5. Applications

The importance of the in vivo Raman spectroscopy is the number of potential biomedical applications. One application is the in vivo noninvasive diagnosis, and most research papers focus on cancer and skin diagnosis. In this section, a wide overview over applications in cancer and skin diagnosis is given, with a focus on developments over the past 5 years.

#### 5.1. Cancer diagnosis

One of the most common clinical targets under investigation with Raman spectroscopy is cancer due to the possibility to measure biological samples minimally invasive, in vivo, and without labeling. One important step that enables the introduction of in vivo measurements of cancer in

hollow organs is the development of fiber-optic Raman probes that can be implemented during endoscopy [33].

5.1.4. Skin cancer

5.2. Skin diseases

5.2.1. Atopic dermatitis

A clinical study of 453 patients to investigate different types of skin cancer was published in 2012 by Lui et al. [45]. The instrument used by the authors allowed an acquisition time of approximately 1s and the software preprocessed the spectra immediately, which allowed to investigate skin lesions in real time. Benign and malignant skin lesions including melanomas, basal cell carcinomas, squamous cell carcinomas, actinic keratoses, atypical nevi, melanocytic nevi, blue nevi, and seborrheic keratosis were investigated and discriminated by multivariate analysis tools with sensitivities between 95 and 99%. Lim et al. determined the diagnostic capability of a multimodal spectral diagnosis for in vivo noninvasive disease diagnosis of melanoma and nonmelanoma skin cancers [46]. They acquired reflectance, fluorescence, and Raman spectra from 137 lesions in 76 patients using optical fiber–based systems. They obtained the best classification for nonmelanoma skin cancers when using multimodal approach. On the other hand, the best melanoma classification occurred when using Raman spectroscopy alone. A Raman probe to detect invasive brain cancer in situ in real time in patients was developed by Jermyn et al. [47]. They demonstrated that Raman spectroscopy can accurately detect grade 2–4 gliomas in vivo during human brain cancer surgery and it was possible to differentiate between cancer cell–invaded brain and normal brain, with sensitivity and specificity greater than 90%. Additionally, this approach can classify in real time, making it

Raman Spectroscopy for In Vivo Medical Diagnosis http://dx.doi.org/10.5772/intechopen.72933 301

Several published works have used Raman spectroscopy to analyze the molecular composition of skin and correlate it with history of atopic dermatitis (AD) and filaggrin gene (FLG) mutations; Kezic et al. measured NMFs noninvasively on the skin of 137 Irish children with a history of moderate to severe AD [48]. González et al. detected the presence of the protein filaggrin in the skin of newborns using Raman spectroscopy and PCA as an early detection procedure for filaggrin-related AD [49]. In order to detect the presence of filaggrin in the Raman spectra, the coefficients of the principal components for each of the skin spectra from newborns were calculated. The first and second principal components accounted for 93.86% of all the explained variance of the original data. Figure 3 shows a graph of these two principal components, also known as scores plot. In the figure, the gray solid circles correspond to those infants who developed AD; the rest of the subjects are grouped together around the location of the filaggrin spectrum, represented as a black solid circle. The geometrical distance of each Raman spectra to the spectrum of filaggrin in the principal component plane indicates the amount of filaggrin in the subjects. Lower distances indicate higher amount of filaggrin and higher distances indicate lees amount of filaggrin or a filaggrin with a different molecular

This result indicates that this approach can be used to identify the persons who are more susceptible to develop AD, making it possible to use this technique as a method for early detection of AD. González et al. validated the use of Raman spectroscopy as a noninvasive

an invaluable tool for surgical procedure and decision making.

structure than the molecule that was taken as a reference spectrum.

#### 5.1.1. Lung cancer

Short et al. designed a Raman probe for in vivo detection of lung cancer during autofluorescence bronchoscopy [34], and they demonstrated the potential of Raman for in vivo diagnosis of lung cancer by reducing the false positives of autofluorescence bronchoscopy [35].
