρ=0.52) at high noise levels compared with VRA (ρ=0.19). The methods with simulated fluorescence added to artificial material exhibited a similar shape of fluorescence in both cases (ρ=0.95 for VRA and ρ=0.93 for EMD). For synthetic data, Raman spectra of vitamin E were used and the results showed a good performance comparing both methods (ρ=0.95 for EMD and ρ=0.99 for VRA). Finally, in biological data, EMD and VRA displayed a similar behavior (ρ=0.85 for EMD and ρ=0.96 for VRA), but with the advantage that EMD maintains small amplitude Raman peaks. The results suggest that EMD could be an effective method for denoising biological Raman spectra, EMD is able to retain information and correctly eliminates the fluorescence without parameter tuning.