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Raman microscopy imaging as a valuable tool to support histopathological evaluation of thyroid lesions

5 May | By Julietta V. Rau
Raman microscopy imaging as a valuable tool to support histopathological evaluation of thyroid lesions
Image source: private


Histopathological evaluation is currently the ‘gold standard’ of diagnosis in clinics. However, being based on the morphological evaluation, it is subjected to inter- and intra-observer variability and sampling errors even among the experts, especially for some kind of pathologies. Moreover, a recent paradigm change versus the reduced thyroid cancer over-treatment necessitates for a new clinical tool to reliably identify neoplastic lesions and to improve the efficiency in differentiation between benign and malignant neoplasms, especially what regards small carcinomas and progressively growing number of thyroid nodules. The Fine Needle Aspiration biopsy (FNA), coupled with cytological assessment, is the traditional procedure for their diagnosis. Some of them possess indeterminate morphological features and represent a clinical problem. Molecular analysis diagnostics recently introduced in clinical practice has improved the situation, but currently remains a costly procedure.


The necessity to support the histological evaluation by biochemical composition information could be covered by spectroscopic methods, able to provide the detailed information on tissue/cell biochemistry. With this regard, spectroscopic tools can be very suitable to obtain the detailed knowledge on biochemical composition for each specific pathology, precancerous states, benign abnormalities and any other tissue or cell alteration, as long as it is connected to biochemical composition changes. Among the spectroscopic techniques, Raman Spectroscopy (RS) is one of the most promising one, providing high molecular specificity, accuracy and sensitivity, thus holding the potential to reduce the false positive or false negative rates in clinical diagnostics. High chemical specificity, non-destructivity, minimal sample preparation, absence of problems connected to water environment are among the main advantages of RS. 


Modern RS microscopes allow paired morphological and biochemical characterizations and are applicable for the imaging-mapping of relatively large tissue areas, coupled with high resolution and point-by-point spectral analysis of biochemical composition. The developments in this field made important steps towards maximizing the acquisition speed and spectral accuracy.


A group of researchers led by Dr. Julietta V. Rau, in close collaboration with medical personnel from the Pathology and Surgery Units of the Campus Bio-medico of Rome, performed Raman microscopic investigation aimed to biochemically differentiate between healthy and neoplastic thyroid tissues, by analyzing the main variants (classical and follicular) of Papillary Thyroid Carcinoma (PTC), the most common type of thyroid cancer. They performed Raman imaging of large tissue areas, collecting numerous Raman biochemical maps. Multivariate statistical methods were applied to translate Raman spectra differences into diagnostically useful information for a reliable tissue classification. Moreover, specific biochemical features of the PTC profile, characterized by the significant presence of carotenoids with respect to the healthy tissue, were identified.


The achieved diagnostic sensitivity, specificity and accuracy are compatible with the clinical use, both for the PTC diagnosis and for the differential diagnosis between classical and follicular variants of PTC, the latter being a significant challenging point for thyroid nodules evaluation. The next research goal is related to very arduous follicular patterned thyroid lesions (carcinoma versus adenoma), subjected to inter-observer variability. For this kind of pathology the histological evaluation assures only about 70% of reliability. For such cases, the combined histological and Raman microscopy analyses can allow clear-cut integration of morphological and biochemical observations, with the improved efficiency and accuracy in decision-making for diagnosis of thyroid tissues.


Original publication: Rau, J. V. et al. RAMAN spectroscopy imaging improves the diagnosis of papillary thyroid carcinoma. Sci. Rep. 6, 35117; doi: 10.1038/srep35117 (2016)


 

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